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Sample records for ventricular myocyte hypertrophy

  1. Some growth factors stimulate cultured adult rabbit ventricular myocyte hypertrophy in the absence of mechanical loading

    Science.gov (United States)

    Decker, R. S.; Cook, M. G.; Behnke-Barclay, M.; Decker, M. L.

    1995-01-01

    Cultured adult rabbit cardiac myocytes treated with recombinant growth factors display enhanced rates of protein accumulation (ie, growth) in response to insulin and insulin-like growth factors (IGFs), but epidermal growth factor, acidic or basic fibroblast growth factor, and platelet-derived growth factor failed to increase contractile protein synthesis or growth of the heart cells. Insulin and IGF-1 increased growth rates by stimulating anabolic while simultaneously inhibiting catabolic pathways, whereas IGF-2 elevated growth modestly by apparently inhibiting lysosomal proteolysis. Neutralizing antibodies directed against either IGF-1 or IGF-2 or IGF binding protein 3 blocked protein accumulation. A monoclonal antibody directed against the IGF-1 receptor also inhibited changes in protein turnover provoked by recombinant human IGF-1 but not IGF-2. Of the other growth factors tested, only transforming growth factor-beta 1 increased the fractional rate of myosin heavy chain (MHC) synthesis, with beta-MHC synthesis being elevated and alpha-MHC synthesis being suppressed. However, the other growth factors were able to modestly stimulate the rate of DNA synthesis in this preparation. Bromodeoxyuridine labeling revealed that these growth factors increased DNA synthesis in myocytes and nonmyocytes alike, but the heart cells displayed neither karyokinesis or cytokinesis. In contrast, cocultures of cardiac myocytes and nonmyocytes and nonmyocyte-conditioned culture medium failed to enhance the rate of cardiac MHC synthesis or its accumulation, implying that quiescent heart cells do not respond to "conditioning" by cardiac nonmyocytes. These findings demonstrated that insulin and the IGFs promote passively loaded cultured adult rabbit heart cells to hypertrophy but suggest that other growth factors tested may be limited in this regard.

  2. Ventricular hypertrophy--physiological mechanisms.

    Science.gov (United States)

    Vaughan Williams, E M

    1986-01-01

    Adult cardiac myocytes are incapable of mitosis. Dead cells are replaced by connective tissue so that after myocardial infarction (MI), function can only be restored by compensatory hypertrophy of the surviving myocardium. In physiological hypertrophy in response to exercise, high altitude, or mild hypertension, additional myoplasm expands cell diameter in an orderly fashion; Z-lines are in register and the normal ratio of volume densities of contractile elements, mitochondria, and capillaries is conserved. In hypertrophy induced by aortic or pulmonary artery banding or by experimental or congenital hypertension, the borderline between physiological and pathological hypertrophy may be crossed, causing disorganization of fibers and an unfavourable contractile element to capillary ratio. There was, therefore, a need for a graded model of hypertrophy, which involves simulating an altitude of 6,000 m at sea level by supplying rabbits with appropriate nitrogen/oxygen mixtures. In this environment, 50% right ventricular hypertrophy can be achieved without alteration of left ventricular weight or hematocrit. Longer exposures produced 100% right ventricular hypertrophy, with only moderate increases in hematocrit and left ventricular weight. It is well known that adrenergic stimulation causes cardiac hypertrophy, and it has been suggested that release of a trophic factor from sympathetic nerves, either noradrenaline or a protein, might be a necessary stimulus for growth. If so, long-term treatment of post-MI patients with beta-adrenergic blocking agents could inhibit a desirable compensatory hypertrophy of the surviving myocardium. In the above model it has been found, however, that neither beta-blockade nor chemical sympathectomy with guanethidine or 6-hydroxydopamine had any effect on the hypertrophy, nor did treatment with verapamil or nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Trophic effect of human pericardial fluid on adult cardiac myocytes. Differential role of fibroblast growth factor-2 and factors related to ventricular hypertrophy.

    Science.gov (United States)

    Corda, S; Mebazaa, A; Gandolfini, M P; Fitting, C; Marotte, F; Peynet, J; Charlemagne, D; Cavaillon, J M; Payen, D; Rappaport, L; Samuel, J L

    1997-11-01

    Pericardial fluid (PF) may contain myocardial growth factors that exert paracrine actions on cardiac myocytes. The aims of this study were (1) to investigate the effects of human PF and serum, collected from patients undergoing cardiac surgery, on the growth of cultured adult rat cardiac myocytes and (2) to relate the growth activity of both fluids to the adaptive changes in overloaded human hearts. Both PF and serum increased the rate of protein synthesis, measured by [14C]phenylalanine incorporation in adult rat cardiomyocytes (PF, +71.9 +/- 8.2% [n = 17]; serum, +14.9 +/- 6.5% [n = 13]; both P < .01 versus control medium). The effects of both PF and serum on cardiomyocyte growth correlated positively with the respective left ventricular (LV) mass. However, the magnitude of change with PF was 3-fold greater than with serum (P < .01). These trophic effects of PF were mimicked by exogenous basic fibroblast growth factor (FGF2) and inhibited by anti-FGF2 antibodies and transforming growth factor-beta (TGF-beta), suggesting a relationship to FGF2. In addition, FGF2 concentration in PF was 20 times greater than in serum. On the other hand, the LV mass-dependent trophic effect, present in both fluids, was independent of FGF2 concentration or other factors, such as angiotensin II, atrial natriuretic factor, and TGF-beta. These data suggest that FGF2 in human PF is a major determining factor in normal myocyte growth, whereas unidentified LV mass-dependent factor(s), present in both PF and serum, participates in the development of ventricular hypertrophy. PMID:9351441

  4. Mitochondria and left ventricular hypertrophy

    Institute of Scientific and Technical Information of China (English)

    Haiyan Zhu; Shiwen Wang

    2008-01-01

    @@ Introduction Left ventricular hypertrophy (LVH) is one of the vicious organ damages of essential hypertension.It contributes a lot to high mortality of essential hypertension due to sudden cardiac death,ventricular arrhythmia and heart failure.Many factors involve in the pathogenesis of hypertension-induced LVH including inherited variants as well as environmental factors.

  5. Left ventricular hypertrophy in patients treated with regular hemodialyses

    OpenAIRE

    Petrović Dejan; Stojimirović Biljana

    2008-01-01

    Left ventricular hypertrophy is the main risk factor for development of cardiovascular morbidity and mortality in patients on hemodialysis. Left ventricular hypertrophy is found in 75% of the patients treated with hemodialysis. Risk factors for left ventricular hypertrophy in patients on hemodialysis include: blood flow through arterial-venous fistula, anemia, hypertension, increased extracellular fluid volume, oxidative stress, microinflammation, hyperhomocysteinemia, secondary hyperpara- th...

  6. Left ventricular hypertrophy : virtuous intentions, malign consequences

    NARCIS (Netherlands)

    Pokharel, S; Sharma, UC; Pinto, YM

    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 Ca2+ homeostasis, there ar

  7. Cellular mechanisms of reduced sarcoplasmic reticulum Ca2+ content in L-thyroxin-induced rat ventricular hypertrophy

    Institute of Scientific and Technical Information of China (English)

    Lai-jing SONG; Guan-lei WANG; Jie LIU; Qin-ying QIU; Jing-hua OU; Yong-yuan GUAN

    2008-01-01

    Aim:To examine how the sarcoplasmic reticulum (SR) Ca2+ content changes and the underlying mechanism in L-thyroxin-induced cardiac hypertrophy. Methods:Echocardiography was used to confirm the establishment of the cardiac hypertro-phy model. The confocal microscopy and fluorescent indicator Fluo-3 was ap-plied to examine the intracellular Ca2+ concentration ([Ca2+]I), the Ca2+ sparks, and the caffeine-induced Ca2+ transient in freshly isolated cardiac ventricular myocytes. The activity of sarcolemmal and SR Ca2+-ATPase 2a (SERCA2a) in the ventricular tissue was also measured, respectively. Results:L-thyroxin (1 mg/kg injection for 10 d) induces left ventricular cardiac hypertrophy with normal myocardial function. The decreased caffeine-induced Ca2+ transient in the Ca2+-free solution was detected. The spontaneous Ca2+ sparks in hypertrophied myocytes occurred more frequently than in normal cells, with similar duration and spatial spread, but smaller amplitude. Then the basal [Ca2+]I increase was observed in quiescent left ventricular myocytes from hyperthyroidism rats. The activity of sarcolemmal and SR Ca2+-ATPase was decreased in the hypertrophied ventricle tissue. Conclusion:The results suggested that the reduced SR Ca2+ content may be associated with an increased Ca2+ leak and reduced SERCA2a activity, contributing to abnormal intracellular Ca2+ handling during hypertrophy in hyperthyroidism rats.

  8. Effects of Angiotensin Ⅱ on Expression of the Gap Junction Channel Protein Connexin 43 in Neonatal Rat Ventricular Myocytes

    Institute of Scientific and Technical Information of China (English)

    Jun Yang; Wei Wu

    2007-01-01

    To study the effects of angiotensin Ⅱ,as a mediator of cardiac hypertrophy,on expression of connexin 43 (Cx43) in cultured neonatal rat ventricular myocytes and correlation of expression of Cx43 and cardiomyocyte hypertrophy.Methods Cardiomyocytes were isolated from newborn SD rats.Angiotensin Ⅱ was added into the media to induce myocyte hypertrophy.Cultures were exposed to 10 ~6 mol/L angiotensin Ⅱ for 72 h,Cx43 expression was characterized by RT-PCR and Immunofluorescence methods.Results Immunofluorescence analysis revealed decreased Cx43 immunoreactivity in cells treated for 72 h with angiotensin Ⅱ.RT-PCR analysis demonstrated there was an obvious decrease of Cx43 mRNA level in cells exposed to angiotensin Ⅱ for 72 h.The changes of expression of connexin 43 were related to its entrance into S phase of the cell cycle.Cultured neonatal rat cardiomyocytes were exposed for 72 h to increase concentrations of angiotensin Ⅱ ( 1.0 × 10-9 ~ 1.0 × 10-6mol/L),resulting in significantly decreased Cx43 expression.Conclusions Angiotensin Ⅱ leads to a concentration-dependent decrease in Cx43 protein in cultured neonatal rat ventricular myocytes by decreasing Cx43 mRNA synthesis.Signal transduction pathways activated by angiotensin Ⅱ under pathophysiologic conditions of cardiac hypertrophy could initiate remodeling of gap junctions.

  9. Echocardiographic left ventricular hypertrophy in Chinese endurance athletes.

    OpenAIRE

    Lo, Y S; Chin, M K

    1990-01-01

    Most echocardiographic data on the athletic heart syndrome originate from the United States and Western Europe. There are no published data on echocardiographically documented left ventricular hypertrophy in Asian athletes. We investigated the echocardiographic changes which take place with endurance training by studying eight Hong Kong national cyclists. This study confirms that left ventricular hypertrophy and increased left ventricular end-diastolic dimensions are common findings in Chines...

  10. Dynamic Changes in Sarcoplasmic Reticulum Structure in Ventricular Myocytes

    Directory of Open Access Journals (Sweden)

    Amanda L. Vega

    2011-01-01

    sarcoplasmic reticulum (SR and the sarcolemma where Ca2+ release is activated. Here, we tested the hypothesis that the SR is a structurally inert organelle in ventricular myocytes. Our data suggest that rather than being static, the SR undergoes frequent dynamic structural changes. SR boutons expressing functional ryanodine receptors moved throughout the cell, approaching or moving away from the sarcolemma of ventricular myocytes. These changes in SR structure occurred in the absence of changes in [Ca2+] during EC coupling. Microtubules and the molecular motors dynein and kinesin 1(Kif5b were important regulators of SR motility. These findings support a model in which the SR is a motile organelle capable of molecular motor protein-driven structural changes.

  11. Atorvastatin prevents connexin43 remodeling in hypertrophied left ventricular myocardium of spontaneously hypertensive rats

    Institute of Scientific and Technical Information of China (English)

    CHEN Hong-juan; YAO Lei; CHEN Tu-gang; YU Min; WANG Li-hong; CHEN Jun-zhu

    2007-01-01

    Background Connexin43 (Cx43) is the predominant gap junction protein in heart and is involved in the control of cell-to-cell communication to modulate the contractility and the electrical coupling of cardiac myocytes. Left ventricular(LV) hypertrophy is accompanied by changes of Cx43 expression. Recent studies have demonstrated that statins reduced cardiac hypertrophy. However, it is unknown whether statins can affect Cx43 expression in hypertrophied left ventricular myocardium. This study was designed to assess the effects of atorvastatin on LV hypertrophy and Cx43 expression in spontaneously hypertensive rats (SHR).Methods Nine-week old SHRs were randomly divided into two groups. Some received atorvastatin at 30 mg/kg by oral gavage once daily for 8 weeks (SHR-A); others received vehicle. Age-matched Wistar-Kyoto rats (WKY) received atorvastatin or vehicle for 8 weeks were used as controls. At the end of the experiment, we investigated LV hypertrophy and the expression of Cx43 in LV myocardium in four groups. Cx43 expression was investigated by the methods of Western blotting, immunohistochemistry, and transmission electron microscope. LV hypertrophy was accessed by pathological analysis and plasma brain natriuretic peptide (BNP) level.Results LV hypertrophy was prominent in untreated SHR. In SHR, LV myocardium Cx43 level was upregulated, and the distribution of Cx43 was displaced from their usual locations to other sites at various distances away from the intercalated disks. After atorvastatin treatment, myocardium Cx43 level was reduced in SHR-A, and the distribution of Cx43 gap junction became much regular and confined to intercalated disk. Statins also prevented LV hypertrophy in SHR.Conclusions These results provide novel in vivo evidence for the key role of Cx43 gap junctions in LV hypertrophy and the possible mechanism in anti-hypertrophic effect of statins. Atorvastatin treatment may have beneficial effects on LV hypertrophy in spontaneously hypertensive

  12. A unified theory of calcium alternans in ventricular myocytes

    Science.gov (United States)

    Qu, Zhilin; Liu, Michael B.; Nivala, Michael

    2016-01-01

    Intracellular calcium (Ca2+) alternans is a dynamical phenomenon in ventricular myocytes, which is linked to the genesis of lethal arrhythmias. Iterated map models of intracellular Ca2+ cycling dynamics in ventricular myocytes under periodic pacing have been developed to study the mechanisms of Ca2+ alternans. Two mechanisms of Ca2+ alternans have been demonstrated in these models: one relies mainly on fractional sarcoplasmic reticulum Ca2+ release and uptake, and the other on refractoriness and other properties of Ca2+ sparks. Each of the two mechanisms can partially explain the experimental observations, but both have their inconsistencies with the experimental results. Here we developed an iterated map model that is composed of two coupled iterated maps, which unifies the two mechanisms into a single cohesive mathematical framework. The unified theory can consistently explain the seemingly contradictory experimental observations and shows that the two mechanisms work synergistically to promote Ca2+ alternans. Predictions of the theory were examined in a physiologically-detailed spatial Ca2+ cycling model of ventricular myocytes. PMID:27762397

  13. Voluntary exercise-induced changes in beta2-adrenoceptor signalling in rat ventricular myocytes.

    Science.gov (United States)

    Stones, Rachel; Natali, Antonio; Billeter, Rudolf; Harrison, Simon; White, Ed

    2008-09-01

    Regular exercise is beneficial to cardiovascular health. We tested whether mild voluntary exercise training modifies key myocardial parameters [ventricular mass, intracellular calcium ([Ca2+]i) handling and the response to beta-adrenoceptor (beta-AR) stimulation] in a manner distinct from that reported for beneficial, intensive training and pathological hypertrophic stimuli. Female rats performed voluntary wheel-running exercise for 6-7 weeks. The mRNA expression of target proteins was measured in left ventricular tissue using real-time reverse transcriptase-polymerase chain reaction. Simultaneous measurement of cell shortening and [Ca2+]i transients were made in single left ventricular myocytes and the inotropic response to beta1- and beta2-AR stimulation was measured. Voluntary exercise training resulted in cardiac hypertrophy, the heart weight to body weight ratio being significantly greater in trained compared with sedentary animals. However, voluntary exercise caused no significant alteration in the size or time course of myocyte shortening and [Ca2+]i transients or in the mRNA levels of key proteins that regulate Ca2+ handling. The positive inotropic response to beta1-AR stimulation and the level of beta1-AR mRNA were unaltered by voluntary exercise but both mRNA levels and inotropic response to beta2-AR stimulation were significantly reduced in trained animals. The beta2-AR inotropic response was restored by exposure to pertussis toxin. We propose that in contrast to pathological stimuli and to beneficial, intense exercise training, modulation of Ca2+ handling is not a major adaptive mechanism in the response to mild voluntary exercise. In addition, and in a reversal of the situation seen in heart failure, voluntary exercise training maintains the beta1-AR response but reduces the beta2-AR response. Therefore, although voluntary exercise induces cardiac hypertrophy, there are distinct differences between its effects on key myocardial regulatory mechanisms

  14. ROLE OF CALCINEURIN IN ANGIOTENSIN II INDUCED CARDIAC MYOCYTE HYPERTROPHY OF RATS

    Institute of Scientific and Technical Information of China (English)

    符民桂; 张继峰; 许松; 庞永政; 刘乃奎; 唐朝枢

    2001-01-01

    Objective. The present study investigated the role of calcineurin in angiotensin II(AngII) induced cardiac myocyte hypertrophy of rats. Method. The primary cardiac myocytes were cultured under the standard conditions. The calcineurin activity in AngII treated cardiomyocytes was tested by using PNPP;protein synethsis rate was assessed by 3H leucine incorporation; atrial natriuretic factor(ANF) Mrna level was determined by Northern blot analysis. Cell viability was estimated by lactate dehydrogenase(LDH) levels in cultured medium and by dyed cell numbers. Result. After stimulation of 10,100 and 1 000nmol/L of AngII, calcineurin activities in the cardiomyocytes were increased by 13% ,57% (P< 0.05) and 228% (P< 0.01) respectively, compared with control group. Cyclosporin A(CsA), a specific inhibitor of calcineurin, markedly inhibited the calcineurin activity and decreased the 3H leucine incorporation in AngII treated cardiomyocytes in a dose dependent manner. It was also found that CsA slightly reduced the Mrna level of ANF gene in AngII stimulated cardiomyocytes. Conclusion. During AngII induced cardiac myocyte hypertrophy, calcineurin signal pathway is activated, and inhibition of the pathway can attenuate AngII induced cardiac myocyte hypertrophy, which suggests that the calcineurin signal pathway may play an important role in AngII induced myocardial hypertrophy of rats.

  15. Arterial baroreflex function and left ventricular hypertrophy

    Institute of Scientific and Technical Information of China (English)

    MIAO Chao-Yu; SU Ding-Feng

    2004-01-01

    It is well known that the arterial baroreflex(ABR)plays a key role in the regulation of heart rate and stabilization of blood pressure.Currently,it appears that ABR dysfunction is involved in the pathophysiology of cardiovascular disease states.Since the mid-1990s,a number of studies have been carried out in our laboratory to explore the pathological significance of ABR function in cardiovascular damage.This minireview summarizes our research work on the topic of ABR and left ventricular hypertrophy(LVH).On the basis of discussion concerning the importance of ABR dysfunction in hypertensive LVH and sinoaortic denervation-induced LVH,we advance a new strategy for reversal of LVH,that is,restoration of impaired ABR function.We tested this hypothesis in animal models with ABR deficiency.It was found that improvement of impaird ABR function with long-term treatment of ketanserin or candesartan was accompanied by reversal of LVH.The preliminary results indicate that it is feasible to target ABR for treatment of LVH.

  16. Ectopic automaticity induced in ventricular myocytes by transgenic overexpression of HCN2.

    Science.gov (United States)

    Oshita, Kensuke; Itoh, Masayuki; Hirashima, Shingo; Kuwabara, Yoshihiro; Ishihara, Keiko; Kuwahara, Koichiro; Nakao, Kazuwa; Kimura, Takeshi; Nakamura, Kei-Ichiro; Ushijima, Kazuo; Takano, Makoto

    2015-03-01

    Hyperpolarization-activated cyclic nucleotide-gated channels (HCNs) are expressed in the ventricles of fetal hearts but are normally down-regulated as development progresses. In the hypertrophied heart, however, these channels are re-expressed and generate a hyperpolarization-activated, nonselective cation current (Ih), which evidence suggests may increase susceptibility to arrhythmia. To test this hypothesis, we generated and analyzed transgenic mice overexpressing HCN2 specifically in their hearts (HCN2-Tg). Under physiological conditions, HCN2-Tg mice exhibited no discernible abnormalities. After the application of isoproterenol (ISO), however, ECG recordings from HCN2-Tg mice showed intermittent atrioventricular dissociation followed by idioventricular rhythm. Consistent with this observation, 0.3 μmol/L ISO-induced spontaneous action potentials (SAPs) in 76% of HCN2-Tg ventricular myocytes. In the remaining 24%, ISO significantly depolarized the resting membrane potential (RMP), and the late repolarization phase of evoked action potentials (APs) was significantly longer than in WT myocytes. Analysis of membrane currents revealed that these differences are attributable to the Ih tail current. These findings suggest HCN2 channel activity reduces the repolarization reserve of the ventricular action potential and increases ectopic automaticity under pathological conditions such as excessive β-adrenergic stimulation. PMID:25562801

  17. Global intracoronary infusion of allogeneic cardiosphere-derived cells improves ventricular function and stimulates endogenous myocyte regeneration throughout the heart in swine with hibernating myocardium.

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    Gen Suzuki

    Full Text Available Cardiosphere-derived cells (CDCs improve ventricular function and reduce fibrotic volume when administered via an infarct-related artery using the "stop-flow" technique. Unfortunately, myocyte loss and dysfunction occur globally in many patients with ischemic and non-ischemic cardiomyopathy, necessitating an approach to distribute CDCs throughout the entire heart. We therefore determined whether global intracoronary infusion of CDCs under continuous flow improves contractile function and stimulates new myocyte formation.Swine with hibernating myocardium from a chronic LAD occlusion were studied 3-months after instrumentation (n = 25. CDCs isolated from myocardial biopsies were infused into each major coronary artery (∼ 33 × 10(6 icCDCs. Global icCDC infusion was safe and while ∼ 3% of injected CDCs were retained, they did not affect ventricular function or myocyte proliferation in normal animals. In contrast, four-weeks after icCDCs were administered to animals with hibernating myocardium, %LADWT increased from 23 ± 6 to 51 ± 5% (p<0.01. In diseased hearts, myocyte proliferation (phospho-histone-H3 increased in hibernating and remote regions with a concomitant increase in myocyte nuclear density. These effects were accompanied by reductions in myocyte diameter consistent with new myocyte formation. Only rare myocytes arose from sex-mismatched donor CDCs.Global icCDC infusion under continuous flow is feasible and improves contractile function, regresses myocyte cellular hypertrophy and increases myocyte proliferation in diseased but not normal hearts. New myocytes arising via differentiation of injected cells are rare, implicating stimulation of endogenous myocyte regeneration as the primary mechanism of repair.

  18. CyPA-CD147-ERK1/2-cyclin D2 signaling pathway is upregulated during rat left ventricular hypertrophy.

    Science.gov (United States)

    Tang, Fu-Cai; Wang, Hong-Yan; Ma, Ming-Ming; Guan, Tian-Wang; Pan, Long; Yao, Dun-Chen; Chen, Ya-Lan; Chen, Wei-Bei; Tu, Yong-Sheng; Fu, Xiao-Dong

    2015-08-25

    The changes of serum cyclophilin A (CyPA), its receptor CD147 and the downstream signaling pathway during the process of cardiac hypertrophy remain unknown. The present study aims to investigate the relationships between CyPA-CD147-ERK1/2-cyclin D2 signaling pathway and the development of cardiac hypertrophy. Left ventricular hypertrophy was prepared by 2-kidney, 2-clip in Sprague-Dawley rats and observed for 1 week, 4 and 8 weeks. Left ventricular hypertrophy was evaluated by ratio of left ventricular heart weight to body weight (LVW/BW) and cardiomyocyte cross sectional area (CSA). CyPA levels in serum were determined with a rat CyPA ELISA kit. Expressions of CyPA, CD147, phospho-ERK1/2 and cyclin D2 in left ventricular myocytes were determined by Western blot and immunostaining. Compared with sham groups, systolic blood pressure reached hypertensive levels at 4 weeks in 2K2C groups. LVW/BW and CSA in 2K2C groups were significantly increased at 4 and 8 weeks after clipping. ELISA results indicated a prominent increase in serum CyPA level associated with the degree of left ventricular hypertrophy. Western blot revealed that the expressions of CyPA, CD147, phospho-ERK1/2 and cyclin D2 in left ventricular tissues were also remarkably increased as the cardiac hypertrophy developed. The results of the present study demonstrates that serum CyPA and CyPA-CD147-ERK1/2-cyclin D2 signaling pathway in ventricular tissues are time-dependently upregulated and activated with the process of left ventricular hypertrophy. These data suggest that CyPA-CD147 signaling cascade might play a role in the pathogenesis of left ventricular hypertrophy, and CyPA might be a prognosticator of the degree of left ventricular hypertrophy. PMID:26300251

  19. 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....

  20. Electrocardiographic Criteria for Left Ventricular Hypertrophy in Children

    OpenAIRE

    Rijnbeek, Peter R; van Herpen, Gerard; Kapusta, Livia; ten Harkel, A. Derk Jan; Witsenburg, Maarten; Kors, Jan A.

    2008-01-01

    Previous studies to determine the sensitivity of the electrocardiogram (ECG) for left ventricular hypertrophy (LVH) in children had their imperfections: they were not done on an unselected hospital population, several criteria used in adults were not applied to children, and obsolete limits of normal for the ECG parameters were used. Furthermore, left ventricular mass (LVM) was taken as the reference standard for LVH, with no regard for other clinical evidence. The study population consisted ...

  1. Effect of Sodium Tanshinone Ⅱ A Sulfonate on Cardiac Myocyte Hypertrophy and Its Underlying Mechanism

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Objective:To investigate the effects of sodium tanshinone Ⅱ A sulfonate (STS) on the hypertrophy induced by angiotensin Ⅱ (Ang Ⅱ) in primary cultured neonatal rat cardiac myocytes.Methods:The effect of STS on cytotoxicity was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-3,5-phenytetrazoliumromide (MTT) assay.As indexes for cardiocyte hypertrophy,cell size was determined by phase contrast microscopy and protein synthesis rate was measured by 3H-leucine incorporation.The proto-oncogene c-fos mRNA expression of cardiocytes was assessed using reverse transcription polymerase chain reaction (RT-PCR).Results:STS could inhibit cardiocyte hypertrophy,increase the protein synthesis rate and enhance proto-oncogene c-los mRNA expression in cardiocytes induced by Ang Ⅱ (P<0.01),with an effect similar to that of Valsartan,the Ang Ⅱ receptor antagonist.Conclusion:STS can prevent the hypertrophy of cardiac myocytes induced by Ang Ⅱ,which may be related to its inhibition of the expression of proto-oncogene c-fos mRNA.

  2. Four Genetic Loci Influencing Electrocardiographic Indices of Left Ventricular Hypertrophy

    NARCIS (Netherlands)

    Shah, Sonia; Nelson, Christopher P.; Gaunt, Tom R.; van der Harst, Pim; Barnes, Timothy; Braund, Peter S.; Lawlor, Debbie A.; Casas, Juan-Pablo; Padmanabhan, Sandosh; Drenos, Fotios; Kivimaki, Mika; Talmud, Philippa J.; Humphries, Steve E.; Whittaker, John; Morris, Richard W.; Whincup, Peter H.; Dominiczak, Anna; Munroe, Patricia B.; Johnson, Toby; Goodall, Alison H.; Cambien, Francois; Diemert, Patrick; Hengstenberg, Christian; Ouwehand, Willem H.; Felix, Janine F.; Glazer, Nicole L.; Tomaszewski, Maciej; Burton, Paul R.; Tobin, Martin D.; van Veldhuisen, Dirk J.; de Boer, Rudolf A.; Navis, Gerjan; van Gilst, Wiek H.; Mayosi, Bongani M.; Thompson, John R.; Kumari, Meena; MacFarlane, Peter W.; Day, Ian N. M.; Hingorani, Aroon D.; Samani, Nilesh J.

    2011-01-01

    Background-Presence of left ventricular hypertrophy on an ECG (ECG-LVH) is widely assessed clinically and provides prognostic information in some settings. There is evidence for significant heritability of ECG-LVH. We conducted a large-scale gene-centric association analysis of 4 commonly measured i

  3. Electrocardiographic criteria for left ventricular hypertrophy in children

    NARCIS (Netherlands)

    P.R. Rijnbeek (Peter); G. van Herpen (Gerard); L. Kapusta (Livia); A.D.J. ten Harkel (Arend); M. Witsenburg (Maarten); J.A. Kors (Jan)

    2008-01-01

    textabstractPrevious studies to determine the sensitivity of the electrocardiogram (ECG) for left ventricular hypertrophy (LVH) in children had their imperfections: they were not done on an unselected hospital population, several criteria used in adults were not applied to children, and obsolete lim

  4. Electrocardiographic criteria for left ventricular hypertrophy in children.

    NARCIS (Netherlands)

    Rijnbeek, P.R.; Herpen, G van; Kapusta, L.; Harkel, AD Ten; Witsenburg, M.; Kors, J.A.

    2008-01-01

    Previous studies to determine the sensitivity of the electrocardiogram (ECG) for left ventricular hypertrophy (LVH) in children had their imperfections: they were not done on an unselected hospital population, several criteria used in adults were not applied to children, and obsolete limits of norma

  5. Stimulation of isolated ventricular myocytes within an open architecture microarray.

    Science.gov (United States)

    Klauke, Norbert; Smith, Godfrey L; Cooper, Jonathan M

    2005-03-01

    This paper is concerned with the physiological responses of single heart cells within microfluidic chambers, in response to stimulation by integrated microelectrodes. To enable these investigations, which included the measurement of action potential duration, intracellular Ca2+ and cell shortening, a series of microfluidic chambers (50 microm wide, 180 microm long, 400 microm high, 500 microm pitch) and connecting channels (200 microm wide, 5000 microm long, 50 microm high, 500 microm pitch) were replica-moulded into the silicone elastomer, polydimethylsiloxane (PDMS). The structures were formed against a master of posts and lines, photolithograhically patterned into the high aspect ratio photoresist SU-8. The chambers within the slab of PDMS were aligned against pairs of stimulating gold microelectrodes (50 microm long, 20 microm wide, 0.1-10 microm thick, 180 microm apart) patterned on a microscope coverslip base, thus defining cavities of approximately 4 nL volume. The assembly was filled with physiological saline and single isolated rabbit ventricular myocytes were introduced by micropipetting, thus creating limited volumes of saline above individual myocytes that could be varied between 4 nL and > or = 4 microL. The application of transient current pulses to the cells via the electrodes caused transient contractions with constant amplitude (recorded as changes in sarcomere length), confirming that excitation contraction coupling (EC coupling) remained functional in these limited volumes. Continuous monitoring of the intracellular Ca2+ (using calcium sensitive dyes) showed, that in the absence of bath perfusion, the amplitude of the transients remained constant for approximately 3 min in the 4-nL volume and approximately 20 min for the 4 microL volume. Beyond this time, the cells became unexcitable until the bath was renewed. The action potential duration (APD) was recorded at stimulation frequencies of 1 Hz and 0.5 Hz using potential sensitive dyes and was

  6. Left Ventricular Hypertrophy: Major Risk Factor in Patients with Hypertension: Update and Practical Clinical Applications

    Directory of Open Access Journals (Sweden)

    Richard E. Katholi

    2011-01-01

    Full Text Available Left ventricular hypertrophy is a maladaptive response to chronic pressure overload and an important risk factor for atrial fibrillation, diastolic heart failure, systolic heart failure, and sudden death in patients with hypertension. Since not all patients with hypertension develop left ventricular hypertrophy, there are clinical findings that should be kept in mind that may alert the physician to the presence of left ventricular hypertrophy so a more definitive evaluation can be performed using an echocardiogram or cardiovascular magnetic resonance. Controlling arterial pressure, sodium restriction, and weight loss independently facilitate the regression of left ventricular hypertrophy. Choice of antihypertensive agents may be important when treating a patient with hypertensive left ventricular hypertrophy. Angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers followed by calcium channel antagonists most rapidly facilitate the regression of left ventricular hypertrophy. With the regression of left ventricular hypertrophy, diastolic function and coronary flow reserve usually improve, and cardiovascular risk decreases.

