WorldWideScience

Sample records for ventricular hypertrophy induced

  1. Deletion of Interleukin-6 Attenuates Pressure Overload-Induced Left Ventricular Hypertrophy and Dysfunction

    Science.gov (United States)

    Afzal, Muhammad R.; Samanta, Anweshan; Xuan, Yu-Ting; Girgis, Magdy; Elias, Harold K; Zhu, Yanqing; Davani, Arash; Yang, Yanjuan; Chen, Xing; Ye, Sheng; Wang, Ou-Li; Chen, Lei; Hauptman, Jeryl; Vincent, Robert J.; Dawn, Buddhadeb

    2016-01-01

    Rationale The role of interleukin (IL)-6 in the pathogenesis of cardiac myocyte hypertrophy remains controversial. Objective To conclusively determine whether IL-6 signaling is essential for the development of pressure overload-induced left ventricular (LV) hypertrophy, and to elucidate the underlying molecular pathways. Methods and Results Wild-type (WT) and IL-6 knockout (IL-6−/−) mice underwent sham surgery or transverse aortic constriction (TAC) to induce pressure overload. Serial echocardiograms and terminal hemodynamic studies revealed attenuated LV hypertrophy and superior preservation of LV function in IL-6−/− mice after TAC. The extents of LV remodeling, fibrosis, and apoptosis were reduced in IL-6−/− hearts after TAC. Transcriptional and protein assays of myocardial tissue identified CaMKII and STAT3 activation as important underlying mechanisms during cardiac hypertrophy induced by TAC. The involvement of these pathways in myocyte hypertrophy was verified in isolated cardiac myocytes from WT and IL-6−/− mice exposed to pro-hypertrophy agents. Furthermore, overexpression of CaMKII in H9c2 cells increased STAT3 phosphorylation, and exposure of H9c2 cells to IL-6 resulted in STAT3 activation that was attenuated by CaMKII inhibition. Together these results identify the importance of CaMKII-dependent activation of STAT3 during cardiac myocyte hypertrophy via IL-6 signaling. Conclusions Genetic deletion of IL-6 attenuates TAC-induced LV hypertrophy and dysfunction, indicating a critical role played by IL-6 in the pathogenesis of LV hypertrophy in response to pressure overload. CaMKII plays an important role in IL-6-induced STAT3 activation and consequent cardiac myocyte hypertrophy. These findings may have significant therapeutic implications for LV hypertrophy and failure in patients with hypertension. PMID:27126808

  2. Diagnostic electrocardiographic dyad criteria of emphysema in left ventricular hypertrophy.

    Science.gov (United States)

    Lanjewar, Swapnil S; Chhabra, Lovely; Chaubey, Vinod K; Joshi, Saurabh; Kulkarni, Ganesh; Kothagundla, Chandrasekhar; Kaul, Sudesh; Spodick, David H

    2013-01-01

    The electrocardiographic diagnostic dyad of emphysema, namely a combination of the frontal vertical P-vector and a narrow QRS duration, can serve as a quasidiagnostic marker for emphysema, with specificity close to 100%. We postulated that the presence of left ventricular hypertrophy in emphysema may affect the sensitivity of this electrocardiographic criterion given that left ventricular hypertrophy generates prominent left ventricular forces and may increase the QRS duration. We reviewed the electrocardiograms and echocardiograms for 73 patients with emphysema. The patients were divided into two groups based on the presence or absence of echocardiographic evidence of left ventricular hypertrophy. The P-vector, QRS duration, and forced expiratory volume in one second (FEV1) were computed and compared between the two subgroups. There was no statistically significant difference in qualitative lung function (FEV1) between the subgroups. There was no statistically significant difference in mean P-vector between the subgroups. The mean QRS duration was significantly longer in patients with left ventricular hypertrophy as compared with those without left ventricular hypertrophy. The presence of left ventricular hypertrophy may not affect the sensitivity of the P-vector verticalization when used as a lone criterion for diagnosing emphysema. However, the presence of left ventricular hypertrophy may significantly reduce the sensitivity of the electrocardiographic diagnostic dyad in emphysema, as it causes a widening of the QRS duration.

  3. Diagnostic electrocardiographic dyad criteria of emphysema in left ventricular hypertrophy

    Directory of Open Access Journals (Sweden)

    Lanjewar SS

    2013-11-01

    Full Text Available Swapnil S Lanjewar,1 Lovely Chhabra,1 Vinod K Chaubey,1 Saurabh Joshi,1 Ganesh Kulkarni,1 Chandrasekhar Kothagundla,1 Sudesh Kaul,1 David H Spodick21Department of Internal Medicine, 2Department of Cardiovascular Medicine, Saint Vincent Hospital, University of Massachusetts Medical School, Worcester, MA, USABackground: The electrocardiographic diagnostic dyad of emphysema, namely a combination of the frontal vertical P-vector and a narrow QRS duration, can serve as a quasidiagnostic marker for emphysema, with specificity close to 100%. We postulated that the presence of left ventricular hypertrophy in emphysema may affect the sensitivity of this electrocardiographic criterion given that left ventricular hypertrophy generates prominent left ventricular forces and may increase the QRS duration.Methods: We reviewed the electrocardiograms and echocardiograms for 73 patients with emphysema. The patients were divided into two groups based on the presence or absence of echocardiographic evidence of left ventricular hypertrophy. The P-vector, QRS duration, and forced expiratory volume in one second (FEV1 were computed and compared between the two subgroups.Results: There was no statistically significant difference in qualitative lung function (FEV1 between the subgroups. There was no statistically significant difference in mean P-vector between the subgroups. The mean QRS duration was significantly longer in patients with left ventricular hypertrophy as compared with those without left ventricular hypertrophy.Conclusion: The presence of left ventricular hypertrophy may not affect the sensitivity of the P-vector verticalization when used as a lone criterion for diagnosing emphysema. However, the presence of left ventricular hypertrophy may significantly reduce the sensitivity of the electrocardiographic diagnostic dyad in emphysema, as it causes a widening of the QRS duration.Keywords: emphysema, electrocardiogram, left ventricular hypertrophy, chronic

  4. Left ventricular hypertrophy in children, adolescents and young adults with sickle cell anemia

    Directory of Open Access Journals (Sweden)

    Gustavo Baptista de Almeida Faro

    2015-10-01

    Full Text Available OBJECTIVE: The aims of this study were to estimate the frequency of left ventricular hypertrophy and to identify variables associated with this condition in under 25-year-old patients with sickle cell anemia.METHODS: A cross-sectional study was performed of children, adolescents and young adults with sickle cell anemia submitted to a transthoracic Doppler echocardiography. The mass of the left ventricle was determined by the formula of Devereux et al. with correction for height, and the percentile curves of gender and age were applied. Individuals with rheumatic and congenital heart disease were excluded. The patients were divided into two groups according to the presence or absence of left ventricular hypertrophy and compared according to clinical, echocardiographic and laboratory variables.RESULTS: A total of 37.6% of the patients had left ventricular hypertrophy in this sample. There was no difference between the groups of patients with and without hypertrophy according to pathological history or clinical characteristics, except possibly for the use of hydroxyurea, more often used in the group without left ventricular hypertrophy. Patients with left ventricular hypertrophy presented larger left atria and lower hemoglobin and hematocrit levels, reticulocyte index and a higher albumin:creatinine ratio in urine.CONCLUSION: Left ventricular hypertrophy was observed in more than one-third of the young patients with sickle cell anemia with this finding being inversely correlated to the hemoglobin and hematocrit levels, and reticulocyte index and directly associated to a higher albumin/creatinine ratio. It is possible that hydroxyurea had had a protective effect on the development of left ventricular hypertrophy.

  5. [Effect of down-regulation of IKs repolarization-reserve on ventricular arrhythmogenesis in a guinea pig model of cardiac hypertrophy].

    Science.gov (United States)

    Wang, Hegui; Huang, Ting; Wang, Zheng; Ge, Nannan; Ke, Yongsheng

    2018-04-28

    To observe the changes of rapidly activated delayed rectifier potassium channel (IKr) and slowly activated delayed rectifier potassium channel (IKs) in cardiac hypertrophy and to evaluate the effects of IKr and IKs blocker on the incidence of ventricular arrhythmias in guinea pigs with left ventricular hypertrophy (LVH).
 Methods: Guinea pigs were divided into a sham operation group and a left ventricular hypertrophy (LVH) group. LVH model was prepared. Whole cell patch-clamp technique was used to record IKr and IKs tail currents in a guinea pig model with LVH. The changes of QTc and the incidence rate of ventricular arrhythmias in LVH guinea pigs were observed by using the IKr and IKs blockers.
 Results: Compared with cardiac cells in the control group, the interventricular septal thickness at end systole (IVSs), left ventricular posterior wall thickness at end systole (LVPWs), QTc interval and cell capacitance in guinea pigs with LVH were significantly increased (Pguinea pigs with LVH compared with the control guinea pigs. In contrast, IKs blocker produced modest increase in QTc interval in guinea pigs of control group with no increase in LVH animals. IKs blocker did not induce ventricular arrhythmias incidence in either control or LVH animals.
 Conclusion: The cardiac hypertrophy-induced arrhythmogenesis is due to the down-regulation 
of IKs.

  6. Left ventricular hypertrophy: virtuous intentions, malign consequences.

    Science.gov (United States)

    Pokharel, Saraswati; Sharma, Umesh C; Pinto, Yigal M

    2003-06-01

    Left ventricular hypertrophy (LVH) is currently the focus of intense cardiovascular research, with the resultant rapid evolution of novel concepts relating to its exceedingly complex pathophysiology. In addition to the alterations in signal transduction and disturbances in Ca(2+) homeostasis, there are structural changes in myofilaments, disorganization of the cytoskeletal framework and increased collagen synthesis. LVH is associated with progressive left ventricular remodeling that culminates to heart failure. The modern treatment of left ventricular hypertrophy is now largely based on the hypothesis that neuroendocrine activation is important in the progression of the disease and inhibition of neurohormones is likely to have long-term benefit with regard to morbidity and mortality. Drugs specifically designed to unload the left ventricle, such as diuretics and vasodilators, appears to be less effective in reducing LV mass and improving prognosis. Thus, the evolution of treatment for LVH itself has provided much enlightenment for our understanding of the fundamental biology of the disorder.

  7. Pathophysiologic assessment of left ventricular hypertrophy and strain in asymptomatic patients with essential hypertension

    International Nuclear Information System (INIS)

    Pringle, S.D.; Macfarlane, P.W.; McKillop, J.H.; Lorimer, A.R.; Dunn, F.G.

    1989-01-01

    To investigate the significance of the electrocardiographic (ECG) pattern of left ventricular hypertrophy and strain, two groups of asymptomatic patients with essential hypertension were compared. The patients were similar in terms of age, smoking habit, serum cholesterol and blood pressure levels, but differed in the presence (Group I, n = 23) or absence (Group II, n = 23) of the ECG pattern of left ventricular hypertrophy and strain. Group I patients had significantly more episodes of exercise-induced ST segment depression (14 versus 4, p less than 0.05) and reversible thallium perfusion abnormalities (11 of 23 versus 3 of 23, p less than 0.05) despite similar exercise capacity and absence of chest pain. Nonsustained ventricular tachycardia was detected on 24 h ambulatory ECG monitoring in two patients in Group I, but no patient in Group II. Coronary arteriography performed in 20 Group I patients demonstrated significant coronary artery disease in 8 patients. This study has shown that there is a subgroup of hypertensive patients with ECG left ventricular hypertrophy and strain who have covert coronary artery disease. This can be detected by thallium perfusion scintigraphy, and may contribute to the increased risk known to be associated with this ECG abnormality

  8. Role of bone marrow-derived CD11c+ dendritic cells in systolic overload-induced left ventricular inflammation, fibrosis and hypertrophy.

    Science.gov (United States)

    Wang, Huan; Kwak, Dongmin; Fassett, John; Liu, Xiaohong; Yao, Wu; Weng, Xinyu; Xu, Xin; Xu, Yawei; Bache, Robert J; Mueller, Daniel L; Chen, Yingjie

    2017-05-01

    Inflammatory responses play an important role in the development of left ventricular (LV) hypertrophy and dysfunction. Recent studies demonstrated that increased T-cell infiltration and T-cell activation contribute to LV hypertrophy and dysfunction. Dendritic cells (DCs) are professional antigen-presenting cells that orchestrate immune responses, especially by modulating T-cell function. In this study, we investigated the role of bone marrow-derived CD11c + DCs in transverse aortic constriction (TAC)-induced LV fibrosis and hypertrophy in mice. We observed that TAC increased the number of CD11c + cells and the percentage of CD11c + MHCII + (major histocompatibility complex class II molecule positive) DCs in the LV, spleen and peripheral blood in mice. Using bone marrow chimeras and an inducible CD11c + DC ablation model, we found that depletion of bone marrow-derived CD11c + DCs significantly attenuated LV fibrosis and hypertrophy in mice exposed to 24 weeks of moderate TAC. CD11c + DC ablation significantly reduced TAC-induced myocardial inflammation as indicated by reduced myocardial CD45 + cells, CD11b + cells, CD8 + T cells and activated effector CD8 + CD44 + T cells in LV tissues. Moreover, pulsing of autologous DCs with LV homogenates from TAC mice promoted T-cell proliferation. These data indicate that bone marrow-derived CD11c + DCs play a maladaptive role in hemodynamic overload-induced cardiac inflammation, hypertrophy and fibrosis through the presentation of cardiac self-antigens to T cells.

  9. Second statement of the working group on electrocardiographic diagnosis of left ventricular hypertrophy

    DEFF Research Database (Denmark)

    Bacharova, Ljuba; Estes, E Harvey; Bang, Lia E

    2011-01-01

    The Working Group on Electrocardiographic Diagnosis of Left Ventricular Hypertrophy, appointed by the Editor of the Journal of Electrocardiology, presents the alternative conceptual model for the ECG diagnosis of left ventricular hypertrophy (LVH). It is stressed that ECG is a record of electrica...

  10. Left ventricular hypertrophy : virtuous intentions, malign consequences

    NARCIS (Netherlands)

    Pokharel, S; Sharma, UC; Pinto, YM

    Left ventricular hypertrophy (LVH) is currently the focus of intense cardiovascular research, with the resultant rapid evolution of novel concepts relating to its exceedingly complex pathophysiology. In addition to the alterations in signal transduction and disturbances in Ca2+ homeostasis, there

  11. Left ventricular hypertrophy: virtuous intentions, malign consequences

    NARCIS (Netherlands)

    Pokharel, Saraswati; Sharma, Umesh C.; Pinto, Yigal M.

    2003-01-01

    Left ventricular hypertrophy (LVH) is currently the focus of intense cardiovascular research, with the resultant rapid evolution of novel concepts relating to its exceedingly complex pathophysiology. In addition to the alterations in signal transduction and disturbances in Ca(2+) homeostasis, there

  12. Effects of Resistance Training on Ventricular Function and Hypertrophy in a Rat Model

    Science.gov (United States)

    Barauna, Valério Garrone; Rosa, Kaleizu Teodoro; Irigoyen, Maria Cláudia; de Oliveira, Edilamar Menezes

    2007-01-01

    Objective: The purpose of this study was to follow the ventricular function and cardiac hypertrophy in rats undergoing a resistance-training program for a period of 3 months. Design: Forty animals were divided into two major groups: control (n=16) and resistance trained (n=24). From the resistance-trained group, 12 animals were resistance trained for 1 month and another 12 for 3 months. The resistance-training protocol was performed with 4 sets of 12 repetitions using 65% to 75% of one repetition maximum (maximum lifted weight with the exercise apparatus). Methods: Echocardiographic analysis was performed at the beginning of the resistance-training period and at the end of each month. The repetition maximum was measured every 2 weeks. Cardiac hypertrophy was determined by echocardiography, by the absolute weight of the cardiac chambers and by histology of the left ventricle. Results: Before resistance training, both groups had similar repetition maximums, ranging from 1.8-fold to 2-fold the body weight; however, at the end of the resistance-training period, the repetition maximum of the resistance-trained group was 6-fold greater than the body weight. The left ventricular mass as assessed by echocardiography was 8%, 12% and 16% larger in the resistance-trained group than in the control group in the first, second and third months, respectively. This hypertrophy showed a similar increase in the interventricular septum and in the free posterior wall mass. There was no reduction in the end-diastolic left ventricular internal diameter during the 3-month resistance-training period. Systolic function did not differ between the groups throughout the resistance-training period. Conclusion: Resistance training induces the development of concentric cardiac hypertrophy without ventricular dysfunction or cavity reduction. Although diastolic function was not completely investigated, we cannot exclude the possibility that resistance training results in diastolic dysfunction. PMID

  13. Association of heart failure hospitalizations with combined electrocardiography and echocardiography criteria for left ventricular hypertrophy

    DEFF Research Database (Denmark)

    Gerdts, Eva; Okin, Peter M; Boman, Kurt

    2012-01-01

    The value of performing echocardiography in hypertensive patients with electrocardiographic left ventricular hypertrophy (LVH) is uncertain.......The value of performing echocardiography in hypertensive patients with electrocardiographic left ventricular hypertrophy (LVH) is uncertain....

  14. Screening for Fabry Disease in Left Ventricular Hypertrophy: Documentation of a Novel Mutation

    Energy Technology Data Exchange (ETDEWEB)

    Baptista, Ana, E-mail: baptista-ana@hotmail.com; Magalhães, Pedro; Leão, Sílvia; Carvalho, Sofia; Mateus, Pedro; Moreira, Ilídio [Centro Hospitalar de Trás-os-Montes e Alto Douro, Unidade de Vila Real (Portugal)

    2015-08-15

    Fabry disease is a lysosomal storage disease caused by enzyme α-galactosidase A deficiency as a result of mutations in the GLA gene. Cardiac involvement is characterized by progressive left ventricular hypertrophy. To estimate the prevalence of Fabry disease in a population with left ventricular hypertrophy. The patients were assessed for the presence of left ventricular hypertrophy defined as a left ventricular mass index ≥ 96 g/m{sup 2} for women or ≥ 116 g/m{sup 2} for men. Severe aortic stenosis and arterial hypertension with mild left ventricular hypertrophy were exclusion criteria. All patients included were assessed for enzyme α-galactosidase A activity using dry spot testing. Genetic study was performed whenever the enzyme activity was decreased. A total of 47 patients with a mean left ventricular mass index of 141.1 g/m{sup 2} (± 28.5; 99.2 to 228.5 g/m{sup 2}] were included. Most of the patients were females (51.1%). Nine (19.1%) showed decreased α-galactosidase A activity, but only one positive genetic test − [GLA] c.785G>T; p.W262L (exon 5), a mutation not previously described in the literature. This clinical investigation was able to establish the association between the mutation and the clinical presentation. In a population of patients with left ventricular hypertrophy, we documented a Fabry disease prevalence of 2.1%. This novel case was defined in the sequence of a mutation of unknown meaning in the GLA gene with further pathogenicity study. Thus, this study permitted the definition of a novel causal mutation for Fabry disease - [GLA] c.785G>T; p.W262L (exon 5)

  15. Screening for Fabry Disease in Left Ventricular Hypertrophy: Documentation of a Novel Mutation

    International Nuclear Information System (INIS)

    Baptista, Ana; Magalhães, Pedro; Leão, Sílvia; Carvalho, Sofia; Mateus, Pedro; Moreira, Ilídio

    2015-01-01

    Fabry disease is a lysosomal storage disease caused by enzyme α-galactosidase A deficiency as a result of mutations in the GLA gene. Cardiac involvement is characterized by progressive left ventricular hypertrophy. To estimate the prevalence of Fabry disease in a population with left ventricular hypertrophy. The patients were assessed for the presence of left ventricular hypertrophy defined as a left ventricular mass index ≥ 96 g/m 2 for women or ≥ 116 g/m 2 for men. Severe aortic stenosis and arterial hypertension with mild left ventricular hypertrophy were exclusion criteria. All patients included were assessed for enzyme α-galactosidase A activity using dry spot testing. Genetic study was performed whenever the enzyme activity was decreased. A total of 47 patients with a mean left ventricular mass index of 141.1 g/m 2 (± 28.5; 99.2 to 228.5 g/m 2 ] were included. Most of the patients were females (51.1%). Nine (19.1%) showed decreased α-galactosidase A activity, but only one positive genetic test − [GLA] c.785G>T; p.W262L (exon 5), a mutation not previously described in the literature. This clinical investigation was able to establish the association between the mutation and the clinical presentation. In a population of patients with left ventricular hypertrophy, we documented a Fabry disease prevalence of 2.1%. This novel case was defined in the sequence of a mutation of unknown meaning in the GLA gene with further pathogenicity study. Thus, this study permitted the definition of a novel causal mutation for Fabry disease - [GLA] c.785G>T; p.W262L (exon 5)

  16. Screening for Fabry Disease in Left Ventricular Hypertrophy: Documentation of a Novel Mutation

    Directory of Open Access Journals (Sweden)

    Ana Baptista

    2015-01-01

    Full Text Available Abstract Background: Fabry disease is a lysosomal storage disease caused by enzyme α-galactosidase A deficiency as a result of mutations in the GLA gene. Cardiac involvement is characterized by progressive left ventricular hypertrophy. Objective: To estimate the prevalence of Fabry disease in a population with left ventricular hypertrophy. Methods: The patients were assessed for the presence of left ventricular hypertrophy defined as a left ventricular mass index ≥ 96 g/m2 for women or ≥ 116 g/m2 for men. Severe aortic stenosis and arterial hypertension with mild left ventricular hypertrophy were exclusion criteria. All patients included were assessed for enzyme α-galactosidase A activity using dry spot testing. Genetic study was performed whenever the enzyme activity was decreased. Results: A total of 47 patients with a mean left ventricular mass index of 141.1 g/m2 (± 28.5; 99.2 to 228.5 g/m2] were included. Most of the patients were females (51.1%. Nine (19.1% showed decreased α-galactosidase A activity, but only one positive genetic test − [GLA] c.785G>T; p.W262L (exon 5, a mutation not previously described in the literature. This clinical investigation was able to establish the association between the mutation and the clinical presentation. Conclusion: In a population of patients with left ventricular hypertrophy, we documented a Fabry disease prevalence of 2.1%. This novel case was defined in the sequence of a mutation of unknown meaning in the GLA gene with further pathogenicity study. Thus, this study permitted the definition of a novel causal mutation for Fabry disease - [GLA] c.785G>T; p.W262L (exon 5.

  17. Hypertension and left ventricular hypertrophy in liquidators of consequences of the Chernobyl nuclear accident

    International Nuclear Information System (INIS)

    Shal'nova, S.A.; Smolenskij, A.V.; Shamarin, V.M.; Ehktova, T.V.; Berzak, N.V.; Zemtsova, N.A.; Timofeeva, S.G.; Zhavoronkova, E.A.; Muromtseva, G.A.; Arkad'eva, M.A.; Deev, A.D.

    1998-01-01

    Echocardiography was used for the study of prevalence of left ventricular hypertrophy in 839 liquidators of consequences of the Chernobyl accident. Prevalence of left ventricular hypertrophy (left ventricular myocardial mass 134 g/m 2 ) was 10.3, 13.4 and 22.5 % in liquidators with normal blood pressure, borderline hypertension and hypertension, respectively. Liquidators with normal blood pressure had significantly greater left ventricular myocardial mass than normotensive men from general population while liquidators and non liquidators with hypertension had equal values of this parameter [ru

  18. beta-Adrenergic and cholinergic receptors in hypertension-induced hypertrophy

    International Nuclear Information System (INIS)

    Vatner, D.E.; Kirby, D.A.; Homcy, C.J.; Vatner, S.F.

    1985-01-01

    Perinephritic hypertension was produced in dogs by wrapping one kidney with silk and removing the contralateral kidney 1 week later. Mean arterial pressure rose from 104 +/- 3 to 156 +/- 11 mm Hg, while left ventricular free wall weight, normalized for body weight, was increased by 49%. Muscarinic, cholinergic receptor density measured with [ 3 H]-quinuclidinyl benzilate, fell in hypertensive left ventricles (181 +/- 19 fmol/mg, n = 6; p less than 0.01) as compared with that found in normal left ventricles (272 +/- 16 fmol/mg, n = 8), while receptor affinity was not changed. The beta-adrenergic receptor density, measured by binding studies with [ 3 H]-dihydroalprenolol, rose in the hypertensive left ventricles (108 +/- 10 fmol/mg, n = 7; p less than 0.01) as compared with that found in normal left ventricles (68.6 +/- 5.2 fmol/mg, n = 15), while beta-adrenergic receptor affinity decreased in the hypertensive left ventricles (10.4 +/- 1.2 nM) compared with that found in the normal left ventricles (5.0 +/- 0.7 nM). Plasma norepinephrine levels were similar in the two groups, but myocardial norepinephrine levels were depressed (p less than 0.05) in dogs with hypertension. Moderate left ventricular hypertrophy induced by long-term aortic banding in dogs resulted in elevations in beta-adrenergic receptor density (115 +/- 14 fmol/mg) and decreases in affinity (10.4 +/- 2.2 nM) similar to those observed in the dogs with left ventricular hypertrophy induced by hypertension. Thus, these results suggest that perinephritic hypertension in the dog induces divergent effects on cholinergic and beta-adrenergic receptor density. The increased beta-adrenergic receptor density and decreased affinity may be a characteristic of left ventricular hypertrophy rather than hypertension

  19. N-terminal pro B-type natriuretic peptide predicts mortality in patients with left ventricular hypertrophy.

    Science.gov (United States)

    Garcia, Santiago; Akbar, Muhammad S; Ali, Syed S; Kamdar, Forum; Tsai, Michael Y; Duprez, Daniel A

    2010-09-03

    Left ventricular hypertrophy adversely affects outcomes in patients with hypertension. Whether N-terminal pro B-type natriuretic peptide (NT-proBNP) adds incremental prognostic information in patients with hypertension and left ventricular hypertrophy (LVH) is not well established. We aimed to study the prognostic value of NT-proBNP in hypertensive patients with LVH. Echocardiography was performed in 232 patients (mean age 61±15, 102 males, 130 females) for the diagnosis of left ventricular hypertrophy. Left ventricular mass was measured according to The American Society of Echocardiography guidelines. A blood sample was taken for NT-proBNP determination. NT-proBNP levels were analyzed in quartiles after log transformation. Long term survival was established by review of electronic medical records. Arterial hypertension was present in 130 patients (56%) and left ventricular hypertrophy was present in 105 patients (45%). In patients with left ventricular hypertrophy, NT-proBNP levels predicted long term survival (Chi-square=10, p=0.01). After adjusting by age, presence of coronary artery disease, ejection fraction, diabetes status, and hypertension; patients in highest NT pro-BNP quartile were twice as likely to die when compared to patients in the lowest NT-ptoBNP quartile (OR=2.2, 95% CI=1.0-4.6, p=0.03). NT-proBNP is an independent predictor of survival in patients with hypertension and increased left ventricular mass. Copyright © 2009 Elsevier B.V. All rights reserved.

  20. Skin Sodium Concentration Correlates with Left Ventricular Hypertrophy in CKD.

    Science.gov (United States)

    Schneider, Markus P; Raff, Ulrike; Kopp, Christoph; Scheppach, Johannes B; Toncar, Sebastian; Wanner, Christoph; Schlieper, Georg; Saritas, Turgay; Floege, Jürgen; Schmid, Matthias; Birukov, Anna; Dahlmann, Anke; Linz, Peter; Janka, Rolf; Uder, Michael; Schmieder, Roland E; Titze, Jens M; Eckardt, Kai-Uwe

    2017-06-01

    The pathogenesis of left ventricular hypertrophy in patients with CKD is incompletely understood. Sodium intake, which is usually assessed by measuring urinary sodium excretion, has been inconsistently linked with left ventricular hypertrophy. However, tissues such as skin and muscle may store sodium. Using 23 sodium-magnetic resonance imaging, a technique recently developed for the assessment of tissue sodium content in humans, we determined skin sodium content at the level of the calf in 99 patients with mild to moderate CKD (42 women; median [range] age, 65 [23-78] years). We also assessed total body overhydration (bioimpedance spectroscopy), 24-hour BP, and left ventricular mass (cardiac magnetic resonance imaging). Skin sodium content, but not total body overhydration, correlated with systolic BP ( r =0.33, P =0.002). Moreover, skin sodium content correlated more strongly than total body overhydration did with left ventricular mass ( r =0.56, P skin sodium content is a strong explanatory variable for left ventricular mass, unaffected by BP and total body overhydration. In conclusion, we found skin sodium content to be closely linked to left ventricular mass in patients with CKD. Interventions that reduce skin sodium content might improve cardiovascular outcomes in these patients. Copyright © 2017 by the American Society of Nephrology.

  1. Population-specific left ventricular hypertrophy in three groups from the northeastern region of India.

    Science.gov (United States)

    Borah, P K; Hazarika, N C; Biswas, D; Kalita, H C; Mahanta, J

    2010-01-01

    People living in the hills are continuously exposed to strenuous physical activity for their day-to-day work. Besides hypertension, left ventricular hypertrophy in different populations may be related to continuous physical activity. Electrocardiogram, blood pressure and sociodemographic information of 12 252 subjects > or = 30 years of age from three different population groups living in Mizoram (hilly) and Assam (plain) were recorded. Of them, 8058 were from Mizoram and 3180 and 1014 were Indigenous Assamese and tea garden workers of Assam. Among the subjects from Mizoram the percentage of smokers (41.9%), mean (SD) BMI (21.9 [3.8]) and waist-hip ratio (0.87 [0.02]) were significantly higher than in those from other groups. Tea garden workers had a higher mean systolic blood pressure (145.2 [25.7]) and diastolic blood pressure (87.6 [13.6]). The prevalence of left ventricular hypertrophy was highest among tea garden workers (16.5%) followed by people from Mizoram (3.7%) and the indigenous Assamese (2%) people. In spite of a significantly higher prevalence of hypertension among the indigenous Assamese community than among those from Mizoram, left ventricular hypertrophy was found to be lower in the former. High prevalence of left ventricular hypertrophy among tea garden workers was possibly related to a higher prevalence of hypertension but the higher prevalence of left ventricular hypertrophy among people from Mizoram might be related to more physical activity.

  2. Limited Relationship of Voltage Criteria for Electrocardiogram Left Ventricular Hypertrophy to Cardiovascular Mortality.

    Science.gov (United States)

    Ha, Le Dung; Elbadawi, Ayman; Froelicher, Victor F

    2018-01-01

    Numerous methods have been proposed for diagnosing left ventricular hypertrophy using the electrocardiogram. They have limited sensitivity for recognizing pathological hypertrophy, at least in part due to their inability to distinguish pathological from physiological hypertrophy. Our objective is to compare the major electrocardiogram-left ventricular hypertrophy criteria using cardiovascular mortality as a surrogate for pathological hypertrophy. This study was a retrospective analysis of 16,253 veterans electrocardiogram-left ventricular hypertrophy, and there were 744 cardiovascular deaths (annual cardiovascular mortality 0.25%). Receiver operating characteristic analysis demonstrated that the greatest area under the curve (AUC) for classification of cardiovascular death was obtained using the Romhilt-Estes score (0.63; 95% confidence interval, 0.61-0.65). Most of the voltage-only criteria had nondiagnostic area under the curves, with the Cornell being the best at 0.59 (95% confidence interval, 0.57-0.62). When the components of the Romhilt-Estes score were examined using step-wise Wald analysis, the voltage criteria dropped from the model. The Romhilt-Estes score ≥ 4, the Cornell, and the Peguero had the highest association with cardiovascular mortality (adjusted hazard ratios 2.2, 2.0, and 2.1, consecutively). None of the electrocardiogram leads with voltage criteria exhibited sufficient classification power for clinical use. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. Longitudinal strain bull's eye plot patterns in patients with cardiomyopathy and concentric left ventricular hypertrophy.

    Science.gov (United States)

    Liu, Dan; Hu, Kai; Nordbeck, Peter; Ertl, Georg; Störk, Stefan; Weidemann, Frank

    2016-05-10

    Despite substantial advances in the imaging techniques and pathophysiological understanding over the last decades, identification of the underlying causes of left ventricular hypertrophy by means of echocardiographic examination remains a challenge in current clinical practice. The longitudinal strain bull's eye plot derived from 2D speckle tracking imaging offers an intuitive visual overview of the global and regional left ventricular myocardial function in a single diagram. The bull's eye mapping is clinically feasible and the plot patterns could provide clues to the etiology of cardiomyopathies. The present review summarizes the longitudinal strain, bull's eye plot features in patients with various cardiomyopathies and concentric left ventricular hypertrophy and the bull's eye plot features might serve as one of the cardiac workup steps on evaluating patients with left ventricular hypertrophy.

  4. Left ventricular hypertrophy among chronic kidney disease patients ...

    African Journals Online (AJOL)

    Introduction: The presence of left ventricular hypertrophy (LVH) in patients with Chronic Kidney Disease (CKD) is associated with worsening cardiovascular outcomes. There is a dearth of data on LVH in Ghanaian CKD patients. Methods: This was a cross sectional study carried out at the Komfo Anokye Teaching Hospital ...

  5. Inhibition of Uncoupling Protein 2 Attenuates Cardiac Hypertrophy Induced by Transverse Aortic Constriction in Mice

    Directory of Open Access Journals (Sweden)

    Xiao-Bing Ji

    2015-07-01

    Full Text Available Background: Uncoupling protein 2 (UCP2 is critical in regulating energy metabolism. Due to the significant change in energy metabolism of myocardium upon pressure overload, we hypothesize that UCP2 could contribute to the etiology of cardiac hypertrophy. Methods: Adult male C57BL/6J mice were subjected to pressure overload by using transverse aortic constriction (TAC, and then received genipin (a UCP2 selective inhibitor; 25 mg/kg/d, ip or vehicle for three weeks prior to histologic assessment of myocardial hypertrophy. ATP concentration, ROS level, and myocardial apoptosis were also examined. A parallel set of experiments was also conducted in UCP2-/- mice. Results: TAC induced left ventricular hypertrophy, as reflected by increased ventricular weight/thickness and increased size of myocardial cell (vs. sham controls. ATP concentration was decreased; ROS level was increased. Apoptosis and fibrosis markers were increased. TAC increased mitochondrial UCP2 expression in the myocardium at both mRNA and protein levels. Genipin treatment attenuated cardiac hypertrophy and the histologic/biochemical changes described above. Hypertrophy and associated changes induced by TAC in UCP2-/- mice were much less pronounced than in WT mice. Conclusions: Blocking UCP2 expression attenuates cardiac hypertrophy induced by pressure overload.

  6. Left Ventricular Hypertrophy in Pediatric Hypertension: A Mini Review

    Directory of Open Access Journals (Sweden)

    Robert P. Woroniecki

    2017-05-01

    Full Text Available Adults with arterial hypertension (HTN have stroke, myocardial infarction, end-stage renal disease (ESRD, or die at higher rates than those without. In children, HTN leads to target organ damage, which includes kidney, brain, eye, blood vessels, and heart, which precedes “hard outcomes” observed in adults. Left ventricular hypertrophy (LVH or an anatomic and pathologic increase in left ventricular mass (LVM in response to the HTN is a pediatric surrogate marker for HTN-induced morbidity and mortality in adults. This mini review discusses current definitions, clinically relevant methods of LVM measurements and normalization methods, its epidemiology, management, and issue of reversibility in children with HTN. Pediatric definition of LVH and abnormal LVM is not uniformed. With multiple definitions, prevalence of pediatric HTN-induced LVH is difficult to ascertain. In addition while in adults cardiac magnetic resonance imaging is considered “the gold standard” for LVM and LVH determination, pediatric data are limited to “special populations”: ESRD, transplant, and obese children. We summarize available data on pediatric LVH treatment and reversibility and offer future directions in addressing LVH in children with HTN.

  7. Factors influencing left ventricular hypertrophy in children and adolescents with or without family history of premature myocardial infarction

    Directory of Open Access Journals (Sweden)

    Seyyed Mohsen Hosseini

    2014-01-01

    Result : The results showed that among the studied variables, gender, age, body mass index, and blood pressure were associated with the left ventricular hypertrophy. Conclusion: Considering the results and previous studies in this field, it was observed that left ventricular hypertrophy exists at early ages, which is very dangerous and can lead to heart diseases at early ages. Factors such as being overweight, having high blood pressure, and being male cause left ventricular hypertrophy and lead to undiagnosable heart diseases.

  8. Study on thallium-201 myocardial perfusion scanning for detection of right ventricular hypertrophy in chronic pulmonary disease

    International Nuclear Information System (INIS)

    Kawai, Seiki

    1980-01-01

    Thallium-201 myocardial perfusion scanning was performed in 34 patients with chronic pulmonary disease for the purpose of detecting right ventricular hypertrophy. Thallium-201 activity ratio of left ventricle plus ventricular septum/right ventricle (TAR) was significantly correlated with hemodynamic findings such as pulmonary arterial mean pressure (r = -0.75, p 2 (p < 0.001). Assuming that TAR < 2 or TAR = 2 would indicate pulmonary hypertension, sensitivity was 95%, specificity 79%, validity score 75%, false positive 14% and false negative was 8%. TAR was compared with left to right ventricular mass ratio using Fulton's method in 6 autopsied patients in whom thallium-201 myocardial perfusion scanning were performed within three months before death. TAR closely correlated with left to right ventricular mass ratio (r = 0.978, p < 0.001). The comparison of validity of TAR with those of electrocardiographic interpretation according to WHO, Sasamoto, Roman or Milnor for the detection of right ventricular hypertrophy revealed the former was much superior to all of latters. From the results obtained, it may be inferred that TAR reflects the degree of pulmonary hypertension and anatomical right ventricular hypertrophy and is a useful non-invasive method to detect right ventricular hypertrophy in chronic pulmonary disease. (J.P.N.)

  9. Periodontitis and myocardial hypertrophy.

    Science.gov (United States)

    Suzuki, Jun-Ichi; Sato, Hiroki; Kaneko, Makoto; Yoshida, Asuka; Aoyama, Norio; Akimoto, Shouta; Wakayama, Kouji; Kumagai, Hidetoshi; Ikeda, Yuichi; Akazawa, Hiroshi; Izumi, Yuichi; Isobe, Mitsuaki; Komuro, Issei

    2017-04-01

    There is a deep relationship between cardiovascular disease and periodontitis. It has been reported that myocardial hypertrophy may be affected by periodontitis in clinical settings. Although these clinical observations had some study limitations, they strongly suggest a direct association between severity of periodontitis and left ventricular hypertrophy. However, the detailed mechanisms between myocardial hypertrophy and periodontitis have not yet been elucidated. Recently, we demonstrated that periodontal bacteria infection is closely related to myocardial hypertrophy. In murine transverse aortic constriction models, a periodontal pathogen, Aggregatibacter actinomycetemcomitans markedly enhanced cardiac hypertrophy with matrix metalloproteinase-2 activation, while another pathogen Porphyromonas gingivalis (P.g.) did not accelerate these pathological changes. In the isoproterenol-induced myocardial hypertrophy model, P.g. induced myocardial hypertrophy through Toll-like receptor-2 signaling. From our results and other reports, regulation of chronic inflammation induced by periodontitis may have a key role in the treatment of myocardial hypertrophy. In this article, we review the pathophysiological mechanism between myocardial hypertrophy and periodontitis.

  10. Four-group classification of left ventricular hypertrophy based on ventricular concentricity and dilatation identifies a low-risk subset of eccentric hypertrophy in hypertensive patients

    DEFF Research Database (Denmark)

    Bang, Casper N; Gerdts, Eva; Aurigemma, Gerard P

    2014-01-01

    BACKGROUND: Left ventricular hypertrophy (LVH; high LV mass [LVM]) is traditionally classified as concentric or eccentric based on LV relative wall thickness. We evaluated the prediction of subsequent adverse events in a new 4-group LVH classification based on LV dilatation (high LV end...

  11. Ameliorative role of gemfibrozil against partial abdominal aortic constriction-induced cardiac hypertrophy in rats.

    Science.gov (United States)

    Singh, Amrit Pal; Singh, Randhir; Krishan, Pawan

    2015-04-01

    Fibrates are peroxisome proliferator-activated receptor-α agonists and are clinically used for treatment of dyslipidemia and hypertriglyceridemia. Fenofibrate is reported as a cardioprotective agent in various models of cardiac dysfunction; however, limited literature is available regarding the role of gemfibrozil as a possible cardioprotective agent, especially in a non-obese model of cardiac remodelling. The present study investigated the role of gemfibrozil against partial abdominal aortic constriction-induced cardiac hypertrophy in rats. Cardiac hypertrophy was induced by partial abdominal aortic constriction in rats and they survived for 4 weeks. The cardiac hypertrophy was assessed by measuring left ventricular weight to body weight ratio, left ventricular wall thickness, and protein and collagen content. The oxidative stress in the cardiac tissues was assessed by measuring thiobarbituric acid-reactive substances, superoxide anion generation, and reduced glutathione level. The haematoxylin-eosin and picrosirius red staining was used to observe cardiomyocyte diameter and collagen deposition, respectively. Moreover, serum levels of cholesterol, high-density lipoproteins, triglycerides, and glucose were also measured. Gemfibrozil (30 mg/kg, p.o.) was administered since the first day of partial abdominal aortic constriction and continued for 4 weeks. The partial abdominal aortic constriction-induced cardiac oxidative stress and hypertrophy are indicated by significant change in various parameters used in the present study that were ameliorated with gemfibrozil treatment in rats. No significant change in serum parameters was observed between various groups used in the present study. It is concluded that gemfibrozil ameliorates partial abdominal aortic constriction-induced cardiac oxidative stress and hypertrophy and in rats.

  12. Pattern of left ventricular hypertrophy seen on transthoracic echo in patients with hypertensive cardiomyopathy when compared with idiopathic hypertrophic cardiomyopathy

    International Nuclear Information System (INIS)

    Mirza, S. J.; Radaideh, G. A.

    2013-01-01

    Objective: To explore the pattern of left ventricular hypertrophy caused by hypertension and to compare it with idiopathic hypertrophic cardiomyopathy. Methods: The retrospective study was conducted at the echocardiography lab of Rashid Hospital, Dubai, from January 2009 to January 2010. Cases of 11 patients with significant left ventricular hypertrophy (septum >15mm) due to underlying hypertension were analysed and compared with 11 cases of idiopathic hypertrophic cardiography (septum >15mm) to assess the two groups with similar baseline echocardiographic features. Minitab software was used for statistical analysis. Results: Although the pattern of hypertrophy in hypertensive patients was more concentric (n=5; 45%), there was also asymmetrical septal hypertrophy in 4 (36%) cases, particularly the elderly with sigmoid shape septum. There was evidence of resting mid-cavity gradient due to reduced left ventricular end-systolic diameter in 4 (36%) cases. Conclusion: Although the equation between hypertension and left ventricular hypertrophy is more concentric, but it can be associated with left ventricular outflow tract obstruction and significant mid-cavity gradients similar to that seen in idiopathic hypertrophic cardiomyopathy. (author)

  13. Ventricular premature contraction in hypertrophic cardiomyopathy and essential hypertension with left ventricular hypertrophy

    International Nuclear Information System (INIS)

    Kobiki, Naoki

    1989-01-01

    In order to investigate the relationship of different morbid states of the hypertrophied myocardium to the appearance of ventricular premature contraction (VPC), we compared the VPC findings from Holter ECG with those of UCG and stress thallium-201 myocardial SPECT scintigraphy (stress scinti) in 31 patients with hypertrophic cardiomyopathy (HCM) and 20 with essential hypertension (HT). The HCM patients consisted of 21 with asymmetric hypertrophy (ASH), 3 with symmetric hypertrophy (SH), and 7 with apical hypertrophy (APH). We recognized positive findings on the stress scinti such as fixed perfusion defect (FD) or reversible perfusion defect (RD) in 11 patients (ASH 10, APH 1) out of 31 patients with HCM (35%). Positive findings were observed in only one patient out of 20 with HT (5%). We recognized a high grade VPC (grade 4a and 4b of Lown's criteria) in 8 of 11 scinti positive patients with HCM (ASH 7, APH 1)(73%), while high grade VPC appeared in 5 (all of them are ASH) out of 20 scinti negative patients with HCM (25%). Therefore, these findings suggest that high grade VPCs in HCM occur in relation to a myocardial perfusion defect. (author)

  14. Thymosin Beta 4 protects mice from monocrotaline-induced pulmonary hypertension and right ventricular hypertrophy.

    Directory of Open Access Journals (Sweden)

    Chuanyu Wei

    Full Text Available Pulmonary hypertension (PH is a progressive vascular disease of pulmonary arteries that impedes ejection of blood by the right ventricle. As a result there is an increase in pulmonary vascular resistance and pulmonary arterial pressure causing right ventricular hypertrophy (RVH and RV failure. The pathology of PAH involves vascular cell remodeling including pulmonary arterial endothelial cell (PAEC dysfunction and pulmonary arterial smooth muscle cell (PASMC proliferation. Current therapies are limited to reverse the vascular remodeling. Investigating a key molecule is required for development of new therapeutic intervention. Thymosin beta-4 (Tβ4 is a ubiquitous G-actin sequestering protein with diverse biological function and promotes wound healing and modulates inflammatory responses. However, it remains unknown whether Tβ4 has any protective role in PH. The purpose of this study is to evaluate the whether Tβ4 can be used as a vascular-protective agent. In monocrotaline (MCT-induced PH mouse model, we showed that mice treated with Tβ4 significantly attenuated the systolic pressure and RVH, compared to the MCT treated mice. Our data revealed for the first time that Tβ4 selectively targets Notch3-Col 3A-CTGF gene axis in preventing MCT-induced PH and RVH. Our study may provide pre-clinical evidence for Tβ4 and may consider as vasculo-protective agent for the treatment of PH induced RVH.

  15. Regression of electrocardiographic left ventricular hypertrophy during antihypertensive therapy and reduction in sudden cardiac death: the LIFE Study

    DEFF Research Database (Denmark)

    Wachtell, Kristian; Okin, Peter M; Olsen, Michael H

    2007-01-01

    BACKGROUND: Sudden cardiac death (SCD) occurs more often in patients with ECG left ventricular (LV) hypertrophy. However, whether LV hypertrophy regression is associated with a reduced risk of SCD remains unclear. METHODS AND RESULTS: The Losartan Intervention for End Point Reduction in Hypertens......BACKGROUND: Sudden cardiac death (SCD) occurs more often in patients with ECG left ventricular (LV) hypertrophy. However, whether LV hypertrophy regression is associated with a reduced risk of SCD remains unclear. METHODS AND RESULTS: The Losartan Intervention for End Point Reduction...... risk of SCD independently of treatment modality, blood pressure reduction, prevalent coronary heart disease, and other cardiovascular risk factors in hypertensive patients with LV hypertrophy. Udgivelsesdato: 2007-Aug-14...

  16. Tissue characteristics in left ventricular hypertrophy using magnetic resonance imaging

    International Nuclear Information System (INIS)

    Yoshida, Shigeru; Ueno, Yuji; Arita, Mikio; Nishio, Ichiro; Masuyama, Yoshiaki

    1988-01-01

    For 15 normotensive patients with asymmetric septal hypertrophy (ASH), 10 hypertensive patients with concentric hypertrophy (CH), and five normal subjects (N), we examined changes in myocardial T 1 and T 2 values related to the cardiac cycle. The usefulness of those values in differentiating diseases with left ventricular hypertrophy was evaluated. Left ventricular (LV) short-axis spin echo images and inversion recovery images were obtained at endsystolic and diastolic cardiac phases, and T 1 and T 2 images were calculated. The regional wall thickness (WT) and T 1 and T 2 values were measured in the anterior septum, anterior wall, lateral wall, posterior wall and posterior septum. Myocardial T 1 and T 2 values were significantly decreased in systole (T 1 : 185.6±37.9 msec, T 2 : 24.4±6.3 msec, mean±SD) compared to those in diastole (T 1 : 249.2±56.7 msec, T 2 : 31.7±9.4 msec). In both the ASH and CH groups, significant correlations were observed between diastolic T 1 values and WT (ASH: r = 0.80, p 2 values and WT (ASH: r = 0.58, p 1 values in the ASH group (343.4±40.5 msec) were significantly higher than those of the CH group (247.3±21.4 msec), although the mean wall thickness values were similar in both groups. The T 1 /WT and T 2 /WT were significantly lower in the CH group than those in the ASH and N groups. In conclusion, myocardial T 1 and T 2 values were related not only to the cardiac cycle, but to wall thickness and to types of hypertrophy. The T 1 and T 2 values may be useful for distinguishing hypertrophic cardiomyopathy from hypertrophy due to hypertension. (author)

  17. Differential diagnosis of left ventricular hypertrophy: usefulness of multimodality imaging and tissue characterization with cardiac magnetic resonance.

    Science.gov (United States)

    Izgi, Cemil; Vassiliou, Vassilis; Baksi, A John; Prasad, Sanjay K

    2016-11-01

    Differential diagnosis of asymmetrical left ventricular hypertrophy may be challenging, particularly in patients with history of hypertension. A middle-aged man underwent an echocardiographic examination during workup for hypertension, which unexpectedly showed significant asymmetrical septal hypertrophy and raised suspicion for hypertrophic cardiomyopathy. Cardiovascular magnetic resonance confirmed the asymmetrical hypertrophy. No myocardial late gadolinium contrast enhancement was seen. However, precontrast T1 mapping revealed a low native myocardial T1 value. This was highly suggestive of Anderson-Fabry disease, which was subsequently proved with very low alpha galactosidase enzyme levels and mutation analysis. The case illustrates clinical usefulness of multimodality imaging and the novel tissue characterization techniques for assessment of left ventricular hypertrophy. © 2016, Wiley Periodicals, Inc.

  18. Associations of Blood Pressure Dipping Patterns With Left Ventricular Mass and Left Ventricular Hypertrophy in Blacks: The Jackson Heart Study.

    Science.gov (United States)

    Abdalla, Marwah; Caughey, Melissa C; Tanner, Rikki M; Booth, John N; Diaz, Keith M; Anstey, D Edmund; Sims, Mario; Ravenell, Joseph; Muntner, Paul; Viera, Anthony J; Shimbo, Daichi

    2017-04-05

    Abnormal diurnal blood pressure (BP), including nondipping patterns, assessed using ambulatory BP monitoring, have been associated with increased cardiovascular risk among white and Asian adults. We examined the associations of BP dipping patterns (dipping, nondipping, and reverse dipping) with cardiovascular target organ damage (left ventricular mass index and left ventricular hypertrophy), among participants from the Jackson Heart Study, an exclusively black population-based cohort. Analyses included 1015 participants who completed ambulatory BP monitoring and had echocardiography data from the baseline visit. Participants were categorized based on the nighttime to daytime systolic BP ratio into 3 patterns: dipping pattern (≤0.90), nondipping pattern (>0.90 to ≤1.00), and reverse dipping pattern (>1.00). The prevalence of dipping, nondipping, and reverse dipping patterns was 33.6%, 48.2%, and 18.2%, respectively. In a fully adjusted model, which included antihypertensive medication use and clinic and daytime systolic BP, the mean differences in left ventricular mass index between reverse dipping pattern versus dipping pattern was 8.3±2.1 g/m 2 ( P pattern versus dipping pattern was -1.0±1.6 g/m 2 ( P =0.536). Compared with participants with a dipping pattern, the prevalence ratio for having left ventricular hypertrophy was 1.65 (95% CI, 1.05-2.58) and 0.96 (95% CI, 0.63-1.97) for those with a reverse dipping pattern and nondipping pattern, respectively. In this population-based study of blacks, a reverse dipping pattern was associated with increased left ventricular mass index and a higher prevalence of left ventricular hypertrophy. Identification of a reverse dipping pattern on ambulatory BP monitoring may help identify black at increased risk for cardiovascular target organ damage. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  19. The 4th Report of the Working Group on ECG diagnosis of Left Ventricular Hypertrophy

    DEFF Research Database (Denmark)

    Bacharova, Ljuba; Estes, Harvey E; Schocken, Douglas D

    2016-01-01

    The 4th Report provides a brief review of publications focused on the electrocardiographic diagnosis of left ventricular hypertrophy published during the period of 2010 to 2016 by the members of the Working Group on ECG diagnosis of Left Ventricular Hypertrophy. The Working Group recommended...... that ECG research and clinical attention be redirected from the estimation of LVM to the identification of electrical remodeling, to better understanding the sequence of events connecting electrical remodeling to outcomes. The need for a re-definition of terms and for a new paradigm is also stressed....

  20. Left ventricular hypertrophy in valvular aortic stenosis: mechanisms and clinical implications.

    Science.gov (United States)

    Rader, Florian; Sachdev, Esha; Arsanjani, Reza; Siegel, Robert J

    2015-04-01

    Valvular aortic stenosis is the second most prevalent adult valve disease in the United States and causes progressive pressure overload, invariably leading to life-threatening complications. Surgical aortic valve replacement and, more recently, transcatheter aortic valve replacement effectively relieve the hemodynamic burden and improve the symptoms and survival of affected individuals. However, according to current American College of Cardiology/American Heart Association guidelines on the management of valvular heart disease, the indications for aortic valve replacement, including transcatheter aortic valve replacement, are based primarily on the development of clinical symptoms, because their presence indicates a dismal prognosis. Left ventricular hypertrophy develops in a sizeable proportion of patients before the onset of symptoms, and a growing body of literature demonstrates that regression of left ventricular hypertrophy resulting from aortic stenosis is incomplete after aortic valve replacement and associated with adverse early postoperative outcomes and worse long-term outcomes. Thus, reliance on the development of symptoms alone without consideration of structural abnormalities of the myocardium for optimal timing of aortic valve replacement potentially constitutes a missed opportunity to prevent postoperative morbidity and mortality from severe aortic stenosis, especially in the face of the quickly expanding indications of lower-risk transcatheter aortic valve replacement. The purpose of this review is to discuss the mechanisms and clinical implications of left ventricular hypertrophy in severe valvular aortic stenosis, which may eventually move to center stage as an indication for aortic valve replacement in the asymptomatic patient. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Crucial role of rho-kinase in pressure overload-induced right ventricular hypertrophy and dysfunction in mice.

    Science.gov (United States)

    Ikeda, Shohei; Satoh, Kimio; Kikuchi, Nobuhiro; Miyata, Satoshi; Suzuki, Kota; Omura, Junichi; Shimizu, Toru; Kobayashi, Kenta; Kobayashi, Kazuto; Fukumoto, Yoshihiro; Sakata, Yasuhiko; Shimokawa, Hiroaki

    2014-06-01

    Right ventricular (RV) failure is the leading cause of death in various cardiopulmonary diseases, including pulmonary hypertension. It is generally considered that the RV is vulnerable to pressure overload as compared with the left ventricle (LV). However, as compared with LV failure, the molecular mechanisms of RV failure are poorly understood, and hence therapeutic targets of the disorder remain to be elucidated. Thus, we aimed to identify molecular therapeutic targets for RV failure in a mouse model of pressure overload. To induce pressure overload to respective ventricles, we performed pulmonary artery constriction or transverse aortic constriction in mice. We first performed microarray analysis and found that the molecules related to RhoA/Rho-kinase and integrin pathways were significantly upregulated in the RV with pulmonary artery constriction compared with the LV with transverse aortic constriction. Then, we examined the responses of both ventricles to chronic pressure overload in vivo. We demonstrated that compared with transverse aortic constriction, pulmonary artery constriction caused greater extents of mortality, Rho-kinase expression (especially ROCK2 isoform), and oxidative stress in pressure-overloaded RV, reflecting the weakness of the RV in response to pressure overload. Furthermore, mice with myocardial-specific overexpression of dominant-negative Rho-kinase showed resistance to pressure overload-induced hypertrophy and dysfunction associated with reduced oxidative stress. Finally, dominant-negative Rho-kinase mice showed a significantly improved long-term survival in both pulmonary artery constriction and transverse aortic constriction as compared with littermate controls. These results indicate that the Rho-kinase pathway plays a crucial role in RV hypertrophy and dysfunction, suggesting that the pathway is a novel therapeutic target of RV failure in humans. © 2014 American Heart Association, Inc.

  2. Development of left ventricular hypertrophy in a novel porcine model of mitral regurgitation

    DEFF Research Database (Denmark)

    Ravn, Nathja; Zois, Nora Elisabeth; Moesgaard, Sophia Gry

    2014-01-01

    OBJECTIVES: We aimed to develop a porcine model for chronic nonischemic mitral regurgitation (MR) to investigate left ventricular (LV) enlargement and eccentric hypertrophy. DESIGN: Nonischemic MR was induced in 30 pigs by open-chest immobilization of the posterior mitral leaflet by transannular...... (LVIDd) from baseline to follow-up was significantly higher in the sMR group compared to that of the control group (P = 0.0017). Furthermore, LV weight was significantly increased in the mMR (P = 0.047) and the sMR (P = 0.0087) groups compared to that of the control group. CONCLUSIONS: A new model...

  3. SERUM IGF-I AND HORMONAL RESPONSES TO INCREMENTAL EXERCISE IN ATHLETES WITH AND WITHOUT LEFT VENTRICULAR HYPERTROPHY

    Directory of Open Access Journals (Sweden)

    Aleksandra Zebrowska

    2009-03-01

    Full Text Available We investigated the response of insulin-like growth factor (IGF- I, insulin-like growth factor binding protein-3 (IGFBP-3 and some hormones, i.e., testosterone (T, growth hormone (GH, cortisol (C, and insulin (I, to maximal exercise in road cyclists with and without diagnosed left ventricular hypertrophy. M-mode and two-dimensional Doppler echocardiography was performed in 30 professional male endurance athletes and a group of 14 healthy untrained subjects using a Hewlett-Packard Image Point HX ultrasound system with standard imaging transducers. Echocardiography and an incremental physical exercise test were performed during the competitive season. Venous blood samples were drawn before and immediately after the maximal cycling exercise test for determination of somatomedin and hormonal concentrations. The basal concentration of IGF-I was statistically higher (p < 0.05 in athletes with left ventricular muscle hypertrophy (LVH when compared to athletes with a normal upper limit of the left ventricular wall (LVN (p < 0.05 and to the control group (CG (p < 0.01. The IGF-I level increased significantly at maximal intensity of incremental exercise in CG (p < 0.01, LVN (p < 0.05 and LVH (p < 0.05 compared to respective values at rest. Long-term endurance training induced an increase in resting (p < 0.01 and post-exercise (p < 0.05 IGF-I/IGFBP-3 ratio in athletes with LVH compared to LVN. The testosterone (T level was lower in LVH at rest compared to LVN and CG groups (p < 0.05. These results indicate that resting serum IGF-I concentration were higher in trained subjects with LVH compared to athletes without LVH. Serum IGF- I/IGFBP-3 elevation at rest and after exercise might suggest that IGF-I act as a potent stimulant of left ventricular hypertrophy in chronically trained endurance athletes

  4. Influence of left ventricular hypertrophy on infarct size and left ventricular ejection fraction in ST-elevation myocardial infarction

    International Nuclear Information System (INIS)

    Małek, Łukasz A.; Śpiewak, Mateusz; Kłopotowski, Mariusz; Petryka, Joanna; Mazurkiewicz, Łukasz; Kruk, Mariusz; Kępka, Cezary; Miśko, Jolanta; Rużyłło, Witold; Witkowski, Adam

    2012-01-01

    Background: Left ventricular hypertrophy (LVH) predisposes to larger infarct size, which may be underestimated by the left ventricular ejection fraction (LVEF) due to supranormal systolic performance often present in patients with LVH. The aim of the study was to compare infarct size and LVEF in patients with ST-segment elevation myocardial infarction (STEMI) and increased left ventricular mass on cardiac magnetic resonance (CMR). Methods: The study included unselected group of 52 patients (61 ± 11 years, 69% male) with first STEMI who had CMR after median 5 days from the onset of the event. Left ventricular hypertrophy (LVH) was defined as left ventricular mass index exceeding 95th percentile of references values for age and gender. Infarct size was assessed with means of late gadolinium enhancement (LGE). Results: LVH was found in 16 patients (31%). In comparison to the rest of the group, patients with LVH had higher absolute and relative infarct mass (p = 0.002 and p = 0.02, respectively). LVH was related to higher prevalence of microvascular obstruction and myocardial haemorrhage and higher number of LV segments with transmural necrosis (p = 0.02, p = 0.01 and p = 0.01, respectively). Despite marked difference in the infarct size between both studied subgroups there was no difference in LVEF and mean number of dysfunctional LV segments. Conclusions: Patients with LVH undergoing STEMI have larger infarct size underestimated by the LV systolic performance in comparison to patients without LVH.

  5. Cytoskeletal role in the transition from compensated to decompensated hypertrophy during adult canine left ventricular pressure overloading

    Science.gov (United States)

    Tagawa, H.; Koide, M.; Sato, H.; Zile, M. R.; Carabello, B. A.; Cooper, G. 4th

    1998-01-01

    Increased microtubule density causes cardiocyte contractile dysfunction in right ventricular (RV) pressure-overload hypertrophy, and these linked phenotypic and contractile abnormalities persist and progress during the transition to failure. Although more severe in cells from failing than hypertrophied RVs, the mechanical defects are normalized in each case by microtubule depolymerization. To define the role of increased microtubule density in left ventricular (LV) pressure-overload hypertrophy and failure, in a given LV we examined ventricular mechanics, sarcomere mechanics, and free tubulin and microtubule levels in control dogs and in dogs with aortic stenosis both with LV hypertrophy alone and with initially compensated hypertrophy that had progressed to LV muscle failure. In comparing initial values with those at study 8 weeks later, dogs with hypertrophy alone had a very substantial increase in LV mass but preservation of a normal ejection fraction and mean systolic wall stress. Dogs with hypertrophy and associated failure had a substantial but lesser increase in LV mass and a reduction in ejection fraction, as well as a marked increase in mean systolic wall stress. Cardiocyte contractile function was equivalent, and unaffected by microtubule depolymerization, in cells from control LVs and those with compensated hypertrophy. In contrast, cardiocyte contractile function in cells from failing LVs was quite depressed but was normalized by microtubule depolymerization. Microtubules were increased only in failing LVs. These contractile and cytoskeletal changes, when assayed longitudinally in a given dog by biopsy, appeared in failing ventricles only when wall stress began to increase and function began to decrease. Thus, the microtubule-based cardiocyte contractile dysfunction characteristic of pressure-hypertrophied myocardium, originally described in the RV, obtains equally in the LV but is shown here to have a specific association with increased wall stress.

  6. Non-gated computed tomography of left ventricular hypertrophy

    International Nuclear Information System (INIS)

    Harada, Junta

    1983-01-01

    Non-ECG gated computed tomography (CT) of the heart was carried out in 19 cases with cardiovascular diseases; 4 with mitral stenosis, 3 with aortic valve disease, 2 with combined valve disease, 8 with hypertrophic cardiomyopathy and one myocardial infarction and one aortic aneurysm. All cardiac diseases were studied by echocardiography and 13 of them further investigated by intracadiac catheterization. The interventricular septum and the apical and posterolateral wall of the left ventricle were segmentally evaluated as to relative wall thickness of myocardium on CT. The wall thickness was directly measured on left ventricular cine angiograms in 13 cases. O-G vector calculated by CT was compatible with the palne of vectorcardiography in evaluating left ventricular hypertorphy. Conclusion were as follows: 1) The degree and site of myocardial hypertrophy were detected by CT with satisfaction. 2) The area of ventricular myocardium increased in aortic valve disease and hypertrophic cardiomyopathy. 3) The direction and magnitude of O-G vector calculated by CT were well correlated to the half area of QRS loop in horizontal plane of vectorcardiography. (author)

  7. Chronic activation of hypothalamic oxytocin neurons improves cardiac function during left ventricular hypertrophy-induced heart failure.

    Science.gov (United States)

    Garrott, Kara; Dyavanapalli, Jhansi; Cauley, Edmund; Dwyer, Mary Kate; Kuzmiak-Glancy, Sarah; Wang, Xin; Mendelowitz, David; Kay, Matthew W

    2017-09-01

    A distinctive hallmark of heart failure (HF) is autonomic imbalance, consisting of increased sympathetic activity, and decreased parasympathetic tone. Recent work suggests that activation of hypothalamic oxytocin (OXT) neurons could improve autonomic balance during HF. We hypothesized that a novel method of chronic selective activation of hypothalamic OXT neurons will improve cardiac function and reduce inflammation and fibrosis in a rat model of HF. Two groups of male Sprague-Dawley rats underwent trans-ascending aortic constriction (TAC) to induce left ventricular (LV) hypertrophy that progresses to HF. In one TAC group, OXT neurons in the paraventricular nucleus of the hypothalamus were chronically activated by selective expression and activation of excitatory DREADDs receptors with daily injections of clozapine N-oxide (CNO) (TAC + OXT). Two additional age-matched groups received either saline injections (Control) or CNO injections for excitatory DREADDs activation (OXT NORM). Heart rate (HR), LV developed pressure (LVDP), and coronary flow rate were measured in isolated heart experiments. Isoproterenol (0.01 nM-1.0 µM) was administered to evaluate β-adrenergic sensitivity. We found that increases in cellular hypertrophy and myocardial collagen density in TAC were blunted in TAC + OXT animals. Inflammatory cytokine IL-1β expression was more than twice higher in TAC than all other hearts. LVDP, rate pressure product (RPP), contractility, and relaxation were depressed in TAC compared with all other groups. The response of TAC and TAC + OXT hearts to isoproterenol was blunted, with no significant increase in RPP, contractility, or relaxation. However, HR in TAC + OXT animals increased to match Control at higher doses of isoproterenol. Activation of hypothalamic OXT neurons to elevate parasympathetic tone reduced cellular hypertrophy, levels of IL-1β, and fibrosis during TAC-induced HF in rats. Cardiac contractility parameters were

  8. Thallium-201: quantitation of right ventricular hypertrophy in chronically hypoxic rats

    International Nuclear Information System (INIS)

    Rabinovitch, M.; Fisher, K.; Gamble, W.; Reid, L.; Treves, S.

    1979-01-01

    Sprague Dawley rats were divided into two groups. Ten were kept in room air and 10 in hypobaric hypoxia (air at 380 m Hg). After two weeks all were injected intravenously with 50 μCi of 201 Tl and sacrificed. The right and left ventricles were separated, weighed, and measured for radioactivity in a gamma well counter. Left and right ventricular mass ratios (MR) correlated with 201 Tl radioactivity ratios (TAR) in both control and hypoxic rats: r = 0.962 where MR = 0.863 TAR + 0.27. Myocardial 201 Tl uptake reflects and quantitates normal and abnormal ventricular mass, the abnormal mass in this model consisting of right ventricular hypertrophy associated with hypoxic pulmonary hypertension

  9. Trichostatin A accentuates doxorubicin-induced hypertrophy in cardiac myocytes.

    Science.gov (United States)

    Karagiannis, Tom C; Lin, Ann J E; Ververis, Katherine; Chang, Lisa; Tang, Michelle M; Okabe, Jun; El-Osta, Assam

    2010-10-01

    Histone deacetylase inhibitors represent a new class of anticancer therapeutics and the expectation is that they will be most effective when used in combination with conventional cancer therapies, such as the anthracycline, doxorubicin. The dose-limiting side effect of doxorubicin is severe cardiotoxicity and evaluation of the effects of combinations of the anthracycline with histone deacetylase inhibitors in relevant models is important. We used a well-established in vitro model of doxorubicin-induced hypertrophy to examine the effects of the prototypical histone deacetylase inhibitor, Trichostatin A. Our findings indicate that doxorubicin modulates the expression of the hypertrophy-associated genes, ventricular myosin light chain-2, the alpha isoform of myosin heavy chain and atrial natriuretic peptide, an effect which is augmented by Trichostatin A. Furthermore, we show that Trichostatin A amplifies doxorubicin-induced DNA double strand breaks, as assessed by γH2AX formation. More generally, our findings highlight the importance of investigating potential side effects that may be associated with emerging combination therapies for cancer.

  10. Microtubule depolymerization normalizes in vivo myocardial contractile function in dogs with pressure-overload left ventricular hypertrophy

    Science.gov (United States)

    Koide, M.; Hamawaki, M.; Narishige, T.; Sato, H.; Nemoto, S.; DeFreyte, G.; Zile, M. R.; Cooper G, I. V.; Carabello, B. A.

    2000-01-01

    BACKGROUND: Because initially compensatory myocardial hypertrophy in response to pressure overloading may eventually decompensate to myocardial failure, mechanisms responsible for this transition have long been sought. One such mechanism established in vitro is densification of the cellular microtubule network, which imposes a viscous load that inhibits cardiocyte contraction. METHODS AND RESULTS: In the present study, we extended this in vitro finding to the in vivo level and tested the hypothesis that this cytoskeletal abnormality is important in the in vivo contractile dysfunction that occurs in experimental aortic stenosis in the adult dog. In 8 dogs in which gradual stenosis of the ascending aorta had caused severe left ventricular (LV) pressure overloading (gradient, 152+/-16 mm Hg) with contractile dysfunction, LV function was measured at baseline and 1 hour after the intravenous administration of colchicine. Cardiocytes obtained by biopsy before and after in vivo colchicine administration were examined in tandem. Microtubule depolymerization restored LV contractile function both in vivo and in vitro. CONCLUSIONS: These and additional corroborative data show that increased cardiocyte microtubule network density is an important mechanism for the ventricular contractile dysfunction that develops in large mammals with adult-onset pressure-overload-induced cardiac hypertrophy.

  11. The DD genotype of the angiotensin converting enzyme gene is negatively associated with right ventricular hypertrophy in male patients with chronic obstructive pulmonary disease

    NARCIS (Netherlands)

    van Suylen, R. J.; Wouters, E. F.; Pennings, H. J.; Cheriex, E. C.; van Pol, P. E.; Ambergen, A. W.; Vermelis, A. M.; Daemen, M. J.

    1999-01-01

    The renin angiotensin system plays an important role in the development of pulmonary artery remodeling and right ventricular hypertrophy in hypoxia-induced pulmonary hypertension as may occur in patients with COPD. Several polymorphisms of genes encoding for components of the renin angiotensin

  12. Relationship of left ventricular systolic function to persistence or development of electrocardiographic left ventricular hypertrophy in hypertensive patients

    DEFF Research Database (Denmark)

    Okin, Peter M; Wachtell, Kristian; Gerdts, Eva

    2014-01-01

    left ventricular systolic function in patients with new or persistent ECG LVH. METHODS: Baseline and year-3 ECG LVH and left ventricular midwall shortening (MWS) were examined in 725 hypertensive patients in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) echocardiographic...... 1.03-3.50, P = 0.040) at year 3. CONCLUSION: Persistence or development of new ECG LVH during antihypertensive therapy is associated with an increased risk of left ventricular systolic dysfunction after 3 years' follow-up. These findings provide insight into a possible mechanism by which changes......BACKGROUND: Persistence or development of ECG left ventricular hypertrophy (LVH) by Cornell product criteria is associated with an increased risk of developing heart failure compared with regression or continued absence of LVH. We postulated that this association might be in part mediated via worse...

  13. Role of Oxidative Stress in Thyroid Hormone-Induced Cardiomyocyte Hypertrophy and Associated Cardiac Dysfunction: An Undisclosed Story

    Directory of Open Access Journals (Sweden)

    Mohammad T. Elnakish

    2015-01-01

    Full Text Available Cardiac hypertrophy is the most documented cardiomyopathy following hyperthyroidism in experimental animals. Thyroid hormone-induced cardiac hypertrophy is described as a relative ventricular hypertrophy that encompasses the whole heart and is linked with contractile abnormalities in both right and left ventricles. The increase in oxidative stress that takes place in experimental hyperthyroidism proposes that reactive oxygen species are key players in the cardiomyopathy frequently reported in this endocrine disorder. The goal of this review is to shed light on the effects of thyroid hormones on the development of oxidative stress in the heart along with the subsequent cellular and molecular changes. In particular, we will review the role of thyroid hormone-induced oxidative stress in the development of cardiomyocyte hypertrophy and associated cardiac dysfunction, as well as the potential effectiveness of antioxidant treatments in attenuating these hyperthyroidism-induced abnormalities in experimental animal models.

  14. Clinical impact of ' in-treatment' wall motion abnormalities in hypertensive patients with left ventricular hypertrophy: the LIFE study

    DEFF Research Database (Denmark)

    Cicala, S.; Simone, G. de; Wachtell, K.

    2008-01-01

    Objectives Left ventricular systolic wall motion abnormalities have prognostic value. Whether wall motion detected by serial echocardiographic examinations predicts prognosis in hypertensive patients with left ventricular hypertrophy ( LVH) without clinically recognized atherosclerotic disease ha...

  15. Evaluation of ECG criteria for left ventricular hypertrophy before and after aortic valve replacement using magnetic resonance Imaging

    NARCIS (Netherlands)

    Beyerbacht, Hugo P.; Bax, Jeroen J.; Lamb, Hildo J.; van der Laarse, Arnoud; Vliegen, Hubert W.; de Roos, Albert; Zwinderman, Aeilko H.; van der Wall, Ernst E.

    2003-01-01

    PURPOSE: Evaluation of different electrocardiographic criteria for left ventricular hypertrophy (ECG-LVH criteria) using left ventricular mass index (LVMI) determined by magnetic resonance imaging (MRI). In addition, the relation between LVMI regression after aortic valve replacement and

  16. Relationship between obesity and left ventricular hypertrophy in children

    Directory of Open Access Journals (Sweden)

    Johnny Rompis

    2016-10-01

    Full Text Available Background Obesity is a chronic metabolic disorder associated with cardiovascular disease (CVD increasing morbidity-mortality rates. It is apparent that a variety of adaptations/alterations in cardiac structure and function occurs as excessive adipose tissue accumulates. This leads to a decrease in diastolic compliance, eventually resulting in an increase in left ventricular filling pressure and left ventricular enlargement. Objective To evaluate left ventricular hypertrophy (LVH among  obese using electrocardiographic (ECG criteria. Methods A cross-sectional study was conducted on 74 children aged 10-15 years from February 2009 to October 2009. The subjects were divided into obese and control groups. Physical examination and standard 12 lead electrocardiography (ECG were done in both groups. Results Of 37 obese children, LVH were featured in 3 subjects, while in control group, only 1 child had LVH (P= 0.304. We found that mean RV6 in obese and control group were 9.8446 (SD 3.5854 and 11.9662 (SD 3.2857, respectively (P=0.005. As an additional findings, we found that birth weight was related to obesity in children. Conclusion There is no relation between obesity and left ventricular using ECG criteria in obese children aged 10-15 years.

  17. Left Ventricular Hypertrophy: An allometric comparative analysis of different ECG markers

    International Nuclear Information System (INIS)

    Bonomini, MP; Valentinuzzi, M E; Arini, P D; Ingallina, F; Barone, V

    2011-01-01

    Allometry, in general biology, measures the relative growth of a part in relation to the whole living organism. Left ventricular hypertrophy (LVH) is the heart adaptation to excessive load (systolic or diastolic). The increase in left ventricular mass leads to an increase in the electrocardiographic voltages. Based on clinical data, we compared the allometric behavior of three different ECG markers of LVH. To do this, the allometric fit AECG δ + β (VM) relating left ventricular mass (estimated from ecocardiographic data) and ECG amplitudes (expressed as the Cornell-Voltage, Sokolow and the ECG overall voltage indexes) were compared. Besides, sensitivity and specificity for each index were analyzed. The more sensitive the ECG criteria, the better the allometric fit. In conclusion: The allometric paradigm should be regarded as the way to design new and more sensitive ECG-based LVH markers.

  18. Impact of fasting glucose on electrocardiographic left ventricular hypertrophy in an elderly general population

    DEFF Research Database (Denmark)

    Diederichsen, Søren Z; Pareek, Manan; Nielsen, Mette L

    2015-01-01

    OBJECTIVE: To evaluate relationships between fasting plasma glucose (FPG), other cardiovascular risk markers and left ventricular hypertrophy (LVH) as detected by electrocardiography. METHODS: Subjects were selected randomly from groups defined by FPG. Traditional risk markers were assessed. LVH...

  19. Impact of hypertension on left ventricular structure in patients with asymptomatic aortic valve stenosis (a SEAS substudy)

    DEFF Research Database (Denmark)

    Rieck, Ashild E; Cramariuc, Dana; Staal, Eva M

    2010-01-01

    Both hypertension and aortic valve stenosis induce left ventricular hypertrophy. However, less is known about the influence of concomitant hypertension on left ventricular structure in patients with aortic valve stenosis.......Both hypertension and aortic valve stenosis induce left ventricular hypertrophy. However, less is known about the influence of concomitant hypertension on left ventricular structure in patients with aortic valve stenosis....

  20. Taxifolin protects against cardiac hypertrophy and fibrosis during biomechanical stress of pressure overload

    International Nuclear Information System (INIS)

    Guo, Haipeng; Zhang, Xin; Cui, Yuqian; Zhou, Heng; Xu, Dachun; Shan, Tichao; Zhang, Fan; Guo, Yuan; Chen, Yuguo; Wu, Dawei

    2015-01-01

    Cardiac hypertrophy is a key pathophysiological component to biomechanical stress, which has been considered to be an independent and predictive risk factor for adverse cardiovascular events. Taxifolin (TAX) is a typical plant flavonoid, which has long been used clinically for treatment of cardiovascular and cerebrovascular diseases. However, very little is known about whether TAX can influence the development of cardiac hypertrophy. In vitro studies, we found that TAX concentration-dependently inhibited angiotensin II (Ang II) induced hypertrophy and protein synthesis in cardiac myocytes. Then we established a mouse model by transverse aortic constriction (TAC) to further confirm our findings. It was demonstrated that TAX prevented pressure overload induced cardiac hypertrophy in mice, as assessed by ventricular mass/body weight, echocardiographic parameters, myocyte cross-sectional area, and the expression of ANP, BNP and β-MHC. The excess production of reactive oxygen species (ROS) played critical role in the development of cardiac hypertrophy. TAX arrested oxidative stress and decreased the expression of 4-HNE induced by pressure overload. Moreover, TAX negatively modulated TAC-induced phosphorylation of ERK1/2 and JNK1/2. Further studies showed that TAX significantly attenuated left ventricular fibrosis and collagen synthesis through abrogating the phosphorylation of Smad2 and Smad2/3 nuclear translocation. These results demonstrated that TAX could inhibit cardiac hypertrophy and attenuate ventricular fibrosis after pressure overload. These beneficial effects were at least through the inhibition of the excess production of ROS, ERK1/2, JNK1/2 and Smad signaling pathways. Therefore, TAX might be a potential candidate for the treatment of cardiac hypertrophy and fibrosis. - Highlights: • We focus on the protective effect of taxifolin on cardiac remodeling. • Taxifolin inhibited cardiac hypertrophy and attenuated ventricular fibrosis. • Taxifolin

  1. Taxifolin protects against cardiac hypertrophy and fibrosis during biomechanical stress of pressure overload

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Haipeng; Zhang, Xin [Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan (China); Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Cui, Yuqian [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Zhou, Heng [Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan (China); Xu, Dachun [Department of Cardiology, Shanghai Tenth People' s Hospital of Tongji University, Shanghai (China); Shan, Tichao; Zhang, Fan [Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan (China); Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Guo, Yuan [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Chen, Yuguo, E-mail: chen919085@163.com [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Department of Emergency, Qilu Hospital of Shandong University, Jinan (China); Wu, Dawei, E-mail: wdwu55@163.com [Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan (China); Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China)

    2015-09-01

    Cardiac hypertrophy is a key pathophysiological component to biomechanical stress, which has been considered to be an independent and predictive risk factor for adverse cardiovascular events. Taxifolin (TAX) is a typical plant flavonoid, which has long been used clinically for treatment of cardiovascular and cerebrovascular diseases. However, very little is known about whether TAX can influence the development of cardiac hypertrophy. In vitro studies, we found that TAX concentration-dependently inhibited angiotensin II (Ang II) induced hypertrophy and protein synthesis in cardiac myocytes. Then we established a mouse model by transverse aortic constriction (TAC) to further confirm our findings. It was demonstrated that TAX prevented pressure overload induced cardiac hypertrophy in mice, as assessed by ventricular mass/body weight, echocardiographic parameters, myocyte cross-sectional area, and the expression of ANP, BNP and β-MHC. The excess production of reactive oxygen species (ROS) played critical role in the development of cardiac hypertrophy. TAX arrested oxidative stress and decreased the expression of 4-HNE induced by pressure overload. Moreover, TAX negatively modulated TAC-induced phosphorylation of ERK1/2 and JNK1/2. Further studies showed that TAX significantly attenuated left ventricular fibrosis and collagen synthesis through abrogating the phosphorylation of Smad2 and Smad2/3 nuclear translocation. These results demonstrated that TAX could inhibit cardiac hypertrophy and attenuate ventricular fibrosis after pressure overload. These beneficial effects were at least through the inhibition of the excess production of ROS, ERK1/2, JNK1/2 and Smad signaling pathways. Therefore, TAX might be a potential candidate for the treatment of cardiac hypertrophy and fibrosis. - Highlights: • We focus on the protective effect of taxifolin on cardiac remodeling. • Taxifolin inhibited cardiac hypertrophy and attenuated ventricular fibrosis. • Taxifolin

  2. Molecular and cellular characterization of cardiac overload-induced hypertrophy and failure

    NARCIS (Netherlands)

    Umar, Soban

    2009-01-01

    In neonatal rat ventricular cardiomyocytes (NRVCs), we activated integrins by RGD to test whether integrin stimulation produced hypertrophy. Effect of RGD was compared with pro-hypertrophic effects of phenylephrine (chapter 2). Ventricular failure is associated with disturbed collagen turnover.

  3. SIRT1 Functions as an Important Regulator of Estrogen-Mediated Cardiomyocyte Protection in Angiotensin II-Induced Heart Hypertrophy

    Directory of Open Access Journals (Sweden)

    Tao Shen

    2014-01-01

    Full Text Available Background. Sirtuin 1 (SIRT1 is a member of the sirtuin family, which could activate cell survival machinery and has been shown to be protective in regulation of heart function. Here, we determined the mechanism by which SIRT1 regulates Angiotensin II- (AngII- induced cardiac hypertrophy and injury in vivo and in vitro. Methods. We analyzed SIRT1 expression in the hearts of control and AngII-induced mouse hypertrophy. Female C57BL/6 mice were ovariectomized and pretreated with 17β-estradiol to measure SIRT1 expression. Protein synthesis, cardiomyocyte surface area analysis, qRT-PCR, TUNEL staining, and Western blot were performed on AngII-induced mouse heart hypertrophy samples and cultured neonatal rat ventricular myocytes (NRVMs to investigate the function of SIRT1. Results. SIRT1 expression was slightly upregulated in AngII-induced mouse heart hypertrophy in vivo and in vitro, accompanied by elevated cardiomyocyte apoptosis. SIRT1 overexpression relieves AngII-induced cardiomyocyte hypertrophy and apoptosis. 17β-Estradiol was able to protect cardiomyocytes from AngII-induced injury with a profound upregulation of SIRT1 and activation of AMPK. Moreover, estrogen receptor inhibitor ICI 182,780 and SIRT1 inhibitor niacinamide could block SIRT1’s protective effect. Conclusions. These results indicate that SIRT1 functions as an important regulator of estrogen-mediated cardiomyocyte protection during AngII-induced heart hypertrophy and injury.

  4. A novel hydrodynamic approach of drag-reducing polymers to improve left ventricular hypertrophy and aortic remodeling in spontaneously hypertensive rats

    Directory of Open Access Journals (Sweden)

    Zhang X

    2016-12-01

    Full Text Available Xinlu Zhang,1,* Xu Wang,2,* Feng Hu,1 Boda Zhou,3 Hai-Bin Chen,1 Daogang Zha,1 Yili Liu,1 Yansong Guo,4 Lemin Zheng,2 Jiancheng Xiu1 1Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, 2The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, and Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, Peking University Health Science Center, 3Department of Cardiology, Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, and Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides of Ministry of Health, Peking University Third Hospital, Beijing, 4Department of Cardiovascular Medicine, Fujian Provincial Hospital, Fuzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Drag-reducing polymers (DRPs, when added in minute concentrations, have been shown to decrease peripheral vascular resistance. In this study, the effect of DRPs on the hypertension-induced left ventricular hypertrophy and aortic remodeling was evaluated in spontaneously hypertensive rats (SHR. Male SHR and age-matched Wistar rats were divided into four groups and received intravenous injection of normal saline (NS or DRPs. Body weight (BW, heart rate (HR and systolic blood pressure (SBP were measured. Echocardiography was used to evaluate the changes in left ventricle (LV function and global wall motion. The LV and aorta were stained by hematoxylin and eosin. Cell size of cardiomyocytes and aortic medial thickness were evaluated for each section. The expression of endothelin-1 (ET-1 of LV and aorta was examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR and immunohistochemistry. There was no significant difference in the increase of SBP among SHR + NS, SHR + 10DRP and SHR + 20DRP groups. SHR + NS group had markedly smaller left ventricular end

  5. Serum uric acid is associated with left ventricular hypertrophy independent of serum parathyroid hormone in male cardiac patients.

    Directory of Open Access Journals (Sweden)

    Shu-ichi Fujita

    Full Text Available BACKGROUND: Several studies have shown that serum uric acid (UA is associated with left ventricular (LV hypertrophy. Serum levels of parathyroid hormone (PTH, which has bbe shown to be correlated with UA, is also known to be associated with cardiac hypertrophy; however, whether the association between UA and cardiac hypertrophy is independent of PTH remains unknown. PURPOSE: We investigated whether the relationship between serum uric acid (UA and LV hypertrophy is independent of intact PTH and other calcium-phosphate metabolism-related factors in cardiac patients. METHODS AND RESULTS: In a retrospective study, the association between UA and left ventricular mass index was assessed among 116 male cardiac patients (mean age 65 ± 12 years who were not taking UA lowering drugs. The median UA value was 5.9 mg/dL. Neither age nor body mass index differed significantly among the UA quartile groups. Patients with higher UA levels were more likely to be taking loop diuretics. UA showed a significant correlation with intact PTH (R = 0.34, P<0.001 but not with other calcium-phosphate metabolism-related factors. Linear regression analysis showed that log-transformed UA showed a significant association with left ventricular mass index, and this relationship was found to be significant exclusively in patients who were not taking loop and/or thiazide diuretics. Multivariate logistic regression analysis showed that log-transformed UA was independently associated with LV hypertrophy with an odds ratio of 2.79 (95% confidence interval 1.48-5.28, P = 0.002 per one standard deviation increase. CONCLUSIONS: Among cardiac patients, serum UA was associated with LV hypertrophy, and this relationship was, at least in part, independent of intact PTH levels, which showed a significant correlation with UA in the same population.

  6. Lysyl oxidase overexpression accelerates cardiac remodeling and aggravates angiotensin II-induced hypertrophy.

    Science.gov (United States)

    Galán, María; Varona, Saray; Guadall, Anna; Orriols, Mar; Navas, Miquel; Aguiló, Silvia; de Diego, Alicia; Navarro, María A; García-Dorado, David; Rodríguez-Sinovas, Antonio; Martínez-González, José; Rodriguez, Cristina

    2017-09-01

    Lysyl oxidase (LOX) controls matrix remodeling, a key process that underlies cardiovascular diseases and heart failure; however, a lack of suitable animal models has limited our knowledge with regard to the contribution of LOX to cardiac dysfunction. Here, we assessed the impact of LOX overexpression on ventricular function and cardiac hypertrophy in a transgenic LOX (TgLOX) mouse model with a strong cardiac expression of human LOX. TgLOX mice exhibited high expression of the transgene in cardiomyocytes and cardiofibroblasts, which are associated with enhanced LOX activity and H 2 O 2 production and with cardiofibroblast reprogramming. LOX overexpression promoted an age-associated concentric remodeling of the left ventricle and impaired diastolic function. Furthermore, LOX transgenesis aggravated angiotensin II (Ang II)-induced cardiac hypertrophy and dysfunction, which triggered a greater fibrotic response that was characterized by stronger collagen deposition and cross-linking and high expression of fibrotic markers. In addition, LOX transgenesis increased the Ang II-induced myocardial inflammatory infiltrate, exacerbated expression of proinflammatory markers, and decreased that of cardioprotective factors. Mechanistically, LOX overexpression enhanced oxidative stress and potentiated the Ang II-mediated cardiac activation of p38 MAPK while reducing AMPK activation. Our findings suggest that LOX induces an age-dependent disturbance of diastolic function and aggravates Ang II-induced hypertrophy, which provides novel insights into the role of LOX in cardiac performance.-Galán, M., Varona, S., Guadall, A., Orriols, M., Navas, M., Aguiló, S., de Diego, A., Navarro, M. A., García-Dorado, D., Rodríguez-Sinovas, A., Martínez-González, J., Rodriguez, C. Lysyl oxidase overexpression accelerates cardiac remodeling and aggravates angiotensin II-induced hypertrophy. © FASEB.

  7. "Heart rate-dependent" electrocardiographic diagnosis of left ventricular hypertrophy.

    Science.gov (United States)

    Madias, John E

    2013-05-01

    A case is presented revealing the common phenomenon of heart rate-dependent diagnosis of electrocardiographic (ECG) diagnosis of left ventricular hypertrophy (LVH), which consists of satisfaction of LVH criteria only at faster rates whereas ECGs with a slow heart rate do not satisfy such criteria. The mechanism of the phenomenon has been attributed to the tachycardia-mediated underfilling of the left ventricle bringing the electrical "centroid" of the heart closer to the recording electrodes, which results in augmentation of the amplitude of QRS complexes, particularly in leads V2-V4. ©2012, The Author. Journal compilation ©2012 Wiley Periodicals, Inc.

  8. Eccentric and concentric cardiac hypertrophy induced by exercise training: microRNAs and molecular determinants.

    Science.gov (United States)

    Fernandes, T; Soci, U P R; Oliveira, E M

    2011-09-01

    Among the molecular, biochemical and cellular processes that orchestrate the development of the different phenotypes of cardiac hypertrophy in response to physiological stimuli or pathological insults, the specific contribution of exercise training has recently become appreciated. Physiological cardiac hypertrophy involves complex cardiac remodeling that occurs as an adaptive response to static or dynamic chronic exercise, but the stimuli and molecular mechanisms underlying transduction of the hemodynamic overload into myocardial growth are poorly understood. This review summarizes the physiological stimuli that induce concentric and eccentric physiological hypertrophy, and discusses the molecular mechanisms, sarcomeric organization, and signaling pathway involved, also showing that the cardiac markers of pathological hypertrophy (atrial natriuretic factor, β-myosin heavy chain and α-skeletal actin) are not increased. There is no fibrosis and no cardiac dysfunction in eccentric or concentric hypertrophy induced by exercise training. Therefore, the renin-angiotensin system has been implicated as one of the regulatory mechanisms for the control of cardiac function and structure. Here, we show that the angiotensin II type 1 (AT1) receptor is locally activated in pathological and physiological cardiac hypertrophy, although with exercise training it can be stimulated independently of the involvement of angiotensin II. Recently, microRNAs (miRs) have been investigated as a possible therapeutic approach since they regulate the translation of the target mRNAs involved in cardiac hypertrophy; however, miRs in relation to physiological hypertrophy have not been extensively investigated. We summarize here profiling studies that have examined miRs in pathological and physiological cardiac hypertrophy. An understanding of physiological cardiac remodeling may provide a strategy to improve ventricular function in cardiac dysfunction.

  9. Eccentric and concentric cardiac hypertrophy induced by exercise training: microRNAs and molecular determinants

    Directory of Open Access Journals (Sweden)

    T. Fernandes

    2011-09-01

    Full Text Available Among the molecular, biochemical and cellular processes that orchestrate the development of the different phenotypes of cardiac hypertrophy in response to physiological stimuli or pathological insults, the specific contribution of exercise training has recently become appreciated. Physiological cardiac hypertrophy involves complex cardiac remodeling that occurs as an adaptive response to static or dynamic chronic exercise, but the stimuli and molecular mechanisms underlying transduction of the hemodynamic overload into myocardial growth are poorly understood. This review summarizes the physiological stimuli that induce concentric and eccentric physiological hypertrophy, and discusses the molecular mechanisms, sarcomeric organization, and signaling pathway involved, also showing that the cardiac markers of pathological hypertrophy (atrial natriuretic factor, β-myosin heavy chain and α-skeletal actin are not increased. There is no fibrosis and no cardiac dysfunction in eccentric or concentric hypertrophy induced by exercise training. Therefore, the renin-angiotensin system has been implicated as one of the regulatory mechanisms for the control of cardiac function and structure. Here, we show that the angiotensin II type 1 (AT1 receptor is locally activated in pathological and physiological cardiac hypertrophy, although with exercise training it can be stimulated independently of the involvement of angiotensin II. Recently, microRNAs (miRs have been investigated as a possible therapeutic approach since they regulate the translation of the target mRNAs involved in cardiac hypertrophy; however, miRs in relation to physiological hypertrophy have not been extensively investigated. We summarize here profiling studies that have examined miRs in pathological and physiological cardiac hypertrophy. An understanding of physiological cardiac remodeling may provide a strategy to improve ventricular function in cardiac dysfunction.

  10. The Relationship of Carotid Arterial Stiffness and Left Ventricular Concentric Hypertrophy in Hypertension.

    Science.gov (United States)

    Jaroch, Joanna; Łoboz-Grudzień, Krystyna; Magda, Stefania; Florescu, Maria; Bociąga, Zbigniew; Ciobanu, Andrea O; Kruszyńska, Ewa; Dudek, Krzysztof; Vinereanu, Dragos

    2016-01-01

    Left ventricular hypertrophy (LVH) and geometry patterns vary in different hemodynamic profiles The concentric hypertrophy (CH) pattern has been proved to have the worst prognosis. The aim of the study was to test the hypothesis that carotid artery stiffness, as a marker of vascular damage, is associated with CH, independently of other potential determinants such as demographic factors (age, sex, BMI), clinical parameters (smoking, diabetes, creatinine level) and hemodynamic variables (blood pressure, pulse pressure [PP]). The study involved 262 subjects (89 men): 202 patients with hypertension (153 untreated, 49 on medication), aged 55.7 ± 10 years, and 60 age-matched normal controls. The subjects were examined by echocardiography and carotid ultrasound with a high-resolution echo-tracking system. Based on the left ventricular mass index (LVMI) and relative wall thickness (RWT), the patients with hypertension were divided into four patterns of LVH and geometry: normal geometry (N, n = 57), concentric remodeling (CR, n = 48), concentric hypertrophy CH (n = 62) and eccentric hypertrophy (EH, n = 35). Intima-media thickness (IMT) and the parameters of arterial stiffness were also assessed using the β stiffness index (β), Young elastic modulus (Ep), arterial compliance (AC), one-point pulse wave velocity (PWVβ) and the wave reflection augmentation index (AI). Univariate analysis showed that the following variables are significant in determining CH: β > 8.4, Ep > 136 kPa, PWVβ > 7.1 m/s, AI > 21.9%, systolic BP > 151 mm Hg, PP > 54, IMT > 0.56 and the presence of diabetes. However, by multivariate analysis only AI (OR 3.65, p = 0.003), PWVβ > 7.1 m/s (OR 2.86, p = 0.014), systolic BP (OR 3.12, p = 0037) and the presence of diabetes (OR 3.75, p = 0.007) were associated independently with the occurrence of CH. Concentric hypertrophy in hypertension is strongly associated with carotid arterial stiffness and wave reflection parameters, independently of the influence

  11. Chronic low-level arsenite exposure through drinking water increases blood pressure and promotes concentric left ventricular hypertrophy in female mice.