  7. Modeling CICR in rat ventricular myocytes: voltage clamp studies

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    Palade Philip T

    2010-11-01

    Full Text Available Abstract Background The past thirty-five years have seen an intense search for the molecular mechanisms underlying calcium-induced calcium-release (CICR in cardiac myocytes, with voltage clamp (VC studies being the leading tool employed. Several VC protocols including lowering of extracellular calcium to affect Ca2+ loading of the sarcoplasmic reticulum (SR, and administration of blockers caffeine and thapsigargin have been utilized to probe the phenomena surrounding SR Ca2+ release. Here, we develop a deterministic mathematical model of a rat ventricular myocyte under VC conditions, to better understand mechanisms underlying the response of an isolated cell to calcium perturbation. Motivation for the study was to pinpoint key control variables influencing CICR and examine the role of CICR in the context of a physiological control system regulating cytosolic Ca2+ concentration ([Ca2+]myo. Methods The cell model consists of an electrical-equivalent model for the cell membrane and a fluid-compartment model describing the flux of ionic species between the extracellular and several intracellular compartments (cell cytosol, SR and the dyadic coupling unit (DCU, in which resides the mechanistic basis of CICR. The DCU is described as a controller-actuator mechanism, internally stabilized by negative feedback control of the unit's two diametrically-opposed Ca2+ channels (trigger-channel and release-channel. It releases Ca2+ flux into the cyto-plasm and is in turn enclosed within a negative feedback loop involving the SERCA pump, regulating[Ca2+]myo. Results Our model reproduces measured VC data published by several laboratories, and generates graded Ca2+ release at high Ca2+ gain in a homeostatically-controlled environment where [Ca2+]myo is precisely regulated. We elucidate the importance of the DCU elements in this process, particularly the role of the ryanodine receptor in controlling SR Ca2+ release, its activation by trigger Ca2+, and its

  8. Raloxifene acutely suppresses ventricular myocyte contractility through inhibition of the L-type calcium current

    OpenAIRE

    Liew, Reginald; Stagg, Mark A; MacLeod, Kenneth T; Collins, Peter

    2004-01-01

    The selective oestrogen (ER) receptor modulator, raloxifene, is widely used in the treatment of postmenopausal osteoporosis, but may also possess cardioprotective properties. We investigated whether it directly suppresses myocyte contractility through Ca2+ channel antagonism in a similar way to 17β-oestradiol.Cell shortening and Ca2+ transients were measured in single guinea-pig ventricular myocytes field-stimulated (1 Hz, 37°C) in a superfusion chamber. Electrophysiological recordings were p...

  9. Left Ventricular Hypertrophy: Major Risk Factor in Patients with Hypertension: Update and Practical Clinical Applications

    OpenAIRE

    Katholi, Richard E.; Couri, Daniel M.

    2011-01-01

    Left ventricular hypertrophy is a maladaptive response to chronic pressure overload and an important risk factor for atrial fibrillation, diastolic heart failure, systolic heart failure, and sudden death in patients with hypertension. Since not all patients with hypertension develop left ventricular hypertrophy, there are clinical findings that should be kept in mind that may alert the physician to the presence of left ventricular hypertrophy so a more definitive evaluation can be performed u...

  10. Continual electric field stimulation preserves contractile function of adult ventricular myocytes in primary culture.

    Science.gov (United States)

    Berger, H J; Prasad, S K; Davidoff, A J; Pimental, D; Ellingsen, O; Marsh, J D; Smith, T W; Kelly, R A

    1994-01-01

    To model with greater fidelity the electromechanical function of freshly isolated heart muscle cells in primary culture, we describe a technique for the continual electrical stimulation of adult myocytes at physiological frequencies for several days. A reusable plastic cover was constructed to fit standard, disposable 175-cm2 tissue culture flasks and to hold parallel graphite electrodes along the long axis of each flask, which treated a uniform electric field that resulted in a capture efficiency of ventricular myocytes of 75-80%. Computer-controlled amplifiers were designed to be capable of driving a number of flasks concurrently, each containing up to 4 x 10(6) myocytes, over a range of stimulation frequencies (from 0.1 to 7.0 Hz) with reversal of electrode polarity after each stimulus to prevent the development of pH gradients around each electrode. Unlike quiescent, unstimulated myocytes, the amplitude of contraction, and velocities of shortening and relaxation did not change in myocytes paced at 3-5 Hz for up to 72 h. The maintenance of normal contractile function in paced myocytes required mechanical contraction per se, since paced myocytes that remained quiescent due to the inclusion of 2.5 microM verapamil in the culture medium for 48 h also exhibited a decline in contractility when paced after verapamil removal. Similarly, pacing increased peak calcium current compared with quiescent cells that had not been paced. Thus myocyte contraction at physiological frequencies induced by continual uniform electric field stimulation in short-term primary culture in defining medium maintains some biophysical parameters of myocyte phenotype that are similar to those observed in freshly isolated adult ventricular myocytes.

  11. Study of transmembrane La3+ movement in rat ventricular myocytes by the patch-clamp technique

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    We have studied transmembrane La3+ movement in rat ventricular myocytes for the first time by using the whole-cell patch-clamp recording mode. La3+ (0.01-5.0 mmol/L) could not bring out inward currents through the L-type calcium channel in rat ventricular myocytes, while it could enter the cells by the same way carried by 1μmol/L ionomycin. When the outward Na+ concentration gradient is formed, La3+ can enter the cells via Na-Ca exchange, and the exchange currentsincrease with the increase of external La3+ concentrations. But compared with Na-Ca exchange currents in the same concentration, the former is only 14%-38% of the latter. The patch-clamp experiment indicates that La3+ normally can not enter ventricular myocytes through L-type calcium channel, but it can enter the cells via Na-Ca exchange.

  12. Docosahexaenoic acid has influence on action potentials and transient outward potassium currents of ventricular myocytes

    Directory of Open Access Journals (Sweden)

    Yang Zhen-Yu

    2010-04-01

    Full Text Available Abstract Background There are many reports about the anti-arrhythmic effects of ω-3 polyunsaturated fatty acids, however, the mechanisms are still not completely delineated. The purpose of this study was to investigate the characteristics of action potentials and transient outward potassium currents (Ito of Sprague-Dawley rat ventricular myocytes and the effects of docosahexaenoic acid (DHA on action potentials and Ito. Methods The calcium-tolerant rat ventricular myocytes were isolated by enzyme digestion. Action potentials and Ito of epicardial, mid-cardial and endocardial ventricular myocytes were recorded by whole-cell patch clamp technique. Results 1. Action potential durations (APDs were prolonged from epicardial to endocardial ventricular myocytes (P 2. Ito current densities were decreased from epicardial to endocardial ventricular myocytes, which were 59.50 ± 15.99 pA/pF, 29.15 ± 5.53 pA/pF, and 12.29 ± 3.62 pA/pF, respectively at +70 mV test potential (P 3. APDs were gradually prolonged with the increase of DHA concentrations from 1 μmol/L to 100 μmol/L, however, APDs changes were not significant as DHA concentrations were in the range of 0 μmol/L to 1 μmol/L. 4. Ito currents were gradually reduced with the increase of DHA concentrations from 1 μmol/L to 100 μmol/L, and its half-inhibited concentration was 5.3 μmol/L. The results showed that there were regional differences in the distribution of action potentials and Ito in rat epicardial, mid-cardial and endocardial ventricular myocytes. APDs were prolonged and Ito current densities were gradually reduced with the increase of DHA concentrations. Conclusion The anti-arrhythmia mechanisms of DHA are complex, however, the effects of DHA on action potentials and Ito may be one of the important causes.

  13. Left Ventricular Hypertrophy in Rhesus Macaques (Macaca mulatta) at the California National Primate Research Center (1992-2014).

    Science.gov (United States)

    Reader, J Rachel; Canfield, Don R; Lane, Jennifer F; Kanthaswamy, Sreetharan; Ardeshir, Amir; Allen, A Mark; Tarara, Ross P

    2016-04-01

    Necropsy records and associated clinical histories from the rhesus macaque colony at the California National Primate Research Center were reviewed to identify mortality related to cardiac abnormalities involving left ventricular hypertrophy (LVH). Over a 21-y period, 162 cases (female, 90; male, 72) of idiopathic LVH were identified. Macaques presented to necropsy with prominent concentric hypertrophy of the left ventricle associated with striking reduction of the ventricular lumen. Among all LVH cases, 74 macaques (female, 39; male, 35), mostly young adults, presented for spontaneous (sudden) death; more than 50% of these 74 cases were associated with a recent history of sedation or intraspecific aggression. The risk of sudden death in the 6- to 9-y-old age group was significantly higher in male macaques. Subtle histologic cardiac lesions included karyomegaly and increased cardiac myocyte diameter. Pedigree analyses based on rhesus macaque LVH probands suggested a strong genetic predisposition for the condition. In humans, hypertrophic cardiomyopathy (HCM) is defined by the presence of unexplained left ventricular hypertrophy, associated with diverse clinical outcomes ranging from asymptomatic disease to sudden death. Although the overall risk of disease complications such as sudden death, end-stage heart failure, and stroke is low (1% to 2%) in patients with HCM, the absolute risk can vary dramatically. Prima facie comparison of HCM and LVH suggest that further study may allow the development of spontaneously occurring LVH in rhesus macaques as a useful model of HCM, to better understand the pathogenesis of this remarkably heterogeneous disease.

  14. Left Ventricular Hypertrophy in Rhesus Macaques (Macaca mulatta) at the California National Primate Research Center (1992–2014)

    Science.gov (United States)

    Reader, J Rachel; Canfield, Don R; Lane, Jennifer F; Kanthaswamy, Sreetharan; Ardeshir, Amir; Allen, A Mark; Tarara, Ross P

    2016-01-01

    Necropsy records and associated clinical histories from the rhesus macaque colony at the California National Primate Research Center were reviewed to identify mortality related to cardiac abnormalities involving left ventricular hypertrophy (LVH). Over a 21-y period, 162 cases (female, 90; male, 72) of idiopathic LVH were identified. Macaques presented to necropsy with prominent concentric hypertrophy of the left ventricle associated with striking reduction of the ventricular lumen. Among all LVH cases, 74 macaques (female, 39; male, 35), mostly young adults, presented for spontaneous (sudden) death; more than 50% of these 74 cases were associated with a recent history of sedation or intraspecific aggression. The risk of sudden death in the 6- to 9-y-old age group was significantly higher in male macaques. Subtle histologic cardiac lesions included karyomegaly and increased cardiac myocyte diameter. Pedigree analyses based on rhesus macaque LVH probands suggested a strong genetic predisposition for the condition. In humans, hypertrophic cardiomyopathy (HCM) is defined by the presence of unexplained left ventricular hypertrophy, associated with diverse clinical outcomes ranging from asymptomatic disease to sudden death. Although the overall risk of disease complications such as sudden death, end-stage heart failure, and stroke is low (1% to 2%) in patients with HCM, the absolute risk can vary dramatically. Prima facie comparison of HCM and LVH suggest that further study may allow the development of spontaneously occurring LVH in rhesus macaques as a useful model of HCM, to better understand the pathogenesis of this remarkably heterogeneous disease. PMID:27053572

  15. IGF-1 induces skeletal myocyte hypertrophy through calcineurin in association with GATA-2 and NF-ATc1

    Science.gov (United States)

    Musaro, A.; McCullagh, K. J.; Naya, F. J.; Olson, E. N.; Rosenthal, N.

    1999-01-01

    Localized synthesis of insulin-like growth factors (IGFs) has been broadly implicated in skeletal muscle growth, hypertrophy and regeneration. Virally delivered IGF-1 genes induce local skeletal muscle hypertrophy and attenuate age-related skeletal muscle atrophy, restoring and improving muscle mass and strength in mice. Here we show that the molecular pathways underlying the hypertrophic action of IGF-1 in skeletal muscle are similar to those responsible for cardiac hypertrophy. Transfected IGF-1 gene expression in postmitotic skeletal myocytes activates calcineurin-mediated calcium signalling by inducing calcineurin transcripts and nuclear localization of calcineurin protein. Expression of activated calcineurin mimics the effects of IGF-1, whereas expression of a dominant-negative calcineurin mutant or addition of cyclosporin, a calcineurin inhibitor, represses myocyte differentiation and hypertrophy. Either IGF-1 or activated calcineurin induces expression of the transcription factor GATA-2, which accumulates in a subset of myocyte nuclei, where it associates with calcineurin and a specific dephosphorylated isoform of the transcription factor NF-ATc1. Thus, IGF-1 induces calcineurin-mediated signalling and activation of GATA-2, a marker of skeletal muscle hypertrophy, which cooperates with selected NF-ATc isoforms to activate gene expression programs.

  16. Metabolites of MDMA induce oxidative stress and contractile dysfunction in adult rat left ventricular myocytes

    OpenAIRE

    Shenouda, Sylvia K.; Varner, Kurt J.; Carvalho, Felix; Lucchesi, Pamela A.

    2009-01-01

    Repeated administration of MDMA (ecstasy) produces eccentric left ventricular (LV) dilation and diastolic dysfunction. While the mechanism(s) underlying this toxicity are unknown; oxidative stress plays an important role. MDMA is metabolized into redox cycling metabolites that produce superoxide. In this study, we demonstrated that metabolites of MDMA induce oxidative stress and contractile dysfunction in adult rat left ventricular myocytes. Metabolites of MDMA used in this study included: al...

  17. 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 electrical...

  18. Direct differentiation of atrial and ventricular myocytes from human embryonic stem cells by alternating retinoid signals

    Institute of Scientific and Technical Information of China (English)

    Qiangzhe Zhang; Li Chen; Tian Tian; Xin Wang; Pu Li; Jurgen Hescheler; Guangju Ji; Yue Ma; Junjie Jiang; Pengcheng Han; Qi Yuan; Jing Zhang; Xiaoqian Zhang; Yanyan Xu; Henghua Cao; Qingzhang Meng

    2011-01-01

    Although myocyte cell transplantation studies have suggested a promising therapeutic potential for myocardial infarction, a major obstacle to the development of clinical therapies for myocardial repair is the difficulties associated with obtaining relatively homogeneous ventricular myocytes for transplantation. Human embryonic stem cells (hESCs)are a promising source of cardiomyocytes. Here we report that retinoid signaling regulates the fate specification of atrial versus ventricular myocytes during cardiac differentiation of hESCs. We found that both Noggin and the panretinoic acid receptor antagonist BMS-189453 (RAi) significantly increased the cardiac differentiation efficiency of hESCs. To investigate retinoid functions, we compared Noggin+RAi-treated cultures with Noggin+RA-treated cultures. Our results showed that the expression levels of the ventricular-specific gene IRX-4 were radically elevated in Noggin+RAi-treated cultures. MLC-2V, another ventricular-specific marker, was expressed in the majority of the cardiomyocytes in Noggin+RAi-treated cultures, hut not in the cardiomyocytes of Noggin+RA-treated cultures. Flow cytometry analysis and electrophysiologicai studies indicated that with 64.7 ± 0.88% (mean ± s.e.m) cardiac differentiation efficiency, 83% of the cardiomyocytes in Noggin+RAi-treated cultures had embryonic ventricular-like action potentials (APs). With 50.7 ± 1.76% cardiac differentiation efficiency, 94% of the cardiomyocytes in Noggin+RA-treated cultures had embryonic atrial-like APs. These results were further confirmed by imaging studies that assessed the patterns and properties of the Ca2+ sparks of the cardiomyocytes from the two cultures. These findings demonstrate that retinoid signaling specifies the atrial versus ventricular differentiation of hESCs. This study also shows that relatively homogeneous embryonic atrial- and ventricular-like myocyte populations can be efficiently derived from hESCs by specifically regulating Noggin

  19. Cardiac arrhythmias and left ventricular hypertrophy in systemic hypertension

    International Nuclear Information System (INIS)

    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)

  20. How reliable is the electrocardiogram in detecting left ventricular hypertrophy in hypertension?

    OpenAIRE

    Vijan, S. G.; Manning, G; Millar-Craig, M W

    1991-01-01

    This paper assesses the sensitivity and specificity of the electrocardiogram in detecting left ventricular hypertrophy in 75 hypertensive patients. Each patient underwent a 12 lead electrocardiogram and echocardiogram. Left ventricular mass index, using echocardiogram, was calculated according to the Penn convention and left ventricular hypertrophy was assessed by standard electrocardiographic criteria. The electrocardiogram was found to be very specific but insensitive in the detection of le...

  1. FAK-related nonkinase attenuates hypertrophy induced by angiotensin-Ⅱ in cultured neonatal rat cardiac myocytes

    Institute of Scientific and Technical Information of China (English)

    Jin QIN; Zheng-xiang LIU

    2006-01-01

    Aim: To examine the inhibitory effect of FAK-related nonkinase (FRNK) in cardiac hypertrophy in vitro and investigate the possible mechanisms. Methods: A functional fragment of FRNK cDNA was amplified by reverse transcription-polymerase chain reaction and cloned into the vector pcDNA3.1. Hypertrophy in neonatal rat cardiac myocytes was established with angiotensin-Ⅱ stimulation. The pcDNA3.1-FRNK or pcDNA3.1 was respectively transfected into cardiomyocytes by Lipofectamine 2000. The surface area and mRNA expression of atrial natriuretic peptide (ANP) of myocytes were employed to detect cardiac hypertrophy. NF-κB p65 protein in nuclear extracts, phosphorylation levels of ERK1/2 (p-ERK1/2) and AKT (p-AKT), as well as total ERK1/2, and AKT in variant treated cardiomyocytes were determined by Western blot. Results: Under the stimulation of angiotensin Ⅱ, the surface area of myocytes and levels of ANP mRNA were significantly increased. But transient transfection with pcDNA3.1-FRNK in advance may reduce the surface area and expression of ANP mRNA of hypertrophic myocytes. The protein levels of NF-κB p65 in nuclear extracts and p-ERK1/2, p-AKT in FRNK treated cardiomyocytes were significantly decreased compared with that in angiotensin-Ⅱ induced cardiomyocytes, while different treatments had little effect on total ERK1/2 and AKT. Conclusion: FRNK may inhibit angiotensin-Ⅱ-induced cardiomyocyte hypertrophy via decreasing phosphorylation levels at ERK1/2 and AKT, consequently downregulating nuclear translocation of NF-κB p65.

  2. PKC translocation and ERK1/2 activation in compensated right ventricular hypertrophy secondary to chronic emphysema.

    Directory of Open Access Journals (Sweden)

    Litwin Sheldon E

    2005-05-01

    Full Text Available Abstract Background Right ventricular hypertrophy (RVH is an important complication of chronic lung disease. However, the signal transduction pathways involved as well as the physiological changes to the right ventricle have not been investigated. Emphysema was produced in male, Syrian Golden hamsters by intra-tracheal instillation of 250 IU/kg elastase (Emp, n = 17. Saline treated animals served as controls (Con, n = 15. Results Nine months later, Emp hamsters had 75% greater lung volume, and evidence of RVH at the gross and myocyte level (RV:tibia length Emp 6.84 ± 1.18 vs. Con 5.14 ± 1.11 mg/mm; myocyte cross sectional area Emp 3737 vs. Con 2695 μm2, but not left ventricular hypertrophy. Serial echocardiographic analysis from baseline to nine months after induction of emphysema revealed increasing right ventricular internal dimension and decreased pulmonary artery acceleration time only in Emp hamsters. There was an increase in translocation of PKC βI and PKC ε from cytosolic to membranous cell fractions in RV of Emp hamsters. Phosphorylation of PKC ε was unchanged. Translocation of PKC α and βII were unchanged. Emp animals had a 22% increase in phospho-ERK 1/2, but no change in levels of total ERK 1/2 compared to Con. Conclusion These data suggest that PKC βI, ε and ERK 1/2 may play a role in mediating compensated RVH secondary to emphysema and may have clinical relevance in the pathogenesis of RVH.

  3. MEF2C silencing attenuates load-induced left ventricular hypertrophy by modulating mTOR/S6K pathway in mice.

    Directory of Open Access Journals (Sweden)

    Ana Helena M Pereira

    Full Text Available BACKGROUND: The activation of the members of the myocyte enhancer factor-2 family (MEF2A, B, C and D of transcription factors promotes cardiac hypertrophy and failure. However, the role of its individual components in the pathogenesis of cardiac hypertrophy remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we investigated whether MEF2C plays a role in mediating the left ventricular hypertrophy by pressure overload in mice. The knockdown of myocardial MEF2C induced by specific small interfering RNA (siRNA has been shown to attenuate hypertrophy, interstitial fibrosis and the rise of ANP levels in aortic banded mice. We detected that the depletion of MEF2C also results in lowered levels of both PGC-1alpha and mitochondrial DNA in the overloaded left ventricle, associated with enhanced AMP:ATP ratio. Additionally, MEF2C depletion was accompanied by defective activation of S6K in response to pressure overload. Treatment with the amino acid leucine stimulated S6K and suppressed the attenuation of left ventricular hypertrophy and fibrosis in the aforementioned aortic banded mice. CONCLUSION/SIGNIFICANCE: These findings represent new evidences that MEF2C depletion attenuates the hypertrophic responses to mechanical stress and highlight the potential of MEF2C to be a target for new therapies to cardiac hypertrophy and failure.

  4. Effect of osmotic stress on spontaneous calcium sparks in rat ventricular myocytes

    Institute of Scientific and Technical Information of China (English)

    Hong XIE; Pei-hong ZHU

    2006-01-01

    Aim: To study whether the volume of cardiomyocytes and their functions would change under severe pathological conditions or osmotic stress. To clarify the role of ryanodine receptors/calcium release channels (RyRs) in the functional change, the effect of osmotic stress on spontaneous Ca2+ sparks in rat ventricular myocytes was investigated. Methods: A laser scanning confocal microscope was used to detect spontaneous Ca2+ sparks of intact or saponin permeabilized myocytes loaded with Fluo-4. High and low tonicity was obtained by adding sucrose and reducing NaCl concentration in the external medium, respectively. Results: In intact myocytes the frequency of Ca2+ sparks was increased and decreased by hyperosmotic (1.5 T) and hyposmotic (0.6 T) exposure, respectively. In addition, hyperosmotic exposure increased the temporal parameters and decreased the spatial parameter of Ca2+ sparks, while opposite changes occurred with hyposmotic exposure. The spatio-temporal properties of Ca2+ sparks were slightly affected by altering [K+]i (50-200 mmol/L) in saponin permeabilized myocytes in the presence of 8% dextran. It was observed that the spatio-temporal parameters of the Ca2+ sparks in permeabilized myocytes were dose-dependently altered by dextran. The propagating velocity of Ca2+ waves in intact and permeabilized myocyte was also affected by osmotic pressure or dextran. Conclusion: The effect of osmotic stress on the frequency of spontaneous Ca2+ sparks might be ascribed to the change of myoplasmic Ca2+ and Ca2+ content in the sarcoplasmic reticulum, while the effect on the spatio-temporal properties is caused by the alteration of Ca2+ diffusion mainly resulting from the morphological change of the myocytes.

  5. Dynamics of the inward rectifier K+ current during the action potential of guinea pig ventricular myocytes.

    OpenAIRE

    Ibarra, J; Morley, G E; Delmar, M

    1991-01-01

    The potassium selective, inward rectifier current (IK1) is known to be responsible for maintaining the resting membrane potential of quiescent ventricular myocytes. However, the contribution of this current to the different phases of the cardiac action potential has not been adequately established. In the present study, we have used the action potential clamp (APC) technique to characterize the dynamic changes of a cesium-sensitive (i.e., Ik1) current which occur during the action potential. ...

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

    International Nuclear Information System (INIS)

    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/m2) 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

  7. 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...

  8. Functional analysis of Na+/K+-ATPase isoform distribution in rat ventricular myocytes.

    Science.gov (United States)

    Despa, Sanda; Bers, Donald M

    2007-07-01

    The Na(+)/K(+)-ATPase (NKA) is the main route for Na(+) extrusion from cardiac myocytes. Different NKA alpha-subunit isoforms are present in the heart. NKA-alpha1 is predominant, although there is a variable amount of NKA-alpha2 in adult ventricular myocytes of most species. It has been proposed that NKA-alpha2 is localized mainly in T-tubules (TT), where it could regulate local Na(+)/Ca(2+) exchange and thus cardiac myocyte Ca(2+). However, there is controversy as to where NKA-alpha1 vs. NKA-alpha2 are localized in ventricular myocytes. Here, we assess the TT vs. external sarcolemma (ESL) distribution functionally using formamide-induced detubulation of rat ventricular myocytes, NKA current (I(Pump)) measurements and the different ouabain sensitivity of NKA-alpha1 (low) and NKA-alpha2 (high) in rat heart. Ouabain-dependent I(Pump) inhibition in control myocytes indicates a high-affinity NKA isoform (NKA-alpha2, K(1/2) = 0.38 +/- 0.16 microM) that accounts for 29.5 +/- 1.3% of I(Pump) and a low-affinity isoform (NKA-alpha1, K(1/2) = 141 +/- 17 microM) that accounts for 70.5% of I(Pump). Detubulation decreased cell capacitance from 164 +/- 6 to 120 +/- 8 pF and reduced I(Pump) density from 1.24 +/- 0.05 to 1.02 +/- 0.05 pA/pF, indicating that the functional density of NKA is significantly higher in TT vs. ESL. In detubulated myocytes, NKA-alpha2 accounted for only 18.2 +/- 1.1% of I(Pump). Thus, approximately 63% of I(Pump) generated by NKA-alpha2 is from the TT (although TT are only 27% of the total sarcolemma), and the NKA-alpha2/NKA-alpha1 ratio in TT is significantly higher than in the ESL. The functional density of NKA-alpha2 is approximately 4.5 times higher in the T-tubules vs. ESL, whereas NKA-alpha1 is almost uniformly distributed between the TT and ESL. PMID:17392375

  9. Left Ventricular Hypertrophy Evaluation in Obese Hypertensive Patients: Effect of Left Ventricular Mass Index Criteria

    Directory of Open Access Journals (Sweden)

    Eduardo Cantoni Rosa

    2002-04-01

    Full Text Available PURPOSE: To evaluate left ventricular mass (LVM index in hypertensive and normotensive obese individuals. METHODS: Using M mode echocardiography, 544 essential hypertensive and 106 normotensive patients were evaluated, and LVM was indexed for body surface area (LVM/BSA and for height² (LVM/h². The 2 indexes were then compared in both populations, in subgroups stratified according to body mass index (BMI: or = 30kg/m². RESULTS: The BSA index does not allow identification of significant differences between BMI subgroups. Indexing by height² provides significantly increased values for high BMI subgroups in normotensive and hypertensive populations. CONCLUSION: Left ventricular hypertrophy (LVH has been underestimated in the obese with the use of LVM/BSA because this index considers obesity as a physiological variable. Indexing by height² allows differences between BMI subgroups to become apparent and seems to be more appropriate for detecting LVH in obese populations.

  10. Haemochromatosis genotype and iron overload: association with hypertension and left ventricular hypertrophy

    DEFF Research Database (Denmark)

    Ellervik, C; Tybjaerg-Hansen, A; Appleyard, M;

    2010-01-01

    We hypothesized that there is an association between haemochromatosis genotype C282Y/C282Y and/or iron overload and risk of hypertension and/or left ventricular hypertrophy (LVH).......We hypothesized that there is an association between haemochromatosis genotype C282Y/C282Y and/or iron overload and risk of hypertension and/or left ventricular hypertrophy (LVH)....

  11. Effects of Glucose on Transmembrane Ionic Current of Ventricular Myocytes in Guinea Pig

    Institute of Scientific and Technical Information of China (English)

    AIJing; JIAOJun-dong; WANGHe; DUZhi-min; YANGBao-feng

    2004-01-01

    Aim To determine the effects of glucose oi1APD, IK1, IK, ICa-L of ventricular myocytes in guinea pigs. Methods Whole-cell patch-clamp technique was used to record the changed action potential ionic current induced by glucose of single cell in guinea pig ventricular myocytes, to compare the action of 0, 10 and 20 mmol·L-1 glucoses on transmembrane ionic current. Results (1) Compared with 10 mmol·L-1 glucose concentrations, 0 and 20 mmol·L-1 glucose both shortened APD of ventricular myocytes (P<0.05). (2) The inward components of IK1 density were maximal when the glucose concentration was at 10 mmol·L-1. Normalized 1-V relationships showed that both 0 and 20 mmol·L-1 glucose produced a left-shift of I-V curve. The reverse potential changed from-72.4 mV to-64.6 mV. (3) Compared with 10 mmol·L-1, both 0 and 20 mmol·L-1 glucose markedly increased the ICa-L amplitude and density. The ICa-L current density was (-8.0350.82) pA/pF (n=8) at a test potential of 10 mV when the glucose concentration was 10 mmol·L-1. But its current density decreased to (-5.45±0.67) pA/pF and (-6.50±0.56) pA/pF when glucose concentrations were 0 and 20 mmol·L-1, respectively. (4) The current densities of IK were (18.96±2.86) pA/pF, (8.66±1.87) pA/pF, and(15.32:1:3.12) pA/pF, at ±70mV for 0, 10 and 20 mmol·L-1 glucoses, respectively. Conclusion Glucose in different concentrations has different effects on APD, IK1, IK, and ICa-L of single ventricular myocyte in guinea pigs. There are similar actions of 0 and 20 mmol·L-1 glucoses on the transmembrane ionic current of ventricular myocytes in guinea pigs.

  12. Left ventricular systolic response to exercise in patients with systemic hypertension without left ventricular hypertrophy.

    Science.gov (United States)

    Christian, T F; Zinsmeister, A R; Miller, T D; Clements, I P; Gibbons, R J

    1990-05-15

    Supine exercise radionuclide angiography was performed in 367 men to assess left ventricular (LV) systolic response to exercise; 58 had systemic hypertension without LV hypertrophy on a resting electrocardiogram and 309 were normotensive. All patients met the following criteria defining a low pretest likelihood of coronary artery disease: age less than 50 years; normal electrocardiographic response to exercise; absence of typical or atypical chest pain; and exercise heart rate greater than 120 beats/min. Patients taking beta-receptor blockers were excluded. There were no significant differences between hypertensive and normotensive groups in peak exercise heart rate, workload or exercise duration. However, hypertensive patients had significantly higher peak exercise systolic blood pressures and peak exercise rate-pressure products. There were no differences between patients with and without hypertension in resting ejection fraction, peak exercise ejection fraction (hypertensive patients 0.71 +/- 0.01, normotensive patients 0.70 +/- 0.05) or change in ejection fraction at peak exercise (hypertensive patients 0.07 +/- 0.01, normotensive patients 0.07 +/- 0.04). Diastolic and systolic ventricular volumes tended to be smaller in the hypertensive patients, but the difference was not statistically significant. The change in systolic volume with exercise was similar in the 2 groups (hypertensive -10 +/- 3 ml/m2, normotensive -10 +/- 1 ml/m2). In the absence of electrocardiographic evidence of LV hypertrophy, systemic hypertension does not influence LV systolic response to exercise. PMID:2140008

  13. 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. 

  14. 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.

  15. Laminar structure of the heart: ventricular myocyte arrangement and connective tissue architecture in the dog.

    Science.gov (United States)

    LeGrice, I J; Smaill, B H; Chai, L Z; Edgar, S G; Gavin, J B; Hunter, P J

    1995-08-01

    We have studied the three-dimensional arrangement of ventricular muscle cells and the associated extracellular connective tissue matrix in dog hearts. Four hearts were potassium-arrested, excised, and perfusion-fixed at zero transmural pressure. Full-thickness segments were cut from the right and left ventricular walls at a series of precisely located sites. Morphology was visualized macroscopically and with scanning electron microscopy in 1) transmural planes of section and 2) planes tangential to the epicardial surface. The appearance of all specimens was consistent with an ordered laminar arrangement of myocytes with extensive cleavage planes between muscle layers. These planes ran radially from endocardium toward epicardium in transmural section and coincided with the local muscle fiber orientation in tangential section. Stereological techniques were used to quantify aspects of this organization. There was no consistent variation in the cellular organization of muscle layers (48.4 +/- 20.4 microns thick and 4 +/- 2 myocytes across) transmurally or in different ventricular regions (23 sites in 6 segments), but there was significant transmural variation in the coupling between adjacent layers. The number of branches between layers decreased twofold from subepicardium to midwall, whereas the length distribution of perimysial collagen fibers connecting muscle layers was greatest in the midwall. We conclude that ventricular myocardium is not a uniformly branching continuum but a laminar hierarchy in which it is possible to identify three axes of material symmetry at any point.

  16. The Effect and Mechanism of Forsinopril on Ventricular Hypertrophy of SHR and Left Ventricular Pressure overloading Rat

    Institute of Scientific and Technical Information of China (English)

    黄恺; 戴闺柱

    2002-01-01

    The effects and mechanism of long-term angiotensin converting enzyme inhibitor (ACEI)Forsinopril on left ventricular hypertrophy of spontaneous hypertension rat (SHR) and left ventricular pressure overloading rat were studied. The left ventricular index (left ventricle weight/body weight) was used to evaluate left ventricular hypertrophy and the in situ hybridization to investigate the TGF-β1 gene expression in left ventricle. The results showed that Forsinopril significantly decreased the left ventricular index of both SHR and left ventricle pressure overloading rat. Forsinopril reduced the integral photic density of TGF-β1 gene statement from 2. 836± 0. 314 to 1.91 ± 0. 217(P<0.01, n=8 ) of SHR rat and from 3. 071±0. 456 to 2. 37640. 379 (P<0.01, n=8) of left ventricular pressure overloading rat respectively. It was concluded that Forsinopril could prevent the occurrence of left ventricular hypertrophy and reduce the TGF-β1 gene expression in left ventricle of both SHR and left ventricular pressure overloading rat significantly.

  17. Gene Product Expression of Cyclin D2 and p16 During the Transition from Cardiac Myocyte Hyperplasia to Hypertrophy

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The current study was to investigate mRNA expression of cyclin D2 and p16 during the transition from cardiac myocyte hyperplasia to hypertrophy. Cultured cardiac myocytes (CM) and fibroblasts (FC) obtained from 1-day-old Sparague-Dawley rats were used in this study. We have determined (1) hyperplasia by cell growth curve and fluorescence activated cell sorting (FACS); and (2) ultrastructure by electron microscope observation; and (3) expressions of cyclin D2 mRNA and p16 mRNA by using in situ hybridization and image analysis. The results were shown (1) Results of cell growth curve and FACS analysis showed CM could proliferate in the first 3 cultured days (4 days in postnatal development). But the ability decreased quickly, concomitant with the differentiation. (2) The ultrastructure of CM showed the large amount of myofilaments and mitochondrion and FC showed moderate amount of rough endoplasmic reticulum. (3) The expression of cyclin D2 mRNA in 3-, 4-, 5-day CM group was 0.89 times(p<0.05), 0.80 times (p<0.05)and 0.56 times (p<0.01)of that in 1-day group respectively. P16 mRNA in 2-, 3-, 4-, 5-day CM group were 1.63 times(p<0.01),1.72 times(p<0.01),1.99 times (p<0.01)and 2.84 times (p<0.01) of that in 1-day group respectively. It can be concluded that cultured neonatal rat cardiac myocytes could proliferate during the first 3 cultured days, but the ability of proliferation decreased, from the fourth day, concomitant with differentiation. Cyclin D2 and p16 have the key roles during the transition from myocyte hyperplasia to hypertrophy.

  18. Determinants of Left Ventricular Mass and Hypertrophy in Hemodialysis Patients Assessed by Cardiac Magnetic Resonance Imaging

    OpenAIRE

    Patel, Rajan K.; Oliver, Scott; Patrick B. Mark; Powell, Joanna R.; McQuarrie, Emily P.; Traynor, James P.; Dargie, Henry J; Jardine, Alan G

    2009-01-01

    Background and objectives: Left ventricular hypertrophy (LVH) is an independent risk factor for premature cardiovascular death in hemodialysis (HD) patients and one of the three forms of uremic cardiomyopathy. Cardiovascular magnetic resonance (CMR) is a volume-independent technique to assess cardiac structure. We used CMR to assess the determinants of left ventricular mass (LVM) and LVH in HD patients.

  19. Prognostic significance of left ventricular diastolic dysfunction in patients with left ventricular hypertrophy and systemic hypertension (the LIFE Study)

    DEFF Research Database (Denmark)

    Wachtell, Kristian; Palmieri, Vittorio; Gerdts, Eva;

    2010-01-01

    Patients with hypertension and left ventricular (LV) hypertrophy commonly have impaired diastolic filling. However, it remains unknown whether changes in LV diastolic filling variables are associated with cardiovascular morbidity and mortality. In this study, 778 patients with hypertension with...... account. In conclusion, antihypertensive treatment in patients with hypertension with electrocardiographic LV hypertrophy resulted in significant improvement in transmitral flow patterns; this was not associated with reduced cardiovascular morbidity and mortality. However, normal in-treatment LV filling...

  20. 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.

  1. 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.

  2. Cardiac Biomarkers and Left Ventricular Hypertrophy in Asymptomatic Hemodialysis Patients

    Directory of Open Access Journals (Sweden)

    Reneta Yovcheva Koycheva

    2015-12-01

    Full Text Available BACKGROUND: Cardiac biomarkers are often elevated in dialysis patients showing the presence of left ventricular dysfunction. The aim of the study is to establish the plasma levels of high-sensitivity cardiac troponin T (hs TnT, precursor of B-natriuretic peptide (NT-proBNP and high sensitivity C-reactive protein (hs CRP and their relation to the presence of left ventricular hypertrophy (LVH in patients undergoing hemodialysis without signs of acute coronary syndrome or heart failure. MATERIAL AND METHODS: Were studied 48 patients - 26 men and 22 women. Pre and postdialysis levels of hs cTnT, NT-proBNP and hs CRP were measured at week interim procedure. Patients were divided in two groups according to the presence of echocardiographic evidence of LVH - gr A - 40 patients (with LVH, and gr B - 8 patients (without LVH. RESULTS: In the whole group of patients was found elevated predialysis levels of all three biomarkers with significant increase (p < 0.05 after dialysis with low-flux dialyzers. Predialysis values of NT-proBNP show moderate positive correlation with hs cTnT (r = 0.47 and weaker with hs CRP (r = 0.163. Such dependence is observed in postdialysis values of these biomarkers. There is a strong positive correlation between the pre and postdialysis levels: for hs cTnT (r = 0.966, for NT-proBNP (r = 0.918 and for hs CRP (r = 0.859. It was found a significant difference in the mean values of hs cTnT in gr. A and gr. B (0.07 ± 0.01 versus 0.03 ± 0.01 ng /mL, p < 0.05 and NT-proBNP (15,605.8 ± 2,072.5 versus 2,745.5 ± 533.55 pg /mL, p < 0.05. Not find a significant difference in hs CRP in both groups. CONCLUSIONS: The results indicate the relationship of the studied cardiac biomarkers with LVH in asymptomatic patients undergoing hemodialysis treatment.

  3. STIM1 enhances SR Ca2+ content through binding phospholamban in rat ventricular myocytes.

    Science.gov (United States)

    Zhao, Guiling; Li, Tianyu; Brochet, Didier X P; Rosenberg, Paul B; Lederer, W J

    2015-08-25

    In ventricular myocytes, the physiological function of stromal interaction molecule 1 (STIM1), an endo/sarcoplasmic reticulum (ER/SR) Ca(2+) sensor, is unclear with respect to its cellular localization, its Ca(2+)-dependent mobilization, and its action on Ca(2+) signaling. Confocal microscopy was used to measure Ca(2+) signaling and to track the cellular movement of STIM1 with mCherry and immunofluorescence in freshly isolated adult rat ventricular myocytes and those in short-term primary culture. We found that endogenous STIM1 was expressed at low but measureable levels along the Z-disk, in a pattern of puncta and linear segments consistent with the STIM1 localizing to the junctional SR (jSR). Depleting SR Ca(2+) using thapsigargin (2-10 µM) changed neither the STIM1 distribution pattern nor its mobilization rate, evaluated by diffusion coefficient measurements using fluorescence recovery after photobleaching. Two-dimensional blue native polyacrylamide gel electrophoresis and coimmunoprecipitation showed that STIM1 in the heart exists mainly as a large protein complex, possibly a multimer, which is not altered by SR Ca(2+) depletion. Additionally, we found no store-operated Ca(2+) entry in control or STIM1 overexpressing ventricular myocytes. Nevertheless, STIM1 overexpressing cells show increased SR Ca(2+) content and increased SR Ca(2+) leak. These changes in Ca(2+) signaling in the SR appear to be due to STIM1 binding to phospholamban and thereby indirectly activating SERCA2a (Sarco/endoplasmic reticulum Ca(2+) ATPase). We conclude that STIM1 binding to phospholamban contributes to the regulation of SERCA2a activity in the steady state and rate of SR Ca(2+) leak and that these actions are independent of store-operated Ca(2+) entry, a process that is absent in normal heart cells. PMID:26261328

  4. Ca2+ paradox injury mediated through TRPC channels in mouse ventricular myocytes.

    Science.gov (United States)

    Kojima, Akiko; Kitagawa, Hirotoshi; Omatsu-Kanbe, Mariko; Matsuura, Hiroshi; Nosaka, Shuichi

    2010-12-01

    BACKGROUND AND PURPOSE The Ca(2+) paradox is an important phenomenon associated with Ca(2+) overload-mediated cellular injury in myocardium. The present study was undertaken to elucidate molecular and cellular mechanisms for the development of the Ca(2+) paradox. EXPERIMENTAL APPROACH Fluorescence imaging was performed on fluo-3 loaded quiescent mouse ventricular myocytes using confocal laser scanning microscope. KEY RESULTS The Ca(2+) paradox was readily evoked by restoration of the extracellular Ca(2+) following 10-20 min of nominally Ca(2+)-free superfusion. The Ca(2+) paradox was significantly reduced by blockers of transient receptor potential canonical (TRPC) channels (2-aminoethoxydiphenyl borate, Gd(3+), La(3+)) and anti-TRPC1 antibody. The sarcoplasmic reticulum (SR) Ca(2+) content, assessed by caffeine application, gradually declined during Ca(2+)-free superfusion, which was further accelerated by metabolic inhibition. Block of SR Ca(2+) leak by tetracaine prevented Ca(2+) paradox. The Na(+) /Ca(2+) exchange (NCX) blocker KB-R7943 significantly inhibited Ca(2+) paradox when applied throughout superfusion period, but had little effect when added for a period of 3 min before and during Ca(2+) restoration. The SR Ca(2+) content was better preserved during Ca(2+) depletion by KB-R7943. Immunocytochemistry confirmed the expression of TRPC1, in addition to TRPC3 and TRPC4, in mouse ventricular myocytes. CONCLUSIONS AND IMPLICATIONS These results provide evidence that (i) the Ca(2+) paradox is primarily mediated by Ca(2+) entry through TRPC (probably TRPC1) channels that are presumably activated by SR Ca(2+) depletion; and (ii) reverse mode NCX contributes little to the Ca(2+) paradox, whereas inhibition of NCX during Ca(2+) depletion improves SR Ca(2+) loading, and is associated with reduced incidence of Ca(2+) paradox in mouse ventricular myocytes.

  5. p42/p44 mitogen-activated protein kinases inhibit atrial natriuretic peptide mRNA transcription in gp130-mediated hypertrophic ventricular myocytes

    Institute of Scientific and Technical Information of China (English)

    Zhan-Ling Dong; Yang Wang; Tian-Fa Li; Shao-Jiang Zheng; Yue-Qiong Kong; You-Ling Lan; Jun-Li Guo; Shi-Gan Fu

    2014-01-01

    Objective:To understand the role ofANP mRNA transcription regulation in gp130-mediated cardiomyocyte hypertrophy, and the involved mitogen-activated protein kinase kinase(MEK)-extracellular signal-regulated kinase(ERK, also called p42/p44MAPK) signaling pathway. Methods:Isolated neonatal ventricular myocytes were treated with different concentrations of CT-1(10-9,10-8 and10-7 mol/L).MTT was used to analyze the viability andRT-PCR was used to detectANP mRNA levels in cardiomyocyte.To inhibit p42/p44MAPK activity in hypertrophic cardiomyocytes, the cells were pretreated with a specificMEK1 inhibitor.Results:CT-1 significantly inducedANP mRNA expression and the viability of cardiomyocytes in a dose- and time-dependent manner.Furthermore, blocking p42/p44MAPK activity by the special MEK1 inhibitor upregulated theANP mRNA.Conclusions: p42/p44MAPK have an important role in suppressingANP mRNA transcription and cell activity in gp130-mediated hypertrophic ventricular myocytes.

  6. Purinergic facilitation of ATP-sensitive potassium current in rat ventricular myocytes

    OpenAIRE

    Babenko, Andrey P.; Vassort, Guy

    1997-01-01

    The effects of different purinergic agonists on the cardiac adenosine 5′-triphosphate (ATP)-sensitive potassium current (IK(ATP)), appearing during dialysis of rat isolated ventricular myocytes with a low-ATP (100 μM) internal solution under whole-cell patch-clamp conditions, were examined in the presence of a P1 purinoceptor antagonist.The extracellular application of ATP in the micromolar range induced, besides known inward currents through cationic and chloride channels, the facilitation o...

  7. Effects of oleic acid on the high threshold barium current in seabass Dicentrarchus labrax ventricular myocytes

    OpenAIRE

    Chatelier, Aurelien; Imbert, Nathalie; Zambonino, Jose-luis; McKenzie, David; Bois, P.

    2006-01-01

    The present study employed a patch clamp technique in isolated seabass ventricular myocytes to investigate the hypothesis that oleic acid (OA), a mono-unsaturated fatty acid, can exert direct effects upon whole-cell barium currents. Acute application of free OA caused a dose-dependent depression of the whole-cell barium current that was evoked by a voltage step to 0 mV from a holding potential of -80 mV. The derived 50% inhibitory concentration (IC50) was 12.49 +/- 0.27 mu mol l(-1). At a con...

  8. The Role of Obesity in the Development of Left Ventricular Hypertrophy Among Children and Adolescents.

    Science.gov (United States)

    Brady, Tammy M

    2016-01-01

    Both obesity and hypertension have increased substantially among children over the last several decades. At the same time, mounting evidence has pointed to the role of these and other cardiovascular disease risk factors on the development of end organ damage such as left ventricular hypertrophy in children. While traditionally thought to occur in response to an increased afterload as in systemic hypertension, evidence demonstrates that obesity is associated with left ventricular hypertrophy independent of blood pressure. Both hemodynamic and non-hemodynamic factors contribute to the pathogenesis of obesity-related left ventricular remodeling. However, more contemporary research suggests that adiposity and blood pressure have a greater effect on left ventricular geometry when present together than when present alone. Normalization of left ventricular mass in obese hypertensive individuals requires achievement of both normotension and weight loss. Additional strategies are needed to promote the cardiovascular health of children, with greater emphasis placed on obesity prevention.

  9. 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......, transmitral peak E velocities and peak A velocities; and lower E/A ratio (all P hypertensive patients with greater left ventricular mass and prevalence of left ventricular hypertrophy, but normal left ventricular chamber systolic function with increased...

  10. Contribution of NHE-1 to cell length cardiac shortening of normal and failing rabbit myocytes

    NARCIS (Netherlands)

    M.M.G.J. van Borren; J.G. Zegers; A. Baartscheer; J.H. Ravesloot

    2006-01-01

    At the same intracellular pH (pH(i)) Na+/H+ exchange (NHE-1) fluxes of ventricular myocytes of hypertrophied failing hearts (HFH) are increased. We assessed how NHE-1 affected cell length shortening. pH(i) was measured fluorimetrically in resting and twitching (1 - 3 Hz)normal and HFH rabbit myocyte

  11. Effects of rutin from leaves and flowers of buckwheat (Fagopyrum esculentum Moench.) on angiotensin II-induced hypertrophy of cardiac myocytes and proliferation of fibroblasts

    OpenAIRE

    Han, Shu-ying; Chu, Jin-Xiu; Li, Guang-min; Zhu, Li-Sha; Shi, Rui-Fang

    2010-01-01

    Rutin was isolated from dried leaves and flowers of buckwheat (Fagopyrum esculentum Moench.). The effects of rutin on angiotensin II-induced hypertrophy of cultured cardiac myocytes and proliferation of cardiac fibroblasts of neonatal rats were evaluated by analyzing the cell surface area, measuring the protein synthesis rate through 3H-leucine incorporation, and the MTT method. Rutin (0.8 to 8.0 mg/l) exhibited a strong inhibition on the hypertrophy and proliferation. The results...

  12. 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 pat...

  13. Beneficial effect of isradipine on the development of left ventricular hypertrophy in mild hypertension

    DEFF Research Database (Denmark)

    Mehlsen, J; Fornitz, Gitte Gleerup; Haedersdal, C;

    1993-01-01

    The objective of this study was to analyze the long-term hemodynamic effects of the calcium antagonist isradipine in mild hypertension compared with those of the beta 1-selective adrenoceptor antagonist atenolol, focusing in particular on the development of cardiac hypertrophy. Ten male patients...... isradipine (254 +/- 55 g). The results indicate that antihypertensive treatment with isradipine as monotherapy may prevent the development of left ventricular hypertrophy whereas treatment with atenolol as monotherapy does not appear to offer this possibility....

  14. Heuristic problems in defining the three-dimensional arrangement of the ventricular myocytes.

    Science.gov (United States)

    Anderson, Robert H; Ho, Siew Yen; Sanchez-Quintana, Damian; Redmann, Klaus; Lunkenheimer, Paul P

    2006-06-01

    There is lack of consensus concerning the three-dimensional arrangement of the myocytes within the ventricular muscle masses. Bioengineers are seeking to model the structure of the heart. Although the success of such models depends on the accuracy of the anatomic evidence, most of them have been based on concepts that are far from anatomical reality, which ignore many significant previous accounts of anatomy presented over the past 400 years. During the 19th century, Pettigrew emphasized that the heart was built on the basis of a modified blood vessel rather than in the form of skeletal muscles. This fact was reemphasized by Lev and Simkins as well as Grant in the 20th century, but the caveats listed by these authors have been ignored by proponents of two current concepts, which state either that the myocardium is arranged in the form of a "unique myocardial band," or that the walls of the ventricles are sequestrated in uniform fashion by laminar sheets of fibrous tissue extending from epicardium to endocardium. These two concepts are themselves incompatible and are further at variance with the majority of anatomic studies, which have emphasized the regional heterogeneity to be found in the three-dimensional packing of the myocytes within a supporting matrix of fibrous tissue. We reemphasize the significance of this three-dimensional muscular mesh, showing how the presence of intruding aggregates of myocytes extending in oblique transmural fashion also contends against the notion that all myocytes are orientated with their long axes parallel to the epicardial and enodcardial surfaces.

  15. Tetrahydroacridine inhibits voltage-dependent Na+ current in guinea-pig ventricular myocytes

    Institute of Scientific and Technical Information of China (English)

    Wei WANG; Yi-ping WANG; Guo-yuan HU

    2004-01-01

    AIM: To study the effects of tetrahydroacridine (tacrine) on voltage-gated Na+ channels in cardiac tissues.METHODS: Single ventricular myocytes were enzymatically dissociated from adult guinea-pig heart. Voltagedependent Na+ current was recorded using whole cell voltage-clamp technique. RESULTS: (1) Tacrine reversibly inhibited Na+ current with an IC50 value of 120 μmol/L (95 % confidence range: 108-133 μmol/L). (2) The inhibitory effects of tacrine on Na+ current exhibited both a tonic nature and use-dependence. (3) Tacrine at 100 μmol/L caused a negative shift (about 10 mV) in the voltage-dependence of steady-state inactivation of Na+ current, and retarded its recovery from inactivation, but did not affect its activation curve. (4) Intracellular application of tacrine significantly inhibited Na+ current. CONCLUSION: In addition to blocking other voltage-gated ion channels,tacrine blocked Na+ channels in guinea-pig ventricular myocytes. Tactine acted as inactivation stabilizer of Na+channels in cardiac tissues.

  16. Biphasic effects of haloperidol on sodium currents in guinea pig ventricular myocytes

    Institute of Scientific and Technical Information of China (English)

    Lu-feng CHENG; Dong YAN; Subat TURDI; Parhat KERRAM

    2007-01-01

    Aim: To study the effects of haloperidol on sodium currents (INa) in guinea pig ventricular myocytes. Method: Whole-cell patch clamp technique was employed to evaluate the effects of haloperidol on INa, in individual ventricular myocytes.Results: Haloperidol (0.1-3 μmol/L) inhibited INa in a concentration-dependent manner with an IC50 of 0.253±0.015 μmol/L. The inhibition rate of haloperidol (0.3 μmol/L) on INa was 22.14%±0.02%, and the maximum conductance was reduced.Haloperidol significantly reduced the midpoints for the activation and inactiva-tion of INa by 2.09 and 4.09 mV, respectively. The time constant of recovery was increased. The increase in time intervals could only recover by 90.14%±1.4% (n=6); however, haloperidol at 0.03 μmol/L enhanced INa conductance. The mid-points for the activation and inactivation of INa were shifted by 1.38 and 5.69 mV,respectively, at this concentration of haloperidol.Conclusion: Haloperidol dis-played a biphasic effect on INa in guinea pig cardiac myocytes. High concentra-tions of haloperidol inhibited INa, while lower concentrations of haloperidol shifted the activation and inactivation curve to the left. Full recovery of recovery curve was not achieved after 0.3 μmol/L haloperidol administration, indicating that the drug affects the inactivated state of sodium channels.

  17. 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)

  18. 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.

  19. Laminar arrangement of ventricular myocytes influences electrical behavior of the heart.

    Science.gov (United States)

    Hooks, Darren A; Trew, Mark L; Caldwell, Bryan J; Sands, Gregory B; LeGrice, Ian J; Smaill, Bruce H

    2007-11-01

    The response of the heart to electrical shock, electrical propagation in sinus rhythm, and the spatiotemporal dynamics of ventricular fibrillation all depend critically on the electrical anisotropy of cardiac tissue. A long-held view of cardiac electrical anisotropy is that electrical conductivity is greatest along the myocyte axis allowing most rapid propagation of electrical activation in this direction, and that conductivity is isotropic transverse to the myocyte axis supporting a slower uniform spread of activation in this plane. In this context, knowledge of conductivity in two directions, parallel and transverse to the myofiber axis, is sufficient to characterize the electrical action of the heart. Here we present new experimental data that challenge this view. We have used a novel combination of intramural electrical mapping, and experiment-specific computer modeling, to demonstrate that left ventricular myocardium has unique bulk conductivities associated with three microstructurally-defined axes. We show that voltage fields induced by intramural current injection are influenced by not only myofiber direction, but also the transmural arrangement of muscle layers or myolaminae. Computer models of these experiments, in which measured 3D tissue structure was reconstructed in-silico, best matched recorded voltages with conductivities in the myofiber direction, and parallel and normal to myolaminae, set in the ratio 4:2:1, respectively. These findings redefine cardiac tissue as an electrically orthotropic substrate and enhance our understanding of how external shocks may act to successfully reset the fibrillating heart into a uniform electrical state. More generally, the mechanisms governing the destabilization of coordinated electrical propagation into ventricular arrhythmia need to be evaluated in the light of this discovery.

  20. Validation of an in vitro contractility assay using canine ventricular myocytes

    International Nuclear Information System (INIS)

    Measurement of cardiac contractility is a logical part of pre-clinical safety assessment in a drug discovery project, particularly if a risk has been identified or is suspected based on the primary- or non-target pharmacology. However, there are limited validated assays available that can be used to screen several compounds in order to identify and eliminate inotropic liability from a chemical series. We have therefore sought to develop an in vitro model with sufficient throughput for this purpose. Dog ventricular myocytes were isolated using a collagenase perfusion technique and placed in a perfused recording chamber on the stage of a microscope at ∼ 36 °C. Myocytes were stimulated to contract at a pacing frequency of 1 Hz and a digital, cell geometry measurement system (IonOptix™) was used to measure sarcomere shortening in single myocytes. After perfusion with vehicle (0.1% DMSO), concentration–effect curves were constructed for each compound in 4–30 myocytes taken from 1 or 2 dog hearts. The validation test-set was 22 negative and 8 positive inotropes, and 21 inactive compounds, as defined by their effect in dog, cynolomolgous monkey or humans. By comparing the outcome of the assay to the known in vivo contractility effects, the assay sensitivity was 81%, specificity was 75%, and accuracy was 78%. With a throughput of 6–8 compounds/week from 1 cell isolation, this assay may be of value to drug discovery projects to screen for direct contractility effects and, if a hazard is identified, help identify inactive compounds. -- Highlights: ► Cardiac contractility is an important physiological function of the heart. ► Assessment of contractility is a logical part of pre-clinical drug safety testing. ► There are limited validated assays that predict effects of compounds on contractility. ► Using dog myocytes, we have developed an in vitro cardiac contractility assay. ► The assay predicted the in vivo contractility with a good level of accuracy.

  1. Effect of resveratrol on L-type calcium current in rat ventricular myocytes

    Institute of Scientific and Technical Information of China (English)

    Li-ping ZHANG; Jing-xiang YIN; Zheng LIU; Yi ZHANG; Qing-shan WANG; Juan ZHAO

    2006-01-01

    Aim: To study the effect of resveratrol on L-type calcium current (ICa-L) in isolated rat ventricular myocytes and the mechanisms underlying these effects. Methods:ICa-L was examined in isolated single rat ventricular myocytes by using the whole cell patch-clamp recording technique. Results: Resveratrol (10-40 μmol/L) reduced the peak amplitude of ICa-L and shifted the current-voltage (I-V) curve upwards in a concentration-dependent manner. Resveratrol (10, 20, 40 μmol/L)decreased the peak amplitude of ICa-L from -14.2± 1.5 pA/pF to -10.5± 1.5 pA/pF (P<0.05), -7.5±2.4 pA/pF (P<0.01), and -5.2±1.2 pA/pF (P<0.01), respectively.Resveratrol (40 μmol/L) shifted the steady-state activation curve of ICa-L to the right and changed the half-activation potential (V0.5) from -19.4±0.4 mV to -15.4±1.9 mV (P<0.05). Resveratrol at a concentration of 40 μmol/L did not affect the steady-state inactivation curve of ICa-L, but did markedly shift the timedependent recovery curve of ICa-L to the right, and slow down the recovery of ICa-L from inactivation. Sodium orthovanadate (Na3VO4; 1 mmol/L), a potent inhibitor of tyrosine phosphatase, significantly inhibited the effects of resveratrol (P<0.01). Conclusion: Resveratrol inhibited ICa- L mainly by inhibiting the activation of L-type calcium channels and slowing down the recovery of L-type calcium channels from inactivation. This inhibitory effect of resveratrol was mediated by the inhibition of protein tyrosine kinase in rat ventricular myocytes.

  2. 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 ...

  3. 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 of base...

  4. 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 ...

  5. Association of arterial stiffness and electrocardiography-determined left ventricular hypertrophy with left ventricular diastolic dysfunction.

    Directory of Open Access Journals (Sweden)

    Po-Chao Hsu

    Full Text Available OBJECTIVES: Increased arterial stiffness is associated with left ventricular diastolic dysfunction (LVDD, but this association may be influenced by left ventricular (LV performance. Left ventricular hypertrophy (LVH is not only a significant determinant of LV performance, but is also correlated with LVDD. This study is designed to compare LV diastolic function among patients divided by brachial-ankle pulse wave velocity (baPWV and electrocardiography (ECG-determined LVH and to assess whether increased baPWV and ECG-determined LVH are independently associated with LVDD. METHODS: This cross-sectional study enrolled 270 patients and classified them into four groups according to the median value of baPWV and with/without ECG-determined LVH. The baPWV was measured using an ABI-form device. ECG-determined LVH was defined by Sokolow-Lyon criterion. LVDD was defined as impaired relaxation, pseudonormal, and restrictive mitral inflow patterns. Groups 1, 2, 3, and 4 were patients with lower baPWV and without ECG-determined LVH, lower baPWV but with ECG-determined LVH, higher baPWV but without ECG-determined LVH, and higher baPWV and with ECG-determined LVH respectively. RESULTS: Early diastolic mitral velocity (Ea was gradually decreased from group 1 to group 4 (p≦0.027. Patients in group 4 had the highest prevalence of LVDD (all p<0.001. After multivariate analysis, both baPWV and ECG-determined LVH were independent determinants of Ea (β = -0.02, P<0.001; β = -1.77, P<0.001 respectively and LVDD (odds ratio = 1.02, P = 0.011 and odds ratio = 3.53, P = 0.013 respectively. CONCLUSION: Our study showed the group with higher baPWV and ECG-determined LVH had the lowest Ea and highest prevalence of LVDD. In addition, both baPWV and ECG-determined LVH were independently associated with Ea and LVDD. Hence, assessment of arterial stiffness by baPWV and LVH by ECG may be useful in identifying the high risk group of LVDD.

  6. Ultraviolet photoalteration of late Na+ current in guinea-pig ventricular myocytes.

    Science.gov (United States)

    La, C; You, Y; Zhabyeyev, P; Pelzer, D J; McDonald, T F

    2006-03-01

    UV irradiation has multiple effects on mammalian cells, including modification of ion channel function. The present study was undertaken to investigate the response of membrane currents in guinea-pig ventricular myocytes to the type A (355, 380 nm) irradiation commonly used in Ca(2+) imaging studies. Myocytes configured for whole-cell voltage clamp were generally held at -80 mV, dialyzed with K(+)-, Na(+)-free pipette solution, and bathed with K(+)-free Tyrode's solution at 22 degrees C. During experiments that lasted for approximately 35 min, UVA irradiation caused a progressive increase in slowly-inactivating inward current elicited by 200-ms depolarizations from -80 to -40 mV, but had little effect on background current or on L-type Ca(2+) current. Trials with depolarized holding potential, Ca(2+) channel blockers, and tetrodotoxin (TTX) established that the current induced by irradiation was late (slowly-inactivating) Na(+) current (I(Na)). The amplitude of the late inward current sensitive to 100 microM: TTX was increased by 3.5-fold after 20-30 min of irradiation. UVA modulation of late I(Na) may (i) interfere with imaging studies, and (ii) provide a paradigm for investigation of intracellular factors likely to influence slow inactivation of cardiac I(Na). PMID:16783617

  7. Dissociation enzyme effects on the biophysical properties of calcium current in acutely isolated rat ventricular myocytes

    Directory of Open Access Journals (Sweden)

    Julio Álvarez

    2013-04-01

    Full Text Available Proteolytic enzymes such as collagenase, trypsin and pronase E are widely used to acutely dissociate adult cardiomyocytes. There is some evidence that enzyme treatment can alter ionic channels. The aim of the present investigation was to compare the characteristics of the L-type Ca2+ current (ICaL of rat ventricular cardiomyocytes dissociated with two enzyme combinations: collagenase + trypsin (C+T and collagenase + pronase E (C+P. ICaL density (pA/pF was significantly lower (~ 2 pA/pF in myocytes isolated with the C+P combination. However, its inactivation time course was barely affected. As well, the voltage dependency of ICaL kinetics was not affected by the C+P treatment. Our results suggest that, compared to the C+T, treatment with the C+P enzyme combination could decrease the number of functional (expressed channels in the sarcolemma.

  8. Comprehensive analyses of ventricular myocyte models identify targets exhibiting favorable rate dependence.

    Directory of Open Access Journals (Sweden)

    Megan A Cummins

    2014-03-01

    Full Text Available Reverse rate dependence is a problematic property of antiarrhythmic drugs that prolong the cardiac action potential (AP. The prolongation caused by reverse rate dependent agents is greater at slow heart rates, resulting in both reduced arrhythmia suppression at fast rates and increased arrhythmia risk at slow rates. The opposite property, forward rate dependence, would theoretically overcome these parallel problems, yet forward rate dependent (FRD antiarrhythmics remain elusive. Moreover, there is evidence that reverse rate dependence is an intrinsic property of perturbations to the AP. We have addressed the possibility of forward rate dependence by performing a comprehensive analysis of 13 ventricular myocyte models. By simulating populations of myocytes with varying properties and analyzing population results statistically, we simultaneously predicted the rate-dependent effects of changes in multiple model parameters. An average of 40 parameters were tested in each model, and effects on AP duration were assessed at slow (0.2 Hz and fast (2 Hz rates. The analysis identified a variety of FRD ionic current perturbations and generated specific predictions regarding their mechanisms. For instance, an increase in L-type calcium current is FRD when this is accompanied by indirect, rate-dependent changes in slow delayed rectifier potassium current. A comparison of predictions across models identified inward rectifier potassium current and the sodium-potassium pump as the two targets most likely to produce FRD AP prolongation. Finally, a statistical analysis of results from the 13 models demonstrated that models displaying minimal rate-dependent changes in AP shape have little capacity for FRD perturbations, whereas models with large shape changes have considerable FRD potential. This can explain differences between species and between ventricular cell types. Overall, this study provides new insights, both specific and general, into the determinants of

  9. Vasodilators and regression of left ventricular hypertrophy. Hydralazine versus prazosin in hypertensive humans.

    Science.gov (United States)

    Leenen, F H; Smith, D L; Farkas, R M; Reeves, R A; Marquez-Julio, A

    1987-05-01

    Long-term treatment of hypertensive rats with arterial vasodilators may further increase left ventricular hypertrophy. Since left ventricular hypertrophy may be an important determinant of outcome in hypertension, the long-term effects of arterial vasodilation with hydralazine on left ventricular mass and function were compared with those of an alternative third-line drug, the alpha1 blocker prazosin, in patients still hypertensive despite combined diuretic and beta blocker therapy. A single-blind, randomized, two-group parallel design was employed. Both treatments induced a sustained antihypertensive effect, with hydralazine showing more effect on supine blood pressure, and prazosin having more effect on standing pressure. Heart rate, cardiac output, and volume status showed only minor changes. Plasma norepinephrine showed a sustained increase when measured in both the supine and standing positions, but the increases were similar for the two treatments. Supine and standing plasma renin activity increased only during long-term treatment with hydralazine. Prazosin induced a progressive decrease in left ventricular mass over time (-34 +/- 15 g/m2 at 12 months), but hydralazine did not (-9 +/- 10 g/m2 after 12 months). Stepwise regression indicated that a decrease in systolic blood pressure was associated with a decrease in left ventricular mass with both treatments, but an increase in plasma norepinephrine was associated with an increase in left ventricular mass only with hydralazine, suggesting that increased sympathetic activity may affect left ventricular mass via cardiac alpha1 receptors. Thus, if regression of left ventricular hypertrophy is a worthwhile therapeutic goal, hydralazine and analogous arterial vasodilators are not drugs of choice.

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

    International Nuclear Information System (INIS)

    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

  11. Characteristics of the inward-rectifying potassium current in mouse ventricular myocytes and its relation to early after-depolarization

    Institute of Scientific and Technical Information of China (English)

    周盈颖; 郝雪梅; 范劲松; 刘泰(木逢)

    1996-01-01

    The properties of the inward-rectifying potassium current (IK1) were studied in the single myocytes isolated from adult mouse ventricles by the whole-cell patch-damp technique for the first time. Most of the properties of IK1 including channel conductances, activation, inactivation, rectification and external K+ sensitivity in mouse ventricular myocyte were similar to those in other species, but the current-voltage (1-V) curve of mouse ventricular myocyte showed no negative slope, i.e the slope in the range of membrane potential 50 mV positive to the reversal potential (VRev) was virtually flat and remained at a low current level ((59±39) pA). Under the superfusion of Tyrode’s solution with 3mmol/L K+ and 3mmol/L Cs+, IK1 in the above region nearly decreased to zero, and then the early after-depolarization (EAD) occurred. The results suggest that this distinctive characteristic of IK1 in mouse ventricular myocyte may relate to the high susceptibility to EA0 in mouse myocardium. The inhibition of IK1 se

  12. 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...