    Science.gov (United States)

    Sanchez-Soria, Pablo; Broka, Derrick; Monks, Sarah L; Camenisch, Todd D

    2012-04-01

    Cardiovascular disease is the leading cause of death in the United States and worldwide. High incidence of cardiovascular diseases has been linked to populations with elevated arsenic content in their drinking water. Although this correlation has been established in many epidemiological studies, a lack of experimental models to study mechanisms of arsenic-related cardiovascular pathogenesis has limited our understanding of how arsenic exposure predisposes for development of hypertension and increased cardiovascular mortality. Our studies show that mice chronically exposed to drinking water containing 100 parts per billion (ppb) sodium arsenite for 22 weeks show an increase in both systolic and diastolic blood pressure. Echocardiographic analyses as well as histological assessment show concentric left ventricular hypertrophy, a primary cardiac manifestation of chronic hypertension. Live imaging by echocardiography shows a 43% increase in left ventricular mass in arsenic-treated animals. Relative wall thickness (RWT) was calculated showing that all the arsenic-exposed animals show an RWT greater than 0.45, indicating concentric hypertrophy. Importantly, left ventricular hypertrophy, although often associated with chronic hypertension, is an independent risk factor for cardiovascular-related mortalities. These results suggest that chronic low-level arsenite exposure promotes the development of hypertension and the comorbidity of concentric hypertrophy.

  12. UCP3 Ablation Exacerbates High-Salt Induced Cardiac Hypertrophy and Cardiac Dysfunction

    Directory of Open Access Journals (Sweden)

    Hongmei Lang

    2018-04-01

    Full Text Available Background/Aims: Excessive salt intake and left ventricular hypertrophy (LVH are both critical for the development of hypertension and heart failure. The uncoupling protein 3 (UCP3 plays a cardio-protective role in early heart failure development. However, the potential role for UCP3 in salt intake and LVH is unclear. Methods: UCP3-/- and C57BL/6 mice were placed on either a normal-salt (NS, 0.5% or a high-salt (HS, 8% diet for 24 weeks. The cardiac function, endurance capacity, energy expenditure, and mitochondrial functional capacity were measured in each group. Results: Elevated blood pressure was only observed in HS-fed UCP3-/- mice. High salt induced cardiac hypertrophy and dysfunction were observed in both C57BL/6 and UCP3-/- mice. However, the cardiac lesions were more profound in HS-fed UCP3-/- mice. Furthermore, HS-fed UCP3-/-mice experienced more severe mitochondrial respiratory dysfunction compared with HS-fed C57BL/6 mice, represented by the decreased volume of oxygen consumption and heat production at the whole-body level. Conclusion: UCP3 protein was involved in the incidence of high-salt induced hypertension and the progression of cardiac dysfunction in the early stages of heart failure. UCP3 ablation exacerbated high-salt-induced cardiac hypertrophy and cardiac dysfunction.

  13. Decreasing Compensatory Ability of Concentric Ventricular Hypertrophy in Aortic-Banded Rat Hearts

    Directory of Open Access Journals (Sweden)

    Alexandre Lewalle

    2018-02-01

    Full Text Available The cardiac system compensates for variations in physiological and pathophysiological conditions through a dynamic remodeling at the organ, tissue, and intracellular levels in order to maintain function. However, on longer time scales following the onset of ventricular pressure overload, such remodeling may begin to inhibit physiological function and ultimately lead to heart failure. This progression from compensatory to decompensatory behavior is poorly understood, in particular owing to the absence of a unified perspective of the concomitantly remodeling subsystems. To address this issue, the present study investigates the evolution of compensatory mechanisms, in response to overload, by integrating diffusion-tensor MRI, echocardiography, and intracellular and hemodynamic measurements within consistent computational simulations of aortic-banded rat hearts. This approach allows a comparison of the relative leverage of different cardiac properties (geometry, passive mechanical stiffness, fiber configuration, diastolic and peak calcium concentrations, calcium-binding affinity, and aortic impedance to affect cardiac contraction. Measurements indicate that, following aortic banding, an ejection fraction (EF of 75% was maintained, relative to control rats, despite significant remodeling of the left-ventricular wall thickness (increasing by ~90% over 4 weeks. Applying our framework, we identified the left-ventricular wall thickness (concentric hypertrophy and the intracellular calcium dynamics as playing the dominant roles in preserving EF acutely, whereas the significance of hypertrophy decreased subsequently. This trend suggests an increasing reliance on intracellular mechanisms (average increase ~50%, rather than on anatomical features (average decrease ~60%, to achieve compensation of pump function in the early phase of heart failure.

  14. Electrocardiographic left ventricular hypertrophy without echocardiographic abnormalities evaluated by myocardial perfusion and fatty acid metabolic imaging

    International Nuclear Information System (INIS)

    Narita, Michihiro; Kurihara, Tadashi

    2000-01-01

    The pathophysiologic process in patients with electrocardiographic left ventricular hypertrophy with ST, T changes but without echocardiographic abnormalities was investigated by myocardial perfusion imaging and fatty acid metabolic imaging. Exercise stress 99m Tc-methoxy-isobutyl isonitrile (MIBI) imaging and rest 123 I-beta-methyl-p-iodophenyl pentadecanoic acid (BMIPP) imaging were performed in 59 patients with electrocardiographic hypertrophy including 29 without apparent cause including hypertension and echocardiographic hypertrophy, and 30 with essential hypertension. Coronary angiography was performed in 6 patients without hypertension and 4 with hypertension and biopsy specimens were obtained from the left ventricular apex from 6 patients without hypertension. Myocardial perfusion and 123 I-BMIPP images were classified into 3 types: normal, increased accumulation of the isotope at the left ventricular apex (high uptake) and defect. Transient perfusion abnormality and apical defect observed by 123 I-BMIPP imaging were more frequent in patients without hypertension than in patients with hypertension (32% vs. 17%, p=0.04671 in perfusion; 62% vs. 30%, p=0.0236 in 123 I-BMIPP). Eighteen normotensive patients with apical defect by 123 I-BMIPP imaging included 3 of 10 patients with normal perfusion at exercise, 6 of 10 patients with high uptake and 9 of 9 patients with perfusion defect. The defect size revealed by 123 I-BMIPP imaging was greater than that of the perfusion abnormality. Coronary stenoses were not observed and myocardial specimens showed myocardial disarray with hypertrophy. Moreover, 9 patients with hypertension and apical defects by 123 I-BMIPP showed 3 different types of perfusion. Many patients without hypertension show a pathologic process similar to hypertrophic cardiomyopathy. Perfusion and 123 I-BMIPP imaging are useful for the identification of these patients. (author)

  15. Cardiac arrhythmias and left ventricular hypertrophy in systemic hypertension

    International Nuclear Information System (INIS)

    Sultana, R.; Sultana, N.; Rashid, A.; Rasheed, S.Z.; Ahmed, M.; Ishaq, M.; Samad, A.

    2010-01-01

    Background: Hypertensive left ventricular hypertrophy (LVH) is associated with increased risk of arrhythmias and mortality. Objective was to investigate the prevalence of cardiac arrhythmias and LVH in systemic hypertension. Methods: In all subjects blood pressure was measured, electrocardiography and echocardiography was done. Holter monitoring and exercise test perform in certain cases. There were 500 hypertensive patients, 156 (31.2%) men and 344 (69%) women >30 years of age in the study. Among them 177 (35.4%) were diabetic, 224 (45%) were dyslipidemia, 188 (37.6%) were smokers, and 14 (3%) had homocysteinemia. Mean systolic BP (SBP) was 180 +- 20 mm Hg and diastolic BP (DBP) was 95 +- 12 in male and female patients. Left ventricular mass index (LVMI) was 119.2 +- 30 2 2gm/m in male while 103 +- 22 gm/m in female patients. Palpitation was seen in 126 (25%) male and 299 (59.8%) female patients. Atrial fibrillation was noted in 108 (21.6%) male and 125 (25%) female patients, 30 (6%) male and 82 (16.4%) female patients had atrial flutter. Ventricular tachycardia was noted in 37 (7.4%) male and 59 (11.8%) female patients. Holter monitoring showed significant premature ventricular contractions (PVC'S) in 109 (21.8%) male and 128 (25.69%) female patients while Holter showed atrial arrhythmias (APC'S) in 89 (17.8%) males and 119 (23.8%) females. Angiography findings diagnosed coronary artery disease in 119 (23.8%) with CAD male and 225 (45%) without CAD while 47 (9.4%) females presented with CAD and 109 (21.8%) without CAD. Conclusion: A significant association has been demonstrated between hypertension and arrhythmias. Diastolic dysfunction of the left ventricle, left atrial size and function, as well as LVH have been suggested as the underlying risk factors for supraventricular, ventricular arrhythmias and sudden death in hypertensives with LVH. (author)

  16. Cardiac arrhythmias and left ventricular hypertrophy in systemic hypertension

    Energy Technology Data Exchange (ETDEWEB)

    Sultana, R; Sultana, N; Rashid, A; Rasheed, S Z; Ahmed, M; Ishaq, M; Samad, A [Karachi Institute of Heart Diseases, Karachi (Pakistan)

    2010-10-15

    Background: Hypertensive left ventricular hypertrophy (LVH) is associated with increased risk of arrhythmias and mortality. Objective was to investigate the prevalence of cardiac arrhythmias and LVH in systemic hypertension. Methods: In all subjects blood pressure was measured, electrocardiography and echocardiography was done. Holter monitoring and exercise test perform in certain cases. There were 500 hypertensive patients, 156 (31.2%) men and 344 (69%) women >30 years of age in the study. Among them 177 (35.4%) were diabetic, 224 (45%) were dyslipidemia, 188 (37.6%) were smokers, and 14 (3%) had homocysteinemia. Mean systolic BP (SBP) was 180 +- 20 mm Hg and diastolic BP (DBP) was 95 +- 12 in male and female patients. Left ventricular mass index (LVMI) was 119.2 +- 30 2 2gm/m in male while 103 +- 22 gm/m in female patients. Palpitation was seen in 126 (25%) male and 299 (59.8%) female patients. Atrial fibrillation was noted in 108 (21.6%) male and 125 (25%) female patients, 30 (6%) male and 82 (16.4%) female patients had atrial flutter. Ventricular tachycardia was noted in 37 (7.4%) male and 59 (11.8%) female patients. Holter monitoring showed significant premature ventricular contractions (PVC'S) in 109 (21.8%) male and 128 (25.69%) female patients while Holter showed atrial arrhythmias (APC'S) in 89 (17.8%) males and 119 (23.8%) females. Angiography findings diagnosed coronary artery disease in 119 (23.8%) with CAD male and 225 (45%) without CAD while 47 (9.4%) females presented with CAD and 109 (21.8%) without CAD. Conclusion: A significant association has been demonstrated between hypertension and arrhythmias. Diastolic dysfunction of the left ventricle, left atrial size and function, as well as LVH have been suggested as the underlying risk factors for supraventricular, ventricular arrhythmias and sudden death in hypertensives with LVH. (author)

  17. A clinical study of thallium-201 scintigraphy in hypertensive patients with and without left ventricular hypertrophy

    International Nuclear Information System (INIS)

    Ouyang Wei; He Guorong; Liu Jinhua; Huang Yuying; Qian Xuexian

    2001-01-01

    Objective: Based on coronary angiography, thallium-201 myocardial scintigraphy was evaluated in hypertensive patients with and without left ventricular hypertrophy, and the causes of its perfusion abnormalities were discussed. Methods: Thallium-201 myocardial scintigraphy was performed on 85 patients with clinically suspected coronary artery disease. Coronary angiography was performed on patients with perfusion abnormalities in one month after scintigraphy. Results: The rate of 201 Tl perfusion abnormalities in hypertensive patients with hypertrophy (85.7%) was higher than normal blood pressure (39.3%, P 201 Tl perfusion abnormalities occur in hypertensive patients with hypertrophy. The perfusion abnormalities may be caused not only by coronary large vessel disease, but also by coronary microvascular disease

  18. Association of pulse pressure with new-onset atrial fibrillation in patients with hypertension and left ventricular hypertrophy

    DEFF Research Database (Denmark)

    Larstorp, Anne Cecilie K; Ariansen, Inger; Gjesdal, Knut

    2012-01-01

    , and mean arterial pressure. When evaluated in the same model, the predictive effect of systolic and diastolic blood pressures together was similar to that of PP. In this population of patients with hypertension and left ventricular hypertrophy, PP was the strongest single blood pressure predictor of new......Previous studies have found pulse pressure (PP), a marker of arterial stiffness, to be an independent predictor of atrial fibrillation (AF) in general and hypertensive populations. We examined whether PP predicted new-onset AF in comparison with other blood pressure components in the Losartan...... Intervention For Endpoint reduction in hypertension study, a double-blind, randomized (losartan versus atenolol), parallel-group study, including 9193 patients with hypertension and electrocardiographic left ventricular hypertrophy. In 8810 patients with neither a history of AF nor AF at baseline, Minnesota...

  19. Blood pressure and left ventricular hypertrophy during American-style football participation.

    Science.gov (United States)

    Weiner, Rory B; Wang, Francis; Isaacs, Stephanie K; Malhotra, Rajeev; Berkstresser, Brant; Kim, Jonathan H; Hutter, Adolph M; Picard, Michael H; Wang, Thomas J; Baggish, Aaron L

    2013-07-30

    Hypertension, a strong determinant of cardiovascular disease risk, has been documented among elite, professional American-style football (ASF) players. The risk of increased blood pressure (BP) and early adulthood hypertension among the substantially larger population of collegiate ASF athletes is not known. We conducted a prospective, longitudinal study to examine BP, the incidence of hypertension, and left ventricular remodeling among collegiate ASF athletes. Resting BP and left ventricular structure were assessed before and after a single season of competitive ASF participation in 6 consecutive groups of first-year university athletes (n=113). ASF participation was associated with significant increases in systolic BP (116±8 versus 125±13 mm Hg; Phistory of hypertension were the strongest independent predictors of postseason BP. Among linemen, there was a significant increase in the prevalence of concentric left ventricular hypertrophy (2 of 64 [3%] versus 20 of 64 [31%]; P<0.001) and change in left ventricular mass correlated with intraseason change in systolic BP (R=0.46, P<0.001). Collegiate ASF athletes may be at risk for clinically relevant increases in BP and the development of hypertension. Enhanced surveillance and carefully selected interventions may represent important opportunities to improve later-life cardiovascular health outcomes in this population.

  20. Dipyridamole-thallium tests are predictive of severe cardiac arrhythmias in patients with left ventricular hypertrophy

    International Nuclear Information System (INIS)

    Saragoca, M.A.; Canziani, M.E.; Gil, M.A.; Castiglioni, M.L.; Cassiolato, J.L.; Barbieri, A.; Lima, V.C.; Draibe, S.A.; Martinez, E.E.

    1991-01-01

    In a population of patients with chronic renal failure (CRF) and a high prevalence of left ventricular hypertrophy (LVH) undergoing chronic hemodialysis, the authors investigated the association between the results of dipyridamole-thallium tests (DTTs) and the occurrence of ventricular arrhythmias. They observed a positive significant association between positive DTTs and the occurrence of severe forms of ventricular arrhythmias. A significant association was also observed between the presence of severe LVH and the occurrence of severe ventricular arrhythmias. However, no association was found between the presence of LVH and the positivity of the DTT. As most of their patients with positive DTTs had unimpaired coronary circulations, they conclude that positive DTTs, although falsely indicative of impaired myocardial blood supply, does have an important clinical relevance, indicating increased risk of morbidity (and, possibly, mortality) due to ventricular arrhythmias in a population of CRF patients submitted to chronic renal function replacement program

  1. Neurotransmission to parasympathetic cardiac vagal neurons in the brain stem is altered with left ventricular hypertrophy-induced heart failure.

    Science.gov (United States)

    Cauley, Edmund; Wang, Xin; Dyavanapalli, Jhansi; Sun, Ke; Garrott, Kara; Kuzmiak-Glancy, Sarah; Kay, Matthew W; Mendelowitz, David

    2015-10-01

    Hypertension, cardiac hypertrophy, and heart failure (HF) are widespread and debilitating cardiovascular diseases that affect nearly 23 million people worldwide. A distinctive hallmark of these cardiovascular diseases is autonomic imbalance, with increased sympathetic activity and decreased parasympathetic vagal tone. Recent device-based approaches, such as implantable vagal stimulators that stimulate a multitude of visceral sensory and motor fibers in the vagus nerve, are being evaluated as new therapeutic approaches for these and other diseases. However, little is known about how parasympathetic activity to the heart is altered with these diseases, and this lack of knowledge is an obstacle in the goal of devising selective interventions that can target and selectively restore parasympathetic activity to the heart. To identify the changes that occur within the brain stem to diminish the parasympathetic cardiac activity, left ventricular hypertrophy was elicited in rats by aortic pressure overload using a transaortic constriction approach. Cardiac vagal neurons (CVNs) in the brain stem that generate parasympathetic activity to the heart were identified with a retrograde tracer and studied using patch-clamp electrophysiological recordings in vitro. Animals with left cardiac hypertrophy had diminished excitation of CVNs, which was mediated both by an augmented frequency of spontaneous inhibitory GABAergic neurotransmission (with no alteration of inhibitory glycinergic activity) as well as a diminished amplitude and frequency of excitatory neurotransmission to CVNs. Opportunities to alter these network pathways and neurotransmitter receptors provide future targets of intervention in the goal to restore parasympathetic activity and autonomic balance to the heart in cardiac hypertrophy and other cardiovascular diseases. Copyright © 2015 the American Physiological Society.

  2. Electrocardiographic left ventricular hypertrophy in GUSTO IV ACS: an important risk marker of mortality in women

    DEFF Research Database (Denmark)

    Westerhout, Cynthia M; Lauer, Michael S; Fu, Yuling

    2007-01-01

    AIM: To examine the association of left ventricular hypertrophy (LVH) on admission electrocardiography with adverse outcomes in acute coronary syndrome (ACS) patients. METHODS AND RESULTS: A total of 7443 non-ST-elevation ACS patients in Global Utilization of STrategies to Open occluded arteries ...

  3. Release of atrial natriuretic peptide from rat myocardium in vitro: effect of minoxidil-induced hypertrophy.

    Science.gov (United States)

    Kinnunen, P.; Taskinen, T.; Leppäluoto, J.; Ruskoaho, H.

    1990-01-01

    1. Ventricular hypertrophy is characterized by stimulation of ventricular synthesis of atrial natriuretic peptide (ANP). To examine the role of ventricular ANP levels in the secretion of ANP into the circulation, atrial and ventricular levels of immunoreactive-ANP (IR-ANP) as well as ANP messenger RNA (mRNA), and the release of IR-ANP from isolated perfused hearts, both before and after atrialectomy, were measured simultaneously in control and minoxidil-treated Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. 2. IR-ANP levels in the ventricles of untreated, 12 month-old SHR with severe ventricular hypertrophy were increased when compared to age-matched WKY rats. Minoxidil treatment for 8 weeks in both strains resulted in a decrease in mean arterial pressure and increases in ventricular weight to body weight ratios, plasma IR-ANP concentrations (in WKY from 133 +/- 20 to 281 +/- 34 pg ml-1, P less than 0.01; in SHR from 184 +/- 38 to 339 +/- 61 pg ml-1, P less than 0.05), and in ventricular IR-ANP contents (in WKY: 53%; in SHR: 41%). A highly significant correlation was found between ventricular IR-ANP content and ventricular weight to body weight ratio (r = 0.59, P less than 0.001, n = 26). 3. When studied in vitro, in isolated perfused heart preparations, the hypertrophied ventricular tissue after atrialectomy secreted more ANP into the perfusate than ventricles of the control hearts; ventricles contributed 28%, 22%, 18% and 15% of the total ANP release to perfusate in the minoxidil-treated SHR, control SHR, minoxidil-treated WKY and control WKY, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2141796

  4. Increased sarcolemmal Na+/H+ exchange activity in hypertrophied myocytes from dogs with chronic atrioventricular block

    NARCIS (Netherlands)

    van Borren, Marcel M. G. J.; Vos, Marc A.; Houtman, Marien J. C.; Antoons, Gudrun; Ravesloot, Jan H.

    2013-01-01

    Dogs with compensated biventricular hypertrophy due to chronic atrioventricular block (cAVB), are more susceptible to develop drug-induced Torsade-de-Pointes arrhythmias and sudden cardiac death. It has been suggested that the increased Na+ influx in hypertrophied cAVB ventricular myocytes

  5. Coronary artery calcification and ECG pattern of left ventricular hypertrophy or strain identify different healthy individuals at risk

    DEFF Research Database (Denmark)

    Diederichsen, Søren Zöga; Gerke, Oke; Olsen, Michael Hecht

    2013-01-01

    PURPOSE:: To improve risk stratification for development of ischaemic heart disease, several markers have been proposed. Both the presence of coronary artery calcification (CAC) and ECG pattern of left ventricular hypertrophy/strain have been shown to provide independent prognostic information....... In this study, we investigated the association between established risk factors, ECG measurements and the presence of coronary artery calcification. METHOD:: A random sample of healthy men and women aged 50 or 60 years were invited to the screening study. Established risk factors were measured. A noncontrast...... computed tomographic (CT) scan was performed to assess the CAC score. ECG analysis included left ventricular hypertrophy (LVH) using the Sokolow-Lyon criteria and the Cornell voltage × QRS duration product, and strain pattern based on ST segment depression and T-wave abnormalities. The association between...

  6. The characteristics of myocardial fatty acid metabolism in patients with left ventricular hypertrophy

    International Nuclear Information System (INIS)

    Isobe, Naoki; Toyama, Takuji; Hoshizaki, Hiroshi

    1999-01-01

    We evaluated the characteristics of myocardial fatty acid metabolism in patients with left ventricular hypertrophy (LVH). Myocardial imaging with 123 I-beta-methyl iodophenyl pentadecanoic acid (BMIPP) was performed in 28 patients with hypertrophic cardiomyopathy (HCM), 15 patients with hypertensive heart disease (HHD), 13 patients with aortic stenosis (AS) and 8 normal controls (NC). The patients with HCM consisted of 13 patients of asymmetric septal hypertrophy (ASH), 7 patients of diffuse hypertrophy (Diffuse-HCM) and 8 patients of apical hypertrophy (APH). Planar and SPECT images of BMIPP were acquired 15 minutes and 4 hours after tracer injection. Resting 201 Tl SPECT images and echocardiography were also performed on other days. We calculated heart/mediastinum count ratio and washout rate of BMIPP by using planar image. In patients with LVH, the incidence of reduced BMIPP uptake was more frequent than that of reduced 201 Tl uptake. In delayed images, more than 60% of patients with LVH reduced BMIPP uptake, especially remarkable for patients with ASH and APH. The washout rate of all cardiac hypertrophic disorders was tended to be higher than that of normal subjects. Reduced BMIPP uptake was frequently found in septal portion of anterior and inferior wall in patients with ASH, in inferior wall in patients with Diffuse-HCM and HHD, in apex in patients with APH and AS. These results suggest that BMIPP scintigraphy can differentiate three types of cardiac hypertrophy. (author)

  7. 123I-MIBG myocardial imaging in hypertensive patients. Abnormality progresses with left ventricular hypertrophy

    International Nuclear Information System (INIS)

    Mitani, Isao; Sumita, Shinichi; Takahashi, Nobukazu; Ochiai, Hisao; Ishii, Masao

    1996-01-01

    Twenty-seven patients with essential hypertension were prospectively studied with 123 I-labeled metaiodobenzyl-guanidine ( 123 I-MIBG) to assess the presence and location of impaired sympathetic innervation in hypertrophied myocardium. Thirteen patients had left ventricular hypertrophy on echocardiography, and 14 had normal echocardiograms. The wash-out ratio of 123 I-MIBG in these two groups did not differ significantly (35.3±6.1 and 35.4±5.1) but was higher than in control subjects (29.4±6.7). The delayed heart-to-mediastinum count ratio was lower in the patients with hypertrophy than in the patients without hypertrophy (1.93±0.28 and 2.22±0.21; p<0.05) and the control subjects (1.93±0.28 and 2.33±0.25; p<0.05). On SPECT imaging, abnormalities in segmental uptake were frequent at the posterior and postero-lateral wall in both groups, although the hypertrophic group had more significant impairment. Our results lead to the hypothesis that hypertension in more advanced stages may be associated not only with hypertrophic changes but also with more advanced regional impairment of cardiac sympathetic innervation. (author)

  8. Whole-exome sequencing and an iPSC-derived cardiomyocyte model provides a powerful platform for gene discovery in left ventricular hypertrophy

    Directory of Open Access Journals (Sweden)

    Degui eZhi

    2012-05-01

    Full Text Available Rationale: Left ventricular hypertrophy (LVH is a heritable predictor of cardiovascular disease, particularly in blacks. Objective: Determine the feasibility of combining evidence from two distinct but complimentary experimental approaches to identify novel genetic predictors of increased LV mass . Methods: Whole exome sequencing (WES was conducted in 7 African American sibling trios ascertained on high average familial LV mass indexed to height (LVMHT. WES identified 31,426 missense or nonsense mutations (MS/NS which were examined for association with LVMHT using linear mixed models adjusted for age, sex, body weight, and family relationship. To functionally assess WES findings, human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM were stimulated to induce hypertrophy; mRNA sequencing was used to determine expression differences associated with hypertrophy onset. Results: After correction for multiple testing, 295 MS/NS variants in 265 genes were associated with LVMHT. We identified 44 of 265 WES genes differentially expressed (P<0.05 in hypertrophied cells. To further prioritize these 44 candidates, 7 supportive statistical and annotation-based criteria were used to evaluate the relevance of these genes. Five genes, HLA-B, HTT, MTSS1, SLC5A12, THBS1, were each supported by 3 criteria. THBS1 encodes an adhesive glycoprotein that promotes matrix preservation in pressure-overload LVH and harbors conserved and predicted damaging variants. Conclusions: Combining evidence from cutting-edge genetic and cellular experiments can enable identification of novel LVH risk loci.

  9. Left ventricular hypertrophy in normoalbuminuric type 2 diabetic patients not taking antihypertensive treatment

    DEFF Research Database (Denmark)

    Sato, A; Tarnow, L; Nielsen, F S

    2005-01-01

    BACKGROUND: Left ventricular hypertrophy (LVH) is an independent risk factor for myocardial ischaemia, cardiac arrhythmia, sudden death, and heart failure, all common findings in patients with type 2 diabetes. AIM: To determine the prevalence of, and risk factors for, LVH in normoalbuminuric type 2...... diabetic patients not taking antihypertensive treatment. DESIGN: Cross-sectional study. METHODS: From 1994 to 1998, M-mode echocardiography was performed by one experienced examiner in 262 consecutive, normoalbuminuric Caucasian type 2 diabetic patients, all with blood pressure ... of diabetes and blood pressure were not. Similar results were obtained for left ventricular mass index. DISCUSSION: LVH was frequent in our normoalbuminuric type 2 diabetic patients not taking antihypertensive treatment. Several potentially modifiable risk factors, such as raised BMI, poor glycaemic control...

  10. Impact of diabetes on treatment-induced changes in left ventricular structure and function in hypertensive patients with left ventricular hypertrophy. The LIFE study

    DEFF Research Database (Denmark)

    Gerdts, E; Okin, P M; Omvik, P

    2009-01-01

    in diabetic and non-diabetic groups during treatment (33/18 vs. 28/16mmHg (ns)), diabetes was associated with higher prevalence of persistent LVH (47 vs. 39%, pdiabetes independently predicted less LV mass reduction and less improvement in stress-corrected LV midwall......BACKGROUND AND AIM: Diabetes is associated with left ventricular hypertrophy (LVH) and impaired systolic function in hypertensive patients, but less is known about its impact on LVH regression and functional improvement during antihypertensive treatment. METHODS AND RESULTS: We performed annual...... echocardiography in 730 non-diabetic and 93 diabetic patients (aged 55-80 years) with hypertension and electrocardiographic LVH during 4.8-year losartan- or atenolol-based treatment in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. Baseline mean blood pressure (BP) and LV mass did...

  11. Exercise-induced arterial hypertension - an independent factor for hypertrophy and a ticking clock for cardiac fatigue or atrial fibrillation in athletes?

    Science.gov (United States)

    Leischik, Roman; Spelsberg, Norman; Niggemann, Hiltrud; Dworrak, Birgit; Tiroch, Klaus

    2014-01-01

    Background : Exercise-induced arterial hypertension (EIAH) leads to myocardial hypertrophy and is associated with a poor prognosis. EIAH might be related to the "cardiac fatigue" caused by endurance training. The goal of this study was to examine whether there is any relationship between EIAH and left ventricular hypertrophy in Ironman-triathletes. We used echocardiography and spiroergometry to determine the left ventricular mass (LVM), the aerobic/anaerobic thresholds and the steady-state blood pressure of 51 healthy male triathletes. The main inclusion criterion was the participation in at least one middle or long distance triathlon. When comparing triathletes with LVM 220g there was a significant difference between blood pressure values (BP) at the anaerobic threshold (185.2± 21.5 mmHg vs. 198.8 ±22.3 mmHg, p=0.037). The spiroergometric results were: maximum oxygen uptake (relative VO 2max) 57.3 ±7.5ml/min/kg vs. 59.8±9.5ml/min/kg (p=ns). Cut-point analysis for the relationship of BP >170 mmHg at the aerobic threshold and the probability of LVM >220g showed a sensitivity of 95.8%, a specificity of 33.3%, with a positive predictive value of 56.8 %, a good negative predictive value of 90%. The probability of LVM >220g increased with higher BP during exercise (OR: 1.027, 95% CI 1.002-1.052, p= 0.034) or with higher training volume (OR: 1.23, 95% CI 1.04 -1.47, p = 0.019). Echocardiography showed predominantly concentric remodelling, followed by concentric hypertrophy. Significant left ventricular hypertrophy with LVM >220g is associated with higher arterial blood pressure at the aerobic or anaerobic threshold. The endurance athletes with EIAH may require a therapeutic intervention to at least prevent extensive stiffening of the heart muscle and exercise-induced cardiac fatigue.

  12. Relations among impaired coronary flow reserve, left ventricular hypertrophy and thallium perfusion defects in hypertensive patients without obstructive coronary artery disease

    International Nuclear Information System (INIS)

    Houghton, J.L.; Frank, M.J.; Carr, A.A.; von Dohlen, T.W.; Prisant, L.M.

    1990-01-01

    Invasive Doppler catheter-derived coronary flow reserve, echocardiographic measurements of left ventricular hypertrophy and intravenous dipyridamole-limited stress thallium-201 scintigraphy were compared in 48 patients (40 were hypertensive or diabetic) with clinical ischemic heart disease and no or minor coronary artery disease. Abnormal vasodilator reserve (ratio less than 3:1) occurred in 50% of the study group and markedly abnormal reserve (less than or equal to 2:1) occurred in 27%. Coronary vasodilator reserve was significantly lower (2.2 +/- 0.8 versus 3.5 +/- 1.3, p = 0.003) and indexed left ventricular mass significantly higher (152.6 +/- 42.2 versus 113.6 +/- 24.0 g, p = 0.0007) in patients with a positive (n = 11) versus a negative (n = 32) thallium perfusion scan. Coronary flow reserve was linearly related in coronary basal flow velocity as follows: y = -0.17x + 4.59; r = -0.57; p = 0.00002. The decrement in flow reserve was not linearly related to the degree of left ventricular hypertrophy. Abnormal vasodilator reserve subsets found in hypertensive patients were defined on the basis of basal flow velocity, indexed left ventricular mass and clinical factors. In this series, diabetes did not cause a detectable additional decrement in flow reserve above that found with hypertension alone. These findings demonstrate that thallium perfusion defects are associated with depressed coronary vasodilator reserve in hypertensive patients without obstructive coronary artery disease. Left ventricular hypertrophy by indexed mass criteria is predictive of which hypertensive patients are likely to have thallium defects

  13. Quercetin prevents left ventricular hypertrophy in the Apo E knockout mouse

    Directory of Open Access Journals (Sweden)

    Elena Ulasova

    2013-01-01

    Full Text Available Hypercholesterolemia is a risk factor for the development of hypertrophic cardiomyopathy. Nevertheless, there are few studies aimed at determining the effects of dietary compounds on early or mild cardiac hypertrophy associated with dyslipidemia. Here we describe left ventricular (LV hypertrophy in 12 week-old Apo E−/− hypercholesterolemic mice. The LV end diastolic posterior wall thickness and overall LV mass were significantly increased in Apo E−/− mice compared with wild type (WT controls. Fractional shortening, LV end diastolic diameter, and hemodynamic parameters were unchanged from WT mice. Oral low dose quercetin (QCN; 0.1 µmol QCN/kg body weight for 6 weeks significantly reduced total cholesterol and very low density lipoprotein in the plasma of Apo E−/− mice. QCN treatment also significantly decreased LV posterior wall thickness and LV mass in Apo E−/− mice. Myocardial geometry and function were unaffected in WT mice by QCN treatment. These data suggest that dietary polyphenolic compounds such as QCN may be effective modulators of plasma cholesterol and could prevent maladaptive myocardial remodeling.

  14. Chronic sustained inflammation links to left ventricular hypertrophy and aortic valve sclerosis: a new link between S100/RAGE and FGF23.

    Science.gov (United States)

    Yan, Ling; Bowman, Marion A Hofmann

    Cardiovascular disease including left ventricular hypertrophy, diastolic dysfunction and ectopic valvular calcification are common in patients with chronic kidney disease (CKD). Both S100A12 and fibroblast growth factor 23 (FGF23) have been identified as biomarkers of cardiovascular morbidity and mortality in patients with CKD. We tested the hypothesis that human S100/calgranulin would accelerate cardiovascular disease in mice subjected to CKD. This review paper focuses on S100 proteins and their receptor for advanced glycation end products (RAGE) and summarizes recent findings obtained in novel developed transgenic hBAC-S100 mice that express S100A12 and S100A8/9 proteins. A bacterial artificial chromosome of the human S100/calgranulin gene cluster containing the genes and regulatory elements for S100A8, S100A9 and S100A12 was expressed in C57BL/6J mice (hBAC-S100). CKD was induced by ureteral ligation, and hBAC-S100 mice and WT mice were studied after 10 weeks of chronic uremia. hBAC-S100 mice with CKD showed increased FGF23 in the heart, left ventricular hypertrophy (LVH), diastolic dysfunction, focal cartilaginous metaplasia and calcification of the mitral and aortic valve annulus together with aortic valve sclerosis. This phenotype was not observed in WT mice with CKD or in hBAC-S100 mice lacking RAGE with CKD, suggesting that the inflammatory milieu mediated by S100/RAGE promotes pathological cardiac hypertrophy in CKD. In vitro, inflammatory stimuli including IL-6, TNFα, LPS, or serum from hBAC-S100 mice up regulated FGF23 mRNA and protein in primary murine neonatal and adult cardiac fibroblasts. Taken together, our study shows that myeloid-derived human S100/calgranulin is associated with the development of cardiac hypertrophy and ectopic cardiac calcification in a RAGE dependent manner in a mouse model of CKD. We speculate that FGF23 produced by cardiac fibroblasts in response to cytokines may act in a paracrine manner to accelerate LVH and diastolic

  15. Enalaprilato na prevenção da hipertrofia ventricular esquerda induzida pelo isoproterenol Enalaprilat prevents the left ventricular hypertrophy induced by isoproterenol

    Directory of Open Access Journals (Sweden)

    Eduardo A. S. Costa

    1997-07-01

    Full Text Available OBJETIVO: Avaliar se o enalaprilato, droga inibidora da enzima de conversão da angiotensina I, previne a hipertrofia ventricular esquerda (HVE induzida pelo isoproterenol. MÉTODOS: Foram divididos em 4 grupos, 72 ratos Wistar-EPM: CON controle; ENA, tratados com enalaprilato (1mg/kg via subcutânea (sc por 8 dias; ISO, tratados com isoproterenol (0,3mg/kg via sc/8 dias e ENA+ISO, tratados simultaneamente com ambas as drogas. Em 10 animais de cada grupo foram determinadas a freqüência cardíaca (FC e a pressão arterial (PA e verificado o peso de ventrículo esquerdo (VE. Em 8 animais de cada grupo, fragmento do VE foi corado com hematoxilina-eosina e picro-sírius e preparado para estudo morfométrico e ultra-estrutural, respectivamente, com microscópio de luz e eletrônico. RESULTADOS: Nos grupos estudados (CON, ENA, ISO e ISO+ENA não ocorreram variações na PA. Os grupos ISO e ISO+ENA exibiram aumentos significantes na FC. O grupo ISO apresentou aumento significativo do peso do VE (PU= 0,821g e PS= 0,204g, quando comparado ao grupo CON. O grupo ENA não exibiu modificação de peso do VE quando comparado ao grupo CON (PU= 0,590g e PS= 0,139g. No grupo ENA+ISO (PU= 0,737g e PS= 0,177g constatou-se diferença de peso ao ser comparado aos grupos ISO e CON. A análise morfométrica e ultra-estrutural mostraram que o ISO induziu hipertrofia dos cardiomiócitos e aumento do tecido conjuntivo com depósito de fibras colágenas do tipo I. O enalaprilato associado com isoproterenol atenuou importantemente aquela manifestação. CONCLUSÃO: O enalaprilato inibiu a ação do isoproterenol sobre os cardiomiócitos, evitando parcialmente, na dose utilizada, a HVE e diminuindo também a quantidade de fibras colágenas.PURPOSE: To evaluate whether the enalaprilat, angiotensin I enzyme conversion inhibitor, could prevent the left ventricular hypertrophy (LVH induced by isoproterenol. METHODS: Seventy two adult Wistar-EPM rats were divided into four

  16. Patients with FGF23-related hypophosphatemic rickets/osteomalacia do not present with left ventricular hypertrophy.

    Science.gov (United States)

    Takashi, Yuichi; Kinoshita, Yuka; Hori, Michiko; Ito, Nobuaki; Taguchi, Manabu; Fukumoto, Seiji

    2017-05-01

    Fibroblast growth factor 23 (FGF23) is a hormone regulating phosphate metabolism. Excessive actions of FGF23 cause several types of FGF23-related hypophosphatemic rickets/osteomalacia. Recently, it was reported that FGF23 levels were independently correlated with left ventricular hypertrophy (LVH) in patients with chronic kidney disease (CKD). In addition, FGF23 was also shown to cause cardiac hypertrophy directly acting on cardiomyocytes. However, there is no study indicating the correlation between FGF23 and LVH in adult patients with FGF23-related hypophosphatemic rickets/osteomalacia. Therefore, we examined the existence of LVH in these patients. We recruited consecutive 24 patients with FGF23-related hypophosphatemic diseases. Their serum intact FGF23 levels and the parameters associated with LVH, including left ventricular mass index (LVMI), relative wall thickness (RWT), Sokolow-Lyon voltage, and Cornell product, were measured. The correlations between FGF23 and these parameters were examined. The participants did not show LVH on the whole. In addition, no significant correlation was observed by these examinations. It seems unlikely that FGF23 levels are the apparent determinant of the cardiac mass in patients with FGF23-related hypophosphatemic rickets/osteomalacia.

  17. Clinical value of regression of electrocardiographic left ventricular hypertrophy after aortic valve replacement.

    Science.gov (United States)

    Yamabe, Sayuri; Dohi, Yoshihiro; Higashi, Akifumi; Kinoshita, Hiroki; Sada, Yoshiharu; Hidaka, Takayuki; Kurisu, Satoshi; Shiode, Nobuo; Kihara, Yasuki

    2016-09-01

    Electrocardiographic left ventricular hypertrophy (ECG-LVH) gradually regressed after aortic valve replacement (AVR) in patients with severe aortic stenosis. Sokolow-Lyon voltage (SV1 + RV5/6) is possibly the most widely used criterion for ECG-LVH. The aim of this study was to determine whether decrease in Sokolow-Lyon voltage reflects left ventricular reverse remodeling detected by echocardiography after AVR. Of 129 consecutive patients who underwent AVR for severe aortic stenosis, 38 patients with preoperative ECG-LVH, defined by SV1 + RV5/6 of ≥3.5 mV, were enrolled in this study. Electrocardiography and echocardiography were performed preoperatively and 1 year postoperatively. The patients were divided into ECG-LVH regression group (n = 19) and non-regression group (n = 19) according to the median value of the absolute regression in SV1 + RV5/6. Multivariate logistic regression analysis was performed to assess determinants of ECG-LVH regression among echocardiographic indices. ECG-LVH regression group showed significantly greater decrease in left ventricular mass index and left ventricular dimensions than Non-regression group. ECG-LVH regression was independently determined by decrease in the left ventricular mass index [odds ratio (OR) 1.28, 95 % confidence interval (CI) 1.03-1.69, p = 0.048], left ventricular end-diastolic dimension (OR 1.18, 95 % CI 1.03-1.41, p = 0.014), and left ventricular end-systolic dimension (OR 1.24, 95 % CI 1.06-1.52, p = 0.0047). ECG-LVH regression could be a marker of the effect of AVR on both reducing the left ventricular mass index and left ventricular dimensions. The effect of AVR on reverse remodeling can be estimated, at least in part, by regression of ECG-LVH.

  18. Association between routine and standardized blood pressure measurements and left ventricular hypertrophy among patients on hemodialysis.

    Science.gov (United States)

    Khangura, Jaspreet; Culleton, Bruce F; Manns, Braden J; Zhang, Jianguo; Barnieh, Lianne; Walsh, Michael; Klarenbach, Scott W; Tonelli, Marcello; Sarna, Magdalena; Hemmelgarn, Brenda R

    2010-06-24

    Left ventricular (LV) hypertrophy is common among patients on hemodialysis. While a relationship between blood pressure (BP) and LV hypertrophy has been established, it is unclear which BP measurement method is the strongest correlate of LV hypertrophy. We sought to determine agreement between various blood pressure measurement methods, as well as identify which method was the strongest correlate of LV hypertrophy among patients on hemodialysis. This was a post-hoc analysis of data from a randomized controlled trial. We evaluated the agreement between seven BP measurement methods: standardized measurement at baseline; single pre- and post-dialysis, as well as mean intra-dialytic measurement at baseline; and cumulative pre-, intra- and post-dialysis readings (an average of 12 monthly readings based on a single day per month). Agreement was assessed using Lin's concordance correlation coefficient (CCC) and the Bland Altman method. Association between BP measurement method and LV hypertrophy on baseline cardiac MRI was determined using receiver operating characteristic curves and area under the curve (AUC). Agreement between BP measurement methods in the 39 patients on hemodialysis varied considerably, from a CCC of 0.35 to 0.94, with overlapping 95% confidence intervals. Pre-dialysis measurements were the weakest predictors of LV hypertrophy while standardized, post- and inter-dialytic measurements had similar and strong (AUC 0.79 to 0.80) predictive power for LV hypertrophy. A single standardized BP has strong predictive power for LV hypertrophy and performs just as well as more resource intensive cumulative measurements, whereas pre-dialysis blood pressure measurements have the weakest predictive power for LV hypertrophy. Current guidelines, which recommend using pre-dialysis measurements, should be revisited to confirm these results.

  19. Left atrial systolic force in hypertensive patients with left ventricular hypertrophy: the LIFE study

    DEFF Research Database (Denmark)

    Chinali, M.; Simone, G. de; Wachtell, K.

    2008-01-01

    In hypertensive patients without prevalent cardiovascular disease, enhanced left atrial systolic force is associated with left ventricular hypertrophy and increased preload. It also predicts cardiovascular events in a population with high prevalence of obesity. Relations between left atrial...... systolic force and left ventricular geometry and function have not been investigated in high-risk hypertrophic hypertensive patients. Participants in the Losartan Intervention For Endpoint reduction in hypertension echocardiography substudy without prevalent cardiovascular disease or atrial fibrillation (n...... = 567) underwent standard Doppler echocardiography. Left atrial systolic force was obtained from the mitral orifice area and Doppler mitral peak A velocity. Patients were divided into groups with normal or increased left atrial systolic force (>14.33 kdyn). Left atrial systolic force was high in 297...

  20. Left ventricular hypertrophy and risk of fatal and non-fatal stroke EUROSTROKE: a collaborative study among research centres in Europe

    NARCIS (Netherlands)

    M.L. Bots (Michiel); J. Tuomilehto; D.E. Grobbee (Diederick); P.J. Koudstaal (Peter Jan); Y. Nikitin; J.T. Salonen; P.C. Elwood; S. Malyutina; A. Freire de Concalves; J. Sivenius; A. di Carlo; P. Lagiou

    2002-01-01

    textabstractBACKGROUND: This study investigated the association between electrocardiographically assessed left ventricular hypertrophy (LVH) and fatal, non-fatal, haemorrhagic and ischaemic stroke in four European cohorts participating in EUROSTROKE. METHODS: EUROSTROKE is a

  1. Chronic high-fat diet-induced obesity decreased survival and increased hypertrophy of rats with experimental eccentric hypertrophy from chronic aortic regurgitation.

    Science.gov (United States)

    Dhahri, Wahiba; Drolet, Marie-Claude; Roussel, Elise; Couet, Jacques; Arsenault, Marie

    2014-09-24

    The composition of a diet can influence myocardial metabolism and development of left ventricular hypertrophy (LVH). The impact of a high-fat diet in chronic left ventricular volume overload (VO) causing eccentric LVH is unknown. This study examined the effects of chronic ingestion of a high-fat diet in rats with chronic VO caused by severe aortic valve regurgitation (AR) on LVH, function and on myocardial energetics and survival. Male Wistar rats were divided in four groups: Shams on control or high-fat (HF) diet (15 rats/group) and AR rats fed with the same diets (ARC (n = 56) and ARHF (n = 32)). HF diet was started one week before AR induction and the protocol was stopped 30 weeks later. As expected, AR caused significant LV dilation and hypertrophy and this was exacerbated in the ARHF group. Moreover, survival in the ARHF group was significantly decreased compared the ARC group. Although the sham animals on HF also developed significant obesity compared to those on control diet, this was not associated with heart hypertrophy. The HF diet in AR rats partially countered the expected shift in myocardial energy substrate preference usually observed in heart hypertrophy (from fatty acids towards glucose). Systolic function was decreased in AR rats but HF diet had no impact on this parameter. The response to HF diet of different fatty acid oxidation markers as well as the increase in glucose transporter-4 translocation to the plasma membrane compared to ARC was blunted in AR animals compared to those on control diet. HF diet for 30 weeks decreased survival of AR rats and worsened eccentric hypertrophy without affecting systolic function. The expected adaptation of myocardial energetics to volume-overload left ventricle hypertrophy in AR animals seemed to be impaired by the high-fat diet suggesting less metabolic flexibility.

  2. Evaluation of left ventricular hypertrophy using thallium-201 myocardial scintigraphy, echocardiography and vectorcardiography

    International Nuclear Information System (INIS)

    Tsukahara, Yasunori; Owada, Kenji; Suzuki, Shigebumi

    1983-01-01

    Thallium-201 ( 201 Tl) myocardial scintigraphy was performed in 40 patients with left ventricular hypertrophy(LVH). Twelve out of 40 patients had pressure overloading (Aortic stenosis: 5, Hypertension: 7), 14 patients had volume overloading (Aortic regurgitation: 9, Mitral regurgitation: 5) and 14 had idiopathic cardiomyopathy (Hypertrophic type (HCM): 8, Congestive type (CCM): 6), respectively. LV area, LV uptake index and Wall uptake ratio were calculated from left anterior oblique view of 201 Tl myocardial images. These three indices of both pressure overloading and volume overloading were significantly higher than those of controls. The degree of LVH was indicated by both LV area and LV uptake index. LV area was significantly larger in volume overloading than in pressure overloading. In idiopathic cardiomyopathy, these three indices of HCM and LV area and LV uptake index of CCM were significantly increased compared with those of controls. LV area of CCM was significantly larger than that of HCM, while Wall uptake ratio of HCM was significantly higher than that of CCM. LV uptake index and Wall uptake ratio of HCM became higher according as left ventricular cavity became smaller. LV area of CCM became larger in proportion as left ventricular cavity became larger and as left ventricular wall thickness became thinner. (author)

  3. Clustered metabolic abnormalities blunt regression of hypertensive left ventricular hypertrophy: the LIFE study

    DEFF Research Database (Denmark)

    de Simone, G; Okin, P M; Gerdts, E

    2009-01-01

    BACKGROUND AND AIMS: Clusters of metabolic abnormalities resembling phenotypes of metabolic syndrome predicted outcome in the LIFE study, independently of single risk markers, including obesity, diabetes and baseline ECG left ventricular hypertrophy (LVH). We examined whether clusters of two......-duration product (CP) over 5 years was assessed using a quadratic polynomial contrast, adjusting for age, sex, prevalent cardiovascular disease and treatment arm (losartan or atenolol). At baseline, despite similar blood pressures, CP was greater in the presence than in the absence of MetAb (p

  4. Uncontrolled hypertension is associated with coronary artery calcification and electrocardiographic left ventricular hypertrophy

    DEFF Research Database (Denmark)

    Nielsen, Mette Lundgren; Pareek, Manan; Gerke, O

    2015-01-01

    We conducted a 1:2 matched case-control study in order to evaluate whether the prevalence of coronary artery calcium (CAC) and electrocardiographic left ventricular hypertrophy (LVH) or strain was higher in patients with uncontrolled hypertension than in subjects from the general population......, and evaluate the association between CAC and LVH in patients with uncontrolled hypertension. Cases were patients with uncontrolled hypertension, whereas the controls were random individuals from the general population without cardiovascular disease. CAC score was assessed using a non-contrast computed...

  5. Left Ventricular Hypertrophy in Children with Hypertension: in Search of a Definition.

    Science.gov (United States)

    Sethna, Christine B; Leisman, Daniel E

    2016-08-01

    The purpose of this review is to provide background on the importance of left ventricular hypertrophy (LVH) in children with hypertension, to highlight various diagnostic modalities and measures for defining LVH, and to demonstrate the need for standardization and a consensus definition for LVH in the pediatric population. There is no clear consensus among specialists performing echocardiograms and treating clinicians on the definition of LVH in children with hypertension. In fact, there is considerable variation in every step of the evaluation of pediatric LVH. There is variation in every step of the assessment of LVH in the pediatric population. This variation exists in imaging modality, the type of measurement used, the method of calculating left ventricular mass (LVM), the method of indexing LVM to body size, the normalization method for the index used, the reference data used, the inclusion of confounders, the implementation in clinical practice, and the format for echocardiography reporting.

  6. Association between routine and standardized blood pressure measurements and left ventricular hypertrophy among patients on hemodialysis

    Directory of Open Access Journals (Sweden)

    Walsh Michael

    2010-06-01

    Full Text Available Abstract Background Left ventricular (LV hypertrophy is common among patients on hemodialysis. While a relationship between blood pressure (BP and LV hypertrophy has been established, it is unclear which BP measurement method is the strongest correlate of LV hypertrophy. We sought to determine agreement between various blood pressure measurement methods, as well as identify which method was the strongest correlate of LV hypertrophy among patients on hemodialysis. Methods This was a post-hoc analysis of data from a randomized controlled trial. We evaluated the agreement between seven BP measurement methods: standardized measurement at baseline; single pre- and post-dialysis, as well as mean intra-dialytic measurement at baseline; and cumulative pre-, intra- and post-dialysis readings (an average of 12 monthly readings based on a single day per month. Agreement was assessed using Lin's concordance correlation coefficient (CCC and the Bland Altman method. Association between BP measurement method and LV hypertrophy on baseline cardiac MRI was determined using receiver operating characteristic curves and area under the curve (AUC. Results Agreement between BP measurement methods in the 39 patients on hemodialysis varied considerably, from a CCC of 0.35 to 0.94, with overlapping 95% confidence intervals. Pre-dialysis measurements were the weakest predictors of LV hypertrophy while standardized, post- and inter-dialytic measurements had similar and strong (AUC 0.79 to 0.80 predictive power for LV hypertrophy. Conclusions A single standardized BP has strong predictive power for LV hypertrophy and performs just as well as more resource intensive cumulative measurements, whereas pre-dialysis blood pressure measurements have the weakest predictive power for LV hypertrophy. Current guidelines, which recommend using pre-dialysis measurements, should be revisited to confirm these results.

  7. The left atrium, atrial fibrillation, and the risk of stroke in hypertensive patients with left ventricular hypertrophy

    DEFF Research Database (Denmark)

    Wachtell, K.; Devereux, R.B.; Lyle, P.A.

    2008-01-01

    was superior to atenolol-based treatment for reducing new-onset AF and complications, especially stroke, associated with new-onset or pre-existing AF. Potential mechanisms of AF prevention by angiotensin receptor blockade supported by LIFE results include greater reduction in left atrial size and LV......The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study provided extensive data on predisposing factors, consequences, and prevention of atrial fibrillation (AF) in patients with hypertension and left ventricular (LV) hypertrophy. Randomized losartan-based treatment...... hypertrophy. Differential effects of antihypertensive treatment on the left atrium and left ventricle may help prevent AF and reduce risk of stroke associated with hypertensive heart disease Udgivelsesdato: 2008/12...

  8. Prevalencia de hipertrofia ventricular izquierda en pacientes diabéticos Prevalence of left ventricular hypertrophy in diabetic patients

    Directory of Open Access Journals (Sweden)

    Diego Valarezo-Sevilla

    2013-03-01

    Full Text Available Con el objetivo de establecer la prevalencia de hipertrofia ventricular izquierda (HVI en pacientes con diabetes mellitus tipo 2 (DM, se realizó un estudio transversal en estos pacientes, estableciendo sus características antropométricas, presión arterial y control metabólico. Para evaluar la presencia de HVI se empleó ecocardiografía transtorácica. El estudio incluyó 91 pacientes, en los cuales la prevalencia de HVI fue de 63,7%, siendo más frecuente en mujeres que en varones (p=0,001. Adicionalmente, se encontró un 46,2% de pacientes con disfunción diastólica del ventrículo izquierdo. Se concluye que existe una importante prevalencia de HVI en pacientes diabéticos sin antecedentes de causas definidas de hipertrofia. No se encontró relación con sexo, control metabólico, IMC y tiempo de diagnósticoIn order to establish the prevalence of left ventricular hypertrophy (LVH in patients with type 2 diabetes mellitus, (DM a cross-sectional study was conducted in these patients studying their anthropometric characteristics, blood pressure and metabolic control. To evaluate the presence of LVH, a trans-thoracic echocardiogram was used. The study included 91 patients, finding a 63.7% prevalence of HVI, with women being more affected than men (p=0.001. Additionally, 46.2% of patients were found to have diastolic dysfunction of the left ventricle. We conclude that there is an important prevalence of LVH in diabetic patients without defined causes of hypertrophy. There was no association with sex, metabolic control, BMI and time of diagnosis

  9. Myocardial perfusion in type 2 diabetes with left ventricular hypertrophy

    DEFF Research Database (Denmark)

    Hesse, Birger; Meyer, Christian; Nielsen, Flemming S

    2004-01-01

    The purpose of this study was to assess whether acute angiotensin-converting enzyme (ACE) inhibition would improve myocardial perfusion and perfusion reserve in a subpopulation of normotensive patients with diabetes and left ventricular hypertrophy (LVH), both independent risk factors of coronary...... disease. Using positron emission tomography (PET), we investigated the response of regional myocardial perfusion to acute ACE inhibition with i.v. infusion of perindoprilat (vs saline infusion as control, minimum interval 3 days) in 12 diabetic patients with LVH. Myocardial perfusion was quantified...... with controls, maximal perfusion was reduced in patients (1.8+/-0.6 vs 2.5+/-1.0 ml min(-1) g(-1); P2.7+/-1.0 vs 3.6+/-1.3; P=0.059). During perindoprilat infusion, myocardial perfusion reserve in patients increased to 3.9+/-0.9 ( P

  10. Left ventricular filling patterns in patients with systemic hypertension and left ventricular hypertrophy (the LIFE study). Losartan Intervention For Endpoint

    DEFF Research Database (Denmark)

    Wachtell, K; Smith, G; Gerdts, E

    2000-01-01

    Abnormal left ventricular (LV) filling may exist in early stages of hypertension. Whether this finding is related to LV hypertrophy is currently controversial. This study was undertaken to assess relations between abnormal diastolic LV filling and LV geometry in a large series of hypertensive...... (sex-adjusted Cornell voltage duration criteria or Sokolow-Lyon voltage criteria) after 14 days of placebo treatment. The patients' mean age was 67+/-7 years and 44% were women. One hundred forty patients (19%) had normal LV geometric pattern, 79 (11%) had concentric remodeling, 342 (45%) had eccentric...

  11. Psoriasis is associated with subsequent atrial fibrillation in hypertensive patients with left ventricular hypertrophy

    DEFF Research Database (Denmark)

    Bang, Casper N; Okin, Peter M; Køber, Lars

    2014-01-01

    BACKGROUND: Inflammation contributes to the pathogenesis of psoriasis as well as atrial fibrillation. The impact of psoriasis and its association with new-onset atrial fibrillation was assessed in hypertensive patients with left ventricular hypertrophy (LVH). METHODS: The predictive value...... or developed psoriasis and new-onset atrial fibrillation occurred in 506 patients (7.1%) during a mean follow-up of 4.7 ± 1.1 years. At baseline, the psoriasis patients were younger (65 ± 7 vs. 67 ± 7 years) and had less left ventricle hypertrophy by ECG Sokolow-Lyon voltage (27.6 ± 9.7 vs. 30.1 ± 10.4 mm...... of baseline or incident psoriasis for new-onset atrial fibrillation was evaluated in 7099 hypertensive patients with electrocardiographic LVH with no history of atrial fibrillation or other cardiovascular disease, in sinus rhythm on their baseline electrocardiogram. RESULTS: A total of 154 patients (2.2%) had...

  12. Serum uric acid is associated with new-onset diabetes in hypertensive patients with left ventricular hypertrophy: The LIFE Study

    DEFF Research Database (Denmark)

    Wiik, Benedicte P; Larstorp, Anne C K; Høieggen, Aud

    2010-01-01

    It is unclear whether serum uric acid (SUA) is associated with development of new-onset diabetes (NOD) in patients with hypertension and left ventricular hypertrophy (LVH). The aim of the present investigation was to test the hypothesis that SUA predicts development of NOD in these patients....

  13. Effect of Thymol on Serum Antioxidant Capacity of Rats Following Myocardial Hypertrophy

    Directory of Open Access Journals (Sweden)

    Mohabbat Jamhiri

    2017-07-01

    Full Text Available Abstract Background: Oxidative stress plays an important role in the pathogenesis of hypertension- induced cardiac hypertrophy. Plants are a rich source of antioxidant compounds. Thymol is a natural monoterpen phenol which is plentiful in some plants and shows many biological effects. The aim of the present study was to assess the effects of thymol on activity of antioxidant enzyme catalase, malondialdehyde (MDA level and the activity of the inhibition of free radical DPPH (2,2-Diphenyl-1-picryl-hydrazyl, following left ventricular hypertrophy in rats. Materials and Methods: In this experimental study, rats were divided into hypertrophied group without any treatment (H group and rats pretreated with 25 and 50 mg/kg/day of thymol (Thy25+H and Thy50+H groups, respectively. Intact animals were served as control (Ctl. Animal model of left ventricular hypertrophy was induced by abdominal aortic banding. Serum catalase (CAT activity, malondialdehyde (MDA level and the activity of inhibition of free radicals DPPH were determined by the biochemical methods. Results: In Thy25+H and Thy50+H groups, the CAT activity was increased significantly in serum (p<0.01, vs. Ctl. Also, serum level of MDA was decreased significantly compared to the group H in Thy25+H and Thy50+H groups (p<0.05 and p<0.001, respectively. The effect of inhibiting DPPH free radicals was increased significantly in Thy25+H and Thy50+H groups compared to the group H (p<0.001 and p<0.05, respectively. Conclusion: The findings of this study suggest that thymol as an antioxidant causes cardioprotective effects and as well as prevents left ventricular hypertrophy via augmentation of serum antioxidant capacity.

  14. Left ventricular mass in male adolescent athletes and non-athletes

    Directory of Open Access Journals (Sweden)

    Erling David Kaunang

    2014-10-01

    Full Text Available Background Systematic exercise leads to increased left ventricular mass, which may be misleading in a differential diagnosis of heart disease in athletes (physiologic hypertrophy versus pathologic hypertrophy. T he cause of left ventricular hypertrophy is an important risk factor in the morbidity and mortality of cardiovascular diseases. Objective To compare left ventricular mass and left ventricular hypertrophy in male adolescent athletes and non-athletes. Methods We conducted a cross-sectional, analytic study, from September to December 2012 in male adolescents aged 15-18 years. The case group included athletes from the Bina Taruna Football Club Manado, while the control group included non-athlete adolescents. All subjects underwent history-taking, physical examinations and further supporting examinations. Left ventricular mass was measured by cardiovascular echocardiography (Esaote Mylab 4.0 and calculated based on a formula. Left ventricular hypertrophy was defined as left ventricular mass of > 134 g/m2 body surface area. Results Subjects' mean left ventricular masses were 359.69 (SD 188.4; 95%CI 283.58 to 435.81 grams in the athlete group and 173.04 (SD 50.69; 95%CI 152.56 to 103.51 grams in the non· athlete group, a statistically significant difference (P=0.0001. Ventricular hypertrophy was found 76.9% compared to 11.5% in  the non-athlete group (P= 0.0001. Conclusion Left ventricular mass in athletes is bigger than in non-athletes. In addition, left ventricular hypertrophy is more cornmon in male adolescent athletes than in non-athletes.

  15. Relationship between plasma xanthine oxidoreductase activity and left ventricular ejection fraction and hypertrophy among cardiac patients.

    Directory of Open Access Journals (Sweden)

    Yuki Fujimura

    Full Text Available Xanthine oxidoreductase (XOR, which catalyzes purine catabolism, has two interconvertible forms, xanthine dehydrogenase and xanthine oxidase, the latter of which produces superoxide during uric acid (UA synthesis. An association between plasma XOR activity and cardiovascular and renal outcomes has been previously suggested. We investigated the potential association between cardiac parameters and plasma XOR activity among cardiology patients.Plasma XOR activity was measured by [13C2,15N2]xanthine coupled with liquid chromatography/triplequadrupole mass spectrometry. Among 270 patients who were not taking UA-lowering drugs, XOR activity was associated with body mass index (BMI, alanine aminotransferase (ALT, HbA1c and renal function. Although XOR activity was not associated with serum UA overall, patients with chronic kidney disease (CKD, those with higher XOR activity had higher serum UA among patients without CKD. Compared with patients with the lowest XOR activity quartile, those with higher three XOR activity quartiles more frequently had left ventricular hypertrophy. In addition, plasma XOR activity showed a U-shaped association with low left ventricular ejection fraction (LVEF and increased plasma B-type natriuretic peptide (BNP levels, and these associations were independent of age, gender, BMI, ALT, HbA1C, serum UA, and CKD stages.Among cardiac patients, left ventricular hypertrophy, low LVEF, and increased BNP were significantly associated with plasma XOR activity independent of various confounding factors. Whether pharmaceutical modification of plasma XOR activity might inhibit cardiac remodeling and improve cardiovascular outcome should be investigated in future studies.

  16. G protein-coupled receptor 56 regulates mechanical overload-induced muscle hypertrophy.

    Science.gov (United States)

    White, James P; Wrann, Christiane D; Rao, Rajesh R; Nair, Sreekumaran K; Jedrychowski, Mark P; You, Jae-Sung; Martínez-Redondo, Vicente; Gygi, Steven P; Ruas, Jorge L; Hornberger, Troy A; Wu, Zhidan; Glass, David J; Piao, Xianhua; Spiegelman, Bruce M

    2014-11-04

    Peroxisome proliferator-activated receptor gamma coactivator 1-alpha 4 (PGC-1α4) is a protein isoform derived by alternative splicing of the PGC1α mRNA and has been shown to promote muscle hypertrophy. We show here that G protein-coupled receptor 56 (GPR56) is a transcriptional target of PGC-1α4 and is induced in humans by resistance exercise. Furthermore, the anabolic effects of PGC-1α4 in cultured murine muscle cells are dependent on GPR56 signaling, because knockdown of GPR56 attenuates PGC-1α4-induced muscle hypertrophy in vitro. Forced expression of GPR56 results in myotube hypertrophy through the expression of insulin-like growth factor 1, which is dependent on Gα12/13 signaling. A murine model of overload-induced muscle hypertrophy is associated with increased expression of both GPR56 and its ligand collagen type III, whereas genetic ablation of GPR56 expression attenuates overload-induced muscle hypertrophy and associated anabolic signaling. These data illustrate a signaling pathway through GPR56 which regulates muscle hypertrophy associated with resistance/loading-type exercise.

  17. Loss of Akap1 Exacerbates Pressure Overload-Induced Cardiac Hypertrophy and Heart Failure

    Directory of Open Access Journals (Sweden)

    Gabriele G. Schiattarella

    2018-05-01

    Full Text Available Left ventricular hypertrophy (LVH is a major contributor to the development of heart failure (HF. Alterations in cyclic adenosine monophosphate (cAMP-dependent signaling pathways participate in cardiomyocyte hypertrophy and mitochondrial dysfunction occurring in LVH and HF. cAMP signals are received and integrated by a family of cAMP-dependent protein kinase A (PKA anchor proteins (AKAPs, tethering PKA to discrete cellular locations. AKAPs encoded by the Akap1 gene (mitoAKAPs promote PKA mitochondrial targeting, regulating mitochondrial structure and function, reactive oxygen species production, and cell survival. To determine the role of mitoAKAPs in LVH development, in the present investigation, mice with global genetic deletion of Akap1 (Akap1-/-, Akap1 heterozygous (Akap1+/-, and their wild-type (wt littermates underwent transverse aortic constriction (TAC or SHAM procedure for 1 week. In wt mice, pressure overload induced the downregulation of AKAP121, the major cardiac mitoAKAP. Compared to wt, Akap1-/- mice did not display basal alterations in cardiac structure or function and cardiomyocyte size or fibrosis. However, loss of Akap1 exacerbated LVH and cardiomyocyte hypertrophy induced by pressure overload and accelerated the progression toward HF in TAC mice, and these changes were not observed upon prevention of AKAP121 degradation in seven in absentia homolog 2 (Siah2 knockout mice (Siah2-/-. Loss of Akap1 was also associated to a significant increase in cardiac apoptosis as well as lack of activation of Akt signaling after pressure overload. Taken together, these results demonstrate that in vivo genetic deletion of Akap1 enhances LVH development and accelerates pressure overload-induced cardiac dysfunction, pointing at Akap1 as a novel repressor of pathological LVH. These results confirm and extend the important role of mitoAKAPs in cardiac response to stress.

  18. Loss of Akap1 Exacerbates Pressure Overload-Induced Cardiac Hypertrophy and Heart Failure.

    Science.gov (United States)

    Schiattarella, Gabriele G; Boccella, Nicola; Paolillo, Roberta; Cattaneo, Fabio; Trimarco, Valentina; Franzone, Anna; D'Apice, Stefania; Giugliano, Giuseppe; Rinaldi, Laura; Borzacchiello, Domenica; Gentile, Alessandra; Lombardi, Assunta; Feliciello, Antonio; Esposito, Giovanni; Perrino, Cinzia

    2018-01-01

    Left ventricular hypertrophy (LVH) is a major contributor to the development of heart failure (HF). Alterations in cyclic adenosine monophosphate (cAMP)-dependent signaling pathways participate in cardiomyocyte hypertrophy and mitochondrial dysfunction occurring in LVH and HF. cAMP signals are received and integrated by a family of cAMP-dependent protein kinase A (PKA) anchor proteins (AKAPs), tethering PKA to discrete cellular locations. AKAPs encoded by the Akap1 gene (mitoAKAPs) promote PKA mitochondrial targeting, regulating mitochondrial structure and function, reactive oxygen species production, and cell survival. To determine the role of mitoAKAPs in LVH development, in the present investigation, mice with global genetic deletion of Akap1 ( Akap1 -/- ), Akap1 heterozygous ( Akap1 +/- ), and their wild-type ( wt ) littermates underwent transverse aortic constriction (TAC) or SHAM procedure for 1 week. In wt mice, pressure overload induced the downregulation of AKAP121, the major cardiac mitoAKAP. Compared to wt, Akap1 -/- mice did not display basal alterations in cardiac structure or function and cardiomyocyte size or fibrosis. However, loss of Akap1 exacerbated LVH and cardiomyocyte hypertrophy induced by pressure overload and accelerated the progression toward HF in TAC mice, and these changes were not observed upon prevention of AKAP121 degradation in seven in absentia homolog 2 ( Siah2 ) knockout mice ( Siah2 -/- ). Loss of Akap1 was also associated to a significant increase in cardiac apoptosis as well as lack of activation of Akt signaling after pressure overload. Taken together, these results demonstrate that in vivo genetic deletion of Akap1 enhances LVH development and accelerates pressure overload-induced cardiac dysfunction, pointing at Akap1 as a novel repressor of pathological LVH. These results confirm and extend the important role of mitoAKAPs in cardiac response to stress.

  19. Reliability of Left Ventricular Hypertrophy by ECG Criteria in Children with Syncope: Do the Criteria Need to be Revised?

    Science.gov (United States)

    Banerjee, Maalika M; Ramesh Iyer, V; Nandi, Deipanjan; Vetter, Victoria L; Banerjee, Anirban

    2016-04-01

    In the outpatient setting, children who present with syncope routinely undergo electrocardiograms (ECG). Because of concerns for hypertrophic cardiomyopathy, children with syncope meeting ECG criteria for left ventricular hypertrophy (LVH) will frequently undergo an echocardiogram. Our objectives were to determine whether Davignon criteria for ECG waves overestimate LVH in children presenting with syncope, and to study the usefulness of echocardiography in these children. We hypothesize that the Davignon criteria presently used for interpretation of ECGs overestimate LVH, resulting in unnecessary echocardiography in this clinical setting. The clinical database of The Children's Hospital of Philadelphia was evaluated from 2002 to 2012 to identify children between 9 and 16 years of age, who presented with non-exercise-induced, isolated syncope. From this group of patients, only those with clear-cut evidence of LVH (by Davignon criteria), who also underwent an echocardiogram, were selected. A total of 136 children with syncope were identified as having LVH by Davignon ECG criteria. None of these patients manifested any evidence of hypertrophic cardiomyopathy, with normal ventricular septum (average Z-score -0.68 ± 0.84), LV posterior wall (average Z-score -0.66 ± 1.18) and LV mass (average Z-score 0.52 ± 1.29). No significant correlation was found between summed RV6 plus SV1 and LV mass. Correlations between additional ECG parameters and measures of LVH by echocardiography were similarly poor. In children presenting with syncope and LVH by ECG, there was no evidence of true LVH by echocardiography. We propose that the Davignon ECG criteria for interpreting LVH in children overestimate the degree of hypertrophy in these children and the yield of echocardiography is extremely low.

  20. Impact of left ventricular geometry on prognosis in hypertensive patients with left ventricular hypertrophy (the LIFE study)

    DEFF Research Database (Denmark)

    Gerdts, E.; Cramariuc, D.; Simone, G. de

    2008-01-01

    , and myocardial infarction) in 937 hypertensive patients with LV hypertrophy during 4.8 years losartan- or atenolol-based treatment in the Losartan Intervention for Endpoint reduction in hypertension (LIFE) echocardiography substudy. METHODS AND RESULTS: LV geometry was determined from LV mass/body surface area......AIMS: Less is known about the relation between in-treatment left ventricular (LV) geometry and risk of cardiovascular events. We assessed LV geometric patterns on baseline and annual echocardiograms as time-varying predictors of the primary composite endpoint (cardiovascular death, stroke...... including LV geometric patterns as time-varying variables and adjusting for treatment, Framingham risk score, race, and time-varying systolic blood pressure, the patterns independently predicted higher risk of primary composite endpoints [HR 2.99 (1.16-7.71) for concentric remodelling, HR 1.79 (1...

  1. Possible involvement of mitochondrial energy-producing ability in the development of right ventricular failure in monocrotaline-induced pulmonary hypertensive rats.

    Science.gov (United States)

    Daicho, Takuya; Yagi, Tatsuya; Abe, Yohei; Ohara, Meiko; Marunouchi, Tetsuro; Takeo, Satoshi; Tanonaka, Kouichi

    2009-09-01

    The present study was undertaken to explore the possible involvement of alterations in the mitochondrial energy-producing ability in the development of the right ventricular failure in monocrotaline-administered rats. The rats at the 6th week after subcutaneous injection of 60 mg/kg monocrotaline revealed marked myocardial hypertrophy and fibrosis, that is, severe cardiac remodeling. The time-course study on the cardiac hemodynamics of the monocrotaline-administered rat by the cannula and echocardiographic methods showed a reduction in cardiac double product, a decrease in cardiac output index, and an increase in the right ventricular Tei index, suggesting that the right ventricular failure was induced at the 6th week after monocrotaline administration in rats. The mitochondrial oxygen consumption rate of the right ventricular muscle isolated from the monocrotaline-administered animal was decreased, which was associated with a reduction in myocardial high-energy phosphates. Furthermore, the decrease in mitochondrial oxygen consumption rate was inversely related to the increase in the right ventricular Tei index of the monocrotaline-administered rats. These results suggest that impairment of the mitochondrial energy-producing ability is involved in the development of the right ventricular failure in monocrotaline-induced pulmonary hypertensive rats.

  2. Systolic left ventricular function according to left ventricular concentricity and dilatation in hypertensive patients

    DEFF Research Database (Denmark)

    Bang, Casper; Gerdts, Eva; Aurigemma, Gerard P

    2013-01-01

    Left ventricular hypertrophy [LVH, high left ventricular mass (LVM)] is traditionally classified as concentric or eccentric based on left ventricular relative wall thickness. We evaluated left ventricular systolic function in a new four-group LVH classification based on left ventricular dilatation...... [high left ventricular end-diastolic volume (EDV) index and concentricity (LVM/EDV)] in hypertensive patients....

  3. [Sigmoid septum: A variant of the ventricular hypertrophy or of the hypertrophic cardiomyopathy?].

    Science.gov (United States)

    Gentille-Lorente, Delicia; Salvadó-Usach, Teresa

    2016-01-01

    Sigmoid septum and hypertrophic cardiomyopathy presenting with left ventricular hypertrophy and, although they appear to be different entities, often involve problems in the differential diagnosis. This study was carried out to assess the prevalence and characteristics of the echocardiographic sigmoid septum and its differential findings regarding hypertrophic cardiomyopathy. Descriptive, observational and prospective study. A total of 1,770 patients were studied by echocardiography. Sigmoid septum (focal and isolated hypertrophy of the basal interventricular septum≥13mm in men and ≥12mm in women, exceeding ≥50% of the median septum thickness) was classified as «Type 1» (≤14mm) and «Type 2» (≥15mm). There were 59 cases of sigmoid septum (prevalence of 3.3%): 26 (1.5%) patients with type 1 (50% male) and 33 (1.9%) patients with type 2 (72.7% male); there were 25 (1.4%) cases of hypertrophic cardiomyopathy (76% male). The group with type 2 sigmoid septum differed from hypertrophic cardiomyopathy in: was older (73±10.5years; P<.0001), with more hypertension (84.8%; P<.0001), lower glomerular filtering (73.3±21.4ml/min; P=.007), lower repolarization abnormalities (18.2%; P=.004) and Cornell index (in men, 22.2±11mm; P=.041), more diastolic dysfunction (75%; P=.0089) and in ventricular morphology and fibrosis location in magnetic resonance. Regarding the hypertrophic cardiomyopathy, patients with type 2 sigmoid septum are older and generally hypertensive; otherwise, often they have no clear differences in their clinical, electrocardiographic or echocardiographic characteristics. Therefore, cardiac resonance is helpful in the differential diagnosis. Copyright © 2016 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

  4. Melatonin protects against myocardial hypertrophy induced by lipopolysaccharide.

    Science.gov (United States)

    Lu, Qi; Yi, Xin; Cheng, Xiang; Sun, Xiaohui; Yang, Xiangjun

    2015-04-01

    Melatonin is thought to have the ability of antiatherogenic, antioxidant, and vasodilatory. It is not only a promising protective in acute myocardial infarction but is also a useful tool in the treatment of pathological remodeling. However, its role in myocardial hypertrophy remains unclear. In this study, we investigated the protective effects of melatonin on myocardial hypertrophy induced by lipopolysaccharide (LPS) and to identify their precise mechanisms. The cultured myocardial cell was divided into six groups: control group, LPS group, LPS + ethanol (4%), LPS + melatonin (1.5 mg/ml) group, LPS + melatonin (3 mg/ml) group, and LPS + melatonin (6 mg/ml) group. The morphologic change of myocardial cell was observed by inverted phase contrast microscope. The protein level of myocardial cell was measured by Coomassie brilliant blue protein kit. The secretion level of tumor necrosis factor-α (TNF-α) was evaluated by enzyme-linked immunosorbent assay (ELISA). Ca(2+) transient in Fura-2/AM-loaded cells was measured by Till image system. The expression of Ca(2+)/calmodulin-dependent kinase II (CaMKII) and calcineurin (CaN) was measured by Western blot analysis. Our data demonstrated that LPS induced myocardial hypertrophy, promoted the secretion levels of TNF-α, and increased Ca(2+) transient level and the expression of CaMKII and CaN. Administration of melatonin 30 min prior to LPS stimulation dose-dependently attenuated myocardial hypertrophy. In conclusion, the results revealed that melatonin had the potential to protect against myocardial hypertrophy induced by LPS in vitro through downregulation of the TNF-α expression and retains the intracellular Ca(2+) homeostasis.

  5. Procollagen type III amino terminal peptide and myocardial fibrosis: A study in hypertensive patients with and without left ventricular hypertrophy.

    Science.gov (United States)

    dos Santos Moreira, Carlos; Serejo, Fátima; Alcântara, Paula; Ramalhinho, Vítor; Braz Nogueira, J

    2015-05-01

    An exaggerated accumulation of type I and type III fibrillar collagens occurs throughout the free wall and interventricular septum of patients with primary hypertension and left ventricular hypertrophy (LVH). In the present study the serum concentration of procollagen type III amino terminal peptide (PIIIP) was measured to determine the value of this peptide as a potential marker of ventricular fibrosis in hypertensive patients, particularly those with LVH. The study population consisted of patients with never-treated mild to moderate essential hypertension and 30 normotensive control subjects. Clinical, echocardiographic, electrocardiographic and biochemical parameters were assessed in all patients. Heart rate, body mass index and levels of blood pressure were increased in hypertensives, particularly those with LVH, compared to normotensive controls. Posterior wall thickness, left ventricular (LV) mass and LV mass index, and serum PIIIP concentration were also increased in hypertensives, with significant differences between the two hypertensive groups. The ratio between maximal early and late transmitral flow velocity measured during diastole was lower in hypertensives, particularly those with LVH, than in normotensive controls. The increase in PIIIP indicates that type III collagen synthesis increases in hypertensives, particularly those with LVH, implying that alterations in the heart in hypertension are the result not solely of hypertrophied LV muscle, but also of increased collagen deposition within the ventricular wall and around the coronary vessels. Thus, measurement of serum PIIIP could be a practical and useful tool in the non-invasive assessment of myocardial remodeling in hypertension. Copyright © 2014 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  6. 19-Hydroxyeicosatetraenoic acid and isoniazid protect against angiotensin II-induced cardiac hypertrophy

    Energy Technology Data Exchange (ETDEWEB)

    Elkhatali, Samya; El-Sherbeni, Ahmed A.; Elshenawy, Osama H. [Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta T6G 2E1 (Canada); Abdelhamid, Ghada [Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta T6G 2E1 (Canada); Department of Pharmacology and Toxicology, Faculty of Pharmacy, Helwan University, Helwan (Egypt); El-Kadi, Ayman O.S., E-mail: aelkadi@ualberta.ca [Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta T6G 2E1 (Canada)

    2015-12-15

    We have recently demonstrated that 19-hydroxyeicosatetraenoic acid (19-HETE) is the major subterminal-HETE formed in the heart tissue, and its formation was decreased during cardiac hypertrophy. In the current study, we examined whether 19-HETE confers cardioprotection against angiotensin II (Ang II)-induced cardiac hypertrophy. The effect of Ang II, with and without 19-HETE (20 μM), on the development of cellular hypertrophy in cardiomyocyte RL-14 cells was assessed by real-time PCR. Also, cardiac hypertrophy was induced in Sprague–Dawley rats by Ang II, and the effect of increasing 19-HETE by isoniazid (INH; 200 mg/kg/day) was assessed by heart weight and echocardiography. Also, alterations in cardiac cytochrome P450 (CYP) and their associated arachidonic acid (AA) metabolites were determined by real-time PCR, Western blotting and liquid-chromatography–mass-spectrometry. Our results demonstrated that 19-HETE conferred a cardioprotective effect against Ang II-induced cellular hypertrophy in vitro, as indicated by the significant reduction in β/α-myosin heavy chain ratio. In vivo, INH improved heart dimensions, and reversed the increase in heart weight to tibia length ratio caused by Ang II. We found a significant increase in cardiac 19-HETE, as well as a significant reduction in AA and its metabolite, 20-HETE. In conclusion, 19-HETE, incubated with cardiomyocytes in vitro or induced in the heart by INH in vivo, provides cardioprotection against Ang II-induced hypertrophy. This further confirms the role of CYP, and their associated AA metabolites in the development of cardiac hypertrophy. - Highlights: • We found 19-hydroxy arachidonic acid to protect cardiomyocytes from hypertrophy. • We validated the use of isoniazid as a cardiac 19-hydroxy arachidonic acid inducer. • We found isoniazid to increase protective and inhibit toxic eicosanoides. • We found isoniazid to protect against angiotensin-induced cardiac hypertrophy. • This will help to

  7. The Impact of a Non-Functional Thyroid Receptor Beta upon Triiodotironine-Induced Cardiac Hypertrophy in Mice

    Directory of Open Access Journals (Sweden)

    Güínever Eustáquio do Império

    2015-08-01

    Full Text Available Background/Aims: Thyroid hormone (TH signalling is critical for heart function. The heart expresses thyroid hormone receptors (THRs; THRα1 and THRβ1. We aimed to investigate the regulation mechanisms of the THRβ isoform, its association with gene expression changes and implications for cardiac function. Methods: The experiments were performed using adult male mice expressing TRβΔ337T, which contains the Δ337T mutation of the human THRB gene and impairs ligand binding. Cardiac function and RNA expression were studied after hypo-or hyperthyroidism inductions. T3-induced cardiac hypertrophy was not observed in TRβΔ337T mice, showing the fundamental role of THRβ in cardiac hypertrophy. Results: We identified a group of independently regulated THRβ genes, which includes Adrb2, Myh7 and Hcn2 that were normally regulated by T3 in the TRβΔ337T group. However, Adrb1, Myh6 and Atp2a2 were regulated via THRβ. The TRβΔ337T mice exhibited a contractile deficit, decreased ejection fraction and stroke volume, as assessed by echocardiography. In our model, miR-208a and miR-199a may contribute to THRβ-mediated cardiac hypertrophy, as indicated by the absence of T3-regulated ventricular expression in TRβΔ337T mice. Conclusion: THRβ has important role in the regulation of specific mRNA and miRNA in T3-induced cardiac hypertrophic growth and in the alteration of heart functions.

  8. Regression of left ventricular hypertrophy and microalbuminuria changes during antihypertensive treatment.

    Science.gov (United States)

    Rodilla, Enrique; Pascual, Jose Maria; Costa, Jose Antonio; Martin, Joaquin; Gonzalez, Carmen; Redon, Josep

    2013-08-01

    The objective of the present study was to assess the regression of left ventricular hypertrophy (LVH) during antihypertensive treatment, and its relationship with the changes in microalbuminuria. One hundred and sixty-eight previously untreated patients with echocardiographic LVH, 46 (27%) with microalbuminuria, were followed during a median period of 13 months (range 6-23 months) and treated with lifestyle changes and antihypertensive drugs. Twenty-four-hour ambulatory blood pressure monitoring, echocardiography and urinary albumin excretion were assessed at the beginning and at the end of the study period. Left ventricular mass index (LVMI) was reduced from 137 [interquartile interval (IQI), 129-154] to 121 (IQI, 104-137) g/m (P 50%) had the same odds of achieving regression of LVH as patients with normoalbuminuria (ORm 1.1; 95% CI 0.38-3.25; P = 0.85). However, those with microalbuminuria at baseline, who did not regress, had less probability of achieving LVH regression than the normoalbuminuric patients (OR 0.26; 95% CI 0.07-0.90; P = 0.03) even when adjusted for age, sex, initial LVMI, GFR, blood pressure and angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin receptor blocker (ARB) treatment during the follow-up. Patients who do not have a significant reduction in microalbuminuria have less chance of achieving LVH regression, independent of blood pressure reduction.

  9. Telomere length is associated with ACE I/D polymorphism in hypertensive patients with left ventricular hypertrophy

    DEFF Research Database (Denmark)

    Fyhrquist, Frej; Eriksson, Anders; Saijonmaa, Outi

    2013-01-01

    INTRODUCTION: Short telomeres are often associated with cardiovascular risk factors and age-related diseases, while the angiotensin converting enzyme (ACE) gene insertion/deletion polymorphism (DD, ID, II) has shown such associations less consistently. We hypothesized that telomere length...... and association of telomere length with cardiovascular risk is affected by ACE (I/D) genotype. METHODS: We measured leucocyte telomere length (LTL) by Southern blot and analysed ACE I/D genotypes in 1249 subjects with hypertension and left ventricular hypertrophy (LVH). We examined interactions of ACE I...

  10. Impact of abdominal obesity and ambulatory blood pressure in the diagnosis of left ventricular hypertrophy in never treated hypertensives.

    Science.gov (United States)

    Rodilla, Enrique; Costa, José A; Martín, Joaquin; González, Carmen; Pascual, Jose M; Redon, Josep

    2014-03-20

    The principal objective was to assess the prevalence of left ventricular hypertrophy (LVH) in hypertensive, never treated patients, depending on adjustment for body surface or height. Secondary objectives were to determine geometric alterations of the left ventricle and to analyze the interdependence of hypertension and obesity to induce LVH. Cross-sectional study that included 750 patients (387 men) aged 47 (13, SD) years who underwent ambulatory blood pressure (ABPM) monitoring and echocardiography. The prevalence of LVH was 40.4% (303 patients), adjusted for body surface area (BSA, LVHBSA), and 61.7% (463 patients), adjusted for height(2.7) (LVHheight(2.7)). In a multivariate logistic analysis, systolic BP24h, gender and presence of elevated microalbuminuria were associated with both LVHBSA and LVHheight(2.7). Increased waist circumference was the strongest independent predictor of LVHheight(2.7), but was not associated with LVHBSA. We found a significant interaction between abdominal obesity and systolic BP24h in LVHheight(2.7). Concentric remodelling seems to be the most prevalent alteration of left ventricular geometry in early stages of hypertension (37.5%). The impact of obesity as predictor of LVH in never treated hypertensives is present only when left ventricular mass (LVM) is indexed to height(2.7). Obesity interacts with systolic BP24h in an additive but not merely synergistic manner. Systolic BP24h is the strongest determinant of LVH when indexed for BSA. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  11. Exogenous cathepsin V protein protects human cardiomyocytes HCM from angiotensin Ⅱ-Induced hypertrophy.

    Science.gov (United States)

    Huang, Kun; Gao, Lu; Yang, Ming; Wang, Jiliang; Wang, Zheng; Wang, Lin; Wang, Guobin; Li, Huili

    2017-08-01

    Angiotensin (Ang) Ⅱ-induced cardiac hypertrophy can deteriorate to heart failure, a leading cause of mortality. Endogenous Cathepsin V (CTSV) has been reported to be cardioprotective against hypertrophy. However, little is known about the effect of exogenous CTSV on cardiac hypertrophy. We used the human cardiomyocytes HCM as a cell model to investigate the effects of exogenous CTSV on Ang Ⅱ-induced cardiac cell hypertrophy. Cell surface area and expression of classical markers of hypertrophy were analyzed. We further explored the mechanism of CTSV cardioprotective by assessing the levels and activities of PI3K/Akt/mTOR and MAPK signaling pathway proteins. We found that pre-treating cardiomyocytes with CTSV could significantly inhibit Ang Ⅱ-induced hypertrophy. The mRNA expression of hypertrophy markers ANP, BNP and β-MHC was obviously elevated in Ang Ⅱ-treated cardiac cells. Whereas, exogenous CTSV effectively halted this elevation. Further study revealed that the protective effects of exogenous CTSV might be mediated by repressing the phosphorylation of proteins in the PI3K/Akt/mTOR and MAPK pathways. Based on our results, we concluded that exogenous CTSV inhibited Ang Ⅱ-induced hypertrophy in HCM cells by inhibiting PI3K/Akt/mTOR. This study provides experimental evidence for the application of CTSV protein for the treatment of cardiac hypertrophy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Influence of hypertensive left ventricular hypertrophy on detection of ischemic area with exercise thallium-201 myocardial scintigraphy

    International Nuclear Information System (INIS)

    Toyama, Takuji; Nishimura, Tsunehiko; Uehara, Toshiisa

    1992-01-01

    Sixty-four patients with single left anterior descending artery disease having effort angina (group A: 40 patients with hypertrophic hypertension, group B: 10 patients with hypertrophic hypertension, group C: 14 patients with non-hypertrophic hypertension) were assessed to determine the influence of hypertensive left ventricular (LV) hypertrophy on detection of ischemic area. The criterion of hypertrophy by two-dimensional echocardiography was >12 mm in the wall thickness of interventricular septal or posterior wall. Population in Group B might show low detectability in ischemic area by 201 Tl myocardial scintigraphy (positive thallium rate 60%, defect score 2.7±3.6), and high lung thallium uptake and high frequence of ECG positive among three groups. In semiquantitative analysis, the washout rate of the posterolateral wall and %RD (delayed %uptake-initial %uptake) of the septal wall in patients with Group B were lowest among three groups. However, the washout rate in the septal wall against the posterior wall, and the initial %uptake and the delayed %uptake of the septal wall were not significantly different among three groups. We could conclude that the decreased washout rate in nonischemic area with hypertensive LV hypertrophy might make the ischemic area masked. (author)

  13. Aortic embolization of an Edwards SAPIEN prosthesis due to sigmoid left ventricular hypertrophy: Case report.

    Science.gov (United States)

    Yuksel, Isa Öner; Koklu, Erkan; Arslan, Sakir; Cagirci, Goksel; Kucukseymen, Selcuk

    2016-06-01

    Transcatheter aortic valve implantation (TAVI) is considered an alternative therapy in high-risk patients with severe aortic stenosis. Although a minimally invasive procedure, it is not free from complications, one of which is valve embolization at the time of TAVI. We present a case of embolization of a balloon-expandable aortic valve due to sigmoid left ventricular hypertrophy and managed with a second valve without surgery. The embolized valve was repositioned in the aortic arch between the left common carotid artery and the brachiocephalic trunk. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  14. Association of Interarm Systolic Blood Pressure Difference with Atherosclerosis and Left Ventricular Hypertrophy

    Science.gov (United States)

    Su, Ho-Ming; Lin, Tsung-Hsien; Hsu, Po-Chao; Chu, Chun-Yuan; Lee, Wen-Hsien; Chen, Szu-Chia; Lee, Chee-Siong; Voon, Wen-Chol; Lai, Wen-Ter; Sheu, Sheng-Hsiung

    2012-01-01

    An interarm systolic blood pressure (SBP) difference of 10 mmHg or more have been associated with peripheral artery disease and adverse cardiovascular outcomes. We investigated whether an association exists between this difference and ankle-brachial index (ABI), brachial-ankle pulse wave velocity (baPWV), and echocardiographic parameters. A total of 1120 patients were included in the study. The bilateral arm blood pressures were measured simultaneously by an ABI-form device. The values of ABI and baPWV were also obtained from the same device. Clinical data, ABIdifference ≥10 mmHg were compared and analyzed. We performed two multivariate forward analyses for determining the factors associated with an interarm SBP difference ≥10 mmHg [model 1: significant variables in univariate analysis except left ventricular mass index (LVMI); model 2: significant variables in univariate analysis except ABIdifference ≥10 mmHg. Female, hypertension, and high body mass index were also associated with an interarm SBP difference ≥10 mmHg. Our study demonstrated that ABIdifference of 10 mmHg or more. Detection of an interarm SBP difference may provide a simple method of detecting patients at increased risk of atherosclerosis and left ventricular hypertrophy. PMID:22927905

  15. Evaluation of myocardial disorders in patients with dilated cardiomyopathy and left ventricular eccentric hypertrophy

    International Nuclear Information System (INIS)

    Yamazaki, Junichi; Ohsawa, Hidefumi; Uchi, Takashi

    1992-01-01

    201 Tl myocardial SPECT was performed in cases of dilated cardiomyopathy and valvular heart disease with left ventricular eccentric hypertrophy, and the two groups were compared from the standpoint of the mechanism of onset of myocardial disorders. Significant coefficients of correlation were seen between the Tl score and LVDd (r=0.792, r=0.785) and Tl score and LVEF (r=-0.634, r=-0.555) in both dilated cardiomyopathy and valvular heart disease. In cases of valvular heart disease, significant correlation coefficients (r=-0.756, r=-0.720) between LVDd and r-WR (relative-washout rate), and Tl score and r-WR were observed, but no such correlation was seen in dilated cardiomyopathy. In valvular heart disease, a decrease in myocardial perfusion associated with enlargement of the left ventricle appeared, while in dilated cardiomyopathy, there was a marked decrease in LVEF in proportion to the thallium defect. Therefore, it was assumed that left ventricular wall disorders occur due to myocardial metabolic disorders and coronary microcirculation disorders. (author)

  16. Electrocardiographic Measures of Left Ventricular Hypertrophy in the Antihypertensive and Lipid-Lowering to Prevent Heart Attack Trial

    OpenAIRE

    Ernst, Michael E.; Davis, Barry R.; Soliman, Elsayed Z.; Prineas, Ronald J.; Okin, Peter M.; Ghosh, Alokananda; Cushman, William C.; Einhorn, Paula T.; Oparil, Suzanne; Grimm, Richard H.

    2016-01-01

    Left ventricular hypertrophy (LVH) predicts cardiovascular risk in hypertensive patients. We analyzed baseline/follow-up ECGs in 26,376 ALLHAT participants randomized to amlodipine (A), lisinopril (L), or chlorthalidone (C). Prevalent/incident LVH were examined using continuous and categorical classifications of Cornell voltage. At 2- and 4-years, prevalence of LVH in the C-group (5.57%; 6.14%) was not statistically different from A-group (2-years: 5.47%; p=0.806, 4-years: 6.54%; p=0.857), or...

  17. PERIOPERATIVE PERIOD FOLLOWING HEART TRANSPLANTATION WITH SEVERE LEFT VENTRICULAR HYPERTROPHY

    Directory of Open Access Journals (Sweden)

    V. N. Poptsov

    2012-01-01

    Full Text Available Use donor hearts with left ventricular hypertrophy (LVH is controversial. This category of heart recipients has increasing risk of early graft failure. We proposed that heart transplantation (HT with LVH ≥1.5 cm may be successful if performed in selective category patients from alternate transplant list. This study included 10 pati- ents (2 female and 8 male at the age 26–62 (44 ± 3, who needed urgent HT. This study showed that recipients with LVH ≥1.5 cm demanded more high and long inotropic support with adrenalin and dopamine, more fre- quent use of levosimendan infusion (in 40% of cases and intraaortic balloon conterpulsation (in 50% of cases. However we didn’t observed any difference in survival rate (90.0% vs 89.0% and ICU time (4.8 ± 0.6 days vs 4.1 ± 0.4 days between HT recipients with and without LVH. Our study showed that HT from donor with LVH ≥1.5 cm may be performed in patients, demanding urgent HT, with acceptable early posttransplant results. 

  18. Herbal Supplement Ameliorates Cardiac Hypertrophy in Rats with CCl4-Induced Liver Cirrhosis

    Directory of Open Access Journals (Sweden)

    Ping-Chun Li

    2012-01-01

    Full Text Available We used the carbon tetrachloride (CCl4 induced liver cirrhosis model to test the molecular mechanism of action involved in cirrhosis-associated cardiac hypertrophy and the effectiveness of Ocimum gratissimum extract (OGE and silymarin against cardiac hypertrophy. We treated male wistar rats with CCl4 and either OGE (0.02 g/kg B.W. or 0.04 g/kg B.W. or silymarin (0.2 g/kg B.W.. Cardiac eccentric hypertrophy was induced by CCl4 along with cirrhosis and increased expression of cardiac hypertrophy related genes NFAT, TAGA4, and NBP, and the interleukin-6 (IL-6 signaling pathway related genes MEK5, ERK5, JAK, and STAT3. OGE or silymarin co-treatment attenuated CCl4-induced cardiac abnormalities, and lowered expression of genes which were elevated by this hepatotoxin. Our results suggest that the IL-6 signaling pathway may be related to CCl4-induced cardiac hypertrophy. OGE and silymarin were able to lower liver fibrosis, which reduces the chance of cardiac hypertrophy perhaps by lowering the expressions of IL-6 signaling pathway related genes. We conclude that treatment of cirrhosis using herbal supplements is a viable option for protecting cardiac tissues against cirrhosis-related cardiac hypertrophy.

  19. The effect of 12 weeks of aerobic exercise on plasma levels of fibroblast growth factor 23, Angiotensin converting enzyme and left ventricular hypertrophy in hypertensive elderly women

    Directory of Open Access Journals (Sweden)

    Z Keshavarzi

    2017-06-01

    Conclusion: The results of this study demonstrated that aerobic exercise has a positive effect on heart function and serum levels of ACE, and can potentially reverse cardiac dysfunction associated with left ventricular hypertrophy.

  20. Secoisolariciresinol diglucoside attenuates cardiac hypertrophy and oxidative stress in monocrotaline-induced right heart dysfunction.

    Science.gov (United States)

    Puukila, Stephanie; Fernandes, Rafael Oliveira; Türck, Patrick; Carraro, Cristina Campos; Bonetto, Jéssica Hellen Poletto; de Lima-Seolin, Bruna Gazzi; da Rosa Araujo, Alex Sander; Belló-Klein, Adriane; Boreham, Douglas; Khaper, Neelam

    2017-08-01

    Pulmonary arterial hypertension (PAH) occurs when remodeling of pulmonary vessels leads to increased pulmonary vascular resistance resulting in increased pulmonary arterial pressure. Increased pulmonary arterial pressure results in right ventricle hypertrophy and eventually heart failure. Oxidative stress has been implicated in the pathogenesis of PAH and may play a role in the regulation of cellular signaling involved in cardiac response to pressure overload. Secoisolariciresinol diglucoside (SDG), a component from flaxseed, has been shown to reduce cardiac oxidative stress in various pathophysiological conditions. We investigated the potential protective effects of SDG in a monocrotaline-induced model of PAH. Five- to six-week-old male Wistar rats were given a single intraperitoneal injection of monocrotaline (60 mg/kg) and sacrificed 21 days later where heart, lung, and plasma were collected. SDG (25 mg/kg) was given via gavage as either a 21-day co-treatment or pre-treatment of 14 days before monocrotaline administration and continued for 21 days. Monocrotaline led to right ventricle hypertrophy, increased lipid peroxidation, and elevated plasma levels of alanine transaminase (ALT) and aspartate transaminase (AST). Co-treatment with SDG did not attenuate hypertrophy or ALT and AST levels but decreased reactive oxygen species (ROS) levels and catalase and superoxide dismutase activity compared to the monocrotaline-treated group. Pre-treatment with SDG decreased right ventricle hypertrophy, ROS levels, lipid peroxidation, catalase, superoxide dismutase, and glutathione peroxidase activity and plasma levels of ALT and AST when compared to the monocrotaline group. These findings indicate that pre-treatment with SDG provided better protection than co-treatment in this model of right heart dysfunction, suggesting an important role for SDG in PAH and right ventricular remodeling.

  1. Cinnamaldehyde impairs high glucose-induced hypertrophy in renal interstitial fibroblasts

    International Nuclear Information System (INIS)

    Chao, Louis Kuoping; Chang, W.-T.; Shih, Y.-W.; Huang, J.-S.

    2010-01-01

    Cinnamaldehyde is a major and a bioactive compound isolated from the leaves of Cinnamomum osmophloeum kaneh. To explore whether cinnamaldehyde was linked to altered high glucose (HG)-mediated renal tubulointerstitial fibrosis in diabetic nephropathy (DN), the molecular mechanisms of cinnamaldehyde responsible for inhibition of HG-induced hypertrophy in renal interstitial fibroblasts were examined. We found that cinnamaldehyde caused inhibition of HG-induced cellular mitogenesis rather than cell death by either necrosis or apoptosis. There were no changes in caspase 3 activity, cleaved poly(ADP-ribose) polymerase (PARP) protein expression, and mitochondrial cytochrome c release in HG or cinnamaldehyde treatments in these cells. HG-induced extracellular signal-regulated kinase (ERK)/c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (MAPK) (but not the Janus kinase 2/signal transducers and activators of transcription) activation was markedly blocked by cinnamaldehyde. The ability of cinnamaldehyde to inhibit HG-induced hypertrophy was verified by the observation that it significantly decreased cell size, cellular hypertrophy index, and protein levels of collagen IV, fibronectin, and α-smooth muscle actin (α-SMA). The results obtained in this study suggest that cinnamaldehyde treatment of renal interstitial fibroblasts that have been stimulated by HG reduces their ability to proliferate and hypertrophy through mechanisms that may be dependent on inactivation of the ERK/JNK/p38 MAPK pathway.

  2. Experimental and clinical study of cardiac hypertrophy by thallium-201 myocardial scintigraphy

    International Nuclear Information System (INIS)

    Torii, Yukio

    1983-01-01

    I studied experimentally the myocardial uptake of 201 Tl in cardiac hypertrophy in rat, and clinically evaluated cardiac shape and dimension in the patients with various types of cardiac hypertrophy. Experimentally, both myocardial blood flow (MBF) and Tl uptake were increased with cardiac weight. There were negative correlations between the extraction fraction and MBF. Tl uptake in Hypertrophy is not always dependent on MBF and affected by the altered metabolism of hypertrophied myocardium. Clinical study was performed in 29 normal subjects and in 90 patients with heart disease. The measurements of left ventricular (LV) size by Tl scintigraphy were well correlated with them by echocardiography. Aortic stenosis and hypertensive heart disease showed thick wall and spherical shape. Both mitral (MR) and aortic (AR) regurgitation showed ventricular dilatation, spherical shape (in chronic MR) and ellipsoid shape (in acute MR and in AR). Decreased ventricular size but normal shape was observed in mitral stenosis and cor pulmonale. Hypertrophic cardiomyopathy showed thick wall with asymmetric septal hypertrophy, while congestive cardiomyopathy showed thin wall with marked ventricular dilatation and spherical shape. I conclude that heart disease has characteristic figures in dimension and shape which may be reflecting cardiac performance or compensating for the load to the heart, and that 201 Tl scintigraphy is useful evaluating cardiac morphology as well as in diagnosing myocardial ischemia. (J.P.N.)

  3. Muscular and systemic correlates of resistance training-induced muscle hypertrophy.

    Science.gov (United States)

    Mitchell, Cameron J; Churchward-Venne, Tyler A; Bellamy, Leeann; Parise, Gianni; Baker, Steven K; Phillips, Stuart M

    2013-01-01

    To determine relationships between post-exercise changes in systemic [testosterone, growth hormone (GH), insulin like grow factor 1 (IGF-1) and interleukin 6 (IL-6)], or intramuscular [skeletal muscle androgen receptor (AR) protein content and p70S6K phosphorylation status] factors in a moderately-sized cohort of young men exhibiting divergent resistance training-mediated muscle hypertrophy. Twenty three adult males completed 4 sessions•wk⁻¹ of resistance training for 16 wk. Muscle biopsies were obtained before and after the training period and acutely 1 and 5 h after the first training session. Serum hormones and cytokines were measured immediately, 15, 30 and 60 minutes following the first and last training sessions of the study. Mean fiber area increased by 20% (range: -7 to 80%; P<0.001). Protein content of the AR was unchanged with training (fold change = 1.17 ± 0.61; P=0.19); however, there was a significant correlation between the changes in AR content and fiber area (r=0.60, P=0.023). Phosphorylation of p70S6K was elevated 5 hours following exercise, which was correlated with gains in mean fiber area (r=0.54, P=0.007). There was no relationship between the magnitude of the pre- or post-training exercise-induced changes in free testosterone, GH, or IGF-1 concentration and muscle fiber hypertrophy; however, the magnitude of the post exercise IL-6 response was correlated with muscle hypertrophy (r=0.48, P=0.019). Post-exercise increases in circulating hormones are not related to hypertrophy following training. Exercise-induced changes in IL-6 correlated with hypertrophy, but the mechanism for the role of IL-6 in hypertrophy is not known. Acute increases, in p70S6K phosphorylation and changes in muscle AR protein content correlated with muscle hypertrophy implicating intramuscular rather than systemic processes in mediating hypertrophy.

  4. Left ventricular hypertrophy is associated with increased infarct size and decreased myocardial salvage in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention

    DEFF Research Database (Denmark)

    Nepper-Christensen, Lars; Lønborg, Jacob; Ahtarovski, Kiril Aleksov

    2017-01-01

    Background--Approximately one third of patients with ST-segment elevation myocardial infarction (STEMI) have left ventricular hypertrophy (LVH), which is associated with impaired outcome. However, the causal association between LVH and outcome in STEMI is unknown. We evaluated the association bet...

  5. Irisin is a pro-myogenic factor that induces skeletal muscle hypertrophy and rescues denervation-induced atrophy.

    Science.gov (United States)

    Reza, Musarrat Maisha; Subramaniyam, Nathiya; Sim, Chu Ming; Ge, Xiaojia; Sathiakumar, Durgalakshmi; McFarlane, Craig; Sharma, Mridula; Kambadur, Ravi

    2017-10-24

    Exercise induces expression of the myokine irisin, which is known to promote browning of white adipose tissue and has been shown to mediate beneficial effects following exercise. Here we show that irisin induces expression of a number of pro-myogenic and exercise response genes in myotubes. Irisin increases myogenic differentiation and myoblast fusion via activation of IL6 signaling. Injection of irisin in mice induces significant hypertrophy and enhances grip strength of uninjured muscle. Following skeletal muscle injury, irisin injection improves regeneration and induces hypertrophy. The effects of irisin on hypertrophy are due to activation of satellite cells and enhanced protein synthesis. In addition, irisin injection rescues loss of skeletal muscle mass following denervation by enhancing satellite cell activation and reducing protein degradation. These data suggest that irisin functions as a pro-myogenic factor in mice.

  6. GSK-3β/NFAT Signaling Is Involved in Testosterone-Induced Cardiac Myocyte Hypertrophy.

    Directory of Open Access Journals (Sweden)

    Javier Duran

    Full Text Available Testosterone induces cardiac hypertrophy through a mechanism that involves a concerted crosstalk between cytosolic and nuclear signaling pathways. Nuclear factor of activated T-cells (NFAT is associated with the promotion of cardiac hypertrophy, glycogen synthase kinase-3β (GSK-3β is considered to function as a negative regulator, mainly by modulating NFAT activity. However, the role played by calcineurin-NFAT and GSK-3β signaling in testosterone-induced cardiac hypertrophy has remained unknown. Here, we determined that testosterone stimulates cardiac myocyte hypertrophy through NFAT activation and GSK-3β inhibition. Testosterone increased the activity of NFAT-luciferase (NFAT-Luc in a time- and dose-dependent manner, with the activity peaking after 24 h of stimulation with 100 nM testosterone. NFAT-Luc activity induced by testosterone was blocked by the calcineurin inhibitors FK506 and cyclosporine A and by 11R-VIVIT, a specific peptide inhibitor of NFAT. Conversely, testosterone inhibited GSK-3β activity as determined by increased GSK-3β phosphorylation at Ser9 and β-catenin protein accumulation, and also by reduction in β-catenin phosphorylation at residues Ser33, Ser37, and Thr41. GSK-3β inhibition with 1-azakenpaullone or a GSK-3β-targeting siRNA increased NFAT-Luc activity, whereas overexpression of a constitutively active GSK-3β mutant (GSK-3βS9A inhibited NFAT-Luc activation mediated by testosterone. Testosterone-induced cardiac myocyte hypertrophy was established by increased cardiac myocyte size and [3H]-leucine incorporation (as a measurement of cellular protein synthesis. Calcineurin-NFAT inhibition abolished and GSK-3β inhibition promoted the hypertrophy stimulated by testosterone. GSK-3β activation by GSK-3βS9A blocked the increase of hypertrophic markers induced by testosterone. Moreover, inhibition of intracellular androgen receptor prevented testosterone-induced NFAT-Luc activation. Collectively, these results

  7. Plzf as a Candidate Gene Predisposing the Spontaneously Hypertensive Rat to Hypertension, Left Ventricular Hypertrophy, and Interstitial Fibrosis

    Czech Academy of Sciences Publication Activity Database

    Liška, F.; Mancini, M.; Krupková, M.; Chylíková, B.; Křenová, D.; Šeda, O.; Šilhavý, Jan; Mlejnek, Petr; Landa, Vladimír; Zídek, Václav; d´Amati, G.; Pravenec, Michal; Křen, Vladimír

    2014-01-01

    Roč. 27, č. 1 (2014), s. 99-106 ISSN 0895-7061 R&D Projects: GA ČR(CZ) GAP301/10/0756; GA ČR(CZ) GAP301/12/0696; GA MŠk(CZ) LL1204; GA MŠk(CZ) 7E10067 Grant - others:Univerzita Karlova(CZ) PRVOUK-P25/LF1/2 Institutional support: RVO:67985823 Keywords : hypertension * left ventricular hypertrophy * myocardial interstitial fibrosis * spontaneously hypertensive rat * Plzf (promyelocytic leukemia zinc finger) gene Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.852, year: 2014

  8. Relation of maximum blood pressure during exercise and regular physical activity in normotensive men with left ventricular mass and hypertrophy. MARATHOM Investigators. Medida de la Actividad fisica y su Relación Ambiental con Todos los Lípidos en el HOMbre.

    Science.gov (United States)

    Molina, L; Elosua, R; Marrugat, J; Pons, S

    1999-10-15

    The relation between maximum systolic blood pressure (BP) during exercise and left ventricular (LV) mass is controversial. Physical activity also induces LV mass increase. The objective was to assess the relation between BP response to exercise and LV mass in normotensive men, taking into account physical activity practice. A cross-sectional study was performed. Three hundred eighteen healthy normotensive men, aged between 20 and 60 years, participated in this study. The Minnesota questionnaire was used to assess physical activity practice. An echocardiogram and a maximum exercise test were performed. LV mass was calculated and indexed to body surface area. LV hypertrophy was defined as a ventricular mass index > or =134 g/m2. BP was measured at the moment of maximum effort. Hypertensive response was considered when BP was > or =210 mm Hg. In the multiple linear regression model, maximum systolic BP was associated with LV mass index and correlation coefficient was 0.27 (SE 0.07). Physical activity practice and age were also associated with LV mass. An association between hypertensive response to exercise and LV hypertrophy was observed (odds ratio 3.16). Thus, BP response to exercise is associated with LV mass and men with systolic BP response > or =210 mm Hg present a 3-times higher risk of LV hypertrophy than those not reaching this limit. Physical activity practice is related to LV mass, but not to LV hypertrophy.

  9. Maternal left ventricular hypertrophy and diastolic dysfunction and brain natriuretic peptide concentration in early- and late-onset pre-eclampsia.

    Science.gov (United States)

    Borges, V T M; Zanati, S G; Peraçoli, M T S; Poiati, J R; Romão-Veiga, M; Peraçoli, J C; Thilaganathan, B

    2018-04-01

    Pre-eclampsia (PE) is associated with maternal cardiac remodeling and diastolic dysfunction. The aim of this study was to assess and compare maternal left ventricular structure and diastolic function and levels of brain natriuretic peptide (BNP) in women with early-onset (< 34 weeks' gestation) vs those with late-onset (≥ 34 weeks' gestation) PE. This was a prospective, cross-sectional, observational study of 30 women with early-onset PE, 32 with late-onset PE and 23 normotensive controls. Maternal cardiac structure and diastolic function were assessed by echocardiography and plasma levels of BNP were measured by enzyme immunoassay. Early- and late-onset PE were associated with increased left ventricular mass index and relative wall thickness compared with normotensive controls. In women with early-onset PE, the prevalence of concentric hypertrophy (40%) and diastolic dysfunction (23%) was also significantly higher (both P < 0.05) compared with women with late-onset PE (16% for both). Maternal serum BNP levels were significantly higher (P < 0.05) in women with early-onset PE and correlated with relative wall thickness and left ventricular mass index. Early-onset PE is associated with more severe cardiac impairment than is late-onset PE, as evidenced by an increased prevalence of concentric hypertrophy, diastolic dysfunction and higher levels of BNP. These findings suggest that early-onset PE causes greater myocardial damage, increasing the risk of both peripartum and postpartum cardiovascular morbidity. Although these cardiovascular effects are easily identified by echocardiographic parameters and measuring BNP, further studies are needed to assess their clinical utility. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

  10. Intermittent cardiac overload results in adaptive hypertrophy and provides protection against left ventricular acute pressure overload insult.

    Science.gov (United States)

    Moreira-Gonçalves, Daniel; Henriques-Coelho, Tiago; Fonseca, Hélder; Ferreira, Rita; Padrão, Ana Isabel; Santa, Cátia; Vieira, Sara; Silva, Ana Filipa; Amado, Francisco; Leite-Moreira, Adelino; Duarte, José Alberto

    2015-09-01

    The present study aimed to test whether a chronic intermittent workload could induce an adaptive cardiac phenotype Chronic intermittent workload induced features of adaptive hypertrophy This was paralleled by protection against acute pressure overload insult The heart may adapt favourably to balanced demands, regardless of the nature of the stimuli. The present study aimed to test whether submitting the healthy heart to intermittent and tolerable amounts of workload, independently of its nature, could result in an adaptive cardiac phenotype. Male Wistar rats were subjected to treadmill running (Ex) (n = 20), intermittent cardiac overload with dobutamine (ITO) (2 mg kg(-1) , s.c.; n = 20) or placebo administration (Cont) (n = 20) for 5 days week(-1) for 8 weeks. Animals were then killed for histological and biochemical analysis or subjected to left ventricular haemodynamic evaluation under baseline conditions, in response to isovolumetric contractions and to sustained LV acute pressure overload (35% increase in peak systolic pressure maintained for 2 h). Baseline cardiac function was enhanced only in Ex, whereas the response to isovolumetric heartbeats was improved in both ITO and Ex. By contrast to the Cont group, in which rats developed diastolic dysfunction with sustained acute pressure overload, ITO and Ex showed increased tolerance to this stress test. Both ITO and Ex developed cardiomyocyte hypertrophy without fibrosis, no overexpression of osteopontin-1 or β-myosin heavy chain, and increased expression of sarcoplasmic reticulum Ca(2+) protein. Regarding hypertrophic pathways, ITO and Ex showed activation of the protein kinase B/mammalian target of rapamycin pathway but not calcineurin. Mitochondrial complex IV and V activities were also increased in ITO and Ex. Chronic submission to controlled intermittent cardiac overload, independently of its nature, results in an adaptive cardiac phenotype. Features of the cardiac overload, such as the duration and

  11. Hipertrofia ventricular e mortalidade cardiovascular em pacientes de hemodiálise de baixo nível educacional Hipertrofia ventricular y mortalidad cardiovascular en pacientes de hemodiálisis de bajo nivel educativo Ventricular hypertrophy and cardiovascular mortality in hemodialysis patients with low educational level

    Directory of Open Access Journals (Sweden)

    Rosana dos Santos e Silva Martin

    2012-01-01

    escolaridad tienen hipertrofia ventricular más intensa. OBJETIVO: Ampliar estudio previo y verificar si la hipertrofia ventricular izquierda puede justificar la asociación entre escolaridad y mortalidad cardiovascular de pacientes en hemodiálisis. MÉTODOS: Fueron evaluados 113 pacientes entre enero de 2005 y marzo de 2008 y seguidos hasta octubre de 2010. Fueron trazadas curvas de sobrevida comparando la mortalidad cardiovascular, y por todas las causas de los pacientes con escolaridad de hasta tres años (mediana de la escolaridad y pacientes con escolaridad igual o superior a cuatro años. Fueron construidos modelos múltiples de Cox ajustados para las variables de confusión. RESULTADOS: Se observó asociación entre nivel de escolaridad e hipertrofia ventricular. La diferencia estadística de mortalidad de origen cardiovascular y por todas las causas entre los diferentes niveles de escolaridad ocurrió a los cinco años y medio de seguimiento. En el modelo de Cox, la hipertrofia ventricular y la proteína-C reactiva se asociaron a la mortalidad por todas las causas y de origen cardiovascular. La etiología de la insuficiencia renal se asoció a la mortalidad por todas las causas y la creatinina se asoció a la mortalidad de origen cardiovascular. La asociación entre escolaridad y mortalidad perdió significación estadística en el modelo ajustado. CONCLUSÓN: Los resultados del presente trabajo confirman estudio previo y demuestran, además, que la mayor mortalidad cardiovascular observada en los pacientes con menor escolaridad puede ser explicada por factores de riesgo de orden bioquímico y de morfología cardíaca.BACKGROUND: Left ventricular hypertrophy is a strong predictor of mortality in chronic kidney patients. A previous study of our group has shown that chronic kidney patients with low educational level has more severe ventricular hypertrophy. OBJECTIVE: To extend a previous study and to assess whether left ventricular hypertrophy can explain the

  12. Chronic infusion of enalaprilat into hypothalamic paraventricular nucleus attenuates angiotensin II-induced hypertension and cardiac hypertrophy by restoring neurotransmitters and cytokines

    International Nuclear Information System (INIS)

    Kang, Yu-Ming; Zhang, Dong-Mei; Yu, Xiao-Jing; Yang, Qing; Qi, Jie; Su, Qing; Suo, Yu-Ping; Yue, Li-Ying; Zhu, Guo-Qing; Qin, Da-Nian

    2014-01-01

    The renin–angiotensin system (RAS) in the brain is involved in the pathogenesis of hypertension. We hypothesized that inhibition of angiotensin-converting enzyme (ACE) in the hypothalamic paraventricular nucleus (PVN) attenuates angiotensin II (ANG II)-induced hypertension via restoring neurotransmitters and cytokines. Rats underwent subcutaneous infusions of ANG II or saline and bilateral PVN infusions of ACE inhibitor enalaprilat (ENL, 2.5 μg/h) or vehicle for 4 weeks. ANG II infusion resulted in higher mean arterial pressure and cardiac hypertrophy as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, and mRNA expressions of cardiac atrial natriuretic peptide and beta-myosin heavy chain. These ANG II-infused rats had higher PVN levels of glutamate, norepinephrine, tyrosine hydroxylase, pro-inflammatory cytokines (PICs) and the chemokine monocyte chemoattractant protein-1, and lower PVN levels of gamma-aminobutyric acid, interleukin (IL)-10 and the 67-kDa isoform of glutamate decarboxylase (GAD67), and higher plasma levels of PICs, norepinephrine and aldosterone, and lower plasma IL-10, and higher renal sympathetic nerve activity. However, PVN treatment with ENL attenuated these changes. PVN microinjection of ANG II induced increases in IL-1β and IL-6, and a decrease in IL-10 in the PVN, and pretreatment with angiotensin II type 1 receptor (AT1-R) antagonist losartan attenuated these changes. These findings suggest that ANG II infusion induces an imbalance between excitatory and inhibitory neurotransmitters and an imbalance between pro- and anti-inflammatory cytokines in the PVN, and PVN inhibition of the RAS restores neurotransmitters and cytokines in the PVN, thereby attenuating ANG II-induced hypertension and cardiac hypertrophy. - Highlights: • Chronic ANG II infusion results in sympathetic hyperactivity and cardiac hypertrophy. • PVN inhibition of ACE

  13. Chronic infusion of enalaprilat into hypothalamic paraventricular nucleus attenuates angiotensin II-induced hypertension and cardiac hypertrophy by restoring neurotransmitters and cytokines

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Yu-Ming, E-mail: ykang@mail.xjtu.edu.cn [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Zhang, Dong-Mei [Department of Physiology, Dalian Medical University, Dalian 116044 (China); Yu, Xiao-Jing; Yang, Qing; Qi, Jie; Su, Qing [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Suo, Yu-Ping [Department of Obstetrics and Gynecology, Shanxi Provincial People' s Hospital, Taiyuan 030012 (China); Yue, Li-Ying [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Zhu, Guo-Qing [Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing 210029 (China); Qin, Da-Nian, E-mail: dnqin@stu.edu.cn [Department of Physiology, Shantou University Medical College, Shantou 515041 (China)

    2014-02-01

    The renin–angiotensin system (RAS) in the brain is involved in the pathogenesis of hypertension. We hypothesized that inhibition of angiotensin-converting enzyme (ACE) in the hypothalamic paraventricular nucleus (PVN) attenuates angiotensin II (ANG II)-induced hypertension via restoring neurotransmitters and cytokines. Rats underwent subcutaneous infusions of ANG II or saline and bilateral PVN infusions of ACE inhibitor enalaprilat (ENL, 2.5 μg/h) or vehicle for 4 weeks. ANG II infusion resulted in higher mean arterial pressure and cardiac hypertrophy as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, and mRNA expressions of cardiac atrial natriuretic peptide and beta-myosin heavy chain. These ANG II-infused rats had higher PVN levels of glutamate, norepinephrine, tyrosine hydroxylase, pro-inflammatory cytokines (PICs) and the chemokine monocyte chemoattractant protein-1, and lower PVN levels of gamma-aminobutyric acid, interleukin (IL)-10 and the 67-kDa isoform of glutamate decarboxylase (GAD67), and higher plasma levels of PICs, norepinephrine and aldosterone, and lower plasma IL-10, and higher renal sympathetic nerve activity. However, PVN treatment with ENL attenuated these changes. PVN microinjection of ANG II induced increases in IL-1β and IL-6, and a decrease in IL-10 in the PVN, and pretreatment with angiotensin II type 1 receptor (AT1-R) antagonist losartan attenuated these changes. These findings suggest that ANG II infusion induces an imbalance between excitatory and inhibitory neurotransmitters and an imbalance between pro- and anti-inflammatory cytokines in the PVN, and PVN inhibition of the RAS restores neurotransmitters and cytokines in the PVN, thereby attenuating ANG II-induced hypertension and cardiac hypertrophy. - Highlights: • Chronic ANG II infusion results in sympathetic hyperactivity and cardiac hypertrophy. • PVN inhibition of ACE

  14. Left ventricular mass in borderline hypertension assessed by echo cardiography

    International Nuclear Information System (INIS)

    Mezzasalma, L.; Ghione, S.; Palonebo, C.

    1989-01-01

    The relationship between clinical measurement of blood pressure (BP) and left ventricular hypertrophy in arterial hypertension appears to be weak in most studies. On the contrary, stronger correlations with target organ damage in general, and left ventricular hypertrophy in particular, have been reported for blood pressure measurements obtained by ambulatory monitoring; this finding may indicate a possible role for blood pressure response to naturally occurring stresses in determining left ventricular hypertrophy. Aim of this study was to investigate, in 18 patients with borderline arterial hypertension, the relationships between echocardiographically assessed left ventricular mass and, respectively, casual BP and BP responses to some standardized stress tests. Only three patients had a diastolic wall thickness of the interventricular septum and of the posterior wall ≥1.2 cm and none had a pathologically increased left ventricular mass index. The following statistically significant correlations were found: casual diastolic BP vs. left ventricular mass index (r=0.53, p<0.02), systolic BP response to bicycle exercise test vs. left ventricular mass index (r=0.55, p<0.05). Multiple regression analysis showed that almost fifty percent of the variability of left ventricular mass index could be predicted by these two BP measurements. These findings suggest that besides the chronically increased afterload, also the transient hypertensive responses to naturally occuring physical stresses may have a role in determining the extent of cardiac structural changes in borderline hypertensive patients. In addition, they indicate a direct relation between left ventricular mass and blood pressure levels also in borderline hypertension, as previously shown for established hypertension, despite the fact that left ventricular hypertrophy represents only an occasional finding in early stages of hypertension

  15. Transcriptional profile of isoproterenol-induced cardiomyopathy and comparison to exercise-induced cardiac hypertrophy and human cardiac failure

    Directory of Open Access Journals (Sweden)

    McIver Lauren J

    2009-12-01

    Full Text Available Abstract Background Isoproterenol-induced cardiac hypertrophy in mice has been used in a number of studies to model human cardiac disease. In this study, we compared the transcriptional response of the heart in this model to other animal models of heart failure, as well as to the transcriptional response of human hearts suffering heart failure. Results We performed microarray analyses on RNA from mice with isoproterenol-induced cardiac hypertrophy and mice with exercise-induced physiological hypertrophy and identified 865 and 2,534 genes that were significantly altered in pathological and physiological cardiac hypertrophy models, respectively. We compared our results to 18 different microarray data sets (318 individual arrays representing various other animal models and four human cardiac diseases and identified a canonical set of 64 genes that are generally altered in failing hearts. We also produced a pairwise similarity matrix to illustrate relatedness of animal models with human heart disease and identified ischemia as the human condition that most resembles isoproterenol treatment. Conclusion The overall patterns of gene expression are consistent with observed structural and molecular differences between normal and maladaptive cardiac hypertrophy and support a role for the immune system (or immune cell infiltration in the pathology of stress-induced hypertrophy. Cross-study comparisons such as the results presented here provide targets for further research of cardiac disease that might generally apply to maladaptive cardiac stresses and are also a means of identifying which animal models best recapitulate human disease at the transcriptional level.

  16. Muscular and systemic correlates of resistance training-induced muscle hypertrophy.

    Directory of Open Access Journals (Sweden)

    Cameron J Mitchell

    Full Text Available PURPOSE: To determine relationships between post-exercise changes in systemic [testosterone, growth hormone (GH, insulin like grow factor 1 (IGF-1 and interleukin 6 (IL-6], or intramuscular [skeletal muscle androgen receptor (AR protein content and p70S6K phosphorylation status] factors in a moderately-sized cohort of young men exhibiting divergent resistance training-mediated muscle hypertrophy. METHODS: Twenty three adult males completed 4 sessions•wk⁻¹ of resistance training for 16 wk. Muscle biopsies were obtained before and after the training period and acutely 1 and 5 h after the first training session. Serum hormones and cytokines were measured immediately, 15, 30 and 60 minutes following the first and last training sessions of the study. RESULTS: Mean fiber area increased by 20% (range: -7 to 80%; P<0.001. Protein content of the AR was unchanged with training (fold change = 1.17 ± 0.61; P=0.19; however, there was a significant correlation between the changes in AR content and fiber area (r=0.60, P=0.023. Phosphorylation of p70S6K was elevated 5 hours following exercise, which was correlated with gains in mean fiber area (r=0.54, P=0.007. There was no relationship between the magnitude of the pre- or post-training exercise-induced changes in free testosterone, GH, or IGF-1 concentration and muscle fiber hypertrophy; however, the magnitude of the post exercise IL-6 response was correlated with muscle hypertrophy (r=0.48, P=0.019. CONCLUSION: Post-exercise increases in circulating hormones are not related to hypertrophy following training. Exercise-induced changes in IL-6 correlated with hypertrophy, but the mechanism for the role of IL-6 in hypertrophy is not known. Acute increases, in p70S6K phosphorylation and changes in muscle AR protein content correlated with muscle hypertrophy implicating intramuscular rather than systemic processes in mediating hypertrophy.

  17. MiR-139-3p is related to left ventricular hypertrophy and cardiomyocyte apoptosis in two-kidney one-clip hypertensive rats

    Directory of Open Access Journals (Sweden)

    Yang Xiaomin

    2015-01-01

    Full Text Available MicroRNAs (miRNAs are important post-transcriptional regulators of gene expression in many physiological and pathological processes. Previous studies have reported the role of miR-139-3p in cancer. However, its specific roles and functions in the heart undergoing hypertrophy have yet to be fully elucidated. In the present study, a significant upregulation of miR-139-3p expression was demonstrated in the left ventricular myocardium of two-kidney one-clip (2K1C hypertensive rats using microarray and quantitative real-time PCR (qRT-PCR. Based on computational analysis, we observed that miR-139-3p can control the expression of mitogen-activated protein kinase 1 (MAPK1 as a target gene, which is essential for the induction of cardiac hypertrophy and cardiomyocyte apoptosis. This study provides first information that the highly expressed miR-139-3p might be closely involved in MAPK1-mediated cardiac hypertrophy and cardiomyocyte apoptotic processes in 2K1C rat.

  18. Recognition of regional hypertrophy in hypertrophic cardiomyopathy using thallium-201 emission-computed tomography: comparison with two-dimensional echocardiography

    International Nuclear Information System (INIS)

    Suzuki, Y.; Kadota, K.; Nohara, R.

    1984-01-01

    The configuration of the hypertrophied myocardium was evaluated by thallium-201 emission-computed tomography and 2-dimensional (2-D) sector scan in 10 patients with obstructive hypertrophic cardiomyopathy (HC), 10 with nonobstructive HC with giant negative T waves and 10 with concentric left ventricular (LV) hypertrophy. Thallium-201 myocardial imaging was reconstructed into multiple 12-mm-thick slices in 3 planes. The thickness ratio of the ventricular septum and the LV posterior wall in the short-axis plane and the ratio of the ventricular septum and the apical wall in the long-axis plane were analyzed. In the patients with obstructive HC the ventricular septal wall thickness index was increased, and the ratio of septal to posterior wall thickness index (1.45 +/- 0.23) was greater than that in the patients with nonobstructive HC with giant negative T waves or in those with concentric LV hypertrophy (1.03 +/- 0.20 and 0.98 +/- 0.11, respectively; p less than 0.01 for each). In the patients with nonobstructive HC with giant negative T waves, increased apical wall thickness with apical cavity obliteration was characteristic, and the ratio of ventricular septal to apical wall thickness index (0.66 +/- 0.14) was less than that in the patients with obstructive HC or in those with concentric LV hypertrophy (1.46 +/- 0.38 and 1.04 +/- 0.09, respectively; p less than 0.001 for each). In contrast, technically satisfactory 2-D sector scanning (83%) demonstrated various configurations of the hypertrophied ventricularseptum, but could not detect apical hypertrophy in 4 of the 10 patients with nonobstructive HC with giant negative T waves whose LV cineangiograms demonstrated apical hypertrophy. Thus, thallium-201 emission-computed tomography is useful in evaluating the characteristics of LV hypertrophy and assists 2-D sector scan, especially in patients with apical hypertrophy in HC

  19. Local renin–angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy

    OpenAIRE

    Kobori, H; Ichihara, A; Miyashita, Y; Hayashi, M; Saruta, T

    1999-01-01

    We have reported previously that thyroid hormone activates the circulating and tissue renin–angiotensin systems without involving the sympathetic nervous system, which contributes to cardiac hypertrophy in hyperthyroidism. This study examined whether the circulating or tissue renin–angiotensin system plays the principal role in hyperthyroidism-induced cardiac hypertrophy. The circulating renin–angiotensin system in Sprague–Dawley rats was fixed by chronic angiotensin II infusion (40 ng/ min, ...

  20. SIRT1 may play a crucial role in overload-induced hypertrophy of skeletal muscle.

    Science.gov (United States)

    Koltai, Erika; Bori, Zoltán; Chabert, Clovis; Dubouchaud, Hervé; Naito, Hisashi; Machida, Shuichi; Davies, Kelvin Ja; Murlasits, Zsolt; Fry, Andrew C; Boldogh, Istvan; Radak, Zsolt

    2017-06-01

    Silent mating type information regulation 2 homologue 1 (SIRT1) activity and content increased significantly in overload-induced hypertrophy. SIRT1-mediated signalling through Akt, the endothelial nitric oxide synthase mediated pathway, regulates anabolic process in the hypertrophy of skeletal muscle. The regulation of catabolic signalling via forkhead box O 1 and protein ubiquitination is SIRT1 dependent. Overload-induced changes in microRNA levels regulate SIRT1 and insulin-like growth factor 1 signalling. Significant skeletal muscle mass guarantees functional wellbeing and is important for high level performance in many sports. Although the molecular mechanism for skeletal muscle hypertrophy has been well studied, it still is not completely understood. In the present study, we used a functional overload model to induce plantaris muscle hypertrophy by surgically removing the soleus and gastrocnemius muscles in rats. Two weeks of muscle ablation resulted in a 40% increase in muscle mass, which was associated with a significant increase in silent mating type information regulation 2 homologue 1 (SIRT1) content and activity (P overload-induced hypertrophy. These findings, along with the well-known regulatory roles that SIRT1 plays in modulating both anabolic and catabolic pathways, allow us to propose the hypothesis that SIRT1 may actually play a crucial causal role in overload-induced hypertrophy of skeletal muscle. This hypothesis will now require rigorous direct and functional testing. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

  1. Effect of prophylactic digitalization on the development of myocardial hypertrophy.

    Science.gov (United States)

    Cutilletta, A F; Rudnik, M; Arcilla, R A; Straube, R

    1977-11-01

    The effect of prophylactic digitalization on the development of left ventricular hypertrophy was studied in adult rats. Digitoxin, 0.1 mg/100 g body wt or solvent was given daily for 1 wk prior to either aortic constriction or sham operation and was continued until the animals were killed, either 1 or 4 wk after surgery. A hemodynamic study was done in those animals killed 1 wk after surgery; hearts of all animals were examined for evidence of myocardial hypertrophy. Constriction of the ascending aorta had no significant effect on cardiac output but did reduce peak flow velocity and flow acceleration. An increase in left ventricular mass, RNA, and hydroxyproline was found in the animals with aortic constriction. Digitoxin treatment did not alter peak flow velocity or flow acceleration, but did significantly increase isovolumic (dP/dt)P-1. Digitoxin had no effect on body weight, heart weight, RNA, or hydroxyproline in either the sham-operated animals or in the animals with aortic constriction. Therefore, despite plasma digitoxin levels sufficient to affect myocardial contractility, left ventricular hypertrophy still developed after aortic constriction.

  2. How does pressure overload cause cardiac hypertrophy and dysfunction? High-ouabain affinity cardiac Na+ pumps are crucial.

    Science.gov (United States)

    Blaustein, Mordecai P

    2017-11-01

    Left ventricular hypertrophy is frequently observed in hypertensive patients and is believed to be due to the pressure overload and cardiomyocyte stretch. Three recent reports on mice with genetically engineered Na + pumps, however, have demonstrated that cardiac ouabain-sensitive α 2 -Na + pumps play a key role in the pathogenesis of transaortic constriction-induced hypertrophy. Hypertrophy was delayed/attenuated in mice with mutant, ouabain-resistant α 2 -Na + pumps and in mice with cardiac-selective knockout or transgenic overexpression of α 2 -Na + pumps. The latter, seemingly paradoxical, findings can be explained by comparing the numbers of available (ouabain-free) high-affinity (α 2 ) ouabain-binding sites in wild-type, knockout, and transgenic hearts. Conversely, hypertrophy was accelerated in α 2 -ouabain-resistant (R) mice in which the normally ouabain-resistant α 1 -Na + pumps were mutated to an ouabain-sensitive (S) form (α 1 S/S α 2 R/R or "SWAP" vs. wild-type or α 1 R/R α 2 S/S mice). Furthermore, transaortic constriction-induced hypertrophy in SWAP mice was prevented/reversed by immunoneutralizing circulating endogenous ouabain (EO). These findings show that EO and its receptor, ouabain-sensitive α 2 , are critical factors in pressure overload-induced cardiac hypertrophy. This complements reports linking elevated plasma EO to hypertension, cardiac hypertrophy, and failure in humans and elucidates the underappreciated role of the EO-Na + pump pathway in cardiovascular disease. Copyright © 2017 the American Physiological Society.

  3. Stress induced right ventricular dysfunction: An indication of reversible right ventricular ischaemia

    International Nuclear Information System (INIS)

    Underwood, S.R.; Walton, S.; Emanuel, R.W.; Swanton, R.H.; Campos Costa, D.; Laming, P.J.; Ell, P.J.

    1987-01-01

    Stress induced changes in left ventricular ejection fraction are widely used in the detection and assessment of coronary artery disease. This study demonstrates that right ventricular dysfunction may also occur, and assesses its significance in terms of coronary artery anatomy. This study involved 14 normal subjects and 26 with coronary artery disease investigated by equilibrium radionuclide ventriculography, at rest and during maximal dynamic exercise. Mean normal resting right ventricular ejection fraction (RVEF) was 0.40 (SD 0.118), and all normal subjects increased RVEF with stress (mean ΔRVEF+0.13 SD 0.099). Mean ΔRVEF in the subjects with coronary artery disease was significantly lower at 0.00 (SD 0.080), but there was overlap between the two groups. The largest falls in RVEF were seen if the right coronary artery was occluded without retrograde filling. In this subgroup with the most severely compromised right ventricular perfusion (nine subjects), RVEF always fell with stress, and mean ΔRVEF was -0.08 (SD 0.050). There was no significant correlation between ΔLVEF and ΔRVEF, implying that the right ventricular dysfunction was due to right ventricular ischaemia, rather than secondary to left ventricular dysfunction. Stress induced right ventricular ischaemia can therefore be detected readily by radionuclide ventriculography. (orig.)

  4. Nocturnal Intermittent Hypoxia Is Associated With Left Ventricular Hypertrophy in Middle-Aged Men With Hypertension and Obstructive Sleep Apnea.

    Science.gov (United States)

    Yamaguchi, Tasuku; Takata, Yoshifumi; Usui, Yasuhiro; Asanuma, Ryoko; Nishihata, Yosuke; Kato, Kota; Shiina, Kazuki; Yamashina, Akira

    2016-03-01

    Obstructive sleep apnea (OSA) and left ventricular (LV) hypertrophy are considered to be closely associated. However, the relationship has not yet been fully demonstrated and is hence still controversial. The purpose of this study was to assess in hypertensive male patients the relationship between OSA and cardiac structure using a new index, namely, integrated area of desaturation (IAD), in addition to the apnea-hypopnea index (AHI) that is currently the most frequently used index of sleep-disordered breathing. In our cross-sectional study, 223 hypertensive men younger than 65 years with sleep apnea and normal cardiac function were enrolled. All subjects were evaluated by fully attended polysomnography. Cardiac structure and function were evaluated by echocardiography. LV mass index significantly correlated with IAD (r = 0.203, P intermittent hypoxia defined by IAD may be associated with LV hypertrophy in men with well-controlled hypertension and obstructive sleep apnea. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. Dimensional correlates of left ventricular dilation in the presence of hypertrophy.

    Science.gov (United States)

    Al-Nouri, M B; Ford, L E; Wix, H

    1983-01-01

    Twelve normal subjects, 50 patients with valvular heart disease, and 14 with hypertension were studied. Those with valvular disease were divided into two groups: 28 with angiographically measured ejection fractions greater than or equal to 0.6 and 22 with ejection fractions less than 0.6. The echocardiographically measured ventricular thickness divided by radius ratio (t/r) was approximately proportional to peak systolic pressure (P) in all groups having ejection fractions greater than or equal to 0.6, so that the t/r divided by P ratios were nearly the same. Patients with ejection fractions less than 0.6 had significantly lower t/r divided by P values. No single component of the t/r divided by P ratio would identify the patients with lower ejection fractions. The t/r divided by P ratios in 14 hypertensive patients were nearly identical to the ratios in six patients with aortic stenosis and ejection fractions greater than or equal to 0.6, indicating that an aortic valve gradient does not cause a grossly abnormal form of pressure hypertrophy. The t/r ratio is thus a double sensitive, noninvasive index of dilation when correlated with systolic pressure.

  6. Relationship of left atrial enlargement to persistence or development of ECG left ventricular hypertrophy in hypertensive patients: implications for the development of new atrial fibrillation

    DEFF Research Database (Denmark)

    Okin, Peter M; Gerdts, Eva; Wachtell, Kristian

    2010-01-01

    Persistence and development of ECG left ventricular hypertrophy (LVH) by Cornell product criteria are associated with an increased risk of atrial fibrillation compared with regression or continued absence of LVH. We postulated that this association might be in part mediated via greater left atrial...... enlargement (LAE) in patients with new and persistent ECG LVH....

  7. Exercise-induced arterial hypertension - an independent factor for hypertrophy and a ticking clock for cardiac fatigue or atrial fibrillation in athletes? [v1; ref status: indexed, http://f1000r.es/3b4

    Directory of Open Access Journals (Sweden)

    Roman Leischik

    2014-05-01

    Full Text Available Background: Exercise-induced arterial hypertension (EIAH leads to myocardial hypertrophy and is associated with a poor prognosis. EIAH might be related to the “cardiac fatigue” caused by endurance training. The goal of this study was to examine whether there is any relationship between EIAH and left ventricular hypertrophy in Ironman-triathletes. Methods: We used echocardiography and spiroergometry to determine the left ventricular mass (LVM, the aerobic/anaerobic thresholds and the steady-state blood pressure of 51 healthy male triathletes. The main inclusion criterion was the participation in at least one middle or long distance triathlon. Results: When comparing triathletes with LVM 220g there was a significant difference between blood pressure values (BP at the anaerobic threshold (185.2± 21.5 mmHg vs. 198.8 ±22.3 mmHg, p=0.037. The spiroergometric results were: maximum oxygen uptake (relative VO2max 57.3 ±7.5ml/min/kg vs. 59.8±9.5ml/min/kg (p=ns. Cut-point analysis for the relationship of BP >170 mmHg at the aerobic threshold and the probability of LVM >220g showed a sensitivity of 95.8%, a specificity of 33.3%, with a positive predictive value of 56.8 %, a good negative predictive value of 90%. The probability of LVM >220g increased with higher BP during exercise (OR: 1.027, 95% CI 1.002-1.052, p= 0.034 or with higher training volume (OR: 1.23, 95% CI 1.04 -1.47, p = 0.019. Echocardiography showed predominantly concentric remodelling, followed by concentric hypertrophy. Conclusion: Significant left ventricular hypertrophy with LVM >220g is associated with higher arterial blood pressure at the aerobic or anaerobic threshold. The endurance athletes with EIAH may require a therapeutic intervention to at least prevent extensive stiffening of the heart muscle and exercise-induced cardiac fatigue.

  8. Local renin-angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy.

    Science.gov (United States)

    Kobori, H; Ichihara, A; Miyashita, Y; Hayashi, M; Saruta, T

    1999-01-01

    We have reported previously that thyroid hormone activates the circulating and tissue renin-angiotensin systems without involving the sympathetic nervous system, which contributes to cardiac hypertrophy in hyperthyroidism. This study examined whether the circulating or tissue renin-angiotensin system plays the principal role in hyperthyroidism-induced cardiac hypertrophy. The circulating renin-angiotensin system in Sprague-Dawley rats was fixed by chronic angiotensin II infusion (40 ng/min, 28 days) via mini-osmotic pumps. Daily i.p. injection of thyroxine (0.1 mg/kg per day, 28 days) was used to mimic hyperthyroidism. Serum free tri-iodothyronine, plasma renin activity, plasma angiotensin II, cardiac renin and cardiac angiotensin II were measured with RIAs. The cardiac expression of renin mRNA was evaluated by semiquantitative reverse transcriptase-polymerase chain reaction. Plasma renin activity and plasma angiotensin II were kept constant in the angiotensin II and angiotensin II+thyroxine groups (0.12+/-0.03 and 0.15+/-0.03 microgram/h per liter, 126+/-5 and 130+/-5 ng/l respectively) (means+/-s.e.m.). Despite stabilization of the circulating renin-angiotensin system, thyroid hormone induced cardiac hypertrophy (5.0+/-0.5 vs 3.5+/-0.1 mg/g) in conjunction with the increases in cardiac expression of renin mRNA, cardiac renin and cardiac angiotensin II (74+/-2 vs 48+/-2%, 6.5+/-0.8 vs 3.8+/-0.4 ng/h per g, 231+/-30 vs 149+/-2 pg/g respectively). These results indicate that the local renin-angiotensin system plays the primary role in the development of hyperthyroidism-induced cardiac hypertrophy.

  9. Role of hypoxia-inducible factor in diabetic myocardial hypertrophy ...

    African Journals Online (AJOL)

    Purpose: This study was carried out to investigate the role of hypoxia-inducible factor (HIF) in diabetic cardiomyopathy in vitro. Methods: Hypoxia was induced chemically in H9C2 cells (cardiac hypertrophy model), and the cells were treated with phenylephrine (PE), deferoxamine (DFO), PE + DFO, and HIF-1α siRNA under ...

  10. Renin angiotensin system and cardiac hypertrophy after sinoaortic denervation in rats

    Directory of Open Access Journals (Sweden)

    Aline Cristina Piratello

    2010-01-01

    Full Text Available OBJECTIVE: The aim of this study was to evaluate the role of angiotensin I, II and 1-7 on left ventricular hypertrophy of Wistar and spontaneously hypertensive rats submitted to sinoaortic denervation. METHODS: Ten weeks after sinoaortic denervation, hemodynamic and morphofunctional parameters were analyzed, and the left ventricle was dissected for biochemical analyses. RESULTS: Hypertensive groups (controls and denervated showed an increase on mean blood pressure compared with normotensive ones (controls and denervated. Blood pressure variability was higher in denervated groups than in their respective controls. Left ventricular mass and collagen content were increased in the normotensive denervated and in both spontaneously hypertensive groups compared with Wistar controls. Both hypertensive groups presented a higher concentration of angiotensin II than Wistar controls, whereas angiotensin 1-7 concentration was decreased in the hypertensive denervated group in relation to the Wistar groups. There was no difference in angiotensin I concentration among groups. CONCLUSION: Our results suggest that not only blood pressure variability and reduced baroreflex sensitivity but also elevated levels of angiotensin II and a reduced concentration of angiotensin 1-7 may contribute to the development of left ventricular hypertrophy. These data indicate that baroreflex dysfunction associated with changes in the renin angiotensin system may be predictive factors of left ventricular hypertrophy and cardiac failure.

  11. In utero premature closure of the ductus arteriosus presenting as isolated right ventricular hypertrophy.

    Science.gov (United States)

    Long, Webb E; Wilson, Allen D; Srinivasan, Shardha; Seeger, Kimberly J; Maginot, Kathleen R

    2009-10-01

    The etiology of isolated right ventricular hypertrophy (RVH) is distinct from other forms of hypertrophic cardiomyopathy. RVH is typically seen in the setting of pulmonary valve stenosis or Tetralogy of Fallot. A rare cause of isolated RVH is premature closure of the patent ductus arteriosus (PDA) in utero that results in pulmonary hypertension. This can have a range of outcomes, from spontaneous resolution to fetal demise. This case report describes a term infant who presented with respiratory distress and striking isolated RVH, pulmonary hypertension, and no PDA. She was treated conservatively with supplemental oxygen. The patient was gradually weaned off oxygen over the course of two weeks and follow-up echocardiography showed resolution of her RVH and pulmonary hypertension by 14 weeks of age. The presentation and course of this patient with severe isolated RVH is consistent with spontaneous premature closure of the ductus arteriosus in utero.

  12. Patterns of left ventricular remodeling among patients with essential and secondary hypertension.

    Science.gov (United States)

    Radulescu, Dan; Stoicescu, Laurentiu; Buzdugan, Elena; Donca, Valer

    2013-12-01

    High blood pressure causes left ventricular hypertrophy, which is a negative prognostic factor among hypertensive patients. To assess left ventricular geometric remodeling patterns in patients with essential hypertension or with hypertension secondary to parenchymal renal disease. We analyzed data from echocardiograms performed in 250 patients with essential hypertension (150 females) and 100 patients with secondary hypertension (60 females). The interventricular septum and the left ventricular posterior wall thickness were measured in the parasternal long-axis. Left ventricular mass was calculated using the Devereaux formula. The most common remodeling type in females and males with essential hypertension were eccentric and concentric left ventricular hypertrophy (cLVH), respectively. Among patients with secondary arterial hypertension, cLVH was most commonly observed in both genders. The prevalence of left ventricular hypertrophy was higher among patients with secondary hypertension. The left ventricular mass index and the relative left ventricular wall thickness were higher in males and also in the secondary hypertension group. Age, blood pressure values and the duration of hypertension, influenced remodeling patterns. We documented a higher prevalence of LVH among patients with secondary hypertension. The type of ventricular remodeling depends on gender, age, type of hypertension, blood pressure values and the duration of hypertension.

  13. Thyroid hormone-induced hypertrophy in mesenchymal stem cell chondrogenesis is mediated by bone morphogenetic protein-4.

    Science.gov (United States)

    Karl, Alexandra; Olbrich, Norman; Pfeifer, Christian; Berner, Arne; Zellner, Johannes; Kujat, Richard; Angele, Peter; Nerlich, Michael; Mueller, Michael B

    2014-01-01

    Chondrogenic differentiating mesenchymal stem cells (MSCs) express markers of hypertrophic growth plate chondrocytes. As hypertrophic cartilage undergoes ossification, this is a concern for the application of MSCs in articular cartilage tissue engineering. To identify mechanisms that elicit this phenomenon, we used an in vitro hypertrophy model of chondrifying MSCs for differential gene expression analysis and functional experiments with the focus on bone morphogenetic protein (BMP) signaling. Hypertrophy was induced in chondrogenic MSC pellet cultures by transforming growth factor β (TGFβ) and dexamethasone withdrawal and addition of triiodothyronine. Differential gene expression analysis of BMPs and their receptors was performed. Based on these results, the in vitro hypertrophy model was used to investigate the effect of recombinant BMP4 and the BMP inhibitor Noggin. The enhancement of hypertrophy could be shown clearly by an increased cell size, alkaline phosphatase activity, and collagen type X deposition. Upon induction of hypertrophy, BMP4 and the BMP receptor 1B were upregulated. Addition of BMP4 further enhanced hypertrophy in the absence, but not in the presence of TGFβ and dexamethasone. Thyroid hormone induced hypertrophy by upregulation of BMP4 and this induced enhancement of hypertrophy could be blocked by the BMP antagonist Noggin. BMP signaling is an important modulator of the late differentiation stages in MSC chondrogenesis and the thyroid hormone induces this pathway. As cartilage tissue engineering constructs will be exposed to this factor in vivo, this study provides important insight into the biology of MSC-based cartilage. Furthermore, the possibility to engineer hypertrophic cartilage may be helpful for critical bone defect repair.

  14. Amlodipine decreases fibrosis and cardiac hypertrophy in spontaneously hypertensive rats: persistent effects after withdrawal.

    Science.gov (United States)

    Sevilla, María A; Voces, Felipe; Carrón, Rosalía; Guerrero, Estela I; Ardanaz, Noelia; San Román, Luis; Arévalo, Miguel A; Montero, María J

    2004-07-02

    Our objective was to examine the effect of chronic treatment with amlodipine on blood pressure, left ventricular hypertrophy, and fibrosis in spontaneously hypertensive rats and the persistence of such an effect after drug withdrawal. We investigated the effects of treatment with 2, 8 and 20 mg/kg/day of amlodipine given orally for six months and at three months after drug withdrawal. Systolic blood pressure was measured using the tail-cuff method. At the end of the study period, the heart was excised, the left ventricle was isolated, and the left ventricle weight/body weight ratio was calculated as a left ventricular hypertrophy index. Fibrosis, expressed as collagen volume fraction, was evaluated using an automated image-analysis system on sections stained with Sirius red. Age-matched untreated Wistar-Kyoto and SHR were used as normotensive and hypertensive controls, respectively. Systolic blood pressure was reduced in the treated SHR in a dose-dependent way and after amlodipine withdrawal it increased progressively, without reaching the values of the hypertensive controls. Cardiac hypertrophy was reduced by 8 and 20 mg/kg/day amlodipine, but when treatment was withdrawn only the group treated with 8 mg/kg/day maintained significant differences versus the hypertensive controls. All three doses of amlodipine reduced cardiac fibrosis and this regression persisted with the two highest doses after three months without treatment. We concluded that antihypertensive treatment with amlodipine is accompanied by a reduction in left ventricular hypertrophy and regression in collagen deposition. Treatment was more effective in preventing fibrosis than in preventing ventricular hypertrophy after drug withdrawal. Copyright 2004 Elsevier Inc.

  15. Melatonin attenuates angiotensin II-induced cardiomyocyte hypertrophy through the CyPA/CD147 signaling pathway.

    Science.gov (United States)

    Su, Hongyan; Li, Jingyuan; Chen, Tongshuai; Li, Na; Xiao, Jie; Wang, Shujian; Guo, Xiaobin; Yang, Yi; Bu, Peili

    2016-11-01

    Melatonin is well known for its cardioprotective effects; however, whether melatonin exerts therapeutic effects on cardiomyocyte hypertrophy remains to be investigated, as do the mechanisms underlying these effects, if they exist. Cyclophilin A (CyPA) and its corresponding receptor, CD147, which exists in a variety of cells, play crucial roles in modulating reactive oxygen species (ROS) production. In this study, we explored the role of the CyPA/CD147 signaling pathway in angiotensin II (Ang II)-induced cardiomyocyte hypertrophy and the protective effects exerted by melatonin against Ang II-induced injury in cultured H9C2 cells. Cyclosporine A, a specific CyPA/CD147 signaling pathway inhibitor, was used to manipulate CyPA/CD147 activity. H9C2 cells were then subjected to Ang II or CyPA treatment in either the absence or presence of melatonin. Our results indicate that Ang II induces cardiomyocyte hypertrophy through the CyPA/CD147 signaling pathway and promotes ROS production, which can be blocked by melatonin pretreatment in a concentration-dependent manner, in cultured H9C2 cells and that CyPA/CD147 signaling pathway inhibition protects against Ang II-induced cardiomyocyte hypertrophy. The protective effects of melatonin against Ang II-induced cardiomyocyte hypertrophy depend at least partially on CyPA/CD147 inhibition.

  16. The Molecular Basis for Load-Induced Skeletal Muscle Hypertrophy

    Science.gov (United States)

    Marcotte, George R.; West, Daniel W.D.; Baar, Keith

    2016-01-01

    In a mature (weight neutral) animal, an increase in muscle mass only occurs when the muscle is loaded sufficiently to cause an increase in myofibrillar protein balance. A tight relationship between muscle hypertrophy, acute increases in protein balance, and the activity of the mechanistic target of rapamycin complex 1 (mTORC1) was demonstrated 15 years ago. Since then, our understanding of the signals that regulate load-induced hypertrophy has evolved considerably. For example, we now know that mechanical load activates mTORC1 in the same way as growth factors, by moving TSC2 (a primary inhibitor of mTORC1) away from its target (the mTORC activator) Rheb. However, the kinase that phosphorylates and moves TSC2 is different in the two processes. Similarly, we have learned that a distinct pathway exists whereby amino acids activate mTORC1 by moving it to Rheb. While mTORC1 remains at the forefront of load-induced hypertrophy, the importance of other pathways that regulate muscle mass are becoming clearer. Myostatin, is best known for its control of developmental muscle size. However, new mechanisms to explain how loading regulates this process are suggesting that it could play an important role in hypertrophic muscle growth as well. Lastly, new mechanisms are highlighted for how β2 receptor agonists could be involved in load-induced muscle growth and why these agents are being developed as non-exercise-based therapies for muscle atrophy. Overall, the results highlight how studying the mechanism of load-induced skeletal muscle mass is leading the development of pharmaceutical interventions to promote muscle growth in those unwilling or unable to perform resistance exercise. PMID:25359125

  17. The role of secondary hyperparathyroidism in left ventricular hypertrophy of patients under chronic hemodialysis

    Directory of Open Access Journals (Sweden)

    Randon R.B.

    2005-01-01

    Full Text Available End-stage renal disease (ESRD patients frequently develop structural cardiac abnormalities, particularly left ventricular hypertrophy (LVH. The mechanisms involved in these processes are not completely understood. In the present study, we evaluated a possible association between parathyroid hormone (PTH levels and left ventricular mass (LVM in patients with ESRD. Stable uremic patients on intermittent hemodialysis treatment were evaluated by standard two-dimensional echocardiography and their sera were analyzed for intact PTH. Forty-one patients (mean age 45 years, range 18 to 61 years, 61% males, who had been on hemodialysis for 3 to 186 months, were evaluated. Patients were stratified into 3 groups according to serum PTH: low levels (280 pg/ml; group III = 21 patients. A positive statistically significant association between LVM index and PTH was identified (r = 0.34; P = 0.03, Pearson's correlation coefficient in the sample as a whole. In subgroup analyses, we did not observe significant associations in the low and intermediate PTH groups; nevertheless, PTH and LVM index were correlated in patients with high PTH levels (r = 0.62; P = 0.003. LVM index was also inversely associated with hemoglobin (r = -0.34; P = 0.03. In multivariate analysis, after adjustment for age, hemoglobin, body mass index, and blood pressure, the only independent predictor of LVM index was PTH level. Therefore, PTH is an independent predictor of LVH in patients undergoing chronic hemodialysis. Secondary hyperparathyroidism may contribute to the elevated cardiovascular morbidity associated with LVH in ESRD.

  18. Left Ventricular Geometry In Nigerians With Type II Diabetes Mellitus ...

    African Journals Online (AJOL)

    Background: Left ventricular hypertrophy is independently associated with increased incidence of cardiovascular disease, cardiovascular and all cause mortality. In a relatively healthy hypertensive adult population, type II diabetes is associated with higher left ventricular mass, concentric left ventricular geometry and lower ...

  19. Aortic stenosis with abnormal eccentric left ventricular remodeling secondary to hypothyroidism in a Bourdeaux Mastiff

    Directory of Open Access Journals (Sweden)

    Guilherme Augusto Minozzo

    Full Text Available ABSTRACT: This paper describes a case of congenital aortic stenosis with eccentric left ventricular hypertrophy associated with hypothyroidism in a 1-year-old Bourdeaux Mastiff dog. The dog had ascites, apathy, alopecic and erythematous skin lesions in different parts of the body. A two-dimensional echocardiogram revealed aortic valve stenosis, with poststenotic dilation in the ascending aorta. The same exam showed eccentric hypertrophy and dilation of the left ventricle during systole and diastole. Aortic stenosis usually results in concentric left ventricular hypertrophy instead of eccentric hypertrophy; and therefore, this finding was very unusual. Hypothyroidism, which is uncommon in young dogs, may be incriminated as the cause of ventricular dilation, making this report even more interesting. Because hypothyroidism would only result in dilatation, the eccentric hypertrophy was attributed to pressure overload caused by aortic stenosis. Thus, cardiac alterations of this case represent a paradoxical association of both diseases.

  20. ECONOMIC BENEFITS OF LEFT VENTRICULAR HYPERTROPHY REGRESSION IN PATIENTS WITH ARTERIAL HYPERTENSION

    Directory of Open Access Journals (Sweden)

    E. I. Tarlovskaya

    2011-01-01

    Full Text Available Aim. To evaluate by modelling the economic benefits of left ventricular hypertrophy (LVH regression in patients with arterial hypertension (HT due to therapy with fixed combination of valsartan/amlodipine.  Material and methods. 20 patients (15 females and 5 males, aged 18 to 70 years with essential HT accompanied by metabolic syndrome with a history of previous ineffective antihypertensive therapy were included into the study. All patients were treated with fixed combination of amlodipine/valsartan in doses of 5/160 and 10/160 mg depending on blood pressure (BP level. Treatment duration was 24 weeks. Changes in BP level, LVH regression were assessed. Economic evaluation was performed on the basis of modelling with the specialized software Decision Tree 4.xla. Results. Effect of fixed amlodipine/valsartan combination therapy on LVH was used to estimate treatment effectiveness and to build the model. Patients were distributed according to left ventricular (LV mass (at baseline and after 24 weeks of therapy. Significant decrease in LV mass from 205.8±50.4 to 181.9±45.1 g (p<0.05 was revealed. The model took into account economic and frequency factors for 10 year prognosis: this therapy prevents 36 deaths, 6 strokes, 24 myocardial infarction per 1000 patients. Absence of need in treatment of these prevented events can save 2 516 772.42 RUR for every 1 000 patients. It would reduce the total costs per patient during 10 years. Conclusion. Treatment with amlodipine/valsartan single pill combination has not only clinical advantages, but also pharmacoeconomic benefits. This combination reduces risk of acute myocardial infarction and death more effectively. Treatment with fixed valsartan/amlodipine combination saves maximum years of life with less cost during 10 years. Despite of higher pharmacotherapy costs, fixed valsartan/amlodipine combination reduces total costs due to prevention of fatal and nonfatal cardiovascular events.

  1. Local renin–angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy

    Science.gov (United States)

    Kobori, H; Ichihara, A; Miyashita, Y; Hayashi, M; Saruta, T

    2008-01-01

    We have reported previously that thyroid hormone activates the circulating and tissue renin–angiotensin systems without involving the sympathetic nervous system, which contributes to cardiac hypertrophy in hyperthyroidism. This study examined whether the circulating or tissue renin–angiotensin system plays the principal role in hyperthyroidism-induced cardiac hypertrophy. The circulating renin–angiotensin system in Sprague–Dawley rats was fixed by chronic angiotensin II infusion (40 ng/ min, 28 days) via mini-osmotic pumps. Daily i.p. injection of thyroxine (0·1 mg/kg per day, 28 days) was used to mimic hyperthyroidism. Serum free tri-iodothyronine, plasma renin activity, plasma angiotensin II, cardiac renin and cardiac angiotensin II were measured with RIAs. The cardiac expression of renin mRNA was evaluated by semiquantitative reverse transcriptase-polymerase chain reaction. Plasma renin activity and plasma angiotensin II were kept constant in the angiotensin II and angiotensin II+thyroxine groups (0·12 ± 0·03 and 0·15 ± 0·03 μg/h per liter, 126 ± 5 and 130 ± 5 ng/l respectively) (means ± s.e.m.). Despite stabilization of the circulating renin–angiotensin system, thyroid hormone induced cardiac hypertrophy (5·0 ± 0·5 vs 3·5 ± 0·1 mg/g) in conjunction with the increases in cardiac expression of renin mRNA, cardiac renin and cardiac angiotensin II (74 ± 2 vs 48 ± 2%, 6·5 ± 0·8 vs 3·8 ± 0·4 ng/h per g, 231 ± 30 vs 149 ± 2 pg/g respectively). These results indicate that the local renin–angiotensin system plays the primary role in the development of hyperthyroidism-induced cardiac hypertrophy. PMID:9854175

  2. Muscle hypertrophy induced by myostatin inhibition accelerates degeneration in dysferlinopathy.

    Science.gov (United States)

    Lee, Yun-Sil; Lehar, Adam; Sebald, Suzanne; Liu, Min; Swaggart, Kayleigh A; Talbot, C Conover; Pytel, Peter; Barton, Elisabeth R; McNally, Elizabeth M; Lee, Se-Jin

    2015-10-15

    Myostatin is a secreted signaling molecule that normally acts to limit muscle growth. As a result, there is extensive effort directed at developing drugs capable of targeting myostatin to treat patients with muscle loss. One potential concern with this therapeutic approach in patients with muscle degenerative diseases like muscular dystrophy is that inducing hypertrophy may increase stress on dystrophic fibers, thereby accelerating disease progression. To investigate this possibility, we examined the effect of blocking the myostatin pathway in dysferlin-deficient (Dysf(-/-)) mice, in which membrane repair is compromised, either by transgenic expression of follistatin in skeletal muscle or by systemic administration of the soluble form of the activin type IIB receptor (ACVR2B/Fc). Here, we show that myostatin inhibition by follistatin transgene expression in Dysf(-/-) mice results in early improvement in histopathology but ultimately exacerbates muscle degeneration; this effect was not observed in dystrophin-deficient (mdx) mice, suggesting that accelerated degeneration induced by follistatin transgene expression is specific to mice lacking dysferlin. Dysf(-/-) mice injected with ACVR2B/Fc showed significant increases in muscle mass and amelioration of fibrotic changes normally seen in 8-month-old Dysf(-/-) mice. Despite these potentially beneficial effects, ACVR2B/Fc treatment caused increases in serum CK levels in some Dysf(-/-) mice, indicating possible muscle damage induced by hypertrophy. These findings suggest that depending on the disease context, inducing muscle hypertrophy by myostatin blockade may have detrimental effects, which need to be weighed against the potential gains in muscle growth and decreased fibrosis. © The Author 2015. Published by Oxford University Press.

  3. Investigating β-adrenergic-induced cardiac hypertrophy through computational approach: classical and non-classical pathways.

    Science.gov (United States)

    Khalilimeybodi, Ali; Daneshmehr, Alireza; Sharif-Kashani, Babak

    2018-07-01

    The chronic stimulation of β-adrenergic receptors plays a crucial role in cardiac hypertrophy and its progression to heart failure. In β-adrenergic signaling, in addition to the well-established classical pathway, Gs/AC/cAMP/PKA, activation of non-classical pathways such as Gi/PI3K/Akt/GSK3β and Gi/Ras/Raf/MEK/ERK contribute in cardiac hypertrophy. The signaling network of β-adrenergic-induced hypertrophy is very complex and not fully understood. So, we use a computational approach to investigate the dynamic response and contribution of β-adrenergic mediators in cardiac hypertrophy. The proposed computational model provides insights into the effects of β-adrenergic classical and non-classical pathways on the activity of hypertrophic transcription factors CREB and GATA4. The results illustrate that the model captures the dynamics of the main signaling mediators and reproduces the experimental observations well. The results also show that despite the low portion of β2 receptors out of total cardiac β-adrenergic receptors, their contribution in the activation of hypertrophic mediators and regulation of β-adrenergic-induced hypertrophy is noticeable and variations in β1/β2 receptors ratio greatly affect the ISO-induced hypertrophic response. The model results illustrate that GSK3β deactivation after β-adrenergic receptor stimulation has a major influence on CREB and GATA4 activation and consequent cardiac hypertrophy. Also, it is found through sensitivity analysis that PKB (Akt) activation has both pro-hypertrophic and anti-hypertrophic effects in β-adrenergic signaling.

  4. AMPKγ3 is dispensable for skeletal muscle hypertrophy induced by functional overload.

    Science.gov (United States)

    Riedl, Isabelle; Osler, Megan E; Björnholm, Marie; Egan, Brendan; Nader, Gustavo A; Chibalin, Alexander V; Zierath, Juleen R

    2016-03-15

    Mechanisms regulating skeletal muscle growth involve a balance between the activity of serine/threonine protein kinases, including the mammalian target of rapamycin (mTOR) and 5'-AMP-activated protein kinase (AMPK). The contribution of different AMPK subunits to the regulation of cell growth size remains inadequately characterized. Using AMPKγ3 mutant-overexpressing transgenic Tg-Prkag3(225Q) and AMPKγ3-knockout (Prkag3(-/-)) mice, we investigated the requirement for the AMPKγ3 isoform in functional overload-induced muscle hypertrophy. Although the genetic disruption of the γ3 isoform did not impair muscle growth, control sham-operated AMPKγ3-transgenic mice displayed heavier plantaris muscles in response to overload hypertrophy and underwent smaller mass gain and lower Igf1 expression compared with wild-type littermates. The mTOR signaling pathway was upregulated with functional overload but unchanged between genetically modified animals and wild-type littermates. Differences in AMPK-related signaling pathways between transgenic, knockout, and wild-type mice did not impact muscle hypertrophy. Glycogen content was increased following overload in wild-type mice. In conclusion, our functional, transcriptional, and signaling data provide evidence against the involvement of the AMPKγ3 isoform in the regulation of skeletal muscle hypertrophy. Thus, the AMPKγ3 isoform is dispensable for functional overload-induced muscle growth. Mechanical loading can override signaling pathways that act as negative effectors of mTOR signaling and consequently promote skeletal muscle hypertrophy. Copyright © 2016 the American Physiological Society.

  5. Early regression of severe left ventricular hypertrophy after transcatheter aortic valve replacement is associated with decreased hospitalizations.

    Science.gov (United States)

    Lindman, Brian R; Stewart, William J; Pibarot, Philippe; Hahn, Rebecca T; Otto, Catherine M; Xu, Ke; Devereux, Richard B; Weissman, Neil J; Enriquez-Sarano, Maurice; Szeto, Wilson Y; Makkar, Raj; Miller, D Craig; Lerakis, Stamatios; Kapadia, Samir; Bowers, Bruce; Greason, Kevin L; McAndrew, Thomas C; Lei, Yang; Leon, Martin B; Douglas, Pamela S

    2014-06-01

    This study sought to examine the relationship between left ventricular mass (LVM) regression and clinical outcomes after transcatheter aortic valve replacement (TAVR). LVM regression after valve replacement for aortic stenosis is assumed to be a favorable effect of LV unloading, but its relationship to improved clinical outcomes is unclear. Of 2,115 patients with symptomatic aortic stenosis at high surgical risk receiving TAVR in the PARTNER (Placement of Aortic Transcatheter Valves) randomized trial or continued access registry, 690 had both severe LV hypertrophy (left ventricular mass index [LVMi] ≥ 149 g/m(2) men, ≥ 122 g/m(2) women) at baseline and an LVMi measurement at 30-day post-TAVR follow-up. Clinical outcomes were compared for patients with greater than versus lesser than median percentage change in LVMi between baseline and 30 days using Cox proportional hazard models to evaluate event rates from 30 to 365 days. Compared with patients with lesser regression, patients with greater LVMi regression had a similar rate of all-cause mortality (14.1% vs. 14.3%, p = 0.99), but a lower rate of rehospitalization (9.5% vs. 18.5%, hazard ratio [HR]: 0.50, 95% confidence interval [CI]: 0.32 to 0.78; p = 0.002) and a lower rate of rehospitalization specifically for heart failure (7.3% vs. 13.6%, p = 0.01). The association with a lower rate of rehospitalization was consistent across subgroups and remained significant after multivariable adjustment (HR: 0.53, 95% CI: 0.34 to 0.84; p = 0.007). Patients with greater LVMi regression had lower B-type natriuretic peptide (p = 0.002) and a trend toward better quality of life (p = 0.06) at 1-year follow-up than did those with lesser regression. In high-risk patients with severe aortic stenosis and severe LV hypertrophy undergoing TAVR, those with greater early LVM regression had one-half the rate of rehospitalization over the subsequent year compared to those with lesser regression. Copyright © 2014 American College of

  6. Sildenafil attenuates pulmonary inflammation and fibrin deposition, mortality and right ventricular hypertrophy in neonatal hyperoxic lung injury

    Directory of Open Access Journals (Sweden)

    Boersma Hester

    2009-04-01

    Full Text Available Abstract Background Phosphodiesterase-5 inhibition with sildenafil has been used to treat severe pulmonary hypertension and bronchopulmonary dysplasia (BPD, a chronic lung disease in very preterm infants who were mechanically ventilated for respiratory distress syndrome. Methods Sildenafil treatment was investigated in 2 models of experimental BPD: a lethal neonatal model, in which rat pups were continuously exposed to hyperoxia and treated daily with sildenafil (50–150 mg/kg body weight/day; injected subcutaneously and a neonatal lung injury-recovery model in which rat pups were exposed to hyperoxia for 9 days, followed by 9 days of recovery in room air and started sildenafil treatment on day 6 of hyperoxia exposure. Parameters investigated include survival, histopathology, fibrin deposition, alveolar vascular leakage, right ventricular hypertrophy, and differential mRNA expression in lung and heart tissue. Results Prophylactic treatment with an optimal dose of sildenafil (2 × 50 mg/kg/day significantly increased lung cGMP levels, prolonged median survival, reduced fibrin deposition, total protein content in bronchoalveolar lavage fluid, inflammation and septum thickness. Treatment with sildenafil partially corrected the differential mRNA expression of amphiregulin, plasminogen activator inhibitor-1, fibroblast growth factor receptor-4 and vascular endothelial growth factor receptor-2 in the lung and of brain and c-type natriuretic peptides and the natriuretic peptide receptors NPR-A, -B, and -C in the right ventricle. In the lethal and injury-recovery model we demonstrated improved alveolarization and angiogenesis by attenuating mean linear intercept and arteriolar wall thickness and increasing pulmonary blood vessel density, and right ventricular hypertrophy (RVH. Conclusion Sildenafil treatment, started simultaneously with exposure to hyperoxia after birth, prolongs survival, increases pulmonary cGMP levels, reduces the pulmonary

  7. Down-regulation of hypoxia-inducible factor-1 alpha and vascular endothelial growth factor by HEXIM1 attenuates myocardial angiogenesis in hypoxic mice.

    Science.gov (United States)

    Yoshikawa, Noritada; Shimizu, Noriaki; Ojima, Hidenori; Kobayashi, Hiroshi; Hosono, Osamu; Tanaka, Hirotoshi

    2014-10-24

    Pulmonary hypertension (PH) sustains elevation of pulmonary vascular resistance and ultimately leads to right ventricular (RV) hypertrophy and failure and death. Recently, proangiogenic factors hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) have been known to promote left ventricular myocardial angiogenesis and lead to cardiac hypertrophy, and this would be involved in RV hypertrophy of PH patients. Previously, we revealed that overexpression of HEXIM1 prevents endothelin-1-induced cardiomyocyte hypertrophy and hypertrophic genes expression, and that cardiomyocyte-specific HEXIM1 transgenic mice ameliorates RV hypertrophy in hypoxia-induced PH model. Given these results, here we analyzed the effect of HEXIM1 on the expression of HIF-1α and VEGF and on myocardial angiogenesis of RV in PH. We revealed that overexpression of HEXIM1 prevented hypoxia-induced expression of HIF-1α protein and its target genes including VEGF in the cultured cardiac myocytes and fibroblasts, and that cardiomyocyte-specific HEXIM1 transgenic mice repressed RV myocardial angiogenesis in hypoxia-induced PH model. Thus, we conclude that HEXIM1 could prevent RV hypertrophy, at least in part, via suppression of myocardial angiogenesis through down-regulation of HIF-1α and VEGF in the myocardium under hypoxic condition. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Association of the beta-1 adrenergic receptor carboxyl terminal variants with left ventricular hypertrophy among diabetic and non-diabetic survivors of acute myocardial infarction

    Directory of Open Access Journals (Sweden)

    Hakalahti Anna E

    2010-08-01

    Full Text Available Abstract Background The beta-1 adrenergic receptor (β1AR plays a fundamental role in the regulation of cardiovascular functions. It carries a nonsynonymous single nucleotide polymorphism in its carboxyl terminal tail (Arg389Gly, which has been shown to associate with various echocardiographic parameters linked to left ventricular hypertrophy (LVH. Diabetes mellitus (DM, on the other hand, represents a risk factor for LVH. We investigated the possible association between the Arg389Gly polymorphism and LVH among non-diabetic and diabetic acute myocardial infarction (AMI survivors. Methods The study population consisted of 452 AMI survivors, 20.6% of whom had diagnosed DM. Left ventricular parameters were measured with two-dimensional guided M-mode echocardiography 2-7 days after AMI, and the Arg389Gly polymorphism was determined using a polymerase chain reaction-restriction fragment length polymorphism assay. Results The Arg389 homozygotes in the whole study population had a significantly increased left ventricular mass index (LVMI when compared to the Gly389 carriers (either Gly389 homozygotes or Arg389/Gly389 heterozygotes [62.7 vs. 58.4, respectively (p = 0.023]. In particular, the Arg389 homozygotes displayed thicker diastolic interventricular septal (IVSd measures when compared to the Gly389 carriers [13.2 vs. 12.3 mm, respectively (p = 0.004]. When the euglycemic and diabetic patients were analyzed separately, the latter had significantly increased LVMI and diastolic left ventricular posterior wall (LVPWd values compared to the euglycemic patients [LVMI = 69.1 vs. 58.8 (p = 0.001 and LVPWd = 14.2 vs. 12.3 mm (p Conclusions The data suggest an association between the β1AR Arg389Gly polymorphism and LVH, particularly the septal hypertrophy. The Arg389 variant appears to confer a higher risk of developing LVH than the corresponding Gly389 variant among patients who have suffered AMI. This association cannot be considered to be universal

  9. Electrically induced muscle cramps induce hypertrophy of calf muscles in healthy adults.

    Science.gov (United States)

    Behringer, M; Moser, M; Montag, J; McCourt, M; Tenner, D; Mester, J

    2015-06-01

    Skeletal muscles usually cramp at short lengths, where the tension that can be exerted by muscle fibers is low. Since high tension is an important anabolic stimulus, it is questionable if cramps can induce hypertrophy and strength gains. In the present study we investigated if electrically induced cramps (EIMCs) can elicit these adaptations. 15 healthy male adults were randomly assigned to an intervention (IG; n=10) and a control group (CG; n=5). The cramp protocol (CP) applied twice a week to one leg of the IG, consisted of 3x6 EIMCs, of 5 s each. Calf muscles of the opposite leg were stimulated equally, but were hindered from cramping by fixating the ankle at 0° plantar flexion (nCP). After six weeks, the cross sectional area of the triceps surae was similarly increased in both the CP (+9.0±3.4%) and the nCP (+6.8±3.7%). By contrast, force of maximal voluntary contractions, measured at 0° and 30° plantar flexion, increased significantly only in nCP (0°: +8.5±8.8%; 30°: 11.7±13.7%). The present data indicate that muscle cramps can induce hypertrophy in calf muscles, though lacking high tension as an important anabolic stimulus.

  10. IGF and myostatin pathways are respectively induced during the earlier and the later stages of skeletal muscle hypertrophy induced by clenbuterol, a β₂-adrenergic agonist.

    Science.gov (United States)

    Abo, Tokuhisa; Iida, Ryo-Hei; Kaneko, Syuhei; Suga, Takeo; Yamada, Hiroyuki; Hamada, Yoshiki; Yamane, Akira

    2012-12-01

    Clenbuterol, a β₂-adrenergic agonist, increases the hypertrophy of skeletal muscle. Insulin-like growth factor (IGF) is reported to work as a potent positive regulator in the clenbuterol-induced hypertrophy of skeletal muscles. However, the precise regulatory mechanism for the hypertrophy of skeletal muscle induced by clenbuterol is unknown. Myostatin, a member of the TGFβ super family, is a negative regulator of muscle growth. The aim of the present study is to elucidate the function of myostatin and IGF in the hypertrophy of rat masseter muscle induced by clenbuterol. To investigate the function of myostatin and IGF in regulatory mechanism for the clenbuterol-induced hypertrophy of skeletal muscles, we analysed the expression of myostatin and phosphorylation levels of myostatin and IGF signaling components in the masseter muscle of rat to which clenbuterol was orally administered for 21 days. Hypertrophy of the rat masseter muscle was induced between 3 and 14 days of oral administration of clenbuterol and was terminated at 21 days. The expression of myostatin and the phosphorylation of smad2/3 were elevated at 21 days. The phosphorylation of IGF receptor 1 (IGFR1) and akt1 was elevated at 3 and 7 days. These results suggest that myostatin functions as a negative regulator in the later stages in the hypertrophy of rat masseter muscle induced by clenbuterol, whereas IGF works as a positive regulator in the earlier stages. Copyright © 2012 John Wiley & Sons, Ltd.

  11. Echocardiographic assessment of the different left ventricular geometric patterns in hypertensive patients

    Directory of Open Access Journals (Sweden)

    Delma Maria Cunha

    2001-01-01

    Full Text Available OBJECTIVE: To identiy left ventricular geometric patterns in hypertensive patients on echocardiography, and to correlate those patterns with casual blood pressure measurements and with the parameters obtained on a 24-hour ambulatory blood pressure monitoring. METHODS: We studied sixty hypertensive patients, grouped according to the Joint National Committee stages of hypertension.. Using the single- and two-dimensional Doppler Echocardiography, we analyzed the left ventricular mass and the geometric patterns through the correlation of left ventricular mass index and relative wall thickness. On ambulatory blood pressure monitoring we assessed the means and pressure loads in the different geometric patterns detected on echocardiography RESULTS: We identified three left ventricular geometric patterns: 1 concentric hypertrophy, in 25% of the patients; 2 concentric remodeling, in 25%; and 3 normal geometry, in 50%. Casual systolic blood pressure was higher in the group with concentric hypertrophy than in the other groups (p=0.001. Mean systolic pressure in the 24h, daytime and nighttime periods was also higher in patients with concentric hypertrophy, as compared to the other groups (p=0.003, p=0.004 and p=0.007. Daytime systolic load and nighttime diastolic load were higher in patients with concentric hypertrophy ( p=0.004 and p=0.01, respectively. CONCLUSIONS: Left ventricular geometric patterns show significant correlation with casual systolic blood pressure, and with means and pressure loads on ambulatory blood pressure monitoring.

  12. Cycle training induces muscle hypertrophy and strength gain: strategies and mechanisms.

    Science.gov (United States)

    Ozaki, Hayao; Loenneke, J P; Thiebaud, R S; Abe, T

    2015-03-01

    Cycle training is widely performed as a major part of any exercise program seeking to improve aerobic capacity and cardiovascular health. However, the effect of cycle training on muscle size and strength gain still requires further insight, even though it is known that professional cyclists display larger muscle size compared to controls. Therefore, the purpose of this review is to discuss the effects of cycle training on muscle size and strength of the lower extremity and the possible mechanisms for increasing muscle size with cycle training. It is plausible that cycle training requires a longer period to significantly increase muscle size compared to typical resistance training due to a much slower hypertrophy rate. Cycle training induces muscle hypertrophy similarly between young and older age groups, while strength gain seems to favor older adults, which suggests that the probability for improving in muscle quality appears to be higher in older adults compared to young adults. For young adults, higher-intensity intermittent cycling may be required to achieve strength gains. It also appears that muscle hypertrophy induced by cycle training results from the positive changes in muscle protein net balance.

  13. Asymmetric septal hypertrophy of sporadic form with abnormal thallium perfusion and myocardial enzymes

    International Nuclear Information System (INIS)

    Nagata, Seiki; Minamikawa, Tetsuhiro; Park, Yung-Dae; Nishimura, Tsunehiko; Yutani, Chikao; Ohmori, Fumio; Sakakibara, Hiroshi; Nimura, Yasuharu

    1986-01-01

    Asymmetric septal hypertrophy with abnormal thallium scintigram and elevated cardiac enzymes were observed in five patients and were studied with special reference to the clinical significance of their clinicopathological features. They were not familial cardiomyopathy patients. Two of the five patients (Cases 1 and 2) exhibited the clinical features characteristic of hypertrophic cardiomyopathy without abnormal thallium perfusion and serum cardiac enzyme levels. A right endomyocardial biopsy for Case 1 disclosed myocardial fibrosis in addition to hypertrophy and disarray of myocardial fibers. The left ventricular cavities of two other patients (Cases 4 and 5) tended to be dilated with signs of impaired systolic function and asymmetric septal hypertrophy. A regional area of reduced thickness was observed in the medial portion of the left ventricular posterior wall of Case 4. The remaining case (Case 3) exhibited left ventricular dilatation and reduced left ventricular systolic function, disproportionate hypertrophy, and had clinical signs of congestive heart failure. Necropsy disclosed massive fibrosis and diffuse disarray of myocardial fibers. Some patients with familial hypertrophic cardiomyopathy progress to exhibit clinical features of dilated cardiomyopathy in the termimal stages, and have massive fibrosis of the myocardium histologically. Thallium scintigraphic abnormalities and elevated serum levels of cardiac enzymes, especially the LDH 1 isoenzyme, in patients with hypertrophic cardiomyopathy may be a meaningful indicator of such progression in its early stages. The five patients in the present study exhibited a variety of clinical and histological features which may comprise a spectrum of clinical conditions during the progression from hypertrophic cardiomyopathy to a condition like dilated cardiomyopathy, similar to that in familial patients. This progression and the factors promoting it should be studied further in the near future. (author)

  14. Evaluation of myocardial disorders in patients with dilated cardiomyopathy and left ventricular eccentric hypertrophy; By sup 201 Tl myocardial SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Yamazaki, Junichi; Ohsawa, Hidefumi; Uchi, Takashi (Toho Univ., Tokyo (Japan). School of Medicine) (and others)

    1992-03-01

    {sup 201}Tl myocardial SPECT was performed in cases of dilated cardiomyopathy and valvular heart disease with left ventricular eccentric hypertrophy, and the two groups were compared from the standpoint of the mechanism of onset of myocardial disorders. Significant coefficients of correlation were seen between the Tl score and LVDd (r=0.792, r=0.785) and Tl score and LVEF (r=-0.634, r=-0.555) in both dilated cardiomyopathy and valvular heart disease. In cases of valvular heart disease, significant correlation coefficients (r=-0.756, r=-0.720) between LVDd and r-WR (relative-washout rate), and Tl score and r-WR were observed, but no such correlation was seen in dilated cardiomyopathy. In valvular heart disease, a decrease in myocardial perfusion associated with enlargement of the left ventricle appeared, while in dilated cardiomyopathy, there was a marked decrease in LVEF in proportion to the thallium defect. Therefore, it was assumed that left ventricular wall disorders occur due to myocardial metabolic disorders and coronary microcirculation disorders. (author).

  15. Role of heterotrimeric G protein and calcium in cardiomyocyte hypertrophy induced by IGF-1.

    Science.gov (United States)

    Carrasco, Loreto; Cea, Paola; Rocco, Paola; Peña-Oyarzún, Daniel; Rivera-Mejias, Pablo; Sotomayor-Flores, Cristian; Quiroga, Clara; Criollo, Alfredo; Ibarra, Cristian; Chiong, Mario; Lavandero, Sergio

    2014-04-01

    In the heart, insulin-like growth factor-1 (IGF-1) is a peptide with pro-hypertrophic and anti-apoptotic actions. The pro-hypertrophic properties of IGF-1 have been attributed to the extracellular regulated kinase (ERK) pathway. Recently, we reported that IGF-1 also increases intracellular Ca(2+) levels through a pertussis toxin (PTX)-sensitive G protein. Here we investigate whether this Ca(2+) signal is involved in IGF-1-induced cardiomyocyte hypertrophy. Our results show that the IGF-1-induced increase in Ca(2+) level is abolished by the IGF-1 receptor tyrosine kinase inhibitor AG538, PTX and the peptide inhibitor of Gβγ signaling, βARKct. Increases in the activities of Ca(2+) -dependent enzymes calcineurin, calmodulin kinase II (CaMKII), and protein kinase Cα (PKCα) were observed at 5 min after IGF-1 exposure. AG538, PTX, βARKct, and the dominant negative PKCα prevented the IGF-1-dependent phosphorylation of ERK1/2. Participation of calcineurin and CaMKII in ERK phosphorylation was discounted. IGF-1-induced cardiomyocyte hypertrophy, determined by cell size and β-myosin heavy chain (β-MHC), was prevented by AG538, PTX, βARKct, dominant negative PKCα, and the MEK1/2 inhibitor PD98059. Inhibition of calcineurin with CAIN did not abolish IGF-1-induced cardiac hypertrophy. We conclude that IGF-1 induces hypertrophy in cultured cardiomyocytes by activation of the receptor tyrosine kinase activity/βγ-subunits of a PTX-sensitive G protein/Ca(2+) /PKCα/ERK pathway without the participation of calcineurin. © 2013 Wiley Periodicals, Inc.

  16. Acromegaly-induced cardiomyopathy with dobutamine-induced outflow tract obstruction.

    Science.gov (United States)

    Abdelsalam, Mahmoud A; Nippoldt, Todd B; Geske, Jeffrey B

    2016-03-09

    A 50-year-old man with a history of acromegaly was referred for preoperative cardiac evaluation preceding trans-sphenoidal resection of a pituitary macroadenoma. Dobutamine stress echocardiography was negative for myocardial ischaemia. Resting left ventricular (LV) LV ejection fraction (LVEF) was 64% and there was hypertrophy of ventricular septum (18 mm) without resting LV outflow tract obstruction. With 40 µg/kg/min of dobutamine, the LVEF became hyperdynamic at 80%, and there was a maximal instantaneous LV outflow tract gradient of 77 mm Hg. There was no delayed myocardial enhancement on cardiac MRI and the pattern of hypertrophy was concentric. Acromegaly-induced cardiomyopathy can mimic hypertrophic cardiomyopathy in the setting of dobutamine provocation. Because cardiomyopathy is an important cause of mortality in acromegaly, diagnosis and appropriate management are critical to improve survival. 2016 BMJ Publishing Group Ltd.

  17. Prognostic importance of hemoglobin in hypertensive patients with electrocardiographic left ventricular hypertrophy: the Losartan Intervention For End point reduction in hypertension (LIFE) study

    DEFF Research Database (Denmark)

    Olsen, Michael Hecht; Wachtell, Kristian; Beevers, Gareth

    2008-01-01

    BACKGROUND: The prognostic importance of hemoglobin is controversial. We investigated the prognostic importance of baseline and in-treatment hemoglobin in the LIFE study. METHODS: Eight thousand one hundred ninety-four LIFE patients with hypertension and left ventricular hypertrophy with available...... with the same gender-specific definitions for high and low hemoglobin as time-varying covariates with adjustment for treatment allocation and established risk factors and diseases, hemoglobin in the lowest decile was associated with higher rates of all-cause mortality (HR 3.03, 95% CI 1.89-4.85, P

  18. Protection of MICU1 against myocardial hypertrophy induced by angiotensin Ⅱ

    Directory of Open Access Journals (Sweden)

    Yi YANG

    2017-12-01

    Full Text Available Objective To investigate the role of mitochondrial calcium uptake 1 (MICU1 in myocardial hypertrophy of mice and underlying mechanism. Methods The model of myocardial hypertrophy was established via incubation of mouse cardiac myocytes (MCM with 300nmol/L angiotensin Ⅱ (Ang Ⅱ for 48 hours in vitro. After that, MICU1 specific small interfering RNA (siRNA was delivered to knockdown MICU1 levels in MCM. On the other hand, adenovirus-mediated over-expression of MICU1 was transfected into MCM. Accordingly, the expressions of ANP and BNP in myocardial cells were measured by qRT- PCR. Mitochondrial membrane potential and ATP contents were detected by JC-1 assay kit and ATP assay kit, respectively. Then, Western blotting and qRT-PCR were used to detect the levels of MICU1 in myocardial cells. The mitochondrial Ca2+ contents were measured via atomic absorption flame spectroscopy. The size of myocardial cells was determined by α-actinin staining. Results Mitochondrial membrane potential and ATP contents in hypertrophic cardiomyocytes induced by AngⅡ were both decreased. Meanwhile, myocardial hypertrophy significantly increased mitochondrial Ca2+ contents but decreased MICU1 levels. With the method of genetic intervention, we found that MICU1 deficiency exacerbated mitochondrial Ca2+ overload, increased cell surface and elevated the expression of BNP. Conversely, the overexpression of MICU1 obviously decreased mitochondrial Ca2+ overload, cell surface of MCM and expressions of ANP and BNP. Conclusion MICU1 alleviates AngⅡ-induced myocardial hypertrophy via inhibiting mitochondrial Ca2+ overload. DOI: 10.11855/j.issn.0577-7402.2017.12.05

  19. Effect of taurine on advanced glycation end products-induced hypertrophy in renal tubular epithelial cells

    International Nuclear Information System (INIS)

    Huang, J.-S.; Chuang, L.-Y.; Guh, J.-Y.; Yang, Y.-L.; Hsu, M.-S.