  13. Current-Voltage Relationship for Late Na(+) Current in Adult Rat Ventricular Myocytes.

    Science.gov (United States)

    Clark, R B; Giles, W R

    2016-01-01

    It is now well established that the slowly inactivating component of the Na(+) current (INa-L) in the mammalian heart is a significant regulator of the action potential waveform. This insight has led to detailed studies of the role of INa-L in a number of important and challenging pathophysiological settings. These include genetically based ventricular arrhythmias (LQT 1, 2, and 3), ventricular arrhythmias arising from progressive cardiomyopathies (including diabetic), and proarrhythmic abnormalities that develop during local or global ventricular ischemia. Inhibition of INa-L may also be a useful strategy for management of atrial flutter and fibrillation. Many important biophysical parameters that characterize INa-L have been identified; and INa-L as an antiarrhythmia drug target has been studied extensively. However, relatively little information is available regarding (1) the ion transfer or current-voltage relationship for INa-L or (2) the time course of its reactivation at membrane potentials similar to the resting or diastolic membrane potential in mammalian ventricle. This chapter is based on our preliminary findings concerning these two very important physiological/biophysical descriptors for INa-L. Our results were obtained using whole-cell voltage clamp methods applied to enzymatically isolated rat ventricular myocytes. A chemical agent, BDF 9148, which was once considered to be a drug candidate in the Na(+)-dependent inotropic agent category has been used to markedly enhance INa-L current. BDF acts in a potent, selective, and reversible fashion. These BDF 9148 effects are compared and contrasted with the prototypical activator of INa-L, a sea anemone toxin, ATX II. PMID:27586292

  14. Intracellular Ca2+ Modulation during Short Exposure to Ischemia-Mimetic Factors in Isolated Rat Ventricular Myocytes

    OpenAIRE

    Danijel, Pravdic; Nikolina, Vladic; Zeljko, Bosnjak J

    2009-01-01

    We investigated the effects of different ischemia-mimetic factors on intracellular Ca2+ concentration ([Ca2+]i). Ventricular myocytes were isolated from adult Wistar rats, and [Ca2+]i was measured using fluorescent indicator fluo-4 AM by confocal microscopy. Intracellular pH was measured using c5-(and-6)-carboxy SNARF-1 AM, a dual emission pH-sensitive ionophore. Myocytes were exposed to hypoxia, extracellular acidosis (pHo 6.8), Na-lactate (10 mM), or to combination of those factors for 25 m...

  15. 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.

  16. The Relation Between Hypertrophied Myocardium and Ventricular Fibrillation Threshold in Spontaneously Hypertensive Rats

    Institute of Scientific and Technical Information of China (English)

    Huang Zhibin; Wu Wei; Deng Yijun; Fang Chang; Wei Yulin; Zhou Shuxian; Wang Jingfeng

    2006-01-01

    Objectives To investigate the relation between hypertrophied myocardium and ventricular fibrillation threshold in spontaneously hypertensive rats (SHR). Methods 20 male SHR were randomly divided into two groups: 10 week group (n=10) and 18 week group (n=10). 10week male Wistar rats were controlled group (n=10). The systolic blood pressure (SBP), heart mass index (HMI), ventricular effective refractory period (VERP) and ventricular fibrillation threshold(VFT) were measured respectively.Results ① The SBP and HMI of SHR were significantly higher than those of Wistar rats(P<0.001).The VFT of SHR were significantly lower than that of Wistar rats (P < 0.001). ②In SHR, the SBP and HMI of 18 week SHR were significantly higher than those of 10 week SHR (P < 0.001). The VFT of 18 week SHR were significantly lower than that of 10 week SHR (P<0.001). ③There were no significant difference of VERP among 10 week SHR, 18 week SHR and Wistar rats(P > 0.05). ④There was no relationship between HMI and VFT or SBP in Wistar rats. There was significant relationship between HMI and VFT or SBP in different age spontaneously hypertensive rats. ⑤HMI, age and species of animal were the major influent factors of VFT. Conclusions The VFT of hypertrophied myocardium decreased. The higher the degree of hypertrophy of myocardium and the higher the systolic blood pressure were, the lower the ventricular fibrillation threshold was.

  17. Acute effects of levosimendan in experimental models of right ventricular hypertrophy and failure

    DEFF Research Database (Denmark)

    Vildbrad, Mads D; Andersen, Asger; Holmboe, Sarah;

    2014-01-01

    Pulmonary arterial hypertension (PAH) is a fatal disease, and the ultimate cause of death is right ventricular (RV) failure. In this study, we investigated the acute hemodynamic effects of levosimendan in two rat models of RV hypertrophy and failure. Wistar rats were randomized to receive sham....... PTB and MCT injection caused hypertrophy, dilatation, and failure of the RV compared with sham surgery. Levosimendan increased RV end systolic pressure (sham surgery: 16.0% ± 3.8% [P = 0.0038]; MCT: 9.9% ± 3.1% [P = 0.018]; PTB: 24.5% ± 3.3% [P = 0.0001]; mean ± SEM) compared with placebo...

  18. The Effects of Puerarin on Rat Ventricular Myocytes and the Potential Mechanism

    Science.gov (United States)

    Xu, Hao; Zhao, Manxi; Liang, Shenghui; Huang, Quanshu; Xiao, Yunchuan; Ye, Liang; Wang, Qinyi; He, Longmei; Ma, Lanxiang; Zhang, Hua; Zhang, Li; Jiang, Hui; Ke, Xiao; Gu, Yuchun

    2016-01-01

    Puerarin, a known isoflavone, is commonly found as a Chinese herb medicine. It is widely used in China to treat cardiac diseases such as angina, cardiac infarction and arrhythmia. However, its cardioprotective mechanism remains unclear. In this study, puerarin significantly prolonged ventricular action potential duration (APD) with a dosage dependent manner in the micromolar range on isolated rat ventricular myocytes. However, submicromolar puerarin had no effect on resting membrane potential (RMP), action potential amplitude (APA) and maximal velocity of depolarization (Vmax) of action potential. Only above the concentration of 10 mM, puerarin exhibited more aggressive effect on action potential, and shifted RMP to the positive direction. Millimolar concentrations of puerarin significantly inhibited inward rectified K+ channels in a dosage dependent manner, and exhibited bigger effects upon Kir2.1 vs Kir2.3 in transfected HEK293 cells. As low as micromolar range concentrations of puerarin significantly inhibited Kv7.1 and IKs. These inhibitory effects may due to the direct inhibition of puerarin upon channels not via the PKA-dependent pathway. These results provided direct preclinical evidence that puerarin prolonged APD via its inhibitory effect upon Kv7.1 and IKs, contributing to a better understanding the mechanism of puerarin cardioprotection in the treatment of cardiovascular diseases. PMID:27762288

  19. Differences of promethazine and terfenadine on ion channels in guinea pig ventricular myocytes

    Institute of Scientific and Technical Information of China (English)

    LI Xue-wen; NIU Shuan-cheng; ZHANG Xuan-ping; L(U) Ji-yuan; BAI Feng; ZHANG Ling; WU Bo-wei

    2006-01-01

    @@ Promethazine, a first generation antihistamine,has an antiarrhythmic effect on ischemia-reperfusion inducing arrhythmias1 and experimental arrhythmias.2 However, terfenadine as a second generation of antihistamine, has been reported to elicit hypotension, bradycardia, prolongation of the QTc interval and torsades de pointes (TdP) like ventricular arrhythmia.3 This may be due to the blockage on rectifier postassium current (Ik) of terfenadine, resulting in the prolongation of the action potential duration (APD) and dispersion of the repolarization duration, which might provoke a specific form of polymorphic ventricular tachydysrhythmia, i.e. TdP.4 In clinical practice,however, the class Ⅲ antiarrhythmic agents, which target on the Ik and prolong the action potential duration and QTc interval, rarely lead to arrhythmias.Other actions must be considered to underlie the arrhythmogenic tendency of terfenadine besides its inhibition on Ik. Though both promethazine and terfenadine block the H1 receptor, there must be a different pharmacology profile between the two compounds on ion channels of cardiac myocytes.Whole-cell patch clamp technique was used to investigate the effects of these two antagonists of the H1 receptor on the main ion currents in cardiac electrical activities.

  20. Left ventricular remodeling and hypertrophy in patients with aortic stenosis: insights from cardiovascular magnetic resonance

    Directory of Open Access Journals (Sweden)

    Dweck Marc R

    2012-07-01

    Full Text Available Abstract Background Cardiovascular magnetic resonance (CMR is the gold standard non-invasive method for determining left ventricular (LV mass and volume but has not been used previously to characterise the LV remodeling response in aortic stenosis. We sought to investigate the degree and patterns of hypertrophy in aortic stenosis using CMR. Methods Patients with moderate or severe aortic stenosis, normal coronary arteries and no other significant valve lesions or cardiomyopathy were scanned by CMR with valve severity assessed by planimetry and velocity mapping. The extent and patterns of hypertrophy were investigated using measurements of the LV mass index, indexed LV volumes and the LV mass/volume ratio. Asymmetric forms of remodeling and hypertrophy were defined by a regional wall thickening ≥13 mm and >1.5-fold the thickness of the opposing myocardial segment. Results Ninety-one patients (61±21 years; 57 male with aortic stenosis (aortic valve area 0.93±0.32cm2 were recruited. The severity of aortic stenosis was unrelated to the degree (r2=0.012, P=0.43 and pattern (P=0.22 of hypertrophy. By univariate analysis, only male sex demonstrated an association with LV mass index (P=0.02. Six patterns of LV adaption were observed: normal ventricular geometry (n=11, concentric remodeling (n=11, asymmetric remodeling (n=11, concentric hypertrophy (n=34, asymmetric hypertrophy (n=14 and LV decompensation (n=10. Asymmetric patterns displayed considerable overlap in appearances (wall thickness 17±2mm with hypertrophic cardiomyopathy. Conclusions We have demonstrated that in patients with moderate and severe aortic stenosis, the pattern of LV adaption and degree of hypertrophy do not closely correlate with the severity of valve narrowing and that asymmetric patterns of wall thickening are common. Trial registration ClinicalTrials.gov Reference Number: NCT00930735

  1. Wnt5a attenuates hypoxia-induced pulmonary arteriolar remodeling and right ventricular hypertrophy in mice.

    Science.gov (United States)

    Jin, Yuling; Wang, Wang; Chai, Sanbao; Liu, Jie; Yang, Ting; Wang, Jun

    2015-12-01

    Hypoxic pulmonary hypertension (HPH), which is characterized by pulmonary arteriolar remodeling and right ventricular hypertrophy, is still a life-threatening disease with the current treatment strategies. The underlying molecular mechanisms of HPH remain unclear. Our previously published study showed that Wnt5a, one of the ligands in the Wnt family, was critically involved in the inhibition of hypoxia-induced pulmonary arterial smooth muscle cell proliferation by downregulation of β-catenin/cyclin D1 in vitro. In this study, we investigated the possible functions and mechanisms of Wnt5a in HPH in vivo. Recombinant mouse Wnt5a (rmWnt5a) or phosphate buffered saline (PBS) was administered to male C57/BL6 mice weekly from the first day to the end of the two or four weeks after exposed to hypoxia (10% O2). Hypoxia-induced pulmonary hypertension was associated with a marked increase in β-catenin/cyclin D1 expression in lungs. Right ventricular systolic pressure and right ventricular hypertrophy index were reduced in animals treated with rmWnt5a compared with PBS. Histology showed less pulmonary vascular remodeling and right ventricular hypertrophy in the group treated with rmWnt5a than with PBS. Treatment with rmWnt5a resulted in a concomitant reduction in β-catenin/cyclin D1 levels in lungs. These data demonstrate that Wnt5a exerts its beneficial effects on HPH by regulating pulmonary vascular remodeling and right ventricular hypertrophy in a manner that is associated with reduction in β-catenin/cyclin D1 signaling. A therapy targeting the β-catenin/cyclin D1 signaling pathway might be a potential strategy for HPH treatment.

  2. Ultrasonic evaluation of the relationship between left ventricular hypertrophy or left ventricular geometry and endothelial function in patients with essential hypertension

    Institute of Scientific and Technical Information of China (English)

    Jing Dong; Pingyang Zhang; Xuehong Feng; Chong Wang; Pei Wang

    2009-01-01

    Objective: To assess the relationship between left ventricular hypertrophy (LVH) or left ventricular geometry (LVG) and endothelial function in patients with essential hypertension (EH). Methods: Seventy-six patients and 30 normal subjects were first examined by echocardiography. Brachial artery dilatation induced by reactive hyperemia (DIRH) or nitroglycerin (DING) was detected using high-resolution ultrasonography. Results: DIRH was lower in patients with hypertension than in the controls, and the decrease in DIRH was greater in the patients with LVH than that in patients without LVH (4.36±2.54% vs 8.56+1.87 %; P 0.05). While there was no significant difference in DIRH between the patients with normal left ventricular geometry or cardiac remodeling, the patients showing either eccentric or concentric left ventricular hypertrophy had lower DIRH than the patients with normal left ventricular geometry or cardiac remodeling. The DIRH was the lowest in patients with concentric hypertrophy. Although bivariate analysis showed that the left ventricular mass index (LVMI) correlated well with the brachial artery dilatation induced by reactive hyperemia, diastolic blood pressure and mean blood pressure (r=-0.61, P < 0.0001; r=0.27, P < 0.05; r=0.31, P < 0.05, respectively), a multivariate stepwise regression demonstrated that LVMI correlated only with the brachial artery dilatation induced by reactive hyperemia. Conclusion: Left ventricular hypertrophy was related to endothelial dysfunction in essential hypertension. The endothelial dysfunction might be basic and important in the progression of left ventricular hypertrophy.

  3. Effects of Losartan on L-type Calcium Current in Hypertrophied RatMyocytes

    Institute of Scientific and Technical Information of China (English)

    FuLiying; LiYang; ChengLan; WangFang; XiaGuojin; YaoWeixing

    2001-01-01

    Objective To investigate the alterations of L-type calcium current (IcaL) in abdominal aorticligation-induced hypertrophied rat hearts and the effect of losartan on these alterations. METHODS Cardiachypertrophy was induced by abdominal aortic ligation in rats. To record IcaL, whole-cell patch-clamp technique wasused. RESULTS Membrane capacitance was larger in hypertrophied cells (148±29 pF) than in sham-operated cells(102±14 pF, P<0.01) and losartan-treated cells (118±27, P<0.01). The maximal peak IcaL Was increased from-835±124 pA in sham-operated cells to -1404+_417 pA in hypertrophied cells (P<0.01), the corresponding IcaL density was increased from -7.5±1.8 pA.pF1 to -10.5±2.2 pA.pF1 (P<0.01), while they were reduced to -956-2:170pF (P<0.01) and -8.2±1.6 pA.pF1 (P<0.05) respectively in losartan-treated cells. The membrane potential of halfmaximal activation of the hypertrophied cells (-20.6±1.0 mV) shifted to more negative potentials than sham-operatedcells (-15.6±1.6 mV, P<0.01) and lorsartan-treated cells (-17.4±1.0 mV, P<0.01). The slope of the activation curveof hypertrophied cells (5.7±0.4) was decreased slightly than sham-operated cells (6.4±0.5, P<0.05). The membranepotential of half maximal inactivation of hypertrophied cells (-27.6±1.9 mV) shifted to more positive potentials thansham-operated cells (-31.4±2.2 mV, P<0.05). The slope of inactivation curves were not different in the three groups.

  4. Echocardiographic Partition Values and Prevalence of Left Ventricular Hypertrophy in Hypertensive Jamaicans

    Directory of Open Access Journals (Sweden)

    Chiranjivi Potu

    2012-02-01

    Full Text Available Left ventricular hypertrophy (LVH detected by either electrocardiography or echo- cardiography has been shown to be an extremely strong predictor of morbidity and mortality in patients with essential hypertension and in members of the general population. Alternative to LVH, left ventricular geometrical patterns offer incremental prognostic value beyond that provided by the other cardiovascular risk factors including left ventricular mass (LVM. Combination of LVM and relative wall thickness (RWT can be used to identify different left ventricular geometrical patterns. Various indexation methods normalised for LVM have been shown to offer prognostic significance. There was no prior study on the prevalence of LVH and geometric patterns in hypertensive patients in Jamaica using multiple partition values. Our study was designed to estimate the prevalence of LVH and geometrical patterns in a hypertensive Caribbean population in Jamaica using 10 different published cut-off values.

  5. 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

    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...

  6. Effect of Salvia Miltiorrhiza on Left Ventricular Hypertrophy and Cardiac Aldosterone in Spontaneously Hypertensive Rats

    Institute of Scientific and Technical Information of China (English)

    韩少杰; 郑智; 任大宏

    2002-01-01

    Summary: Chronic treatment with Salvia Miltiorrhiza preventing left ventricular hypertrophy(LVH) and its possible mechanism-inhibiting the action of cardiac aldosterone in spontaneouslyhypertensive rats (SHR) were investigated. Normotensive Wistar-kyoto (WKY) rats and SHRswere used. Part of SHRs was treated with Salvia Miltiorrhiza for 12 weeks. Systolic blood pres-sure (SBP) and left ventricular mass index were measured. Sections of heart tissue were stainedwith HE method and VanGieson method. Collagen volume fraction was determined in the left ven-tricle by automatically quantitative morphometry. Cardiac aldosterone concentration was measuredby radioimmunoassay. The results indicated that compared with WKY rats, SHRs exhibited high-er SBP, left ventricular collagen volume fraction, and aldosterone concentration (all P<0. 05).After the treatment with Salvia Miltiorrhiza, SBP, left ventricular collagen volume fraction, andaldosterone concentration in SHR were decreased as compared with control group (P<0. 05) ex-cept SBP. It was concluded that chronic treatment with Salvia Miltiorrhiza could prevent left ven-tricular hypertrophy in SHR, significantly inhibit collagen compositions in left ventricle. Themechanism was probably related with the inhibition of the cardiac aldosterone action.

  7. Lung function and left ventricular hypertrophy in morbidly obese candidates for bariatric surgery

    Science.gov (United States)

    Müller, Paulo de Tarso; Domingos, Hamilton; Patusco, Luiz Armando Pereira; Rapello, Gabriel Victor Guimarães

    2015-01-01

    Objective: To look for correlations between lung function and cardiac dimension variables in morbidly obese patients, in order to test the hypothesis that the relative size of the small airways is independently correlated with left ventricular hypertrophy. Methods: This was a retrospective study involving 192 medical records containing a clinical protocol employed in candidates for bariatric surgery between January of 2006 and December of 2010. Results: Of the 192 patients evaluated, 39 (10 males and 29 females) met the inclusion criteria. The mean BMI of the patients was 49.2 ± 7.6 kg/m2, and the mean age was 35.5 ± 7.7 years. The FEF25-75/FVC, % correlated significantly with left ventricular posterior wall thickness and relative left ventricular posterior wall thickness, those correlations remaining statistically significant (r = −0.355 and r = −0.349, respectively) after adjustment for weight, gender, and history of systemic arterial hypertension. Stepwise multivariate linear regression analysis showed that FVC and FEV1 were the major determinants of left ventricular mass (in grams or indexed to body surface area). Conclusions: A reduction in the relative size of the small airways appears to be independently correlated with obesity-related cardiac hypertrophy, regardless of factors affecting respiratory mechanics (BMI and weight), gender, or history of systemic arterial hypertension. However, FEV1 and FVC might be important predictors of left ventricular mass in morbidly obese individuals. PMID:26578134

  8. Left ventricular diverticulum with marked hypertrophy of the left ventricular apex revealed by thallium-201 myocardial emission CT

    International Nuclear Information System (INIS)

    A case of left ventricular apical diverticulum with marked hypertrophy of the left ventricular apical wall revealed by thallium-201 myocardial emission CT is reported. A 23-year-old woman was admitted to our hospital for evaluation of chest oppression. She was known to have had a heart murmur soon after birth, but she grew uneventfully, partaking in normal exercise. At the age of 21, she began to feel chest oppression during exercise. As the attacks became frequent, she was admitted to our hospital. Physical examination revealed an ejection systolic murmur in the second left intercostal space. Electrocardiography showed ST depression and T inversion in leads III, a VF and V4-6. M-mode echocardiography was normal. Two-dimensional echocardiography showed a small diverticulum at the apex of the left ventricle, which was also recognized by left ventriculography. It was about 8 x 12 mm in size. Thallium-201 myocardial emission CT disclosed marked uptake in the apex of the left ventricle, suggesting apical hypertrophy. Stress thallium-201 myocardial emission CT was negative. Coronary angiography was normal. The cause of chest oppression in this patient is uncertain, but the small diverticulum and hypertrophy of the cardiac apex may play a role in its pathogenesis. (author)

  9. Progressive Left Ventricular Hypertrophy after Heart Transplantation: Insights and Mechanisms Suggested by Multimodal Images.

    Science.gov (United States)

    Ananthasubramaniam, Karthik; Garikapati, Kiran; Williams, Celeste T

    2016-02-01

    Immunosuppression is the typical measure to prevent rejection after heart transplantation. Although rejection is the usual cause of cardiac hypertrophy, numerous other factors warrant consideration. Calcineurin inhibitors rarely cause hypertrophic cardiomyopathy; the few relevant reports have described children after orthotopic kidney or liver transplantation. We present the case of a 73-year-old woman, an asymptomatic orthotopic heart transplantation patient, in whom chronic immunosuppression with prednisone and cyclosporine apparently caused a phenotype of hypertrophic cardiomyopathy. The natural course of her midapical hypertrophy was revealed by single-photon-emission computed tomography, positron-emission tomography, and 2-dimensional echocardiography. Clinicians and radiographers should be alert to progressive left ventricular hypertrophy and various perfusion patterns in heart transplantation patients even in the absence of underlying coronary artery disease. Toward this end, we recommend that advanced imaging methods be used to their fullest extent. PMID:27047289

  10. Left Ventricular Hypertrophy in Chronic Kidney Disease Patients: From Pathophysiology to Treatment

    OpenAIRE

    Di Lullo, Luca; Gorini, Antonio; Russo, Domenico; Santoboni, Alberto; Ronco, Claudio

    2015-01-01

    Cardiovascular diseases represent the main causes of morbidity and mortality in patients with chronic kidney disease (CKD). According to a well-established classification, cardiovascular involvement in CKD can be set in the context of cardiorenal syndrome type 4. Left ventricular hypertrophy (LVH) represents a key feature to provide an accurate picture of systolic-diastolic left heart involvement in CKD patients. Cardiovascular involvement is present in about 80% of prevalent hemodialysis pat...

  11. Validation study of candidate single nucleotide polymorphisms associated with left ventricular hypertrophy in the Korean population

    OpenAIRE

    Park, Jin-Kyu; Kim, Mi Kyung; Choi, Bo Youl; Jung, Yusun; Song, Kyuyoung; Kim, Yu Mi; Shin, Jinho

    2015-01-01

    Background Left ventricular hypertrophy (LVH) is a valid predictor for cardiovascular mortality and morbidity regardless of age, gender, and race. The HyperGEN study conducted a genome-wide association study and identified twelve single nucleotide polymorphisms (SNPs) associated with LVH. The aim of this study was to validate these candidate SNPs in the Korean population. Methods Among 1637 individuals from the Korean Multi-Rural Communities Cohort Study (MRCohort) of the Korean Genome Epidem...

  12. Diastolic function in various forms of left ventricular hypertrophy: contribution of active Doppler stress echo.

    Science.gov (United States)

    Möckel, M; Störk, T

    1996-11-01

    It has been known for a long time that healthy athletes can develop left ventricular hypertrophy with typical electrocardiographic and echocardiographic findings which lead to the definition of the athlete's heart, as a separate physiological feature. In some cases it is difficult to distinguish between pathological versus physiological myocardial hypertrophy. Diastolic dysfunction is an early sign in the temporal sequence of ischemic events in coronary heart disease. Similar changes occur in other types of heart disease due to arterial hypertension or inflammation processes. Diastolic function is changed even in idiopathic hypertrophic cardiomyopathies. In contrast to these groups of patients, diastolic function remains unchanged or is improved in healthy athletes depending on the type of training (isotonic or isometric exercise). In cases with borderline changes, examinations during physical stress (exercise testing) which provokes an oxygen demand/supply imbalance and consecutively impairs early diastolic filling could clarify if an underlying heart disease is present. Although the physiology of diastolic function is complex, the factors contributing to diastolic disturbances can be differentiated into intrinsic and extrinsic left ventricular (LV) abnormalities. Intrinsic mechanisms include a) impaired LV relaxation, b) increased overall chamber stiffness, c) increased myocardial stiffness and d) increased LV asynchrony. All these factors are part of pathological LV hypertrophy. Factors extrinsic to the LV causing diastolic disorders include a) increased central blood volume, which will increase left ventricular pressure without altering the LV pressure-volume relation, and b) ventricular interaction mediated by pericardial restraint, which may cause a parallel upward shift of the diastolic LV pressure-volume curve. Improved understanding of LV relaxation and filling helps to differentiate pathological and physiological myocardial hypertrophy. Ongoing heart

  13. Effects of Matrine on Aconitine-Induced Electrophysiological Changes in Rat Ventricular Myocytes

    Institute of Scientific and Technical Information of China (English)

    SHANHong-li; YANGBao-feng; ZHOUYu-hong; WANGHe; LIBao-xin

    2004-01-01

    Aim To explore the reason that the antiarrhythmic effect of the extract of traditional Chinese medicinal herb, matrine, is weaker than quinidine and verapamil by comparision of the effect and efficacy of matrine on various kinds of transmembrane ionic currents with those of quinidine and verapamil; and to demonstrate the best targets for antiarrhythinic drugs. Methods Whole-cell patch-clamp techniques were used to record the action potential and ionic currents in single cells of rat ventrictdar myocytes. Aconitine was used to induce the changes of ionic currents, then study the effects of matrine and quinidine, verapamil on aconitine-induced imbalanced channel currents and action potential. Results Aconitine 1μmol·L-1 induced significant changes in transmembrane currents and action potential in single cells of rat ventricular myocytes. APD was significantly prolonged by aconitine. Simtdtaneously, aconitine increased sodium, L-type calcium and in-ward rectifier potassium currents. Matrine 100μmol·L-1 reversed the aconitine-induced changes of sodium current (INa)from (-70.2±10.5) pA/pF to (-39.6±4.0) pA/pF (n=5, P<0.05 vs aconitine) ; L-type calcium current (ICa-L)from (20.4±3.8) pA/pF to (-12.9±2.9) pA/pF (n=6, P<0.01); the inward rectifier potassium current (IK1) from (-32.2±1.08) pA/pF to (-24.0±3.4) pA/pF (n=6, P<0.01 ), and action potential duration. The reversal effectsof quinidine and verapamil on aconitine-induced changes of APD and ionic currents were more marked than matrine. Conclusion Aco-nitine significantly disturbs the normal equilibrium of ion channels in ventricular myecytes. It induces changes of INa, ICa-L, IK1 and prolongation of action potential duration. Matrine at concentration 50 or 100μmol·L-1 statistically significantly suppresses aconitine-induced changes of APD and ionic currents. The potency and efficacy of inhibitory effect of matrine are markedly weaker than those of commonly used verapamil and quinidine.

  14. Effects of Chinese herbs on multiple ion channels in isolated ventricular myocytes

    Institute of Scientific and Technical Information of China (English)

    LI Ning; MA Ke-juan; WU Xiang-feng; SUN Qi; ZHANG Yi-hui; PU Jie-lin

    2007-01-01

    Background Shensong Yangxin (SSYX) is one of the compound recipe of Chinese materia medica. This study was conducted to investigate the effects of SSYX on sodium current (INa), L-type calcium current (ICa,L), transient outward potassium current (Ito), delayed rectifier current (IK), and inward rectifier potassium currents (IK1) in isolated ventricular myocytes.Methods Whole cell patch-clamp technique was used to study ion channel currents in enzymatically isolated guinea pig or rat ventricular myocytes.Results SSYX decreased peak INa by (44.84±7.65)% from 27.21±5.35 to 14.88±2.75 pA/pF (n=5, P<0.05). The medicine significantly inhibited the ICa,L. At concentrations of 0.25, 0.50, and 1.00 g/100 mi, the peak ICa,L was reduced by(19.22±1.10)%, (44.82±6.50)% and (50.69±5.64)%, respectively (n=5, all P<0.05). SSYX lifted the Ⅰ-Ⅴ curve of both INa and ICa,L without changing the threshold, peak and reversal potentials. At the concentration of 0.5%, the drug blocked the transient component of Ito by 50.60% at membrane voltage of 60 mV and negatively shifted the inactive curve and delayed the recovery from channel inactivation. The tail current density of IK was decreased by (30.77±1.11)% (n=5,P<0.05) at membrane voltage of 50 mV after exposure to the medicine and the time-dependent activity of IK was also inhibited. Similar to the effect on IK, the SSYX inhibited IK1 by 33.10% at the test potential of -100 mV with little effect on reversal potential and the rectification property.Conclusions The experiments revealed that SSYX could block multiple ion channels such as INa ICa,L, Ik, Ito and IK1,which may change the action potential duration and contribute to some of its antiarrhythmic effects.

  15. Effect of Xinjikang on left ventricular hypertrophy remodeling in hypertensive rats

    Institute of Scientific and Technical Information of China (English)

    Hong-Bo Liu; Chun-Hua Lin; Guang-Yu Zhou; Guo-Zhen Chen; Wei-Yan Cai

    2013-01-01

    Objective:To investigate the effects ofXinjikang on the left ventricular hypertrophy remodeling and myocardial activity in hypertension.Methods:SixtyWistar rats were randomly divided into four groups.The pressure-loaded left ventricular hypertrophy model was established with abdominal aorta ligation method.Rats inA andB groups were intragastrically administered with physiological saline, whileC andD groups were administered withXinjikang and metoprolol, respectively.The changes in blood pressure,E/A ratio, myocardial pathological morphology, myocardial lipoperoxides and superoxide dismustase activity in four groups were observed and compared before and after treatment. Results:There were statistically significant differences inE/A ratio betweenC group after treatment and model group(P0.05); after treatment the myocardial lipoperoxides and superoxide dismustase contents inC andD groups were improved significantly compared with model group(P<0.05).Conclusions:Xinjikang can improve myocardial injury, restore myocardial parenchyma and myocardial interstitial remodeling functions in hypertensive rats with the left ventricular hypertrophy.

  16. Anti-hypertensive drugs have different effects on ventricular hypertrophy regression

    Directory of Open Access Journals (Sweden)

    Celso Ferreira Filho

    2010-01-01

    Full Text Available OBJECTIVES: There is a direct relationship between the regression of left ventricular hypertrophy (LVH and a decreased risk of mortality. This investigation aimed to describe the effects of anti-hypertensive drugs on cardiac hypertrophy through a meta-analysis of the literature. METHODS: The Medline (via PubMed, Lilacs and Scielo databases were searched using the subject keywords cardiac hypertrophy, antihypertensive and mortality. We aimed to analyze the effect of anti-hypertensive drugs on ventricle hypertrophy. RESULTS: The main drugs we described were enalapril, verapamil, nifedipine, indapamina, losartan, angiotensin-converting enzyme inhibitors and atenolol. These drugs are usually used in follow up programs, however, the studies we investigated used different protocols. Enalapril (angiotensin-converting enzyme inhibitor and verapamil (Ca++ channel blocker caused hypertrophy to regress in LVH rats. The effects of enalapril and nifedipine (Ca++ channel blocker were similar. Indapamina (diuretic had a stronger effect than enalapril, and losartan (angiotensin II receptor type 1 (AT1 receptor antagonist produced better results than atenolol (selective β1 receptor antagonist with respect to LVH regression. CONCLUSION: The anti-hypertensive drugs induced various degrees of hypertrophic regression.

  17. The Effect of Extrogenous Phosphocreatine on L-type Calcium Current in Ischemic Guinea Pig Ventricular Myocytes

    Institute of Scientific and Technical Information of China (English)

    Shi Xiangmin; Li Tiande; Yang Tingshu; Wang Yutang; Shan Zhaoliang

    2005-01-01

    Objectives Heart failure (HF)is one of the most common outcome for all kinds of heart diseases, the effects of energetic therapy on HF remains controversial, especially to ischemic HF. The aim of this study was to explore the effect of exogenous phosphocreatine with different concentration on L-type calcium(ICa-L) current in ischemic ventricular myocytes of guinea pig and to investigate its underlying electrophysiological mechanism for the treatment of ischemic HF. Methods Single ventricular myocytes were isolated enzymatically from left ventricle of guinea pig. Peak ICa-L current were recorded using patch clamp techniques in the whole-cell configuration when myocytes had been superfused with normal Tyrode solution, simple ischemic solution, ischemic solution containing phosphocreatine with different concentration for 10 minutes respectively. Results Peak ICa-L current density of myocytes superfused with simple simulated ischemic solution was remarkably inhibited by 80.6 ±5.2% compared with myocytes superfused with normal Tyrode solution(P<0.05). Ischemic solution containing phosphocreatine of 5, 10, 20, 30mmol/L inhibited Peak ICa-L current density by (53.8±6.7)%, (41.8±8.2)%, (38.1±7.4)%, (36.6±9.7)% respectively.There was no statistical significance among phosphocreation of 10, 20, 30 mmol / L. Conclusions Extrogenous phosphocreatine could reverse the inhibition of ICa-L current under ischemic condition,which could be the ionic basis for the treatment of ischemic heart failure. 0~10 mmol/L phosphocreatine exerted significant dose-effect relationship which no longer existed as concentration more than 10 mmol/L.It is supposed that phosphocreatine increased ICa-Lcurrent by many pathways rather than simple substrate for ATP synthesis.