    2008-01-01

    Mounting evidence indicates that advanced glycation end products (AGE) play a major role in the development of diabetic nephropathy (DN). Taurine is a well documented antioxidant agent. To explore whether taurine was linked to altered AGE-mediated renal tubulointerstitial fibrosis in DN, we examined the molecular mechanisms of taurine responsible for inhibition of AGE-induced hypertrophy in renal tubular epithelial cells. We found that AGE (but not non-glycated BSA) caused inhibition of cellular mitogenesis rather than cell death by either necrosis or apoptosis. There were no changes in caspase 3 activity, bcl-2 protein expression, and mitochondrial cytochrome c release in BSA, AGE, or the antioxidant taurine treatments in these cells. AGE-induced the Raf-1/extracellular signal-regulated kinase (ERK) activation was markedly blocked by taurine. Furthermore, taurine, the Raf-1 kinase inhibitor GW5074, and the ERK kinase inhibitor PD98059 may have the ability to induce cellular proliferation and cell cycle progression from AGE-treated cells. The ability of taurine, GW5074, or PD98059 to inhibit AGE-induced hypertrophy was verified by the observation that it significantly decreased cell size, cellular hypertrophy index, and protein levels of RAGE, p27 Kip1 , collagen IV, and fibronectin. The results obtained in this study suggest that taurine may serve as the potential anti-fibrotic activity in DN through mechanism dependent of its Raf-1/ERK inactivation in AGE-induced hypertrophy in renal tubular epithelial cells

  20. The Association of Long-Functioning Hemodialysis Vascular Access with Prevalence of Left Ventricular Hypertrophy in Kidney Transplant Recipients

    Directory of Open Access Journals (Sweden)

    Aureliusz Kolonko

    2014-01-01

    Full Text Available Left ventricular hypertrophy (LVH is frequently observed in chronic dialysis patients and is also highly prevalent in kidney transplant recipients. This study evaluates the impact of long-functioning hemodialysis vascular access on LVH in single center cohort of kidney transplant recipients. 162 patients at 8.7 ± 1.8 years after kidney transplantation were enrolled. Echocardiography, carotid ultrasound, and assessment of pulse wave velocity were performed. LVH was defined based on left ventricular mass (LVM indexed for body surface area (BSA and height2.7. There were 67 patients with and 95 without patent vascular access. Both study groups were comparable with respect to gender, age, duration of dialysis therapy, and time after transplantation, kidney graft function, and cardiovascular comorbidities. Patients with patent vascular access were characterized by significantly elevated LVM and significantly greater percentage of LVH, based on LVMI/BSA (66.7 versus 48.4%, P=0.02. OR for LVH in patients with patent vascular access was 2.39 (1.19–4.76, P=0.01. Regression analyses confirmed an independent contribution of patent vascular access to higher LVM and increased prevalence of LVH. We concluded that long-lasting patent hemodialysis vascular access after kidney transplantation is associated with the increased prevalence of LVH in kidney transplant recipients.

  1. Size, shape, and stamina: the impact of left ventricular geometry on exercise capacity.

    Science.gov (United States)

    Lam, Carolyn S P; Grewal, Jasmine; Borlaug, Barry A; Ommen, Steve R; Kane, Garvan C; McCully, Robert B; Pellikka, Patricia A

    2010-05-01

    Although several studies have examined the cardiac functional determinants of exercise capacity, few have investigated the effects of structural remodeling. The current study evaluated the association between cardiac geometry and exercise capacity. Subjects with ejection fraction > or = 50% and no valvular disease, myocardial ischemia, or arrhythmias were identified from a large prospective exercise echocardiography database. Left ventricular mass index and relative wall thickness were used to classify geometry into normal, concentric remodeling, eccentric hypertrophy, and concentric hypertrophy. All of the subjects underwent symptom-limited treadmill exercise according to standard Bruce protocol. Maximal exercise tolerance was measured in metabolic equivalents. Of 366 (60+/-14 years; 57% male) subjects, 166 (45%) had normal geometry, 106 (29%) had concentric remodeling, 40 (11%) had eccentric hypertrophy, and 54 (15%) had concentric hypertrophy. Geometry was related to exercise capacity: in descending order, the maximum achieved metabolic equivalents were 9.9+/-2.8 in normal, 8.9+/-2.6 in concentric remodeling, 8.6+/-3.1 in eccentric hypertrophy, and 8.0+/-2.7 in concentric hypertrophy (all P<0.02 versus normal). Left ventricular mass index and relative wall thickness were negatively correlated with exercise tolerance in metabolic equivalents (r=-0.14; P=0.009 and r=-0.21; P<0.001, respectively). Augmentation of heart rate and ejection fraction with exercise were blunted in concentric hypertrophy compared with normal, even after adjusting for medications. In conclusion, the pattern of ventricular remodeling is related to exercise capacity among low-risk adults. Subjects with concentric hypertrophy display the greatest limitation, and this is related to reduced systolic and chronotropic reserve. Reverse remodeling strategies may prevent or treat functional decline in patients with structural heart disease.

  2. Phenotyping of left and right ventricular function in mouse models of compensated hypertrophy and heart failure with cardiac MRI

    NARCIS (Netherlands)

    Nierop, van B.J.; Assen, van H.C.; Deel, van E.D.; Niesen, L.B.P.; Duncker, D.J.; Strijkers, G.J.; Nicolay, K.

    2013-01-01

    Background: Left ventricular (LV) and right ventricular (RV) function have an important impact on symptom occurrence, disease progression and exercise tolerance in pressure overload-induced heart failure, but particularly RV functional changes are not well described in the relevant aortic banding

  3. [Intervention of systolic pressure and left ventricular hypertrophy in rats under cold stress].

    Science.gov (United States)

    Sun, C F; Wang, S G; Peng, Y G; Shi, Y; Du, Y P; Shi, G X; Wen, T; Wang, Y K; Su, H

    2016-06-20

    To investigate the effects of different drugs on systolic blood pressure (SBP) and left ventricular hypertrophy (LVH) in spontaneously hypertensive rats under cold stress. A total of 40 male spontaneously hypertensive rats aged 10 weeks (160~200 g) were given adaptive feeding for 7 days at a temperature of 20±1°C and then randomly divided into control group, cold stress group, metoprolol group, amlodipine group, and benazepril group, with 8 rats in each group. SBP, body weight, and heart rate were measured once a week. After the rats were sacrificed by exsanguination, left ventricular weight (LVW) was measured, and left ventricular weight index (LVWI; mg/g) was calculated. Radioimmunoassay was used to measure the concentrations of endothelin-1 (ET-1) and angiotensin-II (Ang-II) in plasma and myocardium, and the chemical method was used to measure the concentrations of nitric oxide (NO) in plasma and myocardium. RT-PCR was used to measure the mRNA expression of endothelin-A receptor. Compared with the cold stress group, all medication groups showed significant reductions in SBP since week 5 (Pcold stress group showed a significant increase in LVWI compared with the control group (3.38±0.27 mg/g vs 2.89±0.19 mg/g, Pcold stress group (2.98±0.28 mg/g vs 3.38±0.27 mg/g, Pcold stress group showed a significant reduction in plasma NO concentration compared with the control group (104.9±19.5 μmol/L vs 129.3±17.8 μmol/L, Pcold stress group, all the medication groups showed significant increases in blood NO concentration (Pcold stress group showed a significant increase in myocardial ET-1 concentration compared with the control group (6.3±1.5 pg/100 mg vs 4.5±1.9 pg/100 mg, Pcold stress group, the amlodipine group showed a significant reduction in myocardial ET-1 concentration (4.4±1.0 pg/100 mg vs 6.3±1.5 pg/100 mg, Pcold stress group had significantly higher mRNA expression of endothelin-A receptor than the control group (0.86±0.23 vs 0.45±0.16, Pcold

  4. Toll‐Like Receptor‐2 Mediates Adaptive Cardiac Hypertrophy in Response to Pressure Overload Through Interleukin‐1β Upregulation via Nuclear Factor κB Activation

    Science.gov (United States)

    Higashikuni, Yasutomi; Tanaka, Kimie; Kato, Megumi; Nureki, Osamu; Hirata, Yasunobu; Nagai, Ryozo; Komuro, Issei; Sata, Masataka

    2013-01-01

    Background Inflammation is induced in the heart during the development of cardiac hypertrophy. The initiating mechanisms and the role of inflammation in cardiac hypertrophy, however, remain unclear. Toll‐like receptor‐2 (TLR2) recognizes endogenous molecules that induce noninfectious inflammation. Here, we examined the role of TLR2‐mediated inflammation in cardiac hypertrophy. Methods and Results At 2 weeks after transverse aortic constriction, Tlr2−/− mice showed reduced cardiac hypertrophy and fibrosis with greater left ventricular dilatation and impaired systolic function compared with wild‐type mice, which indicated impaired cardiac adaptation in Tlr2−/− mice. Bone marrow transplantation experiment revealed that TLR2 expressed in the heart, but not in bone marrow–derived cells, is important for cardiac adaptive response to pressure overload. In vitro experiments demonstrated that TLR2 signaling can induce cardiomyocyte hypertrophy and fibroblast and vascular endothelial cell proliferation through nuclear factor–κB activation and interleukin‐1β upregulation. Systemic administration of a nuclear factor–κB inhibitor or anti–interleukin‐1β antibodies to wild‐type mice resulted in impaired adaptive cardiac hypertrophy after transverse aortic constriction. We also found that heat shock protein 70, which was increased in murine plasma after transverse aortic constriction, can activate TLR2 signaling in vitro and in vivo. Systemic administration of anti–heat shock protein 70 antibodies to wild‐type mice impaired adaptive cardiac hypertrophy after transverse aortic constriction. Conclusions Our results demonstrate that TLR2‐mediated inflammation induced by extracellularly released heat shock protein 70 is essential for adaptive cardiac hypertrophy in response to pressure overload. Thus, modulation of TLR2 signaling in the heart may provide a novel strategy for treating heart failure due to inadequate adaptation to hemodynamic

  5. Role of IGF-I in follistatin-induced skeletal muscle hypertrophy.

    Science.gov (United States)

    Barbé, Caroline; Kalista, Stéphanie; Loumaye, Audrey; Ritvos, Olli; Lause, Pascale; Ferracin, Benjamin; Thissen, Jean-Paul

    2015-09-15

    Follistatin, a physiological inhibitor of myostatin, induces a dramatic increase in skeletal muscle mass, requiring the type 1 IGF-I receptor/Akt/mTOR pathway. The aim of the present study was to investigate the role of IGF-I and insulin, two ligands of the IGF-I receptor, in the follistatin hypertrophic action on skeletal muscle. In a first step, we showed that follistatin increases muscle mass while being associated with a downregulation of muscle IGF-I expression. In addition, follistatin retained its full hypertrophic effect toward muscle in hypophysectomized animals despite very low concentrations of circulating and muscle IGF-I. Furthermore, follistatin did not increase muscle sensitivity to IGF-I in stimulating phosphorylation of Akt but, surprisingly, decreased it once hypertrophy was present. Taken together, these observations indicate that increased muscle IGF-I production or sensitivity does not contribute to the muscle hypertrophy caused by follistatin. Unlike low IGF-I, low insulin, as obtained by streptozotocin injection, attenuated the hypertrophic action of follistatin on skeletal muscle. Moreover, the full anabolic response to follistatin was restored in this condition by insulin but also by IGF-I infusion. Therefore, follistatin-induced muscle hypertrophy requires the activation of the insulin/IGF-I pathway by either insulin or IGF-I. When insulin or IGF-I alone is missing, follistatin retains its full anabolic effect, but when both are deficient, as in streptozotocin-treated animals, follistatin fails to stimulate muscle growth. Copyright © 2015 the American Physiological Society.

  6. Apigenin ameliorates hypertension-induced cardiac hypertrophy and down-regulates cardiac hypoxia inducible factor-lα in rats.

    Science.gov (United States)

    Zhu, Zeng-Yan; Gao, Tian; Huang, Yan; Xue, Jie; Xie, Mei-Lin

    2016-04-01

    Apigenin is a natural flavonoid compound that can inhibit hypoxia-inducible factor (HIF)-1α expression in cultured tumor cells under hypoxic conditions. Hypertension-induced cardiac hypertrophy is always accompanied by abnormal myocardial glucolipid metabolism due to an increase of HIF-1α. However, whether or not apigenin may ameliorate the cardiac hypertrophy and abnormal myocardial glucolipid metabolism remains unknown. This study aimed to examine the effects of apigenin. Rats with cardiac hypertrophy induced by renovascular hypertension were treated with apigenin 50-100 mg kg(-1) (the doses can be achieved by pharmacological or dietary supplementation for an adult person) by gavage for 4 weeks. The results showed that after treatment with apigenin, the blood pressure, heart weight, heart weight index, cardiomyocyte cross-sectional area, serum angiotensin II, and serum and myocardial free fatty acids were reduced. It is important to note that apigenin decreased the expression level of myocardial HIF-1α protein. Moreover, apigenin simultaneously increased the expression levels of myocardial peroxisome proliferator-activated receptor (PPAR) α, carnitine palmitoyltransferase (CPT)-1, and pyruvate dehydrogenase kinase (PDK)-4 proteins and decreased the expression levels of myocardial PPARγ, glycerol-3-phosphate acyltransferase genes (GPAT), and glucose transporter (GLUT)-4 proteins. These findings demonstrated that apigenin could improve hypertensive cardiac hypertrophy and abnormal myocardial glucolipid metabolism in rats, and its mechanisms might be associated with the down-regulation of myocardial HIF-1α expression and, subsequently increasing the expressions of myocardial PPARα and its target genes CPT-1 and PDK-4, and decreasing the expressions of myocardial PPARγ and its target genes GPAT and GLUT-4.

  7. Phenotyping of left and right ventricular function in mouse models of compensated hypertrophy and heart failure with cardiac MRI

    NARCIS (Netherlands)

    van Nierop, Bastiaan J.; van Assen, Hans C.; van Deel, Elza D.; Niesen, Leonie B. P.; Duncker, Dirk J.; Strijkers, Gustav J.; Nicolay, Klaas

    2013-01-01

    Left ventricular (LV) and right ventricular (RV) function have an important impact on symptom occurrence, disease progression and exercise tolerance in pressure overload-induced heart failure, but particularly RV functional changes are not well described in the relevant aortic banding mouse model.

  8. T-wave inversions related to left ventricular basal hypertrophy and myocardial fibrosis in non-apical hypertrophic cardiomyopathy: A cardiovascular magnetic resonance imaging study

    International Nuclear Information System (INIS)

    Chen, Xiuyu; Zhao, Shihua; Zhao, Tao; Lu, Minjie; Yin, Gang; Jiang, Shiliang; Prasad, Sanjay

    2014-01-01

    Objectives: To investigate the relationship between T-wave inversions and left ventricular (LV) segmental hypertrophy and myocardial fibrosis assessed by cardiovascular magnetic resonance (CMR) in patients with non-apical hypertrophic cardiomyopathy (HCM). Methods: 196 consecutive patients with non-apical HCM underwent late gadolinium enhancement (LGE) CMR and 12-lead electrocardiogram. The distribution and magnitude of LV segmental hypertrophy and LGE were assessed according to the AHA 17-segment model and analyzed in relation to T-wave inversions. Results: Of 196 HCM patients, 144 (73%) exhibited T-wave inversions. 144 (73%) patients had evidence of myocardial fibrosis as defined by LGE, and the prevalence of LGE was significantly higher in patients with T-wave inversions compared with those without T-wave inversions (78% vs. 59%, P = 0.008). T-wave inversions were related to basal anterior and basal anteroseptal LGE (20% vs. 10%, P = 0.04 and 68% vs. 46%, P = 0.005, respectively). In addition, T-wave inversions were associated with greater basal anteroseptal and basal inferior wall thickness (19.5 ± 4.7 mm vs. 16.7 ± 4.5 mm, P < 0.001 and 10.9 ± 3.3 mm vs. 9.6 ± 3.0 mm, P = 0.01, respectively). By logistic regression analysis, basal anteroseptal wall thickness and LGE were independent determinants of T-wave inversions (P = 0.005, P = 0.01, respectively). Conclusions: T-wave inversions in HCM are associated with LGE and wall thickness of the left ventricular basal segments. Moreover, basal anteroseptal wall thickness and LGE are independent determinants of T-wave inversions

  9. T-wave inversions related to left ventricular basal hypertrophy and myocardial fibrosis in non-apical hypertrophic cardiomyopathy: A cardiovascular magnetic resonance imaging study

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Xiuyu, E-mail: cxy0202@126.com [Department of Radiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037 (China); Zhao, Shihua, E-mail: zhaoshihua0202@126.com [Department of Radiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037 (China); Zhao, Tao, E-mail: taozhao0202@126.com [Department of Radiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037 (China); Lu, Minjie, E-mail: lmjkan@126.com [Department of Radiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037 (China); Yin, Gang, E-mail: gangyin0202@126.com [Department of Radiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037 (China); Jiang, Shiliang, E-mail: jiangsl-2011@163.com [Department of Radiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037 (China); Prasad, Sanjay, E-mail: s.prasad@rbht.nhs.uk [NIHR Biomedical Research Unit, Royal Brompton Hospital Sydney Street, London, SW3 6NP (United Kingdom)

    2014-02-15

    Objectives: To investigate the relationship between T-wave inversions and left ventricular (LV) segmental hypertrophy and myocardial fibrosis assessed by cardiovascular magnetic resonance (CMR) in patients with non-apical hypertrophic cardiomyopathy (HCM). Methods: 196 consecutive patients with non-apical HCM underwent late gadolinium enhancement (LGE) CMR and 12-lead electrocardiogram. The distribution and magnitude of LV segmental hypertrophy and LGE were assessed according to the AHA 17-segment model and analyzed in relation to T-wave inversions. Results: Of 196 HCM patients, 144 (73%) exhibited T-wave inversions. 144 (73%) patients had evidence of myocardial fibrosis as defined by LGE, and the prevalence of LGE was significantly higher in patients with T-wave inversions compared with those without T-wave inversions (78% vs. 59%, P = 0.008). T-wave inversions were related to basal anterior and basal anteroseptal LGE (20% vs. 10%, P = 0.04 and 68% vs. 46%, P = 0.005, respectively). In addition, T-wave inversions were associated with greater basal anteroseptal and basal inferior wall thickness (19.5 ± 4.7 mm vs. 16.7 ± 4.5 mm, P < 0.001 and 10.9 ± 3.3 mm vs. 9.6 ± 3.0 mm, P = 0.01, respectively). By logistic regression analysis, basal anteroseptal wall thickness and LGE were independent determinants of T-wave inversions (P = 0.005, P = 0.01, respectively). Conclusions: T-wave inversions in HCM are associated with LGE and wall thickness of the left ventricular basal segments. Moreover, basal anteroseptal wall thickness and LGE are independent determinants of T-wave inversions.

  10. Characteristics of left ventricular hypertrophy estimated by MIBG and BMIPP cardiac scintigraphy in patients undergoing peritoneal dialysis

    Energy Technology Data Exchange (ETDEWEB)

    Ohashi, Hiroshige; Oda, Hiroshi; Ohno, Michiya; Watanabe, Sachirow; Kotoo, Yasunori; Matsuno, Yukihiko [Gifu Prefectural Hospital (Japan)

    2002-12-01

    Left ventricular hypertrophy (LVH) has been reported as a major factor in morbidity and mortality in chronic dialysis patients. However, cardiovascular mortality in peritoneal dialysis (PD) patients with LVH is substantially similar to that in hemodialysis (HD) patients. The present study sought to study whether sympathetic nerve activity and fatty acid metabolism of the myocardium estimated by {sup 123}I metaiodobenzylguanidine (MIBG) and {sup 123}I {beta}-methyl-p-iodophenyl-pentadecanoic acid (BMIPP) myocardial scintigraphy are impaired or not in PD patients with LVH. The underlying disease of 45 PD patients enrolled in this study was chronic glomerulonephritis in all cases. Serum levels of natriuretic peptides (arterial natriuretic peptide (ANP), brain natriuretic peptide (BNP)) and free carnitine and MIBG, BMIPP myocardial scintigraphy and 2-dimensional echocardiography were measured in these 45 PD patients. The following results were obtained. The prevalence of increased left ventricular mass index (LVMI) was 84.4%. LVMI correlated with age, and serum levels of ANP and BNP, and inversely correlated with a heart-to-mediastinum ratio (H/M) estimated by MIBG and BMIPP myocardial scintigraphy. Percentages of the normal image of MIBG and BMIPP measured with a single photon emission computed tomography (SPECT) were 37.8% and 62.2%, respectively. The PD patients showing the diffuse defect of MIBG or BMIPP imaging had the decrease in left ventricular ejection fraction (LVEF). Especially, the serum level of free carnitine was reduced in the PD patients with diffuse defect of BMIPP SPECT. From these results, we concluded that PD patients with LVH showed impaired sympathetic nerve activity and fatty acid metabolism of the myocardium. Metabolic and functional disturbances of the myocardium may influence mortality in PD patients. (author)

  11. Apelin and APJ orchestrate complex tissue-specific control of cardiomyocyte hypertrophy and contractility in the hypertrophy-heart failure transition.

    Science.gov (United States)

    Parikh, Victoria Nicole; Liu, Jing; Shang, Ching; Woods, Christopher; Chang, Alex Chia Yu; Zhao, Mingming; Charo, David N; Grunwald, Zachary; Huang, Yong; Seo, Kinya; Tsao, Philip S; Bernstein, Daniel; Ruiz-Lozano, Pilar; Quertermous, Thomas; Ashley, Euan A

    2018-05-18

    The G protein coupled receptor APJ is a promising therapeutic target for heart failure. Constitutive deletion of APJ in the mouse is protective against the hypertrophy-heart failure transition via elimination of ligand-independent, β-arrestin dependent stretch transduction. However, the cellular origin of this stretch transduction and the details of its interaction with apelin signaling remain unknown. We generated mice with conditional elimination of APJ in the endothelium (APJ endo-/- ) and myocardium (APJ myo-/- ). No baseline difference was observed in LV function in APJ endo-/- , APJ myo-/- or controls (APJ endo+/+ , APJ myo+/+ ). After exposure to transaortic constriction (TAC), APJ endo-/- animals developed left ventricular failure while APJ myo-/- were protected. At the cellular level, carbon fiber stretch of freshly isolated single cardiomyocytes demonstrated decreased contractile response to stretch in APJ -/- cardiomyocytes compared to APJ +/+ cardiomyocytes. Calcium transient did not change with stretch in either APJ -/- or APJ +/+ cardiomyocytes. Application of apelin to APJ +/+ cardiomyocytes resulted in decreased calcium transient. Further, hearts of mice treated with apelin exhibited decreased phosphorylation at Troponin I (cTnI) N-terminal residues (Ser 22,23), consistent with increased calcium sensitivity. These data establish that APJ stretch transduction is mediated specifically by myocardial APJ, that APJ is necessary for stretch-induced increases in contractility, and that apelin opposes APJ's stretch-mediated hypertrophy signaling by lowering calcium transient while maintaining contractility through myofilament calcium sensitization. These findings underscore apelin's unique potential as a therapeutic agent that can simultaneously support cardiac function and protect against the hypertrophy-heart failure transition.

  12. Cyclin D2 is a critical mediator of exercise-induced cardiac hypertrophy.

    Science.gov (United States)

    Luckey, Stephen W; Haines, Chris D; Konhilas, John P; Luczak, Elizabeth D; Messmer-Kratzsch, Antke; Leinwand, Leslie A

    2017-12-01

    A number of signaling pathways underlying pathological cardiac hypertrophy have been identified. However, few studies have probed the functional significance of these signaling pathways in the context of exercise or physiological pathways. Exercise studies were performed on females from six different genetic mouse models that have been shown to exhibit alterations in pathological cardiac adaptation and hypertrophy. These include mice expressing constitutively active glycogen synthase kinase-3β (GSK-3βS9A), an inhibitor of CaMK II (AC3-I), both GSK-3βS9A and AC3-I (GSK-3βS9A/AC3-I), constitutively active Akt (myrAkt), mice deficient in MAPK/ERK kinase kinase-1 (MEKK1 -/- ), and mice deficient in cyclin D2 (cyclin D2 -/- ). Voluntary wheel running performance was similar to NTG littermates for five of the mouse lines. Exercise induced significant cardiac growth in all mouse models except the cyclin D2 -/- mice. Cardiac function was not impacted in the cyclin D2 -/- mice and studies using a phospho-antibody array identified six proteins with increased phosphorylation (greater than 150%) and nine proteins with decreased phosphorylation (greater than 33% decrease) in the hearts of exercised cyclin D2 -/- mice compared to exercised NTG littermate controls. Our results demonstrate that unlike the other hypertrophic signaling molecules tested here, cyclin D2 is an important regulator of both pathologic and physiological hypertrophy. Impact statement This research is relevant as the hypertrophic signaling pathways tested here have only been characterized for their role in pathological hypertrophy, and not in the context of exercise or physiological hypertrophy. By using the same transgenic mouse lines utilized in previous studies, our findings provide a novel and important understanding for the role of these signaling pathways in physiological hypertrophy. We found that alterations in the signaling pathways tested here had no impact on exercise performance. Exercise

  13. Impairment of Excitation-Contraction Coupling in Right Ventricular Hypertrophied Muscle with Fibrosis Induced by Pulmonary Artery Banding.

    Directory of Open Access Journals (Sweden)

    Yoichiro Kusakari

    Full Text Available Interstitial myocardial fibrosis is one of the factors responsible for dysfunction of the heart. However, how interstitial fibrosis affects cardiac function and excitation-contraction coupling (E-C coupling has not yet been clarified. We developed an animal model of right ventricular (RV hypertrophy with fibrosis by pulmonary artery (PA banding in rats. Two, four, and six weeks after the PA-banding operation, the tension and intracellular Ca2+ concentration of RV papillary muscles were simultaneously measured (n = 33. The PA-banding rats were clearly divided into two groups by the presence or absence of apparent interstitial fibrosis in the papillary muscles: F+ or F- group, respectively. The papillary muscle diameter and size of myocytes were almost identical between F+ and F-, although the RV free wall weight was heavier in F+ than in F-. F+ papillary muscles exhibited higher stiffness, lower active tension, and lower Ca2+ responsiveness compared with Sham and F- papillary muscles. In addition, we found that the time to peak Ca2+ had the highest correlation coefficient to percent of fibrosis among other parameters, such as RV weight and active tension of papillary muscles. The phosphorylation level of troponin I in F+ was significantly higher than that in Sham and F-, which supports the idea of lower Ca2+ responsiveness in F+. We also found that connexin 43 in F+ was sparse and disorganized in the intercalated disk area where interstitial fibrosis strongly developed. In the present study, the RV papillary muscles obtained from the PA-banding rats enabled us to directly investigate the relationship between fibrosis and cardiac dysfunction, the impairment of E-C coupling in particular. Our results suggest that interstitial fibrosis worsens cardiac function due to 1 the decrease in Ca2+ responsiveness and 2 the asynchronous activation of each cardiac myocyte in the fibrotic preparation due to sparse cell-to-cell communication.

  14. Association of Post-Saline Load Plasma Aldosterone Levels With Left Ventricular Hypertrophy in Primary Hypertension.

    Science.gov (United States)

    Catena, Cristiana; Verheyen, Nicolas D; Url-Michitsch, Marion; Kraigher-Krainer, Elisabeth; Colussi, GianLuca; Pilz, Stefan; Tomaschitz, Andreas; Pieske, Burkert; Sechi, Leonardo A

    2016-03-01

    Left ventricular hypertrophy (LVH) is an independent risk factor for cardiovascular morbidity in hypertension. Current evidence suggests a contribution to LVH of plasma aldosterone levels that are inappropriately elevated for the salt status. The aim of this study was to investigate whether inappropriate modulation of aldosterone production by a saline load is associated with left ventricular (LV) mass in hypertensive patients. In 90 hypertensive patients free of clinically relevant cardiovascular complications in whom secondary forms of hypertension were ruled out, we performed a standard intravenous saline load (0.9% NaCl, 2 l in 4 hours) with measurement of plasma aldosterone and active renin at baseline and end of infusion. Bi-dimensional echocardiography was performed for the assessment of cardiac morphology and function. LVH was present in 19% of patients who had significantly worse renal function and higher body mass, blood pressure, and plasma aldosterone levels measured both at baseline and after the saline load than patients without LVH. LV mass was directly related to age, body mass, systolic blood pressure, duration of hypertension, baseline, and post-saline load plasma aldosterone levels and inversely to glomerular filtration. Multivariate regression analysis showed independent correlation of LV mass with body mass, systolic blood pressure, and plasma aldosterone levels measured after intravenous saline load, but not at baseline. In patients with hypertension, aldosterone levels measured after intravenous saline load are related to LV mass independent of age, body mass, and blood pressure, suggesting that limited ability of salt to modulate aldosterone production could contribute to LVH. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  15. Analysis of microRNA Expression Profiles Induced by Yiqifumai Injection in Rats with Chronic Heart Failure

    Directory of Open Access Journals (Sweden)

    Yu Zhao

    2018-02-01

    Full Text Available Background: Yiqifumai Injection (YQFM is clinically used to treat various cardiovascular diseases including chronic heart failure (CHF. The efficacy of YQFM for treating heart failure has been suggested, but the mechanism of action for pharmacological effects of YQFM is unclear.Methods: Echocardiography detection, left ventricular intubation evaluation, histopathology and immunohistochemical examination were performed in CHF rats to evaluate the cardioprotective effect of YQFM. Rat miRNA microarray and bioinformatics analysis were employed to investigate the differentially expressed microRNAs. In vitro models of AngII-induced hypertrophy and t-BHP induced oxidative stress in H9c2 myocardial cells were used to validate the anti-hypertrophy and anti-apoptosis effects of YQFM. Measurement of cell surface area, ATP content and cell viability, Real-time PCR and Western blot were performed.Results: YQFM significantly improved the cardiac function of CHF rats by increasing left ventricular ejection fraction and fractional shortening, decreasing left ventricular internal diameter and enhancing cardiac output. Seven microRNAs which have a reversible regulation by YQFM treatment were found. Among them, miR-21-3p and miR-542-3p are related to myocardial hypertrophy and cell proliferation, respectively and were further verified by RT-PCR. Target gene network was established and potential related signaling pathways were predicted. YQFM could significantly alleviate AngII induced hypertrophy in cellular model. It also significantly increased cell viabilities and ATP content in t-BHP induced apoptotic cell model. Western blot analysis showed that YQFM could increase the phosphorylation of Akt.Conclusion: Our findings provided scientific evidence to uncover the mechanism of action of YQFM on miRNAs regulation against CHF by miRNA expression profile technology. The results indicated that YQFM has a potential effect on alleviate cardiac hypertrophy and apoptosis

  16. Pressure overload-induced mild cardiac hypertrophy reduces leftventricular transmural differences in mitochondrial respiratory chainactivity and increases oxidative stress

    Directory of Open Access Journals (Sweden)

    Michel eKINDO

    2012-08-01

    Full Text Available Objective: Increased mechanical stress and contractility characterizes normal left ventricular subendocardium (Endo but whether Endo mitochondrial respiratory chain complex activities is reduced as compared to subepicardium (Epi and whether pressure overload-induced left ventricular hypertrophy (LVH might modulate transmural gradients through increased reactive oxygen species (ROS production is unknown. Methods: LVH was induced by 6 weeks abdominal aortic banding and cardiac structure and function were determined with echocardiography and catheterization in sham-operated and LVH rats (n=10 for each group. Mitochondrial respiration rates, coupling, content and ROS production were measured in LV Endo and Epi, using saponin-permeabilised fibres, Amplex Red fluorescence and citrate synthase activity.Results: In sham, a transmural respiratory gradient was observed with decreases in endo maximal oxidative capacity (-36.7%, P<0.01 and complex IV activity (-57.4%, P<0.05. Mitochondrial hydrogen peroxide (H2O2 production was similar in both LV layers.Aortic banding induced mild LVH (+31.7% LV mass, associated with normal LV fractional shortening and end diastolic pressure. LVH reduced maximal oxidative capacity (-23.6 and -33.3%, increased mitochondrial H2O2 production (+86.9 and +73.1%, free radical leak (+27.2% and +36.3% and citrate synthase activity (+27.2% and +36.3% in Endo and Epi, respectively.Transmural mitochondrial respiratory chain complex IV activity was reduced in LVH (-57.4 vs –12.2%; P=0.02. Conclusions: Endo mitochondrial respiratory chain complexes activities are reduced compared to LV Epi. Mild LVH impairs mitochondrial oxidative capacity, increases oxidative stress and reduces transmural complex IV activity. Further studies will be helpful to determine whether reduced LV transmural gradient in mitochondrial respiration might be a new marker of a transition from uncomplicated toward complicated LVH.

  17. Relationship of left ventricular, elastic and muscular arteries remodeling in patients with uncontrolled arterial hypertension

    Directory of Open Access Journals (Sweden)

    S. Ya. Dotsenko

    2013-04-01

    Full Text Available Introduction. Uncontrolled hypertension is observed in 65-92% of hypertensive patients. It plays an important role in the development of adverse cardiovascular events and survival, which depend on subclinical target organ damage. There are reports on the relationship between ineffective hypertension control and left ventricular (LV hypertrophy or large arteries stiffness. However, the nature of the remodeling in uncontrolled hypertension remains poorly understood. Objective: to study the character and relationship of left ventricular and arterial remodeling depending on effectiveness of hypertension control. Design and method. We performed a study of 363 hypertensive patients (160 men and 203 women aged 50,8 ± 1,2 years without comorbidities, which were divided into 3 groups according to the effectiveness of blood pressure (BP control: 160 patients with controlled hypertension, 142 patients with uncontrolled hypertension and 61 patients with resistant hypertension. Uncontrolled BP based on measured systolic BP≥140 mmHg and diastolic BP≥90 mmHg. Remodeling indexes of left ventricular, elastic (common carotid and muscular (brachial artery were evaluated by the ultrasonic method. The severity and character of diastolic dysfunction, hypertrophy, types of remodeling and stiffness were assessed. Statistical processing of the results was performed using Student's t criterion and Pearson correlation analysis. Results and discussion. According to the results of the study, uncontrolled hypertension affected the development of subclinical cardiovascular lesions negatively. Thus, LV hypertrophy was detected more frequently in the third group (91,8% in resistant hypertension versus 46,8% in controlled hypertension, p<0,05. Differences in LV geometry with increasing of concentric remodeling types were also observed more frequently in the third group, where concentric remodeling and concentric hypertrophy types were founded in 14,8% and 59

  18. Increased mean aliphatic lipid chain length in left ventricular hypertrophy secondary to arterial hypertension: A cross-sectional study.

    Science.gov (United States)

    Evaristi, Maria Francesca; Caubère, Céline; Harmancey, Romain; Desmoulin, Franck; Peacock, William Frank; Berry, Matthieu; Turkieh, Annie; Barutaut, Manon; Galinier, Michel; Dambrin, Camille; Polidori, Carlo; Miceli, Cristina; Chamontin, Bernard; Koukoui, François; Roncalli, Jerôme; Massabuau, Pierre; Smih, Fatima; Rouet, Philippe

    2016-11-01

    About 77.9 million (1 in 4) American adults have high blood pressure. High blood pressure is the primary cause of left ventricular hypertrophy (LVH), which represents a strong predictor of future heart failure and cardiovascular mortality. Previous studies have shown an altered metabolic profile in hypertensive patients with LVH. The goal of this study was to identify blood metabolomic LVH biomarkers by H NMR to provide novel diagnostic tools for rapid LVH detection in populations of hypertensive individuals. This cross-sectional study included 48 hypertensive patients with LVH matched with 48 hypertensive patients with normal LV size, and 24 healthy controls. Two-dimensional targeted M-mode echocardiography was performed to measure left ventricular mass index. Partial least squares discriminant analysis was used for the multivariate analysis of the H NMR spectral data. From the H NMR-based metabolomic profiling, signals coming from methylene (-CH2-) and methyl (-CH3) moieties of aliphatic chains from plasma lipids were identified as discriminant variables. The -CH2-/-CH3 ratio, an indicator of the mean length of the aliphatic lipid chains, was significantly higher (P hypertensive group without LVH and controls. Receiver operating characteristic curve showed that a cutoff of 2.34 provided a 52.08% sensitivity and 85.42% specificity for discriminating LVH (AUC = 0.703, P-value hypertension.

  19. Egr-1 mediated cardiac miR-99 family expression diverges physiological hypertrophy from pathological hypertrophy.

    Science.gov (United States)

    Ramasamy, Subbiah; Velmurugan, Ganesan; Rekha, Balakrishnan; Anusha, Sivakumar; Shanmugha Rajan, K; Shanmugarajan, Suresh; Ramprasath, Tharmarajan; Gopal, Pandi; Tomar, Dhanendra; Karthik, Karuppusamy V; Verma, Suresh Kumar; Garikipati, Venkata Naga Srikanth; Sudarsan, Rajan

    2018-04-01

    The physiological cardiac hypertrophy is an adaptive condition without myocyte cell death, while pathological hypertrophy is a maladaptive condition associated with myocyte cell death. This study explores the miRNome of α-2M-induced physiologically hypertrophied cardiomyocytes and the role of miRNA-99 family during cardiac hypertrophy. Physiological and pathological cardiac hypertrophy was induced in H9c2 cardiomyoblast cell lines using α-2M and isoproterenol respectively. Total RNA isolation and small RNA sequencing were executed for physiological hypertrophy model. The differentially expressed miRNAs and its target mRNAs were validated in animal models. Transcription factor binding sites were predicted in the promoter of specific miRNAs and validated by ChIP-PCR. Subsequently, the selected miRNA was functionally characterized by overexpression and silencing. The effects of silencing of upstream regulator and downstream target gene were studied. Analysis of small RNA reads revealed the differential expression of a large set of miRNAs during hypertrophy, of which miR-99 family was highly downregulated upon α-2M treatment. However, this miR-99 family expression was upregulated during pathological hypertrophy and confirmed in animal models. ChIP-PCR confirms the binding of Egr-1 transcription factor to the miR-99 promoter. Further, silencing of Egr-1 decreased the expression of miR-99. The overexpression or silencing of miR-99 diverges the physiological hypertrophy to pathological hypertrophy and vice versa by regulating Akt-1 pathway. Silencing of Akt-1 replicates the effect of overexpression of miR-99. The results proved Egr-1 mediated regulation of miR-99 family that plays a key role in determining the fate of cardiac hypertrophy by regulating Akt-1 signaling. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. The effect of inter-set rest intervals on resistance exercise-induced muscle hypertrophy.

    Science.gov (United States)

    Henselmans, Menno; Schoenfeld, Brad J

    2014-12-01

    Due to a scarcity of longitudinal trials directly measuring changes in muscle girth, previous recommendations for inter-set rest intervals in resistance training programs designed to stimulate muscular hypertrophy were primarily based on the post-exercise endocrinological response and other mechanisms theoretically related to muscle growth. New research regarding the effects of inter-set rest interval manipulation on resistance training-induced muscular hypertrophy is reviewed here to evaluate current practices and provide directions for future research. Of the studies measuring long-term muscle hypertrophy in groups employing different rest intervals, none have found superior muscle growth in the shorter compared with the longer rest interval group and one study has found the opposite. Rest intervals less than 1 minute can result in acute increases in serum growth hormone levels and these rest intervals also decrease the serum testosterone to cortisol ratio. Long-term adaptations may abate the post-exercise endocrinological response and the relationship between the transient change in hormonal production and chronic muscular hypertrophy is highly contentious and appears to be weak. The relationship between the rest interval-mediated effect on immune system response, muscle damage, metabolic stress, or energy production capacity and muscle hypertrophy is still ambiguous and largely theoretical. In conclusion, the literature does not support the hypothesis that training for muscle hypertrophy requires shorter rest intervals than training for strength development or that predetermined rest intervals are preferable to auto-regulated rest periods in this regard.

  1. Pattern of left ventricular geometry in hypertension: a study of a ...

    African Journals Online (AJOL)

    Background: Hypertension is a leading cause of cardioxasular morbidity and mortality in Nigeria. The main aim of this study was to deterine the prevalence of left ventricular hypertrophy and left ventricular geometric patterns among hypertensives in Kano, Nigeria. Methods: The study was cross-sectional in design, and ...

  2. Association of novel biomarkers of cardiovascular stress with left ventricular hypertrophy and dysfunction: implications for screening.

    Science.gov (United States)

    Xanthakis, Vanessa; Larson, Martin G; Wollert, Kai C; Aragam, Jayashri; Cheng, Susan; Ho, Jennifer; Coglianese, Erin; Levy, Daniel; Colucci, Wilson S; Michael Felker, G; Benjamin, Emelia J; Januzzi, James L; Wang, Thomas J; Vasan, Ramachandran S

    2013-11-07

    Currently available screening tools for left ventricular (LV) hypertrophy (LVH) and systolic dysfunction (LVSD) are either expensive (echocardiography) or perform suboptimally (B-type natriuretic peptide [BNP]). It is unknown whether newer biomarkers are associated with LVH and LVSD and can serve as screening tools. We studied 2460 Framingham Study participants (mean age 58 years, 57% women) with measurements of biomarkers mirroring cardiac biomechanical stress (soluble ST-2 [ST2], growth differentiation factor-15 [GDF-15] and high-sensitivity troponin I [hsTnI]) and BNP. We defined LVH as LV mass/height(2) ≥the sex-specific 80th percentile and LVSD as mild/greater impairment of LV ejection fraction (LVEF) or a fractional shortening statistic for the composite outcome increased from 0.765 with risk factors to 0.770 adding BNP, to 0.774 adding novel biomarkers. The continuous Net Reclassification Improvement was 0.212 (95% CI: 0.119 to 0.305, Pstress biomarkers are associated with LVH and LVSD but may have limited clinical utility as screening tools.

  3. Mouse models for the study of postnatal cardiac hypertrophy

    Directory of Open Access Journals (Sweden)

    A. Del Olmo-Turrubiarte

    2015-06-01

    Full Text Available The main objective of this study was to create a postnatal model for cardiac hypertrophy (CH, in order to explain the mechanisms that are present in childhood cardiac hypertrophy. Five days after implantation, intraperitoneal (IP isoproterenol (ISO was injected for 7 days to pregnant female mice. The fetuses were obtained at 15, 17 and 19 dpc from both groups, also newborns (NB, neonates (7–15 days and young adults (6 weeks of age. Histopathological exams were done on the hearts. Immunohistochemistry and western blot demonstrated GATA4 and PCNA protein expression, qPCR real time the mRNA of adrenergic receptors (α-AR and β-AR, alpha and beta myosins (α-MHC, β-MHC and GATA4. After the administration of ISO, there was no change in the number of offsprings. We observed significant structural changes in the size of the offspring hearts. Morphometric analysis revealed an increase in the size of the left ventricular wall and interventricular septum (IVS. Histopathological analysis demonstrated loss of cellular compaction and presence of left ventricular small fibrous foci after birth. Adrenergic receptors might be responsible for changing a physiological into a pathological hypertrophy. However GATA4 seemed to be the determining factor in the pathology. A new animal model was established for the study of pathologic CH in early postnatal stages.

  4. Compensatory Hypertrophy of Skeletal Muscle: Contractile Characteristics

    Science.gov (United States)

    Ianuzzo, C. D.; Chen, V.

    1977-01-01

    Describes an experiment using rats that demonstrates contractile characteristics of normal and hypertrophied muscle. Compensatory hypertrophy of the plantaris muscle is induced by surgical removal of the synergistic gastrocnemium muscle. Includes methods for determination of contractile properties of normal and hypertrophied muscle and…

  5. The thickened left ventricle: etiology, differential diagnosis and implications for cardiovascular radiology; Der dicke linke Ventrikel. Ursachen und Differenzialdiagnose der linksventrikulaeren Hypertrophie und Implikationen fuer die kardiovaskulaere Radiologie

    Energy Technology Data Exchange (ETDEWEB)

    Bischoff, P.; Barkhausen, J.; Hunold, P. [Universitaetsklinikum Schleswig-Holstein, Luebeck (Germany). Klinik fuer Radiologie und Nuklearmedizin; Radke, P.W. [Universitaetsklinikum Schleswig Holstein, Luebeck (Germany). Medizinische Klinik II

    2012-08-15

    Hypertrophy of the left ventricular myocardium is a common finding and can be reliably detected by echocardiography, CT and MRI. Common causes include diseases associated with increased cardiac afterload as well as primary and secondary cardiomyopathy. With the opportunity to determine functional parameters and myocardial mass precisely as well as to detect structural changes of the cardiac muscle simultaneously, cardiac MRI is the most precise imaging method for quantifying left ventricular hypertrophy as well as determining the cause and the exact characterization of the myocardial changes. It is mandatory, however, to create a flexible, individually adapted examination protocol. This review presents useful diagnostic algorithms in relation to different underlying pathologies in patients with left ventricular hypertrophy. (orig.)

  6. Wolff-Parkinson-White Syndrome with Ventricular Hypertrophy in a Brazilian Family.

    Science.gov (United States)

    van der Steld, Lenises de Paula; Campuzano, Oscar; Pérez-Serra, Alexandra; Moura de Barros Zamorano, Mabel; Sousa Matos, Selma; Brugada, Ramon

    2017-07-10

    BACKGROUND PRKAG2 syndrome diagnosis is already well-defined as Wolff-Parkinson-White syndrome (WPW), ventricular hypertrophy (VH) due to glycogen accumulation, and conduction system disease (CSD). Because of its rarity, there is a lack of literature focused on the treatment. The present study aimed to describe appropriate strategies for the treatment of affected family members with PRKAG2 syndrome with a long follow-up period. CASE REPORT We studied 60 selected individuals from 84 family members (32 males, 53.3%) (mean age 27±16 years). Patients with WPW and/or VH were placed in a group of 18 individuals, in which 11 (61.1%) had VH and WPW, 6 (33.3%) had isolated WPW, and 1 (5.6%) had isolated VH. Palpitations occurred in 16 patients (88.9%), chest pain in 11 (61.1%), dizziness in 13 (72.2%), syncope in 15 (83.3%), and dyspnea in 13 (72%). Sudden cardiac death (SCD) occurred in 2 (11.1%), and 2 patients with cardiac arrest (CA) had asystole and pre-excited atrial flutter-fibrillation (AFL and AF) as the documented mechanism. Transient ischemic attack (TIA) and learning/language disabilities with delayed development were observed. Genetic analysis identified a new missense pathogenic variant (p.K290I) in the PRKAG2 gene. Cardiac histopathology demonstrated the predominance of vacuoles containing glycogen derivative and fibrosis. The treatment was based on hypertension and diabetes mellitus (DM) control, antiarrhythmic drugs (AD), anticoagulation, and radiofrequency catheter ablation (RCA). Six patients (33.3%) underwent pacemaker implantation (PM). CONCLUSIONS The present study describes the clinical treatment for a rare cardiac syndrome caused by a PRKAG2 mutation.

  7. Role of the renin-angiotensin system in cardiac hypertrophy induced in rats by hyperthyroidism.

    Science.gov (United States)

    Kobori, H; Ichihara, A; Suzuki, H; Takenaka, T; Miyashita, Y; Hayashi, M; Saruta, T

    1997-08-01

    This study was conducted to examine whether the renin-angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy without involving the sympathetic nervous system. Sprague-Dawley rats were divided into control-innervated, control-denervated, hyperthyroid-innervated, and hyperthyroid-denervated groups using intraperitoneal injections of thyroxine and 6-hydroxydopamine. After 8 wk, the heart-to-body weight ratio increased in hyperthyroid groups (63%), and this increase was only partially inhibited by sympathetic denervation. Radioimmunoassays and reverse transcription-polymerase chain reaction revealed increased cardiac levels of renin (33%) and angiotensin II (53%) and enhanced cardiac expression of renin mRNA (225%) in the hyperthyroid groups. These increases were unaffected by sympathetic denervation or 24-h bilateral nephrectomy. In addition, losartan and nicardipine decreased systolic blood pressure to the same extent, but only losartan caused regression of thyroxine-induced cardiac hypertrophy. These results suggest that thyroid hormone activates the cardiac renin-angiotensin system without involving the sympathetic nervous system or the circulating renin-angiotensin system; the activated renin-angiotensin system contributes to cardiac hypertrophy in hyperthyroidism.

  8. Extracellular high-mobility group box 1 mediates pressure overload-induced cardiac hypertrophy and heart failure.

    Science.gov (United States)

    Zhang, Lei; Liu, Ming; Jiang, Hong; Yu, Ying; Yu, Peng; Tong, Rui; Wu, Jian; Zhang, Shuning; Yao, Kang; Zou, Yunzeng; Ge, Junbo

    2016-03-01

    Inflammation plays a key role in pressure overload-induced cardiac hypertrophy and heart failure, but the mechanisms have not been fully elucidated. High-mobility group box 1 (HMGB1), which is increased in myocardium under pressure overload, may be involved in pressure overload-induced cardiac injury. The objectives of this study are to determine the role of HMGB1 in cardiac hypertrophy and cardiac dysfunction under pressure overload. Pressure overload was imposed on the heart of male wild-type mice by transverse aortic constriction (TAC), while recombinant HMGB1, HMGB1 box A (a competitive antagonist of HMGB1) or PBS was injected into the LV wall. Moreover, cardiac myocytes were cultured and given sustained mechanical stress. Transthoracic echocardiography was performed after the operation and sections for histological analyses were generated from paraffin-embedded hearts. Relevant proteins and genes were detected. Cardiac HMGB1 expression was increased after TAC, which was accompanied by its translocation from nucleus to both cytoplasm and intercellular space. Exogenous HMGB1 aggravated TAC-induced cardiac hypertrophy and cardiac dysfunction, as demonstrated by echocardiographic analyses, histological analyses and foetal cardiac genes detection. Nevertheless, the aforementioned pathological change induced by TAC could partially be reversed by HMGB1 inhibition. Consistent with the in vivo observations, mechanical stress evoked the release and synthesis of HMGB1 in cultured cardiac myocytes. This study indicates that the activated and up-regulated HMGB1 in myocardium, which might partially be derived from cardiac myocytes under pressure overload, may be of crucial importance in pressure overload-induced cardiac hypertrophy and cardiac dysfunction. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  9. Estrogen receptor beta is involved in skeletal muscle hypertrophy induced by the phytoecdysteroid ecdysterone.

    Science.gov (United States)

    Parr, Maria Kristina; Zhao, Piwen; Haupt, Oliver; Ngueu, Sandrine Tchoukouegno; Hengevoss, Jonas; Fritzemeier, Karl Heinrich; Piechotta, Marion; Schlörer, Nils; Muhn, Peter; Zheng, Wen-Ya; Xie, Ming-Yong; Diel, Patrick

    2014-09-01

    The phytoectysteroid ecdysterone (Ecdy) was reported to stimulate protein synthesis and enhance physical performance. The aim of this study was to investigate underlying molecular mechanisms particularly the role of ER beta (ERβ). In male rats, Ecdy treatment increased muscle fiber size, serum IGF-1 increased, and corticosteron and 17β-estradiol (E2) decreased. In differentiated C2C12 myoblastoma cells, treatment with Ecdy, dihydrotestosterone, IGF-1 but also E2 results in hypertrophy. Hypertrophy induced by E2 and Ecdy could be antagonized with an antiestrogen but not by an antiandrogen. In HEK293 cells transfected with ER alpha (ERα) or ERβ, Ecdy treatment transactivated a reporter gene. To elucidate the role of ERβ in Ecdy-mediated muscle hypertrophy, C2C12 myotubes were treated with ERα (ALPHA) and ERβ (BETA) selective ligands. Ecdy and BETA treatment but not ALPHA induced hypertrophy. The effect of Ecdy, E2, and BETA could be antagonized by an ERβ-selective antagonist (ANTIBETA). In summary, our results indicate that ERβ is involved in the mediation of the anabolic activity of the Ecdy. These findings provide new therapeutic perspectives for the treatment of muscle injuries, sarcopenia, and cachectic disease, but also imply that such a substance could be abused for doping purposes. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Effect of Berberine on PPARα/NO Activation in High Glucose- and Insulin-Induced Cardiomyocyte Hypertrophy

    Directory of Open Access Journals (Sweden)

    Mingfeng Wang

    2013-01-01

    Full Text Available Rhizoma coptidis, the root of Coptis chinensis Franch, has been used in China as a folk medicine in the treatment of diabetes for thousands of years. Berberine, one of the active ingredients of Rhizoma coptidis, has been reported to improve symptoms of diabetes and to treat experimental cardiac hypertrophy, respectively. The objective of this study was to evaluate the potential effect of berberine on cardiomyocyte hypertrophy in diabetes and its possible influence on peroxisome proliferator-activated receptor-α (PPARα/nitric oxide (NO signaling pathway. The cardiomyocyte hypertrophy induced by high glucose (25.5 mmol/L and insulin (0.1 μmol/L (HGI was characterized in rat primary cardiomyocyte by measuring the cell surface area, protein content, and atrial natriuretic factor mRNA expression level. Protein and mRNA expression were measured by western blot and real-time RT-PCR, respectively. The enzymatic activity of NO synthase (NOS was measured using a spectrophotometric assay, and NO concentration was measured using the Griess assay. HGI significantly induced cardiomyocyte hypertrophy and decreased the expression of PPARα and endothelial NOS at the mRNA and protein levels, which occurred in parallel with declining NOS activity and NO concentration. The effect of HGI was inhibited by berberine (0.1 to 100 μmol/L, fenofibrate (0.3 μmol/L, or L-arginine (100 μmol/L. MK886 (0.3 μmol/L, a selective PPARα antagonist, could abolish the effects of berberine and fenofibrate. NG-nitro-L-arginine-methyl ester (100 μmol/L, a NOS inhibitor, could block the effects of L-arginine, but only partially blocked the effects of berberine. These results suggest that berberine can blunt HGI-induced cardiomyocyte hypertrophy in vitro, through the activation of the PPARα/NO signaling pathway.

  11. Characteristics of Left Atrial Deformation Parameters and Their Prognostic Impact in Patients with Pathological Left Ventricular Hypertrophy: Analysis by Speckle Tracking Echocardiography.

    Science.gov (United States)

    Iio, Chiharuko; Inoue, Katsuji; Nishimura, Kazuhisa; Fujii, Akira; Nagai, Takayuki; Suzuki, Jun; Okura, Takafumi; Higaki, Jitsuo; Ogimoto, Akiyoshi

    2015-12-01

    The pathological process of left ventricular (LV) hypertrophy is associated with left atrial (LA) remodeling. This study was aimed to evaluate the prognostic value of LA strain parameters in patients with pathological LV hypertrophy. This study included 95 patients with hypertensive heart disease (HHD: n = 24), hypertrophic cardiomyopathy (HCM: n = 56), cardiac amyloidosis (CA: n = 15), and control subjects (n = 20). We used two-dimensional speckle tracking echocardiography (STE) to analyze LA global strain. LA electromechanical conduction time (EMT) at the septal (EMT-septal) and lateral wall (EMT-lateral), and their time difference (EMT-diff) were calculated. The incidence of cardiac death and heart failure hospitalization was defined as major cardiac events and that of atrial fibrillation as secondary outcome. Left atrial volume index was increased and LA booster strain was decreased in the HCM and CA groups compared with the HHD group. EMT-lateral was increased in the diseased groups compared with the control. EMT-diff was prolonged in the CA group compared with the HCM group. During the follow-up period (mean 3.4 years), major cardiac events and atrial fibrillation occurred in 17 and 13 patients, respectively. The occurrence of atrial fibrillation was associated with CA etiology, E/e', LA volume index, LAa, and EMT-lateral. The incidence of major cardiac events was independently correlated with LA volume index and EMT-diff in multivariate analysis. This study suggested that the EMT-diff could discriminate patients with a high risk of cardiac events among patients with pathological LV hypertrophy. © 2015, Wiley Periodicals, Inc.

  12. Effect of endurance exercise training on left ventricular size and remodeling in older adults with hypertension.

    Science.gov (United States)

    Turner, M J; Spina, R J; Kohrt, W M; Ehsani, A A

    2000-04-01

    It is not known whether exercise training can induce a reduction of blood pressure (BP) and a regression of left ventricular hypertrophy (LVH) in older hypertensive subjects. This study was designed to determine whether endurance exercise training, by lowering BP, can induce regression of LVH and left ventricular (LV) concentric remodeling in older hypertensive adults. We studied 11 older adults with mild to moderate hypertension (BP 152.0 +/- 2.5/91.3 +/- 1.5 mm Hg, mean +/- SE), 65.5 +/- 1.2 years old, who exercised for 6.8 +/- 3.8 months. Seven sedentary hypertensive (BP 153 +/- 3/89 +/- 2 mm Hg) subjects, 68.5 +/- 1 years old, served as controls. LV size and geometry and function were assessed with the use of two-dimensional echocardiography. Exercise training increased aerobic power by 16% (p hypertension.

  13. HSF1 phosphorylation by ERK/GSK3 suppresses RNF126 to sustain IGF-IIR expression for hypertension-induced cardiomyocyte hypertrophy.

    Science.gov (United States)

    Huang, Chih-Yang; Lee, Fa-Lun; Peng, Shu-Fen; Lin, Kuan-Ho; Chen, Ray-Jade; Ho, Tsung-Jung; Tsai, Fu-Jen; Padma, Vijaya V; Kuo, Wei-Wen; Huang, Chih-Yang

    2018-02-01

    Hypertension-induced cardiac hypertrophy and apoptosis are major characteristics of early-stage heart failure (HF). Inhibition of extracellular signal-regulated kinases (ERK) efficaciously suppressed angiotensin II (ANG II)-induced cardiomyocyte hypertrophy and apoptosis by blocking insulin-like growth factor II receptor (IGF-IIR) signaling. However, the detailed mechanism by which ANG II induces ERK-mediated IGF-IIR signaling remains elusive. Here, we found that ANG II activated ERK to upregulate IGF-IIR expression via the angiotensin II type I receptor (AT 1 R). ERK activation subsequently phosphorylates HSF1 at serine 307, leading to a secondary phosphorylation by glycogen synthase kinase III (GSK3) at serine 303. Moreover, we found that ANG II mediated ERK/GSK3-induced IGF-IIR protein stability by downregulating the E3 ubiquitin ligase of IGF-IIR RING finger protein CXXVI (RNF126). The expression of RNF126 decreased following ANG II-induced HSF1 S303 phosphorylation, resulting in IGF-IIR protein stability and increased cardiomyocyte injury. Inhibition of GSK3 significantly alleviated ANG II-induced cardiac hypertrophy in vivo and in vitro. Taken together, these results suggest that HSF1 phosphorylation stabilizes IGF-IIR protein stability by downregulating RNF126 during cardiac hypertrophy. ANG II activates ERK/GSK3 to phosphorylate HSF1, resulting in RNF126 degradation, which stabilizes IGF-IIR protein expression and eventually results in cardiac hypertrophy. HSF1 could be a valuable therapeutic target for cardiac diseases among hypertensive patients. © 2017 Wiley Periodicals, Inc.

  14. EXERCISE-INDUCED VENTRICULAR-TACHYCARDIA - A RARE MANIFESTATION OF DIGITALIS TOXICITY

    NARCIS (Netherlands)

    GOSSELINK, ATM; CRIJNS, HJGM; WIESFELD, ACP; LIE, KI

    Digitalis intoxication is one of the most common adverse drug reactions. Although some arrhythmias are seen more frequently than others, virtually any rhythm disturbance, including ventricular tachycardia, may occur. However, to our knowledge, exercise-induced ventricular tachycardia as a

  15. Alterations in NO/ROS ratio and expression of Trx1 and Prdx2 in isoproterenol-induced cardiac hypertrophy

    Institute of Scientific and Technical Information of China (English)

    Hao Su; Marco Pistolozzi; Xingjuan Shi; Xiaoou Sun; Wen Tan

    2017-01-01

    The development of cardiac hypertrophy is a complicated process,which undergoes a transition from compensatory hypertrophy to heart failure,and the identification of new biomarkers and targets for this disease is greatly needed.Here we investigated the development of isoproterenol (ISO)-induced cardiac hypertrophy in an in vitro experimental model.After the induction of hypertrophy with ISO treatment in H9c2 cells,cell surface area,cell viability,cellular reactive oxygen species (ROS),and nitric oxide (NO) levels were tested.Our data showed that the cell viability,mitochondrial membrane potential,and NO/ROS balance varied during the development of cardiac hypertrophy in H9c2 cells.It was also found that the expression of thioredoxin1 (Trx1) and peroxiredoxin2 (Prdx2) was decreased during the cardiac hypertrophy of H9c2 cells.These results suggest a critical role for Trx1 and Prdx2 in the cardiac hypertrophy of H9c2 cells and in the transition from compensated hypertrophy to de-compensated hypertrophy in H9c2 cells,and our findings may have important implications for the management of this disease.

  16. Long-term treatment with nebivolol improves arterial reactivity and reduces ventricular hypertrophy in spontaneously hypertensive rats.

    Science.gov (United States)

    Guerrero, Estela; Voces, Felipe; Ardanaz, Noelia; Montero, María José; Arévalo, Miguel; Sevilla, María Angeles

    2003-09-01

    The aim of this study was to assess the effects of long-term nebivolol therapy on high blood pressure, impaired endothelial function in aorta, and damage observed in heart and conductance arteries in spontaneously hypertensive rats (SHR). For this purpose, SHR were treated for 9 weeks with nebivolol (8 mg/kg per day). Untreated SHR and Wistar Kyoto rats were used as hypertensive and normotensive controls, respectively. The left ventricle/body weight ratio was used as an index of cardiac hypertrophy, and to evaluate vascular function, responses induced by potassium chloride, noradrenaline, acetylcholine, and sodium nitroprusside were tested on aortic rings. Aortic morphometry and fibrosis were determined in parallel by a quantitative technique. Systolic blood pressure, measured by the tail-cuff method, was lower in treated SHR than in the untreated group (194 +/- 3 versus 150 +/- 4 mm Hg). The cardiac hypertrophy index was significantly reduced by the treatment. In aortic rings, treatment with nebivolol significantly reduced the maximal response to both KCl and NA in SHR. In vessels precontracted with phenylephrine relaxant, activity due to acetylcholine was higher in normotensive rats than in SHR and the treatment significantly improved this response. The effect of sodium nitroprusside on aortic rings was similar in all groups. Medial thickness and collagen content were significantly reduced in comparison with SHR. In conclusion, the chronic antihypertensive effect of nebivolol in SHR was accompanied by an improvement in vascular structure and function and in the cardiac hypertrophy index.

  17. Short-Term Caloric Restriction Suppresses Cardiac Oxidative Stress and Hypertrophy Caused by Chronic Pressure Overload.

    Science.gov (United States)

    Kobara, Miyuki; Furumori-Yukiya, Akiko; Kitamura, Miho; Matsumura, Mihoko; Ohigashi, Makoto; Toba, Hiroe; Nakata, Tetsuo

    2015-08-01

    Caloric restriction (CR) prevents senescent changes, in which reactive oxygen species (ROS) have a critical role. Left ventricular (LV) hypertrophy is a risk factor for cardiovascular diseases. We examined whether CR alters cardiac redox state and hypertrophy from chronic pressure overload. Male c57BL6 mice were subjected to ascending aortic constriction (AAC) with ad libitum caloric intake (AL + AAC group) or 40% restricted caloric intake (CR + AAC group). CR was initiated 2 weeks before AAC and was continued for 4 weeks. Two weeks after constriction, AAC increased LV wall thickness, impaired transmitral flow velocity, and augmented myocyte hypertrophy and fibrosis, in association with enhancement of BNP and collagen III expressions in the AL + AAC group. In the AL + AAC group, oxidative stress in cardiac tissue and mitochondria were enhanced, and NADPH oxidase activity and mitochondrial ROS production were elevated. These changes were significantly attenuated in the CR + AAC group. Additionally, in antioxidant systems, myocardial glutathione peroxidase and superoxide dismutase activities were enhanced in the CR + AAC group. Chronic pressure overload increased cardiac oxidative damage, in association with cardiac hypertrophy and fibrosis. Short-term CR suppressed oxidative stress and improved cardiac function, suggesting that short-term CR could be a useful strategy to prevent pressure overload-induced cardiac injury. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Angiotensin II type 2 receptors and cardiac hypertrophy in women with hypertrophic cardiomyopathy

    NARCIS (Netherlands)

    J. Deinum (Jacob); J.M. van Gool (Jeanette); M.J.M. Kofflard (Marcel); A.H.J. Danser (Jan); F.J. ten Cate (Folkert)

    2001-01-01

    textabstractThe development of left ventricular hypertrophy in subjects with hypertrophic cardiomyopathy (HCM) is variable, suggesting a role for modifying factors such as angiotensin II. Angiotensin II mediates both trophic and antitrophic effects, via angiotensin II type 1

  19. Association of ACE gene D polymorphism with left ventricular hypertrophy in patients with diastolic heart failure: a case-control study.

    Science.gov (United States)

    Bahramali, Ehsan; Rajabi, Mona; Jamshidi, Javad; Mousavi, Seyyed Mohammad; Zarghami, Mehrdad; Manafi, Alireza; Firouzabadi, Negar

    2016-02-09

    To explore the association between ACE gene insertion/deletion (I/D) polymorphism with left ventricular hypertrophy (LVH) in patients with hypertension who have developed heart failure with preserved ejection fraction (HFpEF). Being a major contributor to the development of diastolic heart dysfunction, the renin angiotensin aldosterone system and its genetic variations are thought to induce LVH in hypertensive hearts apart from haemodynamic factors. Case control study. An Iranian referral university hospital. 176 patients with hypertension and a diagnosis of HFpEF on presence of symptoms of heart failure plus Doppler echocardiographic documentation of left ventricular (LV) diastolic dysfunction and/or elevated NT-proBNP levels. Those with significant coronary, valvular, pericardial and structural heart diseases were excluded as well as patients with atrial fibrillation, renal failure and pulmonary causes of dyspnoea. They were divided into two cohorts of 88 cases with and 88 controls without LVH, after determination of LV mass index, using two-dimensional and M-mode echocardiography. The I/D polymorphism of the ACE gene was determined using the PCR method. The D allele was significantly more prevalent among cases with compared with controls without LVH (p=0.0007). Genotype distributions also differed significantly under additive (p=0.005, OR=0.53, 95% CI 0.34 to 0.84) and recessive (p=0.001, OR=0.29, 95% CI 0.13 to 0.66) models. In patients with hypertension who develop HFpEF, the D allele of the ACE gene is probably associated with the development of LVH. With the detrimental effects of LVH on the heart's diastolic properties, this can signify the role of genetic contributors to the development of HFpEF in patients with hypertension and may serve as a future risk predictor for the disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  20. Left ventricular hypertrophy in renal failure review | Arodiwe ...

    African Journals Online (AJOL)

    Renal failure is becoming increasingly common in our enironment. Advances in management like availability of dialysis and transplantation is prolonging the live of patients. As a consequence complication are increasingly being encountered. Cardiovascular complication is one of the commonest; and left ventricular ...

  1. LONG-TERM EFFECTS OF CHLORTHALIDONE VS HYDROCHLOROTHIAZIDE ON ELECTROCARDIOGRAPHIC LEFT VENTRICULAR HYPERTROPHY IN THE MULTIPLE RISK FACTOR INTERVENTION TRIAL

    Science.gov (United States)

    Ernst, Michael E.; Neaton, James D.; Grimm, Richard H.; Collins, Gary; Thomas, William; Soliman, Elsayed Z.; Prineas, Ronald J.

    2011-01-01

    Chlorthalidone (CTD) reduces 24-hour blood pressure more effectively than hydrochlorothiazide (HCTZ), but whether this influences electrocardiographic left ventricular hypertrophy (LVH) is uncertain. One source of comparative data is the Multiple Risk Factor Intervention Trial (MRFIT), which randomly assigned 8,012 hypertensive men to special intervention (SI) or usual care (UC). SI participants could use CTD or HCTZ initially; previous analyses have grouped clinics by their main diuretic used (C-clinics: CTD; H-clinics: HCTZ). After 48 months, SI participants receiving HCTZ were recommended to switch to CTD, in part, because higher mortality was observed for SI compared to UC participants in H-clinics, while the opposite was found in C-clinics. In this analysis, we examined change in continuous measures of electrocardiographic LVH using both an ecologic analysis by previously-reported C- or H-clinic groupings, and an individual participant analysis where use of CTD or HCTZ by SI participants was considered and updated annually. Through 48 months, differences between SI and UC in LVH were larger for C-clinics compared to H-clinics (Sokolow-Lyon: −93.9 vs −54.9 μV, P=0.049; Cornell voltage: −68.1 vs −35.9 μV, P=0.019; Cornell voltage product: −4.6 vs −2.2 μV/ms, P=0.071; left ventricular mass: −4.4 vs −2.8 gm, P=0.002). At the individual participant level, Sokolow-Lyon and left ventricular mass were significantly lower for SI men receiving CTD compared to HCTZ through 48 months and 84 months of follow-up. Our findings on LVH support the idea that greater blood pressure reduction with CTD than HCTZ may have led to differences in mortality observed in MRFIT. PMID:22025372

  2. Electrocardiographic findings in athletes: the prevalence of left ventricular hypertrophy and conduction defects.

    Science.gov (United States)

    Langdeau, J B; Blier, L; Turcotte, H; O'Hara, G; Boulet, L P

    2001-06-01

    To determine whether there are electrocardiographic differences or distinctive abnormalities between athletes and sedentary subjects, and to verify the relationship between vagal activity measured by heart rate variability (SD of all normal-to-normal intervals [SDNN]) and possible electrocardiographic abnormalities. Resting electrocardiograms and heart rate variability measurements were performed separately during a single visit on 100 athletes and 50 nonathlete control subjects aged 18 to 55 years. The athletes were from the following various sports disciplines: long-distance running, mountain biking, cross-country skiing, biathlon, speed skating, swimming and triathlon. There were significantly longer RR intervals, PR intervals and QT intervals in athletes than in control subjects (all P0.05). The prevalence of left ventricular hypertrophy (LVH) and incomplete right bundle branch block (IRBBB) was 10% and 7%, respectively, in athletes, but these conditions were absent in control subjects; among athletes, 2% presented with both conditions. LVH and IRBBB were more common among long-distance runners (six of 14 and four of 14, respectively) and could be attributed to normal, long term adaptation to intense, repeated exercise. LVH was related to age (P=0.04), whereas IRBBB was influenced by the number of years of training in the respective sports discipline (P=0.03). The mean SDNN value was significantly more elevated in athletes (P=0.0001), reflecting a higher parasympathetic tone than in sedentary control subjects. However, there was no relationship between vagal activity and LVH or IRBBB (both P>0.05).

  3. Isolated papillary muscle hypertrophy: A gap in our knowledge of hypertrophic cardiomyopathy?

    Science.gov (United States)

    Ferreira, Catarina; Delgado, Carlos; Vázquez, María; Trinidad, Carmen; Vilar, Manuel

    2014-06-01

    Increased thickness of left ventricular walls is the predominant characteristic and one of the diagnostic criteria of hypertrophic cardiomyopathy (HCM). This case illustrates an uncommon but important finding of isolated hypertrophy of the papillary muscles (PMs), observed in a young woman in whom an abnormal electrocardiogram was initially detected. During the investigation isolated PM hypertrophy was identified. The structural characteristics of the PMs have received scant attention in this setting and there is little information in the literature on this entity, whose real prevalence and clinical significance remain to be determined. The available information relates solitary PM hypertrophy with an early form or a different pattern of HCM. In this case PM hypertrophy was only detected due to the finding of an abnormal electrocardiogram, which prompted further diagnostic tests and a search for possible etiologies. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  4. Apical hypertrophy associated with rapid T wave inversion on the electrocardiogram.

    Science.gov (United States)

    Yamanari, H; Saito, D; Mikio, K; Nakamura, K; Nanba, T; Morita, H; Mizuo, K; Sato, T; Ohe, T

    1995-01-01

    A 53-year-old man who had no chest pain and no family history of heart disease demonstrated a rapid T wave change on an electrocardiogram, from a positive T wave to a giant negative T wave, within 1 year. Echocardiography showed no left ventricular hypertrophy before or after the T wave change. Cine-magnetic resonance imaging revealed focal apical hypertrophy after the appearance of the giant negative T wave. Although T wave inversions sometimes develop within a short period in patients with hypertrophic cardiomyopathy, they are rare in a patient without hypertension or chest pain.

  5. Exercise-Induced Muscle Damage and Hypertrophy: A Closer Look Reveals the Jury is Still Out

    OpenAIRE

    Schoenfeld, Brad; Contreras, Bret

    2018-01-01

    This letter is a response to the paper by Damas et al (2017) titled, “The development of skeletal muscle hypertrophy through resistance training: the role of muscle damage and muscle protein synthesis,” which, in part, endeavored to review the role of exercise-induced muscle damage on muscle hypertrophy. We feel there are a number of issues in interpretation of research and extrapolation that preclude drawing the inference expressed in the paper that muscle damage neither explains nor potenti...

  6. Resveratrol prevents angiotensin II-induced hypertrophy of vascular smooth muscle cells through the transactivation of growth factor receptors.

    Science.gov (United States)

    Hossain, Ekhtear; Anand-Srivastava, Madhu B

    2017-08-01

    We previously showed that augmented levels of endogenous angiotensin II (AngII) contribute to vascular smooth muscle cell (VSMC) hypertrophy through the transactivation of growth factor receptors in spontaneously hypertensive rats. Resveratrol (RV), a polyphenolic component of red wine, has also been shown to attenuate AngII-evoked VSMC hypertrophy; however, the molecular mechanism mediating this response is obscure. The present study was therefore undertaken to examine whether RV could prevent AngII-induced VSMC hypertrophy through the transactivation of growth factor receptor and associated signaling pathways. AngII treatment of VSMC enhanced the protein synthesis that was attenuated towards control levels by RV pretreatment as well as by the inhibitors of NADPH oxidase, c-Src, and growth factor receptors. Furthermore, RV pretreatment also inhibited enhanced levels of superoxide anion, NADPH oxidase activity, increased expression of NADPH oxidase subunits, and phosphorylation of c-Src, EGF-R, PDGE-R, ERK1/2, and AKT1/2. In conclusion, these results indicate that RV attenuates AngII-induced VSMC hypertrophy through the inhibition of enhanced oxidative stress and activation of c-Src, growth factor receptors, and MAPK/AKT signaling. We suggest that RV could be used as a therapeutic agent in the treatment of vascular complications associated with hypertension and hypertrophy.

  7. Regulation of the instantaneous inward rectifier and the delayed outward rectifier potassium channels by Captopril and Angiotensin II via the Phosphoinositide-3 kinase pathway in volume-overload-induced hypertrophied cardiac myocytes.

    Science.gov (United States)

    Alvin, Zikiar V; Laurence, Graham G; Coleman, Bernell R; Zhao, Aiqiu; Hajj-Moussa, Majd; Haddad, Georges E

    2011-07-01

    Early development of cardiac hypertrophy may be beneficial but sustained hypertrophic activation leads to myocardial dysfunction. Regulation of the repolarizing currents can be modulated by the activation of humoral factors, such as angiotensin II (ANG II) through protein kinases. The aim of this work is to assess the regulation of IK and IK1 by ANG II through the PI3-K pathway in hypertrophied ventricular myocytes. Cardiac eccentric hypertrophy was induced through volume-overload in adult male rats by aorto-caval shunt (3 weeks). After one week half of the rats were given captopril (2 weeks; 0.5 g/l/day) and the other half served as control. The voltage-clamp and western blot techniques were used to measure the delayed outward rectifier potassium current (IK) and the instantaneous inward rectifier potassium current (IK1) and Akt activity, respectively. Hypertrophied cardiomyocytes showed reduction in IK and IK1. Treatment with captopril alleviated this difference seen between sham and shunt cardiomyocytes. Acute administration of ANG II (10-6M) to cardiocytes treated with captopril reduced IK and IK1 in shunts, but not in sham. Captopril treatment reversed ANG II effects on IK and IK1 in a PI3-K-independent manner. However in the absence of angiotensin converting enzyme inhibition, ANG II increased both IK and IK1 in a PI3-K-dependent manner in hypertrophied cardiomyocytes. Thus, captopril treatment reveals a negative effect of ANG II on IK and IK1, which is PI3-K independent, whereas in the absence of angiotensin converting enzyme inhibition IK and IK1 regulation is dependent upon PI3-K.

  8. Calcineurin B homologous protein 3 negatively regulates cardiomyocyte hypertrophy via inhibition of glycogen synthase kinase 3 phosphorylation.

    Science.gov (United States)

    Kobayashi, Soushi; Nakamura, Tomoe Y; Wakabayashi, Shigeo

    2015-07-01

    Cardiac hypertrophy is a leading cause of serious heart diseases. Although many signaling molecules are involved in hypertrophy, the functions of some proteins in this process are still unknown. Calcineurin B homologous protein 3 (CHP3)/tescalcin is an EF-hand Ca(2+)-binding protein that is abundantly expressed in the heart; however, the function of CHP3 is unclear. Here, we aimed to identify the cardiac functions of CHP3. CHP3 was expressed in hearts at a wide range of developmental stages and was specifically detected in neonatal rat ventricular myocytes (NRVMs) but not in cardiac fibroblasts in culture. Moreover, knockdown of CHP3 expression using adenoviral-based RNA interference in NRVMs resulted in enlargement of cardiomyocyte size, concomitant with increased expression of a pathological hypertrophy marker ANP. This same treatment elevated glycogen synthase kinase (GSK3α/β) phosphorylation, which is known to inhibit GSK3 function. In contrast, CHP3 overexpression blocked the insulin-induced phosphorylation of GSK3α/β without affecting the phosphorylation of Akt, which is an upstream kinase of GSK3α/β, in HEK293 cells, and it inhibited both IGF-1-induced phosphorylation of GSK3β and cardiomyocyte hypertrophy in NRVMs. Co-immunoprecipitation experiments revealed that GSK3β interacted with CHP3. However, a Ca(2+)-binding-defective mutation of CHP3 (CHP3-D123A) also interacted with GSK3β and had the same inhibitory effect on GSK3α/β phosphorylation, suggesting that the action of CHP3 was independent of Ca(2+). These findings suggest that CHP3 functions as a novel negative regulator of cardiomyocyte hypertrophy via inhibition of GSK3α/β phosphorylation and subsequent enzymatic activation of GSK3α/β. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Hypertension is a conditional factor for the development of cardiac hypertrophy in type 2 diabetic mice.

    Directory of Open Access Journals (Sweden)

    Marc van Bilsen

    Full Text Available BACKGROUND: Type 2 diabetes is frequently associated with co-morbidities, including hypertension. Here we investigated if hypertension is a critical factor in myocardial remodeling and the development of cardiac dysfunction in type 2 diabetic db/db mice. METHODS: Thereto, 14-wks-old male db/db mice and non-diabetic db/+ mice received vehicle or angiotensin II (AngII for 4 wks to induce mild hypertension (n = 9-10 per group. Left ventricular (LV function was assessed by serial echocardiography and during a dobutamine stress test. LV tissue was subjected to molecular and (immunohistochemical analysis to assess effects on hypertrophy, fibrosis and inflammation. RESULTS: Vehicle-treated diabetic mice neither displayed marked myocardial structural remodeling nor cardiac dysfunction. AngII-treatment did not affect body weight and fasting glucose levels, and induced a comparable increase in blood pressure in diabetic and control mice. Nonetheless, AngII-induced LV hypertrophy was significantly more pronounced in diabetic than in control mice as assessed by LV mass (increase +51% and +34%, respectively, p<0.01 and cardiomyocyte size (+53% and +31%, p<0.001. This was associated with enhanced LV mRNA expression of markers of hypertrophy and fibrosis and reduced activation of AMP-activated protein kinase (AMPK, while accumulation of Advanced Glycation End products (AGEs and the expression levels of markers of inflammation were not altered. Moreover, AngII-treatment reduced LV fractional shortening and contractility in diabetic mice, but not in control mice. CONCLUSIONS: Collectively, the present findings indicate that type 2 diabetes in its early stage is not yet associated with adverse cardiac structural changes, but already renders the heart more susceptible to hypertension-induced hypertrophic remodeling.

  10. Fatty acid utilization in pressure-overload hypertrophied rat hearts

    International Nuclear Information System (INIS)

    Reibel, D.K.; O'Rourke, B.

    1986-01-01

    The authors have previously shown that the levels of total tissue coenzyme A and carnitine are reduced in hypertrophied hearts of rats subjected to aortic constriction. It was therefore of interest to determine if these changes were associated with alterations in fatty acid oxidation by the hypertrophied myocardium. Hearts were excised from sham-operated and aortic-constricted rats and perfused at 10 cm H 2 O left atrial filling pressure with a ventricular afterload of 80 cm of H 2 O with buffer containing 1.2 mM 14 C-linoleate. Heart rate and peak systolic pressure were not different in control and hypertrophied hearts. 14 CO 2 production was linear in both groups of hearts between 10 and 30 minutes of perfusion. The rate of fatty acid oxidation determined by 14 CO 2 production during this time was 0.728 +/- 0.06 μmoles/min/g dry in control hearts and 0.710 +/- 0.02 μmoles/min/g dry in hypertrophied hearts. Comparable rates of fatty acid oxidation were associated with comparable rates of O 2 consumption in the two groups of hearts (39.06 +/- 3.50 and 36.78 +/- 2.39 μmoles/g dry/min for control and hypertrophied hearts, respectively). The data indicate that the ability of the hypertrophied heart to oxidize fatty acids under these perfusion conditions is not impaired in spite of significant reductions in tissue levels of coenzyme A and carnitine

  11. Comparison of dobutamine stress echocardiography and technetium-99m sestamibi single-photon emission tomography for the diagnosis of coronary artery disease in hypertensive patients with and without left ventricular hypertrophy

    International Nuclear Information System (INIS)

    Elhendy, A.; Geleijnse, M.L.; Van Domburg, R.T.; Bax, J.J.; Nierop, P.R.; Beerens, S.A.M.; Mohsen Ibrahim, M.; Roelandt, J.R.T.C.; Valkema, R.; Krenning, E.P.

    1998-01-01

    The aim of this study was to compare the accuracy of these two imaging modalities in conjunction with dobutamine stress test for the diagnosis of coronary artery disease in hypertensive patients with and without left ventricular hypertrophy. Dobutamine stress echocardiography in conjunction with sestamibi (MIBI) SPET was performed in 84 patients with the diagnosis of systemic hypertension who had been referred for evaluation of myocardial ischaemia. Significant coronary artery disease (≥50% luminal diameter stenosis) was detected in 66 patients (79%). The sensitivity, specificity and accuracy of the ischaemic pattern at echocardiography for the diagnosis of coronary artery disease were 73% (CI 63%-82%), 83% (CI 75%-91%) and 75% (CI 66%-84%), those for MIBI were 67% (CI 57%-77%), 83% (CI 75%-91%) and 70% (CI 60%-80%) respectively (P = NS vs echocardiography). Significant stenosis was detected in 123 (49%) of the 252 analysed coronary arteries. The sensitivity, specificity and accuracy of echocardiography for the regional diagnosis of coronary artery disease were 63% (CI 56%-69%), 90% (CI 86%-94%) and 77% (CI 72%-82%). Those for MIBI were 58% (CI 51%-64%), 91% (CI 87%-94%) and 75% (CI 69%-80) respectively (P = NS vs echocardiography). Left ventricular hypertrophy was detected in 59 patients (70%) by echocardiography and did not influence the overall or regional specificity of echocardiography or MIBI SPET.(orig./MG) (orig.)

  12. Are left ventricular mass, geometry and function related to vascular changes and/or insulin resistance in long-standing hypertension? ICARUS: a LIFE substudy

    DEFF Research Database (Denmark)

    Olsen, M H; Hjerkinn, E; Wachtell, K

    2003-01-01

    Vascular hypertrophy and insulin resistance have been associated with abnormal left ventricular (LV) geometry in population studies. We wanted to investigate the influence of vascular hypertrophy and insulin resistance on LV hypertrophy and its function in patients with hypertension. In 89 patients...

  13. Solving the cardiac hypertrophy riddle: The angiotensin II-mechanical stress connection.

    Science.gov (United States)

    Zablocki, Daniela; Sadoshima, Junichi

    2013-11-08

    A series of studies conducted 20 years ago, documenting the cardiac hypertrophy phenotype and its underlying signaling mechanism induced by angiotensin II (Ang II) and mechanical stress, showed a remarkable similarity between the effect of the Gαq agonist and that of mechanical forces on cardiac hypertrophy. Subsequent studies confirmed the involvement of autocrine/paracrine mechanisms, including stretch-induced release of Ang II in load-induced cardiac hypertrophy. Recent studies showed that the Ang II type 1 (AT1) receptor is also directly activated by mechanical forces, suggesting that AT1 receptors play an important role in mediating load-induced cardiac hypertrophy through both ligand- and mechanical stress-dependent mechanisms.

  14. Effect of vildagliptin, a dipeptidyl peptidase 4 inhibitor, on cardiac hypertrophy induced by chronic beta-adrenergic stimulation in rats

    Science.gov (United States)

    2014-01-01

    Background Heart failure with left ventricular (LV) hypertrophy is often associated with insulin resistance and inflammation. Recent studies have shown that dipeptidyl peptidase 4 (DPP4) inhibitors improve glucose metabolism and inflammatory status. We therefore evaluated whether vildagliptin, a DPP4 inhibitor, prevents LV hypertrophy and improves diastolic function in isoproterenol-treated rats. Methods Male Wistar rats received vehicle (n = 20), subcutaneous isoproterenol (2.4 mg/kg/day, n = 20) (ISO), subcutaneous isoproterenol (2.4 mg/kg/day + oral vildagliptin (30 mg/kg/day, n = 20) (ISO-VL), or vehicle + oral vildagliptin (30 mg/kg/day, n = 20) (vehicle-VL) for 7 days. Results Blood pressure was similar among the four groups, whereas LV hypertrophy was significantly decreased in the ISO-VL group compared with the ISO group (heart weight/body weight, vehicle: 3.2 ± 0.40, ISO: 4.43 ± 0.39, ISO-VL: 4.14 ± 0.29, vehicle-VL: 3.16 ± 0.16, p vildagliptin lowered the elevated LV end-diastolic pressure observed in the ISO group, but other parameters regarding LV diastolic function such as the decreased minimum dp/dt were not ameliorated in the ISO-VL group. Histological analysis showed that vildagliptin attenuated the increased cardiomyocyte hypertrophy and perivascular fibrosis, but it did not affect angiogenesis in cardiac tissue. In the ISO-VL group, quantitative PCR showed attenuation of increased mRNA expression of tumor necrosis factor-α, interleukin-6, insulin-like growth factor-l, and restoration of decreased mRNA expression of glucose transporter type 4. Conclusions Vildagliptin may prevent LV hypertrophy caused by continuous exposure to isoproterenol in rats. PMID:24521405

  15. Determinants and improvement of electrocardiographic diagnosis of left ventricular hypertrophy in a black African population.

    Directory of Open Access Journals (Sweden)

    Ahmadou M Jingi

    Full Text Available BACKGROUND: Left ventricular hypertrophy (LVH is a major cardiovascular risk factor. The electrocardiogram (ECG has been shown to be a poor tool in detecting LVH due to cardiac and extracardiac factors. We studied the determinants and possibility of improving the test performance of the ECG in a group of Black Africans. METHODS: We studied echocardiograms and electrocardiograms of 182 Cameroonian patients among whom 113 (62.1% were having an echocardiographic LVH. Echocardiographic LVH was defined as Left Ventricular Mass Indexed to height 2.7(LVMI>48 g/m2.7 in men, and >44 g/m 2.7 in women or Body Surface Area ≥116 g/m2 in men, and ≥96 g/m2 in women. Test performances were calculated for 6 classic ECG criteria Sokolow-Lyon, Cornell, Cornell product, Gubner-Ungerleiger, amplitudes of R in aVL, V5 and V6. RESULTS: The most sensitive criteria were Cornell (37.2% and Sokolow-Lyon index (26.5%. The most specific criteria were Gubner (98.6%, RaVL (97.1%, RV5/V6 (95.7% and Cornell product (94.2%. The performance of the ECG in diagnosing LVH significantly increased with the severity of LVH for Cornell index (r = 0.420, p<0.0001 and Sokolow index (r = 0.212, p = 0.002. It decreased with body habitus (r = -0.248, p = 0.001 for Sokolow-Lyon index. Cornell index was less affected (age p = 0.766; body habitus: p = 0.209. After sex-specific adjustment for BMI, Cornell BMI sensitivity increased from 37.2% to 69% (r = 0.472, p<0.0001, and Sokolow-Lyon BMI sensitivity increased from 26.5% to 58.4% (r = 0.270, p<0.001. CONCLUSION: The test performance of the ECG in diagnosing LVH is low in this Black African population, due to extracardiac factors such as age, sex, body habitus, and cardiac factors such as LVH severity and geometry. However, this performance is improved after adjustment for extracardiac factors.

  16. GATA4-mediated cardiac hypertrophy induced by D-myo-inositol 1,4,5-tris-phosphate

    International Nuclear Information System (INIS)

    Zhu Zhiming; Zhu Shanjun; Liu Daoyan; Yu Zengping; Yang Yongjian; Giet, Markus van der; Tepel, Martin

    2005-01-01

    We evaluated the effects of D-myo-inositol 1,4,5-tris-phosphate on cardiac hypertrophy. D-myo-inositol 1,4,5-tris-phosphate augmented cardiac hypertrophy as evidenced by its effects on DNA synthesis, protein synthesis, and expression of immediate-early genes c-myc and c-fos, β-myosin heavy chain, and α-actin. The administration of D-myo-inositol 1,4,5-tris-phosphate increased the expression of nuclear factor of activated T-cells and cardiac-restricted zinc finger transcription factor (GATA4). Real-time quantitative RT-PCR showed that D-myo-inositol 1,4,5-tris-phosphate-induced GATA4 mRNA was significantly enhanced even in the presence of the calcineurin inhibitor, cyclosporine A. The effect of D-myo-inositol 1,4,5-tris-phosphate was blocked after inhibition of inositol-trisphosphate receptors but not after inhibition of c-Raf/mitogen-activated protein kinase kinase (MEK)/mitogen-activated protein kinase (ERK) or p38 mitogen-activated protein kinase pathways. The study shows that D-myo-inositol 1,4,5-tris-phosphate-induced cardiac hypertrophy is mediated by GATA4 but independent from the calcineurin pathway

  17. Left ventricular hypertrophy: The relationship between the electrocardiogram and cardiovascular magnetic resonance imaging.

    Science.gov (United States)

    Bacharova, Ljuba; Ugander, Martin

    2014-11-01

    Conventional assessment of left ventricular hypertrophy (LVH) using the electrocardiogram (ECG), for example, by the Sokolow-Lyon, Romhilt-Estes or Cornell criteria, have relied on assessing changes in the amplitude and/or duration of the QRS complex of the ECG to quantify LV mass. ECG measures of LV mass have typically been validated by imaging with echocardiography or cardiovascular magnetic resonance imaging (CMR). However, LVH can be the result of diverse etiologies, and LVH is also characterized by pathological changes in myocardial tissue characteristics on the genetic, molecular, cellular, and tissue level beyond a pure increase in the number of otherwise normal cardiomyocytes. For example, slowed conduction velocity through the myocardium, which can be due to diffuse myocardial fibrosis, has been shown to be an important determinant of conventional ECG LVH criteria regardless of LV mass. Myocardial tissue characterization by CMR has emerged to not only quantify LV mass, but also detect and quantify the extent and severity of focal or diffuse myocardial fibrosis, edema, inflammation, myocarditis, fatty replacement, myocardial disarray, and myocardial deposition of amyloid proteins (amyloidosis), glycolipids (Fabry disease), or iron (siderosis). This can be undertaken using CMR techniques including late gadolinium enhancement (LGE), T1 mapping, T2 mapping, T2* mapping, extracellular volume fraction (ECV) mapping, fat/water-weighted imaging, and diffusion tensor CMR. This review presents an overview of current and emerging concepts regarding the diagnostic possibilities of both ECG and CMR for LVH in an attempt to narrow gaps in our knowledge regarding the ECG diagnosis of LVH. © 2014 Wiley Periodicals, Inc.

  18. Dynamic right ventricular outflow tract (infundibular) stenosis and pectus excavatum in a dog

    OpenAIRE

    Fournier, Tanya E.

    2008-01-01

    This is the first published report of a dog with dynamic right ventricular outflow tract (infundibular) stenosis, right ventricular hypertrophy, and pectus excavatum. A juvenile dog presented with a grade V/VI left base systolic heart murmur, tachycardia, and pectus excavatum. Diagnosis of the aforementioned conditions was based on radiography, electrocardiography, and echocardiography. At 9 1/2 wk of age the heart murmur was no longer audible and the right ventricular stenosis and hypertroph...

  19. Computational model based approach to analysis ventricular arrhythmias: Effects of dysfunction calcium channels

    Science.gov (United States)

    Gulothungan, G.; Malathi, R.

    2018-04-01

    Disturbed sodium (Na+) and calcium (Ca2+) handling is known to be a major predisposing factor for life-threatening cardiac arrhythmias. Cardiac contractility in ventricular tissue is prominent by Ca2+ channels like voltage dependent Ca2+ channels, sodium-calcium exchanger (Na+-Ca2+x) and sacroplasmicrecticulum (SR) Ca2+ pump and leakage channels. Experimental and clinical possibilities for studying cardiac arrhythmias in human ventricular myocardium are very limited. Therefore, the use of alternative methods such as computer simulations is of great importance. Our aim of this article is to study the impact on action potential (AP) generation and propagation in single ventricular myocyte and ventricular tissue under different dysfunction Ca2+ channels condition. In enhanced activity of Na+-Ca2+x, single myocyte produces AP duration (APD90) and APD50 is significantly smaller (266 ms and 235 ms). Its Na+-Ca2+x current at depolarization is increases 60% from its normal level and repolarization current goes more negative (nonfailing= -0.28 pA/pF and failing= -0.47 pA/pF). Similarly, same enhanced activity of Na+-Ca2+x in 10 mm region of ventricular sheet, raises the plateau potential abruptly, which ultimately affects the diastolic repolarization. Compare with normal ventricular sheet region of 10 mm, 10% of ventricular sheet resting state is reduces and ventricular sheet at time 250 ms is goes to resting state very early. In hypertrophy condition, single myocyte produces APD90 and APD50 is worthy of attention smaller (232 mS and 198 ms). Its sodium-potassium (Na+-K+) pump current is 75% reduces from its control conditions (0.13 pA/pF). Hypertrophy condition, 50% of ventricular sheet is reduces to minimum plateau potential state, that starts the repolarization process very early and reduces the APD. In a single failing SR Ca2+ channels myocyte, recovery of Ca2+ concentration level in SR reduces upto 15% from its control myocytes. At time 290 ms, 70% of ventricular sheet

  20. Reverse right ventricular remodeling after pulmonary endarterectomy in patients with chronic thromboembolic pulmonary hypertension: utility of magnetic resonance imaging to demonstrate restoration of the right ventricle

    NARCIS (Netherlands)

    Reesink, Herre J.; Marcus, J. Tim; Tulevski, Igor I.; Jamieson, Stuart; Kloek, Jaap J.; Vonk Noordegraaf, Anton; Bresser, Paul

    2007-01-01

    OBJECTIVES: Pulmonary arterial hypertension causes right ventricular remodeling; that is, right ventricular dilatation, hypertrophy, and leftward ventricular septal bowing. We studied the effect of pulmonary endarterectomy on the restoration of right ventricular remodeling in patients with chronic

  1. The transcription factor MEF2C mediates cardiomyocyte hypertrophy induced by IGF-1 signaling

    Energy Technology Data Exchange (ETDEWEB)

    Munoz, Juan Pablo; Collao, Andres; Chiong, Mario; Maldonado, Carola; Adasme, Tatiana; Carrasco, Loreto; Ocaranza, Paula; Bravo, Roberto; Gonzalez, Leticia; Diaz-Araya, Guillermo [Centro FONDAP Estudios Moleculares de la Celula, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Facultad de Ciencias Quimicas y Farmaceuticas, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Hidalgo, Cecilia [Centro FONDAP Estudios Moleculares de la Celula, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Instituto de Ciencias Biomedicas, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Lavandero, Sergio, E-mail: slavander@uchile.cl [Centro FONDAP Estudios Moleculares de la Celula, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Facultad de Ciencias Quimicas y Farmaceuticas, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Instituto de Ciencias Biomedicas, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile)

    2009-10-09

    Myocyte enhancer factor 2C (MEF2C) plays an important role in cardiovascular development and is a key transcription factor for cardiac hypertrophy. Here, we describe MEF2C regulation by insulin-like growth factor-1 (IGF-1) and its role in IGF-1-induced cardiac hypertrophy. We found that IGF-1 addition to cultured rat cardiomyocytes activated MEF2C, as evidenced by its increased nuclear localization and DNA binding activity. IGF-1 stimulated MEF2 dependent-gene transcription in a time-dependent manner, as indicated by increased MEF2 promoter-driven reporter gene activity; IGF-1 also induced p38-MAPK phosphorylation, while an inhibitor of p38-MAPK decreased both effects. Additionally, inhibitors of phosphatidylinositol 3-kinase and calcineurin prevented IGF-1-induced MEF2 transcriptional activity. Via MEF2C-dependent signaling, IGF-1 also stimulated transcription of atrial natriuretic factor and skeletal {alpha}-actin but not of fos-lux reporter genes. These novel data suggest that MEF2C activation by IGF-1 mediates the pro-hypertrophic effects of IGF-1 on cardiac gene expression.

  2. The transcription factor MEF2C mediates cardiomyocyte hypertrophy induced by IGF-1 signaling

    International Nuclear Information System (INIS)

    Munoz, Juan Pablo; Collao, Andres; Chiong, Mario; Maldonado, Carola; Adasme, Tatiana; Carrasco, Loreto; Ocaranza, Paula; Bravo, Roberto; Gonzalez, Leticia; Diaz-Araya, Guillermo; Hidalgo, Cecilia; Lavandero, Sergio

    2009-01-01

    Myocyte enhancer factor 2C (MEF2C) plays an important role in cardiovascular development and is a key transcription factor for cardiac hypertrophy. Here, we describe MEF2C regulation by insulin-like growth factor-1 (IGF-1) and its role in IGF-1-induced cardiac hypertrophy. We found that IGF-1 addition to cultured rat cardiomyocytes activated MEF2C, as evidenced by its increased nuclear localization and DNA binding activity. IGF-1 stimulated MEF2 dependent-gene transcription in a time-dependent manner, as indicated by increased MEF2 promoter-driven reporter gene activity; IGF-1 also induced p38-MAPK phosphorylation, while an inhibitor of p38-MAPK decreased both effects. Additionally, inhibitors of phosphatidylinositol 3-kinase and calcineurin prevented IGF-1-induced MEF2 transcriptional activity. Via MEF2C-dependent signaling, IGF-1 also stimulated transcription of atrial natriuretic factor and skeletal α-actin but not of fos-lux reporter genes. These novel data suggest that MEF2C activation by IGF-1 mediates the pro-hypertrophic effects of IGF-1 on cardiac gene expression.

  3. Obesity and exercise-induced ectopic ventricular arrhythmias in apparently healthy middle aged adults.

    Science.gov (United States)

    Sabbag, Avi; Sidi, Yechezkel; Kivity, Shaye; Beinart, Roy; Glikson, Michael; Segev, Shlomo; Goldenberg, Ilan; Maor, Elad

    2016-03-01

    Obesity and overweight are strongly associated with cardiovascular morbidity and mortality. However, there are limited data on the association between excess weight and the risk of ectopic ventricular activity. We investigated the association between body mass index (BMI) and the risk for ectopic ventricular activity (defined as multiple ventricular premature beats (≥3), ventricular bigeminy, nonsustained ventricular tachycardia or sustained ventricular tachycardia) during exercise stress testing among 22,516 apparently healthy men and women who attended periodic health screening examinations between the years 2000 and 2014. All subjects had completed maximal exercise stress testing annually according to the Bruce protocol. Subjects were divided at baseline into three groups: normal weight (BMI ≥ 18.5 kg/m(2) andexercise-induced ectopic ventricular activity arrhythmias was highest among obese subjects, intermediate among overweight subjects and lowest among subjects with normal weight (3.4%, 2.7% and 2.2% respectively; p exercise compared with subjects with normal weight (p = 0.005), and that each 1 kg/m(2) increase in BMI was associated with a significant 4% (p = 0.002) increased adjusted risk for exercise-induced ventricular arrhythmias. Obesity is independently associated with increased likelihood of ectopic ventricular arrhythmia during exercise. © The European Society of Cardiology 2015.

  4. Prolactin induces adrenal hypertrophy

    Directory of Open Access Journals (Sweden)

    E.J. Silva

    2004-02-01

    Full Text Available Although adrenocorticotropic hormone is generally considered to play a major role in the regulation of adrenal glucocorticoid secretion, several reports have suggested that other pituitary hormones (e.g., prolactin also play a significant role in the regulation of adrenal function. The aim of the present study was to measure the adrenocortical cell area and to determine the effects of the transition from the prepubertal to the postpubertal period on the hyperprolactinemic state induced by domperidone (4.0 mg kg-1 day-1, sc. In hyperprolactinemic adult and young rats, the adrenals were heavier, as determined at necropsy, than in the respective controls: adults (30 days: 0.16 ± 0.008 and 0.11 ± 0.007; 46 days: 0.17 ± 0.006 and 0.12 ± 0.008, and 61 days: 0.17 ± 0.008 and 0.10 ± 0.004 mg for treated and control animals, respectively; P < 0.05, and young rats (30 days: 0.19 ± 0.003 and 0.16 ± 0.007, and 60 days: 0.16 ± 0.006 and 0.13 ± 0.009 mg; P < 0.05. We selected randomly a circular area in which we counted the nuclei of adrenocortical cells. The area of zona fasciculata cells was increased in hyperprolactinemic adult and young rats compared to controls: adults: (61 days: 524.90 ± 47.85 and 244.84 ± 9.03 µm² for treated and control animals, respectively; P < 0.05, and young rats: (15 days: 462.30 ± 16.24 and 414.28 ± 18.19; 60 days: 640.51 ± 12.91 and 480.24 ± 22.79 µm²; P < 0.05. Based on these data we conclude that the increase in adrenal weight observed in the hyperprolactinemic animals may be due to prolactin-induced adrenocortical cell hypertrophy.

  5. Left ventricular mass and hypertrophy by echocardiography and cardiac magnetic resonance: the multi-ethnic study of atherosclerosis.

    Science.gov (United States)

    Armstrong, Anderson C; Gjesdal, Ola; Almeida, André; Nacif, Marcelo; Wu, Colin; Bluemke, David A; Brumback, Lyndia; Lima, João A C

    2014-01-01

    Left ventricular mass (LVM) and hypertrophy (LVH) are important parameters, but their use is surrounded by controversies. We compare LVM by echocardiography and cardiac magnetic resonance (CMR), investigating reproducibility aspects and the effect of echocardiography image quality. We also compare indexing methods within and between imaging modalities for classification of LVH and cardiovascular risk. Multi-Ethnic Study of Atherosclerosis enrolled 880 participants in Baltimore city, 146 had echocardiograms and CMR on the same day. LVM was then assessed using standard techniques. Echocardiography image quality was rated (good/limited) according to the parasternal view. LVH was defined after indexing LVM to body surface area, height(1.7) , height(2.7) , or by the predicted LVM from a reference group. Participants were classified for cardiovascular risk according to Framingham score. Pearson's correlation, Bland-Altman plots, percent agreement, and kappa coefficient assessed agreement within and between modalities. Left ventricular mass by echocardiography (140 ± 40 g) and by CMR were correlated (r = 0.8, P echocardiography image quality. The reproducibility profile had strong correlations and agreement for both modalities. Image quality groups had similar characteristics; those with good images compared to CMR slightly superiorly. The prevalence of LVH tended to be higher with higher cardiovascular risk. The agreement for LVH between imaging modalities ranged from 77% to 98% and the kappa coefficient from 0.10 to 0.76. Echocardiography has a reliable performance for LVM assessment and classification of LVH, with limited influence of image quality. Echocardiography and CMR differ in the assessment of LVH, and additional differences rise from the indexing methods. © 2013. This article is a U.S. Government work and is in the public domain in the USA.

  6. EFFECT OF ANTIHYPERTENSIVE THERAPY BASED ON NEW METHOD OF INDIVIDUAL CHOICE OF DRUGS ON LEFT VENTRICULAR HYPERTROPHY IN ELDERLY PATIENTS

    Directory of Open Access Journals (Sweden)

    K. I. Pshenichkin

    2015-12-01

    Full Text Available Aim. To study the effects of antihypertensive therapy based on consideration of individual heart rhythm variability (HRV on left ventricular hypertrophy (LVH in hypertensive elderly patients.Material and methods. 60 hypertensive elderly patients with LVH were included in the study. They were split in two groups (30 people in each one. Patients of the group-I had common antihypertensive therapy. Patients of group-II received medications prescribed with consideration of individual heart rate variability. Holter monitoring with analysis of HRV, 24-hour blood pressure monitoring and ultrasonography were conducted initially and 18 months after treatment beginning.Results. BP control was reached in the majority of patients of both groups. The patients of group-II in comparison with patients of group-I had reduction of low- high frequency power ratio (LF/HF and higher rate of LVH reduction. Relationship between LVH dynamics and ratio LF/HF was found.Conclusion. Arterial hypertension therapy considering individual HRV contributes in LVH reduction in elderly patients.

  7. Patterns of left ventricular remodeling among patients with essential and secondary hypertension

    OpenAIRE

    Radulescu,Dan; Stoicescu,Laurentiu; Buzdugan,Elena; Donca,Valer

    2013-01-01

    Background: High blood pressure causes left ventricular hypertrophy, which is a negative prognostic factor among hypertensive patients. Aim: To assess left ventricular geometric remodeling patterns in patients with essential hypertension or with hypertension secondary to parenchymal renal disease. Material and Methods: We analyzed data from echocardiograms performed in 250patients with essential hypertension (150 females) and 100 patients with secondary hypertension (60 females). The interven...

  8. Pulmonary Hypertension in Wild Type Mice and Animals with Genetic Deficit in KCa2.3 and KCa3.1 Channels

    DEFF Research Database (Denmark)

    Wandall-Frostholm, Christine; Skaarup, Lykke Moran; Sadda, Veeranjaneyulu

    2014-01-01

    to induce pulmonary hypertension. The degree of pulmonary hypertension was evaluated by right ventricular pressure and assessment of right ventricular hypertrophy. Segments of pulmonary arteries were mounted in a wire myograph for functional studies and morphometric studies were performed on lung sections....... Chronic hypoxia induced pulmonary hypertension, right ventricular hypertrophy, increased lung weight, and increased hematocrit levels in either genotype. The K(Ca)3.1(-/-)/K(Ca)2.3(T/T(+DOX)) mice developed structural alterations in the heart with increased right ventricular wall thickness as well...

  9. Gastrodin Inhibits Store-Operated Ca2+ Entry and Alleviates Cardiac Hypertrophy

    Directory of Open Access Journals (Sweden)

    Xiaoqiang Yao

    2017-04-01

    Full Text Available Cardiac hypertrophy is a major risk factor for heart failure, which are among the leading causes of human death. Gastrodin is a small molecule that has been used clinically to treat neurological and vascular diseases for many years without safety issues. In the present study, we examined protective effect of gastrodin against cardiac hypertrophy and explored the underlying mechanism. Phenylephrine and angiotensin II were used to induce cardiac hypertrophy in a mouse model and a cultured cardiomyocyte model. Gastrodin was found to alleviate the cardiac hypertrophy in both models. Mechanistically, gastrodin attenuated the store-operated Ca2+ entry (SOCE by reducing the expression of STIM1 and Orai1, two key proteins in SOCE, in animal models as well as in cultured cardiomyocyte model. Furthermore, suppressing SOCE by RO2959, Orai1-siRNAs or STIM1-siRNAs markedly attenuated the phenylephrine-induced hypertrophy in cultured cardiomyocyte model. Together, these results showed that gastrodin inhibited cardiac hypertrophy and it also reduced the SOCE via its action on the expression of STIM1 and Orai1. Furthermore, suppression of SOCE could reduce the phenylephrine-induced cardiomyocyte hypertrophy, suggesting that SOCE-STIM1-Orai1 is located upstream of hypertrophy.

  10. Histologically Measured Cardiomyocyte Hypertrophy Correlates with Body Height as Strongly as with Body Mass Index

    Directory of Open Access Journals (Sweden)

    Richard E. Tracy

    2011-01-01

    Full Text Available Cardiac myocytes are presumed to enlarge with left ventricular hypertrophy (LVH. This study correlates histologically measured myocytes with lean and fat body mass. Cases of LVH without coronary heart disease and normal controls came from forensic autopsies. The cross-sectional widths of myocytes in H&E-stained paraffin sections followed log normal distributions almost to perfection in all 104 specimens, with constant coefficient of variation across the full range of ventricular weight, as expected if myocytes of all sizes contribute proportionately to hypertrophy. Myocyte sizes increased with height. By regression analysis, height2.7 as a proxy for lean body mass and body mass index (BMI as a proxy for fat body mass, exerted equal effects in the multiple correlation with myocyte volume, and the equation rejected race and sex. In summary, myocyte sizes, as indexes of LVH, suggest that lean and fat body mass may contribute equally.

  11. Gender differences in left ventricular structure and function during antihypertensive treatment: the Losartan Intervention for Endpoint Reduction in Hypertension Study

    DEFF Research Database (Denmark)

    Gerdts, E.; Okin, P.M.; Simone, G. de

    2008-01-01

    . Left ventricular hypertrophy was diagnosed as left ventricular mass divided by height(2.7) >or=46.7 g/m(2.7) and 49.2 g/m(2.7) in women and men, respectively, and systolic function as ejection fraction and stress-corrected midwall fractional shortening. Women included more patients with obesity......, isolated systolic hypertension, and mitral regurgitation (all Pstress-corrected midwall shortening, and prevalence of left ventricular hypertrophy were higher in women at baseline and at the end of study (all P... analyses, female gender also predicted 2% higher mean in-treatment ejection fraction and 2% higher mean stress-corrected midwall shortening (both beta=0.07; Pstress-corrected midwall shortening in spite of less...

  12. PPARalpha siRNA-treated expression profiles uncover the causal sufficiency network for compound-induced liver hypertrophy.

    Directory of Open Access Journals (Sweden)

    Xudong Dai

    2007-03-01

    Full Text Available Uncovering pathways underlying drug-induced toxicity is a fundamental objective in the field of toxicogenomics. Developing mechanism-based toxicity biomarkers requires the identification of such novel pathways and the order of their sufficiency in causing a phenotypic response. Genome-wide RNA interference (RNAi phenotypic screening has emerged as an effective tool in unveiling the genes essential for specific cellular functions and biological activities. However, eliciting the relative contribution of and sufficiency relationships among the genes identified remains challenging. In the rodent, the most widely used animal model in preclinical studies, it is unrealistic to exhaustively examine all potential interactions by RNAi screening. Application of existing computational approaches to infer regulatory networks with biological outcomes in the rodent is limited by the requirements for a large number of targeted permutations. Therefore, we developed a two-step relay method that requires only one targeted perturbation for genome-wide de novo pathway discovery. Using expression profiles in response to small interfering RNAs (siRNAs against the gene for peroxisome proliferator-activated receptor alpha (Ppara, our method unveiled the potential causal sufficiency order network for liver hypertrophy in the rodent. The validity of the inferred 16 causal transcripts or 15 known genes for PPARalpha-induced liver hypertrophy is supported by their ability to predict non-PPARalpha-induced liver hypertrophy with 84% sensitivity and 76% specificity. Simulation shows that the probability of achieving such predictive accuracy without the inferred causal relationship is exceedingly small (p < 0.005. Five of the most sufficient causal genes have been previously disrupted in mouse models; the resulting phenotypic changes in the liver support the inferred causal roles in liver hypertrophy. Our results demonstrate the feasibility of defining pathways mediating drug-induced

  13. Inhibition of Rac1 reduces store overload-induced calcium release and protects against ventricular arrhythmia.

    Science.gov (United States)

    Zhang, Lili; Lu, Xiangru; Gui, Le; Wu, Yan; Sims, Stephen M; Wang, Guoping; Feng, Qingping

    2016-08-01

    Rac1 is a small GTPase and plays key roles in multiple cellular processes including the production of reactive oxygen species (ROS). However, whether Rac1 activation during myocardial ischaemia and reperfusion (I/R) contributes to arrhythmogenesis is not fully understood. We aimed to study the effects of Rac1 inhibition on store overload-induced Ca(2+) release (SOICR) and ventricular arrhythmia during myocardial I/R. Adult Rac1(f/f) and cardiac-specific Rac1 knockdown (Rac1(ckd) ) mice were subjected to myocardial I/R and their electrocardiograms (ECGs) were monitored for ventricular arrhythmia. Myocardial Rac1 activity was increased and ventricular arrhythmia was induced during I/R in Rac1(f/f) mice. Remarkably, I/R-induced ventricular arrhythmia was significantly decreased in Rac1(ckd) compared to Rac1(f/f) mice. Furthermore, treatment with Rac1 inhibitor NSC23766 decreased I/R-induced ventricular arrhythmia. Ca(2+) imaging analysis showed that in response to a 6 mM external Ca(2+) concentration challenge, SOICR was induced with characteristic spontaneous intracellular Ca(2+) waves in Rac1(f/f) cardiomyocytes. Notably, SOICR was diminished by pharmacological and genetic inhibition of Rac1 in adult cardiomyocytes. Moreover, I/R-induced ROS production and ryanodine receptor 2 (RyR2) oxidation were significantly inhibited in the myocardium of Rac1(ckd) mice. We conclude that Rac1 activation induces ventricular arrhythmia during myocardial I/R. Inhibition of Rac1 suppresses SOICR and protects against ventricular arrhythmia. Blockade of Rac1 activation may represent a new paradigm for the treatment of cardiac arrhythmia in ischaemic heart disease. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  14. Endonuclease G is a novel determinant of cardiac hypertrophy and mitochondrial function

    Czech Academy of Sciences Publication Activity Database

    McDermott-Roe, Ch.; Ye, J.; Ahmed, R.; Sun, X. M.; Serafín, A.; Ware, J.; Bottolo, L.; Muckett, P.; Caňas, X.; Zhang, J.; Rowe, G. C.; Buchan, R.; Lu, H.; Braithwaite, A.; Mancini, M.; Hauton, D.; Martí, R.; García-Arumí, E.; Hubner, N.; Jacob, H.; Serikawa, T.; Zídek, Václav; Papoušek, František; Kolář, František; Cardona, M.; Ruiz-Meana, M.; García-Dorado, D.; Comella, J. X.; Felkin, L. E.; Barton, P. J. R.; Arany, Z.; Pravenec, Michal; Petretto, E.; Sanchis, D.; Cook, S.A.

    2011-01-01

    Roč. 478, č. 7367 (2011), s. 114-118 ISSN 0028-0836 R&D Projects: GA MŠk(CZ) 1M0520; GA ČR(CZ) GA301/08/0166 Institutional research plan: CEZ:AV0Z50110509 Keywords : left ventricular hypertrophy * endonuclease G * mitochondrial dysfunction Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 36.280, year: 2011

  15. The endoplasmic reticulum stress-autophagy pathway is involved in apelin-13-induced cardiomyocyte hypertrophy in vitro

    Institute of Scientific and Technical Information of China (English)

    Feng XIE; Di WU; Shi-fang HUANG; Jian-gang CAO; He-ning LI; Lu HE; Mei-qing LIU; Lan-fang LI; Lin-xi CHEN

    2017-01-01

    Apelin is the endogenous ligand for the G protein-coupled receptor APJ,and plays important roles in the cardiovascular system.Our previous studies showed that apelin-13 promotes the hypertrophy of H9c2 rat cardiomyocytes through the PI3K-autophagy pathway.The aim of this study was to explore what roles ER stress and autophagy played in apelin-13-induced hypertrophy of cardiomyocytes in vitro.Treatment of H9c2 cells with apelin-13 (0.001-2 μJmol/L) dose-dependently increased the production of ROS and the expression levels of NADPH oxidase 4 (NOX4).Knockdown of Nox4 with siRNAs effectively prevented the reduction of GSH/GSSG ratio in apelin-13-treated cells.Furthermore,apelin-13 treatment dose-dependently increased the expression of Bip and CHOP,two ER stress markers,in the cells.Knockdown of APJ or Nox4 with the corresponding siRNAs,or application of NADPH inhibitor DPI blocked apelin-13-induced increases in Bip and CHOP expression.Moreover,apelin-13 treatment increased the formation of autophagosome and ER fragments and the LC3 puncta in the ER of the cells.Knockdown of APJ,Nox4,Bip or CHOP with the corresponding siRNAs,or application of DPI or salubrinal attenuated apelin-13-induced overexpression of LC3-Ⅱ/Ⅰ and beclin 1.Finally,knockdown of Nox4,Bip or CHOP with the corresponding siRNAs,or application of salubrinal significantly suppressed apelin-13-induced increases in the cell diameter,volume and protein contents.Our results demonstrate that ER stress-autophagy is involved in apelin-13-induced H9c2 cell hypertrophy.

  16. Right ventricular visualization by Tl-201 myocardial scintigraphy in chronic obstructive pulmonary disease

    Energy Technology Data Exchange (ETDEWEB)

    Fujii, Tadashige; Tanaka, Masao; Takeda, Masashi; Matsuzawa, Yukinori; Handa, Kenjiro; Yoshimura, Kazuhiko [Shinshu Univ., Matsumoto, Nagano (Japan). Faculty of Medicine

    1993-04-01

    Tl-201 myocardial scintigraphy was performed in 130 patients with chronic obstructive pulmonary disease (COPD) to evaluate right ventricular hypertrophy, and the clinical significance of this method was studied. Tl-201 uptake ratios of the right ventricle, which represents the ratio of total counts of the right ventricle to counts of the administered dose of Tl-201, was higher in COPD, especially in pulmonary emphysema and B type COPD by Burrows classification than in controls. The grade of visualization of the right ventricle by visual assessment (RVV) was marked (+++) in only a few cases and moderate (++) in many cases (more than 80%) in all diseases except bronchial asthma. The incidence of right ventricular hypertrophy by electrocardiogram, right-sided heart failure and marked dyspnea (Hugh-Jones 4[center dot]5) were very low in cases with RVV grade ++ and very high in cases with +++. The grade of RVV was related to the severity of pulmonary perfusion impairment, although in diffuse panbronchiolitis the RVV was relatively slight compared with the impairment of perfusion. May parameters of pulmonary function such as %VC, FEV1.0%, RV/TLC, V25, %DLCO, Raw, [Delta]N[sub 2] and PaO[sub 2] showed abnormal values in patients with RVV grade of (++) or (+++) in all diseases except bronchial asthma. In COPD, Tl-201 myocardial scintigraphy seems to be useful for assessment of right ventricular overloading, and for follow-up observation and differentiation between cor pulmonale and right ventricular hypertrophy secondary to cardiac diseases by observing Tl-201 uptake of the lung and left ventricle. (author).

  17. Right ventricular visualization by Tl-201 myocardial scintigraphy in chronic obstructive pulmonary disease

    International Nuclear Information System (INIS)

    Fujii, Tadashige; Tanaka, Masao; Takeda, Masashi; Matsuzawa, Yukinori; Handa, Kenjiro; Yoshimura, Kazuhiko

    1993-01-01

    Tl-201 myocardial scintigraphy was performed in 130 patients with chronic obstructive pulmonary disease (COPD) to evaluate right ventricular hypertrophy, and the clinical significance of this method was studied. Tl-201 uptake ratios of the right ventricle, which represents the ratio of total counts of the right ventricle to counts of the administered dose of Tl-201, was higher in COPD, especially in pulmonary emphysema and B type COPD by Burrows classification than in controls. The grade of visualization of the right ventricle by visual assessment (RVV) was marked (+++) in only a few cases and moderate (++) in many cases (more than 80%) in all diseases except bronchial asthma. The incidence of right ventricular hypertrophy by electrocardiogram, right-sided heart failure and marked dyspnea (Hugh-Jones 4·5) were very low in cases with RVV grade ++ and very high in cases with +++. The grade of RVV was related to the severity of pulmonary perfusion impairment, although in diffuse panbronchiolitis the RVV was relatively slight compared with the impairment of perfusion. May parameters of pulmonary function such as %VC, FEV1.0%, RV/TLC, V25, %DLCO, Raw, ΔN 2 and PaO 2 showed abnormal values in patients with RVV grade of (++) or (+++) in all diseases except bronchial asthma. In COPD, Tl-201 myocardial scintigraphy seems to be useful for assessment of right ventricular overloading, and for follow-up observation and differentiation between cor pulmonale and right ventricular hypertrophy secondary to cardiac diseases by observing Tl-201 uptake of the lung and left ventricle. (author)

  18. Alamandine acts via MrgD to induce AMPK/NO activation against Ang II hypertrophy in cardiomyocytes.

    Science.gov (United States)

    de Jesus, Itamar Couto Guedes; Scalzo, Sergio; Alves, Fabiana; Marques, Kariny; Rocha-Resende, Cibele; Bader, Michael; Santos, Robson A Souza; Guatimosim, Silvia

    2018-02-14

    The renin-angiotensin system (RAS) plays a pivotal role in the pathogenesis of cardiovascular diseases. New members of this system have been characterized and shown to have biologically relevant actions. Alamandine and its receptor MrgD are recently identified components of RAS. In the cardiovascular system alamandine actions included vasodilation, antihypertensive and anti-fibrosis effects. Currently, the actions of alamandine on cardiomyocytes are unknown. Here our goal was twofold: (1) to unravel the signaling molecules activated by the alamandine/MrgD axis in cardiomyocytes; (2) to evaluate the ability of this axis to prevent against Angiotensin II (Ang II)-induced hypertrophy. In cardiomyocytes from C57BL/6 mice, alamandine treatment induced an increase in nitric oxide (NO) production, which was blocked by D-Pro 7 -Ang-(1-7), a MrgD antagonist. This NO rise correlated with increased phosphorylation of AMPK. Alamandine induced NO production was preserved in Mas -/- myocytes, and lost in MrgD -/- cells. Binding of fluorescent-labeled alamandine was observed in wild-type cells, but it was dramatically reduced in MrgD -/- myocytes. We also assessed the consequences of prolonged alamandine exposure to cultured neonatal rat cardiomyocytes (NRCMs) treated with Ang II. Treatment of NRCMs with alamandine prevented Ang II-induced hypertrophy. Moreover, antihypertrophic actions of alamandine were mediated via MrgD and NO, since they could be prevented by D-Pro 7 -Ang-(1-7) or inhibitors of NO synthase or AMPK. β-alanine, a MrgD agonist, recapitulated alamandine's cardioprotective effects in cardiomyocytes. Our data show that alamandine via MrgD induces AMPK/NO signaling to counterregulate Ang II induced hypertrophy. These findings highlight the therapeutic potential of the alamandine/MrgD axis in the heart.

  19. Triptolide Upregulates Myocardial Forkhead Helix Transcription Factor p3 Expression and Attenuates Cardiac Hypertrophy

    Science.gov (United States)

    Ding, Yuan-Yuan; Li, Jing-Mei; Guo, Feng-Jie; Liu, Ya; Tong, Yang-Fei; Pan, Xi-Chun; Lu, Xiao-Lan; Ye, Wen; Chen, Xiao-Hong; Zhang, Hai-Gang

    2016-01-01

    The forkhead/winged helix transcription factor (Fox) p3 can regulate the expression of various genes, and it has been reported that the transfer of Foxp3-positive T cells could ameliorate cardiac hypertrophy and fibrosis. Triptolide (TP) can elevate the expression of Foxp3, but its effects on cardiac hypertrophy remain unclear. In the present study, neonatal rat ventricular myocytes (NRVM) were isolated and stimulated with angiotensin II (1 μmol/L) to induce hypertrophic response. The expression of Foxp3 in NRVM was observed by using immunofluorescence assay. Fifty mice were randomly divided into five groups and received vehicle (control), isoproterenol (Iso, 5 mg/kg, s.c.), one of three doses of TP (10, 30, or 90 μg/kg, i.p.) for 14 days, respectively. The pathological morphology changes were observed after Hematoxylin and eosin, lectin and Masson’s trichrome staining. The levels of serum brain natriuretic peptide (BNP) and troponin I were determined by enzyme-linked immunosorbent assay and chemiluminescence, respectively. The mRNA and protein expressions of α- myosin heavy chain (MHC), β-MHC and Foxp3 were determined using real-time PCR and immunohistochemistry, respectively. It was shown that TP (1, 3, 10 μg/L) treatment significantly decreased cell size, mRNA and protein expression of β-MHC, and upregulated Foxp3 expression in NRVM. TP also decreased heart weight index, left ventricular weight index and, improved myocardial injury and fibrosis; and decreased the cross-scetional area of the myocardium, serum cardiac troponin and BNP. Additionally, TP markedly reduced the mRNA and protein expression of myocardial β-MHC and elevated the mRNA and protein expression of α-MHC and Foxp3 in a dose-dependent manner. In conclusion, TP can effectively ameliorate myocardial damage and inhibit cardiac hypertrophy, which is at least partly related to the elevation of Foxp3 expression in cardiomyocytes. PMID:27965581

  20. The impact of non-dipper circadian rhythm of blood pressure on left ventricular hypertrophy in patients with non-dialysis chronic kidney disease.

    Science.gov (United States)

    Che, Xiajing; Mou, Shan; Zhang, Weiming; Zhang, Minfang; Gu, Leyi; Yan, Yucheng; Ying, Hua; Hu, Chunhua; Qian, Jiaqi; Ni, Zhaohui

    2017-04-01

    Objective The aim of this study was to investigate the correlation between non-dipper circadian rhythm of blood pressure (BP) and left ventricular hypertrophy (LVH) in patients with chronic kidney disease (CKD). Methods and results All 257 patients with stage 1 to 5 CKD were enrolled in the study and classified into a CKD1-3 group and a CKD4-5 group according to renal function. The parameters and circadian rhythm of BP were measured by a GE Marquette Tonoport V Eng dynamic sphygmomanometer, and cardiac structure was examined by echocardiography. The incidence of abnormal circadian BP rhythm (non-dipper rhythm) was quite high (75.4% in all enrolled patients and 71.3% in the patients with normal BP levels) in CKD patients and increased with the deterioration of renal function. Changes of cardiac structure such as LVH in patients with non-dipper BP were more distinct than in patients with dipper BP. The development of left ventricular mass index (LVMI) correlated positively with the incidence of non-dipper BP rhythm. Multiple regression analysis showed that 24-h systolic BP (β = 0.417, P circadian rhythm of blood pressure was quite high in CKD patients and increased with the deterioration of renal function. Non-dipper circadian rhythm of BP is closely related with LVMI.

  1. On the origin of pain in patients with stable essential hypertension and asymmetrical myocardial hypertrophy

    International Nuclear Information System (INIS)

    Shkhvatsabaya, I.K.; Yurenev, A.P.; Dubov, P.B.; Ostroumov, E.N.

    1987-01-01

    A study of 230 patients with essential hypertension, stage 2B, asymmetrical myocardial hypertrophy and chest pains has suggested that the pain syndrome, presenting as ''possible angina'', positive functional tests and reduced label accumulation around the ventricular septum may be indicative of coronary insufficiency

  2. Effects of Roselle on arterial pulse pressure and left ventricular hypertrophy in hypertensive patients.

    Science.gov (United States)

    Al-Shafei, Ahmad I; El-Gendy, Ola A

    2013-12-01

    To characterize the effects of regular Roselle ingestion on blood pressure and left ventricular hypertrophy (LVH) in patients with established moderate essential hypertension. This non-randomized quasi-experimental study was conducted in Kafr El-Shaikh, Egypt, for 8 weeks, from September 2012 to November 2012. The effects of a 4-week period of regular Roselle ingestion followed by a 4-week recovery period on systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), and heart rates (HR) was studied in 2 equal, gender- and age-matched groups (n=50 each; average age - 50+/-5 years) of normotensive subjects, and patients with moderate essential hypertension. Electrocardiographic assessments of LVH were also made prior to, and at the end of both treatment and recovery periods. Pulse pressure (PP) significantly fell from baseline values by 10.9% (normotensive group [NG]), 21.2% (hypertensive group [HG]); SBP by 10% (NG), 19.6% (HG); DBP by 9.5% (NG), 18.7% (HG), and HR by 14.6% (NG), 17.1% (HG) by the end of week 4 of treatment. Following treatment cessation, SBP, DBP, PP, and HR returned to pretreatment levels over 4 weeks. Before intervention, none of the normotensive subjects, but 14 hypertensive patients showed LVH. However, Roselle treatment was associated with regression of LVH in 10 patients with only 4 patients showing LVH after 4 weeks of treatment. This became 10 patients 4 weeks after ceasing treatment. These findings empirically suggest favorable cardiovascular effects of Roselle in patients with established moderate essential hypertension.

  3. Comparison of Left Ventricular Hypertrophy by Electrocardiography and Echocardiography in Children Using Analytics Tool.

    Science.gov (United States)

    Tague, Lauren; Wiggs, Justin; Li, Qianxi; McCarter, Robert; Sherwin, Elizabeth; Weinberg, Jacqueline; Sable, Craig

    2018-05-17

    Left ventricular hypertrophy (LVH) is a common finding on pediatric electrocardiography (ECG) leading to many referrals for echocardiography (echo). This study utilizes a novel analytics tool that combines ECG and echo databases to evaluate ECG as a screening tool for LVH. SQL Server 2012 data warehouse incorporated ECG and echo databases for all patients from a single institution from 2006 to 2016. Customized queries identified patients 0-18 years old with LVH on ECG and an echo performed within 24 h. Using data visualization (Tableau) and analytic (Stata 14) software, ECG and echo findings were compared. Of 437,699 encounters, 4637 met inclusion criteria. ECG had high sensitivity (≥ 90%) but poor specificity (43%), and low positive predictive value (< 20%) for echo abnormalities. ECG performed only 11-22% better than chance (AROC = 0.50). 83% of subjects with LVH on ECG had normal left ventricle (LV) structure and size on echo. African-Americans with LVH were least likely to have an abnormal echo. There was a low correlation between V 6 R on ECG and echo-derived Z score of left ventricle diastolic diameter (r = 0.14) and LV mass index (r = 0.24). The data analytics client was able to mine a database of ECG and echo reports, comparing LVH by ECG and LV measurements and qualitative findings by echo, identifying an abnormal LV by echo in only 17% of cases with LVH on ECG. This novel tool is useful for rapid data mining for both clinical and research endeavors.

  4. A Systems Biology Approach to Investigating Sex Differences in Cardiac Hypertrophy.

    Science.gov (United States)

    Harrington, Josephine; Fillmore, Natasha; Gao, Shouguo; Yang, Yanqin; Zhang, Xue; Liu, Poching; Stoehr, Andrea; Chen, Ye; Springer, Danielle; Zhu, Jun; Wang, Xujing; Murphy, Elizabeth

    2017-08-19

    Heart failure preceded by hypertrophy is a leading cause of death, and sex differences in hypertrophy are well known, although the basis for these sex differences is poorly understood. This study used a systems biology approach to investigate mechanisms underlying sex differences in cardiac hypertrophy. Male and female mice were treated for 2 and 3 weeks with angiotensin II to induce hypertrophy. Sex differences in cardiac hypertrophy were apparent after 3 weeks of treatment. RNA sequencing was performed on hearts, and sex differences in mRNA expression at baseline and following hypertrophy were observed, as well as within-sex differences between baseline and hypertrophy. Sex differences in mRNA were substantial at baseline and reduced somewhat with hypertrophy, as the mRNA differences induced by hypertrophy tended to overwhelm the sex differences. We performed an integrative analysis to identify mRNA networks that were differentially regulated in the 2 sexes by hypertrophy and obtained a network centered on PPARα (peroxisome proliferator-activated receptor α). Mouse experiments further showed that acute inhibition of PPARα blocked sex differences in the development of hypertrophy. The data in this study suggest that PPARα is involved in the sex-dimorphic regulation of cardiac hypertrophy. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  5. Relationship Between 24-Hour Ambulatory Central Systolic Blood Pressure and Left Ventricular Mass: A Prospective Multicenter Study.

    Science.gov (United States)

    Weber, Thomas; Wassertheurer, Siegfried; Schmidt-Trucksäss, Arno; Rodilla, Enrique; Ablasser, Cornelia; Jankowski, Piotr; Lorenza Muiesan, Maria; Giannattasio, Cristina; Mang, Claudia; Wilkinson, Ian; Kellermair, Jörg; Hametner, Bernhard; Pascual, Jose Maria; Zweiker, Robert; Czarnecka, Danuta; Paini, Anna; Salvetti, Massimo; Maloberti, Alessandro; McEniery, Carmel

    2017-12-01

    We investigated the relationship between left ventricular mass and brachial office as well as brachial and central ambulatory systolic blood pressure in 7 European centers. Central systolic pressure was measured with a validated oscillometric device, using a transfer function, and mean/diastolic pressure calibration. M-mode images were obtained by echocardiography, and left ventricular mass was determined by one single reader blinded to blood pressure. We studied 289 participants (137 women) free from antihypertensive drugs (mean age: 50.8 years). Mean office blood pressure was 145/88 mm Hg and mean brachial and central ambulatory systolic pressures were 127 and 128 mm Hg, respectively. Mean left ventricular mass was 93.3 kg/m 2 , and 25.6% had left ventricular hypertrophy. The correlation coefficient between left ventricular mass and brachial office, brachial ambulatory, and central ambulatory systolic pressure was 0.29, 0.41, and 0.47, respectively ( P =0.003 for comparison between brachial office and central ambulatory systolic pressure and 0.32 for comparison between brachial and central ambulatory systolic pressure). The results were consistent for men and women, and young and old participants. The areas under the curve for prediction of left ventricular hypertrophy were 0.618, 0.635, and 0.666 for brachial office, brachial, and central ambulatory systolic pressure, respectively ( P =0.03 for comparison between brachial and central ambulatory systolic pressure). In younger participants, central ambulatory systolic pressure was superior to both other measurements. Central ambulatory systolic pressure, measured with an oscillometric cuff, shows a strong trend toward a closer association with left ventricular mass and hypertrophy than brachial office/ambulatory systolic pressure. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01278732. © 2017 American Heart Association, Inc.

  6. ω-3 Polyunsaturated fatty acids prevent pressure overload-induced ventricular dilation and decrease in mitochondrial enzymes despite no change in adiponectin

    Directory of Open Access Journals (Sweden)

    O'Shea Karen M

    2010-09-01

    Full Text Available Abstract Background Pathological left ventricular (LV hypertrophy frequently progresses to dilated heart failure with suppressed mitochondrial oxidative capacity. Dietary marine ω-3 polyunsaturated fatty acids (ω-3 PUFA up-regulate adiponectin and prevent LV dilation in rats subjected to pressure overload. This study 1 assessed the effects of ω-3 PUFA on LV dilation and down-regulation of mitochondrial enzymes in response to pressure overload; and 2 evaluated the role of adiponectin in mediating the effects of ω-3 PUFA in heart. Methods Wild type (WT and adiponectin-/- mice underwent transverse aortic constriction (TAC and were fed standard chow ± ω-3 PUFA for 6 weeks. At 6 weeks, echocardiography was performed to assess LV function, mice were terminated, and mitochondrial enzyme activities were evaluated. Results TAC induced similar pathological LV hypertrophy compared to sham mice in both strains on both diets. In WT mice TAC increased LV systolic and diastolic volumes and reduced mitochondrial enzyme activities, which were attenuated by ω-3 PUFA without increasing adiponectin. In contrast, adiponectin-/- mice displayed no increase in LV end diastolic and systolic volumes or decrease in mitochondrial enzymes with TAC, and did not respond to ω-3 PUFA. Conclusion These findings suggest ω-3 PUFA attenuates cardiac pathology in response to pressure overload independent of an elevation in adiponectin.

  7. MRI and Neuropsychological Correlates in African Americans with Hypertension and left vEntricular Hypertrophy.

    Science.gov (United States)

    Waldron-Perrine, B; Kisser, J E; Brody, A; Haacke, E M; Dawood, R; Millis, S; Levy, P

    2018-04-17

    African Americans (AA) are at high risk for hypertension (HTN) and poor blood pressure (BP) control. Persistently elevated BP contributes to cardiovascular morbidity. White matter hyperintensities (WMH) are a definable magnetic resonance imaging (MRI) marker of cerebrovascular injury linked to impairments in higher level thinking (i.e., executive functions), memory formation and speed of perceptual-motor processing. This sub-investigation evaluated neuropsychological functioning in association with WMH on brain MRIs in 23 otherwise healthy hypertensive AAs participating in an NIH-funded study of the effects of Vitamin D on BP and cardiac remodeling in AA patients 30-74 years of age with HTN and left ventricular hypertrophy. Neuropsychological assessment included psychomotor processing speed [(Symbol Digit Modality Test (SDMT) and Trail Making Test], executive functioning (Controlled Oral Word Association Test and Trail Making Test Part B), memory (Rey Auditory Verbal Learning Test), and fine motor functioning (Finger Tapping). Significant correlations (p< .05) were found between volume of periventricular lesions and Trails A (r = .51) and dominant hand finger tapping speed (r = -.69) and between subcortical lesion volume and Trails A (r = .60), both dominant (r = -.62) and non-dominant hand finger tapping speed (r = -.76) and oral SDMT (r = -.60); higher lesion volumes correlated to worse neuropsychological performance. Psychomotor tests including the Trail Making Test and finger tapping speed are sensitive indicators of subclinical deficits in mental processing speed and could serve as early markers of deep subcortical cerebrovascular injury in otherwise-healthy individuals with uncontrolled chronic HTN.

  8. R Wave in aVL Lead is a Robust Index of Left Ventricular Hypertrophy: A Cardiac MRI Study.

    Science.gov (United States)

    Courand, Pierre-Yves; Grandjean, Adrien; Charles, Paul; Paget, Vinciane; Khettab, Fouad; Bricca, Giampiero; Boussel, Loïc; Lantelme, Pierre; Harbaoui, Brahim

    2015-08-01

    In patients free from overt cardiac disease, R wave in aVL lead (RaVL) is strongly correlated with left ventricular mass index (LVMI) assessed by transthoracic echocardiography. The aim of the present study was to extend this finding to other settings (cardiomyopathy or conduction disorders), by comparing ECG criteria of left ventricular hypertrophy (LVH) to cardiac MRI (CMR). In 501 patients, CMR and ECG were performed within a median-period of 5 days. CMR LVH cut-offs used were 83 g/m2 in men and 67 g/m2 in women. RaVL was independently correlated with LVMI in patients with or without myocardial infarction (MI) (N = 300 and N = 201, respectively). SV3 was independently correlated with LVMI and LV enlargement only in patients without MI. In the whole cohort, RaVL had area under receiver-operating characteristic curve of 0.729 (specificity 98.3%, sensitivity 19.6%, optimal cut-off 1.1 mV). The performance of RaVL was remarkable in women, in Caucasians, and in the presence of right bundle branch block. It decreased in case of MI. Overall, it is proposed that below 0.5 mV and above 1.0 mV, RaVL is sufficient to exclude or establish LVH. Between 0.5 and 1 mV, composite indices (Cornell voltage or product) should be used. Using this algorithm allowed classifying appropriately 85% of the patients. Our results showed that RaVL is a good index of LVH with a univocal threshold of 1.0 mV in various clinical conditions. SV3 may be combined to RaVL in some conditions, namely LV enlargement to increase its performance. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. Left ventricular structural and functional characteristics in Cushing's syndrome.

    Science.gov (United States)

    Muiesan, Maria Lorenza; Lupia, Mario; Salvetti, Massimo; Grigoletto, Consuelo; Sonino, Nicoletta; Boscaro, Marco; Rosei, Enrico Agabiti; Mantero, Franco; Fallo, Francesco

    2003-06-18

    This study was designed to evaluate left ventricular (LV) anatomy and function in patients with Cushing's syndrome. A high prevalence of LV hypertrophy and concentric remodeling has been reported in Cushing's syndrome, although no data have been reported on LV systolic and diastolic function. Forty-two consecutive patients with Cushing's syndrome and 42 control subjects, matched for age, gender, and blood pressure, were studied. Left ventricular mass index (LVMI) and relative wall thickness (RWT) were measured by echocardiography, endocardial and midwall fractional shortening (FS) were assessed, and diastolic filling was measured by Doppler transmitral flow. The RWT was significantly greater in Cushing patients than in controls. Left ventricular hypertrophy and concentric remodeling were observed in 10 and 26 patients with Cushing's syndrome, respectively. In Cushing patients, midwall FS was significantly reduced compared with controls (16.2 +/- 3% vs. 21 +/- 4.5%, p = 0.01). The ratio of transmitral E and A flow velocities was reduced and E deceleration time was prolonged in Cushing patients compared with controls (p = 0.03 and p < 0.001, respectively). In patients with Cushing's syndrome, cardiac structural changes are associated with reduced midwall systolic performance and with diastolic dysfunction that may contribute to the high risk of cardiovascular events observed in these patients.

  10. Electrocardiographic Measures of Left Ventricular Hypertrophy in the Antihypertensive and Lipid-Lowering to Prevent Heart Attack Trial

    Science.gov (United States)

    Ernst, Michael E.; Davis, Barry R.; Soliman, Elsayed Z.; Prineas, Ronald J.; Okin, Peter M.; Ghosh, Alokananda; Cushman, William C.; Einhorn, Paula T.; Oparil, Suzanne; Grimm, Richard H.

    2016-01-01

    Left ventricular hypertrophy (LVH) predicts cardiovascular risk in hypertensive patients. We analyzed baseline/follow-up ECGs in 26,376 ALLHAT participants randomized to amlodipine (A), lisinopril (L), or chlorthalidone (C). Prevalent/incident LVH were examined using continuous and categorical classifications of Cornell voltage. At 2- and 4-years, prevalence of LVH in the C-group (5.57%; 6.14%) was not statistically different from A-group (2-years: 5.47%; p=0.806, 4-years: 6.54%; p=0.857), or L-group (2-years: 5.64%; p=0.857, 4-years: 6.50%; p=0.430). Incident LVH followed similarly, with no difference at 2-years for C (2.99%) compared to A (2.57%; p=0.173) or L (3.16%; p=0.605), and at 4-years (C=3.52%, A=3.29%, L=3.71%; p=0.521 C vs A, p=0.618 C vs L). Mean Cornell voltage decreased comparably across treatment groups (Δ baseline, 2-years = +3 to -27 μV, ANOVA p=0.8612; 4-years = +10 to -17 μV, ANOVA p=0.9692). We conclude that risk reductions associated with C treatment in secondary endpoints of ALLHAT cannot be attributed to differential improvements in ECG LVH. PMID:27938852

  11. Basal cardiomyopathy develops in rabbits with ventricular tachyarrhythmias induced by a single injection of adrenaline.

    Science.gov (United States)

    Ashida, Terunao; Takato, Tetsuya; Matsuzaki, Gen; Seko, Yoshinori; Fujii, Jun; Kawai, Sachio

    2014-01-01

    We have recently demonstrated that basal cardiomyopathy develops in rabbits with ventricular tachyarrhythmias that have been induced by electrical stimulation of the cervical vagus. This study investigated whether similar basal cardiomyopathy would develop in rabbits with ventricular tachyarrhythmias induced by a single injection of adrenaline. Adrenaline was intravenously infused for 10-360 seconds in anesthetized rabbits. Colloidal carbon was injected after adrenaline infusion. Wall movement velocity of the left ventricular base was assessed by tissue Doppler echocardiography. Animals were killed either 1 week or 3-4 weeks later. Pathological lesions were identified by deposits of carbon particles. Animals were divided into two groups according to the infused dose of adrenaline. The small-dose group (group S, n = 15) received 1-10 μg and the large-dose group (group L, n = 23) received 15-60 μg of adrenaline. Adrenaline infusion induced premature ventricular contractions followed by monomorphic ventricular tachycardias in 22 of 23 animals in group L, but in only 1 of 15 animals in group S. Wall movement velocity of the left ventricular base decreased just after adrenaline infusion, remained low after 1 week, and recovered to near-baseline levels after 3-4 weeks in group L. Unique cardiac lesions identified by deposits of carbon particles were frequently observed on the left ventricular basal portion, almost always associated with the mitral valve and papillary muscles, but were never observed in the apical area. Lesions involving all areas of the left ventricular basal portion were observed in 22 of 23 animals in group L, but in only 2 of 15 animals in group S. Basal cardiomyopathy developed in rabbits with ventricular tachycardias induced by a single injection of adrenaline.

  12. Aerobic exercise protects against pressure overload-induced cardiac dysfunction and hypertrophy via β3-AR-nNOS-NO activation

    Science.gov (United States)

    Li, Wenju; Li, Xiaoli; Zheng, Qiangsun; Niu, Xiaolin

    2017-01-01

    Aerobic exercise confers sustainable protection against cardiac hypertrophy and heart failure (HF). Nitric oxide synthase (NOS) and nitric oxide (NO) are known to play an important role in exercise-mediated cardioprotection, but the mechanism of NOS/NO stimulation during exercise remains unclear. The aim of this study is to determine the role of β3-adrenergic receptors (β3-ARs), NOS activation, and NO metabolites (nitrite and nitrosothiols) in the sustained cardioprotective effects of aerobic exercise. An HF model was constructed by transverse aortic constriction (TAC). Animals were treated with either moderate aerobic exercise by swimming for 9 weeks and/or the β3-AR-specific inhibitor SR59230A at 0.1 mg/kg/hour one day after TAC operation. Myocardial fibrosis, myocyte size, plasma catecholamine (CA) level, cardiac function and geometry were assessed using Masson’s trichrome staining, FITC-labeled wheat germ agglutinin staining, enzyme-linked immuno sorbent assay (ELISA) and echocardiography, respectively. Western blot analysis was performed to elucidate the expression of target proteins. The concentration of myocardial NO production was evaluated using the nitrate reductase method. Myocardial oxidative stress was assessed by detecting the concentration of myocardial super oxidative dismutase (SOD), malonyldialdehyde (MDA), and reactive oxygen species (ROS). Aerobic exercise training improved dilated left ventricular function and partially attenuated the degree of cardiac hypertrophy and fibrosis in TAC mice. Moreover, the increased expression of β3-AR, activation of neuronal NOS (nNOS), and production of NO were detected after aerobic exercise training in TAC mice. However, selective inhibition of β3-AR by SR59230A abolished the upregulation and activation of nNOS induced NO production. Furthermore, aerobic exercise training decreased the myocardial ROS and MDA contents and increased myocardial levels of SOD; both effects were partially attenuated by SR

  13. Aerobic exercise protects against pressure overload-induced cardiac dysfunction and hypertrophy via β3-AR-nNOS-NO activation.

    Science.gov (United States)

    Wang, Bin; Xu, Ming; Li, Wenju; Li, Xiaoli; Zheng, Qiangsun; Niu, Xiaolin

    2017-01-01

    Aerobic exercise confers sustainable protection against cardiac hypertrophy and heart failure (HF). Nitric oxide synthase (NOS) and nitric oxide (NO) are known to play an important role in exercise-mediated cardioprotection, but the mechanism of NOS/NO stimulation during exercise remains unclear. The aim of this study is to determine the role of β3-adrenergic receptors (β3-ARs), NOS activation, and NO metabolites (nitrite and nitrosothiols) in the sustained cardioprotective effects of aerobic exercise. An HF model was constructed by transverse aortic constriction (TAC). Animals were treated with either moderate aerobic exercise by swimming for 9 weeks and/or the β3-AR-specific inhibitor SR59230A at 0.1 mg/kg/hour one day after TAC operation. Myocardial fibrosis, myocyte size, plasma catecholamine (CA) level, cardiac function and geometry were assessed using Masson's trichrome staining, FITC-labeled wheat germ agglutinin staining, enzyme-linked immuno sorbent assay (ELISA) and echocardiography, respectively. Western blot analysis was performed to elucidate the expression of target proteins. The concentration of myocardial NO production was evaluated using the nitrate reductase method. Myocardial oxidative stress was assessed by detecting the concentration of myocardial super oxidative dismutase (SOD), malonyldialdehyde (MDA), and reactive oxygen species (ROS). Aerobic exercise training improved dilated left ventricular function and partially attenuated the degree of cardiac hypertrophy and fibrosis in TAC mice. Moreover, the increased expression of β3-AR, activation of neuronal NOS (nNOS), and production of NO were detected after aerobic exercise training in TAC mice. However, selective inhibition of β3-AR by SR59230A abolished the upregulation and activation of nNOS induced NO production. Furthermore, aerobic exercise training decreased the myocardial ROS and MDA contents and increased myocardial levels of SOD; both effects were partially attenuated by SR59230

  14. Desmodium gangeticum root extract attenuates isoproterenol-induced cardiac hypertrophic growth in rats.

    OpenAIRE

    Divya Hitler; Parthasarathy Arumugam; Mathivanan Narayanasamy; Elangovan Vellaichamy

    2014-01-01

    Context: Desmodium gangeticum (L) DC (Fabaceae; DG), a medicinal plant that grows in tropical habitats, is widely used to treat various ailments including digestive and inflammatory disorders. Aims: To investigate the possible cardioprotective activity of a DG root extract against isoproterenol (ISO)-induced left ventricular cardiac hypertrophy (LVH) in adult Wistar rats. Methods: Daily intraperitoneal administration of ISO (10 mg/kg body weight, single injection) for 7 days induced LVH...

  15. Acute post-exercise myofibrillar protein synthesis is not correlated with resistance training-induced muscle hypertrophy in young men.

    Science.gov (United States)

    Mitchell, Cameron J; Churchward-Venne, Tyler A; Parise, Gianni; Bellamy, Leeann; Baker, Steven K; Smith, Kenneth; Atherton, Philip J; Phillips, Stuart M

    2014-01-01

    Muscle hypertrophy following resistance training (RT) involves activation of myofibrillar protein synthesis (MPS) to expand the myofibrillar protein pool. The degree of hypertrophy following RT is, however, highly variable and thus we sought to determine the relationship between the acute activation of MPS and RT-induced hypertrophy. We measured MPS and signalling protein activation after the first session of resistance exercise (RE) in untrained men (n = 23) and then examined the relation between MPS with magnetic resonance image determined hypertrophy. To measure MPS, young men (24±1 yr; body mass index  = 26.4±0.9 kg•m²) underwent a primed constant infusion of L-[ring-¹³C₆] phenylalanine to measure MPS at rest, and acutely following their first bout of RE prior to 16 wk of RT. Rates of MPS were increased 235±38% (Pmuscle volume and acute rates of MPS measured over 1-3 h (r = 0.02), 3-6 h (r = 0.16) or the aggregate 1-6 h post-exercise period (r = 0.10). Hypertrophy after chronic RT was correlated (r = 0.42, P = 0.05) with phosphorylation of 4E-BP1(Thr37/46) at 1 hour post RE. We conclude that acute measures of MPS following an initial exposure to RE in novices are not correlated with muscle hypertrophy following chronic RT.

  16. TISSUE DOPPLER IMAGING OF LONGITUDINAL MOVEMENT OF A FIBROUS RING OF MITRAL VALVE DURING ISOVOLUMIC PERIODS IN LEFT VENTRICULAR HYPERTROPHY

    Directory of Open Access Journals (Sweden)

    B. Amarjagal

    2007-01-01

    Full Text Available Aim. To study change of rate and duration indicators of longitudinal movement of a fibrous ring of mitral valve (MFR during isovolumic contraction (IVC and relaxation (IVR in hypertensive patients with various degree of a left ventricular hypertrophy (LVH.Material and methods. 80 hypertensive patients with moderate LVH (n=40 and severe LVH (n=40 are examined. The control group was presented by 30 healthy volunteers. Transthoracic echocardiography and Tissue Doppler imaging has been performed with ultrasonic tomograph “HDI 5000” (Philips.Results. Increase in LVH (Smm and Е/Еmm associates with reduction in systolic velocity of movement of medial MFR (Smm. There is direct relation with duration of IVC-negative and IVR-positive components and myocardium mass index. Maximal velocity of IVC-positive component increases and maximal velocity of IVR-negative component decreases when LVH is growing.Conclusion. Velocities curves of IVC and IVR were bi-phase both in healthy persons and in hypertensive patients with LVH. Velocity and duration of positive and negative components of IVC and IVR depended on LVH degree.

  17. TISSUE DOPPLER IMAGING OF LONGITUDINAL MOVEMENT OF A FIBROUS RING OF MITRAL VALVE DURING ISOVOLUMIC PERIODS IN LEFT VENTRICULAR HYPERTROPHY

    Directory of Open Access Journals (Sweden)

    B. Amarjagal

    2015-12-01

    Full Text Available Aim. To study change of rate and duration indicators of longitudinal movement of a fibrous ring of mitral valve (MFR during isovolumic contraction (IVC and relaxation (IVR in hypertensive patients with various degree of a left ventricular hypertrophy (LVH.Material and methods. 80 hypertensive patients with moderate LVH (n=40 and severe LVH (n=40 are examined. The control group was presented by 30 healthy volunteers. Transthoracic echocardiography and Tissue Doppler imaging has been performed with ultrasonic tomograph “HDI 5000” (Philips.Results. Increase in LVH (Smm and Е/Еmm associates with reduction in systolic velocity of movement of medial MFR (Smm. There is direct relation with duration of IVC-negative and IVR-positive components and myocardium mass index. Maximal velocity of IVC-positive component increases and maximal velocity of IVR-negative component decreases when LVH is growing.Conclusion. Velocities curves of IVC and IVR were bi-phase both in healthy persons and in hypertensive patients with LVH. Velocity and duration of positive and negative components of IVC and IVR depended on LVH degree.

  18. Myocardial gene expression of microRNA-133a and myosin heavy and light chains, in conjunction with clinical parameters, predict regression of left ventricular hypertrophy after valve replacement in patients with aortic stenosis.

    Science.gov (United States)

    Villar, Ana V; Merino, David; Wenner, Mareike; Llano, Miguel; Cobo, Manuel; Montalvo, Cecilia; García, Raquel; Martín-Durán, Rafael; Hurlé, Juan M; Hurlé, María A; Nistal, J Francisco

    2011-07-01

    Left ventricular (LV) reverse remodelling after valve replacement in aortic stenosis (AS) has been classically linked to the hydraulic performance of the replacement device, but myocardial status at the time of surgery has received little attention. To establish predictors of LV mass (LVM) regression 1 year after valve replacement in a surgical cohort of patients with AS based on preoperative clinical and echocardiographic parameters and the myocardial gene expression profile at surgery. Transcript levels of remodelling-related proteins and regulators were determined in LV intraoperative biopsies from 46 patients with AS by RT-PCR. Using multiple linear regression analysis, an equation was developed (adjusted R²=0.73; pregression analysis identified microRNA-133a as a significant positive predictor of LVM normalisation, whereas β-myosin heavy chain and BMI constituted negative predictors. Hypertrophy regression 1 year after pressure overload release is related to the preoperative myocardial expression of remodelling-related genes, in conjunction with the patient's clinical background. In this scenario, miR-133 emerges as a key element of the reverse remodelling process. Postoperative improvement of valve haemodynamics does not predict the degree of hypertrophy regression or LVM normalisation. These results led us to reconsider the current reverse remodelling paradigm and (1) to include criteria of hypertrophy reversibility in the decision algorithm used to decide timing for the operation; and (2) to modify other prevailing factors (overweight, diabetes, etc) known to maintain LV hypertrophy.

  19. Influence of microalbuminuria on left ventricular geometry and function in hypertensive patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Picca, Maurizio; Agozzino, Francesco; Pelosi, Giancarlo

    2003-01-01

    An increased urinary albumin excretion (UAE) is associated with an augmented risk of cardiovascular disease in diabetic patients and in non-diabetic subjects. Left ventricular hypertrophy has been demonstrated to be a powerful predictor of cardiovascular morbidity and mortality in arterial hypertension and when the ventricular geometry is concentric the relation is even stronger. This echocardiographic and Doppler study was designed to evaluate the influence of microalbuminuria on the left ventricular geometry and function in hypertensive patients with type 2 diabetes melitus. Forty-two patients (16 males, 26 females, mean age 59.6 +/- 6.7 years) with mild-to-moderate essential hypertension and type 2 diabetes mellitus were enrolled in the study. Twenty-one patients had an elevated UAE (group 1) and 21 a normal UAE (group 2). M-mode (under two-dimensional control) and Doppler echocardiography were performed after a 4-week washout period off antihypertensive therapy. The left ventricular mass index was found to be greater than the partition value of 51 g/m2.7 in both groups but was significantly higher (p diabetes mellitus, an elevated UAE is associated with an increased left ventricular mass index, a higher prevalence of a concentric left ventricular hypertrophy pattern, a depressed midwall systolic performance and a markedly impaired diastolic function...

  20. Chronic high fat diet induces cardiac hypertrophy and fibrosis in mice.

    Science.gov (United States)

    Wang, Zhi; Li, Liaoliao; Zhao, Huijuan; Peng, Shuling; Zuo, Zhiyi

    2015-08-01

    Obesity can cause pathological changes in organs. We determined the effects of chronic high fat diet (HFD) and intermittent fasting, a paradigm providing organ protection, on mouse heart. Seven-week old CD1 male mice were randomly assigned to control, HFD and intermittent fasting groups. Control mice had free access to regular diet (RD). RD was provided every other day to mice in the intermittent fasting group. Mice in HFD group had free access to HFD. Their left ventricles were harvested 11 months after they had been on these diet regimens. HFD increased cardiomyocyte cross-section area and fibrosis. HFD decreased active caspase 3, an apoptosis marker, and the ratio of microtubule-associated protein 1A/1B-light chain 3 (LC3) II/LC3I, an autophagy marker. HFD increased the phospho-glycogen synthase kinase-3β (GSK-3β) at Ser9, a sign of GSK-3β inhibition. Nuclear GATA binding protein 4 and yes-associated protein, two GSK-3β targeting transcription factors that can induce hypertrophy-related gene expression, were increased in HFD-fed mice. Mice on intermittent fasting did not have these changes except for the increased active caspase 3 and decreased ratio of LC3II/LC3I. These results suggest that chronic HFD induces myocardial hypertrophy and fibrosis, which may be mediated by GSK-3β inhibition. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. High-intensity interval training, but not continuous training, reverses right ventricular hypertrophy and dysfunction in a rat model of pulmonary hypertension.

    Science.gov (United States)

    Brown, Mary Beth; Neves, Evandro; Long, Gary; Graber, Jeremy; Gladish, Brett; Wiseman, Andrew; Owens, Matthew; Fisher, Amanda J; Presson, Robert G; Petrache, Irina; Kline, Jeffrey; Lahm, Tim

    2017-02-01

    Exercise is beneficial in pulmonary arterial hypertension (PAH), although studies to date indicate little effect on the elevated pulmonary pressures or maladaptive right ventricle (RV) hypertrophy associated with the disease. For chronic left ventricle failure, high-intensity interval training (HIIT) promotes greater endothelial stimulation and superior benefit than customary continuous exercise training (CExT); however, HIIT has not been tested for PAH. Therefore, here we investigated acute and chronic responses to HIIT vs. CExT in a rat model of monocrotaline (MCT)-induced mild PAH. Six weeks of treadmill training (5 times/wk) were performed, as either 30 min HIIT or 60 min low-intensity CExT. To characterize acute hemodynamic responses to the two approaches, novel recordings of simultaneous pulmonary and systemic pressures during running were obtained at pre- and 2, 4, 6, and 8 wk post-MCT using long-term implantable telemetry. MCT-induced decrement in maximal aerobic capacity was ameliorated by both HIIT and CExT, with less pronounced pulmonary vascular remodeling and no increase in RV inflammation or apoptosis observed. Most importantly, only HIIT lowered RV systolic pressure, RV hypertrophy, and total pulmonary resistance, and prompted higher cardiac index that was complemented by a RV increase in the positive inotrope apelin and reduced fibrosis. HIIT prompted a markedly pulsatile pulmonary pressure during running and was associated with greater lung endothelial nitric oxide synthase after 6 wk. We conclude that HIIT may be superior to CExT for improving hemodynamics and maladaptive RV hypertrophy in PAH. HIIT's superior outcomes may be explained by more favorable pulmonary vascular endothelial adaptation to the pulsatile HIIT stimulus.

  2. Pregestational type 2 diabetes mellitus induces cardiac hypertrophy in the murine embryo through cardiac remodeling and fibrosis.

    Science.gov (United States)

    Lin, Xue; Yang, Penghua; Reece, E Albert; Yang, Peixin

    2017-08-01

    Cardiac hypertrophy is highly prevalent in patients with type 2 diabetes mellitus. Experimental evidence has implied that pregnant women with type 2 diabetes mellitus and their children are at an increased risk of cardiovascular diseases. Our previous mouse model study revealed that maternal type 2 diabetes mellitus induces structural heart defects in their offspring. This study aims to determine whether maternal type 2 diabetes mellitus induces embryonic heart hypertrophy in a murine model of diabetic embryopathy. The type 2 diabetes mellitus embryopathy model was established by feeding 4-week-old female C57BL/6J mice with a high-fat diet for 15 weeks. Cardiac hypertrophy in embryos at embryonic day 17.5 was characterized by measuring heart size and thickness of the right and left ventricle walls and the interventricular septum, as well as the expression of β-myosin heavy chain, atrial natriuretic peptide, insulin-like growth factor-1, desmin, and adrenomedullin. Cardiac remodeling was determined by collagen synthesis and fibronectin synthesis. Fibrosis was evaluated by Masson staining and determining the expression of connective tissue growth factor, osteopontin, and galectin-3 genes. Cell apoptosis also was measured in the developing heart. The thicknesses of the left ventricle walls and the interventricular septum of embryonic hearts exposed to maternal diabetes were significantly thicker than those in the nondiabetic group. Maternal diabetes significantly increased β-myosin heavy chain, atrial natriuretic peptide, insulin-like growth factor-1, and desmin expression, but decreased expression of adrenomedullin. Moreover, collagen synthesis was significantly elevated, whereas fibronectin synthesis was suppressed, in embryonic hearts from diabetic dams, suggesting that cardiac remodeling is a contributing factor to cardiac hypertrophy. The cardiac fibrosis marker, galectin-3, was induced by maternal diabetes. Furthermore, maternal type 2 diabetes mellitus

  3. Application of Fourier Analysis to the ventricular volume curve in a digital system using radioisotopic vetricylography. Study of the diastolic function

    International Nuclear Information System (INIS)

    Ricke, F.; Gonzalez, P.; Pruzzo, R.; Nagel, J.

    1987-01-01

    To assess diastolic and systolic ventricular function, a computerized method was developed using Fourier analysis on left ventricular time activity curves. The ventricular raw curve obtained from radionuclide gate blood pool imaging was substituted by a four harmonics curve. Valuable parameters were then calculated specially peak ejection rate, filling fraction and peak filling rate, which allowed clear-cut differentiation normal subjects from patients with left ventricular hypertrophy. (author)

  4. Quantitative thallium-201 myocardial imaging in assessing right ventricular pressure in patients with congenital heart defects

    International Nuclear Information System (INIS)

    Rabinovitch, M.; Fischer, K.C.; Treves, S.

    1981-01-01

    Thallium-201 myocardial scintigraphy was performed in patients with congenital heart defects to determine whether, by quantification of right ventricular isotope uptake, one could assess the degree of right ventricular hypertrophy and so predict the level of right ventricular pressure. It is shown that quantitative analysis of myocardial imaging with thallium-201 is of use clinically in patients with congenital heart defects, in assessing the severity of pulmonary stenosis or the presence of pulmonary artery hypertension. (author)

  5. Clinical evaluation of left ventricular wall thickness by combined technique with gated planer 201Tl image and gated cardiac pool image

    International Nuclear Information System (INIS)

    Nakai, Kenji; Katsuragawa, Shigehiko; Takahashi, Tsuneo; Matsushita, Kazuo; Kawamura, Akiyoshi

    1983-01-01

    To evaluate the left ventricular (LV) wall thickness, combined technique with gated planer 201-Thallium image and gated cardiac pool image was applied to 6 patients with hypertrophic cardiomyopathy (HCM) and 4 patients with secondary hypertrophy due to hypertension (HHD) proven by electrocardiography and ultrasonic-echocardiography. Scintigraphic pattern of hypertrophy on reconstructed planer 201 Tl image showed diffuse or asymmetrical apical hypertrophy in HHD, asymmetrical septal hypertrophy in HCM. It was very interesting that abnormal perfusion was shown in 201 Tl image, despite symmetrical hypertrophy in echocardiography. This techniques provided useful information for evaluating the LV wall thickness and cardiac performance. (author)

  6. Importance of leptin signaling and signal transducer and activator of transcription-3 activation in mediating the cardiac hypertrophy associated with obesity.

    Science.gov (United States)

    Leifheit-Nestler, Maren; Wagner, Nana-Maria; Gogiraju, Rajinikanth; Didié, Michael; Konstantinides, Stavros; Hasenfuss, Gerd; Schäfer, Katrin

    2013-07-11

    The adipokine leptin and its receptor are expressed in the heart, and leptin has been shown to promote cardiomyocyte hypertrophy in vitro. Obesity is associated with hyperleptinemia and hypothalamic leptin resistance as well as an increased risk to develop cardiac hypertrophy and heart failure. However, the role of cardiac leptin signaling in mediating the cardiomyopathy associated with increased body weight is unclear, in particular, whether it develops subsequently to cardiac leptin resistance or overactivation of hypertrophic signaling pathways via elevated leptin levels. The cardiac phenotype of high-fat diet (HFD)-induced obese wildtype (WT) mice was examined and compared to age-matched genetically obese leptin receptor (LepR)-deficient (LepRdb/db) or lean WT mice. To study the role of leptin-mediated STAT3 activation during obesity-induced cardiac remodeling, mice in which tyrosine residue 1138 within LepR had been replaced with a serine (LepRS1138) were also analyzed. Obesity was associated with hyperleptinemia and elevated cardiac leptin expression in both diet-induced and genetically obese mice. Enhanced LepR and STAT3 phosphorylation levels were detected in hearts of obese WT mice, but not in those with LepR mutations. Moreover, exogenous leptin continued to induce cardiac STAT3 activation in diet-induced obese mice. Although echocardiography revealed signs of cardiac hypertrophy in all obese mice, the increase in left ventricular (LV) mass and diameter was significantly more pronounced in LepRS1138 animals. LepRS1138 mice also exhibited an increased activation of signaling proteins downstream of LepR, including Jak2 (1.8-fold), Src kinase (1.7-fold), protein kinase B (1.3-fold) or C (1.6-fold). Histological analysis of hearts revealed that the inability of leptin to activate STAT3 in LepRdb/db and LepRS1138 mice was associated with reduced cardiac angiogenesis as well as increased apoptosis and fibrosis. Our findings suggest that hearts from obese mice

  7. MicroRNA-1 overexpression blunts cardiomyocyte hypertrophy elicited by thyroid hormone.

    Science.gov (United States)

    Diniz, Gabriela Placoná; Lino, Caroline Antunes; Moreno, Camila Rodrigues; Senger, Nathalia; Barreto-Chaves, Maria Luiza Morais

    2017-12-01

    It is well-known that increased thyroid hormone (TH) levels induce cardiomyocyte growth. MicroRNAs (miRNAs) have been identified as key players in cardiomyocyte hypertrophy, which is associated with increased risk of heart failure. In this study, we evaluated the miR-1 expression in TH-induced cardiac hypertrophy, as well as the potential involvement of miR-1 in cardiomyocyte hypertrophy elicited by TH in vitro. The possible role of type 1 angiotensin II receptor (AT1R) in the effect promoted by TH in miR-1 expression was also evaluated. Neonatal rat cardiac myocytes (NRCMs) were treated with T 3 for 24 hr and Wistar rats were subjected to hyperthyroidism for 14 days combined or not with AT1R blocker. Real Time RT-PCR analysis indicated that miR-1 expression was decreased in cardiac hypertrophy in response to TH in vitro and in vivo, and this effect was unchanged by AT1R blocker. In addition, HDAC4, which is target of miR-1, was increased in NRCMs after T 3 treatment. A gain-of-function study revealed that overexpression of miR-1 prevented T 3 -induced cardiomyocyte hypertrophy and reduced HADC4 mRNA levels in NRCMs. In vivo experiments confirmed the downregulation of miR-1 in cardiac tissue from hyperthyroid animals, which was accompanied by increased HDAC4 mRNA levels. In addition, HDAC inhibitor prevented T 3 -induced cardiomyocyte hypertrophy. Our data reveal a new mechanistic insight into cardiomyocyte growth in response to TH, suggesting that miR-1 plays a role in cardiomyocyte hypertrophy induced by TH potentially via targeting HADC4. © 2017 Wiley Periodicals, Inc.

  8. Role of cyclic AMP sensor Epac1 in masseter muscle hypertrophy and myosin heavy chain transition induced by β2-adrenoceptor stimulation.

    Science.gov (United States)

    Ohnuki, Yoshiki; Umeki, Daisuke; Mototani, Yasumasa; Jin, Huiling; Cai, Wenqian; Shiozawa, Kouichi; Suita, Kenji; Saeki, Yasutake; Fujita, Takayuki; Ishikawa, Yoshihiro; Okumura, Satoshi

    2014-12-15

    The predominant isoform of β-adrenoceptor (β-AR) in skeletal muscle is β2-AR and that in the cardiac muscle is β1-AR. We have reported that Epac1 (exchange protein directly activated by cAMP 1), a new protein kinase A-independent cAMP sensor, does not affect cardiac hypertrophy in response to pressure overload or chronic isoproterenol (isoprenaline) infusion. However, the role of Epac1 in skeletal muscle hypertrophy remains poorly understood. We thus examined the effect of disruption of Epac1, the major Epac isoform in skeletal muscle, on masseter muscle hypertrophy induced by chronic β2-AR stimulation with clenbuterol (CB) in Epac1-null mice (Epac1KO). The masseter muscle weight/tibial length ratio was similar in wild-type (WT) and Epac1KO at baseline and was significantly increased in WT after CB infusion, but this increase was suppressed in Epac1KO. CB treatment significantly increased the proportion of myosin heavy chain (MHC) IIb at the expense of that of MHC IId/x in both WT and Epac1KO, indicating that Epac1 did not mediate the CB-induced MHC isoform transition towards the faster isoform. The mechanism of suppression of CB-mediated hypertrophy in Epac1KO is considered to involve decreased activation of Akt signalling. In addition, CB-induced histone deacetylase 4 (HDAC4) phosphorylation on serine 246 mediated by calmodulin kinase II (CaMKII), which plays a role in skeletal muscle hypertrophy, was suppressed in Epac1KO. Our findings suggest that Epac1 plays a role in β2-AR-mediated masseter muscle hypertrophy, probably through activation of both Akt signalling and CaMKII/HDAC4 signalling. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

  9. Accuracy of ECG indices for diagnosis of left ventricular hypertrophy in people >65 years: results from the ActiFE study.

    Science.gov (United States)

    Laszlo, Roman; Kunz, Katia; Dallmeier, Dhayana; Klenk, Jochen; Denkinger, Michael; Koenig, Wolfgang; Rothenbacher, Dietrich; Steinacker, Juergen Michael

    2017-10-01

    The detection of left ventricular hypertrophy (LVH) is still a common objective of electrocardiography (ECG) in clinical practice. The aim of our study was to evaluate the accuracy of LVH ECG indices in people older than 65 recruited from a population-based cohort (ActiFE-Ulm study). In 432 subjects (mean age 76.2 ± 5.5 years, 51% male), left ventricular mass was echocardiographically determined (Devereux formula) and indexed (LVMI) to body surface area. Several LVH ECG indices (Lewis voltage, Gubner-Ungerleider voltage, Sokolow-Lyon voltage/product, Cornell voltage/product) were calculated with the help of resting ECG data and compared with the echocardiographic assessment. Despite echocardiographic signs of LVH [LVMI > 115 (♂) or >95 g/m 2 (♀)] in 47.5% of all subjects, diagnostic performance of all ECG indices was generally low. Magnitude of all LVH-indices was mainly predicted by frontal QRS axis in multivariate linear regression analysis. In comparison with the literature data from younger subjects, average frontal QRS axis turned counterclockwise. Most probably, age-related counterclockwise turn of frontal QRS axis is mainly explanatory for the decreased magnitude of LVH ECG indices and consecutive worse diagnostic performance of these indices in the elderly. ECG indices for detection of LVH have insufficient predictive values in geriatric subjects and should therefore not be used clinically for this purpose. Nevertheless, due to its established relevancy in cardiac risk stratification in this age group, usage of some established ECG indices might keep its significance even in the age of modern cardiac imaging.

  10. Antifibrillatory effects of renal denervation on ventricular fibrillation in a canine model of pacing-induced heart failure.

    Science.gov (United States)

    Luo, Qingzhi; Jin, Qi; Zhang, Ning; Huang, Shangwei; Han, Yanxin; Lin, Changjian; Ling, Tianyou; Chen, Kang; Pan, Wenqi; Wu, Liqun

    2018-01-01

    What is the central question of this study? In the present study, we investigated the effects of renal denervation on the vulnerability to ventricular fibrillation and the ventricular electrical properties in a rapid pacing-induced heart failure canine model. What is the main finding and its importance? Renal denervation significantly attenuated the process of heart failure and improved left ventricular systolic dysfunction, stabilized ventricular electrophysiological properties and decreased the vulnerability of the heart to ventricular fibrillation during heart failure. Thus, renal denervation can attenuate ventricular electrical remodelling and exert a potential antifibrillatory action in a pacing-induced heart failure canine model. In this study, we investigated the effects of renal denervation (RDN) on the vulnerability to ventricular fibrillation (VF) and the ventricular electrical properties in a canine model of pacing-induced heart failure (HF). Eighteen beagles were divided into the following three groups: control (n = 6), HF (n = 6) and HF+RDN (n = 6). Heart failure was induced by rapid right ventricular pacing. Renal denervation was performed simultaneously with the pacemaker implantation in the HF+RDN group. A 64-unipolar basket catheter was used to perform global endocardial mapping of the left ventricle. The restitution properties and dispersion of refractoriness were estimated from the activation recovery intervals (ARIs) by a pacing protocol. The VF threshold (VFT) was defined as the maximal pacing cycle length required to induce VF using a specific pacing protocol. The defibrillation threshold (DFT) was measured by an up-down algorithm. Renal denervation partly restored left ventricular systolic function and attenuated the process of HF. Compared with the control group, the VFT in the HF group was decreased by 27% (106 ± 8.0 versus 135 ± 10 ms, P Renal denervation significantly flattened the ventricular ARI restitution curve by 15% (1

  11. Co-regulation of the atrial natriuretic factor and cardiac myosin light chain-2 genes during alpha-adrenergic stimulation of neonatal rat ventricular cells. Identification of cis sequences within an embryonic and a constitutive contractile protein gene which mediate inducible expression.

    Science.gov (United States)

    Knowlton, K U; Baracchini, E; Ross, R S; Harris, A N; Henderson, S A; Evans, S M; Glembotski, C C; Chien, K R

    1991-04-25

    To study the mechanisms which mediate the transcriptional activation of cardiac genes during alpha adrenergic stimulation, the present study examined the regulated expression of three cardiac genes, a ventricular embryonic gene (atrial natriuretic factor, ANF), a constitutively expressed contractile protein gene (cardiac MLC-2), and a cardiac sodium channel gene. alpha 1-Adrenergic stimulation activates the expression and release of ANF from neonatal ventricular cells. As assessed by RNase protection analyses, treatment with alpha-adrenergic agonists increases the steady-state levels of ANF mRNA by greater than 15-fold. However, a rat cardiac sodium channel gene mRNA is not induced, indicating that alpha-adrenergic stimulation does not lead to an increase in the expression of all cardiac genes. Studies employing a series of rat ANF luciferase and rat MLC-2 luciferase fusion genes identify 315- and 92-base pair cis regulatory sequences within an embryonic gene (ANF) and a constitutively expressed contractile protein gene (MLC-2), respectively, which mediate alpha-adrenergic-inducible gene expression. Transfection of various ANF luciferase reporters into neonatal rat ventricular cells demonstrated that upstream sequences which mediate tissue-specific expression (-3003 to -638) can be segregated from those responsible for inducibility. The lack of inducibility of a cardiac Na+ channel gene, and the segregation of ANF gene sequences which mediate cardiac specific from those which mediate inducible expression, provides further insight into the relationship between muscle-specific and inducible expression during cardiac myocyte hypertrophy. Based on these results, a testable model is proposed for the induction of embryonic cardiac genes and constitutively expressed contractile protein genes and the noninducibility of a subset of cardiac genes during alpha-adrenergic stimulation of neonatal rat ventricular cells.

  12. Overload-induced skeletal muscle hypertrophy is not impaired in STZ-diabetic rats

    Science.gov (United States)

    Fortes, Marco Aurélio S; Pinheiro, Carlos Hermano J; Guimarães-Ferreira, Lucas; Vitzel, Kaio F; Vasconcelos, Diogo A A; Curi, Rui

    2015-01-01

    The aim of this study was to evaluate the effect of overload-induced hypertrophy on extensor digitorum longus (EDL) and soleus muscles of streptozotocin-induced diabetic rats. The overload-induced hypertrophy and absolute tetanic and twitch forces increases in EDL and soleus muscles were not different between diabetic and control rats. Phospho-Akt and rpS6 contents were increased in EDL muscle after 7 days of overload and returned to the pre-overload values after 30 days. In the soleus muscle, the contents of total and phospho-Akt and total rpS6 were increased in both groups after 7 days. The contents of total Akt in controls and total rpS6 and phospho-Akt in the diabetic rats remained increased after 30 days. mRNA expression after 7 days of overload in the EDL muscle of control and diabetic animals showed an increase in MGF and follistatin and a decrease in myostatin and Axin2. The expression of FAK was increased and of MuRF-1 and atrogin-1 decreased only in the control group, whereas Ankrd2 expression was enhanced only in diabetic rats. In the soleus muscle caused similar changes in both groups: increase in FAK and MGF and decrease in Wnt7a, MuRF-1, atrogin-1, and myostatin. Differences between groups were observed only in the increased expression of follistatin in diabetic animals and decreased Ankrd2 expression in the control group. So, insulin deficiency does not impair the overload-induced hypertrophic response in soleus and EDL muscles. However, different mechanisms seem to be involved in the comparable hypertrophic responses of skeletal muscle in control and diabetic animals. PMID:26197932

  13. MURC/Cavin-4 facilitates recruitment of ERK to caveolae and concentric cardiac hypertrophy induced by α1-adrenergic receptors.

    Science.gov (United States)

    Ogata, Takehiro; Naito, Daisuke; Nakanishi, Naohiko; Hayashi, Yukiko K; Taniguchi, Takuya; Miyagawa, Kotaro; Hamaoka, Tetsuro; Maruyama, Naoki; Matoba, Satoaki; Ikeda, Koji; Yamada, Hiroyuki; Oh, Hidemasa; Ueyama, Tomomi

    2014-03-11

    The actions of catecholamines on adrenergic receptors (ARs) induce sympathetic responses, and sustained activation of the sympathetic nervous system results in disrupted circulatory homeostasis. In cardiomyocytes, α1-ARs localize to flask-shaped membrane microdomains known as "caveolae." Caveolae require both caveolin and cavin proteins for their biogenesis and function. However, the functional roles and molecular interactions of caveolar components in cardiomyocytes are poorly understood. Here, we showed that muscle-restricted coiled-coil protein (MURC)/Cavin-4 regulated α1-AR-induced cardiomyocyte hypertrophy through enhancement of ERK1/2 activation in caveolae. MURC/Cavin-4 was expressed in the caveolae and T tubules of cardiomyocytes. MURC/Cavin-4 overexpression distended the caveolae, whereas MURC/Cavin-4 was not essential for their formation. MURC/Cavin-4 deficiency attenuated cardiac hypertrophy induced by α1-AR stimulation in the presence of caveolae. Interestingly, MURC/Cavin-4 bound to α1A- and α1B-ARs as well as ERK1/2 in caveolae, and spatiotemporally modulated MEK/ERK signaling in response to α1-AR stimulation. Thus, MURC/Cavin-4 facilitates ERK1/2 recruitment to caveolae and efficient α1-AR signaling mediated by caveolae in cardiomyocytes, which provides a unique insight into the molecular mechanisms underlying caveola-mediated signaling in cardiac hypertrophy.

  14. [Importance of hypertensive left ventricular hypertrophy in patients with ischemic events of the heart or brain].

    Science.gov (United States)

    Castilla-Guerra, L; Fernández-Moreno, M C; Aguilera-Saborido, A; Solanella-Soler, J

    2016-01-01

    Hypertensive left ventricular hypertrophy (H-LVH) is a potentially modifiable vascular risk factor (VRF) often overlooked in clinical practice. We aimed to evaluate the frequency of H-LVH in patients with coronary heart disease (CHD) or ischemic stroke (IS). We retrospectively assessed all the echocardiography studies of patients admitted with the diagnosis CHD or IS over a 4-year period. We studied 533 patients, 330 with CHD and 203 with IS. Mean age was 69 (±11) years, 61.5% males. Hypertension was the most common RF: 362 patients (67.9%) (CHD vs. IS: 70 vs. 64.5%; P=NS). H-LVH was seen in 234 patients (43.9%) (CHD vs. IS: 44.8 vs. 42.3%; P=NS). Patients with H-LVH were older and received a greater number of antihypertensive drugs at discharge. Half of patients with hypertension presented H-LVH (184 patients; 50.8%), with similar frequency in both groups (CHD vs. IS: 50.6 vs. 51.1%; P=NS). Neither patients' characteristics nor VRF with the exception of hypertension (P=.0001) were associated with H-LVH. H-LVH is a major VRF in patients with ischemic events in the heart and brain. Nearly half the patients present H-LVH, with a similar frequency in both groups. It is important to identify H-LVH in these patients to optimize treatment and improve long-term prognosis. Copyright © 2015 SEHLELHA. Published by Elsevier España, S.L.U. All rights reserved.

  15. Ventricular dysfunction in children with obstructive sleep apnea: radionuclide assessment

    International Nuclear Information System (INIS)

    Tal, A.; Leiberman, A.; Margulis, G.; Sofer, S.

    1988-01-01

    Ventricular function was evaluated using radionuclide ventriculography in 27 children with oropharyngeal obstruction and clinical features of obstructive sleep apnea. Their mean age was 3.5 years (9 months to 7.5 years). Conventional clinical assessment did not detect cardiac involvement in 25 of 27 children; however, reduced right ventricular ejection fraction (less than 35%) was found in 10 (37%) patients (mean: 19.5 +/- 2.3% SE, range: 8-28%). In 18 patients wall motion abnormality was detected. In 11 children in whom radionuclide ventriculography was performed before and after adenotonsillectomy, right ventricular ejection fraction rose from 24.4 +/- 3.6% to 46.7 +/- 3.4% (P less than 0.005), and in all cases wall motion showed a definite improvement. In five children, left ventricular ejection fraction rose greater than 10% after removal of oropharyngeal obstruction. It is concluded that right ventricular function may be compromised in children with obstructive sleep apnea secondary to adenotonsillar hypertrophy, even before clinical signs of cardiac involvement are present

  16. Perinatal DDT Exposure Induces Hypertension and Cardiac Hypertrophy in Adult Mice.

    Science.gov (United States)

    La Merrill, Michele A; Sethi, Sunjay; Benard, Ludovic; Moshier, Erin; Haraldsson, Borje; Buettner, Christoph

    2016-11-01

    Dichlorodiphenyltrichloroethane (DDT) was used extensively to control malaria, typhus, body lice, and bubonic plague worldwide, until countries began restricting its use in the 1970s. However, the use of DDT to control vector-borne diseases continues in developing countries. Prenatal DDT exposure is associated with elevated blood pressure in humans. We hypothesized that perinatal DDT exposure causes hypertension in adult mice. DDT was administered to C57BL/6J dams from gestational day 11.5 to postnatal day 5. Blood pressure (BP) and myocardial wall thickness were measured in male and female adult offspring. Adult mice were treated with an angiotensin converting enzyme (ACE) inhibitor, captopril, to evaluate sensitivity to amelioration of DDT-associated hypertension by ACE inhibition. We further assessed the influence of DDT exposure on the expression of mRNAs that regulate BP through renal ion transport. Adult mice perinatally exposed to DDT exhibited chronically increased systolic BP, increased myocardial wall thickness, and elevated expression of mRNAs of several renal ion transporters. Captopril completely reversed hypertension in mice perinatally exposed to DDT. These data demonstrate that perinatal exposure to DDT causes hypertension and cardiac hypertrophy in adult offspring. A key mechanism underpinning this hypertension is an overactivated renin angiotensin system because ACE inhibition reverses the hypertension induced by perinatal DDT exposure. Citation: La Merrill M, Sethi S, Benard L, Moshier E, Haraldsson B, Buettner C. 2016. Perinatal DDT exposure induces hypertension and cardiac hypertrophy in adult mice. Environ Health Perspect 124:1722-1727; http://dx.doi.org/10.1289/EHP164.

  17. Androgen interacts with exercise through the mTOR pathway to induce skeletal muscle hypertrophy.

    Science.gov (United States)

    Zeng, Fanxing; Zhao, Hua; Liao, Jingwen

    2017-12-01

    This study was designed to investigate the effects of exogenous androgen and resistance exercise on skeletal muscle hypertrophy and the role of the mammalian target of rapamycin (mTOR) signalling during the process. A total of 24 male Sprague-Dawley rats were randomly assigned to sham operation and dihydrotestosterone (DHT) implantation groups with subgroups subjected to sedentary conditions or resistance exercise (SHAM+SED, SHAM+EX, DHT+SED, and DHT+EX). The experimental procedure lasted for 10 days. The mRNA expression of androgen receptor (AR) and insulin-like growth factor I (IGF-I), the expression of myosin heavy chain (MHC), as well as the phosphorylation statuses of AR, mTOR, p70 ribosomal S6 kinase (p70 S6K ), and eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1) were determined in the white gastrocnemius muscle. The cross sectional area and wet mass of the muscle were also measured. The cross sectional area and MHC expression were significantly higher in SHAM+EX, DHT+SED, and DHT+EX than in SHAM+SED. There was no significant difference among groups in muscle mass. The mRNA expression of AR and IGF-I and the phosphorylation of mTOR, p70 S6K , and 4EBP1 were significantly increased in DHT+SED and SHAM+EX and were significantly enhanced in DHT+EX compared with either DHT or exercise alone. These data show that DHT causes hypertrophy in skeletal muscle and that exercise has a synergistic effect on DHT-induced hypertrophy. Exercise enhances androgen-induced rapid anabolic action, which involves activation of the mTOR pathway.

  18. Role of the renin-angiotensin system in cardiac hypertrophy induced in rats by hyperthyroidism

    OpenAIRE

    KOBORI, HIROYUKI; ICHIHARA, ATSUHIRO; SUZUKI, HIROMICHI; TAKENAKA, TSUNEO; MIYASHITA, YUTAKA; HAYASHI, MATSUHIKO; SARUTA, TAKAO

    1997-01-01

    This study was conducted to examine whether the renin-angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy without involving the sympathetic nervous system. Sprague-Dawley rats were divided into control-innervated, control-denervated, hyperthyroid-innervated, and hyperthyroid-denervated groups using intraperitoneal injections of thyroxine and 6-hydroxydopamine. After 8 wk, the heart-to-body weight ratio increased in hyperthyroid groups (63%), and this increase was onl...

  19. The role of satellite cells in muscle hypertrophy.

    Science.gov (United States)

    Blaauw, Bert; Reggiani, Carlo

    2014-02-01

    The role of satellite cells in muscle hypertrophy has long been a debated issue. In the late 1980s it was shown that proteins remain close to the myonucleus responsible for its synthesis, giving rise to the idea of a nuclear domain. This, together with the observation that during various models of muscle hypertrophy there is an activation of the muscle stem cells, i.e. satellite cells, lead to the idea that satellite cell activation is required for muscle hypertrophy. Thus, satellite cells are not only responsible for muscle repair and regeneration, but also for hypertrophic growth. Further support for this line of thinking was obtained after studies showing that irradiation of skeletal muscle, and therefore elimination of all satellite cells, completely prevented overload-induced hypertrophy. Recently however, using different transgenic approaches, it has become clear that muscle hypertrophy can occur without a contribution of satellite cells, even though in most situations of muscle hypertrophy satellite cells are activated. In this review we will discuss the contribution of satellite cells, and other muscle-resident stem cells, to muscle hypertrophy both in mice as well as in humans.

  20. The effect of postoperative medical treatment on left ventricular mass regression after aortic valve replacement.

    Science.gov (United States)

    Helder, Meghana R K; Ugur, Murat; Bavaria, Joseph E; Kshettry, Vibhu R; Groh, Mark A; Petracek, Michael R; Jones, Kent W; Suri, Rakesh M; Schaff, Hartzell V

    2015-03-01

    The study objective was to analyze factors associated with left ventricular mass regression in patients undergoing aortic valve replacement with a newer bioprosthesis, the Trifecta valve pericardial bioprosthesis (St Jude Medical Inc, St Paul, Minn). A total of 444 patients underwent aortic valve replacement with the Trifecta bioprosthesis from 2007 to 2009 at 6 US institutions. The clinical and echocardiographic data of 200 of these patients who had left ventricular hypertrophy and follow-up studies 1 year postoperatively were reviewed and compared to analyze factors affecting left ventricular mass regression. Mean (standard deviation) age of the 200 study patients was 73 (9) years, 66% were men, and 92% had pure or predominant aortic valve stenosis. Complete left ventricular mass regression was observed in 102 patients (51%) by 1 year postoperatively. In univariate analysis, male sex, implantation of larger valves, larger left ventricular end-diastolic volume, and beta-blocker or calcium-channel blocker treatment at dismissal were significantly associated with complete mass regression. In the multivariate model, odds ratios (95% confidence intervals) indicated that male sex (3.38 [1.39-8.26]) and beta-blocker or calcium-channel blocker treatment at dismissal (3.41 [1.40-8.34]) were associated with increased probability of complete left ventricular mass regression. Patients with higher preoperative systolic blood pressure were less likely to have complete left ventricular mass regression (0.98 [0.97-0.99]). Among patients with left ventricular hypertrophy, postoperative treatment with beta-blockers or calcium-channel blockers may enhance mass regression. This highlights the need for close medical follow-up after operation. Labeled valve size was not predictive of left ventricular mass regression. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  1. Fish protein intake induces fast-muscle hypertrophy and reduces liver lipids and serum glucose levels in rats.

    Science.gov (United States)

    Kawabata, Fuminori; Mizushige, Takafumi; Uozumi, Keisuke; Hayamizu, Kohsuke; Han, Li; Tsuji, Tomoko; Kishida, Taro

    2015-01-01

    In our previous study, fish protein was proven to reduce serum lipids and body fat accumulation by skeletal muscle hypertrophy and enhancing basal energy expenditure in rats. In the present study, we examined the precise effects of fish protein intake on different skeletal muscle fiber types and metabolic gene expression of the muscle. Fish protein increased fast-twitch muscle weight, reduced liver triglycerides and serum glucose levels, compared with the casein diet after 6 or 8 weeks of feeding. Furthermore, fish protein upregulated the gene expressions of a fast-twitch muscle-type marker and a glucose transporter in the muscle. These results suggest that fish protein induces fast-muscle hypertrophy, and the enhancement of basal energy expenditure by muscle hypertrophy and the increase in muscle glucose uptake reduced liver lipids and serum glucose levels. The present results also imply that fish protein intake causes a slow-to-fast shift in muscle fiber type.

  2. Negative feedback regulation of Homer 1a on norepinephrine-dependent cardiac hypertrophy

    Energy Technology Data Exchange (ETDEWEB)

    Chiarello, Carmelina; Bortoloso, Elena; Carpi, Andrea; Furlan, Sandra; Volpe, Pompeo, E-mail: pompeo.volpe@unipd.it

    2013-07-15

    Homers are scaffolding proteins that modulate diverse cell functions being able to assemble signalling complexes. In this study, the presence, sub-cellular distribution and function of Homer 1 was investigated. Homer 1a and Homer 1b/c are constitutively expressed in cardiac muscle of both mouse and rat and in HL-1 cells, a cardiac cell line. As judged by confocal immunofluorescence microscopy, Homer 1a displays sarcomeric and peri-nuclear localization. In cardiomyocytes and cultured HL-1 cells, the hypertrophic agonist norepinephrine (NE) induces α{sub 1}-adrenergic specific Homer 1a over-expression, with a two-to-three-fold increase within 1 h, and no up-regulation of Homer 1b/c, as judged by Western blot and qPCR. In HL-1 cells, plasmid-driven over-expression of Homer 1a partially antagonizes activation of ERK phosphorylation and ANF up-regulation, two well-established, early markers of hypertrophy. At the morphometric level, NE-induced increase of cell size is likewise and partially counteracted by exogenous Homer 1a. Under the same experimental conditions, Homer 1b/c does not have any effect on ANF up-regulation nor on cell hypertrophy. Thus, Homer 1a up-regulation is associated to early stages of cardiac hypertrophy and appears to play a negative feedback regulation on molecular transducers of hypertrophy. -- Highlights: • Homer 1a is constitutively expressed in cardiac tissue. • In HL-1 cells, norepinephrine activates signaling pathways leading to hypertrophy. • Homer 1a up-regulation is an early event of norepinephrine-induced hypertrophy. • Homer 1a plays a negative feedback regulation modulating pathological hypertrophy. • Over-expression of Homer 1a per se does not induce hypertrophy.