  18. Ca(2+)-activated chloride channel activity during Ca(2+) alternans in ventricular myocytes.

    Science.gov (United States)

    Kanaporis, Giedrius; Blatter, Lothar A

    2016-11-01

    Cardiac alternans, defined beat-to-beat alternations in contraction, action potential (AP) morphology or cytosolic Ca transient (CaT) amplitude, is a high risk indicator for cardiac arrhythmias. We investigated mechanisms of cardiac alternans in single rabbit ventricular myocytes. CaTs were monitored simultaneously with membrane currents or APs recorded with the patch clamp technique. A strong correlation between beat-to-beat alternations of AP morphology and CaT alternans was observed. During CaT alternans application of voltage clamp protocols in form of pre-recorded APs revealed a prominent Ca(2+)-dependent membrane current consisting of a large outward component coinciding with AP phases 1 and 2, followed by an inward current during AP repolarization. Approximately 85% of the initial outward current was blocked by Cl(-) channel blocker DIDS or lowering external Cl(-) concentration identifying it as a Ca(2+)-activated Cl(-) current (ICaCC). The data suggest that ICaCC plays a critical role in shaping beat-to-beat alternations in AP morphology during alternans.

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

    Science.gov (United States)

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

    2011-12-01

    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 specifity 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.

  20. Phosphorylation of PTEN increase in pathological right ventricular hypertrophy in rats with chronic hypoxia induced pulmonary hypertension

    Institute of Scientific and Technical Information of China (English)

    Nie Xin; Shi Yiwei; Yu Wenyan; Xu Jianying; Hu Xiaoyun; Du Yongcheng

    2014-01-01

    Background Phosphatase and tensin homologue on chromosome ten (PTEN) acts as a convergent nodal signalling point for cardiomyocyte hypertrophy,growth and survival.However,the role of PTEN in cardiac conditions such as right ventricular hypertrophy caused by chronic hypoxic pulmonary,hypertension remains unclear.This study preliminarily discussed the role of PTEN in the cardiac response to increased pulmonary vascular resistance using the hypoxia-induced PH rats.Methods Male Sprague Dawley rats were exposed to 10% oxygen for 1,3,7,14 or 21 days to induce hypertension and right ventricular hypertrophy.Right ventricular systolic pressure was measured via catheterization.Hypertrophy index was calculated as the ratio of right ventricular mass to left ventricle plus septum mass.Tissue morphology and fibrosis were measured using hematoxylin,eosin and picrosirius red staining.The expression and phosphorylation levels of PTEN in ventricles were determined by real time PCR and Western blotting.Results Hypoxic exposure of rats resulted in pathological hypertrophy,interstitial fibrosis and remodelling of the right ventricle.The phosphorylation of PTEN increased significantly in the hypertrophic right ventricle compared to the normoxic control group.There were no changes in protein expression in either ventricle.Conclusion Hypoxia induced pulmonary hypertension developed pathological right ventricular hypertrophy and remodelling probablv related to an increased phosohorvlation of PTEN.

  1. The association of growth differentiation factor-15 with left ventricular hypertrophy in hypertensive patients.

    Directory of Open Access Journals (Sweden)

    Hao Xue

    Full Text Available Growth differentiation factor-15 (GDF-15 has been identified as an endogenous anti-hypertrophy effect. However, the association of plasma GDF-15 levels with left ventricular hypertrophy (LVH in hypertension is poorly understood. We investigate the effect of plasma GDF-15 levels on left ventricular hypertrophy (LVH in hypertension. We measured the plasma levels of GDF-15 in 299 untreated hypertensive patients which consisted of 99 with LVH and 200 without LVH using immunoradiometric assay. All subjects were examined by the ultrasonic cardiograph to determine Left ventricular (LV internal diameters, septal thickness, and posterior wall thickness. The associations of GDF-15 with left ventricular mass index (LVMI, LV end-systolic and -diastolic diameters, LV wall thickness, and LV ejection fraction were evaluated. We found that plasma GDF-15 levels in hypertensive patients with LVH [median 1101, 25th-75th percentiles (879-1344 ng/L] were higher than that in hypertensive patients without LVH [median 516, 25th-75th percentiles (344-640 ng/L] (P<0.001. After adjustment for traditional covariates, plasma GDF-15 levels were independently related to LVMI (R(2 = 0.53; β = 0.624, P<0.001, LV interventricular septal thickness (R(2 = 0.23; β = 0.087, P<0.01 and LV posterior wall thickness (R(2 = 0.26; β = 0.103, P<0.05. Our cross-sectional data on a hospital-based sample indicate that plasma GDF-15 levels are associated with LVH in hypertensive patients.

  2. Effects of remifentanil on intracellular Ca2+ and its transients induced by electrical stimulation and caffeine in rat ventricular myocytes

    Institute of Scientific and Technical Information of China (English)

    ZHANG Ye; Michael G. Irwin; LI Rui; CHEN Zhiwu; Tak-Ming Wong

    2009-01-01

    Background Preconditioning with remifentanil confers cardioprotection. Since Ca2+ overload is a precipitating factor of injury, we determined the effects of remefentanil on intracellular Ca2+ ([Ca2+]I) and its transients induced by electrical stimulation and caffeine, which reflects Ca2+ handling by Ca2+ handling proteins, in rat ventricular myocytes. Methods Freshly isolated adult male Sprague-Dawley rat myocytes were loaded with Fura-2/AM and [Ca]I was determined by spectrofluorometry. Remifentanil at 0.1-1000 μg/L was administered. Ten minutes after administration, either 0.2 Hz electrical stimulation was applied or 10 mmol/L caffeine was added. The [Ca2+]I, and the amplitude, time resting and 50% decay (t50) of both transients induced by electrical stimulation (E[Ca2+]I) and caffeine (C[Ca2+]I) were determined.Results Remifentanil (0.1-1000.0 μg/L) decreased the [Ca2+]I in a dose-dependent manner. It also decreased the amplitude of both transients dose-dependently. Furthermore, it increased the time to peak and t50 of both transients dose-dependently.Conclusion Remifentanil reduced the [Ca2+]I and suppressed the transients induced by electrical stimulation and caffeine in rat ventricular myocytes.

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

    International Nuclear Information System (INIS)

    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.)

  4. [Left ventricular hypertrophy in the cat - "when hypertrophic cardiomyopathy is not hypertrophic cardiomyopathy"].

    Science.gov (United States)

    Glaus, T; Wess, G

    2010-07-01

    According to WHO classification hypertrophic cardiomyopathy (HCM) is a primary genetic cardiomyopathy. Echocardiographically HCM is characterized by symmetric, asymmetric or focal left ventricular hypertrophy (LVH) without recognizable underlying physical cause. However, echocardiographically HCM in cats may not be distinguishable from other causes of a thick appearing left ventricle. Hypovolemia can look like a hypertrophied ventricle but is basically only pseudohypertrophic. Well recognized and logical physical causes of LVH include systemic hypertension and outflow obstruction. LVH similar to HCM may also be found in feline hyperthyroidism. The context of the disease helps to differentiate these physical / physiological causes of LVH. Difficult to distinguish from HCM, particularly when based on a snapshot of a single echocardiographic exam, are myocarditis and . Only the clinical and echocardiographic course allow a reasonably confident etiological diagnosis and the differentiation between HCM and secondary LVH. PMID:20582898

  5. Evaluation of docosahexaenoic acid in a dog model of hypertension induced left ventricular hypertrophy.

    Science.gov (United States)

    Stanley, William C; Cox, James W; Asemu, Girma; O'Connell, Kelly A; Dabkowski, Erinne R; Xu, Wenhong; Ribeiro, Rogerio F; Shekar, Kadambari C; Hoag, Stephen W; Rastogi, Sharad; Sabbah, Hani N; Daneault, Caroline; des Rosiers, Christine

    2013-12-01

    Marine n-3 polyunsaturated fatty acids alter cardiac phospholipids and prevent cardiac pathology in rodents subjected to pressure overload. This approach has not been evaluated in humans or large animals with hypertension-induced pathological hypertrophy. We evaluated docosahexaenoic acid (DHA) in old female dogs with hypertension caused by 16 weeks of aldosterone infusion. Aldosterone-induced hypertension resulted in concentric left ventricular (LV) hypertrophy and impaired diastolic function in placebo-treated dogs. DHA supplementation increased DHA and depleted arachidonic acid in cardiac phospholipids, but did not improve LV parameters compared to placebo. Surprisingly, DHA significantly increased serum aldosterone concentration and blood pressure compared to placebo. Cardiac mitochondrial yield was decreased in placebo-treated hypertensive dogs compared to normal animals, which was prevented by DHA. Extensive analysis of mitochondrial function found no differences between DHA and placebo groups. In conclusion, DHA did not favorably impact mitochondrial or LV function in aldosterone hypertensive dogs.

  6. Ettects of simvastatin on ion channel currents in ventricular myocytes from rabbit with acute myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    Chao Ding; Xianghua Fu; Li Yang; Huixiao Chen; Junxia Li; Yuying Zhao; Jie Li; Jie Wang

    2008-01-01

    Objective To investigate the effects of simvastatin on membrane ionic currents in left ventricular myocytes after acutemyocardial infarction(AML.so as to explore the ionic mechanism of statin treatment for antiarrhythmia.Methods Fourty-five NewZeland rabbits were randomly divided into three groups:AMI group,simvastatin intervention group(statin group)and sham-operatedcontrol group (CON).Rabbits were infarcted by ligation of the left anterior descending coronary artery after administration of oralisolated enzymatically from the epicardial zone of the infractcd region.Whole cell patch clamp technique was used to record mmbranewas significantly decreased in AMI group(-23.26+5.1 8)compared with CON(-42.78±5.48,P<0.05),while it was significantlyincreased in Stating roup(-39.23±5.45)compared with AMI group(P<0.01);The peak Ica-L current density(at 0 mV) was significantlydecreased in AMI group(-3.23±0.91)compared with CON(-4.56±1.01,P<0.05),while it was significantly increased in Statin group(-4.18±0.95)compared with AMI group(P<0.05);The Ito current density(at+60 mV)was significantly decreased in AMI group(10.41±1.93)compared with CON(17.41±3.13,P<0.01),while it was significantly increased in Statin group(16.21±2.42)compared withattenuate this change without lowering the serum cholesterol level,suggesting that simvastatin reverse this electrical remodeling thuscontributing to the ionic mechanism of statin treatment for antiarrhythmia.

  7. A compartmentalized mathematical model of the β1-adrenergic signaling system in mouse ventricular myocytes.

    Directory of Open Access Journals (Sweden)

    Vladimir E Bondarenko

    Full Text Available The β1-adrenergic signaling system plays an important role in the functioning of cardiac cells. Experimental data shows that the activation of this system produces inotropy, lusitropy, and chronotropy in the heart, such as increased magnitude and relaxation rates of [Ca(2+]i transients and contraction force, and increased heart rhythm. However, excessive stimulation of β1-adrenergic receptors leads to heart dysfunction and heart failure. In this paper, a comprehensive, experimentally based mathematical model of the β1-adrenergic signaling system for mouse ventricular myocytes is developed, which includes major subcellular functional compartments (caveolae, extracaveolae, and cytosol. The model describes biochemical reactions that occur during stimulation of β1-adrenoceptors, changes in ionic currents, and modifications of Ca(2+ handling system. Simulations describe the dynamics of major signaling molecules, such as cyclic AMP and protein kinase A, in different subcellular compartments; the effects of inhibition of phosphodiesterases on cAMP production; kinetics and magnitudes of phosphorylation of ion channels, transporters, and Ca(2+ handling proteins; modifications of action potential shape and duration; magnitudes and relaxation rates of [Ca(2+]i transients; changes in intracellular and transmembrane Ca(2+ fluxes; and [Na(+]i fluxes and dynamics. The model elucidates complex interactions of ionic currents upon activation of β1-adrenoceptors at different stimulation frequencies, which ultimately lead to a relatively modest increase in action potential duration and significant increase in [Ca(2+]i transients. In particular, the model includes two subpopulations of the L-type Ca(2+ channels, in caveolae and extracaveolae compartments, and their effects on the action potential and [Ca(2+]i transients are investigated. The presented model can be used by researchers for the interpretation of experimental data and for the developments of

  8. Ca2+ sparks evoked by depolarization of rat ventricular myocytes involve multiple release sites

    Institute of Scientific and Technical Information of China (English)

    ZANGWei-Jin; YUXiao-Jiang; ZANGYi-Min

    2003-01-01

    AIM:To investigate the fundamental nature of calcium release events (Ca2+‘sparks’) evoked in rat ventricular myocytes during excitation-contraction (E-C) coupling. METHODS: High-resolution line-scan confocal imaging with the fluorescent calcium indicator and patch-clamp techniques were used to study the spontaneous Ca2+ sparks and sparks evoked by depolarization. RESULTS: 1)Line scans oriented along the length of the cell showed that both spontaneous sparks and sparks evoked by depolarization to -35mV appeared to arise at single sites spacing about 1.80μm apart (ie, the sarcomere length), and measurements of their longitudinal spread (full-width at halfmaximal amplitude:FWHM) followed single Gaussian distributions with means of 2.6μm. 2)Different to this,transverse line scans often revealed spontaneous and evoked sparks that appeared to arise near-synchronously from paired sites. Measurements of transverse FWHM of both spontaneous and evoked sparks showed bimodal distributions, which were fit well by the sums of two Gaussian curves with means of 1.8 and 2.9μm for spontaneous sparks and ith means of 1.9 and 3.1 μm for evoked sparks. Relative areas under the two Gaussian curves were 1.73:1 and 1.85:1, respectively, for spontaneous and evoked sparks. CONCLUSIONS: Ca2+ sparks evoked by depolarization are not ′unitary′ events, but often involve multiple sites of origin along Z-lines, as previously shown for spontaneous sparks. Thus, Ca2+ released during sparks directly triggered by influx through L-type Ca2+ channels may, in turn, trigger neighboring sites. The restricted involvement of only a few transverse release sites preserves the essential feature of the ‘local control’ theory of E-C coupling.

  9. Dihydroxyflavonol reduces post-infarction left ventricular remodeling by preventing myocyte apoptosis in the non-infarcted zone in goats

    Institute of Scientific and Technical Information of China (English)

    WANG Sheng; FEI Ke; XU Ya-wei; WANG Liang-xu; Chen Yan-qin

    2009-01-01

    Background Myocyte apoptosis is considered to be the major causative factor of left ventricular (LV) remodeling following myocardial infarction (MI). We previously reported that 3', 4'-dihydroxyflavonol (DiOHF), was able to suppress oxidative stress and preserve the expression of endothelial nitric oxide synthase during myocardial reperfusion injury, which may benefit the reduction of myocyte apoptosis. We therefore aimed to evaluate the potential actions of DiOHF against myocyte apoptosis and post-infarction LV remodeling in this study. Methods Following experimental MI, surgical instrumented goats were randomly assigned into vehicle and DiOHF (2 mg/kg; i.v., daily) groups to receive 4 weeks of reperfusion with corresponding treatments. LV pressure recordings and echocardiogram were performed at baseline, 2 and 4 weeks of reperfusion. Myocardial tissues were collected in the end to determine infarct size and apoptosis related assays. Results LV end-diastolic volume and diameter were significantly increased 4 weeks after MI in the vehicle group, accompanied by reduced posterior wall thickness, septal thickness and LV mass, whereas those changes were markedly prevented by DiOHF treatment. Similarly, significantly reduced infarct size was found in DiOHF group as compared to vehicle group, and DiOHF dramatically inhibited the increase in LV end-diastolic pressure and the reductions in ejection fraction, fraction shortening and dP/dtmax. Moreover, DiOHF treatment significantly reduced the extent of myocyte apoptosis detected by TUNEL assay, enhanced the protein expression of caspase-3, Fas, Bax and cytochrome c in the non-infarcted myocardium in comparison to vehicle. Conclusions Daily DiOHF treatment during the reperfusion period after MI in the ovine hearts markedly reduced the magnitude of post-infarction LV remodeling through the inhibition of myocyte apoptosis in the remote non-infarcted myocardium.

  10. [CLINICAL, BIOCHEMICAL AND HORMONAL PREDICTORS OF LEFT VENTRICULAR HYPERTROPHY IN PATIENTS WITH ACROMEGALY].

    Science.gov (United States)

    Mykytyuk, M R

    2015-01-01

    Examined 76 (26 men and 50 women) patients with active acromegaly aged 20 to 70 years, average age (48.22 ± 12.19). Echocardiographic signs of hypertrophy of the left ventricular (LVH) revealed by 63.2% of patients, including 46%--concentric LVH. Found that high levels of pituitary growth hormone (GH) and insulin like growth factor-1 (IGF-1) were independent predictors of LVH. Influence of GH and IGF-1 on the formation of LVH-mediated through anthropometric parameters and levels of systolic and diastolic blood pressure, which are predictors in patients with acromegaly LVH.

  11. Non-Dipper Status and Left Ventricular Hypertrophy as Predictors of Incident Chronic Kidney Disease

    OpenAIRE

    An, Hye Rim; Park, Sungha; Yoo, Tae-Hyun; Kang, Shin-Wook; Ryu, Jung-Hwa; Lee, Yong Kyu; Yu, Mina; Ryu, Dong-Ryeol; Kim, Seung Jung; KANG, DUK-HEE; Choi, Kyu Bok

    2011-01-01

    We have hypothesized that non-dipper status and left ventricular hypertrophy (LVH) are associated with the development of chronic kidney disease (CKD) in non-diabetic hypertensive patients. This study included 102 patients with an estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2. Ambulatory blood pressure monitoring and echocardiography were performed at the beginning of the study, and the serum creatinine levels were followed. During the average follow-up period of 51 months, ...

  12. The sodium pump modulates the influence of I(Na) on [Ca2+]i transients in mouse ventricular myocytes.

    OpenAIRE

    Su, Z; Sugishita, K; Ritter, M; Li, F; Spitzer, K W; Barry, W H

    2001-01-01

    To investigate whether activity of the sarcolemmal Na pump modulates the influence of sodium current on excitation-contraction (E-C) coupling, we measured [Ca(2+)](i) transients (fluo-3) in single voltage-clamped mouse ventricular myocytes ([Na+](pip) = 15 or 0 mM) when the Na pump was activated (4.4 mM K(+)(o)) and during abrupt inhibition of the pump by exposure to 0 K with a rapid solution-switcher device. After induction of steady state [Ca2+](i) transients by conditioning voltage pulses ...

  13. Effects of acidosis and NO on nicorandil-activated KATP channels in guinea-pig ventricular myocytes

    OpenAIRE

    Moncada, Gustavo A; Kishi, Yukio; Numano, Fujio; Hiraoka, Masayasu; Sawanobori, Tohru

    2000-01-01

    Nicorandil is a hybrid compound of K+ channel opener and nitrate. We investigated a possible interaction of acidosis and nitric oxide (NO)-donors on the nicorandil-activated ATP-sensitive K+ channel (KATP) in guinea-pig ventricular myocytes using the patch-clamp technique.In whole-cell recordings, external application of 300 μM nicorandil activated KATP in the presence of 2 mM intracellular ATP concentration ([ATP]i) at external pH (pHo) 7.4, but the activated current was decreased by reducin...

  14. Prognostic significance of left ventricular diastolic dysfunction in patients with left ventricular hypertrophy and systemic hypertension (the LIFE Study)

    DEFF Research Database (Denmark)

    Wachtell, Kristian; Palmieri, Vittorio; Gerdts, Eva;

    2010-01-01

    Patients with hypertension and left ventricular (LV) hypertrophy commonly have impaired diastolic filling. However, it remains unknown whether changes in LV diastolic filling variables are associated with cardiovascular morbidity and mortality. In this study, 778 patients with hypertension...... valve flow pattern, this was not associated with reduced cardiovascular morbidity and mortality when adjusting for blood pressure, left atrial diameter, LV mass index, and treatment in time-varying Cox analyses. In contrast, lower in-treatment E/A ratios and shorter mitral valve deceleration times were...... associated with less risk for heart failure. Similarly, normal in-treatment transmitral flow pattern was strongly associated with less risk for heart failure (hazard ratio 0.22, 95% confidence interval 0.05 to 0.98, p = 0.048), even when taking in-treatment left atrial diameter and blood pressure...

  15. 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

  16. Accuracy of advanced versus strictly conventional 12-lead ECG for detection and screening of coronary artery disease, left ventricular hypertrophy and left ventricular systolic dysfunction

    OpenAIRE

    Warren Stafford G; Delgado Reynolds; Bauch Terry; Hayat Matthew J; Bungo Michael W; Rahman M; Vrtovec Bojan; Starc Vito; DePalma Jude L; Greco E; Feiveson Alan H; Kulecz Walter B; Schlegel Todd T; Núñez-Medina Tulio; Medina Rubén

    2010-01-01

    Abstract Background Resting conventional 12-lead ECG has low sensitivity for detection of coronary artery disease (CAD) and left ventricular hypertrophy (LVH) and low positive predictive value (PPV) for prediction of left ventricular systolic dysfunction (LVSD). We hypothesized that a ~5-min resting 12-lead advanced ECG test ("A-ECG") that combined results from both the advanced and conventional ECG could more accurately screen for these conditions than strictly conventional ECG. Methods Resu...

  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. Influence of Thromboxane A2 on the Regulation of Adenosine Triphosphate-Sensitive Potassium Channels in Mouse Ventricular Myocytes

    Science.gov (United States)

    Jeong, In Seok; Cho, Hwa Jin; Cho, Jeong Gwan; Kim, Sang Hyung; Na, Kook Joo

    2016-01-01

    Background and Objectives Adenosine triphosphate (ATP)-sensitive potassium (KATP) channels play an important role in myocardial protection. We examined the effects of thromboxane A2 on the regulation of KATP channel activity in single ventricular myocytes. Subjects and Methods Single ventricular myocytes were isolated from the hearts of adult Institute of Cancer Research (ICR) mice by enzymatic digestion. Single channel activity was recorded by excised inside-out and cell-attached patch clamp configurations at −60 mV holding potential during the perfusion of an ATP-free K-5 solution. Results In the excised inside-out patches, the thromboxane A2 analog, U46619, decreased the KATP channel activity in a dose-dependent manner; however, the thromboxane A2 receptor antagonist, SQ29548, did not significantly attenuate the inhibitory effect of U46619. In the cell-attached patches, U46619 inhibited dinitrophenol (DNP)-induced KATP channel activity in a dose-dependent manner, and SQ29548 attenuated the inhibitory effects of U46619 on DNP-induced KATP channel activity. Conclusion Thromboxane A2 may inhibit KATP channel activity, and may have a harmful effect on ischemic myocardium. PMID:27482267

  19. Isoform-specific regulation of the Na+-K+ pump by adenosine in guinea pig ventricular myocytes

    Institute of Scientific and Technical Information of China (English)

    Zhe ZHANG; Hui-cai GUO; Li-nan ZHANG; Yong-li WANG

    2009-01-01

    Aim: The present study investigated the effect of adenosine on Na+-K+ pumps in acutely isolated guinea pig (C, avia sp.) ven-tricular myocytes.Methods: The whole-cell, patch-damp technique was used to record the Na+-K+ pump current (Ip) in acutely isolated guinea pig ventricular myocytes.Results: Adenosine inhibited the high DHO-affinity pump current (Ih) in a concentration-dependent manner, which was blocked by the selective adenosine A1 receptor antagonist DPCPX and the general protein kinase C (PKC) antagonists stau-rosporine, GF 109203X or the specific δ isoform antagonist rottlerin. In addition, the inhibitory action of adenosine was mimicked by a selective A1 receptor agonist CCPA and a specific activator peptide of PKC-δ, PP114. In contrast, the selec-tive A2A receptor agonist CGS21680 and A3 receptor agonist Cl-IB-MECA did not affect lb. Application of the selective A2A receptor antagonist SCH58261 and A3 receptor antagonist MRS1191 also failed to block the effect of adenosine. Further-more, H89, a selective protein kinase A (PKA) antagonist, did not exert any effect on adenosine-induced Ih inhibition.Conclusion: The present study provides the electrophysiological evidence that adenosine can induce significant inhibition of Ih via adenosine A1 receptors and the PKC-δ isoform.

  20. Oxidative Stress Biomarkers and Left Ventricular Hypertrophy in Children with Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Dorota Drożdż

    2016-01-01

    Full Text Available Cardiovascular diseases remain the most frequent cause of morbidity and mortality in patients with chronic kidney disease (CKD. The aim of the study was to assess the association between oxidative stress biomarkers and cardiovascular risk factors and left ventricular hypertrophy in children with CKD. Material and Methods. The studied group consisted of 65 patients aged 1.4–18.6 (mean 11.2 years with stages 1 to 5 CKD. Serum oxidized low-density lipoprotein (oxLDL, protein carbonyl group, creatinine, cystatin C, albumin, lipids, high-sensitivity C-reactive protein, intercellular adhesion molecule-1, insulin, plasma renin activity, and aldosterone levels were measured. Patients were divided into groups depending on CKD stage. Anthropometric measurements, ambulatory blood pressure (BP measurements, and echocardiography with left ventricular mass (LVM calculation were performed. Results. Serum oxLDL strongly correlated with creatinine (R=0.246; p=0.048, cystatin C (R=0.346; p=0.006, total cholesterol (R=0.500; p<0.001, triglycerides (R=0.524; p<0.001, low-density lipoprotein concentrations (R=0.456; p<0.001, and 24 hour BP values of systolic (R=0.492; p=0.002, diastolic (R=0.515; p<0.001, and mean arterial pressure (R=0.537; p<0.001. A significant correlation between oxLDL levels and LVM z-scores (R=0.299; p=0.016 was found. Conclusions. Hypertension and dyslipidemia correlated with lipid oxidation in children with CKD. oxLDLs seem to be valuable markers of oxidative stress in CKD patients, correlating with left ventricular hypertrophy.

  1. Serum cystatin C concentration as an independent marker for hypertensive left ventricular hypertrophy

    Institute of Scientific and Technical Information of China (English)

    Xin Li; Hang Zhu; Peng Li; Qian Xin; Jie Liu; Wei Zhang; You-Hong Xing; Hao Xue

    2013-01-01

    Background Serum cystatin C levels can be used to predict morbidity and mortality in patients with cardiovascular disease. However, the clinical relevance of serum cystatin C levels in patients with hypertensive left ventricular hypertrophy (LVH) has rarely been investigated. We designed the present study to investigate whether serum cystatin C levels are associated with cardiac structural and functional alterations in hypertensive patients. Methods We enrolled 823 hypertensive patients and classified them into two groups:those with LVH (n=287) and those without LVH (n=536). All patients underwent echocardiography and serum cystatin C testing. We analyzed the relationship be-tween serum cystatin C levels and LVH. Results Serum cystatin C levels were higher in hypertensive patients with LVH than in those without LVH (P<0.05). Using linear correlation analysis, we found a positive correlation between serum cystatin C levels and interven-tricular septal thickness (r=0.247, P<0.01), posterior wall thickness (r=0.216, P<0.01), and left ventricular weight index (r=0.347, P<0.01). When analyzed by multiple linear regression, the positive correlations remained between serum cystatin C and interventricular septal thickness (β=0.167, P<0.05), posterior wall thickness (β=0.187, P<0.05), and left ventricular weight index (β=0.245, P<0.01). Con-clusion Serum cystatin C concentration is an independent marker for hypertensive LVH.

  2. 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....

  3. [An unusual case of transient ST-segment elevation during hypertensive crisis in a patient with left ventricular hypertrophy].

    Science.gov (United States)

    Cappelletti, Alberto; Maggio, Silvia; Maranta, Francesco; Mazzavillani, Monica; Margonato, Alberto; Camici, Paolo G

    2012-10-01

    We report the case of a 73-year-old patient with severe left ventricular hypertrophy presenting with acute ST-segment elevation mimicking acute myocardial infarction on ECG during a hypertensive crisis. Unexpectedly, emergency coronary angiography showed no evidence of coronary thrombosis or spasm. Electrocardiographic alterations gradually resolved after lowering blood pressure.

  4. Variants of tumor necrosis factor-induced protein 3 gene are associated with left ventricular hypertrophy in hypertensive patients

    Institute of Scientific and Technical Information of China (English)

    XUE Hao; WANG Shu-xia; WANG Xiao-jian; XIN Ying; WANG Hu; SONG Xiao-dong; SUN Kai; WANG Yi-bo; HUI Ru-tai

    2011-01-01

    Background Tumor necrosis factor-induced protein 3 (TNFAIP3) gene has been shown important in cardiac remodeling. The aim of the present study was to investigate whether the variants of TNFAIP3 gene are associated with left ventricular hypertrophy (LVH) in hypertensive patients.Methods Four representatives of all the other single nucleotide polymorphisms (SNPs) in TNFAIP3 gene were tested for association with hypertrophy in two independent hypertensive populations (n=2120 and n=324).Results We found that only the tag SNP (rs5029939) was consistently lower in the hypertensives with cardiac hypertrophy than in those without cardiac hypertrophy in the two study populations, indicating a protective effect on LVH (odds ratio (OR) (95% confidence interval (CI))0.58 (0.358-0.863), P=0.035; OR (95% CI)=0.477 (0.225-0.815), P<0.05,respectively). Multiple regression analyses confirmed that the patients with G allele of rs5029939 had less thickness in inter-ventricular septum, left ventricular posterior wall, relative wall thickness and left ventricular mass index than did those with CC allele in the hypertensive patients in both study populations (all P<0.01).Conclusion These findings indicate that the SNP (rs5029939) in the TNFAIP3 gene may serve as a novel protective genetic marker for the development of LVH in patients with hypertension.

  5. Correlation Study of PtfV1 with Heart-Qi Deficiency Syndrome in Patients with Hypertensive Left Ventricular Hypertrophy

    Institute of Scientific and Technical Information of China (English)

    杨传华; 陆峰

    2002-01-01

    @@ It is generally believed that the change of p-wave terminal force in lead V1 (PtfV1) is associated with the inner diameter of left atrium, left ventricular compliance,and ventricular diastolic function. The increase of negative value of PtfV1 in essential hypertensive (EH) patients with left ventricular hypertrophy (LVH) indicates the cardiac function may be damaged. In order to explore the relationship between Heart-Qi Deficiency Syndrome (HQDS) of TCM and PtfV1 level in hypertensive LVH patients, correlation analysis of scores of Heart-Qi Deficiency Syndrome and negative value of PtfV1 was made by the authors.

  6. Two functionally different Na/K pumps in cardiac ventricular myocytes

    OpenAIRE

    1995-01-01

    The whole-cell patch-clamp technique was used to voltage clamp acutely isolated myocytes at -60 mV and study effects of ionic environment on Na/K pump activity. In quiescent guinea pig myocytes, normal intracellular Na+ is approximately 6 mM, which gives a total pump current of 0.25 +/- 0.09 pA/pF, and an inward background sodium current of 0.75 +/- 0.26 pA/pF. The average capacitance of a cell is 189 +/- 61 pF. Our main conclusion is the total Na/K pump current comprises currents from two di...

  7. Inhibitory Effect of Cinobufagin on L-Type Ca2+ Currents, Contractility, and Ca2+ Homeostasis of Isolated Adult Rat Ventricular Myocytes

    Directory of Open Access Journals (Sweden)

    Pinya Li

    2014-01-01

    Full Text Available Cinobufagin (CBG, a major bioactive ingredient of the bufanolide steroid compounds of Chan Su, has been widely used to treat coronary heart disease. At present, the effect of CBG on the L-type Ca2+ current (ICa-L of ventricular myocytes remains undefined. The aim of the present study was to characterize the effect of CBG on intracellular Ca2+ ([Ca2+]i handling and cell contractility in rat ventricular myocytes. CBG was investigated by determining its influence on ICa-L, Ca2+ transient, and contractility in rat ventricular myocytes using the whole-cell patch-clamp technique and video-based edge-detection and dual-excitation fluorescence photomultiplier systems. The dose of CBG (10−8 M decreased the maximal inhibition of CBG by 47.93%. CBG reduced ICa-L in a concentration-dependent manner with an IC50 of 4 × 10−10 M, upshifted the current-voltage curve of ICa-L, and shifted the activation and inactivation curves of ICa-L leftward. Moreover, CBG diminished the amplitude of the cell shortening and Ca2+ transients with a decrease in the time to peak (Tp and the time to 50% of the baseline (Tr. CBG inhibited L-type Ca2+ channels, and reduced [Ca2+]i and contractility in adult rat ventricular myocytes. These findings contribute to the understanding of the cardioprotective efficacy of CBG.

  8. Beneficial effect of isradipine on the development of left ventricular hypertrophy in mild hypertension

    DEFF Research Database (Denmark)

    Mehlsen, J; Fornitz, Gitte Gleerup; Haedersdal, C;

    1993-01-01

    with mild essential hypertension were entered into a double-blind crossover study. Examinations were carried out after 2 weeks of placebo run-in, and after 6 and 12 months of active treatment. Mean resting blood pressure was reduced from 115 +/- 12 mm Hg to 106 +/- 12 mm Hg with atenolol, and to 107 +/- 8...... mm Hg with isradipine. The increase in the product of heart rate times blood pressure was significantly greater during isradipine treatment, as was the maximum exercise capacity. Left ventricular mass was increased from 228 +/- 36 g to 305 +/- 68 g with atenolol whereas it remained unchanged......The objective of this study was to analyze the long-term hemodynamic effects of the calcium antagonist isradipine in mild hypertension compared with those of the beta 1-selective adrenoceptor antagonist atenolol, focusing in particular on the development of cardiac hypertrophy. Ten male patients...