  3. Negative feedback regulation of Homer 1a on norepinephrine-dependent cardiac hypertrophy

    International Nuclear Information System (INIS)

    Chiarello, Carmelina; Bortoloso, Elena; Carpi, Andrea; Furlan, Sandra; Volpe, Pompeo

    2013-01-01

    Homers are scaffolding proteins that modulate diverse cell functions being able to assemble signalling complexes. In this study, the presence, sub-cellular distribution and function of Homer 1 was investigated. Homer 1a and Homer 1b/c are constitutively expressed in cardiac muscle of both mouse and rat and in HL-1 cells, a cardiac cell line. As judged by confocal immunofluorescence microscopy, Homer 1a displays sarcomeric and peri-nuclear localization. In cardiomyocytes and cultured HL-1 cells, the hypertrophic agonist norepinephrine (NE) induces α 1 -adrenergic specific Homer 1a over-expression, with a two-to-three-fold increase within 1 h, and no up-regulation of Homer 1b/c, as judged by Western blot and qPCR. In HL-1 cells, plasmid-driven over-expression of Homer 1a partially antagonizes activation of ERK phosphorylation and ANF up-regulation, two well-established, early markers of hypertrophy. At the morphometric level, NE-induced increase of cell size is likewise and partially counteracted by exogenous Homer 1a. Under the same experimental conditions, Homer 1b/c does not have any effect on ANF up-regulation nor on cell hypertrophy. Thus, Homer 1a up-regulation is associated to early stages of cardiac hypertrophy and appears to play a negative feedback regulation on molecular transducers of hypertrophy. -- Highlights: • Homer 1a is constitutively expressed in cardiac tissue. • In HL-1 cells, norepinephrine activates signaling pathways leading to hypertrophy. • Homer 1a up-regulation is an early event of norepinephrine-induced hypertrophy. • Homer 1a plays a negative feedback regulation modulating pathological hypertrophy. • Over-expression of Homer 1a per se does not induce hypertrophy

  4. Clinical evaluation of left ventricular wall thickness by combined technique with gated planer /sup 201/Tl image and gated cardiac pool image

    Energy Technology Data Exchange (ETDEWEB)

    Nakai, Kenji; Katsuragawa, Shigehiko; Takahashi, Tsuneo; Matsushita, Kazuo; Kawamura, Akiyoshi

    1983-11-01

    To evaluate the left ventricular (LV) wall thickness, a combined technique with gated planer 201-thallium image and gated cardiac pool image was applied to 6 patients with hypertrophic cardiomyopathy (HCM) and 4 patients with secondary hypertrophy due to hypertension (HHD) proven by electrocardiography and ultrasonic-echocardiography. Scintigraphic pattern of hypertrophy on reconstructed planer /sup 201/Tl image showed diffuse or asymmetrical apical hypertrophy in HHD, asymmetrical septal hypertrophy in HCM. It was very interesting that abnormal perfusion was shown in /sup 201/Tl image, despite symmetrical hypertrophy in echocardiography. This techniques provided useful information for evaluating the LV wall thickness and cardiac performance.

  5. Patterns of left ventricular geometry and the transition to congestive heart failure with preserved versus depressed ejection fraction (Patrones de geometría ventricular izquierda y la transición a la insuficiencia cardíaca congestiva con fracción de eyección conservada versus deprimida

    Directory of Open Access Journals (Sweden)

    José H. Donis Hernández

    2014-12-01

    Full Text Available Abstract (english Analysis of cross-sectional and follow up clinical studies, of hypertensive patients with the different left ventricular geometric patterns, provide plausible explanations for the transition from hypertensive heart disease to the two distinct phenotypes of systolic and diastolic congestive heart failure. According to the LIFE study treated-uncomplicated patients, with normal ventricular geometry (12%, concentric remodeling (11 % and concentric hypertrophy (34 %, may evolve to the eccentric hypertrophy pattern. Patients with the eccentric hypertrophy pattern have selective sympathetic activation and progressive enlargement of the left ventricular cavity with thinning of its walls. This pattern goes on to a stage of systolic dysfunction with diminished ejection fraction and enhanced degradation of the collagen matrix. On the other hand, patients with the concentric hypertrophy pattern have predominant activation of the renin-angiotensin-aldosterone system and progressive shrinking of the left ventricular cavity with thickening of its walls. This pattern usually precedes the stage of diastolic heart failure with preserved ejection fraction, impairment of relaxation and increased deposition of collagen in the myocardial interstitium. Thus, ventricular remodeling preceding diastolic heart failure is opposite to that of hypertensive patients who go on to develop systolic heart failure. Resumen (español El análisis de los estudios transversales y longitudinales, de pacientes hipertensos con diferentes patrones de geometría ventricular izquierda, permite postular posibles mecanismos fisiopatológicos para explicar la transición de la cardiopatía hipertensiva hacia los dos fenotipos conocidos de insuficiencia cardiaca. De acuerdo con el estudio LIFE, los pacientes hipertensos no complicados, con patrones de geometría ventricular normal (12 %, remodelado concéntrico (11 % e hipertrofia concéntrica (34 %, pueden evolucionar hacia

  6. Diffuse interstitial fibrosis assessed by cardiac magnetic resonance is associated with dispersion of ventricular repolarization in patients with hypertrophic cardiomyopathy

    Directory of Open Access Journals (Sweden)

    David Hurtado-de-Mendoza, MD

    2017-06-01

    Conclusion: Diffuse interstitial fibrosis is associated with increased dispersion of ventricular repolarization in leads, reflecting electrical activity in the hypertrophied septum. Interstitial fibrosis combined with ion channel/gap junction remodeling in the septum could lead to inhomogeneity of ventricular refractoriness, resulting in increased QTc dispersion in leads V1–V4.

  7. Gallic acid prevents isoproterenol-induced cardiac hypertrophy and fibrosis through regulation of JNK2 signaling and Smad3 binding activity

    Science.gov (United States)

    Ryu, Yuhee; Jin, Li; Kee, Hae Jin; Piao, Zhe Hao; Cho, Jae Yeong; Kim, Gwi Ran; Choi, Sin Young; Lin, Ming Quan; Jeong, Myung Ho

    2016-01-01

    Gallic acid, a type of phenolic acid, has been shown to have beneficial effects in inflammation, vascular calcification, and metabolic diseases. The present study was aimed at determining the effect and regulatory mechanism of gallic acid in cardiac hypertrophy and fibrosis. Cardiac hypertrophy was induced by isoproterenol (ISP) in mice and primary neonatal cardiomyocytes. Gallic acid pretreatment attenuated concentric cardiac hypertrophy. It downregulated the expression of atrial natriuretic peptide, brain natriuretic peptide, and beta-myosin heavy chain in vivo and in vitro. Moreover, it prevented interstitial collagen deposition and expression of fibrosis-associated genes. Upregulation of collagen type I by Smad3 overexpression was observed in cardiac myoblast H9c2 cells but not in cardiac fibroblasts. Gallic acid reduced the DNA binding activity of phosphorylated Smad3 in Smad binding sites of collagen type I promoter in rat cardiac fibroblasts. Furthermore, it decreased the ISP-induced phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal regulated kinase (ERK) protein in mice. JNK2 overexpression reduced collagen type I and Smad3 expression as well as GATA4 expression in H9c2 cells and cardiac fibroblasts. Gallic acid might be a novel therapeutic agent for the prevention of cardiac hypertrophy and fibrosis by regulating the JNK2 and Smad3 signaling pathway. PMID:27703224

  8. Time course of gene expression during mouse skeletal muscle hypertrophy.

    Science.gov (United States)

    Chaillou, Thomas; Lee, Jonah D; England, Jonathan H; Esser, Karyn A; McCarthy, John J

    2013-10-01

    The purpose of this study was to perform a comprehensive transcriptome analysis during skeletal muscle hypertrophy to identify signaling pathways that are operative throughout the hypertrophic response. Global gene expression patterns were determined from microarray results on days 1, 3, 5, 7, 10, and 14 during plantaris muscle hypertrophy induced by synergist ablation in adult mice. Principal component analysis and the number of differentially expressed genes (cutoffs ≥2-fold increase or ≥50% decrease compared with control muscle) revealed three gene expression patterns during overload-induced hypertrophy: early (1 day), intermediate (3, 5, and 7 days), and late (10 and 14 days) patterns. Based on the robust changes in total RNA content and in the number of differentially expressed genes, we focused our attention on the intermediate gene expression pattern. Ingenuity Pathway Analysis revealed a downregulation of genes encoding components of the branched-chain amino acid degradation pathway during hypertrophy. Among these genes, five were predicted by Ingenuity Pathway Analysis or previously shown to be regulated by the transcription factor Kruppel-like factor-15, which was also downregulated during hypertrophy. Moreover, the integrin-linked kinase signaling pathway was activated during hypertrophy, and the downregulation of muscle-specific micro-RNA-1 correlated with the upregulation of five predicted targets associated with the integrin-linked kinase pathway. In conclusion, we identified two novel pathways that may be involved in muscle hypertrophy, as well as two upstream regulators (Kruppel-like factor-15 and micro-RNA-1) that provide targets for future studies investigating the importance of these pathways in muscle hypertrophy.

  9. Repeated blood flow restriction induces muscle fiber hypertrophy.

    Science.gov (United States)

    Sudo, Mizuki; Ando, Soichi; Kano, Yutaka

    2017-02-01

    We recently developed an animal model to investigate the effects of eccentric contraction (ECC) and blood flow restriction (BFR) on muscle tissue at the cellular level. This study clarified the effects of repeated BFR, ECC, and BFR combined with ECC (BFR+ECC) on muscle fiber hypertrophy. Male Wistar rats were assigned to 3 groups: BFR, ECC, and BFR+ECC. The contralateral leg in the BFR group served as a control (CONT). Muscle fiber cross-sectional area (CSA) of the tibialis anterior was determined after the respective treatments for 6 weeks. CSA was greater in the BFR+ECC group than in the CONT (P muscle fiber hypertrophy at the cellular level. Muscle Nerve 55: 274-276, 2017. © 2016 Wiley Periodicals, Inc.

  10. Patient-prosthesis mismatch and left ventricular remodelling after implantation of Shelhigh SuperStentless aortic valve prostheses.

    Science.gov (United States)

    Germing, A; Lindstaedt, M; Holt, S; Reber, D; Mügge, A; Laczkovics, A; Fritz, M

    2008-08-01

    Aortic valve replacement is a standard procedure for the treatment of severe aortic valve stenosis. Due to lower flow velocities stentless valves are associated with a more effective regression of left ventricular hypertrophy in comparison to stented valves. However, mismatch between body surface area and valve size supports unfavourable hemodynamic results. The aim of the study was to analyze hemodynamic parameters by echocardiography after implantation of the Shelhigh SuperStentless bioprosthesis and to analyze the occurrence of patient-prosthesis mismatch and left ventricular remodelling in this specific valve type. A total of 20 patients with severe aortic stenosis underwent implantation of a Shelhigh Super Stentless prosthesis. Clinical and echocardiographic assessment was done prior to, immediate after and six months after surgery. All surgical procedures were successful, no surgery-related complication was documented perioperatively. One patient died after development of multiorgan failure. Echocardiography during the first eight days after surgery showed mean gradients of 16 mmHg, mean valve orifice areas of 1.8 cm(2) and indexed effective orifice areas at 0.95 cm(2)/m(2). Six-months follow-up data were obtained in 19/20 patients. There were no relevant changes in echocardiographic hemodynamic findings at the time of follow-up measurements. Significant regression of left ventricular hypertrophy was shown (P=0.0088). A patient-prosthesis mismatch occurred in one patient (0.54 cm(2)/m(2)). No recurrent symptoms were documented. Patient-prosthesis mismatch after implantation of SuperStentless Shelhigh prosthesis is rare. A significant regression of left ventricular hypertrophy could be shown after six months. Hemodynamic valve function assessed by echocardiography may be predicted early after surgery.

  11. Right ventricular involvement in cardiac sarcoidosis demonstrated with cardiac magnetic resonance.

    Science.gov (United States)

    Smedema, Jan-Peter; van Geuns, Robert-Jan; Ainslie, Gillian; Ector, Joris; Heidbuchel, Hein; Crijns, Harry J G M

    2017-11-01

    Cardiac involvement in sarcoidosis is reported in up to 30% of patients. Left ventricular involvement demonstrated by contrast-enhanced cardiac magnetic resonance has been well validated. We sought to determine the prevalence and distribution of right ventricular late gadolinium enhancement in patients diagnosed with pulmonary sarcoidosis. We prospectively evaluated 87 patients diagnosed with pulmonary sarcoidosis with contrast-enhanced cardiac magnetic resonance for right ventricular involvement. Pulmonary artery pressures were non-invasively evaluated with Doppler echocardiography. Patient characteristics were compared between the groups with and without right ventricular involvement, and right ventricular enhancement was correlated with pulmonary hypertension, ventricular mass, volume, and systolic function. Left ventricular late gadolinium enhancement was demonstrated in 30 patients (34%). Fourteen patients (16%) had right ventricular late gadolinium enhancement, with sole right ventricular enhancement in only two patients. The pattern of right ventricular enhancement consisted of right ventricular outflow tract enhancement in 1 patient, free wall enhancement in 8 patients, ventricular insertion point enhancement in 10 patients, and enhancement of the right side of the interventricular septum in 11 patients. Pulmonary arterial hypertension correlated with the presence of right ventricular enhancement (P Right ventricular enhancement correlated with systolic ventricular dysfunction (P Right ventricular enhancement was present in 16% of patients diagnosed with pulmonary sarcoidosis and in 48% of patients with left ventricular enhancement. The presence of right ventricular enhancement correlated with pulmonary arterial hypertension, right ventricular systolic dysfunction, hypertrophy, and dilation. © 2017 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

  12. Ischemic preconditioning effect of prodromal angina is attenuated in acute myocardial infarction patients with hypertensive left ventricular hypertrophy

    International Nuclear Information System (INIS)

    Takeuchi, Toshiharu; Kikuchi, Kenjiro; Hasebe, Naoyuki; Ishii, Yoshinao

    2011-01-01

    Several animal experiments on acute myocardial infarction (AMI) have shown that the cardioprotective effects of ischemic preconditioning are more significant in hypertensive subjects. However, because there are no clinical data on the impact of hypertension on ischemic preconditioning in patients with AMI, whether clinical ischemic preconditioning of prodromal angina was beneficial in AMI patients with hypertension was investigated in the present study. 125 patients with a first anterior AMI who had undergone successful reperfusion therapy were divided into 2 groups, with or without hypertension, and into 2 further subgroups based on the presence or absence of prodromal angina. Dual-isotope (thallium-201(TL)/Tc-99m pyrophosphate) single-photon emission computed tomography (SPECT) was performed within 1 week of reperfusion therapy. Left ventricular (LV) function and LV mass index (LVMI) were measured by left ventriculography and echocardiography, respectively. In patients without hypertension, prodromal angina resulted in significantly less myocardial damage on TL-SPECT, better LV ejection fraction and a greater myocardial blush grade compared to patients without prodromal angina. However, these cardioprotective effects of prodromal angina were significantly diminished in hypertensive patients. Importantly, the myocardial salvage effects of prodromal angina showed a significant negative correlation with LVMI, which was significantly greater in hypertensive patients. The cardioprotective effects of prodromal angina were attenuated in patients with hypertension. Hypertensive LV hypertrophy may crucially limit the effects of ischemic preconditioning in AMI. (author)

  13. Predictors of the left ventricular dysfunction induced by ventricular arrhythmia

    Directory of Open Access Journals (Sweden)

    А. І. Vytryhovskiy

    2016-08-01

    Full Text Available The most powerful predictor of life-threatening arrhythmia risk is a combination of low heart rate variability with low ejection fraction (EF of the left ventricle. Aim. To identify predictors of left ventricle dysfunction which is induced by ventricular arrhythmia. Materials and methods. To diagnose structural changes of left ventricular functional capacity and reserves in patients with previous myocardial infarction and patients with high and very high cardiovascular risk by SCORE scale and for establishment the relationship between morphological heart changes and pathological phenomenon of heart turbulence echocardiography and study of heart rate turbulence variability were performed. 603 patients were selected for the research. All patients were divided into groups: group 1 – patients with coronary heart disease, but without associated risk factors, such as smoking, obesity, metabolic syndrome; group 2 – patients who smoke tobacco more than 2 years (very high cardiovascular risk by scale SCORE; group 3 – patients with metabolic syndrome without coronary heart disease or arterial hypertension (very high cardiovascular risk by scale SCORE. The control group consisted of 149 persons. Results. The feature of structural changes in patients with myocardial infarction and in patients with a high cardiovascular risk by SCORE with heart rate turbulence compared with cases without НRT is considerably thickening of the left interventricular septum in systole. Based on this, it can be argued that the emergence of ventricular arrhythmia and accordingly phenomenon of heart rate turbulence in patients with existing cardiovascular diseases and risk factors has both morphological and functional character. Significant difference of echocardioscopy parameters in patients with postinfarction cardiosclerosis and risk factors by the SCORE system was established by index of intraventricular septum thickness in systole, and in persons with high risk – in

  14. Development of nonfibrotic left ventricular hypertrophy in an ANG II-induced chronic ovine hypertension model

    DEFF Research Database (Denmark)

    Klatt, Niklas; Scherschel, Katharina; Schad, Claudia

    2016-01-01

    setting. Therefore, the aim of this study was to establish a minimally invasive ovine hypertension model using chronic angiotensin II (ANG II) treatment and to characterize its effects on cardiac remodeling after 8 weeks. Sheep were implanted with osmotic minipumps filled with either vehicle control (n...... = 7) or ANG II (n = 9) for 8 weeks. Mean arterial blood pressure in the ANG II-treated group increased from 87.4 ± 5.3 to 111.8 ± 6.9 mmHg (P = 0.00013). Cardiovascular magnetic resonance imaging showed an increase in left ventricular mass from 112 ± 12.6 g to 131 ± 18.7 g after 7 weeks (P = 0...... any differences in epicardial conduction velocity and heterogeneity. These data demonstrate that chronic ANG II treatment using osmotic minipumps presents a reliable, minimally invasive approach to establish hypertension and nonfibrotic LVH in sheep....

  15. Longitudinal Assessment of Left Ventricular Mass in Autosomal Dominant Polycystic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Taimur Dad

    2018-05-01

    Full Text Available Introduction: The high burden of cardiovascular morbidity and mortality in autosomal dominant polycystic kidney disease (ADPKD is related to development of hypertension and left ventricular hypertrophy. Blood pressure reduction has been shown to reduce left ventricular mass in ADPKD; however, moderators and predictors of response to lower blood pressure are unknown. Methods: This was a post hoc cohort analysis of HALT PKD study A, a randomized placebo controlled trial examining the effect of low blood pressure and single versus dual renin−angiotensin blockade in early ADPKD. Participants were hypertensive ADPKD patients 15 to 49 years of age with estimated glomerular filtration rate (eGFR > 60 ml/min per 1.73 m2 across 7 centers in the United States. Predictors included age, sex, baseline eGFR, systolic blood pressure, total kidney volume, serum potassium, and urine sodium, potassium, albumin, and aldosterone. Outcome was left ventricular mass index (LVMI measured using 1.5-T magnetic resonance imaging at months 0, 24, 48, and 60. Results: Reduction in LVMI was associated with higher baseline systolic blood pressure and larger kidney volume regardless of blood pressure control group assignment (P < 0.001 for both. Male sex and baseline eGFR were associated with a positive annual slope in LVMI (P < 0.001 and P = 0.07, respectively. Conclusion: Characteristics associated with higher risk of progression in ADPKD, including higher systolic blood pressure, larger kidney volume, and lower eGFR are associated with improvement in LVMI with intensive blood pressure control, whereas male sex is associated with a smaller slope of reduction in LVMI. Keywords: autosomal dominant polycystic kidney disease, hypertension, left ventricular hypertrophy, left ventricular mass index

  16. Deficiency of cardiac Acyl-CoA synthetase-1 induces diastolic dysfunction, but pathologic hypertrophy is reversed by rapamycin

    DEFF Research Database (Denmark)

    Paul, David S; Grevengoed, Trisha J; Pascual, Florencia

    2014-01-01

    In mice with temporally-induced cardiac-specific deficiency of acyl-CoA synthetase-1 (Acsl1(H-/-)), the heart is unable to oxidize long-chain fatty acids and relies primarily on glucose for energy. These metabolic changes result in the development of both a spontaneous cardiac hypertrophy...... and B-type natriuretic peptide. mTOR activation of the related Acsl3 gene, usually associated with pathologic hypertrophy, was also attenuated in the Acsl1(H-/-) hearts, indicating that alternative pathways of fatty acid activation did not compensate for the loss of Acsl1. Compared to controls, Acsl1(H......-/-) hearts exhibited an 8-fold higher uptake of 2-deoxy[1-(14)C]glucose and a 35% lower uptake of the fatty acid analog 2-bromo[1-(14)C]palmitate. These data indicate that Acsl1-deficiency causes diastolic dysfunction and that mTOR activation is linked to the development of cardiac hypertrophy in Acsl1(H...

  17. Matrix metalloproteinase-2 plays a critical role in overload induced skeletal muscle hypertrophy.

    Science.gov (United States)

    Zhang, Qia; Joshi, Sunil K; Lovett, David H; Zhang, Bryon; Bodine, Sue; Kim, Hubert T; Liu, Xuhui

    2014-01-01

    extracellular matrix (ECM) components are instrumental in maintaining homeostasis and muscle fiber functional integrity. Skeletal muscle hypertrophy is associated with ECM remodeling. Specifically, recent studies have reported the involvement of matrix metalloproteinases (MMPs) in muscle ECM remodeling. However, the functional role of MMPs in muscle hypertrophy remains largely unknown. in this study, we examined the role of MMP-2 in skeletal muscle hypertrophy using a previously validated method where the plantaris muscle of mice were subjected to mechanical overload due to the surgical removal of synergist muscles (gastrocnemius and soleus). following two weeks of overload, we observed a significant increase in MMP-2 activity and up-regulation of ECM components and remodeling enzymes in the plantaris muscles of wild-type mice. However, MMP-2 knockout mice developed significantly less hypertrophy and ECM remodeling in response to overload compared to their wild-type littermates. Investigation of protein synthesis rate and Akt/mTOR signaling revealed no difference between wild-type and MMP-2 knockout mice, suggesting that a difference in hypertrophy was independent of protein synthesis. taken together, our results suggest that MMP-2 is a key mediator of ECM remodeling in the setting of skeletal muscle hypertrophy.

  18. N-terminal pro brain natriuretic peptide in arterial hypertension--a marker for left ventricular dimensions and prognosis

    DEFF Research Database (Denmark)

    Hildebrandt, Per; Boesen, Mikael; Olsen, Michael

    2004-01-01

    In arterial hypertension risk factor evaluation, including LV mass measurements, and risk stratification using risk charts or programs, is generally recommended. In heart failure NT-proBNP has been shown to be a marker of LV dimensions and of prognosis. If the same diagnostic and prognostic value...... is present in arterial hypertension, risk factor evaluation would be easier. In 36 patients with arterial hypertension, electrocardiographic LV hypertrophy and preserved left ventricular function, NT-proBNP was eight-fold higher than in healthy subjects. The log NT-proBNP correlated with LV mass index (R=0.......47, P=0.0002) measured by magnetic resonance imaging. In other subjects with arterial hypertension a significant but weak correlation to diastolic properties has been demonstrated. As for prognosis, a recent study in patients with hypertension, electrocardiographic left ventricular hypertrophy...

  19. Effects of hydroxyl radical induced-Injury in atrial versus ventricular myocardium of dog and rabbit

    Directory of Open Access Journals (Sweden)

    Nitisha Hiranandani

    2010-09-01

    Full Text Available Aim: Despite the widespread use of ventricular tissue in the investigation involving hydroxyl-radical (OH* injury, one of the most potent mediators in ischemia-reperfusion injury, little is known about the impact on atrial myocardium. In this study we thus compared the OH*-induced injury response between atrial and right ventricular muscles from both rabbits and dogs under identical experimental conditions. Methods: Small, contracting ventricular and atrial rabbit and dog trabeculae were directly exposed to OH*, and contractile properties were examined and quantified. Results: A brief OH* exposure led to transient rigor like contracture with marked elevation of diastolic tension and depression of developed force. Although the injury response showed similarities between atrial and ventricular myocardium, there were significant differences as well. In rabbit atrial muscles, the development of the contracture and its peak was much faster as compared to ventricular muscles. Also, at the peak of contracture, both rabbit and dog atrial muscles show a lesser degree of contractile dysfunction. Conclusion: These results indicate that both atrial and ventricular muscles develop a rigor like contracture after acute OH*-induced injury, and atrial muscles showed a lesser degree of contractile dysfunction. Comparison of dog versus rabbit tissue shows that the response was similar in magnitude, but slower to develop in dog tissue.

  20. Stunning and Right Ventricular Dysfunction Is Induced by Coronary Balloon Occlusion and Rapid Pacing in Humans: Insights From Right Ventricular Conductance Catheter Studies.

    Science.gov (United States)

    Axell, Richard G; Giblett, Joel P; White, Paul A; Klein, Andrew; Hampton-Til, James; O'Sullivan, Michael; Braganza, Denise; Davies, William R; West, Nick E J; Densem, Cameron G; Hoole, Stephen P

    2017-06-06

    We sought to determine whether right ventricular stunning could be detected after supply (during coronary balloon occlusion [BO]) and supply/demand ischemia (induced by rapid pacing [RP] during transcatheter aortic valve replacement) in humans. Ten subjects with single-vessel right coronary artery disease undergoing percutaneous coronary intervention with normal ventricular function were studied in the BO group. Ten subjects undergoing transfemoral transcatheter aortic valve replacement were studied in the RP group. In both, a conductance catheter was placed into the right ventricle, and pressure volume loops were recorded at baseline and for intervals over 15 minutes after a low-pressure BO for 1 minute or a cumulative duration of RP for up to 1 minute. Ischemia-induced diastolic dysfunction was seen 1 minute after RP (end-diastolic pressure [mm Hg]: 8.1±4.2 versus 12.1±4.1, P right coronary artery balloon occlusion both cause ischemic right ventricular dysfunction with stunning observed later during the procedure. This may have intraoperative implications in patients without right ventricular functional reserve. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  1. Inhibition of TNF-α in hypothalamic paraventricular nucleus attenuates hypertension and cardiac hypertrophy by inhibiting neurohormonal excitation in spontaneously hypertensive rats

    Energy Technology Data Exchange (ETDEWEB)

    Song, Xin-Ai; Jia, Lin-Lin [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Cui, Wei [Department of Endocrinology and Metabolism, First Affiliated Hospital of Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Zhang, Meng [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Chen, Wensheng [Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China); Yuan, Zu-Yi [Department of Cardiovascular Medicine, First Affiliated Hospital of Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Guo, Jing [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Li, Hui-Hua [Key Laboratory of Remodeling-related Cardiovascular Diseases, Department of Pathology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069 (China); Zhu, Guo-Qing [Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing 210029 (China); Liu, Hao, E-mail: haoliu75@163.com [Department of Neurosurgery, First Affiliated Hospital of Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Kang, Yu-Ming, E-mail: ykang@mail.xjtu.edu.cn [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China)

    2014-11-15

    We hypothesized that chronic inhibition of tumor necrosis factor-alpha (TNF-α) in the hypothalamic paraventricular nucleus (PVN) delays the progression of hypertension and attenuates cardiac hypertrophy by up-regulating anti-inflammatory cytokines, reducing pro-inflammatory cytokines (PICs), decreasing nuclear factor-κB (NF-κB) p65 and NAD(P)H oxidase activities, as well as restoring the neurotransmitters balance in the PVN of spontaneously hypertensive rats (SHR). Adult normotensive Wistar–Kyoto (WKY) and SHR rats received bilateral PVN infusion of a TNF-α blocker (pentoxifylline or etanercept) or vehicle for 4 weeks. SHR rats showed higher mean arterial pressure and cardiac hypertrophy compared with WKY rats, as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, and cardiac atrial natriuretic peptide (ANP) and beta-myosin heavy chain (β-MHC) mRNA expressions. Compared with WKY rats, SHR rats had higher PVN levels of tyrosine hydroxylase, PICs, the chemokine monocyte chemoattractant protein-1 (MCP-1), NF-κB p65 activity, mRNA expressions of NOX-2 and NOX-4, and lower PVN levels of IL-10 and 67-kDa isoform of glutamate decarboxylase (GAD67), and higher plasma norepinephrine. PVN infusion of pentoxifylline or etanercept attenuated all these changes in SHR rats. These findings suggest that SHR rats have an imbalance between excitatory and inhibitory neurotransmitters, as well as an imbalance between pro- and anti-inflammatory cytokines in the PVN; and chronic inhibition of TNF-α in the PVN delays the progression of hypertension by restoring the balances of neurotransmitters and cytokines in the PVN, and attenuating PVN NF-κB p65 activity and oxidative stress, thereby attenuating hypertension-induced sympathetic hyperactivity and cardiac hypertrophy. - Highlights: • Spontaneously hypertensive rats exhibit neurohormonal excitation in the PVN. • PVN inhibition of

  2. Cardiomyocyte Overexpression of FABP4 Aggravates Pressure Overload-Induced Heart Hypertrophy.

    Directory of Open Access Journals (Sweden)

    Ji Zhang

    Full Text Available Fatty acid binding protein 4 (FABP4 is a member of the intracellular lipid-binding protein family, responsible for the transportation of fatty acids. It is considered to express mainly in adipose tissues, and be strongly associated with inflammation, obesity, diabetes and cardiovasculardiseases. Here we report that FABP4 is also expressed in cardiomyocytes and plays an important role in regulating heart function under pressure overload. We generated heart-specific transgenic FABP4 (FABP4-TG mice using α myosin-heavy chain (α-MHC promoter and human FABP4 sequence, resulting in over-expression of FABP4 in cardiomyocytes. The FABP4-TG mice displayed normal cardiac morphology and contractile function. When they were subjected to the transverse aorta constriction (TAC procedure, the FABP4-TG mice developed more cardiac hypertrophy correlated with significantly increased ERK phosphorylation, compared with wild type controls. FABP4 over-expression in cardiomyocytes activated phosphor-ERK signal and up-regulate the expression of cardiac hypertrophic marker genes. Conversely, FABP4 induced phosphor-ERK signal and hypertrophic gene expressions can be markedly inhibited by an ERK inhibitor PD098059 as well as the FABP4 inhibitor BMS309403. These results suggest that FABP4 over-expression in cardiomyocytes can aggravate the development of cardiac hypertrophy through the activation of ERK signal pathway.

  3. Acute post-exercise myofibrillar protein synthesis is not correlated with resistance training-induced muscle hypertrophy in young men.

    Directory of Open Access Journals (Sweden)

    Cameron J Mitchell

    Full Text Available Muscle hypertrophy following resistance training (RT involves activation of myofibrillar protein synthesis (MPS to expand the myofibrillar protein pool. The degree of hypertrophy following RT is, however, highly variable and thus we sought to determine the relationship between the acute activation of MPS and RT-induced hypertrophy. We measured MPS and signalling protein activation after the first session of resistance exercise (RE in untrained men (n = 23 and then examined the relation between MPS with magnetic resonance image determined hypertrophy. To measure MPS, young men (24±1 yr; body mass index  = 26.4±0.9 kg•m² underwent a primed constant infusion of L-[ring-¹³C₆] phenylalanine to measure MPS at rest, and acutely following their first bout of RE prior to 16 wk of RT. Rates of MPS were increased 235±38% (P<0.001 above rest 60-180 min post-exercise and 184±28% (P = 0.037 180-360 min post exercise. Quadriceps volume increased 7.9±1.6% (-1.9-24.7% (P<0.001 after training. There was no correlation between changes in quadriceps muscle volume and acute rates of MPS measured over 1-3 h (r = 0.02, 3-6 h (r = 0.16 or the aggregate 1-6 h post-exercise period (r = 0.10. Hypertrophy after chronic RT was correlated (r = 0.42, P = 0.05 with phosphorylation of 4E-BP1(Thr37/46 at 1 hour post RE. We conclude that acute measures of MPS following an initial exposure to RE in novices are not correlated with muscle hypertrophy following chronic RT.

  4. Low serum 25-hydroxyvitamin D levels are associated with left ventricular hypertrophy in essential hypertension.

    Science.gov (United States)

    Fallo, F; Catena, C; Camozzi, V; Luisetto, G; Cosma, C; Plebani, M; Lupia, M; Tona, F; Sechi, L A

    2012-10-01

    Low serum 25-hydroxyvitamin D [25(OH)D] levels may have an important role in predisposing to hypertension and myocardial disease. We investigated the relationship between 25(OH)D and left ventricular (LV) structure and function, assessed by echocardiography, in a series of patients with essential hypertension (EH). Sixty-two newly diagnosed never-treated patients (32 male/30 female), aged 18-65 years, with grade 1-2 hypertension, no diabetes, no obesity, no hyperlipidemia, and no cardiopulmonary, renal, or hepatic disease, were studied. Twenty-four healthy normotensive sex-, age-, BMI-matched subjects served as controls. Hypertensive patients with 25(OH)D deficiency, defined as serum 25(OH)D levels <50 nmol/L, had higher prevalence of LV hypertrophy (LVH) than their 25(OH)D-sufficient counterparts (57.1 vs 17.6%, P = 0.02); no differences between the two groups were found in blood pressure levels as well as in other biochemical and hormone parameters. There was an inverse correlation between LV mass index and 25(OH)D levels (r = -0.366, P < 0.003) and a direct correlation between LV mass index and BMI (r = 0.333, P < 0.006) in the entire hypertensive population. The two variables remained independently associated with LVH at multivariable logistic regression analysis (OR 1.05, P < 0.005 and OR 1.25, P = 0.03, respectively). Prevalence of 25(OH)D deficiency was similar in EH patients and controls (45.1 vs 41.6%, P = 0.89), whereas no correlation between echocardiographic parameters and hormone levels was found. In the absence of major cardiovascular risk factors, 25(OH)D deficiency is a frequent finding in EH patients and is independently associated with LVH. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. Akt1 deficiency diminishes skeletal muscle hypertrophy by reducing satellite cell proliferation.

    Science.gov (United States)

    Moriya, Nobuki; Miyazaki, Mitsunori

    2018-02-14

    Skeletal muscle mass is determined by the net dynamic balance between protein synthesis and degradation. Although the Akt/mechanistic target of rapamycin (mTOR)-dependent pathway plays an important role in promoting protein synthesis and subsequent skeletal muscle hypertrophy, the precise molecular regulation of mTOR activity by the upstream protein kinase Akt is largely unknown. In addition, the activation of satellite cells has been indicated as a key regulator of muscle mass. However, the requirement of satellite cells for load-induced skeletal muscle hypertrophy is still under intense debate. In this study, female germline Akt1 knockout (KO) mice were used to examine whether Akt1 deficiency attenuates load-induced skeletal muscle hypertrophy through suppressing mTOR-dependent signaling and satellite cell proliferation. Akt1 KO mice showed a blunted hypertrophic response of skeletal muscle, with a diminished rate of satellite cell proliferation following mechanical overload. In contrast, Akt1 deficiency did not affect the load-induced activation of mTOR signaling and the subsequent enhanced rate of protein synthesis in skeletal muscle. These observations suggest that the load-induced activation of mTOR signaling occurs independently of Akt1 regulation and that Akt1 plays a critical role in regulating satellite cell proliferation during load-induced muscle hypertrophy.

  6. Ventricular fibrillation induced by coagulating mode bipolar electrocautery during pacemaker implantation in Myotonic Dystrophy type 1 patient.

    Science.gov (United States)

    Russo, Vincenzo; Rago, Anna; DI Meo, Federica; Cioppa, Nadia Della; Papa, Andrea Antonio; Russo, Maria Giovanna; Nigro, Gerardo

    2014-12-01

    The occurrence of ventricular fibrillation, induced by bipolar electrocautery during elective dual chamber pacemaker implantation, is reported in a patient affected by Myotonic Distrophy type 1 with normal left ventricular ejection fraction.

  7. Visualization of hypertrophied papillary muscle mimicking left ventricular mass on gated blood pool and T1-201 myocardial perfusion imaging

    International Nuclear Information System (INIS)

    Bunko, H.; Nakajima, K.; Tonami, N.; Asanoi, H.; Hisada, K.

    1981-01-01

    A sixty-year old man with acute myocardial infarction was incidentally found to have a hypertrophied anterolateral papillary muscle (ALPPM) of the left ventricle on gated blood pool (GBP) and T1-201 myocardial perfusion images. Hypertrophy of the ALPPM was visualized as a movable defect in the lateral basal area on GBP imaging throughout the cardiac cycle and on the TI-201 study as a radionuclide accumulating structure, consistent with the defect in the GBP. A combination of these findings may suggest the presence of a hypertrophied papillary muscle of the left ventricle

  8. Inhibition of NF-κB activity in the hypothalamic paraventricular nucleus attenuates hypertension and cardiac hypertrophy by modulating cytokines and attenuating oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Xiao-Jing [Department of Physiology and Pathophysiology, Xi' an Jiaotong University School of Basic Medical Sciences, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University Health Science Center, Xi' an 710061 (China); Zhang, Dong-Mei [Department of Physiology, Dalian Medical University, Dalian 116044 (China); Jia, Lin-Lin; Qi, Jie; Song, Xin-Ai; Tan, Hong [Department of Physiology and Pathophysiology, Xi' an Jiaotong University School of Basic Medical Sciences, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University Health Science Center, Xi' an 710061 (China); Cui, Wei [Department of Endocrinology and Metabolism, First Affiliated Hospital of Xi' an Jiaotong University, Xi' an Jiaotong University Health Science Center, Xi' an 710061 (China); Chen, Wensheng [Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China); Zhu, Guo-Qing [Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing 210029 (China); Qin, Da-Nian, E-mail: dnqin@stu.edu.cn [Department of Physiology, Shantou University Medical College, Shantou 515041 (China); Kang, Yu-Ming, E-mail: ykang@mail.xjtu.edu.cn [Department of Physiology and Pathophysiology, Xi' an Jiaotong University School of Basic Medical Sciences, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University Health Science Center, Xi' an 710061 (China)

    2015-05-01

    We hypothesized that chronic inhibition of NF-κB activity in the hypothalamic paraventricular nucleus (PVN) delays the progression of hypertension and attenuates cardiac hypertrophy by up-regulating anti-inflammatory cytokines, reducing pro-inflammatory cytokines (PICs), attenuating nuclear factor-κB (NF-κB) p65 and NAD(P)H oxidase in the PVN of young spontaneously hypertensive rats (SHR). Young normotensive Wistar–Kyoto (WKY) and SHR rats received bilateral PVN infusions with NF–κB inhibitor pyrrolidine dithiocarbamate (PDTC) or vehicle for 4 weeks. SHR rats had higher mean arterial pressure and cardiac hypertrophy as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, cardiomyocyte diameters of the left cardiac ventricle, and mRNA expressions of cardiac atrial natriuretic peptide (ANP) and beta-myosin heavy chain (β-MHC). These SHR rats had higher PVN levels of proinflammatory cytokines (PICs), reactive oxygen species (ROS), the chemokine monocyte chemoattractant protein-1 (MCP-1), NAD(P)H oxidase activity, mRNA expression of NOX-2 and NOX-4, and lower PVN IL-10, and higher plasma levels of PICs and NE, and lower plasma IL-10. PVN infusion of NF-κB inhibitor PDTC attenuated all these changes. These findings suggest that NF-κB activation in the PVN increases sympathoexcitation and hypertensive response, which are associated with the increases of PICs and oxidative stress in the PVN; PVN inhibition of NF-κB activity attenuates PICs and oxidative stress in the PVN, thereby attenuates hypertension and cardiac hypertrophy. - Highlights: • Spontaneously hypertensive rats exhibit neurohormonal excitation in the PVN. • PVN inhibition of NF-κB attenuates hypertension-induced cardiac hypertrophy. • PVN inhibition of NF-κB attenuates hypertension-induced neurohormonal excitation. • PVN inhibition of NF-κB attenuates hypertension-induced imbalance of cytokines

  9. Ghrelin and its promoter variant associated with cardiac hypertrophy.

    Science.gov (United States)

    Ukkola, O; Pääkkö, T; Kesäniemi, Y A

    2012-07-01

    The roles of ghrelin, a peptide hormone that has a role in regulating food intake and energy homeostasis, in the cardiovascular system have not yet been unambiguously established. We evaluated the association between plasma ghrelin concentrations and -501A>C single-nucleotide polymorphism (SNP) in the ghrelin gene 5' flanking area and echocardiographic measurements in 1037 middle-aged subjects. Left ventricular mass index (LVMI) was calculated according to Devereux's method. The ambulatory blood pressure (BP) was recorded using the fully automatic SpaceLabs 90207 oscillometric unit. Results suggested that plasma ghrelin was not related to mean ambulatory BP values. However, the highest plasma ghrelin tertile was associated with increased intraventricular septum (P=0.043) and posterior ventricular wall (P=0.002) thicknesses as well as left ventricular mass (P=0.05). After adjustment for age, sex, body mass index and systolic BP, the association persisted between ghrelin tertiles and intraventricular septum (P=0.05) and posterior ventricular wall (P=0.001) thicknesses. The SNP -501A>C polymorphism was associated with LVMI after adjustments for age, sex and systolic BP. In conclusion, ghrelin and its promoter variant are associated with cardiac hypertrophy indexes independent of BP. Positive correlation between ghrelin levels and increased wall thickness parameters may reflect compensatory up-regulation of ghrelin concentrations or direct effects of ghrelin on myocardium. The effects of the SNP seem not to be mediated through its effects on ghrelin plasma levels.

  10. Raf-mediated cardiac hypertrophy in adult Drosophila

    Directory of Open Access Journals (Sweden)

    Lin Yu

    2013-07-01

    In response to stress and extracellular signals, the heart undergoes a process called cardiac hypertrophy during which cardiomyocytes increase in size. If untreated, cardiac hypertrophy can progress to overt heart failure that causes significant morbidity and mortality. The identification of molecular signals that cause or modify cardiomyopathies is necessary to understand how the normal heart progresses to cardiac hypertrophy and heart failure. Receptor tyrosine kinase (RTK signaling is essential for normal human cardiac function, and the inhibition of RTKs can cause dilated cardiomyopathies. However, neither investigations of activated RTK signaling pathways nor the characterization of hypertrophic cardiomyopathy in the adult fly heart has been previously described. Therefore, we developed strategies using Drosophila as a model to circumvent some of the complexities associated with mammalian models of cardiovascular disease. Transgenes encoding activated EGFRA887T, Ras85DV12 and Ras85DV12S35, which preferentially signal to Raf, or constitutively active human or fly Raf caused hypertrophic cardiomyopathy as determined by decreased end diastolic lumen dimensions, abnormal cardiomyocyte fiber morphology and increased heart wall thicknesses. There were no changes in cardiomyocyte cell numbers. Additionally, activated Raf also induced an increase in cardiomyocyte ploidy compared with control hearts. However, preventing increases in cardiomyocyte ploidy using fizzy-related (Fzr RNAi did not rescue Raf-mediated cardiac hypertrophy, suggesting that Raf-mediated polyploidization is not required for cardiac hypertrophy. Similar to mammals, the cardiac-specific expression of RNAi directed against MEK or ERK rescued Raf-mediated cardiac hypertrophy. However, the cardiac-specific expression of activated ERKD334N, which promotes hyperplasia in non-cardiac tissues, did not cause myocyte hypertrophy. These results suggest that ERK is necessary, but not sufficient, for Raf

  11. Effect of candesartan treatment on left ventricular remodeling after aortic valve replacement for aortic stenosis

    DEFF Research Database (Denmark)

    Dahl, Jordi S; Videbaek, Lars; Poulsen, Mikael K

    2010-01-01

    In hypertension, angiotensin receptor blockers can augment regression of left ventricular (LV) hypertrophy. It is not known whether this also is the case after aortic valve replacement (AVR) for severe aortic stenosis (AS). To test the hypothesis that treatment with candesartan in addition to con...

  12. Supplementing exposure to hypoxia with a copper depleted diet does not exacerbate right ventricular remodeling in mice.

    Directory of Open Access Journals (Sweden)

    Ella M Poels

    Full Text Available Pulmonary hypertension and subsequent right ventricular (RV failure are associated with high morbidity and mortality. Prognosis is determined by occurrence of RV failure. Currently, adequate treatment for RV failure is lacking. Further research into the molecular basis for the development of RV failure as well as the development of better murine models of RV failure are therefore imperative. We hypothesize that adding a low-copper diet to chronic hypoxia in mice reinforces their individual effect and that the combination of mild pulmonary vascular remodeling and capillary rarefaction, induces RV failure.Six week old mice were subjected to normoxia (N; 21% O2 or hypoxia (H; 10% O2 during a period of 8 weeks and received either a normal diet (Cu+ or a copper depleted diet (Cu-. Cardiac function was assessed by echocardiography and MRI analysis.Here, we characterized a mouse model of chronic hypoxia combined with a copper depleted diet and demonstrate that eight weeks of chronic hypoxia (10% is sufficient to induce RV hypertrophy and subsequent RV failure. Addition of a low copper diet to hypoxia did not have any further deleterious effects on right ventricular remodeling.

  13. Cohort Study of ECG Left Ventricular Hypertrophy Trajectories: Ethnic Disparities, Associations With Cardiovascular Outcomes, and Clinical Utility.

    Science.gov (United States)

    Iribarren, Carlos; Round, Alfred D; Lu, Meng; Okin, Peter M; McNulty, Edward J

    2017-10-05

    ECG left ventricular hypertrophy (LVH) is a well-known predictor of cardiovascular disease. However, no prior study has characterized patterns of presence/absence of ECG LVH ("ECG LVH trajectories") across the adult lifespan in both sexes and across ethnicities. We examined: (1) correlates of ECG LVH trajectories; (2) the association of ECG LVH trajectories with incident coronary heart disease, transient ischemic attack, ischemic stroke, hemorrhagic stroke, and heart failure; and (3) reclassification of cardiovascular disease risk using ECG LVH trajectories. We performed a cohort study among 75 412 men and 107 954 women in the Northern California Kaiser Permanente Medical Care Program who had available longitudinal exposures of ECG LVH and covariates, followed for a median of 4.8 (range ECG LVH was measured by Cornell voltage-duration product. Adverse trajectories of ECG LVH (persistent, new development, or variable pattern) were more common among blacks and Native American men and were independently related to incident cardiovascular disease with hazard ratios ranging from 1.2 for ECG LVH variable pattern and transient ischemic attack in women to 2.8 for persistent ECG LVH and heart failure in men. ECG LVH trajectories reclassified 4% and 7% of men and women with intermediate coronary heart disease risk, respectively. ECG LVH trajectories were significant indicators of coronary heart disease, stroke, and heart failure risk, independently of level and change in cardiovascular disease risk factors, and may have clinical utility. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  14. Reduction of blood oxygen levels enhances postprandial cardiac hypertrophy in Burmese python (Python bivittatus).

    Science.gov (United States)

    Slay, Christopher E; Enok, Sanne; Hicks, James W; Wang, Tobias

    2014-05-15

    Physiological cardiac hypertrophy is characterized by reversible enlargement of cardiomyocytes and changes in chamber architecture, which increase stroke volume and via augmented convective oxygen transport. Cardiac hypertrophy is known to occur in response to repeated elevations of O2 demand and/or reduced O2 supply in several species of vertebrate ectotherms, including postprandial Burmese pythons (Python bivittatus). Recent data suggest postprandial cardiac hypertrophy in P. bivittatus is a facultative rather than obligatory response to digestion, though the triggers of this response are unknown. Here, we hypothesized that an O2 supply-demand mismatch stimulates postprandial cardiac enlargement in Burmese pythons. To test this hypothesis, we rendered animals anemic prior to feeding, essentially halving blood oxygen content during the postprandial period. Fed anemic animals had heart rates 126% higher than those of fasted controls, which, coupled with a 71% increase in mean arterial pressure, suggests fed anemic animals were experiencing significantly elevated cardiac work. We found significant cardiac hypertrophy in fed anemic animals, which exhibited ventricles 39% larger than those of fasted controls and 28% larger than in fed controls. These findings support our hypothesis that those animals with a greater magnitude of O2 supply-demand mismatch exhibit the largest hearts. The 'low O2 signal' stimulating postprandial cardiac hypertrophy is likely mediated by elevated ventricular wall stress associated with postprandial hemodynamics. © 2014. Published by The Company of Biologists Ltd.

  15. Histone deacetylase inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in DOCA-induced hypertensive rats

    OpenAIRE

    Lee, Eunjo; Song, Min-ji; Lee, Hae-Ahm; Kang, Seol-Hee; Kim, Mina; Yang, Eun Kyoung; Lee, Do Young; Ro, Seonggu; Cho, Joong Myung; Kim, Inkyeom

    2016-01-01

    CG200745 is a novel inhibitor of histone deacetylases (HDACs), initially developed for treatment of various hematological and solid cancers. Because it is water-soluble, it can be administered orally. We hypothesized that the HDAC inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in deoxycorticosterone acetate (DOCA)-induced hypertensive rats. For establishment of hypertension, 40 mg/kg of DOCA was subcutaneously injected four times weekly into Sprague-Dawley rats. All the rats...

  16. Low-intensity interval exercise training attenuates coronary vascular dysfunction and preserves Ca2+-sensitive K+ current in miniature swine with LV hypertrophy

    Science.gov (United States)

    Tharp, Darla L.; Ivey, Jan R.; Ganjam, Venkataseshu K.; Bowles, Douglas K.

    2011-01-01

    Coronary vascular dysfunction has been observed in several models of heart failure (HF). Recent evidence indicates that exercise training is beneficial for patients with HF, but the precise intensity and underlying mechanisms are unknown. Left ventricular (LV) hypertrophy can play a significant role in the development of HF; therefore, the purpose of this study was to assess the effects of low-intensity interval exercise training on coronary vascular function in sedentary (HF) and exercise trained (HF-TR) aortic-banded miniature swine displaying LV hypertrophy. Six months postsurgery, in vivo coronary vascular responses to endothelin-1 (ET-1) and adenosine were measured in the left anterior descending coronary artery. Baseline and maximal coronary vascular conductance were similar between all groups. ET-1-induced reductions in coronary vascular conductance (P < 0.05) were greater in HF vs. sedentary control and HF-TR groups. Pretreatment with the ET type A (ETA) receptor blocker BQ-123 prevented ET-1 hypersensitivity in HF animals. Whole cell voltage clamp was used to characterize composite K+ currents (IK+) in coronary smooth muscle cells. Raising internal Ca2+ from 200 to 500 nM increased Ca2+-sensitive K+ current in HF-TR and control, but not HF animals. In conclusion, an ETA-receptor-mediated hypersensitivity to ET-1, elevated resting LV wall tension, and decreased coronary smooth muscle cell Ca2+-sensitive IK+ was found in sedentary animals with LV hypertrophy. Low-intensity interval exercise training preserved normal coronary vascular function and smooth muscle cell Ca2+-sensitive IK+, illustrating a potential mechanism underlying coronary vascular dysfunction in a large-animal model of LV hypertrophy. Our results demonstrate the potential clinical impact of exercise on coronary vascular function in HF patients displaying pathological LV hypertrophy. PMID:21841018

  17. Changes in Left Ventricular Morphology and Function After Mitral Valve Surgery

    Science.gov (United States)

    Shafii, Alexis E.; Gillinov, A. Marc; Mihaljevic, Tomislav; Stewart, William; Batizy, Lillian H.; Blackstone, Eugene H.

    2015-01-01

    Degenerative mitral valve disease is the leading cause of mitral regurgitation in North America. Surgical intervention has hinged on symptoms and ventricular changes that develop as compensatory ventricular remodeling takes place. In this study, we sought to characterize the temporal response of left ventricular (LV) morphology and function to mitral valve surgery for degenerative disease, and identify preoperative factors that influence reverse remodeling. From 1986–2007, 2,778 patients with isolated degenerative mitral valve disease underwent valve repair (n=2,607/94%) or replacement (n=171/6%) and had at least 1 postoperative transthoracic echocardiogram (TTE); 5,336 TTEs were available for analysis. Multivariable longitudinal repeated-measures analysis was performed to identify factors associated with reverse remodeling. LV dimensions decreased in the first year after surgery (end-diastolic from 5.7±0.80 to 4.9±1.4 cm; end-systolic from 3.4±0.71 to 3.1±1.4 cm). LV mass index decreased from 139±44 to 112±73 g·m−2. Reduction of LV hypertrophy was less pronounced in patients with greater preoperative left heart enlargement (P.2). In conclusion, a positive response toward normalization of LV morphology and function after mitral valve surgery is greatest in the first year. The best response occurs when surgery is performed before left heart dilatation, LV hypertrophy, or LV dysfunction develop. PMID:22534055

  18. HDL mimetic peptide CER-522 treatment regresses left ventricular diastolic dysfunction in cholesterol-fed rabbits.

    Science.gov (United States)

    Merlet, Nolwenn; Busseuil, David; Mihalache-Avram, Teodora; Mecteau, Melanie; Shi, Yanfen; Nachar, Walid; Brand, Genevieve; Brodeur, Mathieu R; Charpentier, Daniel; Rhainds, David; Sy, Gavin; Schwendeman, Anna; Lalwani, Narendra; Dasseux, Jean-Louis; Rhéaume, Eric; Tardif, Jean-Claude

    2016-07-15

    High-density lipoprotein (HDL) infusions induce rapid improvement of experimental atherosclerosis in rabbits but their effect on ventricular function remains unknown. We aimed to evaluate the effects of the HDL mimetic peptide CER-522 on left ventricular diastolic dysfunction (LVDD). Rabbits were fed with a cholesterol- and vitamin D2-enriched diet until mild aortic valve stenosis and hypercholesterolemia-induced LV hypertrophy and LVDD developed. Animals then received saline or 10 or 30mg/kg CER-522 infusions 6 times over 2weeks. We performed serial echocardiograms and LV histology to evaluate the effects of CER-522 therapy on LVDD. LVDD was reduced by CER-522 as shown by multiple parameters including early filling mitral deceleration time, deceleration rate, Em/Am ratio, E/Em ratio, pulmonary venous velocities, and LVDD score. These findings were associated with reduced macrophages (RAM-11 positive cells) in the pericoronary area and LV, and decreased levels of apoptotic cardiomyocytes in CER-522-treated rabbits. CER-522 treatment also resulted in decreased atheromatous plaques and internal elastic lamina area in coronary arteries. CER-522 improves LVDD in rabbits, with reductions of LV macrophage accumulation, cardiomyocyte apoptosis, coronary atherosclerosis and remodelling. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. Role of myocardial hypertrophy on acute and chronic right ventricular performance in relation to chronic volume overload in a porcine model: relevance for the surgical management of tetralogy of Fallot.

    Science.gov (United States)

    Bove, Thierry; Vandekerckhove, Kristof; Bouchez, Stefaan; Wouters, Patrick; Somers, Pamela; Van Nooten, Guido

    2014-06-01

    The age for correction of tetralogy of Fallot has progressively declined to the postnatal period, often despite an increased rate of transannular patch repair. However, the long-term effect of premature exposure to chronic pulmonary insufficiency on the right ventricle remains unknown. On the basis of the relationship between the duration of pressure overload and age, the role of previous pressure load-related hypertrophy on right ventricular (RV) performance after chronic volume overload was investigated in a porcine model. RV hypertrophy (RVH), induced by pulmonary artery banding, was studied in pigs with (RVH plus pulmonary insufficiency [PI]) and without (RVH) subsequent PI. The effect of volume overload was compared between these 2 groups and pigs without RVH but with PI and controls (sham). Both acute and chronic effects on RV function were studied using conductance technology and validated using echocardiography. After chronic volume overload, the end-systolic and end-diastolic volumes were smaller in the RVH+PI group than in the PI group, including a lower pulmonary regurgitation fraction (25% ± 5% vs 35% ± 5%; P = .002). RVH resulted in better preserved systolic function, confirmed by an increased preload recruitable stroke work slope (14.7 ± 1.8 vs 9.3 ± 1.3 Mw.s/mL; P = .025) and higher RV ejection fraction (51% ± 3% vs 45% ± 4%; P = .05). Myocardial stiffness was impaired in the RVH+PI group versus the PI group (β, 0.19 ± 0.03 vs 0.12 ± 0.02 mL(-1); P = .001), presenting restrictive physiology only in the condition associating RVH and PI. The results of the present study have demonstrated that RVH attenuates the RV remodeling process related to chronic PI. It enables better preservation of contractility but at the cost of sustained diastolic impairment. These findings might help to determine the timing and strategy for repair of tetralogy of Fallot when RV outflow tract morphology indicates a definite need for transannular reconstruction

  20. Prognostic implications of left ventricular asymmetry in patients with asymptomatic aortic valve stenosis

    DEFF Research Database (Denmark)

    Sigvardsen, Per Ejlstrup; Larsen, Linnea Hornbech; Carstensen, Helle Gervig

    2018-01-01

    Aims: Left ventricular (LV) regional hypertrophy in the form of LV asymmetry is a common finding in patients with aortic valve stenosis. The aim of this study was to test the hypothesis that LV asymmetry predicts future symptomatic status and indication for aortic valve replacement (AVR) in patie......Aims: Left ventricular (LV) regional hypertrophy in the form of LV asymmetry is a common finding in patients with aortic valve stenosis. The aim of this study was to test the hypothesis that LV asymmetry predicts future symptomatic status and indication for aortic valve replacement (AVR...... occurred in 46 patients (40%). Patients with LV asymmetry had more than 3 times the risk of AVR (hazard ratio: 3.16; 95% CI: 1.77-5.66; P future need of AVR (hazard ratio: 3.10; 95......% CI: 1.44-6.65; P = 0.004), independent of LV geometry, jet velocity, valvular calcification, and pro-BNP. Conclusions: LV asymmetry is an independent predictor of future need for AVR in patients with asymptomatic aortic valve stenosis. It has incremental prognostic value to LV geometry and may...

  1. Endurance training in the spontaneously hypertensive rat: conversion of pathological into physiological cardiac hypertrophy.

    Science.gov (United States)

    Garciarena, Carolina D; Pinilla, Oscar A; Nolly, Mariela B; Laguens, Ruben P; Escudero, Eduardo M; Cingolani, Horacio E; Ennis, Irene L

    2009-04-01

    The effect of endurance training (swimming 90 min/d for 5 days a week for 60 days) on cardiac hypertrophy was investigated in the spontaneously hypertensive rat (SHR). Sedentary SHRs (SHR-Cs) and normotensive Wistar rats were used as controls. Exercise training enhanced myocardial hypertrophy assessed by left ventricular weight/tibial length (228+/-7 versus 251+/-5 mg/cm in SHR-Cs and exercised SHRs [SHR-Es], respectively). Myocyte cross-sectional area increased approximately 40%, collagen volume fraction decreased approximately 50%, and capillary density increased approximately 45% in SHR-Es compared with SHR-Cs. The mRNA abundance of atrial natriuretic factor and myosin light chain 2 was decreased by the swimming routine (100+/-19% versus 41+/-10% and 100+/-8% versus 61+/-9% for atrial natriuretic factor and myosin light chain 2 in SHR-Cs and SHR-Es, respectively). The expression of sarcoplasmic reticulum Ca(2+) pump was significantly augmented, whereas that of Na(+)/Ca(2+) exchanger was unchanged (93+/-7% versus 167+/-8% and 158+/-13% versus 157+/-7%, sarcoplasmic reticulum Ca(2+) pump and Na(+)/Ca(2+) exchanger in SHR-Cs and SHR-Es, respectively; PEndurance training inhibited apoptosis, as reflected by a decrease in caspase 3 activation and poly(ADP-ribose) polymerase-1 cleavage, and normalized calcineurin activity without inducing significant changes in the phosphatidylinositol 3-kinase/Akt pathway. The swimming routine improved midventricular shortening determined by echocardiography (32.4+/-0.9% versus 36.9+/-1.1% in SHR-Cs and SHR-Es, respectively; Pendurance training to convert pathological into physiological hypertrophy improving cardiac performance. The reduction of myocardial fibrosis and calcineurin activity plus the increase in capillary density represent factors to be considered in determining this beneficial effect.

  2. Atorvastatin Improves Ventricular Remodeling after Myocardial Infarction by Interfering with Collagen Metabolism

    Science.gov (United States)

    Reichert, Karla; Pereira do Carmo, Helison Rafael; Galluce Torina, Anali; Diógenes de Carvalho, Daniela; Carvalho Sposito, Andrei; de Souza Vilarinho, Karlos Alexandre; da Mota Silveira-Filho, Lindemberg; Martins de Oliveira, Pedro Paulo

    2016-01-01

    Purpose Therapeutic strategies that modulate ventricular remodeling can be useful after acute myocardial infarction (MI). In particular, statins may exert effects on molecular pathways involved in collagen metabolism. The aim of this study was to determine whether treatment with atorvastatin for 4 weeks would lead to changes in collagen metabolism and ventricular remodeling in a rat model of MI. Methods Male Wistar rats were used in this study. MI was induced in rats by ligation of the left anterior descending coronary artery (LAD). Animals were randomized into three groups, according to treatment: sham surgery without LAD ligation (sham group, n = 14), LAD ligation followed by 10mg atorvastatin/kg/day for 4 weeks (atorvastatin group, n = 24), or LAD ligation followed by saline solution for 4 weeks (control group, n = 27). After 4 weeks, hemodynamic characteristics were obtained by a pressure-volume catheter. Hearts were removed, and the left ventricles were subjected to histologic analysis of the extents of fibrosis and collagen deposition, as well as the myocyte cross-sectional area. Expression levels of mediators involved in collagen metabolism and inflammation were also assessed. Results End-diastolic volume, fibrotic content, and myocyte cross-sectional area were significantly reduced in the atorvastatin compared to the control group. Atorvastatin modulated expression levels of proteins related to collagen metabolism, including MMP1, TIMP1, COL I, PCPE, and SPARC, in remote infarct regions. Atorvastatin had anti-inflammatory effects, as indicated by lower expression levels of TLR4, IL-1, and NF-kB p50. Conclusion Treatment with atorvastatin for 4 weeks was able to attenuate ventricular dysfunction, fibrosis, and left ventricular hypertrophy after MI in rats, perhaps in part through effects on collagen metabolism and inflammation. Atorvastatin may be useful for limiting ventricular remodeling after myocardial ischemic events. PMID:27880844

  3. MicroRNA profiling identifies miR-7-5p and miR-26b-5p as differentially expressed in hypertensive patients with left ventricular hypertrophy

    Directory of Open Access Journals (Sweden)

    C.M. Kaneto

    2017-10-01

    Full Text Available Recent evidence suggests that cell-derived circulating miRNAs may serve as biomarkers of cardiovascular diseases. However, a few studies have investigated the potential of circulating miRNAs as biomarkers for left ventricular hypertrophy (LVH. In this study, we aimed to characterize the miRNA profiles that could distinguish hypertensive patients with LHV, hypertensive patients without LVH and control subjects, and identify potential miRNAs as biomarkers of LVH. LVH was defined by left ventricular mass indexed to body surface area >125 g/m2 in men and >110 g/m2 in women and patients were classified as hypertensive when presenting a systolic blood pressure of 140 mmHg or more, or a diastolic blood pressure of 90 mmHg or more. We employed miRNA PCR array to screen serum miRNAs profiles of patients with LVH, essential hypertension and healthy subjects. We identified 75 differentially expressed miRNAs, including 49 upregulated miRNAs and 26 downregulated miRNAs between LVH and control patients. We chose 2 miRNAs with significant differences for further testing in 59 patients. RT-PCR analysis of serum samples confirmed that miR-7-5p and miR-26b-5p were upregulated in the serum of LVH hypertensive patients compared with healthy subjects. Our findings suggest that these miRNAs may play a role in the pathogenesis of hypertensive LVH and may represent novel biomarkers for this disease.

  4. Postnatal ablation of Foxm1 from cardiomyocytes causes late onset cardiac hypertrophy and fibrosis without exacerbating pressure overload-induced cardiac remodeling.

    Directory of Open Access Journals (Sweden)

    Craig Bolte

    Full Text Available Heart disease remains a leading cause of morbidity and mortality in the industrialized world. Hypertrophic cardiomyopathy is the most common genetic cardiovascular disorder and the most common cause of sudden cardiac death. Foxm1 transcription factor (also known as HFH-11B, Trident, Win or MPP2 plays an important role in the pathogenesis of various cancers and is a critical mediator of post-injury repair in multiple organs. Foxm1 has been previously shown to be essential for heart development and proliferation of embryonic cardiomyocytes. However, the role of Foxm1 in postnatal heart development and in cardiac injury has not been evaluated. To delete Foxm1 in postnatal cardiomyocytes, αMHC-Cre/Foxm1(fl/fl mice were generated. Surprisingly, αMHC-Cre/Foxm1(fl/fl mice exhibited normal cardiomyocyte proliferation at postnatal day seven and had no defects in cardiac structure or function but developed cardiac hypertrophy and fibrosis late in life. The development of cardiomyocyte hypertrophy and cardiac fibrosis in aged Foxm1-deficient mice was associated with reduced expression of Hey2, an important regulator of cardiac homeostasis, and increased expression of genes critical for cardiac remodeling, including MMP9, αSMA, fibronectin and vimentin. We also found that following aortic constriction Foxm1 mRNA and protein were induced in cardiomyocytes. However, Foxm1 deletion did not exacerbate cardiac hypertrophy or fibrosis following chronic pressure overload. Our results demonstrate that Foxm1 regulates genes critical for age-induced cardiomyocyte hypertrophy and cardiac fibrosis.

  5. Reduced Sodium Current in the Lateral Ventricular Wall Induces Inferolateral J-Waves.

    Science.gov (United States)

    Meijborg, Veronique M F; Potse, Mark; Conrath, Chantal E; Belterman, Charly N W; De Bakker, Jacques M T; Coronel, Ruben

    2016-01-01

    J-waves in inferolateral leads are associated with a higher risk for idiopathic ventricular fibrillation. We aimed to test potential mechanisms (depolarization or repolarization dependent) responsible for inferolateral J-waves. We hypothesized that inferolateral J-waves can be caused by regional delayed activation of myocardium that is activated late during normal conditions. Computer simulations were performed to evaluate how J-point elevation is influenced by reducing sodium current conductivity (GNa), increasing transient outward current conductivity (Gto), or cellular uncoupling in three predefined ventricular regions (lateral, anterior, or septal). Two pig hearts were Langendorff-perfused with selective perfusion with a sodium channel blocker of lateral or anterior/septal regions. Volume-conducted pseudo-electrocardiograms (ECG) were recorded to detect the presence of J-waves. Epicardial unipolar electrograms were simultaneously recorded to obtain activation times (AT). Simulation data showed that conduction slowing, caused by reduced sodium current, in lateral, but not in other regions induced inferolateral J-waves. An increase in transient outward potassium current or cellular uncoupling in the lateral zone elicited slight J-point elevations which did not meet J-wave criteria. Additional conduction slowing in the entire heart attenuated J-waves and J-point elevations on the ECG, because of masking by the QRS. Experimental data confirmed that conduction slowing attributed to sodium channel blockade in the left lateral but not in the anterior/septal ventricular region induced inferolateral J-waves. J-waves coincided with the delayed activation. Reduced sodium current in the left lateral ventricular myocardium can cause inferolateral J-waves on the ECG.

  6. The role of Ca2+/calmodulin-dependent protein kinase II and calcineurin in TNF-α-induced myocardial hypertrophy

    International Nuclear Information System (INIS)

    Wang, Gui-Jun; Wang, Hong-Xin; Yao, Yu-Sheng; Guo, Lian-Yi; Liu, Pei

    2012-01-01

    We investigated whether Ca 2+ /calmodulin-dependent kinase II (CaMKII) and calcineurin (CaN) are involved in myocardial hypertrophy induced by tumor necrosis factor α (TNF-α). The cardiomyocytes of neonatal Wistar rats (1-2 days old) were cultured and stimulated by TNF-α (100 µg/L), and Ca 2+ signal transduction was blocked by several antagonists, including BAPTA (4 µM), KN-93 (0.2 µM) and cyclosporin A (CsA, 0.2 µM). Protein content, protein synthesis, cardiomyocyte volumes, [Ca 2+ ] i transients, CaMKIIδ B and CaN were evaluated by the Lowry method, [ 3 H]-leucine incorporation, a computerized image analysis system, a Till imaging system, and Western blot analysis, respectively. TNF-α induced a significant increase in protein content in a dose-dependent manner from 10 µg/L (53.56 µg protein/well) to 100 µg/L (72.18 µg protein/well), and in a time-dependent manner from 12 h (37.42 µg protein/well) to 72 h (42.81 µg protein/well). TNF-α (100 µg/L) significantly increased the amplitude of spontaneous [Ca 2+ ] i transients, the total protein content, cell size, and [ 3 H]-leucine incorporation in cultured cardiomyocytes, which was abolished by 4 µM BAPTA, an intracellular Ca 2+ chelator. The increases in protein content, cell size and [ 3 H]-leucine incorporation were abolished by 0.2 µM KN-93 or 0.2 µM CsA. TNF-α increased the expression of CaMKIIδ B by 35.21% and that of CaN by 22.22% compared to control. These effects were abolished by 4 µM BAPTA, which itself had no effect. These results suggest that TNF-α induces increases in [Ca 2+ ] i , CaMKIIδ B and CaN and promotes cardiac hypertrophy. Therefore, we hypothesize that the Ca 2+ /CaMKII- and CaN-dependent signaling pathways are involved in myocardial hypertrophy induced by TNF-α

  7. Gender and post-ischemic recovery of hypertrophied rat hearts

    Directory of Open Access Journals (Sweden)

    Popov Kirill M

    2006-03-01

    female than male non-hypertrophied hearts. Glucose oxidation was lower in female than male hearts and was unaffected by hypertrophy or ischemia. Consequently, non-oxidative catabolism of glucose after ischemia was lowest in male non-hypertrophied hearts and comparably elevated in hypertrophied hearts of both sexes. These differences in non-oxidative glucose catabolism were inversely related to post-ischemic functional recovery. Conclusion Gender does not significantly influence post-ischemic function of hypertrophied hearts, even though female sex is detrimental to post-ischemic function in non-hypertrophied hearts. Differences in glucose catabolism may contribute to hypertrophy-induced and gender-related differences in post-ischemic function.

  8. Overexpressed connective tissue growth factor in cardiomyocytes attenuates left ventricular remodeling induced by angiotensin II perfusion.

    Science.gov (United States)

    Zhang, Ying; Yan, Hua; Guang, Gong-Chang; Deng, Zheng-Rong

    2017-01-01

    To evaluate the improving effects of specifically overexpressed connective tissue growth factor (CTGF) in cardiomyocytes on mice with hypertension induced by angiotensin II (AngII) perfusion, 24 transgenic mice with cardiac-restricted overexpression of CTGF (Tg-CTGF) were divided into two equal groups that were perfused with acetic acid and AngII, respectively, for 7 days. Another 24 cage-control wild-type C57BL/6 mice (NLC) were divided and treated identically. Blood pressure was detected by caudal artery cannulation. Cardiac structural and functional changes were observed by echocardiography. Cardiac fibrosis was detected by Masson staining. After AngII perfusion, blood pressures of NLC and Tg-CTGF mice, especially those of the formers, significantly increased. Compared with NLC + AngII group, Tg-CTGF + AngII group had significantly lower left ventricular posterior wall thickness at end-diastole and left ventricular posterior wall thickness at end-systole as well as significantly higher left ventricular end-systolic diameter and left ventricular end-diastolic diameter (P tissues (P < 0.05). Tg-CTGF can protect AngII-induced cardiac remodeling of mice with hypertension by mitigating inflammatory response. CTGF may be a therapy target for hypertension-induced myocardial fibrosis, but the detailed mechanism still needs in-depth studies.

  9. Zinc-finger protein 418 overexpression protects against cardiac hypertrophy and fibrosis.

    Directory of Open Access Journals (Sweden)

    Liming Pan

    Full Text Available This study aimed to investigated the effect and mechanism of zinc-finger protein 418 (ZNF418 on cardiac hypertrophy caused by aortic banding (AB, phenylephrine (PE or angiotensin II (Ang II in vivo and in vitro.The expression of ZNF418 in hearts of patients with dilated cardiomyopathy (DCM or hypertrophic cardiomyopathy (HCM and AB-induced cardiac hypertrophy mice, as well as in Ang II- or PE-induced hypertrophic primary cardiomyocytes was detected by western blotting. Then, the expression of ZNF418 was up-regulated or down-regulated in AB-induced cardiac hypertrophy mice and Ang II -induced hypertrophic primary cardiomyocytes. The hypertrophic responses and fibrosis were evaluated by echocardiography and histological analysis. The mRNA levels of hypertrophy markers and fibrotic markers were detected by RT-qPCR. Furthermore, the phosphorylation and total levels of c-Jun were measured by western blotting.ZNF418 was markedly down-regulated in hearts of cardiac hypertrophy and hypertrophic primary cardiomyocytes. Down-regulated ZNF418 exacerbated the myocyte size and fibrosis, moreover increased the mRNA levels of ANP, BNP, β-MHC, MCIP1.4, collagen 1a, collagen III, MMP-2 and fibronection in hearts of AB-treated ZNF418 knockout mice or Ang II-treated cardiomyocytes with AdshZNF418. Conversely, these hypertrophic responses were reduced in the ZNF418 transgenic (TG mice treated by AB and the AdZNF418-transfected primary cardiomyocytes treated by Ang II. Additionally, the deficiency of ZNF418 enhanced the phosphorylation level of c-jun, and overexpression of ZNF418 suppressed the phosphorylation level of c-jun in vivo and in vitro.ZNF418 maybe attenuate hypertrophic responses by inhibiting the activity of c-jun/AP-1.

  10. Prognostic Value of Electrocardiographic Left Ventricular Hypertrophy on Cardiovascular Risk in a Non-hypertensive Community-based Population.

    Science.gov (United States)

    Tanaka, Kentaro; Tanaka, Fumitaka; Onoda, Toshiyuki; Tanno, Kozo; Ohsawa, Masaki; Sakata, Kiyomi; Omama, Shinichi; Ogasawara, Kuniaki; Ishibashi, Yasuhiro; Itai, Kazuyoshi; Kuribayashi, Toru; Okayama, Akira; Nakamura, Motoyuki

    2018-04-06

    The appearance of left ventricular hypertrophy on 12-lead electrocardiography (ECG-LVH) has been clarified to be associated with the risk of incidence of cardiovascular events (CVEs) in hypertensive individuals and the general population, but not enough in non-hypertensive individuals. A total of 4,927 non-hypertensive individuals ≥ 40 years of age who were free of CVE in the general population were followed for the incidence of CVE. ECG-LVH was defined according to criteria of the Sokolow-Lyon (SL) voltage, Cornell voltage (CV), or Cornell voltage product (CP). During the average 9.8 ± 2.0 years of follow-up, 267 individuals (5.4%) had their first CVE. The hazard ratio (HR) for the incidence of CVE after full adjustment by potential confounders significantly increased in the individuals with ECG-LVH by any criteria of the SL voltage, CV, and CP (HR = 1.77, p < 0.001) compared to those with no ECG-LVH. This association was significant also in individuals without any of obesity, dyslipidemia, and diabetes mellitus or those with systolic BP <120 mmHg and diastolic BP < 80mmHg. Furthermore, ECG-LVH by each criteria provided the reclassification improvement for the CVE risk prediction model by the Framingham 10-year risk score (the net reclassification improvement = 0.17 to 0.22, each p value < 0.010). In the absence of hypertension, ECG-LVH parameters are associated with the increased risk of developed CVEs independent of the established risk factors and provide the additional prognostic value in an assessment of the CVE risk using the traditional risk factors.

  11. Increased rho kinase activity in mononuclear cells of dialysis and stage 3-4 chronic kidney disease patients with left ventricular hypertrophy: Cardiovascular risk implications.

    Science.gov (United States)

    Calò, Lorenzo A; Vertolli, Ugo; Pagnin, Elisa; Ravarotto, Verdiana; Davis, Paul A; Lupia, Mario; Naso, Elena; Maiolino, Giuseppe; Naso, Agostino

    2016-03-01

    Cardiovascular disease (CVD) is the leading cause of excess mortality in chronic kidney disease (CKD) and dialysis patients (DP) who have higher prevalence of left ventricular hypertrophy (LVH), the strongest predictor of CV events. Rho kinase (ROCK) activation is linked in hypertensive patients to cardiac remodeling while ROCK inhibition suppresses cardiomyocyte hypertrophy and, in a human clinical condition opposite to hypertension, its downregulation associates with lack of CV remodeling. Information on ROCK activation-LVH link in CKD and DP is lacking. Mononuclear cells (PBMCs) MYPT-1 phosphorylation, a marker of ROCK activity, and the effect of fasudil, a ROCK inhibitor, on MYPT-1 phosphorylation were assessed in 23 DPs, 13 stage 3-4 CKD and 36 healthy subjects (HS) by Western blot. LV mass was assessed by M-mode echocardiography. DP and CKD had higher MYPT-1 phosphorylation compared to HS (p<0.001 and p=0.003). Fasudil (500 and 1000μM) dose dependently reduced MYPT-1 phosphorylation in DP (p<0.01). DP had higher LV mass than CKD (p<0.001). MYPT-1 phosphorylation was higher in patients with LVH (p=0.009) and correlated with LV mass both in DP and CKD with LVH (p<0.001 and p=0.006). In DP and CKD, ROCK activity tracks with LVH. This ROCK activation-LVH link provided in these CVD high-risk patients along with similar findings in hypertensive patients and added to opposite findings in a human model opposite to hypertension and in type 2 diabetic patients, identify ROCK activation as a potential LVH marker and provide further rationale for ROCK activation inhibition as target of therapy in CVD high-risk patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. AKAP13 Rho-GEF and PKD-binding domain deficient mice develop normally but have an abnormal response to β-adrenergic-induced cardiac hypertrophy.

    Directory of Open Access Journals (Sweden)

    Matthew J Spindler

    Full Text Available A-kinase anchoring proteins (AKAPs are scaffolding molecules that coordinate and integrate G-protein signaling events to regulate development, physiology, and disease. One family member, AKAP13, encodes for multiple protein isoforms that contain binding sites for protein kinase A (PKA and D (PKD and an active Rho-guanine nucleotide exchange factor (Rho-GEF domain. In mice, AKAP13 is required for development as null embryos die by embryonic day 10.5 with cardiovascular phenotypes. Additionally, the AKAP13 Rho-GEF and PKD-binding domains mediate cardiomyocyte hypertrophy in cell culture. However, the requirements for the Rho-GEF and PKD-binding domains during development and cardiac hypertrophy are unknown.To determine if these AKAP13 protein domains are required for development, we used gene-trap events to create mutant mice that lacked the Rho-GEF and/or the protein kinase D-binding domains. Surprisingly, heterozygous matings produced mutant mice at Mendelian ratios that had normal viability and fertility. The adult mutant mice also had normal cardiac structure and electrocardiograms. To determine the role of these domains during β-adrenergic-induced cardiac hypertrophy, we stressed the mice with isoproterenol. We found that heart size was increased similarly in mice lacking the Rho-GEF and PKD-binding domains and wild-type controls. However, the mutant hearts had abnormal cardiac contractility as measured by fractional shortening and ejection fraction.These results indicate that the Rho-GEF and PKD-binding domains of AKAP13 are not required for mouse development, normal cardiac architecture, or β-adrenergic-induced cardiac hypertrophic remodeling. However, these domains regulate aspects of β-adrenergic-induced cardiac hypertrophy.

  13. Desmodium gangeticum root extract attenuates isoproterenol-induced cardiac hypertrophic growth in rats.

    Directory of Open Access Journals (Sweden)

    Divya Hitler

    2014-10-01

    Full Text Available Context: Desmodium gangeticum (L DC (Fabaceae; DG, a medicinal plant that grows in tropical habitats, is widely used to treat various ailments including digestive and inflammatory disorders. Aims: To investigate the possible cardioprotective activity of a DG root extract against isoproterenol (ISO-induced left ventricular cardiac hypertrophy (LVH in adult Wistar rats. Methods: Daily intraperitoneal administration of ISO (10 mg/kg body weight, single injection for 7 days induced LVH in rats. The LVH rats were post-treated orally with DG (100 mg/kg body weight for a period of 30 days. Thereafter, changes in heart weight (HW and body weight (BW, HW/BW ratio, percent of hypertrophy, collagen accumulation, activities of matrix metalloproteinase (MMP -2 and -9, superoxide dismutase (SOD and catalase (CAT enzymes, and the level of an oxidative stress marker, lipid peroxide (LPO, were determined. Results: HW/BW ratio, an indicator of hypertrophic growth, was significantly reduced in DG root post-treated LVH rats as compared with that for the non-treated LVH rats. The altered levels of ventricular LPO, collagen, MMPs-2 and -9, and antioxidant enzymes in the ISO-treated animals reverted back to near normal upon DG treatment. Further, the anti-hypertrophic activity of DG was comparable to that of the standard drug losartan (10 mg/kg. Conclusions: The results of the present study suggest that the aqueous root extract of DG exhibited anti-hypertrophic activity in-vivo by inhibiting ISO-induced ROS generation and MMP activities.

  14. Transcriptional profiling of rat skeletal muscle hypertrophy under restriction of blood flow.

    Science.gov (United States)

    Xu, Shouyu; Liu, Xueyun; Chen, Zhenhuang; Li, Gaoquan; Chen, Qin; Zhou, Guoqing; Ma, Ruijie; Yao, Xinmiao; Huang, Xiao

    2016-12-15

    Blood flow restriction (BFR) under low-intensity resistance training (LIRT) can produce similar effects upon muscles to that of high-intensity resistance training (HIRT) while overcoming many of the restrictions to HIRT that occurs in a clinical setting. However, the potential molecular mechanisms of BFR induced muscle hypertrophy remain largely unknown. Here, using a BFR rat model, we aim to better elucidate the mechanisms regulating muscle hypertrophy as induced by BFR and reveal possible clinical therapeutic targets for atrophy cases. We performed genome wide screening with microarray analysis to identify unique differentially expressed genes during rat muscle hypertrophy. We then successfully separated the differentially expressed genes from BRF treated soleus samples by comparing the Affymetrix rat Genome U34 2.0 array with the control. Using qRT-PCR and immunohistochemistry (IHC) we also analyzed other related differentially expressed genes. Results suggested that muscle hypertrophy induced by BFR is essentially regulated by the rate of protein turnover. Specifically, PI3K/AKT and MAPK pathways act as positive regulators in controlling protein synthesis where ubiquitin-proteasome acts as a negative regulator. This represents the first general genome wide level investigation of the gene expression profile in the rat soleus after BFR treatment. This may aid our understanding of the molecular mechanisms regulating and controlling muscle hypertrophy and provide support to the BFR strategies aiming to prevent muscle atrophy in a clinical setting. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Pathophysiology of cardiac hypertrophy and heart failure: signaling pathways and novel therapeutic targets.

    Science.gov (United States)

    Tham, Yow Keat; Bernardo, Bianca C; Ooi, Jenny Y Y; Weeks, Kate L; McMullen, Julie R

    2015-09-01

    The onset of heart failure is typically preceded by cardiac hypertrophy, a response of the heart to increased workload, a cardiac insult such as a heart attack or genetic mutation. Cardiac hypertrophy is usually characterized by an increase in cardiomyocyte size and thickening of ventricular walls. Initially, such growth is an adaptive response to maintain cardiac function; however, in settings of sustained stress and as time progresses, these changes become maladaptive and the heart ultimately fails. In this review, we discuss the key features of pathological cardiac hypertrophy and the numerous mediators that have been found to be involved in the pathogenesis of cardiac hypertrophy affecting gene transcription, calcium handling, protein synthesis, metabolism, autophagy, oxidative stress and inflammation. We also discuss new mediators including signaling proteins, microRNAs, long noncoding RNAs and new findings related to the role of calcineurin and calcium-/calmodulin-dependent protein kinases. We also highlight mediators and processes which contribute to the transition from adaptive cardiac remodeling to maladaptive remodeling and heart failure. Treatment strategies for heart failure commonly include diuretics, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers and β-blockers; however, mortality rates remain high. Here, we discuss new therapeutic approaches (e.g., RNA-based therapies, dietary supplementation, small molecules) either entering clinical trials or in preclinical development. Finally, we address the challenges that remain in translating these discoveries to new and approved therapies for heart failure.

  16. Aortopathy in Congenital Heart Disease in Adults: Aortic Dilatation with Decreased Aortic Elasticity that Impacts Negatively on Left Ventricular Function.

    Science.gov (United States)

    Niwa, Koichiro

    2013-04-01

    Bicuspid aortic valve and/or coarctation of the aorta are consistently associated with ascending aortic and para-coarctation medial abnormalities. Medial abnormalities in the ascending aorta are prevalent in other types of patients with a variety of forms congenital heart disease (CHD), such as single ventricle, persistent truncus arteriosus, transposition of the great arteries, hypoplastic left heart syndrome, tetralogy of Fallot. These abnormalities encompass a wide age range, and may predispose to dilatation, aneurysm, and rupture that necessitates aortic valve and root surgery. This dilatation can develop in CHD patients without stenotic region. These CHDs exhibit ongoing dilatation of the aortic root and reduced aortic elasticity and increased aortic stiffness that may relate to intrinsic properties of the aortic root. The concept of aortic dilatation is shifting a paradigm of aortic dilatation, as so called post stenotic dilatation, to primary intrinsic aortopahy. These aortic dilatation and increased stiffness can induce aortic aneurysm, rupture of the aorta and aortic regurgitation, but also provoke left ventricular hypertrophy, reduced coronary artery flow and left ventricular failure. We can recognize this association of aortic pathophysiological abnormality, aortic dilation and aorto-left ventricular interaction as a new clinical entity: "aortopathy".

  17. Association of myocardial cell necrosis with experimental cardiac hypertrophy

    Energy Technology Data Exchange (ETDEWEB)

    Revis, N W; Cameron, A J.V.

    1979-01-01

    Cardiac hypertrophy was induced in rabbits by injecting thyroxime or isoprenaline, or by surgically constricting the abdominal aorta. An increase in heart weight was associated with a change in the ratios of bound to free forms of five lysosomal enzymes, a change in serum creatine phosphokinase and lactate dehydrogenase, and a change in the morphology of the myocardial cells. Isoprenaline treatment for 5 days induced a maximal change in heart weight, in the ratio of lysosomal enzymes, and in the serum enzymes. Thyroxine treatment was required for 15 days before maximal changes in heart weight, ratio, and serum enzymes were observed. In contrast, coarctation of the aorta caused a progressive change in heart weight, in the ratio of lysosomal enzymes, and in serum enzymes. These results suggest that necrosis of the myocardial cells does indeed accompany cardiac hypertrophy. It was further observed that autophagosomes, degenerating mitochondria in the myocardial cells during the induction of cardiac hypertrophy, and myofibril lysis were found, all of which confirms the suggestion of myocardial cell necrosis in the experimentally enlarged heart.

  18. Mental stress-induced left ventricular dysfunction and adverse outcome in ischemic heart disease patients.

    Science.gov (United States)

    Sun, Julia L; Boyle, Stephen H; Samad, Zainab; Babyak, Michael A; Wilson, Jennifer L; Kuhn, Cynthia; Becker, Richard C; Ortel, Thomas L; Williams, Redford B; Rogers, Joseph G; O'Connor, Christopher M; Velazquez, Eric J; Jiang, Wei

    2017-04-01

    Aims Mental stress-induced myocardial ischemia (MSIMI) occurs in up to 70% of patients with clinically stable ischemic heart disease and is associated with increased risk of adverse prognosis. We aimed to examine the prognostic value of indices of MSIMI and exercise stress-induced myocardial ischemia (ESIMI) in a population of ischemic heart disease patients that was not confined by having a recent positive physical stress test. Methods and results The Responses of Mental Stress Induced Myocardial Ischemia to Escitalopram Treatment (REMIT) study enrolled 310 subjects who underwent mental and exercise stress testing and were followed annually for a median of four years. Study endpoints included time to first and total rate of major adverse cardiovascular events, defined as all-cause mortality and hospitalizations for cardiovascular causes. Cox and negative binomial regression adjusting for age, sex, resting left ventricular ejection fraction, and heart failure status were used to examine associations of indices of MSIMI and ESIMI with study endpoints. The continuous variable of mental stress-induced left ventricular ejection fraction change was significantly associated with both endpoints (all p values mental stress, patients had a 5% increase in the probability of a major adverse cardiovascular event at the median follow-up time and a 20% increase in the number of major adverse cardiovascular events endured over the follow-up period of six years. Indices of ESIMI did not predict endpoints ( ps > 0.05). Conclusion In patients with stable ischemic heart disease, mental, but not exercise, stress-induced left ventricular ejection fraction change significantly predicts risk of future adverse cardiovascular events.

  19. Various manifestations of hypertrophic cardiomyopathy on ultrafast computed tomography

    International Nuclear Information System (INIS)

    Sekiya, Tohru; Karikomi, Masahito; Ohshiro, Masaya; Iwakami, Masayoshi; Takamoto, Toshihiko; Sakamoto, Tsuguya

    1992-01-01

    Ultrafast computed tomography was performed in 30 patients with hypertrophic cardiomyopathy and images were assessed on variability of left ventricular hypertrophy, the pattern of left ventricular contraction, right ventricular hypertrophy, dilatation of the left atrium, and thickening of the mitral valve. Fifteen (50.0%) of 30 patients had asymmetric septal hypertrophy, six (20.0%) had diffuse hypertrophy, and nine (30.0%) had apical hypertrophy. In eleven patients with asymmetric septal hypertrophy and two with apical hypertrophy, non-hypertrophied segments in end-diastole showed vigorous contraction. Sixteen patients showed homogeneous left ventricular contraction and one showed partial apical contraction. Right ventricular hypertrophy was noted in 12 patients (40.0%), dilatation of the left atrium in 13 patients (43.3%), and mitral valve thickening in three (10.0%). Ultrafast computed tomography was useful in the evaluation of apical hypertrophy and right ventricular hypertrophy, which could be difficult to obtain by echocardiography. (author)

  20. Phlorizin Prevents Glomerular Hyperfiltration but not Hypertrophy in Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Slava Malatiali

    2008-01-01

    Full Text Available The relationships of renal and glomerular hypertrophies to development of hyperfiltration and proteinuria early in streptozotocin-induced diabetes were explored. Control, diabetic, phlorizin-treated controls, and diabetic male Fischer rats were used. Phlorizin (an Na+-glucose cotransport inhibitor was given at a dose sufficient to normalize blood glucose. Inulin clearance (Cinulin and protein excretion rate (PER were measured. For morphometry, kidney sections were stained with periodic acid Schiff. At one week, diabetes PER increased 2.8-folds (P<.001, Cinulin increased 80% (P<.01. Kidney wet and dry weights increased 10%–12% (P<.05, and glomerular tuft area increased 9.3% (P<.001. Phlorizin prevented proteinuria, hyperfiltration, and kidney hypertrophy, but not glomerular hypertrophy. Thus, hyperfiltration, proteinuria, and whole kidney hypertrophy were related to hyperglycemia but not to glomerular growth. Diabetic glomerular hypertrophy constitutes an early event in the progression of glomerular pathology which occurs in the absence of mesangial expansion and persists even after changes in protein excretion and GFR are reversed through glycemic control.

  1. Effects of contraction mode and stimulation frequency on electrical stimulation-induced skeletal muscle hypertrophy.

    Science.gov (United States)

    Ashida, Yuki; Himori, Koichi; Tatebayashi, Daisuke; Yamada, Ryotaro; Ogasawara, Riki; Yamada, Takashi

    2018-02-01

    We compared the skeletal muscle hypertrophy resulting from isometric (Iso) or eccentric (Ecc) electrical stimulation (ES) training with different stimulation frequencies. Male Wistar rats were assigned to the Iso and Ecc groups. These were divided into three further subgroups that were stimulated at 10 Hz (Iso-10 and Ecc-10), 30 Hz (Iso-30 and Ecc-30), or 100 Hz (Iso-100 and Ecc-100). In experiment 1, the left plantarflexor muscles were stimulated every other day for 3 wk. In experiment 2, mammalian target of rapamycin complex 1 (mTORC1) signaling was investigated 6 h after one bout of ES. The contralateral right muscle served as a control (non-ES). Ecc contractions comprised forced dorsiflexion combined with ES. The peak torque and torque-time integral during ES were higher in the Ecc group than that in the Iso group in all stimulation frequencies examined. The gastrocnemius muscle weight normalized to body weight in ES side was increased compared with the non-ES side by 6, 7, and 17% in the Ecc-30, Iso-100, and Ecc-100 groups, respectively, with a greater gain in Ecc-100 than the Ecc-30 and Iso-100 groups. The p70S6K (Thr389) phosphorylation level was higher in the Ecc-30 and -100 than in the Iso-30 and -100 groups, respectively. The peak torque and torque-time integral were highly correlated with the magnitude of increase in muscle mass and the phosphorylation of p70S6K. These data suggest that ES-induced muscle hypertrophy and mTORC1 activity are determined by loading intensity and volume during muscle contraction independent of the contraction mode. NEW & NOTEWORTHY Eccentric contraction and high-frequency stimulation (HFS) are regarded as an effective way to increase muscle mass by electrical stimulation (ES) training. However, little is known about whether muscle hypertrophy is affected by contraction mode and stimulation frequency in ES training. Here, we provide the evidence that muscle hypertrophy and mammalian target of rapamycin complex 1 activity are

  2. Voltage dependent potassium channel remodeling in murine intestinal smooth muscle hypertrophy induced by partial obstruction.

    Science.gov (United States)

    Liu, Dong-Hai; Huang, Xu; Guo, Xin; Meng, Xiang-Min; Wu, Yi-Song; Lu, Hong-Li; Zhang, Chun-Mei; Kim, Young-chul; Xu, Wen-Xie

    2014-01-01

    Partial obstruction of the small intestine causes obvious hypertrophy of smooth muscle cells and motility disorder in the bowel proximate to the obstruction. To identify electric remodeling of hypertrophic smooth muscles in partially obstructed murine small intestine, the patch-clamp and intracellular microelectrode recording methods were used to identify the possible electric remodeling and Western blot, immunofluorescence and immunoprecipitation were utilized to examine the channel protein expression and phosphorylation level changes in this research. After 14 days of obstruction, partial obstruction caused obvious smooth muscle hypertrophy in the proximally located intestine. The slow waves of intestinal smooth muscles in the dilated region were significantly suppressed, their amplitude and frequency were reduced, whilst the resting membrane potentials were depolarized compared with normal and sham animals. The current density of voltage dependent potassium channel (KV) was significantly decreased in the hypertrophic smooth muscle cells and the voltage sensitivity of KV activation was altered. The sensitivity of KV currents (IKV) to TEA, a nonselective potassium channel blocker, increased significantly, but the sensitivity of IKv to 4-AP, a KV blocker, stays the same. The protein levels of KV4.3 and KV2.2 were up-regulated in the hypertrophic smooth muscle cell membrane. The serine and threonine phosphorylation levels of KV4.3 and KV2.2 were significantly increased in the hypertrophic smooth muscle cells. Thus this study represents the first identification of KV channel remodeling in murine small intestinal smooth muscle hypertrophy induced by partial obstruction. The enhanced phosphorylations of KV4.3 and KV2.2 may be involved in this process.

  3. VO(2peak), myocardial hypertrophy, and myocardial blood flow in endurance-trained men.

    Science.gov (United States)

    Laaksonen, Marko S; Heinonen, Ilkka; Luotolahti, Matti; Knuuti, Juhani; Kalliokoski, Kari K

    2014-08-01

    Endurance training induces cardiovascular and metabolic adaptations, leading to enhanced endurance capacity and exercise performance. Previous human studies have shown contradictory results in functional myocardial vascular adaptations to exercise training, and we hypothesized that this may be related to different degrees of hypertrophy in the trained heart. We studied the interrelationships between peak aerobic power (V˙O2peak), myocardial blood flow (MBF) at rest and during adenosine-induced vasodilation, and parameters of myocardial hypertrophy in endurance-trained (ET, n = 31) and untrained (n = 17) subjects. MBF and myocardial hypertrophy were studied using positron emission tomography and echocardiography, respectively. Both V˙O2peak (P negatively with adenosine-stimulated MBF, but when LV mass was taken into account as a partial correlate, this correlation disappeared. The present results show that increased LV mass in ET subjects explains the reduced hyperemic myocardial perfusion in this subject population and suggests that excessive LV hypertrophy has negative effect on cardiac blood flow capacity.

  4. Study of the association between left ventricular diastolic impairment and cardiac autonomic neuropathy in diabetic patients using [123I] metaiodobenzylguanidine scintigraphy

    International Nuclear Information System (INIS)

    Suzuki, Rokuro; Tanaka, Shiro; Tojo, Osamu; Ishii, Tomofusa; Sato, Toshihiko; Fujii, Satoru; Tumura, Kei.

    1994-01-01

    The association between left ventricular (LV) diastolic dysfunction and myocardial MIBG accumulation was investigated. The subjects were 14 Type II diabetic patients who had no evidence of ischemic heat disease, LV hypertrophy or dilated cardiomyopathy as determined by exercise Tl-201 myocardial scintigraphy and echocardiography. In 14 diabetic patients, isovolumic relaxation time (IRT) was measured by M-mode echocardiography, and the subjects were subdivided into two groups: Group1, 8 patients with impaired left ventricular diastolic function (IRT≥80 msec), and Group 2, 6 patients with normal left ventricular diastolic function (IRT 123 I-MIBG myocardial scintigraphy was performed, and the myocardial accumulation of 123 I-MIBG was investigated. The ratio of myocardial to mediastinal MIBG uptake was significantly (p<0.01) lower in Group 1 than in Group 2. And scintigraphic defects were significantly (p<0.05) more numerous in Group 1 than in Group 2. Patients in Group 1 had a greater frequency of cardiac autonomic neuropathy evaluated by QTc interval and coefficient of variation of R-R interval, when compared with Group 2. These data suggest that, in diabetic patients with no evidence of ischemic heart disease, LV hypertrophy or dilated cardiomyopathy, impairment of left ventricular diastolic function is associated with cardiac autonomic neuropathy. (author)

  5. Left ventricular mechanical adaptation to chronic aortic regurgitation in intact dogs

    International Nuclear Information System (INIS)

    Florenzano, F.; Glantz, S.A.

    1987-01-01

    Increased and end-diastolic wall stress has been hypothesized to stimulate left ventricular (LV) hypertrophy following volume overload. The authors instrumented intact-chest dogs with radiopaque markers in both ventricles and created volume overload by puncturing one aortic valve cusp. An x-ray system with biplane fluoroscopic and cineradiographic capabilities was used. End-diastolic stress increased immediately, then fell over 3 mo as the heart hypertrophied. End-systolic stress did not change significantly. Chamber contractility, quantified as E/sub max/, the end-systolic pressure-volume line slope, increased. E/sub max/ normalized by multiplying by LV mass increased following the lesion before but not after β-blockade with propranolol and did not change significantly over time, suggesting that chamber contractility changed because of increased mass and sympathetic tone rather than changed intrinsic muscle function. LV mass did not initially correlate with lesion size, but steady-state mass did. Over the range of lesions the authors produced, increased end-diastolic wall stress appears to stimulate hypertrophy at a fixed rate, which stops when end-diastolic wall stress has been reduced to an acceptable level

  6. Discriminating between adaptive and carcinogenic liver hypertrophy in rat studies using logistic ridge regression analysis of toxicogenomic data: The mode of action and predictive models.

    Science.gov (United States)

    Liu, Shujie; Kawamoto, Taisuke; Morita, Osamu; Yoshinari, Kouichi; Honda, Hiroshi

    2017-03-01

    Chemical exposure often results in liver hypertrophy in animal tests, characterized by increased liver weight, hepatocellular hypertrophy, and/or cell proliferation. While most of these changes are considered adaptive responses, there is concern that they may be associated with carcinogenesis. In this study, we have employed a toxicogenomic approach using a logistic ridge regression model to identify genes responsible for liver hypertrophy and hypertrophic hepatocarcinogenesis and to develop a predictive model for assessing hypertrophy-inducing compounds. Logistic regression models have previously been used in the quantification of epidemiological risk factors. DNA microarray data from the Toxicogenomics Project-Genomics Assisted Toxicity Evaluation System were used to identify hypertrophy-related genes that are expressed differently in hypertrophy induced by carcinogens and non-carcinogens. Data were collected for 134 chemicals (72 non-hypertrophy-inducing chemicals, 27 hypertrophy-inducing non-carcinogenic chemicals, and 15 hypertrophy-inducing carcinogenic compounds). After applying logistic ridge regression analysis, 35 genes for liver hypertrophy (e.g., Acot1 and Abcc3) and 13 genes for hypertrophic hepatocarcinogenesis (e.g., Asns and Gpx2) were selected. The predictive models built using these genes were 94.8% and 82.7% accurate, respectively. Pathway analysis of the genes indicates that, aside from a xenobiotic metabolism-related pathway as an adaptive response for liver hypertrophy, amino acid biosynthesis and oxidative responses appear to be involved in hypertrophic hepatocarcinogenesis. Early detection and toxicogenomic characterization of liver hypertrophy using our models may be useful for predicting carcinogenesis. In addition, the identified genes provide novel insight into discrimination between adverse hypertrophy associated with carcinogenesis and adaptive hypertrophy in risk assessment. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Loss of microRNA-22 prevents high-fat diet induced dyslipidemia and increases energy expenditure without affecting cardiac hypertrophy.

    Science.gov (United States)

    Diniz, Gabriela Placoná; Huang, Zhan-Peng; Liu, Jianming; Chen, Jinghai; Ding, Jian; Fonseca, Renata Inzinna; Barreto-Chaves, Maria Luiza; Donato, Jose; Hu, Xiaoyun; Wang, Da-Zhi

    2017-12-15

    Obesity is associated with development of diverse diseases, including cardiovascular diseases and dyslipidemia. MiRNA-22 (miR-22) is a critical regulator of cardiac function and targets genes involved in metabolic processes. Previously, we generated miR-22 null mice and we showed that loss of miR-22 blunted cardiac hypertrophy induced by mechanohormornal stress. In the present study, we examined the role of miR-22 in the cardiac and metabolic alterations promoted by high-fat (HF) diet. We found that loss of miR-22 attenuated the gain of fat mass and prevented dyslipidemia induced by HF diet, although the body weight gain, or glucose intolerance and insulin resistance did not seem to be affected. Mechanistically, loss of miR-22 attenuated the increased expression of genes involved in lipogenesis and inflammation mediated by HF diet. Similarly, we found that miR-22 mediates metabolic alterations and inflammation induced by obesity in the liver. However, loss of miR-22 did not appear to alter HF diet induced cardiac hypertrophy or fibrosis in the heart. Our study therefore establishes miR-22 as an important regulator of dyslipidemia and suggests it may serve as a potential candidate in the treatment of dyslipidemia associated with obesity. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  8. Effect of Resistance Exercise Training Associated with Skeletal Muscle Hypertrophy on Serum Pro-Inflammatory Cytokines in STZ-induced Diabetes

    Directory of Open Access Journals (Sweden)

    Mahdieh Molanouri Shamsi

    2016-06-01

    Full Text Available Skeletal muscle atrophy is associated with type 1 diabetes. Effects of resistance exercise training associated with skeletal muscle hypertrophy on serum inflammatory cytokines was exactly not clarified. Protein levels of inflammatory cytokines IL-6, TNF-α, and interleukin-1beta (IL-1β in serum of healthy and streptozotocin (STZ- induced diabetic rats subjected to resistance exercise training were assessed in this study. Rats were divided into the control, training, control diabetic and diabetic training groups. Training groups performed the resistance training consisted of climbing a 1 m ladder with increasing weight added to the tail. Proteins levels of IL-6, TNF-α and IL-1β in serum were measured by the ELIZA method. The results of this study indicated that resistance training induced skeletal muscle hypertrophy in diabetic samples (P<0.05. Also, Resistance training decrease IL-6 protein levels in serum. Inflammatory cytokines could act as stress factors in diabetes. It seems that this kind of exercise training individually could not change cytokines levels in serum.

  9. Magnetic resonance tissue phase mapping demonstrates altered left ventricular diastolic function in children with chronic kidney disease

    International Nuclear Information System (INIS)

    Gimpel, Charlotte; Pohl, Martin; Jung, Bernd A.; Jung, Sabine; Brado, Johannes; Odening, Katja E.; Schwendinger, Daniel; Burkhardt, Barbara; Geiger, Julia; Arnold, Raoul

    2017-01-01

    Echocardiographic examinations have revealed functional cardiac abnormalities in children with chronic kidney disease. To assess the feasibility of MRI tissue phase mapping in children and to assess regional left ventricular wall movements in children with chronic kidney disease. Twenty pediatric patients with chronic kidney disease (before or after renal transplantation) and 12 healthy controls underwent tissue phase mapping (TPM) to quantify regional left ventricular function through myocardial long (Vz) and short-axis (Vr) velocities at all 3 levels of the left ventricle. Patients and controls (age: 8 years - 20 years) were matched for age, height, weight, gender and heart rate. Patients had higher systolic blood pressure. No patient had left ventricular hypertrophy on MRI or diastolic dysfunction on echocardiography. Fifteen patients underwent tissue Doppler echocardiography, with normal z-scores for mitral early diastolic (V E ), late diastolic (V A ) and peak systolic (V S ) velocities. Throughout all left ventricular levels, peak diastolic Vz and Vr (cm/s) were reduced in patients: Vz base -10.6 ± 1.9 vs. -13.4 ± 2.0 (P < 0.0003), Vz mid -7.8 ± 1.6 vs. -11 ± 1.5 (P < 0.0001), Vz apex -3.8 ± 1.6 vs. -5.3 ± 1.6 (P = 0.01), Vr base -4.2 ± 0.8 vs. -4.9 ± 0.7 (P = 0.01), Vr mid -4.7 ± 0.7 vs. -5.4 ± 0.7 (P = 0.01), Vr apex -4.7 ± 1.4 vs. -5.6 ± 1.1 (P = 0.05). Tissue phase mapping is feasible in children and adolescents. Children with chronic kidney disease show significantly reduced peak diastolic long- and short-axis left ventricular wall velocities, reflecting impaired early diastolic filling. Thus, tissue phase mapping detects chronic kidney disease-related functional myocardial changes before overt left ventricular hypertrophy or echocardiographic diastolic dysfunction occurs. (orig.)

  10. Low-intensity interval exercise training attenuates coronary vascular dysfunction and preserves Ca²⁺-sensitive K⁺ current in miniature swine with LV hypertrophy.

    Science.gov (United States)

    Emter, Craig A; Tharp, Darla L; Ivey, Jan R; Ganjam, Venkataseshu K; Bowles, Douglas K

    2011-10-01

    Coronary vascular dysfunction has been observed in several models of heart failure (HF). Recent evidence indicates that exercise training is beneficial for patients with HF, but the precise intensity and underlying mechanisms are unknown. Left ventricular (LV) hypertrophy can play a significant role in the development of HF; therefore, the purpose of this study was to assess the effects of low-intensity interval exercise training on coronary vascular function in sedentary (HF) and exercise trained (HF-TR) aortic-banded miniature swine displaying LV hypertrophy. Six months postsurgery, in vivo coronary vascular responses to endothelin-1 (ET-1) and adenosine were measured in the left anterior descending coronary artery. Baseline and maximal coronary vascular conductance were similar between all groups. ET-1-induced reductions in coronary vascular conductance (P < 0.05) were greater in HF vs. sedentary control and HF-TR groups. Pretreatment with the ET type A (ET(A)) receptor blocker BQ-123 prevented ET-1 hypersensitivity in HF animals. Whole cell voltage clamp was used to characterize composite K(+) currents (I(K(+))) in coronary smooth muscle cells. Raising internal Ca(2+) from 200 to 500 nM increased Ca(2+)-sensitive K(+) current in HF-TR and control, but not HF animals. In conclusion, an ET(A)-receptor-mediated hypersensitivity to ET-1, elevated resting LV wall tension, and decreased coronary smooth muscle cell Ca(2+)-sensitive I(K(+)) was found in sedentary animals with LV hypertrophy. Low-intensity interval exercise training preserved normal coronary vascular function and smooth muscle cell Ca(2+)-sensitive I(K(+)), illustrating a potential mechanism underlying coronary vascular dysfunction in a large-animal model of LV hypertrophy. Our results demonstrate the potential clinical impact of exercise on coronary vascular function in HF patients displaying pathological LV hypertrophy.

  11. Histone deacetylase inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in DOCA-induced hypertensive rats.

    Science.gov (United States)

    Lee, Eunjo; Song, Min-Ji; Lee, Hae-Ahm; Kang, Seol-Hee; Kim, Mina; Yang, Eun Kyoung; Lee, Do Young; Ro, Seonggu; Cho, Joong Myung; Kim, Inkyeom

    2016-09-01

    CG200745 is a novel inhibitor of histone deacetylases (HDACs), initially developed for treatment of various hematological and solid cancers. Because it is water-soluble, it can be administered orally. We hypothesized that the HDAC inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in deoxycorticosterone acetate (DOCA)-induced hypertensive rats. For establishment of hypertension, 40 mg/kg of DOCA was subcutaneously injected four times weekly into Sprague-Dawley rats. All the rats used in this study including those in the sham group had been unilaterally nephrectomized and allowed free access to drinking water containing 1% NaCl. Systolic blood pressure was measured by the tail-cuff method. Blood chemistry including sodium, potassium, glucose, triglyceride, and cholesterol levels was analyzed. Sections of the heart were visualized after trichrome and hematoxylin and eosin stain. The expression of hypertrophic genes such as atrial natriuretic peptide A (Nppa) and atrial natriuretic peptide B (Nppb) in addition to fibrotic genes such as Collagen-1, Collagen-3, connective tissue growth factor (Ctgf), and Fibronectin were measured by quantitative real-time PCR (qRT-PCR). Injection of DOCA increased systolic blood pressure, heart weight, and cardiac fibrosis, which was attenuated by CG200745. Neither DOCA nor CG200745 affected body weight, vascular contraction and relaxation responses, and blood chemistry. Injection of DOCA increased expression of both hypertrophic and fibrotic genes, which was abrogated by CG200745. These results indicate that CG200745 attenuates cardiac hypertrophy and fibrosis in DOCA-induced hypertensive rats.

  12. The inhibitory effect of salmon calcitonin on tri-iodothyronine induction of early hypertrophy in articular cartilage.

    Directory of Open Access Journals (Sweden)

    Pingping Chen-An

    Full Text Available Salmon calcitonin has chondroprotective effect both in vitro and in vivo, and is therefore being tested as a candidate drug for cartilage degenerative diseases. Recent studies have indicated that different chondrocyte phenotypes may express the calcitonin receptor (CTR differentially. We tested for the presence of the CTR in chondrocytes from tri-iodothyronin (T3-induced bovine articular cartilage explants. Moreover, investigated the effects of human and salmon calcitonin on the explants.Early chondrocyte hypertrophy was induced in bovine articular cartilage explants by stimulation over four days with 20 ng/mL T3. The degree of hypertrophy was investigated by molecular markers of hypertrophy (ALP, IHH, COLX and MMP13, by biochemical markers of cartilage turnover (C2M, P2NP and AGNxII and histology. The expression of the CTR was detected by qPCR and immunohistochemistry. T3-induced explants were treated with salmon or human calcitonin. Calcitonin down-stream signaling was measured by levels of cAMP, and by the molecular markers.Compared with untreated control explants, T3 induction increased expression of the hypertrophic markers (p<0.05, of cartilage turnover (p<0.05, and of CTR (p<0.01. Salmon, but not human, calcitonin induced cAMP release (p<0.001. Salmon calcitonin also inhibited expression of markers of hypertrophy and cartilage turnover (p<0.05.T3 induced early hypertrophy of chondrocytes, which showed an elevated expression of the CTR and was thus a target for salmon calcitonin. Molecular marker levels indicated salmon, but not human, calcitonin protected the cartilage from hypertrophy. These results confirm that salmon calcitonin is able to modulate the CTR and thus have chondroprotective effects.

  13. Effects of valsartan and nebivolol on blood pressure, QT dispersion and left ventricular hypertrophy in hypertensive patients

    Directory of Open Access Journals (Sweden)

    Luminita Lăţea

    2010-06-01

    Full Text Available Objectives: The aim of this study was to analyze the antihypertensiveeffect of Valsartan and Nebivolol and their effects on QT dispersion and left ventricular hypertrophy (LVH in the treatment of naive hypertensive patients.Methods: A prospective study with a six-month follow-up was conducted on hypertensive patients with LVH and mild/ moderate essential hypertension. The patients were randomly assigned to Valsartan (80 to 160 mg/day or Nebivolol (5 to 10 mg/day groups. The study group consistedof 108 patients, 55 in the Valsartan group and 53 in the Nebivolol group.Results: The range of mean systolic blood pressure (SBP varied from 152±17 (baseline to 132±17 mmHg (follow-up in the Valsartan group (p<0.001; from 146±13 to 125±14 mmHg in the Nebivolol group (p<0.001. The decrease in mean diastolic blood pressure (DBP was 9.5±2.5 mmHg in the Valsartan group and 12.3±5.0 mmHg in the Nebivolol group. A significant reduction in QT and corrected QT (Bazett’s formula dispersion was observed in both groups, with a slightly higher reduction in the Valsartan group. Echocardiography showed a decreasein the left ventricle mass (LVM indices (p<0.05 in both groups with a greater reduction in the Valsartan group.Conclusion: Valsartan treatment was as effective as Nebivolol in reducing the 24 hour- SBP after a 6 month treatment. Nebivolol treatment proved to be superior to Valsartan in reducing DBP. Both therapies were effective in reducing the LVH; Valsartan proved to be superior to Nebivolol in reducing the QT interval indexes in relation to blood pressure and LVM reduction.

  14. Role of hypoxia-inducible factor in diabetic myocardial hypertrophy

    African Journals Online (AJOL)

    Diabetes or hyperglycemia disrupts HIF-mediated cardiac hypertrophy adaptive regulatory mechanism [14]. In diabetic retinopathy, abnormal increase of ... detection system. Flow cytometry. After digesting with EDTA-free trypsin, the H9C2 cells were centrifuged at 1000 rpm for 5 min. After discarding the medium, the cells ...

  15. Left ventricular assist device implantation in a patient who had previously undergone apical myectomy for hypertrophic cardiomyopathy.

    Science.gov (United States)

    Cho, Yang Hyun; Deo, Salil V; Topilsky, Yan; Grogan, Martha A; Park, Soon J

    2012-03-01

    Apical hypertrophy is a rare variant of hypertropic cardiomyopathy. These patients may present with end-stage congestive heart failure subsequent to long standing diastolic dysfunction. We report the technique for left ventricular assist device insertion in a patient with previous apical myectomy for hypertrophic cardiomyopathy. © 2012 Wiley Periodicals, Inc.

  16. Myocardial glucose metabolism is different between hypertrophic cardiomyopathy and hypertensive heart disease associated with asymmetrical septal hypertrophy

    International Nuclear Information System (INIS)

    Shiba, Nobuyuki; Kagaya, Yutaka; Ishide, Nobumasa; Takeyama, Daiya; Yamane, Yuriko; Chida, Masanobu; Otani, Hiroki; Shirato, Kunio; Ido, Tatsuo.

    1997-01-01

    Myocardial glucose metabolism has been shown to be heterogeneous in patients with hypertrophic cardiomyopathy (HCM). We tested the hypothesis that myocardial glucose metabolism differs between patients with HCM and those with hypertensive heart disease (HHD) associated with asymmetrical septal hypertrophy. We studied 12 patients with HCM, 7 HHD patients associated with asymmetrical septal hypertrophy using 18 F 2-deoxyglucose (FDG) and positron emission tomography. We calculated % FDG fractional uptake in the interventricular septum and posterolateral wall. Heterogeneity of FDG uptake was evaluated by % interregional coefficient of variation of FDG fractional uptake in each wall segment. In both the interventricular septum and posterolateral wall, % FDG fractional uptake was not significantly different between the two groups. The % interregional coefficient of variation for both interventricular septum (10.6±1.6 vs. 4.1±0.5, p<0.01) and posterolateral wall (5.9±0.7 vs. 3.8±0.5, p< 0.05) was significantly larger in patients with HCM than in HHD patients associated with asymmetrical septal hypertrophy. Echocardiography demonstrated that the degree of asymmetrical septal hypertrophy was similar between the two groups. These results suggest that myocardial glucose metabolism may be more heterogeneous in patients with HCM compared to HHD patients associated with asymmetrical septal hypertrophy, although the left ventricular shape is similar. The difference in the heterogeneity might have resulted from differences in the pathogeneses of the two diseases. (author)

  17. Coarctation induces alterations in basement membranes in the cardiovascular system

    DEFF Research Database (Denmark)

    Lipke, D W; McCarthy, K J; Elton, T S

    1993-01-01

    ventricular hypertrophy was maximal within 5 days. In immunohistochemical studies, fibronectin and laminin were increased and the basement membrane chondroitin sulfate proteoglycan decreased in both the subendothelial space and smooth muscle cell basement membranes of the aorta above the clip compared...... membrane components in the heart and vasculature peaked before maximal cardiac hypertrophy (5 days). These studies indicate that alterations in basement membrane component deposition in the hypertrophied vasculature occur at both transcriptional and translational levels and suggest that the cell attachment...

  18. Discriminating between adaptive and carcinogenic liver hypertrophy in rat studies using logistic ridge regression analysis of toxicogenomic data: The mode of action and predictive models

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Shujie; Kawamoto, Taisuke; Morita, Osamu [R& D, Safety Science Research, Kao Corporation, Tochigi (Japan); Yoshinari, Kouichi [Department of Molecular Toxicology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka (Japan); Honda, Hiroshi, E-mail: honda.hiroshi@kao.co.jp [R& D, Safety Science Research, Kao Corporation, Tochigi (Japan)

    2017-03-01

    Chemical exposure often results in liver hypertrophy in animal tests, characterized by increased liver weight, hepatocellular hypertrophy, and/or cell proliferation. While most of these changes are considered adaptive responses, there is concern that they may be associated with carcinogenesis. In this study, we have employed a toxicogenomic approach using a logistic ridge regression model to identify genes responsible for liver hypertrophy and hypertrophic hepatocarcinogenesis and to develop a predictive model for assessing hypertrophy-inducing compounds. Logistic regression models have previously been used in the quantification of epidemiological risk factors. DNA microarray data from the Toxicogenomics Project-Genomics Assisted Toxicity Evaluation System were used to identify hypertrophy-related genes that are expressed differently in hypertrophy induced by carcinogens and non-carcinogens. Data were collected for 134 chemicals (72 non-hypertrophy-inducing chemicals, 27 hypertrophy-inducing non-carcinogenic chemicals, and 15 hypertrophy-inducing carcinogenic compounds). After applying logistic ridge regression analysis, 35 genes for liver hypertrophy (e.g., Acot1 and Abcc3) and 13 genes for hypertrophic hepatocarcinogenesis (e.g., Asns and Gpx2) were selected. The predictive models built using these genes were 94.8% and 82.7% accurate, respectively. Pathway analysis of the genes indicates that, aside from a xenobiotic metabolism-related pathway as an adaptive response for liver hypertrophy, amino acid biosynthesis and oxidative responses appear to be involved in hypertrophic hepatocarcinogenesis. Early detection and toxicogenomic characterization of liver hypertrophy using our models may be useful for predicting carcinogenesis. In addition, the identified genes provide novel insight into discrimination between adverse hypertrophy associated with carcinogenesis and adaptive hypertrophy in risk assessment. - Highlights: • Hypertrophy (H) and hypertrophic

  19. Discriminating between adaptive and carcinogenic liver hypertrophy in rat studies using logistic ridge regression analysis of toxicogenomic data: The mode of action and predictive models

    International Nuclear Information System (INIS)

    Liu, Shujie; Kawamoto, Taisuke; Morita, Osamu; Yoshinari, Kouichi; Honda, Hiroshi

    2017-01-01

    Chemical exposure often results in liver hypertrophy in animal tests, characterized by increased liver weight, hepatocellular hypertrophy, and/or cell proliferation. While most of these changes are considered adaptive responses, there is concern that they may be associated with carcinogenesis. In this study, we have employed a toxicogenomic approach using a logistic ridge regression model to identify genes responsible for liver hypertrophy and hypertrophic hepatocarcinogenesis and to develop a predictive model for assessing hypertrophy-inducing compounds. Logistic regression models have previously been used in the quantification of epidemiological risk factors. DNA microarray data from the Toxicogenomics Project-Genomics Assisted Toxicity Evaluation System were used to identify hypertrophy-related genes that are expressed differently in hypertrophy induced by carcinogens and non-carcinogens. Data were collected for 134 chemicals (72 non-hypertrophy-inducing chemicals, 27 hypertrophy-inducing non-carcinogenic chemicals, and 15 hypertrophy-inducing carcinogenic compounds). After applying logistic ridge regression analysis, 35 genes for liver hypertrophy (e.g., Acot1 and Abcc3) and 13 genes for hypertrophic hepatocarcinogenesis (e.g., Asns and Gpx2) were selected. The predictive models built using these genes were 94.8% and 82.7% accurate, respectively. Pathway analysis of the genes indicates that, aside from a xenobiotic metabolism-related pathway as an adaptive response for liver hypertrophy, amino acid biosynthesis and oxidative responses appear to be involved in hypertrophic hepatocarcinogenesis. Early detection and toxicogenomic characterization of liver hypertrophy using our models may be useful for predicting carcinogenesis. In addition, the identified genes provide novel insight into discrimination between adverse hypertrophy associated with carcinogenesis and adaptive hypertrophy in risk assessment. - Highlights: • Hypertrophy (H) and hypertrophic

  20. Prolonged corrected QT interval is predictive of future stroke events even in subjects without ECG-diagnosed left ventricular hypertrophy.

    Science.gov (United States)

    Ishikawa, Joji; Ishikawa, Shizukiyo; Kario, Kazuomi

    2015-03-01

    We attempted to evaluate whether subjects who exhibit prolonged corrected QT (QTc) interval (≥440 ms in men and ≥460 ms in women) on ECG, with and without ECG-diagnosed left ventricular hypertrophy (ECG-LVH; Cornell product, ≥244 mV×ms), are at increased risk of stroke. Among the 10 643 subjects, there were a total of 375 stroke events during the follow-up period (128.7±28.1 months; 114 142 person-years). The subjects with prolonged QTc interval (hazard ratio, 2.13; 95% confidence interval, 1.22-3.73) had an increased risk of stroke even after adjustment for ECG-LVH (hazard ratio, 1.71; 95% confidence interval, 1.22-2.40). When we stratified the subjects into those with neither a prolonged QTc interval nor ECG-LVH, those with a prolonged QTc interval but without ECG-LVH, and those with ECG-LVH, multivariate-adjusted Cox proportional hazards analysis demonstrated that the subjects with prolonged QTc intervals but not ECG-LVH (1.2% of all subjects; incidence, 10.7%; hazard ratio, 2.70, 95% confidence interval, 1.48-4.94) and those with ECG-LVH (incidence, 7.9%; hazard ratio, 1.83; 95% confidence interval, 1.31-2.57) had an increased risk of stroke events, compared with those with neither a prolonged QTc interval nor ECG-LVH. In conclusion, prolonged QTc interval was associated with stroke risk even among patients without ECG-LVH in the general population. © 2014 American Heart Association, Inc.

  1. Ventricular Effective Refraction Period and Ventricular Repolarization Analysis in Experimental Tachycardiomyopathy in Swine.

    Science.gov (United States)

    Noszczyk-Nowak, Agnieszka; Pasławska, Urszula; Gajek, Jacek; Janiszewski, Adrian; Pasławski, Robert; Zyśko, Dorota; Nicpoń, Józef

    2016-01-01

    Swine are recognized animal models of human cardiovascular diseases. However, little is known on the CHF-associated changes in the electrophysiological ventricular parameters of humans and animals. The aim of this study was to analyze changes in the durations of ventricular effective refraction period (VERP), QT and QTc intervals of pigs with chronic tachycardia-induced tachycardiomyopathy (TIC). The study was comprised of 28 adult pigs (8 females and 20 males) of the Polish Large White breed. A one-chamber pacemaker was implanted in each of the 28 pigs. Electrocardiographic, echocardiographic and electrophysiological studies were carried out prior to the pacemaker implantation and at subsequent 4-week intervals. All electrocardiographic, echocardiographic and short electrophysiological study measurements in all swine were done under general anesthesia (propofol) after premedication with midazolam, medetomidine, and ketamine. No significant changes in the duration of QT interval and corrected QT interval (QTc) were observed during consecutive weeks of the experiment. The duration of the QTc interval of female pigs was shown to be significantly longer than that of the males throughout the whole study period. Beginning from the 12th week of rapid ventricular pacing, a significant increase in duration of VERP was observed in both male and female pigs. Males and females did not differ significantly in terms of VERP duration determined throughout the whole study period. Ventricular pacing, stimulation with 2 and 3 premature impulses at progressively shorter coupling intervals and an imposed rhythm of 130 bpm or 150 bpm induced transient ventricular tachycardia in one female pig and four male pigs. One episode of permanent ventricular tachycardia was observed. The number of induced arrhythmias increased proportionally to the severity of heart failure and duration of the experiment. However, relatively aggressive protocols of stimulation were required in order to induce

  2. Relationship of central and peripheral blood pressure to left ventricular mass in hypertensive patients.

    Science.gov (United States)

    Pérez-Lahiguera, Francisco J; Rodilla, Enrique; Costa, Jose A; Gonzalez, Carmen; Martín, Joaquin; Pascual, Jose M

    2012-12-01

    The purpose of the present study was to assess the relationship of central and peripheral blood pressure to left ventricular mass. Cross-sectional study that included 392 never treated hypertensive individuals. Measurement of office, 24-h ambulatory, and central blood pressure (obtained using applanation tonometry) and determination of left ventricular mass by echocardiography were performed in all patients. In a multiple regression analysis, with adjustment for age, gender and metabolic syndrome, 24-h blood pressure was more closely related to ventricular mass than the respective office and central blood pressures. Systolic blood pressures always exhibited a higher correlation than diastolic blood pressures in all 3 determinations. The correlation between left ventricular mass index and 24-h systolic blood pressure was higher than that of office (P<.002) or central systolic blood pressures (P<.002). Changes in 24-h systolic blood pressure caused the greatest variations in left ventricular mass index (P<.001). In our population of untreated middle-aged hypertensive patients, left ventricular mass index is more closely related to 24-h ambulatory blood pressure than to office or central blood pressure. Central blood pressure does not enable us to better identify patients with left ventricular hypertrophy. Copyright © 2012 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

  3. Abnormal Mechanical Loading Induces Cartilage Degeneration by Accelerating Meniscus Hypertrophy and Mineralization After ACL Injuries In Vivo.

    Science.gov (United States)

    Du, Guoqing; Zhan, Hongsheng; Ding, Daofang; Wang, Shaowei; Wei, Xiaochun; Wei, Fangyuan; Zhang, Jianzhong; Bilgen, Bahar; Reginato, Anthony M; Fleming, Braden C; Deng, Jin; Wei, Lei

    2016-03-01

    Although patients with an anterior cruciate ligament (ACL) injury have a high risk of developing posttraumatic osteoarthritis (PTOA), the role of meniscus hypertrophy and mineralization in PTOA after an ACL injury remains unknown. The purpose of this study was to determine if menisci respond to abnormal loading and if an ACL injury results in meniscus hypertrophy and calcification. The hypotheses were that (1) abnormal mechanical loading after an ACL injury induces meniscus hypertrophy and mineralization, which correlates to articular cartilage damage in vivo, and (2) abnormal mechanical loading on bovine meniscus explants induces the overexpression of hypertrophic and mineralization markers in vitro. Controlled laboratory study. In vivo guinea pig study (hypothesis 1): Three-month-old male Hartley guinea pigs (n = 9) underwent ACL transection (ACLT) on the right knee; the left knee served as the control. Calcification in the menisci was evaluated by calcein labeling 1 and 5 days before knee harvesting at 5.5 months. Cartilage and meniscus damage and mineralization were quantified by the Osteoarthritis Research Society International score and meniscus grade, respectively. Indian hedgehog (Ihh), matrix metalloproteinase-13 (MMP-13), collagen type X (Col X), progressive ankylosis homolog (ANKH), ectonucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1), alkaline phosphatase (ALP), inorganic pyrophosphate (PPi), and inorganic phosphate (Pi) concentrations were evaluated by immunohistochemistry and enzyme-linked immunosorbent assay. In vitro bovine meniscus explant study (hypothesis 2): Bovine meniscus explants were subjected to 25% strain at 0.3 Hz for 1, 2, and 3 hours. Cell viability was determined using live/dead staining. The levels of mRNA expression and protein levels were measured using real-time quantitative reverse transcription polymerase chain reaction and Western blot after 24, 48, and 72 hours in culture. The conditioned medium was collected for sulfated

  4. Voltage dependent potassium channel remodeling in murine intestinal smooth muscle hypertrophy induced by partial obstruction.

    Directory of Open Access Journals (Sweden)

    Dong-Hai Liu

    Full Text Available Partial obstruction of the small intestine causes obvious hypertrophy of smooth muscle cells and motility disorder in the bowel proximate to the obstruction. To identify electric remodeling of hypertrophic smooth muscles in partially obstructed murine small intestine, the patch-clamp and intracellular microelectrode recording methods were used to identify the possible electric remodeling and Western blot, immunofluorescence and immunoprecipitation were utilized to examine the channel protein expression and phosphorylation level changes in this research. After 14 days of obstruction, partial obstruction caused obvious smooth muscle hypertrophy in the proximally located intestine. The slow waves of intestinal smooth muscles in the dilated region were significantly suppressed, their amplitude and frequency were reduced, whilst the resting membrane potentials were depolarized compared with normal and sham animals. The current density of voltage dependent potassium channel (KV was significantly decreased in the hypertrophic smooth muscle cells and the voltage sensitivity of KV activation was altered. The sensitivity of KV currents (IKV to TEA, a nonselective potassium channel blocker, increased significantly, but the sensitivity of IKv to 4-AP, a KV blocker, stays the same. The protein levels of KV4.3 and KV2.2 were up-regulated in the hypertrophic smooth muscle cell membrane. The serine and threonine phosphorylation levels of KV4.3 and KV2.2 were significantly increased in the hypertrophic smooth muscle cells. Thus this study represents the first identification of KV channel remodeling in murine small intestinal smooth muscle hypertrophy induced by partial obstruction. The enhanced phosphorylations of KV4.3 and KV2.2 may be involved in this process.

  5. Urine albumin/creatinine ratio and echocardiographic left ventricular structure and function in hypertensive patients with electrocardiographic left ventricular hypertrophy: The LIFE Study

    DEFF Research Database (Denmark)

    Wachtell, K.; Palmieri, V.; Olsen, M.H.

    2002-01-01

    in a large hypertensive population. Methods The urine albumin/creatinine ratio (UACR) and echocardiographic measures of LV structure and function were obtained in 833 patients with stage I to III hypertension and LV hypertrophy determined by electrocardiogram (ECG) (Cornell voltage-duration or Sokolow...... geometry and high LV mass are associated with high UACR independent of age, systolic blood pressure, diabetes, and race, suggesting parallel cardiac and microvascular damage....

  6. Pressure-independent relationship of aortic characteristic impedance with left ventricular mass and geometry in untreated hypertension.

    Science.gov (United States)

    Pucci, Giacomo; Hametner, Bernhard; Battista, Francesca; Wassertheurer, Siegfried; Schillaci, Giuseppe

    2015-01-01

    We investigated whether aortic characteristic impedance (Zc), that is, the ratio between the pulsatile change in pressure and flow in the proximal aorta, is related to left ventricular hypertrophy and geometry independently of blood pressure (BP). A total of 438 never-treated hypertensive individuals (men 62%, age 48 ± 11 years, BP 147/90 ± 16/10  mm Hg) underwent echocardiography and 24 h BP monitoring. Aortic pressure waveform was obtained from radial tonometry with a generalized transfer function (SphygmoCor). Using a validated aortic blood flow model based on higher order Windkessel theory (ARCSolver), aortic Zc, forward (Pf) and backward (Pb) wave amplitudes and their ratio (Pb/Pf = reflection magnitude) were calculated from central waveform. After adjusting for age, BMI, and 24-h SBP, aortic Zc was higher in individuals with left ventricular hypertrophy (0.230 ± 0.09 vs. 0.205 ± 0.07 arbitrary units, P = 0.04 in women; 0.232 ± 0.07 vs. 0.214 ± 0.06 arbitrary units, P < 0.05 in men). Women with left ventricular concentric remodeling had higher adjusted Zc (0.225 ± 0.08 vs. 0.203 ± 0.07 arbitrary units, P = 0.04), whereas men did not differ (0.218 ± 0.07 vs. 0.218 ± 0.07 arbitrary units, P = 0.64). After controlling for age, BMI, 24 h SBP, and other relevant variables, aortic Zc independently predicted left ventricular mass (β = 0.14, P < 0.05) and relative wall thickness (β = 0.21, P < 0.01) in women, and left ventricular mass in men (β = 0.11, P < 0.05), whereas other arterial function parameters had no independent relation with left ventricular mass or geometry. Aortic Zc has a significant association with left ventricular mass and a sex-specific one with left ventricular concentric geometry in hypertension. These effects are independent from, and additional to, those of 24 h SBP.

  7. Vitamin D treatment attenuates cardiac FGF23/FGFR4 signaling and hypertrophy in uremic rats.

    Science.gov (United States)

    Leifheit-Nestler, Maren; Grabner, Alexander; Hermann, Laura; Richter, Beatrice; Schmitz, Karin; Fischer, Dagmar-Christiane; Yanucil, Christopher; Faul, Christian; Haffner, Dieter

    2017-09-01

    Vitamin D deficiency and excess of circulating fibroblast growth factor 23 (FGF23) contribute to cardiovascular mortality in patients with chronic kidney disease (CKD). FGF23 activates FGF receptor 4 and (FGFR4) calcineurin/nuclear factor of activated T cells (NFAT) signaling in cardiac myocytes, thereby causing left ventricular hypertrophy (LVH). Here, we determined if 1,25-dihydroxyvitamin D (calcitriol) inhibits FGF23-induced cardiac signaling and LVH. 5/6 nephrectomized (5/6 Nx) rats were treated with different doses of calcitriol for 4 or 10 weeks and cardiac expression of FGF23/FGFR4 and activation of calcineurin/NFAT as well as LVH were analyzed. FGFR4 activation and hypertrophic cell growth were studied in cultured cardiac myocytes that were co-treated with FGF23 and calcitriol. In 5/6Nx rats with LVH, we detected elevated FGF23 expression in bone and myocardium, increased cardiac expression of FGFR4 and elevated cardiac activation of calcineurin/NFAT signaling. Cardiac expression levels of FGF23 and FGFR4 significantly correlated with the presence of LVH in uremic rats. Treatment with calcitriol reduced LVH as well as cardiac FGFR4 expression and calcineurin/NFAT activation. Bone and cardiac FGF23 expression were further stimulated by calcitriol in a dose-dependent manner, but levels of intact cardiac FGF23 protein were suppressed by high-dose calcitriol. In cultured cardiac myocytes, co-treatment with calcitriol blocked FGF23-induced activation of FGFR4 and hypertrophic cell growth. Our data suggest that in CKD, cardioprotective effects of calcitriol stem from its inhibitory actions on the cardiac FGF23/FGFR4 system, and based on their counterbalancing effects on cardiac myocytes, high FGF23 and low calcitriol synergistically contribute to cardiac hypertrophy. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  8. Podocyte hypertrophy precedes apoptosis under experimental diabetic conditions.

    Science.gov (United States)

    Lee, Sun Ha; Moon, Sung Jin; Paeng, Jisun; Kang, Hye-Young; Nam, Bo Young; Kim, Seonghun; Kim, Chan Ho; Lee, Mi Jung; Oh, Hyung Jung; Park, Jung Tak; Han, Seung Hyeok; Yoo, Tae-Hyun; Kang, Shin-Wook

    2015-08-01

    Podocyte hypertrophy and apoptosis are two hallmarks of diabetic glomeruli, but the sequence in which these processes occur remains a matter of debate. Here we investigated the effects of inhibiting hypertrophy on apoptosis, and vice versa, in both podocytes and glomeruli, under diabetic conditions. Hypertrophy and apoptosis were inhibited using an epidermal growth factor receptor inhibitor (PKI 166) and a pan-caspase inhibitor (zAsp-DCB), respectively. We observed significant increases in the protein expression of p27, p21, phospho-eukaryotic elongation factor 4E-binding protein 1, and phospho-p70 S6 ribosomal protein kinase, in both cultured podocytes exposed to high-glucose (HG) medium, and streptozotocin-induced diabetes mellitus (DM) rat glomeruli. These increases were significantly inhibited by PKI 166, but not by zAsp-DCB. In addition, the amount of protein per cell, the relative cell size, and the glomerular volume were all significantly increased under diabetic conditions, and these changes were also blocked by treatment with PKI 166, but not zAsp-DCB. Increased protein expression of cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase, together with increased Bax/Bcl-2 ratios, were also observed in HG-stimulated podocytes and DM glomeruli. Treatment with either zAsp-DCB or PKI 166 resulted in a significant attenuation of these effects. Both PKI 166 and zAsp-DCB also inhibited the increase in number of apoptotic cells, as assessed by Hoechst 33342 staining and TUNEL assay. Under diabetic conditions, inhibition of podocyte hypertrophy results in attenuated apoptosis, whereas blocking apoptosis has no effect on podocyte hypertrophy, suggesting that podocyte hypertrophy precedes apoptosis.

  9. Review in Translational Cardiology: MicroRNAs and Myocardial Fibrosis in Aortic Valve Stenosis, a Deep Insight on Left Ventricular Remodeling.

    Science.gov (United States)

    Iacopo, Fabiani; Lorenzo, Conte; Calogero, Enrico; Matteo, Passiatore; Riccardo, Pugliese Nicola; Veronica, Santini; Valentina, Barletta; Riccardo, Liga; Cristian, Scatena; Maria, Mazzanti Chiara; Vitantonio, Di Bello

    2016-01-01

    MicroRNAs (miRNAs) are a huge class of noncoding RNAs that regulate protein-encoding genes (degradation/inhibition of translation). miRNAs are nowadays recognized as regulators of biological processes underneath cardiovascular disorders including hypertrophy, ischemia, arrhythmias, and valvular disease. In particular, circulating miRNAs are promising biomarkers of pathology. This review gives an overview of studies in aortic valve stenosis (AS), exclusively considering myocardial remodeling processes. We searched through literature (till September 2016), all studies and reviews involving miRNAs and AS (myocardial compartment). Although at the beginning of a new era, clear evidences exist on the potential diagnostic and prognostic implementation of miRNAs in the clinical setting. In particular, for AS, miRNAs are modulators of myocardial remodeling and hypertrophy. In our experience, here presented in summary, the principal findings of our research were a confirm of the pathophysiological role in AS of miRNA-21, in particular, the interdependence between textural miRNA-21 and fibrogenic stimulus induced by an abnormal left ventricular pressure overload. Moreover, circulating miRNA-21 (biomarker) levels are able to reflect the presence of significant myocardial fibrosis (MF). Thus, the combined evaluation of miRNA-21, a marker of MF, and hypertrophy, together with advanced echocardiographic imaging (two-dimensional speckle tracking), could fulfill many existing gaps, renewing older guidelines paradigms, also allowing a better risk prognostic and diagnostic strategies.

  10. Exercise-induced changes in left ventricular global longitudinal strain in asymptomatic severe aortic stenosis.

    Science.gov (United States)

    Lech, Agnieszka K; Dobrowolski, Piotr P; Klisiewicz, Anna; Hoffman, Piotr

    2017-01-01

    The management of patients with asymptomatic severe aortic stenosis (ASAS) is still under discussion. Therefore, it is advisable to search for the parameters of early damage to left ventricular (LV) function. The aim of the study was to assess exercise-induced changes in LV global longitudinal strain (GLS) in ASAS. The ASAS group consisted of 50 patients (26 women and 24 men, aged 38.4 ± 18.1 years) meeting the echocardiographic criteria of severe aortic stenosis (AVA 4 m/s, mean aortic gradient > 40 mm Hg), with normal LV ejection fraction (LVEF ≥ 55%) and sinus rhythm on electrocardiogram, and without significant concomitant valvular heart diseases. The control group consisted of 21 people matched for age and sex. Echocardiographic examinations and echocardiographic stress tests with the assessment of GLS using the speckle tracking imaging were performed. The ASAS group was characterised by statistically significantly higher LV mass index (LVMI) and higher LVEF. GLS values at rest in both groups were within normal limits but were significantly higher in the control group (-18.9 ± 2.4% vs. -20.7 ± 1.7%, p = 0.006). An increase in GLS at peak exercise in both groups was observed, lower in the ASAS group (the difference was not statistically significant: -0.8 ± 3.0% vs. -2.2 ± 3.1%, p = 0.086). Changes in GLS during exercise (ΔGLS) did not correlate with the parameters of the severity of aortic stenosis. In the multivariate model, LVMI proved to be a factor associated with GLS at rest and during exercise. In patients with ASAS, GLS is a non-invasive marker of an early stage of LV myocardial damage associated with myocardial hypertrophy. An increase in GLS during exercise in the ASAS group, smaller than in the control group, indicates a preserved functional reserve of the LV myocardium but smaller than in healthy individuals. The assessment of the clinical usefulness of exercise-induced changes in GLS requires further research.

  11. Thyroxine-induced cardiac hypertrophy: influence of adrenergic nervous system versus renin-angiotensin system on myocyte remodeling.

    Science.gov (United States)

    Hu, L W; Benvenuti, L A; Liberti, E A; Carneiro-Ramos, M S; Barreto-Chaves, M L M

    2003-12-01

    The present study assessed the possible involvement of the renin-angiotensin system (RAS) and the sympathetic nervous system (SNS) in thyroxine (T4)-induced cardiac hypertrophy. Hemodynamic parameters, heart weight (HW), ratio of HW to body weight (HW/BW), and myocyte width were evaluated in absence of thyroid hormone (hypothyroidism) and after T4 administration. Male Wistar rats were used. Some were subjected to thyroidectomies, whereas hyperthyroidism was induced in others via daily intraperitoneal injection of T4 (25 or 100 microg x 100 g BW(-1) x day(-1)) for 7 days. In some cases, T4 administration was combined with the angiotensin I-converting enzyme inhibitor enalapril (Ena), with the angiotensin type 1 (AT1) receptor blocker losartan (Los) or with the beta-adrenergic blocker propanolol (Prop). Hemodynamics and morphology were then evaluated. Systolic blood pressure (SBP) was not altered by administration of either T4 alone or T4 in combination with the specific inhibitors. However, SBP decreased significantly in hypothyroid rats. An increased heart rate was seen after administration of either T4 alone or T4 in combination with either Los or Ena. Although the higher dose of T4 significantly increased HW, HW/BW increased in both T4-treated groups. Ena and Prop inhibited the increase in HW or HW/BW in hyperthyroid rats. Morphologically, both T4 dose levels significantly increased myocyte width, an occurrence prevented by RAS or SNS blockers. There was a good correlation between changes in HW/BW and myocyte width. These results indicate that T4-induced cardiac hypertrophy is associated with both the SNS and the RAS.

  12. Pulmonary endothelial dysfunction induced by unilateral as compared to bilateral thoracic irradiation in rats

    International Nuclear Information System (INIS)

    Ward, W.F.; Molteni, A.; Ts'Ao, C.H.; Solliday, N.H.

    1987-01-01

    Rats were sacrificed 2 months after a single dose of 10-30 Gy of 60 Co gamma rays delivered to either a right unilateral or a bilateral thoracic port. Four indices of lung endothelial function were measured: the activities of angiotensin-converting enzyme (ACE) and plasminogen activator (PLA) and the production of prostacyclin (PGI2) and thromboxane (TXA2). The number of macrophages recovered by bronchoalveolar lavage (BAL) and the degree of right ventricular hypertrophy (an index of pulmonary hypertension) also were determined. Right lung ACE and PLA activity decreased linearly, and PGI2 and TXA2 production increased linearly with increasing radiation dose. The response curves for right unilateral and bilateral thoracic irradiation were not significantly different. In contrast, bilateral irradiation was more toxic than unilateral, since rats exposed to the former exhibited decreased body weight, an increased incidence of pleural effusions, an increase in the number of macrophages recovered by BAL, and right ventricular hypertrophy. These data demonstrate that pulmonary endothelial dysfunction induced by hemithorax irradiation represents a direct response of the endothelium to radiation injury and is not secondary to other phenomena such as shunting of function to the shielded lung

  13. Effect of melatonin, captopril, spironolactone and simvastatin on blood pressure and left ventricular remodelling in spontaneously hypertensive rats

    Czech Academy of Sciences Publication Activity Database

    Šimko, F.; Pecháňová, Olga; Pelouch, Václav; Krajčírovičová, K.; Müllerová, M.; Bednárová, K.; Adamcová, M.; Paulis, L.

    2009-01-01

    Roč. 27, Suppl.6 (2009), S5-S10 ISSN 0263-6352 R&D Projects: GA ČR GA305/09/0336 Institutional research plan: CEZ:AV0Z50110509 Keywords : cardiac hypertrophy * fibrosis * ventricular remodeling Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 4.988, year: 2009

  14. Inhibition of FoxO transcriptional activity prevents muscle fiber atrophy during cachexia and induces hypertrophy

    Science.gov (United States)

    Reed, Sarah A.; Sandesara, Pooja B.; Senf, Sarah M.; Judge, Andrew R.

    2012-01-01

    Cachexia is characterized by inexorable muscle wasting that significantly affects patient prognosis and increases mortality. Therefore, understanding the molecular basis of this muscle wasting is of significant importance. Recent work showed that components of the forkhead box O (FoxO) pathway are increased in skeletal muscle during cachexia. In the current study, we tested the physiological significance of FoxO activation in the progression of muscle atrophy associated with cachexia. FoxO-DNA binding dependent transcription was blocked in the muscles of mice through injection of a dominant negative (DN) FoxO expression plasmid prior to inoculation with Lewis lung carcinoma cells or the induction of sepsis. Expression of DN FoxO inhibited the increased mRNA levels of atrogin-1, MuRF1, cathepsin L, and/or Bnip3 and inhibited muscle fiber atrophy during cancer cachexia and sepsis. Interestingly, during control conditions, expression of DN FoxO decreased myostatin expression, increased MyoD expression and satellite cell proliferation, and induced fiber hypertrophy, which required de novo protein synthesis. Collectively, these data show that FoxO-DNA binding-dependent transcription is necessary for normal muscle fiber atrophy during cancer cachexia and sepsis, and further suggest that basal levels of FoxO play an important role during normal conditions to depress satellite cell activation and limit muscle growth.—Reed, S. A., Sandesara, P. B., Senf, S. F., Judge, A. R. Inhibition of FoxO transcriptional activity prevents muscle fiber atrophy during cachexia and induces hypertrophy. PMID:22102632

  15. Increased left ventricular mass in normotensive type 1 diabetic patients with diabetic nephropathy

    DEFF Research Database (Denmark)

    Sato, A; Tarnow, L; Parving, H H

    1998-01-01

    in normotensive type 1 diabetic patients with and without nephropathy. RESEARCH DESIGN AND METHODS: M-mode and Doppler echocardiography was performed in 17 type 1 diabetic patients with nephropathy (albuminuria [median (range)], 345 (135-2,846) mg/24 h) and compared with 34 normotensive, normoalbuminuric (10 [3......-30] mg/24 h) type 1 diabetic patients matched for arterial blood pressure (mean +/- SD) ([134/77] +/- [13/7] vs. [129/78] +/- [12/7] mmHg), age (40 +/- 11 vs. 42 +/- 10 years), duration of diabetes (28 +/- 7 vs. 28 +/- 6 years), and BMI (24.2 +/- 4.2 vs. 24.6 +/- 2.4 kg/m2). RESULTS: Left ventricular......OBJECTIVE: Diabetic nephropathy increases the risk of premature cardiovascular disease and sudden death, particularly in type 1 diabetic patients. One possible mechanism for this risk may be left ventricular hypertrophy. In our study, we aimed to evaluate left ventricular structure and function...

  16. Isosteviol prevents the prolongation of action potential in hypertrophied cardiomyoctyes by regulating transient outward potassium and L-type calcium channels.

    Science.gov (United States)

    Fan, Zhuo; Lv, Nanying; Luo, Xiao; Tan, Wen

    2017-10-01

    Cardiac hypertrophy is a thickening of the heart muscle that is associated with cardiovascular diseases such as hypertension and myocardial infarction. It occurs initially as an adaptive process against increased workloads and often leads to sudden arrhythmic deaths. Studies suggest that the lethal arrhythmia is attributed to hypertrophy-induced destabilization of cardiac electrical activity, especially the prolongation of the action potential. The reduced activity of I to is demonstrated to be responsible for the ionic mechanism of prolonged action potential duration and arrhythmogeneity. Isosteviol (STV), a derivative of stevioside, plays a protective role in a variety of stress-induced cardiac diseases. Here we report effects of STV on rat ISO-induced hypertrophic cardiomyocytes. STV alleviated ISO-induced hypertrophy of cardiomyocytes by decreasing cell area of hypertrophied cardiomyocytes. STV application prevented the prolongation of action potential which was prominent in hypertrophied cells. The decrease and increase of current densities for I to and I CaL observed in hypertrophied myocytes were both prevented by STV application. In addition, the results of qRT-PCR suggested that the changes of electrophysiological activity of I to and I CaL are correlated to the alterations of the mRNA transcription level. Copyright © 2017. Published by Elsevier B.V.

  17. Global Transcriptomic Profiling of Cardiac Hypertrophy and Fatty Heart Induced by Long-Term High-Energy Diet in Bama Miniature Pigs.

    Directory of Open Access Journals (Sweden)

    Jihan Xia

    Full Text Available A long-term high-energy diet affects human health and leads to obesity and metabolic syndrome in addition to cardiac steatosis and hypertrophy. Ectopic fat accumulation in the heart has been demonstrated to be a risk factor for heart disorders, but the molecular mechanism of heart disease remains largely unknown. Bama miniature pigs were fed a high-fat, high-sucrose diet (HFHSD for 23 months. These pigs developed symptoms of metabolic syndrome and showed cardiac steatosis and hypertrophy with a greatly increased body weight (2.73-fold, P<0.01, insulin level (4.60-fold, P<0.01, heart weight (1.82-fold, P<0.05 and heart volume (1.60-fold, P<0.05 compared with the control pigs. To understand the molecular mechanisms of cardiac steatosis and hypertrophy, nine pig heart cRNA samples were hybridized to porcine GeneChips. Microarray analyses revealed that 1,022 genes were significantly differentially expressed (P<0.05, ≥1.5-fold change, including 591 up-regulated and 431 down-regulated genes in the HFHSD group relative to the control group. KEGG analysis indicated that the observed heart disorder involved the signal transduction-related MAPK, cytokine, and PPAR signaling pathways, energy metabolism-related fatty acid and oxidative phosphorylation signaling pathways, heart function signaling-related focal adhesion, axon guidance, hypertrophic cardiomyopathy and actin cytoskeleton signaling pathways, inflammation and apoptosis pathways, and others. Quantitative RT-PCR assays identified several important differentially expressed heart-related genes, including STAT3, ACSL4, ATF4, FADD, PPP3CA, CD74, SLA-8, VCL, ACTN2 and FGFR1, which may be targets of further research. This study shows that a long-term, high-energy diet induces obesity, cardiac steatosis, and hypertrophy and provides insights into the molecular mechanisms of hypertrophy and fatty heart to facilitate further research.

  18. Enhanced left ventricular mass regression after aortic valve replacement in patients with aortic stenosis is associated with improved long-term survival.

    Science.gov (United States)

    Ali, Ayyaz; Patel, Amit; Ali, Ziad; Abu-Omar, Yasir; Saeed, Amber; Athanasiou, Thanos; Pepper, John

    2011-08-01

    Aortic valve replacement in patients with aortic stenosis is usually followed by regression of left ventricular hypertrophy. More complete resolution of left ventricular hypertrophy is suggested to be associated with superior clinical outcomes; however, its translational impact on long-term survival after aortic valve replacement has not been investigated. Demographic, operative, and clinical data were obtained retrospectively through case note review. Transthoracic echocardiography was used to measure left ventricular mass preoperatively and at annual follow-up visits. Patients were classified according to their reduction in left ventricular mass at 1 year after the operation: group 1, less than 25 g; group 2, 25 to 150 g; and group 3, more than 150 g. Kaplan-Meier and multivariable Cox regression were used. A total of 147 patients were discharged from the hospital after aortic valve replacement for aortic stenosis between 1991 and 2001. Preoperative left ventricular mass was 279 ± 98 g in group 1 (n = 47), 347 ± 104 g in group 2 (n = 62), and 491 ± 183 g in group 3 (n = 38) (P regression such as ischemic heart disease or hypertension, valve type, or valve size used. Ten-year actuarial survival was not statistically different in patients with enhanced left ventricular mass regression when compared with the log-rank test (group 1, 51% ± 9%; group 2, 54% ± 8%; and group 3, 72% ± 10%) (P = .26). After adjustment, left ventricular mass reduction of more than 150 g was demonstrated as an independent predictor of improved long-term survival on multivariate analysis (P = .02). Our study is the first to suggest that enhanced postoperative left ventricular mass regression, specifically in patients undergoing aortic valve replacement for aortic stenosis, may be associated with improved long-term survival. In view of these findings, strategies purported to be associated with superior left ventricular mass regression should be considered when undertaking

  19. Perflurooctanoic acid induces developmental cardiotoxicity in chicken embryos and hatchlings

    International Nuclear Information System (INIS)

    Jiang, Qixiao; Lust, Robert M.; Strynar, Mark J.; Dagnino, Sonia; DeWitt, Jamie C.

    2012-01-01

    Highlights: ► PFOA exposure thinned right ventricular wall thickness in D19 chicken embryo hearts. ► PFOA exposure induced left ventricle hypertrophy in hearts of hatchling chickens. ► PFOA exposure induced altered cardiac function in hatchling chickens. -- Abstract: Perfluorooctanoic acid (PFOA) is a widespread environmental contaminant that is detectable in serum of the general U.S. population. PFOA is a known developmental toxicant that induces mortality in mammalian embryos and is thought to induce toxicity via interaction with the peroxisome proliferator activated receptor alpha (PPARα). As the cardiovascular system is crucial for embryonic survival, PFOA-induced effects on the heart may partially explain embryonic mortality. To assess impacts of PFOA exposure on the developing heart in an avian model, we used histopathology and immunohistochemical staining for myosin to assess morphological alterations in 19-day-old chicken embryo hearts after PFOA exposure. Additionally, echocardiography and cardiac myofibril ATPase activity assays were used to assess functional alterations in 1-day-old hatchling chickens following developmental PFOA exposure. Overall thinning and thinning of a dense layer of myosin in the right ventricular wall were observed in PFOA-exposed chicken embryo hearts. Alteration of multiple cardiac structural and functional parameters, including left ventricular wall thickness, left ventricular volume, heart rate, stroke volume, and ejection fraction were detected with echocardiography in the exposed hatchling chickens. Assessment of ATPase activity indicated that the ratio of cardiac myofibril calcium-independent ATPase activity to calcium-dependent ATPase activity was not affected, which suggests that developmental PFOA exposure may not affect cardiac energetics. In summary, structural and functional characteristics of the heart appear to be developmental targets of PFOA, possibly at the level of cardiomyocytes. Additional studies will

  20. Influence of Maternal Undernutrition and Overfeeding on Cardiac Ciliary Neurotrophic Factor Receptor and Ventricular Size in Fetal Sheep

    Science.gov (United States)

    Dong, Feng; Ford, Stephen P.; Nijland, Mark J.; Nathanielsz, Peter W.; Ren, Jun

    2008-01-01

    Intrauterine nutrition status is reported to correlate with risk of cardiovascular diseases in adulthood. Either under- or over-nutrition during early to mid gestation contributes to altered fetal growth and ventricular geometry. This study was designed to examine myocardial expression of ciliary neurotrophic factor receptor α (CTNFRα) and its down-stream mediator signal transducer and activator of transcription 3 (STAT3) on maternal under- or over-nutrition-induced changes in fetal heart weight. Multiparous ewes were fed with 50% (nutrient-restricted, NR), 100% (control) or 150% (overfed, OF) of NRC requirements from 28 to 78 days of gestation (dG; Term 148 dG). Ewes were euthanized on day 78, and the gravid uteri and fetuses recovered. Ventricular protein expression of CTNFRα, STAT3, phosphorylated STAT3, insulin-like growth factor I receptor (IGF-1R) and IGF binding protein 3 (IGFBP3) were quantitated using western blot. Plasma cortisol levels were higher in both NR and OF fetuses whereas plasma IGF-1 levels were lower and higher, in NR and OF fetuses. Fetal weights were reduced by 29.9% in NR ewes and were increased by 22.2% in fetuses from OF ewes compared to control group. Nutrient restriction did not affect fetal heart or ventricular weights whereas overfeeding increased heart and ventricular weights. Protein expression of CTNFRα in fetal ventricular tissue was reduced in OF group whereas STAT3 and pSTAT3 levels were reduced in both NR and OF groups. Expression of IGF-1R and IGFBP3 was unaffected in either NR or OF group. These data suggested that compared with maternal undernutrition, intrauterine overfeeding during early to mid gestation is associated with increases fetal blood concentrations of cortisol and IGF-1 in association with ventricular hypertrophy where reduced expression of CNTFRα and STAT3 may play a role. PMID:17869083

  1. High-Intensity Exercise Reduces Cardiac Fibrosis and Hypertrophy but Does Not Restore the Nitroso-Redox Imbalance in Diabetic Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Ulises Novoa

    2017-01-01

    Full Text Available Diabetic cardiomyopathy refers to the manifestations in the heart as a result of altered glucose homeostasis, reflected as fibrosis, cellular hypertrophy, increased oxidative stress, and apoptosis, leading to ventricular dysfunction. Since physical exercise has been indicated as cardioprotective, we tested the hypothesis that high-intensity exercise training could reverse the cardiac maladaptations produced by diabetes. For this, diabetes was induced in rats by a single dose of alloxan. Diabetic rats were randomly assigned to a sedentary group or submitted to a program of exercise on a treadmill for 4 weeks at 80% of maximal performance. Another group of normoglycemic rats was used as control. Diabetic rat hearts presented cardiomyocyte hypertrophy and interstitial fibrosis. Chronic exercise reduced both parameters but increased apoptosis. Diabetes increased the myocardial levels of the mRNA and proteins of NADPH oxidases NOX2 and NOX4. These altered levels were not reduced by exercise. Diabetes also increased the level of uncoupled endothelial nitric oxide synthase (eNOS that was not reversed by exercise. Finally, diabetic rats showed a lower degree of phosphorylated phospholamban and reduced levels of SERCA2 that were not restored by high-intensity exercise. These results suggest that high-intensity chronic exercise was able to reverse remodeling in the diabetic heart but was unable to restore the nitroso-redox imbalance imposed by diabetes.

  2. Ventricular Fibrillation Induced by Thiopental Sodium During Anesthesia in a Dog

    OpenAIRE

    SARITAŞ, Zülfikar

    2014-01-01

    In this case report, a sudden devoloped ventricular fibrillation following Pentothal anaesthesia in a dog and the treatment done was subjected. No abnormal findings were detected according to haemotologic and biochemical tests and ECG obtained at the preoperative period. Blood gases analysis and ECG monitoring were performed before anaesthesia induction for this experimental surgery. After the case was premedicated with Xylazine hydrochlorid (2mg/kg im), anaesthesia was induced by pentotha...

  3. Requirement of myomaker-mediated stem cell fusion for skeletal muscle hypertrophy.

    Science.gov (United States)

    Goh, Qingnian; Millay, Douglas P

    2017-02-10

    Fusion of skeletal muscle stem/progenitor cells is required for proper development and regeneration, however the significance of this process during adult muscle hypertrophy has not been explored. In response to muscle overload after synergist ablation in mice, we show that myomaker, a muscle specific membrane protein essential for myoblast fusion, is activated mainly in muscle progenitors and not myofibers. We rendered muscle progenitors fusion-incompetent through genetic deletion of myomaker in muscle stem cells and observed a complete reduction of overload-induced hypertrophy. This blunted hypertrophic response was associated with a reduction in Akt and p70s6k signaling and protein synthesis, suggesting a link between myonuclear accretion and activation of pro-hypertrophic pathways. Furthermore, fusion-incompetent muscle exhibited increased fibrosis after muscle overload, indicating a protective role for normal stem cell activity in reducing myofiber strain associated with hypertrophy. These findings reveal an essential contribution of myomaker-mediated stem cell fusion during physiological adult muscle hypertrophy.

  4. Nicorandil prevents right ventricular remodeling by inhibiting apoptosis and lowering pressure overload in rats with pulmonary arterial hypertension.

    Directory of Open Access Journals (Sweden)

    Xiang-Rong Zuo

    Full Text Available BACKGROUND: Most of the deaths among patients with severe pulmonary arterial hypertension (PAH are caused by progressive right ventricular (RV pathological remodeling, dysfunction, and failure. Nicorandil can inhibit the development of PAH by reducing pulmonary artery pressure and RV hypertrophy. However, whether nicorandil can inhibit apoptosis in RV cardiomyocytes and prevent RV remodeling has been unclear. METHODOLOGY/PRINCIPAL FINDINGS: RV remodeling was induced in rats by intraperitoneal injection of monocrotaline (MCT. RV systolic pressure (RVSP was measured at the end of each week after MCT injection. Blood samples were drawn for brain natriuretic peptide (BNP ELISA analysis. The hearts were excised for histopathological, ultrastructural, immunohistochemical, and Western blotting analyses. The MCT-injected rats exhibited greater mortality and less weight gain and showed significantly increased RVSP and RV hypertrophy during the second week. These worsened during the third week. MCT injection for three weeks caused pathological RV remodeling, characterized by hypertrophy, fibrosis, dysfunction, and RV mitochondrial impairment, as indicated by increased levels of apoptosis. Nicorandil improved survival, weight gain, and RV function, ameliorated RV pressure overload, and prevented maladaptive RV remodeling in PAH rats. Nicorandil also reduced the number of apoptotic cardiomyocytes, with a concomitant increase in Bcl-2/Bax ratio. 5-hydroxydecanoate (5-HD reversed these beneficial effects of nicorandil in MCT-injected rats. CONCLUSIONS/SIGNIFICANCE: Nicorandil inhibits PAH-induced RV remodeling in rats not only by reducing RV pressure overload but also by inhibiting apoptosis in cardiomyocytes through the activation of mitochondrial ATP-sensitive K(+ (mitoK(ATP channels. The use of a mitoK(ATP channel opener such as nicorandil for PAH-associated RV remodeling and dysfunction may represent a new therapeutic strategy for the amelioration of RV

  5. Association between circulating fibroblast growth factor 23, α-Klotho, and the left ventricular ejection fraction and left ventricular mass in cardiology inpatients.

    Directory of Open Access Journals (Sweden)

    Kensaku Shibata

    Full Text Available BACKGROUND: Fibroblast growth factor 23 (FGF23, with its co-receptor Klotho, plays a crucial role in phosphate metabolism. Several recent studies suggested that circulating FGF23 and α-Klotho concentrations might be related to cardiovascular abnormalities in patients with advanced renal failure. PURPOSE: Using data from 100 cardiology inpatients who were not undergoing chronic hemodialysis, the association of circulating levels of FGF23, α-Klotho, and other calcium-phosphate metabolism-related parameters with the left ventricular ejection fraction (LVEF and left ventricular mass (LVM was analyzed. METHODS AND RESULTS: LVEF was measured using the modified Simpson method for apical 4-chamber LV images and the LVM index (LVMI was calculated by dividing the LVM by body surface area. Univariate analysis showed that log transformed FGF23, but not that of α-Klotho, was significantly associated with LVEF and LVMI with a standardized beta of -0.35 (P<0.001 and 0.26 (P<0.05, respectively. After adjusting for age, sex, estimated glomerular filtration rate, and serum concentrations of intact parathyroid hormone, and 25-hydroxyvitamin D as covariates into the statistical model, log-transformed FGF23 was found to be a statistically positive predictor for decreased left ventricular function and left ventricular hypertrophy. CONCLUSIONS: In cardiology department inpatients, circulating FGF23 concentrations were found to be associated with the left ventricular mass and LVEF independent of renal function and other calcium-phosphate metabolism-related parameters. Whether modulation of circulating FGF23 levels would improve cardiac outcome in such a high risk population awaits further investigation.

  6. Effect of hepatocyte growth factor and angiotensin II on rat cardiomyocyte hypertrophy

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Ai-Lan [Department of Cardiology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou (China); Ou, Cai-Wen [The Fourth Affiliated Hospital of Guangzhou Medical University, Guangzhou (China); He, Zhao-Chu [Department of Cardiology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou (China); Liu, Qi-Cai [Experimental Medical Research Center, Guangzhou Medical University, Guangzhou (China); Dong, Qi [Department of Physiology, Guangzhou Medical University, Guangzhou (China); Chen, Min-Sheng [Guangzhou Key Laboratory of Cardiovascular Disease, Guangzhou Institute of Cardiovascular Disease, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou (China)

    2012-10-15

    Angiotensin II (Ang II) plays an important role in cardiomyocyte hypertrophy. The combined effect of hepatocyte growth factor (HGF) and Ang II on cardiomyocytes is unknown. The present study was designed to determine the effect of HGF on cardiomyocyte hypertrophy and to explore the combined effect of HGF and Ang II on cardiomyocyte hypertrophy. Primary cardiomyocytes were isolated from neonatal rat hearts and cultured in vitro. Cells were treated with Ang II (1 µM) alone, HGF (10 ng/mL) alone, and Ang II (1 µM) plus HGF (10 ng/mL) for 24, 48, and 72 h. The amount of [{sup 3}H]-leucine incorporation was then measured to evaluate protein synthesis. The mRNA levels of β-myosin heavy chain and atrial natriuretic factor were determined by real-time PCR to evaluate the presence of fetal phenotypes of gene expression. The cell size of cardiomyocytes was also studied. Ang II (1 µM) increased cardiomyocyte hypertrophy. Similar to Ang II, treatment with 1 µM HGF promoted cardiomyocyte hypertrophy. Moreover, the combination of 1 µM Ang II and 10 ng/mL HGF clearly induced a combined pro-hypertrophy effect on cardiomyocytes. The present study demonstrates for the first time a novel, combined effect of HGF and Ang II in promoting cardiomyocyte hypertrophy.

  7. Magnetic resonance tissue phase mapping demonstrates altered left ventricular diastolic function in children with chronic kidney disease

    Energy Technology Data Exchange (ETDEWEB)

    Gimpel, Charlotte; Pohl, Martin [Medical Center - University of Freiburg, Department of General Pediatrics, Adolescent Medicine and Neonatology, Center for Pediatrics, Freiburg (Germany); Jung, Bernd A. [Inselspital Bern, Institute of Diagnostic, Interventional and Pediatric Radiology, Bern (Switzerland); Jung, Sabine [Medical Center - University of Freiburg, Department of Nuclear Medicine, Freiburg (Germany); Brado, Johannes; Odening, Katja E. [University Heart Center Freiburg, Department of Cardiology and Angiology I, Freiburg (Germany); Schwendinger, Daniel [University Children' s Hospital Zurich, Zurich (Switzerland); Burkhardt, Barbara [University Children' s Hospital Zurich, Pediatric Heart Center, Zurich (Switzerland); Geiger, Julia [University Children' s Hospital Zurich, Department of Radiology, Zurich (Switzerland); Northwestern University, Department of Radiology, Chicago, IL (United States); Arnold, Raoul [University Hospital Heidelberg, Department of Pediatric and Congenital Cardiology, Heidelberg (Germany)

    2017-02-15

    Echocardiographic examinations have revealed functional cardiac abnormalities in children with chronic kidney disease. To assess the feasibility of MRI tissue phase mapping in children and to assess regional left ventricular wall movements in children with chronic kidney disease. Twenty pediatric patients with chronic kidney disease (before or after renal transplantation) and 12 healthy controls underwent tissue phase mapping (TPM) to quantify regional left ventricular function through myocardial long (Vz) and short-axis (Vr) velocities at all 3 levels of the left ventricle. Patients and controls (age: 8 years - 20 years) were matched for age, height, weight, gender and heart rate. Patients had higher systolic blood pressure. No patient had left ventricular hypertrophy on MRI or diastolic dysfunction on echocardiography. Fifteen patients underwent tissue Doppler echocardiography, with normal z-scores for mitral early diastolic (V{sub E}), late diastolic (V{sub A}) and peak systolic (V{sub S}) velocities. Throughout all left ventricular levels, peak diastolic Vz and Vr (cm/s) were reduced in patients: Vz{sub base} -10.6 ± 1.9 vs. -13.4 ± 2.0 (P < 0.0003), Vz{sub mid} -7.8 ± 1.6 vs. -11 ± 1.5 (P < 0.0001), Vz{sub apex} -3.8 ± 1.6 vs. -5.3 ± 1.6 (P = 0.01), Vr{sub base} -4.2 ± 0.8 vs. -4.9 ± 0.7 (P = 0.01), Vr{sub mid} -4.7 ± 0.7 vs. -5.4 ± 0.7 (P = 0.01), Vr{sub apex} -4.7 ± 1.4 vs. -5.6 ± 1.1 (P = 0.05). Tissue phase mapping is feasible in children and adolescents. Children with chronic kidney disease show significantly reduced peak diastolic long- and short-axis left ventricular wall velocities, reflecting impaired early diastolic filling. Thus, tissue phase mapping detects chronic kidney disease-related functional myocardial changes before overt left ventricular hypertrophy or echocardiographic diastolic dysfunction occurs. (orig.)

  8. Double-chambered right ventricle, ventricular septal defect, patent ductus arteriosus in a dog

    Energy Technology Data Exchange (ETDEWEB)

    Morozumi, M. [Togasaki Animal Hospital, Misato, Saitama (Japan); Kurosu, Y.; Kogure, K.; Chimura, S.; Shibata, S.; Kanemoto, I.

    1989-12-15

    A 4-month-old female mongrel puppy was presented with an anophthalmos. On physical examination, systolic murmur was heard at the 4th left intercostal space near the sternum. However the dog appeared healthy without cyanosis and had no history of exercise intolerance. The phonocardiogram revealed a pansystolic murmur and a continuous murmur on the mitral area. A systolic ejection murmur was also recorded on the pulmonic area. The electrocardiogram indicated bi-ventricular hypertrophy. Left ventricular enlargement was seen on chest radiographs. Ventricular septal defect (VSD) and patent ductus arteriosus (PDA) were diagnosed from these findings. PDA closure was performed at 2 years of age. After 2 months from the operation, the dog died during an attempted repair of the VSD. At necropsy, it was found that the double-chambered right ventricle (DCRV) was formed by an anomalous septal band. The VSD was localized on the proximal conus and was 8 mm in diameter. (author)

  9. Double-chambered right ventricle, ventricular septal defect, patent ductus arteriosus in a dog

    International Nuclear Information System (INIS)

    Morozumi, M.; Kurosu, Y.; Kogure, K.; Chimura, S.; Shibata, S.; Kanemoto, I.

    1989-01-01

    A 4-month-old female mongrel puppy was presented with an anophthalmos. On physical examination, systolic murmur was heard at the 4th left intercostal space near the sternum. However the dog appeared healthy without cyanosis and had no history of exercise intolerance. The phonocardiogram revealed a pansystolic murmur and a continuous murmur on the mitral area. A systolic ejection murmur was also recorded on the pulmonic area. The electrocardiogram indicated bi-ventricular hypertrophy. Left ventricular enlargement was seen on chest radiographs. Ventricular septal defect (VSD) and patent ductus arteriosus (PDA) were diagnosed from these findings. PDA closure was performed at 2 years of age. After 2 months from the operation, the dog died during an attempted repair of the VSD. At necropsy, it was found that the double-chambered right ventricle (DCRV) was formed by an anomalous septal band. The VSD was localized on the proximal conus and was 8 mm in diameter. (author)

  10. Prognostic implications of left ventricular mass and geometry following myocardial infarction: the VALIANT (VALsartan In Acute myocardial iNfarcTion) Echocardiographic Study

    DEFF Research Database (Denmark)

    Verma, Anil; Meris, Alessandra; Skali, Hicham

    2008-01-01

    associated with RWT was independent of LVMi. CONCLUSIONS: Increased baseline LV mass and abnormal LV geometry portend an increased risk for morbidity and mortality following high-risk myocardial infarction. Concentric LV hypertrophy carries the greatest risk of adverse cardiovascular events including death...... cardiovascular events. METHODS: Quantitative echocardiographic analyses were performed at baseline in 603 patients from the VALIANT (VALsartan In Acute myocardial iNfarcTion) echocardiographic study. The left ventricular mass index (LVMi) and relative wall thickness (RWT) were calculated. Patients were...... classified into 4 mutually exclusive groups based on RWT and LVMi as follows: normal geometry (normal LVMi and normal RWT), concentric remodeling (normal LVMi and increased RWT), eccentric hypertrophy (increased LVMi and normal RWT), and concentric hypertrophy (increased LVMi and increased RWT). Cox...

  11. N-terminal pro-B-type natriuretic peptide measurement is useful in predicting left ventricular hypertrophy regression after aortic valve replacement in patients with severe aortic stenosis.

    Science.gov (United States)

    Lee, Mirae; Choi, Jin-Oh; Park, Sung-Ji; Kim, Eun Young; Park, PyoWon; Oh, Jae K; Jeon, Eun-Seok

    2015-01-01

    The predictive factors for early left ventricular hypertrophy (LVH) regression after aortic valve replacement (AVR) have not been fully elucidated. This study was conducted to investigate which preoperative parameters predict early LVH regression after AVR. 87 consecutive patients who underwent AVR due to isolated severe aortic stenosis (AS) were analysed. Patients with ejection fraction regression of LVH at the midterm follow-up was determined. In multivariate analysis, including preoperative echocardiographic parameters, only E/e' ratio was associated with midterm LVH regression (OR 1.11, 95% CI 1.01 to 1.22; p=0.035). When preoperative NT-proBNP was added to the analysis, logNT-proBNP was found to be the single significant predictor of midterm LVH regression (OR 2.00, 95% CI 1.08 to 3.71; p=0.028). By receiver operating characteristic curve analysis, a cut-off value of 440 pg/mL for NT-proBNP yielded a sensitivity of 72% and a specificity of 77% for the prediction of LVH regression after AVR. Preoperative NT-proBNP was an independent predictor for early LVH regression after AVR in patients with isolated severe AS.

  12. Cold stress accentuates pressure overload-induced cardiac hypertrophy and contractile dysfunction: role of TRPV1/AMPK-mediated autophagy.

    Science.gov (United States)

    Lu, Songhe; Xu, Dezhong

    2013-12-06

    Severe cold exposure and pressure overload are both known to prompt oxidative stress and pathological alterations in the heart although the interplay between the two remains elusive. Transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation channel activated in response to a variety of exogenous and endogenous physical and chemical stimuli including heat and capsaicin. The aim of this study was to examine the impact of cold exposure on pressure overload-induced cardiac pathological changes and the mechanism involved. Adult male C57 mice were subjected to abdominal aortic constriction (AAC) prior to exposure to cold temperature (4 °C) for 4 weeks. Cardiac geometry and function, levels of TRPV1, mitochondrial, and autophagy-associated proteins including AMPK, mTOR, LC3B, and P62 were evaluated. Sustained cold stress triggered cardiac hypertrophy, compromised depressed myocardial contractile capacity including lessened fractional shortening, peak shortening, and maximal velocity of shortening/relengthening, enhanced ROS production, and mitochondrial injury, the effects of which were negated by the TRPV1 antagonist SB366791. Western blot analysis revealed upregulated TRPV1 level and AMPK phosphorylation, enhanced ratio of LC3II/LC3I, and downregulated P62 following cold exposure. Cold exposure significantly augmented AAC-induced changes in TRPV1, phosphorylation of AMPK, LC3 isoform switch, and p62, the effects of which were negated by SB366791. In summary, these data suggest that cold exposure accentuates pressure overload-induced cardiac hypertrophy and contractile defect possibly through a TRPV1 and autophagy-dependent mechanism. Copyright © 2013. Published by Elsevier Inc.

  13. Gene Polymorphism and Left Ventricular Geometry and Function in Hypertensive Subjects

    Directory of Open Access Journals (Sweden)

    Rosario Scaglione

    2010-01-01

    Full Text Available The distribution of the T29C TGFβ1 gene polymorphism was analyzed in 198 hypertensives with left ventricular hypertrophy (LVH and in 235 hypertensives without LVH. Circulating TGFβ1 levels, procollagen type III levels, microalbuminuria, and left ventricular geometry and function were evaluated in all the hypertensives with LVH subgrouped according to T29C TGFβ1 gene polymorphism. Circulating TGFβ1 was evaluated by ELISA technique, procollagen type III by a specific radioimmunoassay, microalbuminuria by radioimmunoassay, and left ventricular geometry and function by echocardiography. All groups were comparable for gender, age, and sex. Regarding T29C TGFβ1 gene polymorphism, prevalence of TC or CC genotypes was significantly (P<.05 higher in hypertensives with LVH than hypertensives without LVH TC and CC LVH hypertensives were characterized by a higher prevalence of subjects with microalbuminuria (P<.05 TC and CC versus TT, by increased levels of TGFβ1, procollagen type III, urinary albumin excretion, LVM, LVM/h2.7, and lower values of left ventricular ejection fraction (P<.05 TC and CC versus TT. Our data suggest that T29C TGFβ1 gene polymorphism was associated with clinical characteristics adequate to recognize a subset of LVH hypertensives with a higher severity of hypertension.

  14. Dyrk1A-ASF-CaMKIIδ Signaling Is Involved in Valsartan Inhibition of Cardiac Hypertrophy in Renovascular Hypertensive Rats.

    Science.gov (United States)

    Yao, Jian; Qin, Xiaotong; Zhu, Jianhua; Sheng, Hongzhuan

    2016-01-01

    It is known that the expression, activity and alternative splicing of Ca2+/calmodulin-dependent protein kinase IIδ (CaMKIIδ) are dysregulated in the cardiac remodeling process. Recently, we found a further signaling pathway, by which dual-specificity tyrosine phosphorylation-regulated kinase 1A (Dyrk1A) regulates the alternative splicing of CaMKIIδ via the alternative splicing factor (ASF), i.e., Dyrk1A-ASF-CaMKIIδ. In this study, we aimed to investigate whether Dyrk1A-ASF-CaMKIIδ signaling was involved in valsartan inhibition of cardiac hypertrophy in renovascular hypertensive rats. Rats were subjected to two kidney-one clip (2K1C) surgery and then treated with valsartan (30 mg/kg/day) for 8 weeks. Hypertrophic parameter analysis was then performed. Western blot analysis was used to determine the protein expression of Dyrk1A and ASF and RT-PCR was used to analyze the alternative splicing of CaMKIIδ in the left ventricular (LV) sample. Valsartan attenuated cardiac hypertrophy in 2K1C rats but without impairment of cardiac systolic function. Increased protein expression of Dyrk1A and decreased protein expression of ASF were observed in the LV sample of 2K1C rats. Treatment of 2K1C rats with valsartan reversed the changes in Dyrk1A and ASF expression in the LV sample. Valsartan adjusted the 2K1C-induced imbalance in alternative splicing of CaMKIIδ by upregulating the mRNA expression of CaMKIIδC and downregulating the mRNA expression of CaMKIIδA and CaMKIIδB. Valsartan inhibition of cardiac hypertrophy in renovascular hypertensive rats was mediated, at least partly, by Dyrk1A-ASF-CaMKIIδ signaling. © 2015 S. Karger AG, Basel.

  15. Diabetes Mellitus Associates with Increased Right Ventricular Afterload and Remodeling in Pulmonary Arterial Hypertension.

    Science.gov (United States)

    Whitaker, Morgan E; Nair, Vineet; Sinari, Shripad; Dherange, Parinita A; Natarajan, Balaji; Trutter, Lindsey; Brittain, Evan L; Hemnes, Anna R; Austin, Eric D; Patel, Kumar; Black, Stephen M; Garcia, Joe G N; Yuan Md PhD, Jason X; Vanderpool, Rebecca R; Rischard, Franz; Makino, Ayako; Bedrick, Edward J; Desai, Ankit A

    2018-06-01

    Diabetes mellitus is associated with left ventricular hypertrophy and dysfunction. Parallel studies have also reported associations between diabetes mellitus and right ventricular dysfunction and reduced survival in patients with pulmonary arterial hypertension. However, the impact of diabetes mellitus on the pulmonary vasculature has not been well characterized. We hypothesized that diabetes mellitus and hyperglycemia could specifically influence right ventricular afterload and remodeling in patients with Group I pulmonary arterial hypertension, providing a link to their known susceptibility to right ventricular dysfunction. Using an adjusted model for age, sex, pulmonary vascular resistance, and medication use, associations of fasting blood glucose, glycated hemoglobin, and the presence of diabetes mellitus were evaluated with markers of disease severity in 162 patients with pulmonary arterial hypertension. A surrogate measure of increased pulmonary artery stiffness, elevated pulmonary arterial elastance (P = .012), along with reduced log(pulmonary artery capacitance) (P = .006) were significantly associated with the presence of diabetes mellitus in patients with pulmonary arterial hypertension in a fully adjusted model. Similar associations between pulmonary arterial elastance and capacitance were noted with both fasting blood glucose and glycated hemoglobin. Furthermore, right ventricular wall thickness on echocardiography was greater in pulmonary arterial hypertension patients with diabetes, supporting the link between right ventricular remodeling and diabetes. Cumulatively, these data demonstrate that an increase in right ventricular afterload, beyond pulmonary vascular resistance alone, may influence right ventricular remodeling and provide a mechanistic link between the susceptibility to right ventricular dysfunction in patients with both diabetes mellitus and pulmonary arterial hypertension. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. Heat shock transcription factor 1-deficiency attenuates overloading-associated hypertrophy of mouse soleus muscle.

    Science.gov (United States)

    Koya, Tomoyuki; Nishizawa, Sono; Ohno, Yoshitaka; Goto, Ayumi; Ikuta, Akihiro; Suzuki, Miho; Ohira, Tomotaka; Egawa, Tatsuro; Nakai, Akira; Sugiura, Takao; Ohira, Yoshinobu; Yoshioka, Toshitada; Beppu, Moroe; Goto, Katsumasa

    2013-01-01

    Hypertrophic stimuli, such as mechanical stress and overloading, induce stress response, which is mediated by heat shock transcription factor 1 (HSF1), and up-regulate heat shock proteins (HSPs) in mammalian skeletal muscles. Therefore, HSF1-associated stress response may play a key role in loading-associated skeletal muscle hypertrophy. The purpose of this study was to investigate the effects of HSF1-deficiency on skeletal muscle hypertrophy caused by overloading. Functional overloading on the left soleus was performed by cutting the distal tendons of gastrocnemius and plantaris muscles for 4 weeks. The right muscle served as the control. Soleus muscles from both hindlimbs were dissected 2 and 4 weeks after the operation. Hypertrophy of soleus muscle in HSF1-null mice was partially inhibited, compared with that in wild-type (C57BL/6J) mice. Absence of HSF1 partially attenuated the increase of muscle wet weight and fiber cross-sectional area of overloaded soleus muscle. Population of Pax7-positive muscle satellite cells in HSF1-null mice was significantly less than that in wild-type mice following 2 weeks of overloading (pmuscle hypertrophy might be attributed to the greater and prolonged enhancement of IL-6 expression. HSF1 and/or HSF1-mediated stress response may, in part, play a key role in loading-induced skeletal muscle hypertrophy.

  17. TGF-ß1 enhances the BMP-2-induced chondrogenesis of bovine synovial explants and arrests downstream differentiation at an early stage of hypertrophy.

    Science.gov (United States)

    Shintani, Nahoko; Siebenrock, Klaus A; Hunziker, Ernst B

    2013-01-01

    Synovial explants furnish an in-situ population of mesenchymal stem cells for the repair of articular cartilage. Although bone morphogenetic protein 2 (BMP-2) induces the chondrogenesis of bovine synovial explants, the cartilage formed is neither homogeneously distributed nor of an exclusively hyaline type. Furthermore, the downstream differentiation of chondrocytes proceeds to the stage of terminal hypertrophy, which is inextricably coupled with undesired matrix mineralization. With a view to optimizing BMP-2-induced chondrogenesis, the modulating influences of fibroblast growth factor 2 (FGF-2) and transforming growth factor beta 1 (TGF-ß1) were investigated. Explants of bovine calf metacarpal synovium were exposed to BMP-2 (200 ng/ml) for 4 (or 6) weeks. FGF-2 (10 ng/ml) or TGF-ß1 (10 ng/ml) was introduced at the onset of incubation and was present either during the first week of culturing alone or throughout its entire course. FGF-2 enhanced the BMP-2-induced increase in metachromatic staining for glycosaminoglycans (GAGs) only when it was present during the first week of culturing alone. TGF-ß1 enhanced not only the BMP-2-induced increase in metachromasia (to a greater degree than FGF-2), but also the biochemically-assayed accumulation of GAGs, when it was present throughout the entire culturing period; in addition, it arrested the downstream differentiation of cells at an early stage of hypertrophy. These findings were corroborated by an analysis of the gene- and protein-expression levels of key cartilaginous markers and by an estimation of individual cell volume. TGF-ß1 enhances the BMP-2-induced chondrogenesis of bovine synovial explants, improves the hyaline-like properties of the neocartilage, and arrests the downstream differentiation of cells at an early stage of hypertrophy. With the prospect of engineering a mature, truly articular type of cartilage in the context of clinical repair, our findings will be of importance in fine-tuning the

  18. TGF-ß1 enhances the BMP-2-induced chondrogenesis of bovine synovial explants and arrests downstream differentiation at an early stage of hypertrophy.

    Directory of Open Access Journals (Sweden)

    Nahoko Shintani

    Full Text Available Synovial explants furnish an in-situ population of mesenchymal stem cells for the repair of articular cartilage. Although bone morphogenetic protein 2 (BMP-2 induces the chondrogenesis of bovine synovial explants, the cartilage formed is neither homogeneously distributed nor of an exclusively hyaline type. Furthermore, the downstream differentiation of chondrocytes proceeds to the stage of terminal hypertrophy, which is inextricably coupled with undesired matrix mineralization. With a view to optimizing BMP-2-induced chondrogenesis, the modulating influences of fibroblast growth factor 2 (FGF-2 and transforming growth factor beta 1 (TGF-ß1 were investigated.Explants of bovine calf metacarpal synovium were exposed to BMP-2 (200 ng/ml for 4 (or 6 weeks. FGF-2 (10 ng/ml or TGF-ß1 (10 ng/ml was introduced at the onset of incubation and was present either during the first week of culturing alone or throughout its entire course. FGF-2 enhanced the BMP-2-induced increase in metachromatic staining for glycosaminoglycans (GAGs only when it was present during the first week of culturing alone. TGF-ß1 enhanced not only the BMP-2-induced increase in metachromasia (to a greater degree than FGF-2, but also the biochemically-assayed accumulation of GAGs, when it was present throughout the entire culturing period; in addition, it arrested the downstream differentiation of cells at an early stage of hypertrophy. These findings were corroborated by an analysis of the gene- and protein-expression levels of key cartilaginous markers and by an estimation of individual cell volume.TGF-ß1 enhances the BMP-2-induced chondrogenesis of bovine synovial explants, improves the hyaline-like properties of the neocartilage, and arrests the downstream differentiation of cells at an early stage of hypertrophy. With the prospect of engineering a mature, truly articular type of cartilage in the context of clinical repair, our findings will be of importance in fine-tuning the

  19. Vagus nerve stimulation mitigates intrinsic cardiac neuronal remodeling and cardiac hypertrophy induced by chronic pressure overload in guinea pig

    Science.gov (United States)

    Beaumont, Eric; Wright, Gary L.; Southerland, Elizabeth M.; Li, Ying; Chui, Ray; KenKnight, Bruce H.; Armour, J. Andrew

    2016-01-01

    Our objective was to determine whether chronic vagus nerve stimulation (VNS) mitigates pressure overload (PO)-induced remodeling of the cardioneural interface. Guinea pigs (n = 48) were randomized to right or left cervical vagus (RCV or LCV) implant. After 2 wk, chronic left ventricular PO was induced by partial (15–20%) aortic constriction. Of the 31 animals surviving PO induction, 10 were randomized to RCV VNS, 9 to LCV VNS, and 12 to sham VNS. VNS was delivered at 20 Hz and 1.14 ± 0.03 mA at a 22% duty cycle. VNS commenced 10 days after PO induction and was maintained for 40 days. Time-matched controls (n = 9) were evaluated concurrently. Echocardiograms were obtained before and 50 days after PO. At termination, intracellular current-clamp recordings of intrinsic cardiac (IC) neurons were studied in vitro to determine effects of therapy on soma characteristics. Ventricular cardiomyocyte sizes were assessed with histology along with immunoblot analysis of selected proteins in myocardial tissue extracts. In sham-treated animals, PO increased cardiac output (34%, P < 0.004), as well as systolic (114%, P < 0.04) and diastolic (49%, P < 0.002) left ventricular volumes, a hemodynamic response prevented by VNS. PO-induced enhancements of IC synaptic efficacy and muscarinic sensitivity of IC neurons were mitigated by chronic VNS. Increased myocyte size, which doubled in PO (P < 0.05), was mitigated by RCV. PO hypertrophic myocardium displayed decreased glycogen synthase (GS) protein levels and accumulation of the phosphorylated (inactive) form of GS. These PO-induced changes in GS were moderated by left VNS. Chronic VNS targets IC neurons accompanying PO to obtund associated adverse cardiomyocyte remodeling. PMID:26993230

  20. Preventive effects of p-coumaric acid on cardiac hypertrophy and alterations in electrocardiogram, lipids, and lipoproteins in experimentally induced myocardial infarcted rats.

    Science.gov (United States)

    Roy, Abhro Jyoti; Stanely Mainzen Prince, P

    2013-10-01

    The present study evaluated the preventive effects of p-coumaric acid on cardiac hypertrophy and alterations in electrocardiogram, lipids, and lipoproteins in experimentally induced myocardial infarcted rats. Rats were pretreated with p-coumaric acid (8 mg/kg body weight) daily for a period of 7 days and then injected with isoproterenol (100mg/kg body weight) on 8th and 9th day to induce myocardial infarction. Myocardial infarction induced by isoproterenol was indicated by increased level of cardiac sensitive marker and elevated ST-segments in the electrocardiogram. Also, the levels/concentrations of serum and heart cholesterol, triglycerides and free fatty acids were increased in myocardial infarcted rats. Isoproterenol also increased the levels of serum low density and very low density lipoprotein cholesterol and decreased the levels of high density lipoprotein cholesterol. It also enhanced the activity of liver 3-hydroxy-3 methyl glutaryl-Coenzyme-A reductase. p-Coumaric acid pretreatment revealed preventive effects on all the biochemical parameters and electrocardiogram studied in myocardial infarcted rats. The in vitro study confirmed the free radical scavenging property of p-coumaric acid. Thus, p-coumaric acid prevented cardiac hypertrophy and alterations in lipids, lipoproteins, and electrocardiogram, by virtue of its antihypertrophic, antilipidemic, and free radical scavenging effects in isoproterenol induced myocardial infarcted rats. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Prognostic implications of left ventricular mass and geometry following myocardial infarction: the VALIANT (VALsartan In Acute myocardial iNfarcTion) Echocardiographic Study.