  9. Electrocardiographic signs of left ventricular hypertrophy in obese patients: what criteria should be used?

    Science.gov (United States)

    Germano, Giuseppe

    2015-03-01

    Overweight and obesity are estimated at high prevalence and progression in adults; they are major contributors to chronic diseases and a major public health challenge. An obese habitus changes body-surface electrocardiograms (ECGs). Obesity is responsible for geometric changes to the heart and torso, as well as for deleterious electrophysiological changes of the heart. Common ECG changes, reduced voltages in the precordial leads, and axis deviation have made the search for left ventricular hypertrophy (LVH) even more problematic. Identification of LVH by ECG is difficult and time consuming but ECG is fundamental to reveal abnormalities of clinical relevance associated with obesity. The QTc dispersion assessment and the comparison with magnetic resonance imaging are the frontiers to clarify the connection between ECG LVH signs and overweight and obesity. PMID:25091550

  10. 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

    or more metabolic abnormalities (MetAb, including obesity, high plasma glucose without diabetes, low HDL-cholesterol) in addition to hypertension were associated to levels of ECG LVH reduction comparable to that obtained in hypertensive subjects without or with only one additional metabolic abnormality......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...... of metabolic abnormalities resembling phenotypes of metabolic syndrome are related to greater initial ECG LVH in hypertensive patients with value of blood pressure similar to individuals without metabolic abnormalities, and are associated with less reduction of ECG LVH during antihypertensive therapy...

  11. Acetyl-lysine erasers and readers in the control of pulmonary hypertension and right ventricular hypertrophy

    Science.gov (United States)

    Stratton, Matthew S.; McKinsey, Timothy A.

    2016-01-01

    Acetylation of lysine residues within nucleosomal histone tails provides a crucial mechanism for epigenetic control of gene expression. Acetyl groups are coupled to lysine residues by histone acetyltransferases (HATs) and removed by histone deacetylases (HDACs), which are also commonly referred to as “writers” and “erasers”, respectively. In addition to altering the electrostatic properties of histones, lysine acetylation often creates docking sites for bromodomain-containing “reader” proteins. This review focuses on epigenetic control of pulmonary hypertension (PH) and associated right ventricular (RV) cardiac hypertrophy and failure. Effects of small molecule HDAC inhibitors in pre-clinical models of PH are highlighted. Furthermore, we describe the recently discovered role of bromodomain and extraterminal (BET) reader proteins in the control of cardiac hypertrophy, and provide evidence suggesting that one member of this family, BRD4, contributes to the pathogenesis of RV failure. Together, the data suggest intriguing potential for pharmacological epigenetic therapies for the treatment of PH and right-sided heart failure. PMID:25707943

  12. Rapamycin attenuates hypoxia-induced pulmonary vascular remodeling and right ventricular hypertrophy in mice

    Directory of Open Access Journals (Sweden)

    Tillmanns Harald H

    2007-02-01

    Full Text Available Abstract Background Chronic hypoxia induces pulmonary arterial hypertension (PAH. Smooth muscle cell (SMC proliferation and hypertrophy are important contributors to the remodeling that occurs in chronic hypoxic pulmonary vasculature. We hypothesized that rapamycin (RAPA, a potent cell cycle inhibitor, prevents pulmonary hypertension in chronic hypoxic mice. Methods Mice were held either at normoxia (N; 21% O2 or at hypobaric hypoxia (H; 0.5 atm; ~10% O2. RAPA-treated animals (3 mg/kg*d, i.p. were compared to animals injected with vehicle alone. Proliferative activity within the pulmonary arteries was quantified by staining for Ki67 (positive nuclei/vessel and media area was quantified by computer-aided planimetry after immune-labeling for α-smooth muscle actin (pixel/vessel. The ratio of right ventricle to left ventricle plus septum (RV/[LV+S] was used to determine right ventricular hypertrophy. Results Proliferative activity increased by 34% at day 4 in mice held under H (median: 0.38 compared to N (median: 0.28, p = 0.028 which was completely blocked by RAPA (median HO+RAPA: 0.23, p = 0.003. H-induced proliferation had leveled off within 3 weeks. At this time point media area had, however, increased by 53% from 91 (N to 139 (H, p Conclusion Therapy with rapamycin may represent a new strategy for the treatment of pulmonary hypertension.

  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. Incidence of sudden cardiac death associated with coronary artery occlusion in dogs with hypertension and left ventricular hypertrophy is reduced by chronic beta-adrenergic blockade.

    Science.gov (United States)

    Dellsperger, K C; Martins, J B; Clothier, J L; Marcus, M L

    1990-09-01

    Because beta-adrenergic blockade has as one of its many effects altered electrophysiological abnormalities after dogs with left ventricular hypertrophy have been subjected to coronary occlusion, we tested the hypothesis that metoprolol (200-400 mg/day) would reduce mortality rates in dogs with one-kidney, one clip left ventricular hypertrophy while a similar reduction in arterial pressure with enalapril (20-40 mg/day) would not. Dogs with left ventricular hypertrophy were given metoprolol or enalapril for 5-7 days before a 3-hour coronary occlusion. Infarct size and risk area were measured with triphenyltetrazolium chloride stain and barium angiography, respectively. For control (n = 15), left ventricular hypertrophy (n = 17), left ventricular hypertrophy plus metoprolol (n = 12), and left ventricular hypertrophy plus enalapril (n = 15) groups, mean arterial pressure, ratio of infarct size to risk area, and dogs experiencing sudden death were 110 +/- 4, 142 +/- 4, 121 +/- 7, and 120 +/- 3 mm Hg; 44 +/- 5%, 65 +/- 5%, 44 +/- 7%, and 30 +/- 4%; and 27%, 65%, 17%, and 53%, respectively. Thus, the excessive increase in early mortality occurring when dogs with hypertension and left ventricular hypertrophy undergo coronary occlusion is interrupted with beta-blockade, possibly via electrophysiological effects rather than by changes in arterial pressure or infarct size. PMID:1975521

  15. Left Ventricular Hypertrophy in Chronic Kidney Disease Patients: From Pathophysiology to Treatment.

    Science.gov (United States)

    Di Lullo, Luca; Gorini, Antonio; Russo, Domenico; Santoboni, Alberto; Ronco, Claudio

    2015-10-01

    Cardiovascular diseases represent the main causes of morbidity and mortality in patients with chronic kidney disease (CKD). According to a well-established classification, cardiovascular involvement in CKD can be set in the context of cardiorenal syndrome type 4. Left ventricular hypertrophy (LVH) represents a key feature to provide an accurate picture of systolic-diastolic left heart involvement in CKD patients. Cardiovascular involvement is present in about 80% of prevalent hemodialysis patients, and it is evident in CKD patients since stage IIIb-IV renal disease (according to the K/DOQI CKD classification). According to the definition of cardiorenal syndrome type 4, kidney disease is detected before the development of heart failure, although timing of the diagnosis is not always possible. The evaluation of LVH is a bit heterogeneous, and few standard imaging methods can provide the accuracy of either CT- or MRI-derived left ventricular mass. Key principles in the treatment of LVH in CKD patients are mainly based on anemia and blood pressure control, together with the management of secondary hyperparathyroidism and sudden cardiac death prevention. This review is mainly focused on the clinical aspects of CKD-related LVH to provide practical guidelines both for cardiologists and nephrologists in the daily clinical approach to CKD patients. PMID:26648942

  16. Does the ADMA/DDAH/NO pathway modulate early regression of left ventricular hypertrophy with esmolol?

    Science.gov (United States)

    Quintana-Villamandos, Begoña; Delgado-Baeza, Emilio

    2016-02-01

    Hypertensive left ventricular hypertrophy (LVH) is a maladaptive response to chronic pressure overload and a strong independent risk factor for cardiovascular disease. Regression of LVH is associated with improved prognosis. Regression of LVH with antihypertensive therapy (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, calcium channel blockers, and diuretics) has been reported, although only after long-term treatment. Asymmetrical dimethylarginine (ADMA), the most potent endogenous NO synthase inhibitor, is emerging as an important cardiovascular risk factor in patients with arterial hypertension and LVH, and dimethylarginine dimethylaminohydrolase (DDAH) is the mechanism that most frequently leads to accumulation of ADMA (plasma ADMA is cleared in small part by renal excretion, although the bulk of ADMA is degraded by DDAH). Left ventricular mass is strongly modulated by the NO system. As an important inhibitor of the bioavailability of NO, ADMA is an underlying mechanism of LVH. Beta-blockers can induce regression of LVH and reduced plasma ADMA levels. Oxidative stress is increased in patients with LVH, and this in turn increases generation of ADMA. In a previous preclinical study of spontaneously hypertensive rats, we found that short-term treatment (48 h) with esmolol reverses early LVH, increases the bioavailability of NO, and improves antioxidant status in plasma. Therefore, we propose that the ADMA/DDAH/NO pathway could modulate early regression of LVH with esmolol. PMID:26826640

  17. Effects of β2-Adrenergic Antagonist on Cytosolic Ca2+ in Ventricular Myocytes from Infarcted Rat Heart

    Institute of Scientific and Technical Information of China (English)

    Yang Hui; Wu Wei; Zeng Chong; Deng Chunyu; Fang Chang; Chen Shanming

    2006-01-01

    Objectives To investigate the effects of β2-adrenergic antagonist on cytosolic Ca2 +([Ca2+]i) in ventricular myocytes from infarcted rat heart. Methods A ligature was placed around left anterior descending coronary artery of rat hearts. Rats in the control group were sham-operated.Cardiomyocytes were dissociated at two, four, eight weeks after myocardial infarction (MI) and [Ca2+]i was measured via fura-2 fluorescence. The response of cardiomyocytes to isoproterenol in presence or absenceof beta1-adrenergic antagonist atenolol, beta2-adrenergic antagonist ICI118, 551 or non-selective β1,2- adrenergic antagonists propranolol was examined.Results The followings were found that ICI11 8, 551 had no significant effects on the rise of [Ca2+]i induced by isoproterenol in normal ventricular myocytes (P >0.05), ICI118, 551 only significantly attenuated the rise of [Ca2+]i induced by isoproterenol at four weeks and eight weeks after MI (24.5% ±5.7% vs 57.8% ±13.2%, P< 0.01; 12.2%±7.9% vs 44.6%±11.3%, P<0.01). Atenolol had suppressive effects only in the control group and the post-MI group of two weeks (P<0.05), and propranolol had suppressive effects in the control and all the three post-MI groups (P<0.01).Conclusions Beta2-adrenergic antagonist ICI118,551 may exert negative effects on Ca2+ overload initiated by sympathetic stimulation after MI.

  18. Effects of AMP579 and adenosine on L-type Ca2+ current in isolated rat ventricular myocytes

    Institute of Scientific and Technical Information of China (English)

    Xiong WANG; Bo-wei WU; Dong-mei WU

    2005-01-01

    Aim: To compare the effects of AMP579 and adenosine on L-type Ca2+ current (ICa- L) in rat ventricular myocytes and explore the mechanism by which AMP579 acts on ICa-L. Methods: ICa-L was recorded by patch-clamp technique in whole-cell configuration. Results: Adenosine (10 nmol/L to 50 μmol/L) showed no effect on basal ICa- L, but it inhibited the ICa-L induced by isoproterenol 10 nmol/L in a concen tration-dependent manner with the IC50 of 13.06 μmol/L. Similar to adenosine,AMP579 also showed an inhibitory effect on the ICa-L induced by isoproterenol.AMP579 and adenosine (both in 10 μmol/L) suppressed isoproterenol-induced ICa-L by 11.1% and 5.2%, respectively. In addition, AMP579 had a direct inhibitory effect on basal ICa-L in a concentration-dependent manner with IC50 (1.17 μmol/L).PD116948 (30 μmol/L), an adenosine A1 receptor blocker, showed no action on the inhibitory effect of AMP579 on basal ICa-L. However, GF109203X (0.4 μmol/L), a special protein kinase C (PKC) blocker, could abolish the inhibitory effect of AMP579 on basal ICa-L. So the inhibitory effect of AMP579 on basal ICa-L was induced through activating PKC, but not linked to adenosine A1 receptor. Conclusion:AMP579 shows a stronger inhibitory effect than adenosine on the ICa-L induced by isoproterenol. AMP579 also has a strong inhibitory effect on basal ICa-L in rat ventricular myocytes. Activation of PKC is involved in the inhibitory effect of AMP579 on basal ICa-L at downstream-mechanism.

  19. Effects of Ginkgolide B on action potential and calcium,potassium current in guinea pig ventricular myocytes

    Institute of Scientific and Technical Information of China (English)

    Xiao-yan QI; Zhi-xiong ZHANG; You-qiu XU

    2004-01-01

    AIM: To investigate the effect of Ginkgolide B (GB) on action potential (AP), delayed rectifier potassium current (IK), and L-type calcium current (ICa-L) in guinea pig ventricular myocytes. METHODS: Single ventricular myocytes were isolated by an enzymatic dissociation method. AP, IK, ICa-L were recorded by whole-cell patch-clamp technique in either current or voltage clamp mode. RESULTS: GB shortened APD in a concentration-dependent manner. GB 0.1, 1, and 10 μmol/L shortened APD50 by 7.9 % (n=5, P>0.05), 18.4 % (n=5, P<0.01), and 28.9 % (n=6, P<0.01), respectively; APD90 by 12.4 % (n=5, P>0.05), 17.6 % (n=5, P<0.01), 26.4 % (n=5, P<0.01),respectively. GB increased IK in a concentration-dependent manner. GB 0.1, 1, and l0 μmol/L increased IK by 20.1% (n=6, P<0.05), 43.1% (n=6, P<0.01), 55.6 % (n=6, P<0.05); increased IKtail by 10.7 % (n=6, P<0.05),25.1% (n=6, P<0.05), and 37.7 % (n=6, P<0.05), respectively at testing potential of +50 mV and shift the I-V curve of Ik upward. But GB had no significant effect on ICa-L at above concentrations. CONCLUSION: GB significantly shortened APD in a concentration-dependent manner which mainly due to increase of IK.

  20. Effects of the venom of the spider Ornithoctonus hainana on neonatal rat ventricular myocytes cellular and ionic electrophysiology.

    Science.gov (United States)

    Zhang, Yiya; Liu, Jinyan; Liu, Zhonghua; Wang, Meichi; Wang, Jing; Lu, Shanshan; Zhu, Li; Zeng, Xiongzhi; Liang, Songping

    2014-09-01

    Cardiac ion channels are membrane-spanning proteins that allow the passive movement of ions across the cell membrane along its electrochemical gradient, which regulates the resting membrane potential as well as the shape and duration of the cardiac action potential. Additionally, they have been recognized as potential targets for the actions of neurotransmitters, hormones and drugs of cardiac diseases. Spider venoms contain high abundant of toxins that target diverse ion channels and have been considered as a potential resource of new constituents with specific pharmacological properties. However, few peptides from spider venoms were detected as cardiac channel antagonists. In order to explore the effects of the venom of Ornithoctonus hainana on the action potential and ionic currents of neonatal rat ventricular myocytes (NRVMs), whole cell patch clamp technique was used to record action potential duration (APD), sodium current (INa), L calcium current (ICaL), rapidly activating and inactivating transient outward currents (Ito1), rapid (IKr) and slow (IKs) components of the delayed rectifier currents and the inward rectifier currents (IK1). Our results showed that 100 μg/mL venom obviously prolonged APDs. Significantly, the venom could inhibit INa and ICaL effectively, while no evident inhibitory effects on cardiac K(+) channels (Ito1, Iks, Ikr and Ik1) were observed, suggesting that the venom represented a multifaceted pharmacological profile. The effect of venom on Na(+) and Ca(2+) currents of ventricular myocytes revealed that the hainan venom as a rich resource of cardiac channel antagonists might be valuable tools for the investigation of both channels and drug development.

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

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    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.

  2. Nongenomic steroid action: Inhibiting effects on cell-to-cell communication between rat ventricular myocytes

    OpenAIRE

    Verrecchia, Franck; Sarrouilhe, Denis; Hervé, Jean-Claude

    2001-01-01

    Numerous steroids are now believed to possess rapid membrane effects independent of the classical gene activation pathways and are potent modulators of membrane proteins, including voltage-and ligand-operated channels. The effects of steroids on the functional state of the intercellular channels clustered in gap junctions were compared by estimation of either the permeability for a fluorescent dye or the electrical conductance in cardiac myocytes of newborn rat. At 25 μM, the esters of 17β-es...

  3. Mitogen-activated protein kinase signal pathways play an important role in right ventricular hypertrophy of tetralogy of Fallot

    Institute of Scientific and Technical Information of China (English)

    ZHANG Hong-shan; WU Qing-yu; XU Ming; ZHOU Yu-xiang; SHUI Chao-xiang

    2012-01-01

    Background Tetralogy of Fallot (TOF) is the most common malformation of children with an incidence of approximately 10% of congenital heart disease patients.There can be a wide spectrum to the severity of the anatomic defects,which include ventricular septal defect,aortic override,right ventricular outflow tract obstruction,and right ventricular hypertrophy.We examined the relationship between right ventricular hypertrophy in patients with TOF and the gene expression of factors in the mitogen-activated protein kinase (MAPK) signal pathway.Methods To gain insight into the characteristic gene(s) involved in molecular mechanisms of right ventricular hypertrophy in TOF,differential mRNA and micro RNA expression profiles were assessed using expression-based micro array technology on right ventricular biopsies from young TOF patients who underwent primary correction and on normal heart tissue.We then analyzed the gene expression of the MAPK signal pathway using reverse transcription-polymerase chain reaction (RT-PCR) in normals and TOF patients.Results Using the micro RNA chip V3.0 and human whole genome oligonucleotide microarray V1.0 to detect the gene expression,we found 1068 genes showing altered expression of at least two-fold in TOF patients compared to the normal hearts,and 47 micro RNAs that showed a significant difference of at least two-fold in TOF patients.We then analyzed these mRNAs and micro RNAs by target gene predicting software Microcosm Targets version 5.0,and determined those mRNA highly relevant to the right ventricular hypertrophy by RT-PCR method.There were obvious differences in the gene expression of factors in the MAPK signal pathway when using RT-PCR,which was consistent to the results of the cDNA microarray.Conclusion The upregulation of genes in the MAPK signal pathway may be the key events that contribute to right ventricular hypertroohv and stunted angiogenesis in patients with TOF.

  4. 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...

  5. Spiral-wave dynamics in a mathematical model of human ventricular tissue with myocytes and fibroblasts.

    Directory of Open Access Journals (Sweden)

    Alok Ranjan Nayak

    Full Text Available Cardiac fibroblasts, when coupled functionally with myocytes, can modulate the electrophysiological properties of cardiac tissue. We present systematic numerical studies of such modulation of electrophysiological properties in mathematical models for (a single myocyte-fibroblast (MF units and (b two-dimensional (2D arrays of such units; our models build on earlier ones and allow for zero-, one-, and two-sided MF couplings. Our studies of MF units elucidate the dependence of the action-potential (AP morphology on parameters such as [Formula: see text], the fibroblast resting-membrane potential, the fibroblast conductance [Formula: see text], and the MF gap-junctional coupling [Formula: see text]. Furthermore, we find that our MF composite can show autorhythmic and oscillatory behaviors in addition to an excitable response. Our 2D studies use (a both homogeneous and inhomogeneous distributions of fibroblasts, (b various ranges for parameters such as [Formula: see text], and [Formula: see text], and (c intercellular couplings that can be zero-sided, one-sided, and two-sided connections of fibroblasts with myocytes. We show, in particular, that the plane-wave conduction velocity [Formula: see text] decreases as a function of [Formula: see text], for zero-sided and one-sided couplings; however, for two-sided coupling, [Formula: see text] decreases initially and then increases as a function of [Formula: see text], and, eventually, we observe that conduction failure occurs for low values of [Formula: see text]. In our homogeneous studies, we find that the rotation speed and stability of a spiral wave can be controlled either by controlling [Formula: see text] or [Formula: see text]. Our studies with fibroblast inhomogeneities show that a spiral wave can get anchored to a local fibroblast inhomogeneity. We also study the efficacy of a low-amplitude control scheme, which has been suggested for the control of spiral-wave turbulence in mathematical models

  6. Association of Left Atrial Volume With Mortality Among ESRD Patients With Left Ventricular Hypertrophy Referred for Kidney Transplantation

    OpenAIRE

    Patel, Rajan K.; Jardine, Alan G.M.; Patrick B. Mark; Cunningham, Anthony F.; Steedman, Tracey; Powell, Joanna R.; McQuarrie, Emily P.; Stevens, Kathryn K; Dargie, Henry J; Jardine, Alan G

    2010-01-01

    Background Left ventricular hypertrophy (LVH) is common in patients with end-stage renal disease (ESRD) and an independent risk factor for premature cardiovascular death. Left atrial volume (LAV), measured using echocardiography, predicts death in patients with ESRD. Cardiovascular magnetic resonance (CMR) imaging is a volume-independent method of accurately assessing cardiac structure and function in patients with ESRD. Study Design Single-center prospective observational study to assess the...

  7. Changes in electrocardiographic left ventricular hypertrophy and risk of major cardiovascular events in isolated systolic hypertension: the LIFE study

    DEFF Research Database (Denmark)

    Larstorp, A C K; Okin, P M; Devereux, R B;

    2011-01-01

    The predictive value of changes in the severity of electrocardiographic left ventricular hypertrophy (ECG-LVH) during antihypertensive therapy remains unclear in isolated systolic hypertension (ISH). In a Losartan Intervention For Endpoint reduction in hypertension substudy, we included 1320...... patients aged 54–83 years with systolic blood pressure (BP) of 160–200¿mm¿Hg, diastolic BP losartan- or atenolol-based treatment with a mean follow-up of 4.8 years. The composite end point...

  8. Lack of Association Between Common Endothelial Nitric Oxide Synthase Gene Haplotypes and Left Ventricular Hypertrophy in Hypertension

    OpenAIRE

    Georgios D. Kitsios; Stefanidis, Ioannis; Zintzaras, Elias

    2010-01-01

    The endothelial nitric oxide synthase (NOS3) gene has been implicated in the pathogenesis of hypertension-related left ventricular hypertrophy (LVH). Candidate-gene studies have examined the role of NOS3 variation, but reported results are inconsistent. In this study, we investigated the association of three clinically relevant polymorphisms (promoter T786C, intronic 4a/b, and nonsynonymous G894T) in a case–control sample of 230 ethnically homogeneous (Caucasians) patients with essential hype...

  9. Genetic variation in angiotensin-converting enzyme 2 gene is associated with extent of left ventricular hypertrophy in hypertrophic cardiomyopathy

    OpenAIRE

    van der Merwe, Lize; Cloete, Ruben; Revera, Miriam; Heradien, Marshall; Goosen, Althea; Corfield, Valerie A.; Paul A Brink; Moolman-Smook, Johanna C

    2008-01-01

    Hypertrophic cardiomyopathy, a common, inherited cardiac muscle disease, is primarily caused by mutations in sarcomeric protein-encoding genes and is characterized by overgrowth of ventricular muscle that is highly variable in extent and location. This variability has been partially attributed to locus and allelic heterogeneity of the disease-causing gene, but other factors, including unknown genetic factors, also modulate the extent of hypertrophy that develops in response to the defective s...

  10. QRS Voltage-Duration Product in the Identification of Left Ventricular Hypertrophy in Spontaneously Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Bacharova Ljuba

    2002-01-01

    Full Text Available OBJECTIVE - Evaluation of the performance of the QRS voltage-duration product (VDP for detection of left ventricular hypertrophy (LVH in spontaneously hypertensive rats (SHR. METHODS - Orthogonal electrocardiograms (ECG were recorded in male SHR at the age of 12 and 20 weeks, when systolic blood pressure (sBP reached the average values of 165±3 mmHg and 195±12 mmHg, respectively. Age- and sex- matched normotensive Wistar Kyoto (WKY rats were used as controls. VDP was calculated as a product of maximum QRS spatial vector magnitude and QRS duration. Left ventricular mass (LVM was weighed after rats were sacrificed. RESULTS - LVM in SHR at 12 and 20 weeks of age (0.86±0.05 g and 1.05±0.07 g, respectively was significantly higher as compared with that in WKY (0.65±0.07 g and 0.70±0.02 g. The increase in LVM closely correlated with the sBP increase. VDP did not reflect the increase in LVM in SHR. VDP was lower in SHR as compared with that in WKY, and the difference was significant at the age of 20 weeks (18.2mVms compared with 10.7mVms, p<0.01. On the contrary, a significant increase in the VDP was observed in the control WKY at the age of 20 weeks without changes in LVM. The changes in VDP were influenced mainly by the changes in QRSmax. CONCLUSION - LVM was not the major determinant of QRS voltage changes and consequently of the VDP. These data point to the importance of the nonspatial determinants of the recorded QRS voltage in terms of the solid angle theory.

  11. Computational modeling and numerical methods for spatiotemporal calcium cycling in ventricular myocytes

    Directory of Open Access Journals (Sweden)

    Michael eNivala

    2012-05-01

    Full Text Available Intracellular calcium (Ca cycling dynamics in cardiac myocytes is regulated by a complex network of spatially distributed organelles, such as sarcoplasmic reticulum (SR, mitochondria, and myofibrils. In this study, we present a mathematical model of intracellular Ca cycling and numerical and computational methods for computer simulations. The model consists of a coupled Ca release unit (CRU network, which includes a SR domain and a myoplasm domain. Each CRU contains 10 L-type Ca channels and 100 ryanodine receptor channels, with individual channels simulated stochastically using a varient of Gillespie’s method, modified here to handle time-dependent transition rates. Both the SR domain and the myoplasm domain in each CRU are modeled by 5x5x5 voxels to maintain proper Ca diffusion. Advanced numerical algorithms implemented on graphical processing units were used for fast computational simulations. For a myocyte containing 100x20x10 CRUs, a one-second heart time simulation takes about 10 minutes of machine time on a single NVIDIA Tesla C2050. Examples of simulated Ca cycling dynamics, such as Ca sparks, Ca waves, and Ca alternans, are shown.

  12. Role of SERCA and the sarcoplasmic reticulum calcium content on calcium waves propagation in rat ventricular myocytes.

    Science.gov (United States)

    Salazar-Cantú, Ayleen; Pérez-Treviño, Perla; Montalvo-Parra, Dolores; Balderas-Villalobos, Jaime; Gómez-Víquez, Norma L; García, Noemí; Altamirano, Julio

    2016-08-15

    In Ca(2+)-overloaded ventricular myocytes, SERCA is crucial to steadily achieve the critical sarcoplasmic reticulum (SR) Ca(2+) level to trigger and sustain Ca(2+) waves, that propagate at constant rate (ʋwave). High luminal Ca(2+) sensitizes RyR2, thereby increasing Ca(2+) sparks frequency, and the larger RyR2-mediated SR Ca(2+) flux (dF/dt) sequentially activates adjacent RyR2 clusters. Recently, it was proposed that rapid SERCA Ca(2+) reuptake, ahead of the wave front, further sensitizes RyR2, increasing ʋwave. Nevertheless, this is controversial because rapid cytosolic Ca(2+) removal could instead impair RyR2 activation. We assessed whether rapid SR Ca(2+) uptake enhances ʋwave by changing SERCA activity (ҡDecay) over a large range (∼175%). We used normal (Ctrl) and hyperthyroid rat (HT; reduced phospholamban by ∼80%) myocytes treated with thapsigargin or isoproterenol (ISO). We found that ʋwave and dF/dt had a non-linear dependency with ҡDecay, while Ca(2+) waves amplitude was largely unaffected. Furthermore, SR Ca(2+) also showed a non-linear dependency with ҡDecay, however, the relationships ʋwave vs. SR Ca(2+) and ʋwave vs. dF/dt were linear, suggesting that high steady state SR Ca(2+) determines ʋwave, while rapid SERCA Ca(2+) uptake does not. Finally, ISO did not increase ʋwave in HT cells, therefore, ISO-enhanced ʋwave in Ctrl depended on high SR Ca(2+). PMID:27242324

  13. Rare Copy Number Variants Identified Suggest the Regulating Pathways in Hypertension-Related Left Ventricular Hypertrophy.

    Directory of Open Access Journals (Sweden)

    Hoh Boon-Peng

    Full Text Available Left ventricular hypertrophy (LVH is an independent risk factor for cardiovascular morbidity and mortality, and a powerful predictor of adverse cardiovascular outcomes in the hypertensive patients. It has complex multifactorial and polygenic basis for its pathogenesis. We hypothesized that rare copy number variants (CNVs contribute to the LVH pathogenesis in hypertensive patients. Copy number variants (CNV were identified in 258 hypertensive patients, 95 of whom had LVH, after genotyping with a high resolution SNP array. Following stringent filtering criteria, we identified 208 rare, or private CNVs that were only present in our patients with hypertension related LVH. Preliminary findings from Gene Ontology and pathway analysis of this study confirmed the involvement of the genes known to be functionally involved in cardiac development and phenotypes, in line with previously reported transcriptomic studies. Network enrichment analyses suggested that the gene-set was, directly or indirectly, involved in the transcription factors regulating the "foetal cardiac gene programme" which triggered the hypertrophic cascade, confirming previous reports. These findings suggest that multiple, individually rare copy number variants altering genes may contribute to the pathogenesis of hypertension-related LVH. In summary, we have provided further supporting evidence that rare CNV could potentially impact this common and complex disease susceptibility with lower heritability.

  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. Rare Copy Number Variants Identified Suggest the Regulating Pathways in Hypertension-Related Left Ventricular Hypertrophy

    Science.gov (United States)

    Marshall, Christian R.; Majid, Fadhlina; Danuri, Norlaila; Basir, Fashieha; Thiruvahindrapuram, Bhooma; Scherer, Stephen W.; Yusoff, Khalid

    2016-01-01

    Left ventricular hypertrophy (LVH) is an independent risk factor for cardiovascular morbidity and mortality, and a powerful predictor of adverse cardiovascular outcomes in the hypertensive patients. It has complex multifactorial and polygenic basis for its pathogenesis. We hypothesized that rare copy number variants (CNVs) contribute to the LVH pathogenesis in hypertensive patients. Copy number variants (CNV) were identified in 258 hypertensive patients, 95 of whom had LVH, after genotyping with a high resolution SNP array. Following stringent filtering criteria, we identified 208 rare, or private CNVs that were only present in our patients with hypertension related LVH. Preliminary findings from Gene Ontology and pathway analysis of this study confirmed the involvement of the genes known to be functionally involved in cardiac development and phenotypes, in line with previously reported transcriptomic studies. Network enrichment analyses suggested that the gene-set was, directly or indirectly, involved in the transcription factors regulating the “foetal cardiac gene programme” which triggered the hypertrophic cascade, confirming previous reports. These findings suggest that multiple, individually rare copy number variants altering genes may contribute to the pathogenesis of hypertension-related LVH. In summary, we have provided further supporting evidence that rare CNV could potentially impact this common and complex disease susceptibility with lower heritability. PMID:26930585

  16. Tribulosin suppresses apoptosis via PKC epsilon and ERK1/2 signaling pathway during hypoxia/reoxygenation in neonatal rat ventricular cardiac myocytes.

    Science.gov (United States)

    Zhang, Shuang; Li, Hong; Yang, Shi-Jie

    2011-12-01

    Tribulosin (tigogenin 3-O-β-D-xylopyranosyl(1-2)-[β-D-xylopyranosyl (1-3)]-β-D-glucopyranosyl (1-4)-[a-L-rhamnopyranosyl(1-2)]-β-D-galactopyranoside), a component of gross saponins of Tribulus terrestris, has been shown to produce cytoprotective effects in heart. Yet, the precise mechanisms are not fully understood. We examined the mechanisms of tribulosin on myocardial protection. Ventricular myocytes were isolated from the heart of neonatal rats and were exposed to 3 h of hypoxia followed by 2 h reoxygenation. Apoptosis was induced by hypoxia/reoxygenation (H/R), and the expression of protein kinase C epsilon (PKCϵ) and extracellular signal-regulated kinase 1 and 2 (ERK1/2) in cultured neonatal rat cardiac myocytes was detected. The results indicated that treatment with tribulosin in the culture medium protected cardiac myocytes against apoptosis induced by H/R. PKCϵ and ERK1/2 expression increased after pretreated with tribulosin. In the presence of PKCϵ inhibitor co-treated with tribulosin, the expression of ERK1/2 was decreased in H/R cardiac myocytes. While preconditioned with PD98059, ERK1/2 inhibitor, no effects on the expression of PKCϵ were detected. Tribulosin has protective effects on cardiac myocytes against apoptosis induced by H/R injury via PKCϵ and ERK1/2 signaling pathway. PMID:22115037

  17. Enhancement of contraction and L-type Ca(2+) current by murrayafoline-A via protein kinase C in rat ventricular myocytes.

    Science.gov (United States)

    Chidipi, Bojjibabu; Son, Min-Jeong; Kim, Joon-Chul; Lee, Jeong Hyun; Toan, Tran Quoc; Cuong, Nguyen Manh; Lee, Byung Ho; Woo, Sun-Hee

    2016-08-01

    We previously reported that murrayafoline-A (1-methoxy-3-methyl-9H-carbazole, Mu-A) increases the contractility of ventricular myocytes, in part, via enhancing Ca(2+) influx through L-type Ca(2+) channels, and that it increases the Ca(2+) transients by activation of protein kinase C (PKC). In the present study, we further examined the cellular mechanisms for the enhancement of contractility and L-type Ca(2+) current (ICa,L) by Mu-A. Cell shortening and ICa,L were measured in rat ventricular myocytes using a video edge detection method and perforated patch-clamp technique, respectively. We found that the positive inotropic effect of Mu-A was not affected by pre-exposure to the β-adrenoceptor antagonist propranolol, the protein kinase A (PKA) inhibitors KT5720 or H-89, or the phospholipase C inhibitor U73122. Interestingly, the Mu-A-mediated increases in cell shortening and in the rate of contraction were completely suppressed by pre-treatment with the PKC inhibitor GF109203X. The stimulatory effect of Mu-A on ICa,L was not altered by inhibition of PKA (KT5720), G-protein coupled receptors (suramin), or α1-adrenoceptor (prazosin). However, pre-exposure to the PKC inhibitor, GF109203X or chelerythrine, abolished the Mu-A-induced increase in ICa,L. Pre-exposure to the Ca(2+)-calmodulin-dependent protein kinase II (CaMKII) inhibitor KN93 slightly reduced the stimulatory effects on contraction and ICa,L by Mu-A. Phosphorylation of PKC was enhanced by Mu-A in ventricular myocytes. These data suggest that Mu-A increases contraction and ICa,L via PKC in rat ventricular myocytes, and that the PKC-mediated responses in the presence of Mu-A may be partly mediated by CaMKII.

  18. Effect of exercise training on Ca{sup 2+} release units of left ventricular myocytes of spontaneously hypertensive rats

    Energy Technology Data Exchange (ETDEWEB)

    Carneiro-Júnior, M.A. [Universidade Federal do Espírito Santo, Departamento de Ciências Fisiológicas, Vitória, ES (Brazil); Universidade Federal de Viçosa, Laboratório de Biologia do Exercício, Departamento de Educação Física, Viçosa, MG (Brazil); Quintão-Júnior, J.F.; Drummond, L.R.; Lavorato, V.N.; Drummond, F.R. [Universidade Federal de Viçosa, Laboratório de Biologia do Exercício, Departamento de Educação Física, Viçosa, MG (Brazil); Amadeu, M.A.; Oliveira, E.M. [Universidade de São Paulo, Laboratório de Bioquímica e Biologia Molecular do Exercício, Escola de Educação Física e Esportes, São Paulo, SP (Brazil); Felix, L.B. [Universidade Federal de Viçosa, Departamento de Engenharia Elétrica, Viçosa, MG (Brazil); Cruz, J.S. [Universidade Federal de Minas Gerais, Laboratório de Membranas Excitáveis e Biologia Cardiovascular, Departamento de Bioquímica e Imunologia, Belo Horizonte, MG (Brazil); Mill, J.G. [Universidade Federal do Espírito Santo, Departamento de Ciências Fisiológicas, Vitória, ES (Brazil); Natali, A.J.; Prímola-Gomes, T.N. [Universidade Federal de Viçosa, Laboratório de Biologia do Exercício, Departamento de Educação Física, Viçosa, MG (Brazil)

    2014-08-29

    In cardiomyocytes, calcium (Ca{sup 2+}) release units comprise clusters of intracellular Ca{sup 2+} release channels located on the sarcoplasmic reticulum, and hypertension is well established as a cause of defects in calcium release unit function. Our objective was to determine whether endurance exercise training could attenuate the deleterious effects of hypertension on calcium release unit components and Ca{sup 2+} sparks in left ventricular myocytes of spontaneously hypertensive rats. Male Wistar and spontaneously hypertensive rats (4 months of age) were divided into 4 groups: normotensive (NC) and hypertensive control (HC), and normotensive (NT) and hypertensive trained (HT) animals (7 rats per group). NC and HC rats were submitted to a low-intensity treadmill running protocol (5 days/week, 1 h/day, 0% grade, and 50-60% of maximal running speed) for 8 weeks. Gene expression of the ryanodine receptor type 2 (RyR2) and FK506 binding protein (FKBP12.6) increased (270%) and decreased (88%), respectively, in HC compared to NC rats. Endurance exercise training reversed these changes by reducing RyR2 (230%) and normalizing FKBP12.6 gene expression (112%). Hypertension also increased the frequency of Ca{sup 2+} sparks (HC=7.61±0.26 vs NC=4.79±0.19 per 100 µm/s) and decreased its amplitude (HC=0.260±0.08 vs NC=0.324±0.10 ΔF/F{sub 0}), full width at half-maximum amplitude (HC=1.05±0.08 vs NC=1.26±0.01 µm), total duration (HC=11.51±0.12 vs NC=14.97±0.24 ms), time to peak (HC=4.84±0.06 vs NC=6.31±0.14 ms), and time constant of decay (HC=8.68±0.12 vs NC=10.21±0.22 ms). These changes were partially reversed in HT rats (frequency of Ca{sup 2+} sparks=6.26±0.19 µm/s, amplitude=0.282±0.10 ΔF/F{sub 0}, full width at half-maximum amplitude=1.14±0.01 µm, total duration=13.34±0.17 ms, time to peak=5.43±0.08 ms, and time constant of decay=9.43±0.15 ms). Endurance exercise training attenuated the deleterious effects of hypertension on calcium release units of

  19. Effects of Simvastatin on Ion Channel Currents in Ventricular Myocytes from Acute Infarcted Heart of Normocholesterolemic Rabbits

    Institute of Scientific and Technical Information of China (English)

    Chao Ding; Xianghua Fu; Li Yang; Huixiao Chen; Junxia Li; Yuying Zhao; Jie Li; Jie Wang

    2008-01-01

    Objectives To investigate the effects of simvastatin on membrane ionic currents in left ventricular myocytes of rab-bit heart suffering from acute myocardial infarction (AMI), so as to explore the ionic mechanism of statin treatment for antiarrhythmia. Methods Forty-five New Zealand rabbits were randomly divided into three groups: AMI group, simv-astatin intervention group (Statin group) and sham-operated control group (CON). Rabbits were infarcted by ligation of the left anterior descending coronary artery after administration of oral simvastatin 5 mg · kg-1 · d-1 (Statin group) or placebo (AMI group) for 3 days. Single ventricular myocytes were isolated enzymatically from the epicardial zone of the infracted region 72 h later. Whole cell patch clamp technique was used to record membrane ionic currents, inclu-ding sodium current (Ina), L-type calcium current (Ica-L) and transient outward potassium current (Ito). Results ① There was not significant difference in serum cholesterol concentration among three groups. ② The peak Ina current den-sity (at -30 mV) was significantly decreased in AMI group (-25.26±5. 28, n = 13), comparing with CON (-42. 78±5.48, n = 16), P < 0. 05, while it was significantly increased in Statin group (-39. 83±5. 65 pA/pF, n = 12) comparing with AMI group, P <0. 01; The peak I Ca-L current density (at 0 mV) was significantly decreased in AMI group (- 3.43±0. 92 pA/pF, n = 13) comparing with CON (- 4. 56±1.01 pA/pF, n = 15), P < 0. 05, while it was significantly increased in Statin group (-4. 18±0. 96 pA/pF, n = 12) comparing with AMI group, P <0. 05; The Ito current density (at + 60 mV) was significantly decreased in AMI group (11.41±1.94 pA/pF, n = 13) compa-ring with CON (17. 41±3. 13 pA/pF, n = 15), P <0. 01, while it was significantly increased in Statin group (16. 11±2. 43 pA/pF, n = 14) comparing with AMI group, P < 0. 01. Conclusions AMI induces significant down-regula-tion of Ina, I Ca-L and Ito. Pretreatment with

  20. 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 has...... to analyze the primary composite endpoint of cardiovascular death, MI, or stroke and, separately, for fatal and nonfatal MI and hospitalized heart failure. Results During a mean follow-up of 4.8 years, an event was recorded in 67 ( 9%) patients. In Cox models after adjusting for age, gender, treatment, blood...... In hypertensive patients with LVH and no history of cardiovascular disease, ' in- treatment' left ventricular wall motion abnormalities are associated with increased likelihood of subsequent cardiovascular events independent of age, gender, blood pressure lowering, treatment modality, and in- treatment left...

  1. Effects and mechanism of different adrenergic receptor antagonists on left ventricular hypertrophy subsequent to coarctation of abdominal aorta in rats

    Institute of Scientific and Technical Information of China (English)

    HU Qin; LI Long-gui; ZHANG Yun

    2004-01-01

    To study the changes of a collagen-binding protein (Colligin) and myosin heavy chain isoform (α/β-MHC) gene and protein in left ventricular hypertrophy subsequent to coarctation of abdominal aorta in rats and the ef-fects of three kinds of adrenergic receptor blockers: Carvedilol (CAR), Metoprolol (MET) and Terazosin (TER) on these changes, and to elucidate the effects and new mechanism of CAR on left ventricular hypearophy regression. Methods: A model of hypertrophy induced by coarctation of abdominal aorta(CAA) was used in this study. Thirty two male istar rats were divided randomly into four groups 4 weeks after CAA operation: CAA, CAR, MET and TER.emodynamics, ventric-ular remodeling parameters, expressions of Colligin and α/β-MHC mRNA, protein expressions of Collagen Ⅰ /Ⅲ and Colligin were investigated in the four groups and sham operation group. Results: Left ventricle hypertrophy was observed clearly 16 weeks after operation. The ratio of α/β-MHC mRNA decreased, while expressions of Collagen Ⅰ/Ⅲ proteins and Colligin mRNA/protein increased( P < 0.05). CAR could ameliorate left ventricle hypertrophy prior to MET and TER. CAR could also change the expressions of α/β-MHC, Collagen Ⅰ/Ⅲ and Colligin in both gene and protein levels ( P < 0.05), while MET and TER have no effect on them ( P > 0.05). Conclusion: The effects of CAR on extracellular matrix proteins and MHC isoform shift regression of left ventricle may be due to antiproliferative or antioxidative mechanism, which was indepen-dent of beta-adrenergic receptor antagonist.

  2. CAVEOLIN-3 IS UP-REGULATED IN THE PHYSIOLOGICAL LEFT VENTRICULAR HYPERTROPHY INDUCED BY VOLUNTARY EXERCISE TRAINING IN RATS

    Directory of Open Access Journals (Sweden)

    Ikuo Yokoyama

    2002-12-01

    Full Text Available Various substances have been introduced in relation with cardiac hypertrophy almost always with controversy in their roles in signal transduction. Those controversies may attribute to the diversity of cardiac hypertrophy. We previously showed that calcineurin was activated in physiological left ventricular hypertrophy (LVH induced by voluntary exercise training, but not in decompensated pressure-overload LVH. In the current study, we advanced our search for the differences between the voluntary exercise-induced LVH and the pressure-overload LVH into several other hypertrophy-related substances including caveolin. Wistar rats were assigned to one of the following three groups: 10 weeks of voluntary exercise (EX, sedentary regimen (SED, and 4 weeks of ascending aortic constriction (AC. The EX rats voluntarily ran 1.6±1.1 km/day in the specially manufactured cages resulting in LVH (24 % increase in left ventricular weight per body weight ratio. Myocardial tissue homogenate of the EX rats revealed different characteristics in signal transduction of hypertrophy from that of the AC. The EX rats had normal sarcoplasmic reticulum (SR Ca2+ATPase mRNA level and normal myosin heavy chain isozyme pattern assessed by RNA protection assay, while AC rats had decreased SR Ca2+ATPase mRNA level and increased beta myosin heavy chain mRNA level. Myocardial caveolin-3 protein levels assessed by Western blotting increased in the EX rats but decreased in the AC rats. The voluntary exercise-induced LVH differed in signal transduction from the decompensated pressure-overload LVH. Caveolin-3 was induced in the voluntary exercise-induced LVH, while it was decreased in the decompensated pressure-overload LVH

  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. Voluntary exercise-induced changes in β2-adrenoceptor signalling in rat ventricular myocytes

    OpenAIRE

    Stones, Rachel; Natali, Antonio; Billeter, Rudolf; Harrison, Simon; White, Ed

    2008-01-01

    Regular exercise is beneficial to cardiovascular health. We tested whether mild voluntary exercise training modifies key myocardial parameters [ventricular mass, intracellular calcium ([Ca2+]i) handling and the response to β-adrenoceptor (β-AR) stimulation] in a manner distinct from that reported for beneficial, intensive training and pathological hypertrophic stimuli. Female rats performed voluntary wheel-running exercise for 6–7 weeks. The mRNA expression of target proteins was measured in ...

  5. Physiological and pathological left ventricular hypertrophy of comparable degree is associated with characteristic differences of in vivo hemodynamics.

    Science.gov (United States)

    Oláh, Attila; Németh, Balázs Tamás; Mátyás, Csaba; Hidi, László; Lux, Árpád; Ruppert, Mihály; Kellermayer, Dalma; Sayour, Alex Ali; Szabó, Lilla; Török, Marianna; Meltzer, Anna; Gellér, László; Merkely, Béla; Radovits, Tamás

    2016-03-01

    Left ventricular (LV) hypertrophy is a physiological or pathological response of LV myocardium to increased cardiac load. We aimed at investigating and comparing hemodynamic alterations in well-established rat models of physiological hypertrophy (PhyH) and pathological hypertrophy (PaH) by using LV pressure-volume (P-V) analysis. PhyH and PaH were induced in rats by swim training and by abdominal aortic banding, respectively. Morphology of the heart was investigated by echocardiography. Characterization of cardiac function was completed by LV P-V analysis. In addition, histological and molecular biological measurements were performed. Echocardiography revealed myocardial hypertrophy of similar degree in both models, which was confirmed by post-mortem heart weight data. In aortic-banded rats we detected subendocardial fibrosis. Reactivation of fetal gene program could be observed only in the PaH model. PhyH was associated with increased stroke volume, whereas unaltered stroke volume was detected in PaH along with markedly elevated end-systolic pressure values. Sensitive indexes of LV contractility were increased in both models, in parallel with the degree of hypertrophy. Active relaxation was ameliorated in athlete's heart, whereas it showed marked impairment in PaH. Mechanical efficiency and ventriculo-arterial coupling were improved in PhyH, whereas they remained unchanged in PaH. Myocardial gene expression of mitochondrial regulators showed marked differences between PaH and PhyH. We provided the first comparative hemodynamic characterization of PhyH and PaH in relevant rodent models. Increased LV contractility could be observed in both types of LV hypertrophy; characteristic distinction was detected in diastolic function (active relaxation) and mechanoenergetics (mechanical efficiency), which might be explained by mitochondrial differences.

  6. The complex regulation of tanshinone IIA in rats with hypertension-induced left ventricular hypertrophy.

    Science.gov (United States)

    Pang, Hui; Han, Bing; Yu, Tao; Peng, Zhen

    2014-01-01

    Tanshinone IIA has definite protective effects on various cardiovascular diseases. However, in hypertension-induced left ventricular hypertrophy (H-LVH), the signaling pathways of tanshinone IIA in inhibition of remodeling and cardiac dysfunction remain unclear. Two-kidney, one-clip induced hypertensive rats (n = 32) were randomized to receive tanshinone IIA (5, 10, 15 mg/kg per day) or 5% glucose injection (GS). Sham-operated rats (n = 8) received 5%GS as control. Cardiac function and dimensions were assessed by using an echocardiography system. Histological determination of the fibrosis and apoptosis was performed using hematoxylin eosin, Masson's trichrome and TUNEL staining. Matrix metalloproteinase 2 (MMP2) and tissue inhibitor of matrix metalloproteinases type 2 (TIMP2) protein expressions in rat myocardial tissues were detected by immunohistochemistry. Rat cardiomyocytes were isolated by a Langendorff perfusion method. After 48 h culture, the supernatant and cardiomyocytes were collected to determine the potential related proteins impact on cardiac fibrosis and apoptosis. Compared with the sham rats, the heart tissues of H-LVH (5%GS) group suffered severely from the oxidative damage, apoptosis of cardiomyocytes and extracellular matrix (ECM) deposition. In the H-LVH group, tanshinone IIA treated decreased malondialdehyde (MDA) content and increased superoxide dismutase (SOD) activity. Tanshinone IIA inhibited cardiomyocytes apoptosis as confirmed by the reduction of TUNEL positive cardiomyocytes and the down-regulation of Caspase-3 activity and Bax/Bcl-2 ratio. Meanwhile, plasma apelin level increased with down-regulation of APJ receptor. Tanshinone IIA suppressed cardiac fibrosis through regulating the paracrine factors released by cardiomyocytes and the TGF-β/Smads signaling pathway activity. In conclusion, our in vivo study showed that tanshinone IIA could improve heart function by enhancing myocardial contractility, inhibiting ECM deposition

  7. Tear me down: Role of calpain in the development of cardiac ventricular hypertrophy

    OpenAIRE

    Patterson, Cam; Portbury, Andrea; Schisler, Jonathan C; Willis, Monte S.

    2011-01-01

    Cardiac hypertrophy develops most commonly in response to hypertension and is an independent risk factor for the development of heart failure. The mechanisms by which cardiac hypertrophy may be reversed to reduce this risk have not been fully determined to the point where mechanism-specific therapies have been developed. Recently, proteases in the calpain family have been implicated in regulating the development of cardiac hypertrophy in preclinical animal models. In this review, we summarize...

  8. Loss of the eIF2α kinase GCN2 protects mice from pressure overload induced congestive heart failure without affecting ventricular hypertrophy

    Science.gov (United States)

    Lu, Zhongbing; Xu, Xin; Fassett, John; Kwak, Dongmin; Liu, Xiaoyu; Hu, Xinli; Wang, Huan; Guo, Haipeng; Xu, Dachun; Yan, Shuo; McFalls, Edward O.; Lu, Fei; Bache, Robert J.; Chen, Yingjie

    2016-01-01

    In response to a number of stresses, including nutrient deprivation, General Control Nonderepressible 2 kinase (GCN2) attenuates mRNA translation by phosphorylating eukaryotic initiation factor 2 alpha (eIF2αSer51). Energy starvation is known to exacerbate congestive heart failure (CHF) and eIF2αSer51 phosphorylation is increased in the failing heart. However, the impact of GCN2 during the evolution of CHF has not been tested. In this study we examined the influence of GCN2 expression in response to a cardiac stress by inducing chronic pressure overload with Transverse Aortic Constriction (TAC) in Wild Type (WT) and GCN2 knockout (GCN2−/−) mice. Under basal conditions, GCN2−/− had normal LV structure or function but following TAC, demonstrated less contractile dysfunction, less increase of lung weight, less increase of lung inflammation and vascular remodeling, and less myocardial apoptosis and fibrosis compared with WT mice, despite an equivalent degree of LV hypertrophy. As expected, GCN2−/− attenuated TAC induced cardiac eif2αSer51 phosphorylation and preserved Sarcoplasmic reticulum Ca2+ ATPase (Serca2a) expression compared with WT mice. Interestingly, expression of the anti-apoptotic protein Bcl-2 was significantly elevated in GCN2−/− hearts, while in isolated neonatal cardiomyocytes, selective knockdown of GCN2 increased Bcl-2 protein expression and enhanced myocyte resistance to an apoptotic stress. Collectively, our data support the notion that GCN2 impairs the ventricular adaptation to chronic pressure overload by reducing Bcl-2 expression and increasing cardiomyocyte susceptibility to apoptotic stimuli. Our findings suggest that strategies to reduce GCN2 activity in cardiac tissue may be a novel approach to attenuate congestive heart failure development. PMID:24166753

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

    Directory of Open Access Journals (Sweden)

    Bastiaan J van Nierop

    Full Text Available 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 mouse model. Therefore, we quantified time-dependent alterations in the ventricular morphology and function in two models of hypertrophy and heart failure and we studied the relationship between RV and LV function during the transition from hypertrophy to heart failure. METHODS: MRI was used to quantify RV and LV function and morphology in healthy (n = 4 and sham operated (n = 3 C57BL/6 mice, and animals with a mild (n = 5 and a severe aortic constriction (n = 10. RESULTS: Mice subjected to a mild constriction showed increased LV mass (P0.05. Animals with a severe constriction progressively developed LV hypertrophy (P<0.001, depressed LVEF (P<0.001, followed by a declining RVEF (P<0.001 and the development of pulmonary remodeling, as compared to controls during a 10-week follow-up. Myocardial strain, as a measure for local cardiac function, decreased in mice with a severe constriction compared to controls (P<0.05. CONCLUSIONS: Relevant changes in mouse RV and LV function following an aortic constriction could be quantified using MRI. The well-controlled models described here open opportunities to assess the added value of new MRI techniques for the diagnosis of heart failure and to study the impact of new therapeutic strategies on disease progression and symptom occurrence.

  10. Sustained pulmonary hypertension and right ventricular hypertrophy after chronic hypoxia in mice with congenital deficiency of nitric oxide synthase 3.

    OpenAIRE

    Steudel, W.; Scherrer-Crosbie, M; Bloch, K D; Weimann, J.; Huang, P L; Jones, R. C.; Picard, M H; Zapol, W M

    1998-01-01

    Chronic hypoxia induces pulmonary hypertension and right ventricular (RV) hypertrophy. Nitric oxide (NO) has been proposed to modulate the pulmonary vascular response to hypoxia. We investigated the effects of congenital deficiency of endothelial NO synthase (NOS3) on the pulmonary vascular responses to breathing 11% oxygen for 3-6 wk. After 3 wk of hypoxia, RV systolic pressure was greater in NOS3-deficient than in wild-type mice (35+/-2 vs 28+/-1 mmHg, x+/-SE, P < 0.001). Pulmonary artery p...

  11. 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...... but not I/D or II genotype, proportion of short telomeres (...

  12. Computational analysis of the regulation of Ca2+ dynamics in rat ventricular myocytes

    Science.gov (United States)

    Bugenhagen, Scott M.; Beard, Daniel A.

    2015-10-01

    Force-frequency relationships of isolated cardiac myocytes show complex behaviors that are thought to be specific to both the species and the conditions associated with the experimental preparation. Ca2+ signaling plays an important role in shaping the force-frequency relationship, and understanding the properties of the force-frequency relationship in vivo requires an understanding of Ca2+ dynamics under physiologically relevant conditions. Ca2+ signaling is itself a complicated process that is best understood on a quantitative level via biophysically based computational simulation. Although a large number of models are available in the literature, the models are often a conglomeration of components parameterized to data of incompatible species and/or experimental conditions. In addition, few models account for modulation of Ca2+ dynamics via β-adrenergic and calmodulin-dependent protein kinase II (CaMKII) signaling pathways even though they are hypothesized to play an important regulatory role in vivo. Both protein-kinase-A and CaMKII are known to phosphorylate a variety of targets known to be involved in Ca2+ signaling, but the effects of these pathways on the frequency- and inotrope-dependence of Ca2+ dynamics are not currently well understood. In order to better understand Ca2+ dynamics under physiological conditions relevant to rat, a previous computational model is adapted and re-parameterized to a self-consistent dataset obtained under physiological temperature and pacing frequency and updated to include β-adrenergic and CaMKII regulatory pathways. The necessity of specific effector mechanisms of these pathways in capturing inotrope- and frequency-dependence of the data is tested by attempting to fit the data while including and/or excluding those effector components. We find that: (1) β-adrenergic-mediated phosphorylation of the L-type calcium channel (LCC) (and not of phospholamban (PLB)) is sufficient to explain the inotrope-dependence; and (2) that

  13. ECG identification of left ventricular hypertrophy. Relationship of test performance to body habitus.

    Science.gov (United States)

    Okin, P M; Roman, M J; Devereux, R B; Kligfield, P

    1996-01-01

    Obesity is associated with the presence of left ventricular hypertrophy (LVH) and, conversely, with decreased sensitivity of the electrocardiogram (ECG) for LVH due to attenuating effects on QRS amplitudes. Although the Framingham-adjusted Cornell voltage, incorporating age, sex, and body mass index (BMI), was developed to correct for the effects of obesity on the accuracy of the ECG, the impact of body habitus on ECG detection of LVH for newer, more accurate ECG criteria based on the time-voltage area under the QRS complex has not been determined. The authors examined the test accuracy of the Sokolow-Lyon voltage, Cornell voltage, Cornell product (product of QRS duration and Cornell voltage), Framingham-adjusted Cornell voltage, and time-voltage area of the horizontal plane vector QRS for the detection of echocardiographic LVH in relation to body habitus in 250 patients. Normal-weight or overweight status was based on sex-specific population-based BMI partitions. Using partitions with a matched specificity of 98% in the overall population without LVH, the sensitivity of standard ECG criteria varied according to body habitus. Sensitivity of the Framingham-adjusted Cornell voltage was less in normal-weight than in overweight patients (49 vs 59%, P = .0004); there were also trends toward lower sensitivity in normal-weight patients for the Cornell voltage (40 vs 65%, P = .10) and the Cornell product (43 vs 65%, P = NS), but sensitivity of the Sokolow-Lyon voltage was lower in obese than in nonobese patients (18 vs 50%, P = .025). In contrast, the horizontal plane vector area had similar sensitivity in obese and normal-weight patients (76 vs 74%, P = NS). Specificity varied with body habitus only for the Framingham-adjusted Cornell voltage: 100% in normal-weight vs 95% in overweight patients (P habitus. In contrast, accuracy of the Cornell voltage and the Cornell product appears less dependent on BMI, and the time-voltage area of the QRS minimizes the effects of

  14. Electrophysiological effects of Chinese medicine Shen song Yang xin (SSYX) on Chinese miniature swine heart and isolated guinea pig ventricular myocytes

    Institute of Scientific and Technical Information of China (English)

    FENG Li; GONG Jing; JIN Zhen-yi; LI Ning; SUN Li-ping; WU Yi-ling; PU Jie-lin

    2009-01-01

    Background Shen song Yang xin (SSYX) is a compound of Chinese medicine with the effect of increasing heart rate (HR). This study aimed to evaluate its electrophysiological properties at heart and cellular levels. Methods The Chinese miniature swines were randomly assigned to two groups, administered with SSYX or placebo for 4 weeks (n=8 per group). Cardiac electrophysiological study (EPS) was performed before and after drug administration. The guinea pig ventricular myocytes were enzymatically isolated and whole cell voltage-clamp technique was used to evaluate the effect of SSYX on cardiac action potential (AP). Results SSYX treatment accelerated the HR from (141.8±36.0) beats per minute to (163.0±38.0) beats per minute (P=0.013) without changing the other parameters in surface electrocardiogram. After blockage of the autonomic nervous system with metoprolol and atropin, SSYX had no effect on intrinsic HR (IHR), but decreased corrected sinus node recovery time (CSNRT) and sinus atrium conducting time (SACT). Intra cardiac EPS showed that SSYX significantly decreased the A-H and A-V intervals as well as shortened the atrial (A), atrioventricular node (AVN) and ventricular (V) effective refractory period (ERP). In isolated guinea pig ventricular myocytes, the most obvious effect of SSYX on action potential was a shortening of the action potential duration (APD) without change in shape of action potential. The shortening rates of APD30, APD50 and APDgo were 19.5%, 17.8% and 15.3%, respectively. The resting potential (Em) and the interval between the end of APD3o and APD9o did not significantly change.Conclusions The present study demonstrates that SSYX increases the HR and enhances the conducting capacity of the heart in the condition of the intact autonomic nervous system. SSYX homogenously decreases the ERP of the heart and shortens the APD of the myocytes, suggesting its antiarrhythmic effect without proarrhythmia.

  15. Different Na+/K+-ATPase signal pathways was involved in the increase of [Ca2+]i induced by strophanthidin in normal and failing isolated guinea pig ventricular myocytes

    Institute of Scientific and Technical Information of China (English)

    Ya-juan QI; Su-wen SU; Jun-xia LI; Ji-he LI; Fang GUO; Yong-li WANG

    2008-01-01

    Aim: To determine whether different Na+/K+-ATPase signal transduction pathways have positive inotropic effects on normal ventricular myocytes (NC) and failing ventricular myocytes (FC), and are involved in an increase of [Ca2+]i induced by strophanthidin (Str). Methods: A guinea pig model of congestive heart failure was made by constricting descending aorta. The left ventricular myocytes were enzymatically isolated. The effects of 25 μmol/L Str with different signal-transducing inhibitors on contractility and the calcium transient of NC or FC from guinea pigs were simultaneously assessed and compared with those in the 25 μmol/L Str-only group by a video-based, motion-edge detection system. Results: Str at 1, 10, and 25 μmol/L in NC and Str at 0.1, 1, 10, and 25 μmol/L) in FC elevated the calcium transient amplitude and increased the positive inotropic effects in a concentration-dependent manner, respectively. At the same concentration, the effects of Str were more potent in FC than in NC. In FC, both the mitogen-activated protein kinase (MAPK) and reactive oxygen species (ROS) signal transduction pathway of Na+/K+-ATPase were involved in the increase of the calcium transient induced by Str, but only activation of the MAPK pathway increased the calcium transient in NC. However, only the ROS pathway was involved in positive inotropic effects both in NC and FC. Conclusion: The present study suggests that Na+/K+-ATPase signaling pathways involved in the inotropic effects of Str in NC and FC are consistent, and Na+/K+-ATPase signaling pathways involved in the increase of [Ca2+]i by Str in NC and FC are different.

  16. Effect of trimetazidine treatment on the transient outward potassium current of the left ventricular myocytes of rats with streptozotocin-induced type 1 diabetes mellitus

    Energy Technology Data Exchange (ETDEWEB)

    Xiang, Yu-luan; He, Li [Department of Cardiology, the Second Affiliated Hospital, Chongqing Medical University, Chongqing (China); Xiao, Jun [Department of Cardiology, Chongqing Emergency Medical Center, Chongqing (China); Xia, Shuang; Deng, Song-bai [Department of Cardiology, the Second Affiliated Hospital, Chongqing Medical University, Chongqing (China); Xiu, Yun [Institute of Life Science, Chongqing Medical University, Chongqing (China); She, Qiang [Department of Cardiology, the Second Affiliated Hospital, Chongqing Medical University, Chongqing (China)

    2012-02-17

    Cardiovascular complications are a leading cause of mortality in patients with diabetes mellitus (DM). The present study was designed to investigate the effects of trimetazidine (TMZ), an anti-angina drug, on transient outward potassium current (I{sub to}) remodeling in ventricular myocytes and the plasma contents of free fatty acid (FFA) and glucose in DM. Sprague-Dawley rats, 8 weeks old and weighing 200-250 g, were randomly divided into three groups of 20 animals each. The control group was injected with vehicle (1 mM citrate buffer), the DM group was injected with 65 mg/kg streptozotocin (STZ) for induction of type 1 DM, and the DM+TMZ group was injected with the same dose of STZ followed by a 4-week treatment with TMZ (60 mg·kg{sup −1}·day{sup −1}). All animals were then euthanized and their hearts excised and subjected to electrophysiological measurements or gene expression analyses. TMZ exposure significantly reversed the increased plasma FFA level in diabetic rats, but failed to change the plasma glucose level. The amplitude of I{sub to} was significantly decreased in left ventricular myocytes from diabetic rats relative to control animals (6.25 ± 1.45 vs 20.72 ± 2.93 pA/pF at +40 mV). The DM-associated I{sub to} reduction was attenuated by TMZ. Moreover, TMZ treatment reversed the increased expression of the channel-forming alpha subunit Kv1.4 and the decreased expression of Kv4.2 and Kv4.3 in diabetic rat hearts. These data demonstrate that TMZ can normalize, or partially normalize, the increased plasma FFA content, the reduced I{sub to} of ventricular myocytes, and the altered expression Kv1.4, Kv4.2, and Kv4.3 in type 1 DM.

  17. Effect of trimetazidine treatment on the transient outward potassium current of the left ventricular myocytes of rats with streptozotocin-induced type 1 diabetes mellitus

    International Nuclear Information System (INIS)

    Cardiovascular complications are a leading cause of mortality in patients with diabetes mellitus (DM). The present study was designed to investigate the effects of trimetazidine (TMZ), an anti-angina drug, on transient outward potassium current (Ito) remodeling in ventricular myocytes and the plasma contents of free fatty acid (FFA) and glucose in DM. Sprague-Dawley rats, 8 weeks old and weighing 200-250 g, were randomly divided into three groups of 20 animals each. The control group was injected with vehicle (1 mM citrate buffer), the DM group was injected with 65 mg/kg streptozotocin (STZ) for induction of type 1 DM, and the DM+TMZ group was injected with the same dose of STZ followed by a 4-week treatment with TMZ (60 mg·kg−1·day−1). All animals were then euthanized and their hearts excised and subjected to electrophysiological measurements or gene expression analyses. TMZ exposure significantly reversed the increased plasma FFA level in diabetic rats, but failed to change the plasma glucose level. The amplitude of Ito was significantly decreased in left ventricular myocytes from diabetic rats relative to control animals (6.25 ± 1.45 vs 20.72 ± 2.93 pA/pF at +40 mV). The DM-associated Ito reduction was attenuated by TMZ. Moreover, TMZ treatment reversed the increased expression of the channel-forming alpha subunit Kv1.4 and the decreased expression of Kv4.2 and Kv4.3 in diabetic rat hearts. These data demonstrate that TMZ can normalize, or partially normalize, the increased plasma FFA content, the reduced Ito of ventricular myocytes, and the altered expression Kv1.4, Kv4.2, and Kv4.3 in type 1 DM

  18. Use-dependent block of Ca2+ current by moricizine in guinea-pig ventricular myocytes: a possible ionic mechanism of action potential shortening.