    Science.gov (United States)

    Verma, Anil; Meris, Alessandra; Skali, Hicham; Ghali, Jalal K; Arnold, J Malcolm O; Bourgoun, Mikhail; Velazquez, Eric J; McMurray, John J V; Kober, Lars; Pfeffer, Marc A; Califf, Robert M; Solomon, Scott D

    2008-09-01

    This study sought to understand prognostic implications of increased baseline left ventricular (LV) mass and geometric patterns in a high risk acute myocardial infarction. The LV hypertrophy and alterations in LV geometry are associated with an increased risk of adverse cardiovascular events. Quantitative echocardiographic analyses were performed at baseline in 603 patients from the VALIANT (VALsartan In Acute myocardial iNfarcTion) echocardiographic study. The left ventricular mass index (LVMi) and relative wall thickness (RWT) were calculated. Patients were classified into 4 mutually exclusive groups based on RWT and LVMi as follows: normal geometry (normal LVMi and normal RWT), concentric remodeling (normal LVMi and increased RWT), eccentric hypertrophy (increased LVMi and normal RWT), and concentric hypertrophy (increased LVMi and increased RWT). Cox proportional hazards models were used to evaluate the relationships among LVMi, RWT, LV geometry, and clinical outcomes. Mean LVMi and RWT were 98.8 +/- 28.4 g/m(2) and 0.38 +/- 0.08. The risk of death or the composite end point of death from cardiovascular causes, reinfarction, heart failure, stroke, or resuscitation after cardiac arrest was lowest for patients with normal geometry, and increased with concentric remodeling (hazard ratio [HR]: 3.0; 95% confidence interval [CI]: 1.9 to 4.9), eccentric hypertrophy (HR: 3.1; 95% CI: 1.9 to 4.8), and concentric hypertrophy (HR: 5.4; 95% CI: 3.4 to 8.5), after adjusting for baseline covariates. Also, baseline LVMi and RWT were associated with increased mortality and nonfatal cardiovascular outcomes (HR: 1.22 per 10 g/m(2) increase in LVMi; 95% CI: 1.20 to 1.30; p independent of LVMi. Increased baseline LV mass and abnormal LV geometry portend an increased risk for morbidity and mortality following high-risk myocardial infarction. Concentric LV hypertrophy carries the greatest risk of adverse cardiovascular events including death. Higher RWT was associated with an

  2. Dorsal root ganglia hypertrophy as in vivo correlate of oxaliplatin-induced polyneuropathy.

    Directory of Open Access Journals (Sweden)

    Leonidas Apostolidis

    Full Text Available To investigate in vivo morphological and functional correlates of oxaliplatin-induced peripheral neuropathy (OXA-PNP by magnetic resonance neurography (MRN.Twenty patients (7 female, 13 male, 58.9±10.0 years with mild to moderate OXA-PNP and 20 matched controls (8 female, 12 male, 55.7±15.6 years were prospectively enrolled. All patients underwent a detailed neurophysiological examination prior to neuroimaging. A standardized imaging protocol at 3.0 Tesla included the lumbosacral plexus and both sciatic nerves and their branches using T2-weighted fat-saturated sequences and diffusion tensor imaging. Quantitative assessment included volumetry of the dorsal root ganglia (DRG, sciatic nerve normalized T2 (nT2 signal and caliber, and fractional anisotropy (FA, mean diffusivity (MD, axial (AD and radial diffusivity (RD. Additional qualitative evaluation of sciatic, peroneal, and tibial nerves evaluated the presence, degree, and distribution of nerve lesions.DRG hypertrophy in OXA-PNP patients (207.3±47.7mm3 vs. 153.0±47.1mm3 in controls, p = 0.001 was found as significant morphological correlate of the sensory neuronopathy. In contrast, peripheral nerves only exhibited minor morphological alterations qualitatively. Quantitatively, sciatic nerve caliber (27.3±6.7mm2 vs. 27.4±7.4mm2, p = 0.80 and nT2 signal were not significantly changed in patients (1.32±0.22 vs. 1.22±0.26, p = 0.16. AD, RD, and MD showed a non-significant decrease in patients, while FA was unchanged.OXA-PNP manifests with morphological and functional correlates that can be detected in vivo by MRN. We report hypertrophy of the DRG that stands in contrast to experimental and postmortem studies. DRG volume should be further investigated as a biomarker in other sensory peripheral neuropathies and ganglionopathies.

  3. [Asymmetric hypertrophy of the masticatory muscles].

    Science.gov (United States)

    Arzul, L; Corre, P; Khonsari, R H; Mercier, J-M; Piot, B

    2012-06-01

    Hypertrophy of the masticatory muscles most commonly affects the masseter. Less common cases of isolated or associated temporalis hypertrophy are also reported. Parafunctional habits, and more precisely bruxism, can favor the onset of the hypertrophy. This condition is generally idiopathic and can require both medical and/or surgical management. A 29-year-old patient was referred to our department for an asymmetric swelling of the masticatory muscles. Physical examination revealed a bilateral hypertrophy of the masticatory muscles, predominantly affecting the right temporalis and the left masseter. Major bruxism was assessed by premature dental wearing. The additional examinations confirmed the isolated muscle hypertrophy. Benign asymmetric hypertrophy of the masticatory muscles promoted by bruxism was diagnosed. Treatment with injections of type A botulinum toxin was conducted in association with a splint and relaxation. Its effectiveness has been observed at six months. Few cases of unilateral or bilateral temporalis hypertrophy have been reported, added to the more common isolated masseter muscles hypertrophy. The diagnosis requires to rule out secondary hypertrophies and tumors using Magnetic Resonance Imaging. The condition is thought to be favoured by parafunctional habits such as bruxism. The conservative treatment consists in reducing the volume of the masticatory muscles using intramuscular injections of type A botulinum toxin. Other potential conservative treatments are wearing splints and muscle relaxant drugs. Surgical procedures aiming to reduce the muscle volume and/or the bone volume (mandibular gonioplasty) can be proposed. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  4. Ventricular tachycardia induced by weight loss pills

    DEFF Research Database (Denmark)

    Pareek, Manan; Hansson, Nils Henrik; Grove, Erik Lerkevang

    2013-01-01

    A previously healthy 29-year-old man was admitted with palpitations, dizziness, and near-syncope after he had recently started taking weight loss pills purchased on the internet. The pills contained caffeine and ephedrine. An electrocardiogram and telemetry revealed multiple episodes of non......-sustained monomorphic ventricular tachycardia, which was successfully treated with amiodarone. In conclusion, unauthorized weight loss pills can be harmful. In particular, ephedrine-containing drugs carry a risk of ventricular tachycardia and should be discouraged....

  5. Left-liver hypertrophy after therapeutic right-liver radioembolization is substantial but less than after portal vein embolization.

    Science.gov (United States)

    Garlipp, Benjamin; de Baere, Thierry; Damm, Robert; Irmscher, Romy; van Buskirk, Mark; Stübs, Patrick; Deschamps, Frederic; Meyer, Frank; Seidensticker, Ricarda; Mohnike, Konrad; Pech, Maciej; Amthauer, Holger; Lippert, Hans; Ricke, Jens; Seidensticker, Max

    2014-05-01

    In patients with liver malignancies potentially amenable to curative extended right hepatectomy but insufficient size of the future liver remnant (FLR), portal vein embolization (PVE) of the tumor-bearing liver is used to induce contralateral liver hypertrophy but leaves the tumor untreated. Radioembolization (RE) treats the tumor in the embolized lobe along with contralateral hypertrophy induction. We performed a matched-pair analysis to compare the capacity for hypertrophy induction of these two modalities. Patients with right-hepatic secondary liver malignancies with no or negligible left-hepatic tumor involvement who were treated by right-lobar PVE (n = 141) or RE (n = 35) at two centers were matched for criteria known to influence liver regeneration following PVE: 1) baseline FLR/Total liver volume ratio (<25 versus ≥ 25%); 2) prior platinum-containing systemic chemotherapy; 3) embolization of segments 5-8 versus 4-8; and 4) baseline platelet count (<200 versus ≥ 200 Gpt/L).The primary endpoint was relative change in FLR volume from baseline to follow-up. Twenty-six matched pairs were identified. FLR volume increase from baseline to follow-up (median 33 [24-56] days after PVE or 46 [27-79] days after RE) was significant in both groups but PVE produced significantly more FLR hypertrophy than RE (61.5 versus 29%, P < 0.001). Time between treatment and follow-up was not correlated with the degree of contralateral hypertrophy achieved in both groups. Although group differences in patient history and treatment setting were present and some bias cannot be excluded, this was minimized by the matched-pair design, as remaining group differences after matching were found to have no significant influence on contralateral hypertrophy development. PVE induces significantly more contralateral hypertrophy than RE with therapeutic (nonlobectomy) doses. However, contralateral hypertrophy induced by RE is substantial and RE minimizes the risk of tumor progression in the

  6. Office and Home Blood Pressures as Determinants of Electrocardiographic Left Ventricular Hypertrophy Among Black Nigerians Compared With White Flemish.

    Science.gov (United States)

    Odili, Augustine N; Thijs, Lutgarde; Yang, Wen-Yi; Ogedengbe, John O; Nwegbu, Maxwell M; Jacobs, Lotte; Wei, Fang-Fei; Feng, Ying-Mei; Zhang, Zhen-Yu; Kuznetsova, Tatiana; Nawrot, Tim S; Staessen, Jan A

    2017-11-01

    The association of electrocardiographic left ventricular hypertrophy (ECG-LVH) with blood pressure (BP) in Blacks living in sub-Saharan Africa remains poorly documented. In 225 Black Nigerians and 729 White Flemish, we analyzed QRS voltages and voltage-duration products and 12 criteria diagnostic of ECG-LVH in relation to office BP (mean of 5 consecutive readings) and home BP (duplicate morning and evening readings averaged over 1 week). In multivariable analyses, QRS voltage and voltage-duration indexes were generally higher in Blacks than Whites. By using any of 12 criteria, ECG-LVH was more prevalent among Black than White men (54.4% vs. 36.0%) with no ethnic difference among women (17.1%). Precordial voltages and voltage-duration products increased with office and home systolic BP (SBP), and increases were up to 3-fold steeper in Blacks. In Blacks vs. Whites, increases in the Sokolow-Lyon voltage associated with a 10-mm Hg higher SBP were 0.18 mV (95% confidence interval [CI], 0.09-0.26) vs. 0.06 mV (0.02-0.09) and 0.17 mV (0.07-0.28) vs. 0.11 mV (CI, 0.07-0.15) for office and home BP, respectively, with a significant ethnic gradient (P office and home BP in Blacks than Whites. Associations of ECG voltages and voltage-duration products and risk of ECG-LVH with BP are steeper in Black Nigerians compared with a White reference population. In resource-poor settings of sub-Saharan Africa, the ECG in combination with office and home BP is an essential instrument in risk stratification across the entire BP range. © The Author 2017. Published by Oxford University Press on behalf of the American Journal of Hypertension, Ltd.

  7. Tempol improves lipid profile and prevents left ventricular hypertrophy in LDL receptor gene knockout (LDLr-/-) mice on a high-fat diet.

    Science.gov (United States)

    Viana Gonçalves, Igor Cândido; Cerdeira, Cláudio Daniel; Poletti Camara, Eduardo; Dias Garcia, José Antônio; Ribeiro Pereira Lima Brigagão, Maísa; Bessa Veloso Silva, Roberta; Bitencourt Dos Santos, Gérsika

    2017-09-01

    Dyslipidemia is associated with increased risk of cardiovascular disease and atherosclerosis, and hence with high morbidity and mortality. This study investigated the effects of the nitroxide 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (Tempol) on lipid profile and cardiac morphology in low-density lipoprotein (LDL) receptor gene knockout (LDLr-/-) mice. Male LDLr-/- mice (three months old, approximately 22 g weight) were divided into the following groups: controls, including (1) standard chow (SC, n=8) and (2) high-fat diet (HFD, n=8); and treatment, including (3) standard chow + Tempol (SC+T, n=8) (30 mg/kg administered by gavage, once daily) and (4) high-fat diet + Tempol (HFD+T, n=8) (30 mg/kg). After 30 days of the diet/treatment, whole blood was collected for analysis of biochemical parameters (total cholesterol, triglycerides [TG], high-density lipoprotein [HDL], LDL, and very low-density lipoprotein [VLDL]). The heart was removed through thoracotomy and histological analysis of the left ventricle was performed. A significant increase in TG, LDL, and VLDL and marked left ventricular hypertrophy (LVH) were demonstrated in the HFD group relative to the SC group (p<0.05), while Tempol treatment (HFD+T group) significantly (p<0.05) prevented increases in the levels of these lipid profile markers and attenuated LVH compared with the HFD group. In this study, Tempol showed potential for the prevention of events related to serious diseases of the cardiovascular system. Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. False-positive defects in technetium-99m sestamibi myocardial single-photon emission tomography in healthy athletes with left ventricular hypertrophy

    International Nuclear Information System (INIS)

    Bartram, P.; Hanel, B.; Gustafsson, F.; Mortensen, J.; Hesse, B.; Toft, J.; Ali, S.

    1998-01-01

    Exercise ECG and myocardial single-photon emission tomography (SPET) are fundamental in the non-invasive evaluation of patients suspected of having coronary artery disease (CAD). The purpose of the present study was to investigate the influence of physiological left ventricular hypertrophy (LVH) on myocardial sestamibi SPET in healthy young and old athletes. Eighteen young male elite athletes (ten rowers, five power/weight lifters and three triathletes) and 14 well-trained elderly rowers were studied. All underwent a bicycle test as part of a 2-day sestamibi SPET protocol. Attenuation correction was not performed. The studies were evaluated visually and quantitatively analysed by the CEqual program with its reference files and with a file from a local non-athletic age-matched population. Echocardiographic LVH was an inclusion criterion in the young athletes. Exercise ECG was normal in all subjects. In at least three of the young athletes a reversible defect was observed by visual analysis. On quantitative analysis one-third of the young athletes had ''significant'' (>10 pixels) defects compared with both the local reference base and the CEqual reference population. Nearly all defects were found in the anterior or inferior wall. The remaining subjects, including all old rowers, had normal SPET findings. Anterior and inferior wall defects are so common in healthy athletes with physiological LVH that the specificity of myocardial SPET, in contrast to exercise ECG, seems to be too low for evaluation of chest pain in this group. The mechanism of anterior and inferior defects may be related to hot spots (papillary muscles?) in the lateral wall. The specificity of SPET is maintained in athletes without LVH. (orig.)

  9. Akt1/PKB upregulation leads to vascular smooth muscle cell hypertrophy and polyploidization

    Science.gov (United States)

    Hixon, Mary L.; Muro-Cacho, Carlos; Wagner, Mark W.; Obejero-Paz, Carlos; Millie, Elise; Fujio, Yasushi; Kureishi, Yasuko; Hassold, Terry; Walsh, Kenneth; Gualberto, Antonio

    2000-01-01

    Vascular smooth muscle cells (VSMCs) at capacitance arteries of hypertensive individuals and animals undergo marked age- and blood pressure–dependent polyploidization and hypertrophy. We show here that VSMCs at capacitance arteries of rat models of hypertension display high levels of Akt1/PKB protein and activity. Gene transfer of Akt1 to VSMCs isolated from a normotensive rat strain was sufficient to abrogate the activity of the mitotic spindle cell–cycle checkpoint, promoting polyploidization and hypertrophy. Furthermore, the hypertrophic agent angiotensin II induced VSMC polyploidization in an Akt1-dependent manner. These results demonstrate that Akt1 regulates ploidy levels in VSMCs and contributes to vascular smooth muscle polyploidization and hypertrophy during hypertension. PMID:11032861

  10. [Coronary circulation in asymmetrical hypertrophy of the interventricular septum. On a new pathogenic hypothesis].

    Science.gov (United States)

    Sánchez, G; Orea, A; Trevethan, S; Martínez Ríos, M A

    1984-01-01

    Thirty-four patients with left ventricular hypertrophy were studied. In all cases the following parameters were analyzed: 1) Echocardiography:left ventricular diastolic and systolic diameters, ejection fraction, thickness and movement of interventricular septum and posterior wall of the left ventricle (LV) 2) Electrocardiography: R wave voltaje in precordial leads V2, V3 and V5 and electrical axis in frontal plane 3) Catheterization: intracavitary pressures in LV and aortic pressures 4) Left ventriculography: areas of altered contractility 5) Coronariography: distribution pattern of coronary arteries and number of first order branches of circumflex (CA) and anterior descending coronary arteries (ADCA). The population was divided into 2 groups. Group A (GA) was made up of 22 patients with concentric hypertrophy (CH) of the LV (15 with systemic hypertensive heart disease, 6 with aortic valvular stenosis and 1 idiopathic). Echocardiographic findings included posterior wall thickness (PWT) or septal thickness of 1.1. cm or more and interventricular septum-posterior wall thickness ratio (S/PW) of less than 1.3. Group B (GB) included 12 patients with asymmetric septal hypertrophy (ASH), idiopathic in 5, systemic hypertensive heart disease in 4 and aortic valvular stenosis in 3. In these patients the S/PW thickness ratio was greater than 1.3 and the thickness of either wall greater than 1.1. cm. When the data of the two groups were compared there were significant differences in relation to the presence of septal hypertrophy. The R wave voltage in V2, interventricular thickness and S/PW were greater in GB. In addition, septal movement was less in GB than in Group A (0.47 +/- 0.26 cm vs. 0.74 +/- 0.37 cm; P less than 0.05). PWT was also less in Group B than in A (B: 1.01 +/- 0.1 cm, A: 1.2 +/- 0.2 cm; P less than 0.001). The CA in Group B divided into fewer than 4 first order branches to the upper two thirds of the posterior and lateral walls of the LV in 91.6%. This

  11. Living high training low induces physiological cardiac hypertrophy accompanied by down-regulation and redistribution of the renin-angiotensin system

    Science.gov (United States)

    Shi, Wei; Meszaros, J Gary; Zeng, Shao-ju; Sun, Ying-yu; Zuo, Ming-xue

    2013-01-01

    Aim: Living high training low” (LHTL) is an exercise-training protocol that refers living in hypoxia stress and training at normal level of O2. In this study, we investigated whether LHTL caused physiological heart hypertrophy accompanied by changes of biomarkers in renin-angiotensin system in rats. Methods: Adult male SD rats were randomly assigned into 4 groups, and trained on living low-sedentary (LLS, control), living low-training low (LLTL), living high-sedentary (LHS) and living high-training low (LHTL) protocols, respectively, for 4 weeks. Hematological parameters, hemodynamic measurement, heart hypertrophy and plasma angiotensin II (Ang II) level of the rats were measured. The gene and protein expression of angiotensin-converting enzyme (ACE), angiotensinogen (AGT) and angiotensin II receptor I (AT1) in heart tissue was assessed using RT-PCR and immunohistochemistry, respectively. Results: LLTL, LHS and LHTL significantly improved cardiac function, increased hemoglobin concentration and RBC. At the molecular level, LLTL, LHS and LHTL significantly decreased the expression of ACE, AGT and AT1 genes, but increased the expression of ACE and AT1 proteins in heart tissue. Moreover, ACE and AT1 protein expression was significantly increased in the endocardium, but unchanged in the epicardium. Conclusion: LHTL training protocol suppresses ACE, AGT and AT1 gene expression in heart tissue, but increases ACE and AT1 protein expression specifically in the endocardium, suggesting that the physiological heart hypertrophy induced by LHTL is regulated by region-specific expression of renin-angiotensin system components. PMID:23377552

  12. Obesity-associated cardiac pathogenesis in broiler breeder hens: Pathological adaption of cardiac hypertrophy.

    Science.gov (United States)

    Chen, C Y; Lin, H Y; Chen, Y W; Ko, Y J; Liu, Y J; Chen, Y H; Walzem, R L; Chen, S E

    2017-07-01

    Broiler hens consuming feed to appetite (ad libitum; AL) show increased mortality. Feed restriction (R) typically improves reproductive performance and livability of hens. Rapidly growing broilers can exhibit increased mortality due to cardiac insufficiency but it is unknown whether the increased mortality of non-R broiler hens is also due to cardiac compromise. To assess cardiac growth and physiology in fully mature birds, 45-week-old hens were either continued on R rations or assigned to AL feeding for 7 or 21 days. AL hens exhibited increased bodyweight, adiposity, absolute and relative heart weight, ventricular hypertrophy, and cardiac protein/DNA ratio by d 21 (P hens (P Hens allowed AL feeding for 70 d exhibited a higher incidence of mortality (40% vs. 10%) in association with ascites, pericardial effusion, and ventricle dilation. A higher incidence of irregular ECG patterns and rhythmicity consistent with persistently elevated systolic blood pressure and ventricle fibrosis were observed in AL hens (P feeding in broiler hens results in maladaptive cardiac hypertrophy that progresses to overt pathogenesis in contractility and thereby increases mortality. Feed restriction provides clear physiological benefit to heart function of adult broiler hens. © 2017 Poultry Science Association Inc.

  13. VALSARTAN REGULATES MYOCARDIAL AUTOPHAGY AND MITOCHONDRIAL TURNOVER IN EXPERIMENTAL HYPERTENSION

    Science.gov (United States)

    Zhang, Xin; Li, Zi-Lun; Crane, John A.; Jordan, Kyra L.; Pawar, Aditya S.; Textor, Stephen C.; Lerman, Amir; Lerman, Lilach O.

    2014-01-01

    Renovascular hypertension alters cardiac structure and function. Autophagy is activated during left ventricular hypertrophy and linked to adverse cardiac function. The Angiotensin II receptor blocker Valsartan lowers blood pressure and is cardioprotective, but whether it modulates autophagy in the myocardium is unclear. We hypothesized that Valsartan would alleviate autophagy and improve left ventricular myocardial mitochondrial turnover in swine renovascular hypertension. Domestic pigs were randomized to control, unilateral renovascular hypertension, and renovascular hypertension treated with Valsartan (320 mg/day) or conventional triple therapy (Reserpine+hydralazine+hydrochlorothiazide) for 4 weeks post 6-weeks of renovascular hypertension (n=7 each group). Left ventricular remodeling, function and myocardial oxygenation and microcirculation were assessed by multi-detector computer tomography, blood-oxygen-level-dependent magnetic resonance imaging and microcomputer tomography. Myocardial autophagy, markers for mitochondrial degradation and biogenesis, and mitochondrial respiratory-chain proteins were examined ex vivo. Renovascular hypertension induced left ventricular hypertrophy and myocardial hypoxia, enhanced cellular autophagy and mitochondrial degradation, and suppressed mitochondrial biogenesis. Valsartan and triple therapy similarly decreased blood pressure, but Valsartan solely alleviated left ventricular hypertrophy, ameliorated myocardial autophagy and mitophagy, and increased mitochondrial biogenesis. In contrast, triple therapy only slightly attenuated autophagy and preserved mitochondrial proteins, but elicited no improvement in mitophagy. These data suggest a novel potential role of Valsartan in modulating myocardial autophagy and mitochondrial turnover in renovascular hypertension-induced hypertensive heart disease, which may possibly bolster cardiac repair via a blood pressure-independent manner. PMID:24752430

  14. Differences in cardiovascular risk profile between electrocardiographic hypertrophy versus strain in asymptomatic patients with aortic stenosis (from SEAS data)

    DEFF Research Database (Denmark)

    Greve, Anders M; Gerdts, Eva; Boman, Kurt

    2011-01-01

    Electrocardiograms are routinely obtained in clinical follow-up of patients with asymptomatic aortic stenosis (AS). The association with aortic valve, left ventricular (LV) response to long-term pressure load, and clinical covariates is unclear and the clinical value is thus uncertain. Data from...... clinical examination, electrocardiogram, and echocardiogram in 1,563 patients in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study were used. Electrocardiograms were Minnesota coded for arrhythmias and atrioventricular and intraventricular blocks; LV hypertrophy was assessed by Sokolow...

  15. Cardiomyocyte hypertrophy induced by Endonuclease G deficiency requires reactive oxygen radicals accumulation and is inhibitable by the micropeptide humanin.

    Science.gov (United States)

    Blasco, Natividad; Cámara, Yolanda; Núñez, Estefanía; Beà, Aida; Barés, Gisel; Forné, Carles; Ruíz-Meana, Marisol; Girón, Cristina; Barba, Ignasi; García-Arumí, Elena; García-Dorado, David; Vázquez, Jesús; Martí, Ramon; Llovera, Marta; Sanchis, Daniel

    2018-06-01

    The endonuclease G gene (Endog), which codes for a mitochondrial nuclease, was identified as a determinant of cardiac hypertrophy. How ENDOG controls cardiomyocyte growth is still unknown. Thus, we aimed at finding the link between ENDOG activity and cardiomyocyte growth. Endog deficiency induced reactive oxygen species (ROS) accumulation and abnormal growth in neonatal rodent cardiomyocytes, altering the AKT-GSK3β and Class-II histone deacethylases (HDAC) signal transduction pathways. These effects were blocked by ROS scavengers. Lack of ENDOG reduced mitochondrial DNA (mtDNA) replication independently of ROS accumulation. Because mtDNA encodes several subunits of the mitochondrial electron transport chain, whose activity is an important source of cellular ROS, we investigated whether Endog deficiency compromised the expression and activity of the respiratory chain complexes but found no changes in these parameters nor in ATP content. MtDNA also codes for humanin, a micropeptide with possible metabolic functions. Nanomolar concentrations of synthetic humanin restored normal ROS levels and cell size in Endog-deficient cardiomyocytes. These results support the involvement of redox signaling in the control of cardiomyocyte growth by ENDOG and suggest a pathway relating mtDNA content to the regulation of cell growth probably involving humanin, which prevents reactive oxygen radicals accumulation and hypertrophy induced by Endog deficiency. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  16. Zinc Is Indispensable in Exercise-Induced Cardioprotection against Intermittent Hypoxia-Induced Left Ventricular Function Impairment in Rats.

    Directory of Open Access Journals (Sweden)

    Tsung-I Chen

    Full Text Available In obstructive sleep apnea (OSA, recurrent obstruction of the upper airway leads to intermittent hypoxia (IH during sleep, which can result in impairment of cardiac function. Although exercise can have beneficial effects against IH-induced cardiac dysfunction, the mechanism remains unclear. This study aimed to investigate the interactions of zinc and exercise on IH-triggered left ventricular dysfunction in a rat model that mimics IH in OSA patients. Nine-week-old male Sprague-Dawley rats were randomly assigned to either a control group (CON or to a group receiving 10 weeks of exercise training (EXE. During weeks 9 and 10, half the rats in each group were subjected to IH for 8 h per day for 14 days (IHCON, IHEXE, whereas the remainder continued to breathe room air. Rats within each of the CON, IHCON, EXE, and IHEXE groups were further randomly assigned to receive intraperitoneal injections of either zinc chloride, the zinc chelator N,N,N',N'-tetrakis(2-pyridylmethyl ethylenediamine (TPEN, or injection vehicle only. IH induced a lower left ventricular fractional shortening, reduced ejection fraction, higher myocardial levels of inflammatory factors, increased levels oxidative stress, and lower levels of antioxidative capacity, all of which were abolished by zinc treatment. IHEXE rats exhibited higher levels of cardiac function and antioxidant capacity and lower levels of inflammatory factors and oxidative stress than IHCON rats; however, IHEXE rats receiving TPEN did not exhibit these better outcomes. In conclusion, zinc is required for protecting against IH-induced LV functional impairment and likely plays a critical role in exercise-induced cardioprotection by exerting a dual antioxidant and anti-inflammatory effect.

  17. Zinc Is Indispensable in Exercise-Induced Cardioprotection against Intermittent Hypoxia-Induced Left Ventricular Function Impairment in Rats

    Science.gov (United States)

    Chen, Michael Yu-Chih

    2016-01-01

    In obstructive sleep apnea (OSA), recurrent obstruction of the upper airway leads to intermittent hypoxia (IH) during sleep, which can result in impairment of cardiac function. Although exercise can have beneficial effects against IH-induced cardiac dysfunction, the mechanism remains unclear. This study aimed to investigate the interactions of zinc and exercise on IH-triggered left ventricular dysfunction in a rat model that mimics IH in OSA patients. Nine-week-old male Sprague-Dawley rats were randomly assigned to either a control group (CON) or to a group receiving 10 weeks of exercise training (EXE). During weeks 9 and 10, half the rats in each group were subjected to IH for 8 h per day for 14 days (IHCON, IHEXE), whereas the remainder continued to breathe room air. Rats within each of the CON, IHCON, EXE, and IHEXE groups were further randomly assigned to receive intraperitoneal injections of either zinc chloride, the zinc chelator N,N,N',N'-tetrakis(2-pyridylmethyl) ethylenediamine (TPEN), or injection vehicle only. IH induced a lower left ventricular fractional shortening, reduced ejection fraction, higher myocardial levels of inflammatory factors, increased levels oxidative stress, and lower levels of antioxidative capacity, all of which were abolished by zinc treatment. IHEXE rats exhibited higher levels of cardiac function and antioxidant capacity and lower levels of inflammatory factors and oxidative stress than IHCON rats; however, IHEXE rats receiving TPEN did not exhibit these better outcomes. In conclusion, zinc is required for protecting against IH-induced LV functional impairment and likely plays a critical role in exercise-induced cardioprotection by exerting a dual antioxidant and anti-inflammatory effect. PMID:27977796

  18. Effects of valsartan on ventricular arrhythmia induced by programmed electrical stimulation in rats with myocardial infarction

    Science.gov (United States)

    Jiao, Kun-Li; Li, Yi-Gang; Zhang, Peng-Pai; Chen, Ren-Hua; Yu, Yi

    2012-01-01

    Abstract The impact of angiotensin II receptor blockers (ARBs) on electrical remodelling after myocardial infarction (MI) remains unclear. The purpose of the present study was to evaluate the effect of valsartan on incidence of ventricular arrhythmia induced by programmed electrical stimulation (PES) and potential link to changes of myocardial connexins (Cx) 43 expression and distribution in MI rats. Fifty-nine rats were randomly divided into three groups: Sham (n = 20), MI (n = 20) and MI + Val (20 mg/kg/day per gavage, n = 19). After eight weeks, the incidence of PES-induced ventricular tachycardia (VT) and fibrillation (VF) was compared among groups. mRNA and protein expressions of Cx43, angiotensin II type 1 receptor (AT1R) in the LV border zone (BZ) and non-infarct zone (NIZ) were determined by real-time PCR and Western blot, respectively. Connexins 43 protein and collagen distribution were examined by immunohistochemistry in BZ and NIZ sections from MI hearts. Valsartan effectively improved the cardiac function, reduced the prolonged QTc (163.7 ± 3.7 msec. versus 177.8 ± 4.5 msec., P valsartan. The mRNA and protein expressions of Cx43 in BZ were significantly reduced after MI and up-regulated by valsartan. Increased collagen deposition and reduced Cx43 expression in BZ after MI could be partly attenuated by Valsartan. Valsartan reduced the incidence of PES-induced ventricular arrhythmia, this effect was possibly through modulating the myocardial AT1R and Cx43 expression. PMID:22128836

  19. Comparison of the effects of candesartan cilexetil and enalapril maleate on right ventricular myocardial remodeling in dogs with experimentally induced pulmonary stenosis.

    Science.gov (United States)

    Yamane, Tsuyoshi; Fujii, Yoko; Orito, Kensuke; Osamura, Kaori; Kanai, Takao; Wakao, Yoshito

    2008-12-01

    To compare the effects of candesartan cilexetil and enalapril maleate on right ventricular myocardial remodeling in dogs with experimentally induced pulmonary stenosis. 24 Beagles. 18 dogs underwent pulmonary arterial banding (PAB) to induce right ventricular pressure overload, and 6 healthy dogs underwent sham operations (thoracotomy only [sham-operated group]). Dogs that underwent PAB were allocated to receive 1 of 3 treatments (6 dogs/group): candesartan (1 mg/kg, PO, q 24 h [PABC group]), enalapril (0.5 mg/kg, PO, q 24 h [PABE group]), or no treatment (PABNT group). Administration of treatments was commenced the day prior to surgery; control dogs received no cardiac medications. Sixty days after surgery, right ventricular wall thickness was assessed echocardiographically and plasma renin activity, angiotensin-converting enzyme activity, and angiotensin I and II concentrations were assessed; all dogs were euthanatized, and collagenous fiber area, cardiomyocyte diameter, and tissue angiotensin-converting enzyme and chymase-like activities in the right ventricle were evaluated. After 60 days of treatment, right ventricular wall thickness, cardiomyocyte diameter, and collagenous fiber area in the PABNT and PABE groups were significantly increased, compared with values in the PABC and sham-operated groups. Chymase-like activity was markedly greater in the PABE group than in other groups. Results indicated that treatment with candesartan but not enalapril effectively prevented myocardial remodeling in dogs with experimentally induced subacute right ventricular pressure overload.

  20. Adaptations to iron deficiency: cardiac functional responsiveness to norepinephrine, arterial remodeling, and the effect of beta-blockade on cardiac hypertrophy

    Directory of Open Access Journals (Sweden)

    Walker LeeAnn

    2002-01-01

    Full Text Available Abstract Background Iron deficiency (ID results in ventricular hypertrophy, believed to involve sympathetic stimulation. We hypothesized that with ID 1 intravenous norepinephrine would alter heart rate (HR and contractility, 2 abdominal aorta would be larger and more distensible, and 3 the beta-blocker propanolol would reduce hypertrophy. Methods 1 30 CD rats were fed an ID or replete diet for 1 week or 1 month. Norepinephrine was infused via jugular vein; pressure was monitored at carotid artery. Saline infusions were used as a control. The pressure trace was analyzed for HR, contractility, systolic and diastolic pressures. 2 Abdominal aorta catheters inflated the aorta, while digital microscopic images were recorded at stepwise pressures to measure arterial diameter and distensibility. 3 An additional 10 rats (5 ID, 5 control were given a daily injection of propanolol or saline. After 1 month, the hearts were excised and weighed. Results Enhanced contractility, but not HR, was associated with ID hypertrophic hearts. Systolic and diastolic blood pressures were consistent with an increase in arterial diameter associated with ID. Aortic diameter at 100 mmHg and distensibility were increased with ID. Propanolol was associated with an increase in heart to body mass ratio. Conclusions ID cardiac hypertrophy results in an increased inotropic, but not chronotropic response to the sympathetic neurotransmitter, norepinephrine. Increased aortic diameter is consistent with a flow-dependent vascular remodeling; increased distensibility may reflect decreased vascular collagen content. The failure of propanolol to prevent hypertrophy suggests that ID hypertrophy is not mediated via beta-adrenergic neurotransmission.

  1. Impact of secondary hyperparathyroidism on ventricular mass regression after aortic valve replacement for aortic stenosis in hemodialysis-dependent patients.

    Science.gov (United States)

    Takami, Yoshiyuki; Tajima, Kazuyoshi

    2015-07-01

    In hemodialysis (HD)-dependent patients, secondary hyperparathyroidism induces cardiac hypertrophy. This study investigated whether parathyroid hormone (PTH) levels affect the degree of left ventricular (LV) mass regression in HD patients after aortic valve replacement (AVR) for aortic stenosis (AS). We retrospectively obtained preoperative and 2-year postoperative echocardiography and intact PTH measurements in 88 HD patients who underwent AVR, with bioprostheses (n = 35, 40%) and mechanical valves (n = 53, 60%) of effective orifice area >0.80 cm2/m2, between January 1997 and December 2010. The LV mass decreased significantly from 308 ± 88 to 217 ± 68 g at follow-up of 28 ± 4 months after AVR (p regression at follow-up was inversely related to preoperative PTH values (R = 0.44, p = 0.001). The LV mass regression at follow-up was significantly smaller in the patients (n = 47) with PTH ≥100 pg/mL than in those (n = 41) with PTH regression at 2-year follow-up (β = 0.23, r2 = 0.24, p = 0.02). In conclusion, the HD patients with high levels of PTH presented with less LV mass regression after AVR for AS without patient-prosthesis mismatch. Secondary hyperparathyroidism may impair regression of cardiac hypertrophy after AVR in HD patients with AS.

  2. Prevalence of myocardial hypertrophy in a population of asymptomatic Swedish Maine coon cats

    Directory of Open Access Journals (Sweden)

    Häggström Jens

    2008-06-01

    Full Text Available Abstract Background Maine coon cats have a familial disposition for developing hypertrophic cardiomyopathy (HCM with evidence of an autosomal dominant mode of inheritance 1. The current mode to diagnose HCM is by use of echocardiography. However, definite reference criteria have not been established. The objective of the study was to determine the prevalence of echocardigraphic changes consistent with hypertrophic cardiomyopathy in Swedish Maine coon cats, and to compare echocardiographic measurements with previously published reference values. Methods All cats over the age of 8 months owned by breeders living in Stockholm, listed on the website of the Maine Coon breeders in Sweden by February 2001, were invited to participate in the study. Physical examination and M-mode and 2D echocardiographic examinations were performed in all cats. Results Examinations of 42 asymptomatic Maine coon cats (10 males and 32 females were performed. The age of the cats ranged from 0,7 to 9,3 years with a mean of 4,8 ± 2,3 years. Four cats (9,5% had a diastolic interventricular septal (IVSd or left ventricular free wall (LVPWd thickness exceeding 6,0 mm. In 3 of these cats the hypertrophy was segmental. Two cats (4,8% had systolic anterior motion (SAM of the mitral valve without concomitant hypertrophy. Five cats (11,9% had IVSd or LVPWd exceeding 5,0 mm but less than 6,0 mm. Conclusion Depending on the reference values used, the prevalence of HCM in this study varied from 9,5% to 26,2%. Our study suggests that the left ventricular wall thickness of a normal cat is 5,0 mm or less, rather than 6,0 mm, previously used by most cardiologists. Appropriate echocardiographic reference values for Maine coon cats, and diagnostic criteria for HCM need to be further investigated.

  3. Regional left ventricular myocardial contraction abnormalities and asynchrony in patients with hypertrophic cardiomyopathy evaluated by magnetic resonance spatial modulation of magnetization myocardial tagging

    International Nuclear Information System (INIS)

    Mishiro, Yuichiro; Oki, Takashi; Iuchi, Arata

    1999-01-01

    Global left ventricular (LV) pump function is generally preserved in patients with hypertrophic cardiomyopathy (HCM). However, it is unknown whether regional myocardial contractility is impaired, especially in nonhypertrophied regions. The purpose of this study was to evaluate regional LV myocardial contraction in patients with HCM using magnetic resonance (MR) spatial modulation of magnetization (SPAMM) myocardial tagging. The study group comprised 20 patients with asymmetric septal hypertrophy (HCM group) and 16 age-matched normal patients (control group), and data were collected using transthoracic M-mode and 2-dimensional echocardiography, and MR SPAMM myocardial tagging. The systolic strain ratio, maximum systolic strain velocity, and time from end-diastole to maximum systolic strain (ΔT) in the anterior, ventricular septal, inferior and lateral regions for 2 LV short-axis sections at the levels of the chordae tendineae and papillary muscles were measured at 50-ms intervals by MR myocardial tagging. The end-diastolic anterior and ventricular septal wall thicknesses and LV mass index were significantly different between the HCM and control groups. The systolic strain ratio for all 4 walls, particularly the anterior and ventricular septal regions, was significantly lower in the HCM group. In the HCM group, the maximum systolic strain velocity was significantly lower and ΔT was significantly shorter for all 4 walls, particularly the anterior and ventricular septal regions. The standard deviation for the ΔT, calculated from the ΔT for the 8 regions of the 2 LV short-axis sections, was significantly greater in the HCM group. In conclusion, regional LV myocardial contraction is impaired in both hypertrophied and nonhypertrophied regions, and systolic LV wall asynchrony occurs in patients with HCM. (author)

  4. The association of metabolic syndrome with left ventricular mass and geometry in community-based hypertensive patients among Han Chinese

    Directory of Open Access Journals (Sweden)

    Shuxia Wang

    2015-01-01

    Full Text Available Background: The association of metabolic syndrome (MS with left ventricular (LV hypertrophy is controversial. The objective of our study was to investigate the influence of MS on LV mass and geometry in community-based hypertensive patients among Han Chinese. Materials and Methods: This study included 1733 metabolic syndrome patients according to the International Diabetes Federation (IDF definition and 2373 non-MS hypertension patients. LV hypertrophy was diagnosed by the criteria of LV mass ≥49.2 g/m 2.7 for men and 46.7 g/m 2.7 for women. LV geometric patterns (normal, concentric remodeling, concentric or eccentric hypertrophy were calculated according to LV hypertrophy and relative wall thickness. Logistic regression analysis was used to determine odds ratio (OR and 95% confidence interval (CI of MS for LV hypertrophy and LV geometry abnormality. Results: The LV mass and LV mass index were higher in the MS group than in the non-MS group. In multiple adjusted models. LV mass index, LV mass, interventricular septum, and post wall were raised with the increased number of MS disorders. MS was associated with increased LV hypertrophy risk (unadjusted OR 1.38; 95% CI 1.21-1.57; age, sex, and blood pressure (BP; adjusted OR 1.39; 95% CI 1.22-1.59. MS was also associated with increased risk of eccentric hypertrophy in male and female patients. MS was only associated with increased risk of concentric hypertrophy in female patients; and MS was not associated with concentric remodeling. Conclusion: LV mass and LV mass index were associated with the increased number of MS disorders in the Chinese community-based hypertensive population. MS was not only associated with increased LV hypertrophy risk, but also associated with concentric and eccentric LV geometry abnormality, especially in females.

  5. Do metabolites that are produced during resistance exercise enhance muscle hypertrophy?

    Science.gov (United States)

    Dankel, Scott J; Mattocks, Kevin T; Jessee, Matthew B; Buckner, Samuel L; Mouser, J Grant; Loenneke, Jeremy P

    2017-11-01

    Many reviews conclude that metabolites play an important role with respect to muscle hypertrophy during resistance exercise, but their actual physiologic contribution remains unknown. Some have suggested that metabolites may work independently of muscle contraction, while others have suggested that metabolites may play a secondary role in their ability to augment muscle activation via inducing fatigue. Interestingly, the studies used as support for an anabolic role of metabolites use protocols that are not actually designed to test the importance of metabolites independent of muscle contraction. While there is some evidence in vitro that metabolites may induce muscle hypertrophy, the only study attempting to answer this question in humans found no added benefit of pooling metabolites within the muscle post-exercise. As load-induced muscle hypertrophy is thought to work via mechanotransduction (as opposed to being metabolically driven), it seems likely that metabolites simply augment muscle activation and cause the mechanotransduction cascade in a larger proportion of muscle fibers, thereby producing greater muscle growth. A sufficient time under tension also appears necessary, as measurable muscle growth is not observed after repeated maximal testing. Based on current evidence, it is our opinion that metabolites produced during resistance exercise do not have anabolic properties per se, but may be anabolic in their ability to augment muscle activation. Future studies are needed to compare protocols which produce similar levels of muscle activation, but differ in the magnitude of metabolites produced, or duration in which the exercised muscles are exposed to metabolites.

  6. Trpm4 gene invalidation leads to cardiac hypertrophy and electrophysiological alterations.

    Directory of Open Access Journals (Sweden)

    Marie Demion

    Full Text Available RATIONALE: TRPM4 is a non-selective Ca2+-activated cation channel expressed in the heart, particularly in the atria or conduction tissue. Mutations in the Trpm4 gene were recently associated with several human conduction disorders such as Brugada syndrome. TRPM4 channel has also been implicated at the ventricular level, in inotropism or in arrhythmia genesis due to stresses such as ß-adrenergic stimulation, ischemia-reperfusion, and hypoxia re-oxygenation. However, the physiological role of the TRPM4 channel in the healthy heart remains unclear. OBJECTIVES: We aimed to investigate the role of the TRPM4 channel on whole cardiac function with a Trpm4 gene knock-out mouse (Trpm4-/- model. METHODS AND RESULTS: Morpho-functional analysis revealed left ventricular (LV eccentric hypertrophy in Trpm4-/- mice, with an increase in both wall thickness and chamber size in the adult mouse (aged 32 weeks when compared to Trpm4+/+ littermate controls. Immunofluorescence on frozen heart cryosections and qPCR analysis showed no fibrosis or cellular hypertrophy. Instead, cardiomyocytes in Trpm4-/- mice were smaller than Trpm4+/+with a higher density. Immunofluorescent labeling for phospho-histone H3, a mitosis marker, showed that the number of mitotic myocytes was increased 3-fold in the Trpm4-/-neonatal stage, suggesting hyperplasia. Adult Trpm4-/- mice presented multilevel conduction blocks, as attested by PR and QRS lengthening in surface ECGs and confirmed by intracardiac exploration. Trpm4-/-mice also exhibited Luciani-Wenckebach atrioventricular blocks, which were reduced following atropine infusion, suggesting paroxysmal parasympathetic overdrive. In addition, Trpm4-/- mice exhibited shorter action potentials in atrial cells. This shortening was unrelated to modifications of the voltage-gated Ca2+ or K+ currents involved in the repolarizing phase. CONCLUSIONS: TRPM4 has pleiotropic roles in the heart, including the regulation of conduction and cellular

  7. Effect of parathyroid hormone-related protein in an in vitro hypertrophy model for mesenchymal stem cell chondrogenesis.

    Science.gov (United States)

    Mueller, Michael B; Fischer, Maria; Zellner, Johannes; Berner, Arne; Dienstknecht, Thomas; Kujat, Richard; Prantl, Lukas; Nerlich, Michael; Tuan, Rocky S; Angele, Peter

    2013-05-01

    Mesenchymal stem cells (MSCs) express markers of hypertrophic chondrocytes during chondrogenic differentiation. We tested the suitability of parathyroid hormone-related protein (PTHrP), a regulator of chondrocyte hypertrophy in embryonic cartilage development, for the suppression of hypertrophy in an in vitro hypertrophy model of chondrifying MSCs. Chondrogenesis was induced in human MSCs in pellet culture for two weeks and for an additional two weeks cultures were either maintained in standard chondrogenic medium or transferred to a hypertrophy-enhancing medium. PTHrP(1-40) was added to the medium throughout the culture period at concentrations from 1 to 1,000 pM. Pellets were harvested on days one, 14 and 28 for biochemical and histological analysis. Hypertrophic medium clearly enhanced the hypertrophic phenotype, with increased cell size, and strong alkaline phosphatase (ALP) and type X collagen staining. In chondrogenic medium, 1-100 pM PTHrP(1-40) did not inhibit chondrogenic differentiation, whereas 1,000 pM PTHrP(1-40) significantly reduced chondrogenesis. ALP activity was dose-dependently reduced by PTHrP(1-40) at 10-1,000 pM in chondrogenic conditions. Under hypertrophy-enhancing conditions, PTHrP(1-40) did not inhibit the induction of the hypertrophy. At the highest concentration (1,000 pM) in the hypertrophic group, aggregates were partially dedifferentiated and differentiated areas of these aggregates maintained their hypertrophic appearance. PTHrP(1-40) treatment dose-dependently reduced ALP expression in MSC pellets cultured under standard chondrogenic conditions and is thus beneficial for the maintenance of the chondrogenic phenotype in this medium condition. When cultured under hypertrophy-enhancing conditions, PTHrP(1-40) could not diminish the induced enhancement of hypertrophy in the MSC pellets.

  8. Novel Sulfur Metabolites of Garlic Attenuate Cardiac Hypertrophy and Remodeling through Induction of Na+/K+-ATPase Expression.

    Science.gov (United States)

    Khatua, Tarak N; Borkar, Roshan M; Mohammed, Soheb A; Dinda, Amit K; Srinivas, R; Banerjee, Sanjay K

    2017-01-01

    Epidemiologic studies show an inverse correlation between garlic consumption and progression of cardiovascular disease. However, the molecular basis for the beneficial effect of garlic on the heart is not known. Therefore, the objective of the present study was to (1) investigate the effect of raw garlic on isoproterenol (Iso) induced cardiac hypertrophy (2) find the active metabolites of garlic responsible for the beneficial effect. Cardiac hypertrophy was induced in rats by subcutaneous single injection of Iso 5 mg kg -1 day -1 for 15 days and the effect of garlic (250 mg/kg/day orally) was evaluated. Garlic metabolites in in vivo were identified by LC/MS study. The effect of garlic and its metabolites were evaluated against hypertrophy in H9C2 cells. Garlic normalized cardiac oxidative stress after Iso administration. Cardiac pathology and mitochondrial enzyme activities were improved in hypertrophy heart after garlic administration. Decreased Na + /K + -ATPase protein level that observed in hypertrophy heart was increased after garlic administration. We identified three garlic metabolites in rat serum. To confirm the role of garlic metabolites on cardiac hypertrophy, Na + /K + -ATPase expression and intracellular calcium levels were measured after treating H9C2 cells with raw garlic and two of its active metabolites, allyl methyl sulfide and allyl methyl sulfoxide. Raw garlic and both metabolites increased Na + /K + -ATPase protein level and decreased intracellular calcium levels and cell size in Iso treated H9C2 cells. This antihypertrophic effect of garlic and its sulfur metabolites were lost in H9C2 cells in presence of Na + /K + -ATPase inhibitor. In conclusion, garlic and its active metabolites increased Na + /K + -ATPase in rat heart, and attenuated cardiac hypertrophy and associated remodeling. Our data suggest that identified new garlic metabolites may be useful for therapeutic intervention against cardiac hypertrophy.

  9. Genetics Home Reference: myostatin-related muscle hypertrophy

    Science.gov (United States)

    ... Twitter Home Health Conditions Myostatin-related muscle hypertrophy Myostatin-related muscle hypertrophy Printable PDF Open All Close ... Javascript to view the expand/collapse boxes. Description Myostatin-related muscle hypertrophy is a rare condition characterized ...

  10. Myocardial structural, contractile and electrophysiological changes in the guinea-pig heart failure model induced by chronic sympathetic activation

    DEFF Research Database (Denmark)

    Soltysinska, Ewa; Osadchiy, Oleg; Olesen, Søren-Peter

    2011-01-01

    Widely used murine models of adrenergic-induced cardiomyopathy offer little insight into electrical derangements seen in human heart failure owing to profound differences in the characteristics of ventricular repolarization in mice and rats compared with humans. We therefore sought to determine...... whether sustained adrenergic activation may produce a clinically relevant heart failure phenotype in the guinea-pig, an animal species whose ventricular action potential shape and restitution properties resemble those determined in humans. Isoprenaline (ISO), a ß-adrenoceptor agonist, was infused...... at variable dosage and duration using either subcutaneously implanted osmotic minipumps or daily injections, in an attempt to establish the relevant treatment protocol. We found that 3 months of daily ISO injections (final dose of 1 mg kg(-1), i.p.) promote heart failure evidenced by cardiac hypertrophy...

  11. A case of appropriate inappropriate device therapy: Hyperkalemia-induced ventricular oversensing

    Science.gov (United States)

    Oudit, Gavin Y; Cameron, Doug; Harris, Louise

    2008-01-01

    The present case describes a patient who received inappropriate, but potentially life-saving, therapy from her implantable cardioverter defibrillator (ICD) in the setting of acute hyperkalemia (plasma potassium concentration = 8 mM). Hyperkalemia was associated with the development of a slow sinusoidal ventricular tachycardia, at a rate of 100 beats/min to 125 beats/min (610 ms to 480 ms) in a patient who is pacemaker-dependent. There was associated fractionation of the ICD electrogram and T wave oversensing, leading to ventricular oversensing with resultant detection in the ventricular fibrillation rate zone. This was followed by shock therapy, even though the ventricular tachycardia rate was below the programmed detection rate of the ICD. The subsequent emergency treatment of the hyperkalemia normalized the electrogram, corrected the ventricular oversensing and arrhythmia, and restored rate-adaptive single-chamber ventricular pacing. PMID:18340383

  12. Noninvasive reconstruction of the three-dimensional ventricular activation sequence during pacing and ventricular tachycardia in the rabbit heart.

    Science.gov (United States)

    Han, Chengzong; Pogwizd, Steven M; Killingsworth, Cheryl R; He, Bin

    2011-01-01

    Ventricular arrhythmias represent one of leading causes for sudden cardiac death, a significant problem in public health. Noninvasive imaging of cardiac electric activities associated with ventricular arrhythmias plays an important role in better our understanding of the mechanisms and optimizing the treatment options. The present study aims to rigorously validate a novel three-dimensional (3-D) cardiac electrical imaging (3-DCEI) technique with the aid of 3-D intra-cardiac mapping during paced rhythm and ventricular tachycardia (VT) in the rabbit heart. Body surface potentials and intramural bipolar electrical recordings were simultaneously measured in a closed-chest condition in thirteen healthy rabbits. Single-site pacing and dual-site pacing were performed from ventricular walls and septum. VTs and premature ventricular complexes (PVCs) were induced by intravenous norepinephrine (NE). The non-invasively imaged activation sequence correlated well with invasively measured counterparts, with a correlation coefficient of 0.72 and a relative error of 0.30 averaged over all paced beats and NE-induced PVCs and VT beats. The averaged distance from imaged site of initial activation to measured site determined from intra-cardiac mapping was ∼5mm. These promising results suggest that 3-DCEI is feasible to non-invasively localize the origins and image activation sequence of focal ventricular arrhythmias.

  13. Docosahexaenoic acid inhibits monocrotaline-induced pulmonary hypertension via attenuating endoplasmic reticulum stress and inflammation.

    Science.gov (United States)

    Chen, Rui; Zhong, Wei; Shao, Chen; Liu, Peijing; Wang, Cuiping; Wang, Zhongqun; Jiang, Meiping; Lu, Yi; Yan, Jinchuan

    2018-02-01

    Endoplasmic reticulum (ER) stress and inflammation contribute to pulmonary hypertension (PH) pathogenesis. Previously, we confirmed that docosahexaenoic acid (DHA) could improve hypoxia-induced PH. However, little is known about the link between DHA and monocrotaline (MCT)-induced PH. Our aims were, therefore, to evaluate the effects and molecular mechanisms of DHA on MCT-induced PH in rats. Rat PH was induced by MCT. Rats were treated with DHA daily in the prevention group (following MCT injection) and the reversal group (after MCT injection for 2 wk) by gavage. After 4 wk, mean pulmonary arterial pressure (mPAP), right ventricular (RV) hypertrophy index, and morphological and immunohistochemical analyses were evaluated. Rat pulmonary artery smooth muscle cells (PASMCs) were used to investigate the effects of DHA on cell proliferation stimulated by platelet-derived growth factor (PDGF)-BB. DHA decreased mPAP and attenuated pulmonary vascular remodeling and RV hypertrophy, which were associated with suppressed ER stress. DHA blocked the mitogenic effect of PDGF-BB on PASMCs and arrested the cell cycle via inhibiting nuclear factor of activated T cells-1 (NFATc1) expression and activation and regulating cell cycle-related proteins. Moreover, DHA ameliorated inflammation in lung and suppressed macrophage and T lymphocyte accumulation in lung and adventitia of resistance pulmonary arteries. These findings suggest that DHA could protect against MCT-induced PH by reducing ER stress, suppressing cell proliferation and inflammation.

  14. Akurasi Kriteria Voltase Elektrokardiografi Hipertrofi Ventrikel Kiri untuk Membedakan Jenis Geometri Hipertrofi Ventrikel Kiri

    Directory of Open Access Journals (Sweden)

    Octo Tumbur

    2017-08-01

    The different types of left ventricular hypertrophy geometry is associated with different risk of cardiovascular disease. Echocardiography is the gold standard for diagnosis of left ventricular hypertrophy. Electrocardiographic (ECGleft ventricular hypertrophy voltage criteria can distinguish the type of geometry of left ventricular hypertrophy. The purpose of this study to find out the role of various voltage ECG criteria to distinguish the type of geometry of left ventricle hypertrophy. A cross-sectional study doing from June to November 2015 on 100 patients in cardiology clinic and inpatient at Adam Malik Hospital, Medan, through anamnesis, body mass index  measurement, ECG and echocardiography examinations. If the Sokolow-Lyon ECG criteria for left ventricular hypertrophy did not met, normal left ventricular geometry was diagnosed with 60% sensitivity, 72.22% specificity and 71% accuracy. The eccentric left ventricular hypertrophy geometry was diagnosed if Cornel voltage was not fulfilled, with 25% sensitivity, 71.88% specificity and 55% accuracy. The concentric hypertrophy geometry was diagnosed if the RV6/V5 ratio >1, with 55.56% sensitivity, 56.36% specificity and 56% accuracy. If the RV6/V5 ratio >1 are not met, concentric hypertrophic remodeling geometry was diagnosed with a sensitivity of 55.56%, a specificity of 49.45% and an accuracy of 50%. This study also found the sensitivity and specificity for left ventricular hypertrophy in echocardiography of Sokolow-Lyon criteria were 72.22% and 60.00%, the Cornel voltage criteria with a sensitivity of 77.78% and a specificity of 70.00%, and RV6/V5 ratio criteria with a sensitivity of 51.11% and a specificity of 70.00%. The overall sensitivity and specificity was low. In conclusion, various criteria of  ECG left ventricular geometry voltage can differentiate left ventricular hypertrophy geometry types. Sokolow-Lyon and Cornell voltage criteria are more sensitive and specific than the RV6/V5 ratio.

  15. Increased IGF-IEc expression and mechano-growth factor production in intestinal muscle of fibrostenotic Crohn's disease and smooth muscle hypertrophy.

    Science.gov (United States)

    Li, Chao; Vu, Kent; Hazelgrove, Krystina; Kuemmerle, John F

    2015-12-01

    The igf1 gene is alternatively spliced as IGF-IEa and IGF-IEc variants in humans. In fibrostenotic Crohn's disease, the fibrogenic cytokine TGF-β1 induces IGF-IEa expression and IGF-I production in intestinal smooth muscle and results in muscle hyperplasia and collagen I production that contribute to stricture formation. Mechano-growth factor (MGF) derived from IGF-IEc induces skeletal and cardiac muscle hypertrophy following stress. We hypothesized that increased IGF-IEc expression and MGF production mediated smooth muscle hypertrophy also characteristic of fibrostenotic Crohn's disease. IGF-IEc transcripts and MGF protein were increased in muscle cells isolated from fibrostenotic intestine under regulation by endogenous TGF-β1. Erk5 and MEF2C were phosphorylated in vivo in fibrostenotic muscle; both were phosphorylated and colocalized to nucleus in response to synthetic MGF in vitro. Smooth muscle-specific protein expression of α-smooth muscle actin, γ-smooth muscle actin, and smoothelin was increased in affected intestine. Erk5 inhibition or MEF2C siRNA blocked smooth muscle-specific gene expression and hypertrophy induced by synthetic MGF. Conditioned media of cultured fibrostenotic muscle induced muscle hypertrophy that was inhibited by immunoneutralization of endogenous MGF or pro-IGF-IEc. The results indicate that TGF-β1-dependent IGF-IEc expression and MGF production in patients with fibrostenotic Crohn's disease regulates smooth muscle cell hypertrophy a critical factor that contributes to intestinal stricture formation. Copyright © 2015 the American Physiological Society.

  16. Pulmonary arterial hypertension reduces energy efficiency of right, but not left, rat ventricular trabeculae.

    Science.gov (United States)

    Pham, Toan; Nisbet, Linley; Taberner, Andrew; Loiselle, Denis; Han, June-Chiew

    2018-04-01

    Pulmonary arterial hypertension (PAH) triggers right ventricle (RV) hypertrophy and left ventricle (LV) atrophy, which progressively leads to heart failure. We designed experiments under conditions mimicking those encountered by the heart in vivo that allowed us to investigate whether consequent structural and functional remodelling of the ventricles affects their respective energy efficiencies. We found that peak work output was lower in RV trabeculae from PAH rats due to reduced extent and velocity of shortening. However, their suprabasal enthalpy was unaffected due to increased activation heat, resulting in reduced suprabasal efficiency. There was no effect of PAH on LV suprabasal efficiency. We conclude that the mechanism underlying the reduced energy efficiency of hypertrophied RV tissues is attributable to the increased energy cost of Ca 2+ cycling, whereas atrophied LV tissues still maintain normal mechano-energetic performance. Pulmonary arterial hypertension (PAH) greatly increases the afterload on the right ventricle (RV), triggering RV hypertrophy, which progressively leads to RV failure. In contrast, the disease reduces the passive filling pressure of the left ventricle (LV), resulting in LV atrophy. We investigated whether these distinct structural and functional consequences to the ventricles affect their respective energy efficiencies. We studied trabeculae isolated from both ventricles of Wistar rats with monocrotaline-induced PAH and their respective Control groups. Trabeculae were mounted in a calorimeter at 37°C. While contracting at 5 Hz, they were subjected to stress-length work-loops over a wide range of afterloads. They were subsequently required to undergo a series of isometric contractions at various muscle lengths. In both protocols, stress production, length change and suprabasal heat output were simultaneously measured. We found that RV trabeculae from PAH rats generated higher activation heat, but developed normal active stress. Their

  17. Hypertrophy Stimulation at the Onset of Type I Diabetes Maintains the Soleus but Not the EDL Muscle Mass in Wistar Rats

    Science.gov (United States)

    Fortes, Marco A. S.; Scervino, Maria V. M.; Marzuca-Nassr, Gabriel N.; Vitzel, Kaio F.; da Justa Pinheiro, Carlos H.; Curi, Rui

    2017-01-01

    Diabetes mellitus induces a reduction in skeletal muscle mass and strength. Strength training is prescribed as part of treatment since it improves glycemic control and promotes increase of skeletal muscle mass. The mechanisms involved in overload-induced muscle hypertrophy elicited at the establishment of the type I diabetic state was investigated in Wistar rats. The purpose was to examine whether the overload-induced hypertrophy can counteract the hypotrophy associated to the diabetic state. The experiments were performed in oxidative (soleus) or glycolytic (EDL) muscles. PI3K/Akt/mTOR protein synthesis pathway was evaluated 7 days after overload-induced hypertrophy of soleus and of EDL muscles. The mRNA expression of genes associated with different signaling pathways that control muscle hypertrophy was also evaluated: mechanotransduction (FAK), Wnt/β-catenin, myostatin, and follistatin. The soleus and EDL muscles when submitted to overload had similar hypertrophic responses in control and diabetic animals. The increase of absolute and specific twitch and tetanic forces had the same magnitude as muscle hypertrophic response. Hypertrophy of the EDL muscle from diabetic animals mostly involved mechanical loading-stimulated PI3K/Akt/mTOR pathway besides the reduced activation of AMP-activated protein kinase (AMPK) and decrease of myostatin expression. Hypertrophy was more pronounced in the soleus muscle of diabetic animals due to a more potent activation of rpS6 and increased mRNA expression of insulin-like growth factor-1 (IGF-1), mechano-growth factor (MGF) and follistatin, and decrease of myostatin, MuRF-1 and atrogin-1 contents. The signaling changes enabled the soleus muscle mass and force of the diabetic rats to reach the values of the control group. PMID:29123487

  18. Arbutus unedo prevents cardiovascular and morphological alterations in L-NAME-induced hypertensive rats Part I: cardiovascular and renal hemodynamic effects of Arbutus unedo in L-NAME-induced hypertensive rats.

    Science.gov (United States)

    Afkir, Saida; Nguelefack, Telesphore Benoit; Aziz, Mohamed; Zoheir, Johar; Cuisinaud, Guy; Bnouham, Mohamed; Mekhfi, Hassane; Legssyer, Abdelkhaleq; Lahlou, Saad; Ziyyat, Abderrahim

    2008-03-05

    Hypertension induced by nitric oxide synthase inhibition is associated with functional abnormalities of the heart and kidney. The aim of the present study was to investigate whether chronic treatment with Arbutus unedo leaf (AuL) or root (AuR) aqueous extracts can prevent these alterations. Six groups of rats were used: control group received tap water; N(G)-nitro-l-arginine methyl-ester (L-NAME) group treated with L-NAME at 40 mg/kg/day; AuL and AuR groups received simultaneously L-NAME (40 mg/kg/day) and Au leaves or roots extract at the same concentration 250 mg/kg/day; l-arginine and enalapril groups received simultaneously L-NAME (40 mg/kg/day) and l-arginine at 50mg/kg/day or enalapril at 15 mg/kg/day. Treatment of rats during 4 weeks with L-NAME caused an increase of the systolic blood pressure (SBP) accompanied by a ventricular hypertrophy, an impairment of endothelium-dependent vasorelaxation, an increase of the cardiac baroreflex sensitivity and a decrease of water, sodium and potassium excretion. The co-administration of AuL or AuR extracts with L-NAME reduces the development of increased SBP, ameliorates the vascular reactivity as well as the baroreflex sensitivity and normalizes the renal function. AuR reduces the ventricular hypertrophy but AuL do not. Enalapril associated with L-NAME reverses the majority of alterations induced by L-NAME while l-arginine only lightly ameliorates the vascular reactivity. These results show that chronic treatment with Arbutus extract regress the development of hypertension and ameliorate cardiovascular and renal functions in NO deficient hypertension.

  19. Muscular and Systemic Correlates of Resistance Training-Induced Muscle Hypertrophy

    OpenAIRE

    Mitchell, Cameron J.; Churchward-Venne, Tyler A.; Bellamy, Leeann; Parise, Gianni; Baker, Steven K.; Phillips, Stuart M.

    2013-01-01

    PURPOSE: To determine relationships between post-exercise changes in systemic [testosterone, growth hormone (GH), insulin like grow factor 1 (IGF-1) and interleukin 6 (IL-6)], or intramuscular [skeletal muscle androgen receptor (AR) protein content and p70S6K phosphorylation status] factors in a moderately-sized cohort of young men exhibiting divergent resistance training-mediated muscle hypertrophy. METHODS: Twenty three adult males completed 4 sessions•wk⁻¹ of resistance training for 16 wk....

  20. Intermolecular failure of L-type Ca2+ channel and ryanodine receptor signaling in hypertrophy.

    Directory of Open Access Journals (Sweden)

    Ming Xu

    2007-02-01

    Full Text Available Pressure overload-induced hypertrophy is a key step leading to heart failure. The Ca(2+-induced Ca(2+ release (CICR process that governs cardiac contractility is defective in hypertrophy/heart failure, but the molecular mechanisms remain elusive. To examine the intermolecular aspects of CICR during hypertrophy, we utilized loose-patch confocal imaging to visualize the signaling between a single L-type Ca(2+ channel (LCC and ryanodine receptors (RyRs in aortic stenosis rat models of compensated (CHT and decompensated (DHT hypertrophy. We found that the LCC-RyR intermolecular coupling showed a 49% prolongation in coupling latency, a 47% decrease in chance of hit, and a 72% increase in chance of miss in DHT, demonstrating a state of "intermolecular failure." Unexpectedly, these modifications also occurred robustly in CHT due at least partially to decreased expression of junctophilin, indicating that intermolecular failure occurs prior to cellular manifestations. As a result, cell-wide Ca(2+ release, visualized as "Ca(2+ spikes," became desynchronized, which contrasted sharply with unaltered spike integrals and whole-cell Ca(2+ transients in CHT. These data suggested that, within a certain limit, termed the "stability margin," mild intermolecular failure does not damage the cellular integrity of excitation-contraction coupling. Only when the modification steps beyond the stability margin does global failure occur. The discovery of "hidden" intermolecular failure in CHT has important clinical implications.

  1. Compensative hypertrophy of the kidney

    International Nuclear Information System (INIS)

    Raynaud, C.

    1976-01-01

    Several measurement methods are available to practitioners to reveal a compensative hypertrophy. Mensuration of the kidney has the advantage of simplicity but is in fact an unreliable and inaccurate method. Separate clearances in their traditional form have never entered into routine use because of the disadvantages of ureteral catheterism. The use of radioactive tracers avoids this drawback, but clearances calculated in this way are only valid in the absence of obstructive urinary disorders. Solutions have been proposed, but the values obtained are no longer identical with the clearances. The Hg uptake test quantifies quite accurately the function of each kidney. From the results obtained a complete compensative hypertrophy developed on a healthy kidney and an incomplete compensative hypertrophy developed on the diseased kidney have been described. In each of these situations the degree to which compensative hypertrophy develops seems to be fixed at a given level peculiar to each patient [fr

  2. Salbutamol Abuse is Associated with Ventricular Fibrillation

    Directory of Open Access Journals (Sweden)

    Emin UYSAL

    2015-06-01

    Full Text Available SUMMARY: Salbutamol-induced cardiac complications are well-established. Herein, we describe a case of a 24-year female who was admitted to the emergency department because of a suicide attempt with salbutamol (76 mg. Salbutamol abuse induced the development of supraventricular tachycardia and ventricular fibrillation. Regular sinus rhythm was restored with defibrillation. The hypokalemic patient who stayed in the intensive care unit was discharged after 48 hours of hospitalization. Key words: Salbutamol, suicide, ventricular fibrillation

  3. Arrhythmogenic right ventricular dysplasia

    International Nuclear Information System (INIS)

    Vignolo Puglia, W.; Freire Colla, D.; Rivara Urrutia, D.; Lujambio Grene, M.; Arbiza Bruno, T.; Oliveira, G.; Cobas Rodriguez, J.

    1997-01-01

    The arrhythmogenic right ventricular dysplasia is a condition predominantly well defined with arrhythmic events. We analyze three cases diagnosed by the group. These cases were presented as ventricular tachycardia with a morphology of left bundle branch block, presenting one of them aborted sudden death in evolution. The baseline electrocardiogram and signal averaging were abnormal in two of the three cases, like the echocardiogram. The electrophysiological study was able to induce in the three patients with sustained monomorphic ventricular tachycardia morphology of left bundle branch block. The definitive diagnosis was made by right ventriculography in two cases and magnetic resonance imaging in the other. Treatment included antiarrhythmic drugs in the three cases and the placement of an automatic defibrillator which survived a sudden death (Author)

  4. Do stress fractures induce hypertrophy of the grafted fibula? A report of three cases received free vascularized fibular graft treatment for tibial defects.

    Science.gov (United States)

    Qi, Yong; Sun, Hong-Tao; Fan, Yue-Guang; Li, Fei-Meng; Lin, Zhou-Sheng

    2016-06-01

    The presence of large segmental defects of the diaphyseal bone is challenging for orthopedic surgeons. Free vascularized fibular grafting (FVFG) is considered to be a reliable reconstructive procedure. Stress fractures are a common complication following this surgery, and hypertrophy is the main physiological change of the grafted fibula. The exact mechanism of hypertrophy is not completely known. To the best of our knowledge, no studies have examined the possible relationship between stress fractures and hypertrophy. We herein report three cases of patients underwent FVFG. Two of them developed stress fractures and significant hypertrophy, while the remaining patient developed neither stress fractures nor significant hypertrophy. This phenomenon indicates that a relationship may exist between stress fractures and hypertrophy of the grafted fibula, specifically, that the presence of a stress fracture may initiate the process of hypertrophy.

  5. Resistance training-induced changes in integrated myofibrillar protein synthesis are related to hypertrophy only after attenuation of muscle damage.

    Science.gov (United States)

    Damas, Felipe; Phillips, Stuart M; Libardi, Cleiton A; Vechin, Felipe C; Lixandrão, Manoel E; Jannig, Paulo R; Costa, Luiz A R; Bacurau, Aline V; Snijders, Tim; Parise, Gianni; Tricoli, Valmor; Roschel, Hamilton; Ugrinowitsch, Carlos

    2016-09-15

    Skeletal muscle hypertrophy is one of the main outcomes from resistance training (RT), but how it is modulated throughout training is still unknown. We show that changes in myofibrillar protein synthesis (MyoPS) after an initial resistance exercise (RE) bout in the first week of RT (T1) were greater than those seen post-RE at the third (T2) and tenth week (T3) of RT, with values being similar at T2 and T3. Muscle damage (Z-band streaming) was the highest during post-RE recovery at T1, lower at T2 and minimal at T3. When muscle damage was the highest, so was the integrated MyoPS (at T1), but neither were related to hypertrophy; however, integrated MyoPS at T2 and T3 were correlated with hypertrophy. We conclude that muscle hypertrophy is the result of accumulated intermittent increases in MyoPS mainly after a progressive attenuation of muscle damage. Skeletal muscle hypertrophy is one of the main outcomes of resistance training (RT), but how hypertrophy is modulated and the mechanisms regulating it are still unknown. To investigate how muscle hypertrophy is modulated through RT, we measured day-to-day integrated myofibrillar protein synthesis (MyoPS) using deuterium oxide and assessed muscle damage at the beginning (T1), at 3 weeks (T2) and at 10 weeks of RT (T3). Ten young men (27 (1) years, mean (SEM)) had muscle biopsies (vastus lateralis) taken to measure integrated MyoPS and muscle damage (Z-band streaming and indirect parameters) before, and 24 h and 48 h post resistance exercise (post-RE) at T1, T2 and T3. Fibre cross-sectional area (fCSA) was evaluated using biopsies at T1, T2 and T3. Increases in fCSA were observed only at T3 (P = 0.017). Changes in MyoPS post-RE at T1, T2 and T3 were greater at T1 (P Muscle damage was the highest during post-RE recovery at T1, attenuated at T2 and further attenuated at T3. The change in MyoPS post-RE at both T2 and T3, but not at T1, was strongly correlated (r ≈ 0.9, P muscle hypertrophy. Initial Myo

  6. Sildenafil prevents the up-regulation of transient receptor potential canonical channels in the development of cardiomyocyte hypertrophy

    International Nuclear Information System (INIS)

    Kiso, Hironori; Ohba, Takayoshi; Iino, Kenji; Sato, Kazuhiro; Terata, Yutaka; Murakami, Manabu; Ono, Kyoichi; Watanabe, Hiroyuki; Ito, Hiroshi

    2013-01-01

    Highlights: •Transient receptor potential canonical (TRPC1, 3 and 6) are up-regulated by ET-1. •Sildenafil inhibited hypertrophic responses (BNP, Ca entry, NFAT activation). •Sildenafil suppressed TRPC1, 3 and 6 expression. -- Abstract: Background: Transient receptor potential canonical (TRPCs) channels are up-regulated in the development of cardiac hypertrophy. Sildenafil inhibits TRPC6 activation and expression, leading to the prevention of cardiac hypertrophy. However, the effects of sildenafil on the expression of other TRPCs remain unknown. We hypothesized that in addition to its effects of TRPC6, sildenafil blocks the up-regulation of other TRPC channels to suppress cardiomyocyte hypertrophy. Methods and results: In cultured neonatal rat cardiomyocytes, a 48 h treatment with 10 nM endothelin (ET)-1 induced hypertrophic responses characterized by nuclear factor of activated T cells activation and enhancement of brain natriuretic peptide expression and cell surface area. Co-treatment with sildenafil (1 μM, 48 h) inhibited these ET-1-induced hypertrophic responses. Although ET-1 enhanced the gene expression of TRPCs, sildenafil inhibited the enhanced gene expression of TRPC1, C3 and C6. Moreover, co-treatment with sildenafil abolished the augmentation of SOCE in the hypertrophied cardiomyocytes. Conclusions: These results suggest that sildenafil inhibits cardiomyocyte hypertrophy by suppressing the up-regulation of TRPC expression

  7. Overexpression of the human angiotensin II type 1 receptor in the rat heart augments load induced cardiac hypertrophy

    NARCIS (Netherlands)

    Hoffmann, S.; Krause, T.; van Geel, P. P.; Willenbrock, R.; Pagel, I.; Pinto, Y. M.; Buikema, H.; van Gilst, W. H.; Lindschau, C.; Paul, M.; Inagami, T.; Ganten, D.; Urata, H.

    2001-01-01

    Angiotensin II is known to stimulate cardiac hypertrophy and contractility. Most angiotensin II effects are mediated via membrane bound AT1 receptors. However, the role of myocardial AT1 receptors in cardiac hypertrophy and contractility is still rarely defined. To address the hypothesis that

  8. Overexpression of the human angiotensin II type 1 receptor in the rat heart augments load induced cardiac hypertrophy

    NARCIS (Netherlands)

    Hoffmann, S; van Geel, PP; Willenbrock, R; Pagel, [No Value; Pinto, YM; Buikema, H; van Gilst, WH; Lindschau, C; Paul, M; Inagami, T; Ganten, D; Urata, H

    2001-01-01

    Angiotensin II is known to stimulate cardiac hypertrophy and contractility. Most angiotensin II effects are mediated via membrane bound AT(1) receptors. However, the role of myocardial AT(1) receptors in cardiac hypertrophy and contractility is still rarely defined. To address the hypothesis that

  9. Usefulness of Epicardial Area in the Short Axis to Identify Elevated Left Ventricular Mass in Men.

    Science.gov (United States)

    Fitzpatrick, Jesse K; Cohen, Beth E; Rosenblatt, Andrew; Shaw, Richard E; Schiller, Nelson B

    2018-06-15

    Left ventricular (LV) hypertrophy is strongly associated with increased cardiovascular morbidity and mortality. The 2-dimensional LV mass algorithms suffer from measurement variability that can lead to misclassification of patients with LV hypertrophy as normal, or vice versa. Among the 4 echocardiographic measurements required by the 2-dimensional LV mass algorithms, epicardial and endocardial area have the lowest interobserver variation and could be used to corroborate LV mass calculations. We sought cut-off values that are able to discriminate between elevated and normal LV mass based on endocardial or epicardial area alone. Using data from 664 men enrolled in the Mind Your Heart Study, we calculated the correlation of LV mass index with epicardial area and endocardial area. We then used receiver operator characteristic curves to identify epicardial and endocardial area cut-points that could discriminate subjects with normal LV mass and LV hypertrophy. LV mass index was more strongly correlated with epicardial area compared with endocardial area, r = 0.70 versus r = 0.27, respectively. Epicardial area had a significantly higher area under the receiver operator characteristic curve (p versus 0.63 (95% confidence interval 0.57 to 0.71). An epicardial area cut-point of ≥38.0 cm 2 corresponded to a sensitivity of 95.0% and specificity of 54.4% for detecting LV hypertrophy. In conclusion, epicardial area showed promise as a method of rapid screening for LV hypertrophy and could be used to validate formal LV mass calculations. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Dasatinib Attenuates Pressure Overload Induced Cardiac Fibrosis in a Murine Transverse Aortic Constriction Model.

    Directory of Open Access Journals (Sweden)

    Sundaravadivel Balasubramanian

    Full Text Available Reactive cardiac fibrosis resulting from chronic pressure overload (PO compromises ventricular function and contributes to congestive heart failure. We explored whether nonreceptor tyrosine kinases (NTKs play a key role in fibrosis by activating cardiac fibroblasts (CFb, and could potentially serve as a target to reduce PO-induced cardiac fibrosis. Our studies were carried out in PO mouse myocardium induced by transverse aortic constriction (TAC. Administration of a tyrosine kinase inhibitor, dasatinib, via an intraperitoneally implanted mini-osmotic pump at 0.44 mg/kg/day reduced PO-induced accumulation of extracellular matrix (ECM proteins and improved left ventricular geometry and function. Furthermore, dasatinib treatment inhibited NTK activation (primarily Pyk2 and Fak and reduced the level of FSP1 positive cells in the PO myocardium. In vitro studies using cultured mouse CFb showed that dasatinib treatment at 50 nM reduced: (i extracellular accumulation of both collagen and fibronectin, (ii both basal and PDGF-stimulated activation of Pyk2, (iii nuclear accumulation of Ki67, SKP2 and histone-H2B and (iv PDGF-stimulated CFb proliferation and migration. However, dasatinib did not affect cardiomyocyte morphologies in either the ventricular tissue after in vivo administration or in isolated cells after in vitro treatment. Mass spectrometric quantification of dasatinib in cultured cells indicated that the uptake of dasatinib by CFb was greater that that taken up by cardiomyocytes. Dasatinib treatment primarily suppressed PDGF but not insulin-stimulated signaling (Erk versus Akt activation in both CFb and cardiomyocytes. These data indicate that dasatinib treatment at lower doses than that used in chemotherapy has the capacity to reduce hypertrophy-associated fibrosis and improve ventricular function.

  11. Coronary artery disease, left ventricular hypertrophy and diastolic dysfunction are associated with stroke in patients affected by persistent non-valvular atrial fibrillation: a case-control study

    Directory of Open Access Journals (Sweden)

    Andrea Passantino

    2009-04-01

    Full Text Available Persistent non-valvular atrial fibrillation (NVAF is associated with an increased risk of cardiovascular events such as stroke, and its rate is expected to rise because of the ageing population. The absolute rate of stroke depends on age and comorbidity. Risk stratification for stroke in patients with NVAF derives from populations enrolled in randomized clinical trials. However, participants in clinical trials are often not representative of the general population. Many stroke risk stratification scores have been used, but they do not include transthoracic echocardiogram (TTE, pulsate wave Doppler (PWD and tissue Doppler imaging (TDI, simple and non-invasive diagnostic tools. The role of TTE, PWD and TDI findings has not been previously determined. Our study goal was to determine the association between TTE and PWD findings and stroke prevalence in a population of NVAF prone outpatients. Patients were divided into two groups: P for stroke prone and F for stroke free. There were no statistically significant differences between the two groups concerning cardiovascular risk factors, age (p=0.2, sex (p=0.2, smoking (p=0.3, diabetes (p=0.1 and hypercholesterolemia (p=0.2; hypertension was statistically significant (p less than 0.001. There were statistically significant differences concerning coronary artery disease, previous acute myocardial infarction (AMI (p less than 0.05 and non- AMI coronaropathy (p less than 0.04, a higher rate being in the P group. Concerning echo-Doppler findings, a higher statistically significant rate of left ventricular hypertrophy (LVH (p less than  0.05 and left ventricular diastolic dysfunction (p less than 0.001 was found in the P group and dilated left atrium (p Assessment of cardiac blood pool imaging in patients with left ventricular outflow tract stenosis

    International Nuclear Information System (INIS)

    Nakamura, Yutaka; Ono, Yasuo; Kohata, Tohru; Tsubata, Shinichi; Kamiya, Tetsuroh.

    1993-01-01

    We performed cardiac blood pool imagings with Tc-99m at rest and during supine ergometer exercise to evaluate left ventricular performance in 14 patients with left ventricular outflow tract stenosis. All catheterized patients were divided into two subgroups: 8 patients with peak systolic left ventricular to descending aortic pressure gradients of less than 50 mmHg (LPG group) and 6 patients with peak systolic gradients of more than 50 mmHg (HPG group). Control group included 10 patients without stenotic coronary lesions after Kawasaki disease. Left ventricular ejection fraction (LVEF) was obtained as systolic index; both filling fraction during the first third of diastole (1/3FF) and mean filling rate during the first third of diastole (1/3FR mean) were obtained as diastolic indices. None of the patients had abnormal findings on 201 Tl imaging. LVEF at rest in HPG group was significantly higher than those in control group, but LVEF in HPG group did not increase after exercise. It increased significantly in control group and LPG group. 1/3 FF in HPG group was significantly lower not only at rest but also during exercise. 1/3 FR mean at rest was not different significantly among the 3 groups. However, 1/3FR mean during exercise in LPG group was significantly lower; and 1/3 FR mean during exercise was significantly lower in HPG group than LPG group. The ratio of left ventricular muscular mass to left ventricular end-diastolic volume (M/V) calculated from left ventricular cineangiograms was different significantly among the 3 groups. The M/V ratio showed a correlation with LVEF and 1/3 FF both at rest and during exercise. These results would indicate that systolic function was impaired on exercise in severe left ventricular outflow tract stenosis and diastolic function was impaired on exercise in mild and severe left ventricular outflow tract stenosis. This may correlate with left ventricular hypertrophy and interaction of systolic function. (author)

  12. Extracellular signal-regulated kinases 1/2 as regulators of cardiac hypertrophy

    Directory of Open Access Journals (Sweden)

    Michael eMutlak

    2015-07-01

    Full Text Available Cardiac hypertrophy results from increased mechanical load on the heart and through the actions of local and systemic neuro-humoral factors, cytokines and growth factors. These mechanical and neuroendocrine effectors act through stretch, G protein-coupled receptors and tyrosine kinases to induce the activation of a myriad of intracellular signaling pathways including the extracellular signal-regulated kinases 1/2 (ERK1/2. Since most stimuli that provoke myocardial hypertrophy also elicit an acute phosphorylation of the threonine-glutamate-tyrosine (TEY motif within the activation loops of ERK1 and ERK2 kinases, resulting in their activation, ERKs have long been considered promotors of cardiac hypertrophy. Several mouse models were generated in order to directly understand the causal role of ERK1/2 activation in the heart. These models include direct manipulation of ERK1/2 such as overexpression, mutagenesis or knockout models, manipulations of upstream kinases such as MEK1 and manipulations of the phosphatases that depohosphorylate ERK1/2 such as DUSP6. The emerging understanding from these studies, as will be discussed here, is more complex than originally considered. While there is little doubt that ERK1/2 activation or the lack of it modulates the hypertrophic process or the type of hypertrophy that develops, it appears that not all ERK1/2 activation events are the same. While much has been learned, some questions remain regarding the exact role of ERK1/2 in the heart, the upstream events that result in ERK1/2 activation and the downstream effector in hypertrophy.

  13. Pharmacological delayed preconditioning against ischaemia-induced ventricular arrhythmias: effect of an adenosine A1-receptor agonist

    OpenAIRE

    Tissier, Renaud; Souktani, Rachid; Parent de Curzon, Olivier; Lellouche, Nicolas; Henry, Patrick; Giudicelli, Jean-François; Berdeaux, Alain; Ghaleh, Bijan

    2001-01-01

    The goal of this study was to investigate the effects of the delayed pharmacological preconditioning produced by an adenosine A1-receptor agonist (A1-DPC) against ventricular arrhythmias induced by ischaemia and reperfusion, compared to those of ischaemia-induced delayed preconditioning (I-DPC).Eighty-nine instrumented conscious rabbits underwent a 2 consecutive days protocol. On day 1, rabbits were randomly divided into four groups: ‘Control' (saline, i.v.), ‘I-DPC' (six 4-min coronary arter...

  14. Hypertrophy Stimulation at the Onset of Type I Diabetes Maintains the Soleus but Not the EDL Muscle Mass in Wistar Rats

    Directory of Open Access Journals (Sweden)

    Marco A. S. Fortes

    2017-10-01

    Full Text Available Diabetes mellitus induces a reduction in skeletal muscle mass and strength. Strength training is prescribed as part of treatment since it improves glycemic control and promotes increase of skeletal muscle mass. The mechanisms involved in overload-induced muscle hypertrophy elicited at the establishment of the type I diabetic state was investigated in Wistar rats. The purpose was to examine whether the overload-induced hypertrophy can counteract the hypotrophy associated to the diabetic state. The experiments were performed in oxidative (soleus or glycolytic (EDL muscles. PI3K/Akt/mTOR protein synthesis pathway was evaluated 7 days after overload-induced hypertrophy of soleus and of EDL muscles. The mRNA expression of genes associated with different signaling pathways that control muscle hypertrophy was also evaluated: mechanotransduction (FAK, Wnt/β-catenin, myostatin, and follistatin. The soleus and EDL muscles when submitted to overload had similar hypertrophic responses in control and diabetic animals. The increase of absolute and specific twitch and tetanic forces had the same magnitude as muscle hypertrophic response. Hypertrophy of the EDL muscle from diabetic animals mostly involved mechanical loading-stimulated PI3K/Akt/mTOR pathway besides the reduced activation of AMP-activated protein kinase (AMPK and decrease of myostatin expression. Hypertrophy was more pronounced in the soleus muscle of diabetic animals due to a more potent activation of rpS6 and increased mRNA expression of insulin-like growth factor-1 (IGF-1, mechano-growth factor (MGF and follistatin, and decrease of myostatin, MuRF-1 and atrogin-1 contents. The signaling changes enabled the soleus muscle mass and force of the diabetic rats to reach the values of the control group.

  15. Implication of C-type natriuretic peptide-3 signaling in glycosaminoglycan synthesis and chondrocyte hypertrophy during TGF-β1 induced chondrogenic differentiation of chicken bone marrow-derived mesenchymal stem cells.

    Science.gov (United States)

    Kocamaz, Erdogan; Gok, Duygu; Cetinkaya, Ayse; Tufan, A Cevik

    2012-10-01

    This study investigated the involvement of CNP-3, chick homologue for human C-type natriuretic peptide (CNP), in TGF-β1 induced chondrogenic differentiation of chicken bone marrow-derived mesenchymal stem cells (MSCs). Chondrogenic differentiation of MSCs in pellet cultures was induced by TGF-β1. Chondrogenic differentiation and glycosaminoglycan synthesis were analyzed on the basis of basic histology, collagen type II expression, and Alcian blue staining. Antibodies against CNP and NPR-B were used to block their function during these processes. Results revealed that expression of CNP-3 and NPR-B in MSCs were regulated by TGF-β1 in monolayer cultures at mRNA level. In pellet cultures of MSCs, TGF-β1 successfully induced chondrogenic differentiation and glycosaminoglycan synthesis. Addition of CNP into the TGF-β1 supplemented chondrogenic differentiation medium further induced the glycosaminoglycan synthesis and hypertrophy of differentiated chondrocytes in these pellets. Pellets induced with TGF-β1 and treated with antibodies against CNP and NPR-B, did show collagen type II expression, however, Alcian blue staining showing glycosaminoglycan synthesis was significantly suppressed. In conclusion, CNP-3/NPR-B signaling may strongly be involved in synthesis of glycosaminoglycans of the chondrogenic matrix and hypertrophy of differentiated chondrocytes during TGF-β1 induced chondrogenic differentiation of MSCs.

  16. Cellular mechanism underlying hypothermia-induced ventricular tachycardia/ventricular fibrillation in the setting of early repolarization and the protective effect of quinidine, cilostazol, and milrinone.

    Science.gov (United States)

    Gurabi, Zsolt; Koncz, István; Patocskai, Bence; Nesterenko, Vladislav V; Antzelevitch, Charles

    2014-02-01

    Hypothermia has been reported to induce ventricular tachycardia and fibrillation (VT/VF) in patients with early repolarization (ER) pattern. This study examines the cellular mechanisms underlying VT/VF associated with hypothermia in an experimental model of ER syndrome and examines the effectiveness of quinidine, cilostazol, and milrinone to prevent hypothermia-induced arrhythmias. Transmembrane action potentials were simultaneously recorded from 2 epicardial and 1 endocardial site of coronary-perfused canine left ventricular wedge preparations, together with a pseudo-ECG. A combination of NS5806 (3-10 μmol/L) and verapamil (1 μmol/L) was used to pharmacologically model the genetic mutations responsible for ER syndrome. Acetylcholine (3 μmol/L) was used to simulate increased parasympathetic tone, which is known to promote ER. In controls, lowering the temperature of the coronary perfusate to induce mild hypothermia (32°C-34°C) resulted in increased J-wave area on the ECG and accentuated epicardial action potential notch but no arrhythmic activity. In the setting of ER, hypothermia caused further accentuation of the epicardial action potential notch, leading to loss of the action potential dome at some sites but not others, thus creating the substrate for development of phase 2 reentry and VT/VF. Addition of the transient outward current antagonist quinidine (5 μmol/L) or the phosphodiesterase III inhibitors cilostazol (10 μmol/L) or milrinone (5 μmol/L) diminished the ER manifestations and prevented the hypothermia-induced phase 2 reentry and VT/VF. Hypothermia leads to VT/VF in the setting of ER by exaggerating repolarization abnormalities, leading to development of phase 2 reentry. Quinidine, cilostazol, and milrinone suppress the hypothermia-induced VT/VF by reversing the repolarization abnormalities.

  17. L-arginine fails to prevent ventricular remodeling and heart failure in the spontaneously hypertensive rat.

    Science.gov (United States)

    Brooks, Wesley W; Conrad, Chester H; Robinson, Kathleen G; Colucci, Wilson S; Bing, Oscar H L

    2009-02-01

    The effects of long-term oral administration of L-arginine, a substrate for nitric oxide (NO) production, on left ventricular (LV) remodeling, myocardial function and the prevention of heart failure (HF) was compared to the angiotensin-converting enzyme (ACE) inhibitor captopril in a rat model of hypertensive HF (aged spontaneously hypertensive rat (SHR)). SHRs and age-matched normotensive Wistar-Kyoto (WKY) rats were assigned to either no treatment, treatment with L-arginine (7.5 g/l in drinking water) or captopril (1 g/l in drinking water) beginning at 14 months of age, a time when SHRs exhibit stable compensated hypertrophy with no hemodynamic impairment; animals were studied at 23 months of age or at the time of HF. In untreated SHR, relative to WKY, there was significant LV hypertrophy, myocardial fibrosis, and isolated LV muscle performance and response to isoproterenol (ISO) were depressed; and, 7 of 10 SHRs developed HF. Captopril administration to six SHRs attenuated hypertrophy and prevented impaired inotropic responsiveness to ISO, contractile dysfunction, fibrosis, increased passive stiffness, and HF. In contrast, L-arginine administration to SHR increased LV hypertrophy and myocardial fibrosis while cardiac performance was depressed; and 7 of 9 SHRs developed HF. In WKY, L-arginine treatment but not captopril resulted in increased LV weight and the contractile response to ISO was blunted. Neither L-arginine nor captopril treatment of WKY changed fibrosis and HF did not occur. These data demonstrate that in contrast to captopril, long-term treatment with L-arginine exacerbates age-related cardiac hypertrophy, fibrosis, and did not prevent contractile dysfunction or the development of HF in aging SHR.

  18. Tacrolimus-related hypertrophic cardiomyopathy in an adult cardiac transplant patient

    Institute of Scientific and Technical Information of China (English)

    LIU Tong; DONG Jian-zeng; GAO Yun; GAO Yu-long; CHENG Yu-tong; WANG Su; LI Zhi-zhong; ZHANG Hai-bo; MENG Xu; MA Chang-sheng

    2012-01-01

    Left ventricular hypertrophy associated with the use of tacrolimus is a rare complication of solid organ transplantation in adult recipients.We present a cardiac transplant recipient who developed severe concentric left ventricular hypertrophy with congestive heart failure related to myocardial hypertrophy on tacrolimus.Hypertrophy improved when the drug was discontinued and replaced with sirolimus.

  19. Left ventricular remodeling in preclinical experimental mitral regurgitation of dogs.

    Science.gov (United States)

    Dillon, A Ray; Dell'Italia, Louis J; Tillson, Michael; Killingsworth, Cheryl; Denney, Thomas; Hathcock, John; Botzman, Logan

    2012-03-01

    Dogs with experimental mitral regurgitation (MR) provide insights into the left ventricular remodeling in preclinical MR. The early preclinical left ventricular (LV) changes after mitral regurgitation represent progressive dysfunctional remodeling, in that no compensatory response returns the functional stroke volume (SV) to normal even as total SV increases. The gradual disease progression leads to mitral annulus stretch and enlargement of the regurgitant orifice, further increasing the regurgitant volume. Remodeling with loss of collagen weave and extracellular matrix (ECM) is accompanied by stretching and hypertrophy of the cross-sectional area and length of the cardiomyocyte. Isolated ventricular cardiomyocytes demonstrate dysfunction based on decreased cell shortening and reduced intracellular calcium transients before chamber enlargement or decreases in contractility in the whole heart can be clinically appreciated. The genetic response to increased end-diastolic pressure is down-regulation of genes associated with support of the collagen and ECM and up-regulation of genes associated with matrix remodeling. Experiments have not demonstrated any beneficial effects on remodeling from treatments that decrease afterload via blocking the renin-angiotensin system (RAS). Beta-1 receptor blockade and chymase inhibition have altered the progression of the LV remodeling and have supported cardiomyocyte function. The geometry of the LV during the remodeling provides insight into the importance of regional differences in responses to wall stress. Copyright © 2012 Elsevier B.V. All rights reserved.