    OpenAIRE

    Yamane, T; Sunami, A.; Sawanobori, T.; Hiraoka, M

    1993-01-01

    1. Whole cell patch clamp techniques were used to study the effects of moricizine on membrane currents in guinea-pig ventricular myocytes. 2. Application of moricizine caused reversible depression of the time-dependent outward K+ current. 3. The Na+/Ca2+ exchange current was not directly affected by moricizine. 4. Although moricizine hardly affected the L-type Ca2+ current when cells were stimulated at a frequency of 0.1 Hz, it suppressed the current at depolarized holding potentials in a use...

  19. Prevalence and risk factors for left ventricular hypertrophy and left ventricular geometric abnormality in the patients with hypertension among Han Chinese

    Institute of Scientific and Technical Information of China (English)

    WANG Shu-xia; XUE Hao; ZOU Yu-bao; SUN Kai; FU Chun-yan; WANG Hu; HUI Ru-tai

    2012-01-01

    Background Left ventricular hypertrophy (LVH) and geometric abnormality are associated with morbidity and mortality of cardiovascular disease and stroke.Hypertension is the major cause of LVH.Yet the prevalence and other risk factors of LVH and geometric abnormality in Chinese hypertensive population are unknown.The objective of this study was to investigate the prevalence and risk factors of LVH and geometric abnormality in community-based Chinese hypertensive population.Methods The study was a community-based cross-sectional study,and comprised 4270 hypertension patients with integrated clinical and echocardiographic data.Left ventricular mass was measured by transthoracic echocardiography.LVH was diagnosed by using the criteria of over 49.2 g/m27 for men and 46.7 g/m2.7 for women.LV geometric patterns (normal,concentric remodeling,concentric or eccentric hypertrophy) were calculated according to LVH and relative wall thickness.Logistic regression model was used to determine the odds ratio (OR) and 95% confidence intervals (CI) of the risk factors of LVH.Results The prevalence of LVH was 42.7% in 4270 hypertensive patients,with 37.4% in males and 45.4% in females,respectively.The prevalence of concentric remodeling,concentric or eccentric hypertrophy was 24.7%,20.2%,and 22.6%,respectively.In Logistic regression model,female (OR 1.3,95%CI 1,1-1.5,P <0.01),age (OR 1.02,95%CI 1.01-1.03,P <0.01),body mass index (OR 1.2,95%CI 1.15-1.20,P <0.01),systolic blood pressure (OR 1.02,95%CI 1.01-1.03,P <0.01),and serum triglyceride (OR 1.10,95% CI 1.00-1.20,P<0.01) were risk factors of LVH.Female,age,body mass index,systolic blood pressure and serum triglycedde were also risk factors of left ventricular geometric abnormality.Conclusions The echocardiographic LVH is the major complication of patients with hypertension in rural area of China,especially for women.To effectively treat hypertension,weight loss and control of serum triglyceride may

  20. Cardiac MRI assessed left ventricular hypertrophy in differentiating hypertensive heart disease from hypertrophic cardiomyopathy attributable to a sarcomeric gene mutation

    Energy Technology Data Exchange (ETDEWEB)

    Sipola, Petri [Kuopio University Hospital, Department of Clinical Radiology, Kuopio (Finland); University of Eastern Finland, Institute of Clinical Medicine, Faculty of Health Sciences, Kuopio (Finland); Magga, Jarkko; Peuhkurinen, Keijo [Kuopio University Hospital, Department of Medicine, Kuopio (Finland); Husso, Minna [Kuopio University Hospital, Department of Clinical Radiology, Kuopio (Finland); Jaeaeskelaeinen, Pertti; Kuusisto, Johanna [Kuopio University Hospital, Department of Medicine, Kuopio (Finland); Kuopio University Hospital, Heart Center, P.O. Box 1777, Kuopio (Finland)

    2011-07-15

    To evaluate the value of cardiac magnetic resonance imaging (CMRI)-assessed left ventricular hypertrophy (LVH) in differentiating between hypertensive heart disease and hypertrophic cardiomyopathy (HCM). 95 unselected subjects with mild-to-moderate hypertension, 24 patients with HCM attributable to the D175N mutation of the {alpha}-tropomyosin gene and 17 control subjects were studied by cine CMRI. Left ventricular (LV) quantitative and qualitative characteristics were evaluated. LV maximal end-diastolic wall thickness, wall thickness-to-LV volume ratio, end-diastolic septum thickness and septum-to-lateral wall thickness ratio were useful measures for differentiating between LVH due to hypertension and HCM. The most accurate measure for identifying patients with HCM was the LV maximal wall thickness {>=}17 mm, with a sensitivity, specificity, negative predictive value, positive predictive value, and accuracy of 90%, 93%, 86%, 95% and 91%, respectively. LV maximal wall thickness in the anterior wall, or regional bulging in left ventricular wall was found only in patients with HCM. LV mass index was not discriminant between patients with HCM and those with LVH due to hypertension. LV maximal thickness measured by CMRI is the best anatomical parameter in differentiating between LVH due to mild-to-moderate hypertension and HCM attributable to a sarcomeric mutation. CMRI assessment of location and quality of LVH is also of value in differential diagnosis. (orig.)

  1. Resveratrol attenuates the Na(+-dependent intracellular Ca(2+ overload by inhibiting H(2O(2-induced increase in late sodium current in ventricular myocytes.

    Directory of Open Access Journals (Sweden)

    Chunping Qian

    Full Text Available BACKGROUND/AIMS: Resveratrol has been demonstrated to be protective in the cardiovascular system. The aim of this study was to assess the effects of resveratrol on hydrogen peroxide (H(2O(2-induced increase in late sodium current (I(Na.L which augmented the reverse Na(+-Ca(2+ exchanger current (I(NCX, and the diastolic intracellular Ca(2+ concentration in ventricular myocytes. METHODS: I(Na.L, I(NCX, L-type Ca(2+ current (I(Ca.L and intracellular Ca(2+ properties were determined using whole-cell patch-clamp techniques and dual-excitation fluorescence photomultiplier system (IonOptix, respectively, in rabbit ventricular myocytes. RESULTS: Resveratrol (10, 20, 40 and 80 µM decreased I(Na.L in myocytes both in the absence and presence of H(2O(2 (300 µM in a concentration dependent manner. Ranolazine (3-9 µM and tetrodotoxin (TTX, 4 µM, I(Na.L inhibitors, decreased I(Na.L in cardiomyocytes in the presence of 300 µM H(2O(2. H(2O(2 (300 µM increased the reverse I(NCX and this increase was significantly attenuated by either 20 µM resveratrol or 4 µM ranolazine or 4 µM TTX. In addition, 10 µM resveratrol and 2 µM TTX significantly depressed the increase by 150 µM H(2O(2 of the diastolic intracellular Ca(2+ fura-2 fluorescence intensity (FFI, fura-fluorescence intensity change (△FFI, maximal velocity of intracellular Ca(2+ transient rise and decay. As expected, 2 µM TTX had no effect on I(Ca.L. CONCLUSION: Resveratrol protects the cardiomyocytes by inhibiting the H(2O(2-induced augmentation of I(Na.L.and may contribute to the reduction of ischemia-induced lethal arrhythmias.

  2. 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....

  3. High fat/low carbohydrate diet attenuates left ventricular hypertrophy and prevents myosin heavy chain isoform switching induced by chronic hypertenstion

    Science.gov (United States)

    A switch in the expression of myosin heavy chain isoform (MHC) alpha to beta is observed with left ventricular hypertrophy (LVH) and heart failure. This switch is associated with a defect in myocardial energy production and contractile dysfunction. Similar MHC isoform profile is observed in the fe...

  4. Study in Southern India Among Hypertensive Patients Using ECG To Screen Left Ventricular Hypertrophy – Can We Do It in Rural Health Centres?

    OpenAIRE

    Pinto, Jostol; George, Peter; Hegde, Narasimha

    2014-01-01

    Background: Electrocardiogram (ECG) is a cost effective tool to evaluate left ventricular hypertrophy (LVH). However, its reliability is often questionable when compared to the gold standard - echocardiography.The validation of ECG as a tool to diagnose LVH would benefit centres that lack access to echocardiography.

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

    DEFF Research Database (Denmark)

    Ravn, Nathja; Zois, Nora Elisabeth; Moesgaard, Sophia G.;

    2014-01-01

    traction sutures that where applied in transmyocardial fashion. A sham operated control group (n = 13) was included. Echocardiographic LV size and heart weight assessed at euthanasia were used to evaluate the development of LV enlargement and eccentric hypertrophy after 8 weeks follow-up. RESULTS: Eight...

  6. Exercise and cardiovascular outcomes in hypertensive patients in relation to structure and function of left ventricular hypertrophy: the LIFE study

    DEFF Research Database (Denmark)

    Boman, Kurt; Gerdts, Eva; Wachtell, Kristian;

    2009-01-01

    BACKGROUND: Exercise lowers blood pressure and improves cardiovascular function, but little is known about whether exercise impacts cardiovascular morbidity and mortality independent of left ventricular hypertrophy (LVH) and LV geometry. DESIGN: Observational analysis of prospectively obtained...... (never exercise), intermediate (30 min twice/week). During 4.8-year follow-up, 105 patients suffered the primary composite endpoint of myocardial infarction (MI), stroke, or cardiovascular death. MI occurred in 39, stroke in 60, and cardiovascular death in 33 patients. RESULTS: Sedentary individuals (n...... (P = 0.016); and larger left atrium (P = 0.006). Systolic variables did not differ. In Cox regression analysis, physically active compared with sedentary patients had lower risk of primary composite endpoint [odds ratio (OR): 0.42, 95% confidence interval (CI): 0.26-0.68, P cardiovascular...

  7. Positron emission tomographic evaluation of regulation of myocardial perfusion in physiological (elite athletes) and pathological (systemic hypertension) left ventricular hypertrophy

    DEFF Research Database (Denmark)

    Kjaer, Andreas; Meyer, Christian; Wachtell, Kristian;

    2005-01-01

    Myocardial perfusion (MP) may differ in physiologic and pathologic left ventricular hypertrophy (LVH). We compared MP in LVH in elite athletes and patients with hypertension with healthy, age-matched subjects. We included 12 rowers with LVH, 19 patients with hypertension with LVH, and 2 age...... in patients with hypertension did not differ from that of controls. In conclusion, physiologic LVH in athletes is suited for a high peak workload at the cost of only a small increase in basal myocardial oxygen consumption. In contrast, LVH in the presence of hypertension is a good adaptation to the increased...... pressor test. The degree of LVH was similar in athletes and those with hypertension. Compared with controls, athletes had 20% lower baseline MP (p

  8. 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

  9. Histopathological study of time course changes in inter-renal aortic banding-induced left ventricular hypertrophy of mice.

    Science.gov (United States)

    Higashiyama, Hiroyuki; Sugai, Masaki; Inoue, Hirotaka; Mizuyachi, Kaori; Kushida, Hiroshi; Asano, Satoshi; Kinoshita, Mine

    2007-02-01

    The left ventricular hypertrophy (LVH) in response to pressure overload is an important risk factor in cardiac morbidity and mortality. To investigate the time course of histopathological alterations in the LVH in response to pressure overload, histopathological and immunohistochemical examination was performed using the aortic banding-induced mouse LVH model. Five-week-old male CD-1 mice were subjected to the inter-renal aortic banding. Major organs were sampled on 3, 10, 14, 21, 28 or 42 days after banding. Haematoxylin and eosin (H&E) staining, Masson's trichrome staining and immunohistochemistry for proliferating cell nuclear antigen (PCNA), alpha-smooth muscle actin (aSMA), ICAM-1, type I collagen and CD31 was performed and microscopically examined. Three days after aortic banding, acute inflammatory changes, such as macrophages/neutrophil infiltration and vascular wall injury were observed on/around the coronary arteries/arterioles of both ventricles. Intense ICAM-1 immunostaining was observed on the endothelium of the coronary arteries/arterioles. After day 10, vascular wall thickening and perivascular fibrosis was induced on the coronary arteries/arterioles. Immunohistochemistry for aSMA and PCNA demonstrated the proliferation of vascular smooth muscle cells in the media. After day 28, minimal cardiomyocyte hypertrophy was observed at the light microscope level. In the inter-renal aortic banding LVH model, histopathological alterations in early phase were mainly observed on coronary arteries/arterioles. These early phase alterations were thought to be hypertension-related changes in the coronary vasculatures. The cardiomyocyte hypertrophy observed in later phase was minimal at the light microscope level. These evidences would facilitate the understanding of pathophysiology of pressure overload LVH. PMID:17244336

  10. Myocardial phenotypic changes in Na+, K+ ATPase in left ventricular hypertrophy: pharmacological consequences.

    Science.gov (United States)

    Charlemagne, D; Swynghedauw, B

    1995-05-01

    Cardiac adaptation to permanent overload induces several phenotypic changes which finally result in a system which works more economically, together with a slower Vmax. The molecular target of digitalis is the NA+, K+ ATPase, which is a polymorphic molecule. We have recently demonstrated that during cardiac hypertrophy this target is modified and that a shift occurs in the alpha 1 subunit, from the normally present alpha 2 isosubunit to alpha 3, which is a fetal isoform with a lower affinity for sodium and a higher affinity for ouabain. Such a shift explains why, in rat cardiac hypertrophy ouabain is less toxic than normal and is released from its target more slowly. It may also explain at least in part the discrepancies observed in clinical trials on the efficacy of digitalis. PMID:7556267

  11. The cardiopulmonary reflexes of spontaneously hypertensive rats are normalized after regression of left ventricular hypertrophy and hypertension

    Directory of Open Access Journals (Sweden)

    T.A. Uggere

    2000-05-01

    Full Text Available Cardiopulmonary reflexes are activated via changes in cardiac filling pressure (volume-sensitive reflex and chemical stimulation (chemosensitive reflex. The sensitivity of the cardiopulmonary reflexes to these stimuli is impaired in the spontaneously hypertensive rat (SHR and other models of hypertension and is thought to be associated with cardiac hypertrophy. The present study investigated whether the sensitivity of the cardiopulmonary reflexes in SHR is restored when cardiac hypertrophy and hypertension are reduced by enalapril treatment. Untreated SHR and WKY rats were fed a normal diet. Another groups of rats were treated with enalapril (10 mg kg-1 day-1, mixed in the diet; SHRE or WKYE for one month. After treatment, the volume-sensitive reflex was evaluated in each group by determining the decrease in magnitude of the efferent renal sympathetic nerve activity (RSNA produced by acute isotonic saline volume expansion. Chemoreflex sensitivity was evaluated by examining the bradycardia response elicited by phenyldiguanide administration. Cardiac hypertrophy was determined from the left ventricular/body weight (LV/BW ratio. Volume expansion produced an attenuated renal sympathoinhibitory response in SHR as compared to WKY rats. As compared to the levels observed in normotensive WKY rats, however, enalapril treatment restored the volume expansion-induced decrease in RSNA in SHRE. SHR with established hypertension had a higher LV/BW ratio (45% as compared to normotensive WKY rats. With enalapril treatment, the LV/BW ratio was reduced to 19% in SHRE. Finally, the reflex-induced bradycardia response produced by phenyldiguanide was significantly attenuated in SHR compared to WKY rats. Unlike the effects on the volume reflex, the sensitivity of the cardiac chemosensitive reflex to phenyldiguanide was not restored by enalapril treatment in SHRE. Taken together, these results indicate that the impairment of the volume-sensitive, but not the

  12. Ambulatory blood pressure in hypertensive patients with left ventricular hypertrophy: efficacy of first-line combination perindopril/indapamide therapy

    Directory of Open Access Journals (Sweden)

    Rol

    2007-09-01

    Full Text Available Roland Asmar1, Juan Garcia-Puig2, Philippe Gosse3, Yuri A Karpov4, Peter Wilhem De Leeuw5, Dieter Magometschniggs6, Lajos Matos7, Roland Schmieder81Institut Cardiovasculaire, Paris, France; 2Hospital La Paz, Madrid, Spain; 3Hôpital Saint André, Bordeaux, France; 4Russian Academy of Medical Sciences, Moscow, Russia; 5Academisch Ziekenhuis, Maastricht, the Netherlands; 6Institut für Hypertoniker, Vienna, Austria; 7Hungarian Institut of Cardiology, Budapest, Hungary; 8Medizinische FakultÄt, Erlangen GermanyBackground: Ambulatory blood pressure (BP is more sensitive than office BP and is highly correlated with the left ventricular mass (LVM of hypertensive patients with left ventricular hypertrophy (LVH. Methods: In this prospectively designed ancillary study of the PICXEL trial, the effects of first-line combination perindopril/indapamide on ambulatory BP were compared with those of monotherapy with enalapril in 127 patients. Hypertensive patients with LVH received once daily either perindopril 2 mg/indapamide 0.625 mg (n = 65 or enalapril 10 mg (n = 62 for 52 weeks. Dose adjustments were allowed for uncontrolled BP. Twenty-four-hour ambulatory BP and echocardiographic parameters were measured at baseline, week 24, and week 52. Results: At study end, both treatments significantly improved ambulatory BP compared with baseline (p ≤ 0.01. Perindopril/indapamide treatment reduced 24-hour and daytime systolic BP (SBP and pulse pressure (PP significantly more than enalapril treatment (p < 0.01. No significant between-group differences were noted for diastolic BP (DBP or for night-time measurements. Trough/peak ratios were higher with perindopril/indapamide than with enalapril (88.5 vs 65.8 for SBP and 86.7 vs 63.9 for DBP, respectively. The global smoothness index was higher with perindopril/indapamide than with enalapril (6.6 vs 5.2 for SBP and 5.6 vs 4.9 for DBP, respectively. With perindopril/indapamide treatment, LVM index was significantly

  13. Changes in Myocardial Mass Associated with Age and Stress: Reexamination of Ventricular Hypertrophy.

    Science.gov (United States)

    George, Colleen; And Others

    1985-01-01

    One hundred twenty-six rats were studied to determine the effects of exercise, high altitude, and age upon right and left ventricular mass. Chronically hypoxic rats had significantly larger right ventricles but significantly smaller left ventricles than exercised or control rats. (Author/MT)

  14. Dilation and Hypertrophy: A Cell-Based Continuum Mechanics Approach Towards Ventricular Growth and Remodeling

    Science.gov (United States)

    Ulerich, J.; Göktepe, S.; Kuhl, E.

    This manuscript presents a continuum approach towards cardiac growth and remodeling that is capable to predict chronic maladaptation of the heart in response to changes in mechanical loading. It is based on the multiplicative decomposition of the deformation gradient into and elastic and a growth part. Motivated by morphological changes in cardiomyocyte geometry, we introduce an anisotropic growth tensor that can capture both hypertrophic wall thickening and ventricular dilation within one generic concept. In agreement with clinical observations, we propose wall thickening to be a stress-driven phenomenon whereas dilation is introduced as a strain-driven process. The features of the proposed approach are illustrated in terms of the adaptation of thin heart slices and in terms overload-induced dilation in a generic bi-ventricular heart model.

  15. Improvement of left ventricular hypertrophy and arrhythmias after lanreotide-induced GH and IGF-I decrease in acromegaly. A prospective multi-center study.

    Science.gov (United States)

    Lombardi, G; Colao, A; Marzullo, P; Biondi, B; Palmieri, E; Fazio, S

    2002-12-01

    We report the results of a prospective Italian multi-center study of the effects of lanreotide, a slow-release somatostatin analog, on left ventricular morphology and function and on the prevalence of ventricular arrhythmic events in 19 patients with active, newly diagnosed, uncomplicated acromegaly. Cardiac features were evaluated with Doppler-echocardiography and 24-h Holter ECG monitoring at baseline and after 6 months of lanreotide therapy. Fifteen patients (78.9%) had left ventricular hypertrophy. Lanreotide treatment significantly decreased the left ventricular mass (127.8+/-6.9 vs 140.7+/-7.1 g/m2, paffect systolic function, whereas it increased the Doppler-derived early-to-late mitral flow velocity, (E/A) ratio, of early-to-late trans-mitral flow velocity (1.34+/-0.1 vs 1.09+/-0.06, p=0.001). Stroke volume was slightly but not significantly increased after treatment, whereas systolic BP was significantly higher (134+/-14 vs 129+/-13 mmHg, p50/24 h) occurred in 16.6% of patients and were unaffected by treatment. Differently, ventricular premature beats (>50/24 h) occurred in 33.3% of patients before treatment vs 16.5%, after treatment. In conclusion, lanreotide reduced the left ventricular mass, and improved ventricular filling and ventricular arrhythmic profile.

  16. Anemia treatment and left ventricular hypertrophy in non-dialysis chronic kidney disease

    Institute of Scientific and Technical Information of China (English)

    Robert N. Foley; Peter A. McCullough

    2005-01-01

    @@ To this day, the target hemoglobin level that minimizes cardiovascular risk in chronic kidney disease (CKD) patients remains unclear. When one examines the many randomized trials of epoetin therapy in aggregate, enhanced quality of life provides the most cogent argument for hemoglobin levels above 110 g/L. It remains unclear whether treatment of anemia improves longevity, or even a surrogate marker (such as left ventricular [LV] mass index), especially when applied at earlier phases of CKD.

  17. Negative association of endothelial nitric oxide gene polymorphism with hypertension in Turkish patients: effect of ecNOS polymorphism on left ventricular hypertrophy

    OpenAIRE

    Arslan Erol; Barcin Cem; Sezer Murat; Ozbek Ugur; Ekmekci C Gokhan; Olcay Ayhan; Boztosun Bilal; Nisanci Yilmaz

    2006-01-01

    Abstract Background Endothelial nitric oxide synthase produces nitric oxide which is involved in many physiologic regulatory functions. Variable number of tandem repeats in intron 4 of endothelial nitric oxide synthase gene are reported to be associated with blood pressure regulation. Nitric oxide is involved in regulation of cardiomyocyte genes but it is not known If endothelial nitric oxide synthase 4 gene polymorphisms are related with left ventricular hypertrophy. We studied endothelial n...

  18. Effect of microalbuminuria-lowering on regression of left ventricular hypertrophy in children and adolescents with essential hypertension

    Directory of Open Access Journals (Sweden)

    Assadi F ; Translated by: Akbari Asbagh P

    2007-04-01

    Full Text Available Background: Microalbuminuria (MA is associated with increased cardiovascular risk in hypertensive patients, but not many studies have specifically examined the effects of MA-lowering on regression of left ventricular hypertrophy (LVH among pediatric patients with hypertension. Methods: Fifty-five patients with essential hypertension, 11 to 19 years old were prospectively studied. All patients received concomitant therapy of hydrochlorothiazide and angiotensin-converting-enzyme inhibitor. Five patients also required angiotensin-receptor blocker to achieve the blood pressure goal. Baseline and 12-month follow-up measures of left ventricular mass index (LVMI determined by echocardiography and urine microalbumin/creatinine ratio (MA/Cr were collected. MA was defined as MA/Cr>30. LVH was defined as LVMI>38.6 g/m2. The primary end points were 25% or more reductions in MA and the LVMI. Results: Weight (r=0.83, body surface area (r=0.85, body mass index (BMI (r=0.86, systolic blood pressure (SBP (r=0.57, diastolic blood pressure (DBP (r=0.49, mean arterial pressure (r=0.53 and MA (r=0.87 were all univariate correlates of LVMI. In a multiple regression analysis, MA, BMI and SBP were significant correlates of LVMI. MA alone explained 76% of the variance of LVMI, whereas BMI and SBP explained only 1.6% and 0.4% of the variance, respectively. MA was the most significant correlate of follow-up LVMI after BMI and SBP were included in the overall multiple regression models. Conclusion: MA is a strong predictor of LVH in hypertensive children and adolescents. MA-lowering halts the progression of LVH or induces its regression.

  19. Decreased KCNE2 expression participates in the development of cardiac hypertrophy

    Institute of Scientific and Technical Information of China (English)

    DENG Jian-xin; LIU Wen-juan; DING Wen-wen; WANG Gang; LIU Jie

    2016-01-01

    AIM:To investigate whether KCNE 2 participates in the development of pathological hypertrophy .METHODS:Bidirectional ma-nipulations of KCNE2 expression were performed by adenoviral overexpression of KCNE 2 or knockdown of KCNE2 with RNA interfer-ence in PE-induced neonatal rat ventricular myocytes .Then overexpression of KCNE 2 in mouse model of left ventricular hypertrophy in-duced by transverse aortic constriction (TAC) by ultrasound microbubble-mediated gene transfer were used to detect the therapeutic function of KCNE2 in the development of hypertrophy .RESULTS:KCNE2 expression was significantly decreased in PE-induced hy-pertrophic cardiomyocytes and in hypertrophic hearts produced by TAC .Knockdown of KCNE2 in cardiomyocytes reproduced hypertro-phy, whereas overexpression of KCNE2 attenuated PE-induced cardiomyocyte hypertrophy .Knockdown of KCNE2 increased calcineurin activity and nuclear NFAT protein level , and pretreatment with nifedipine or FK 506 attenuated decreased KCNE 2-induced cardiomyo-cyte hypertrophy .Overexpression of KCNE 2 in heart by ultrasound microbubble-mediated gene transfer suppressed the development of hypertrophy and activation of calcineurin-NFAT and MAPK pathways in TAC mice .CONCLUSION:These findings demonstrate that cardiac KCNE2 expression is decreased and contributes to the development of hypertrophy via activation of calcineurin -NFAT and MAPK pathways .

  20. 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.

  1. The effect of systemic hypertension on exercise tomographic thallium-201 imaging in the absence of electrocardiographic left ventricular hypertrophy.

    Science.gov (United States)

    Grogan, M; Christian, T F; Miller, T D; Bailey, K R; Gibbons, R J

    1993-08-01

    This study was designed to assess the effect of systemic hypertension on exercise thallium-201 imaging. The study group consisted of 38 patients with systemic hypertension who were compared with 68 normotensive patients. All patients had a low pretest likelihood of coronary artery disease to minimize the influence of selection bias. Patients with electrocardiographic evidence of left ventricular hypertrophy were excluded. Single-photon emission computed tomographic thallium-201 images were obtained immediately after exercise and 4 hours after exercise. Thallium tomographic images were assessed qualitatively by 14 short-axis segments and were grouped into three coronary distributions. Regional and global quantitative analysis was also performed by using a reference study group at low risk for coronary artery disease. The hypertensive group demonstrated higher resting systolic blood pressure (137 +/- 26 mm Hg vs 120 +/- 14 mm Hg in the normotensive group, p = 0.0002) immediately before exercise. There was no significant difference between hypertensive and normotensive groups in peak exercise systolic blood pressure (181 +/- 31 mm Hg vs 172 +/- mm Hg, p = NS). The normotensive group achieved a significantly higher peak exercise heart rate (162 +/- 18 vs 146 +/- 20 beats/min in the hypertensive group, p = 0.0001) and higher estimated oxygen uptake (11.0 +/- 3.4 vs 9.1 +/- 2.7 metabolic equivalents [METS] in the hypertensive group, p = 0.003). However, rate-pressure products for both groups were nearly identical.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8338002

  2. Independent influence of overweight and obesity on the regression of left ventricular hypertrophy in hypertensive patients: a meta-analysis.

    Science.gov (United States)

    Zhang, Kun; Huang, Feifei; Chen, Jie; Cai, Qingqing; Wang, Tong; Zou, Rong; Zuo, Zhiyi; Wang, Jingfeng; Huang, Hui

    2014-11-01

    Overweight and obesity are associated with adverse cardiovascular outcomes. However, the role of overweight and obesity in left ventricular hypertrophy (LVH) of hypertensive patients is controversial. The aim of the current meta-analysis was to evaluate the influence of overweight and obesity on LVH regression in the hypertensive population.Twenty-eight randomized controlled trials comprising 2403 hypertensive patients (mean age range: 43.8-66.7 years) were identified. Three groups were divided according to body mass index: normal weight, overweight, and obesity groups.Compared with the normal-weight group, LVH regression in the overweight and obesity groups was more obvious with less reduction of systolic blood pressure after antihypertensive therapies (P regressing LVH in overweight and obese hypertensive patients (19.27 g/m, 95% confidence interval [15.25, 23.29], P regression was found in 24-h ambulatory blood pressure monitoring (ABPM) group and in relatively young patients (40-60 years' old) group (P Overweight and obesity are independent risk factors for LVH in hypertensive patients. Intervention at an early age and monitoring by ABPM may facilitate therapy-induced LVH regression in overweight and obese hypertensive patients.

  3. Association of systolic dysfunction with left ventricular hypertrophy and diastolic dysfunction in hypertensive patients.

    Science.gov (United States)

    Piskorz, Daniel; Bongarzoni, Laureano; Citta, Luciano; Citta, Norberto; Citta, Paula; Keller, Luis; Tommasi, Alicia

    2014-01-01

    ntroducción: La presencia de disfunción sistólica no ha sido reconocida en pacientes (p) hipertensos. Objetivos: El objetivo del presente estudio es demostrar que los p hipertensos con hipertrofia ventricular izquierda (HVI) presentan disfunción sistólica, y que ella se incrementa cuando se asocia a disfunción diastólica (DD). Material y métodos: estudio observacional de corte transversal con la muestra recolectada en forma prospectiva de acuerdo a criterios de inclusión y exclusión preestablecidos. La función ventricular izquierda fue evaluada por ecocardiografía convencional, Doppler del orificio valvular mitral y Doppler tisular siguiendo las normativas internacionales. Los p fueron divididos en cuatro grupos de acuerdo a la presencia o ausencia de HVI y DD. Análisis estadístico: test t de students y test de ANOVA, significación estadística velocidad de acortamiento longitudinal de las fibras miocárdicas, medida como onda s con Doppler tisular fue 6,3 +1,1 cm/seg en p HVI+ DD+, 7,2+1,3 cm/seg en p HVI+ DD-, 6,8+1,2 cm/seg en p HVI- DD+, y 7,8+0,6 cm/seg en p HVI- DD- (<0,005). Conclusiones: los p hipertensos presentan disfunción sistólica cuando la HVI está presente y es mayor cuando se asocia a DD.

  4. Follistatin like 1 Regulates Hypertrophy in Heart Failure with Preserved Ejection Fraction

    Science.gov (United States)

    Wilson, Richard M.; Essick, Eric E.; Fowler, Conor T.; Nakamura, Kazuto; van den Hoff, Maurice; Ouchi, Noriyuki; Sam, Flora

    2016-01-01

    Objective We sought to determine whether Fstl1 plays a role in the regulation of cardiac hypertrophy in HFpEF. Background Heart failure (HF) with preserved ejection fraction (HFpEF), accounts for ~50% of all clinical presentations of HF and its prevalence is expected to increase. However, there are no evidence-based therapies for HFpEF; thus, HFpEF represents a major unmet need. Although hypertension is the single most important risk factor for HFpEF, with a prevalence of 60-89% from clinical trials and human HF registries, blood pressure therapy alone is insufficient to prevent and treat HFpEF. Follistatin like 1 (Fstl1), a divergent member of the follistatin family of extracellular glycoproteins, has previously been shown to be elevated in HF with reduced ejection fraction (HFrEF) and associated with increased left ventricular mass. Methods and Results In this study, blood levels of Fstl1 were increased in humans with HFpEF. This increase was also evident in mice with hypertension-induced HFpEF and adult rat ventricular myocytes stimulated with aldosterone. Treatment with recombinant Fstl1 abrogated aldosterone-induced cardiac myocyte hypertrophy, suggesting a role for Fstl1 in the regulation of hypertrophy in HFpEF. There was also a reduction in the E/A ratio, a measure of diastolic dysfunction. Furthermore, HFpEF induced in a mouse model that specifically ablates Fstl1 in cardiac myocytes (cFstl1-KO), showed exacerbation of HFpEF with worsened diastolic dysfunction. In addition, cFstl1-KO-HFpEF mice demonstrated more marked cardiac myocyte hypertrophy with increased molecular markers of anp and bnp expression. Conclusions These findings indicate that Fstl1exerts therapeutic effects by modulating cardiac hypertrophy in HFpEF. PMID:27430031

  5. Identification of caveolar resident proteins in ventricular myocytes using a quantitative proteomic approach: dynamic changes in caveolar composition following adrenoceptor activation.

    Science.gov (United States)

    Wypijewski, Krzysztof J; Tinti, Michele; Chen, Wenzhang; Lamont, Douglas; Ashford, Michael L J; Calaghan, Sarah C; Fuller, William

    2015-03-01

    The lipid raft concept proposes that membrane environments enriched in cholesterol and sphingolipids cluster certain proteins and form platforms to integrate cell signaling. In cardiac muscle, caveolae concentrate signaling molecules and ion transporters, and play a vital role in adrenergic regulation of excitation-contraction coupling, and consequently cardiac contractility. Proteomic analysis of cardiac caveolae is hampered by the presence of contaminants that have sometimes, erroneously, been proposed to be resident in these domains. Here we present the first unbiased analysis of the proteome of cardiac caveolae, and investigate dynamic changes in their protein constituents following adrenoreceptor (AR) stimulation. Rat ventricular myocytes were treated with methyl-β-cyclodextrin (MβCD) to deplete cholesterol and disrupt caveolae. Buoyant caveolin-enriched microdomains (BCEMs) were prepared from MβCD-treated and control cell lysates using a standard discontinuous sucrose gradient. BCEMs were harvested, pelleted, and resolubilized, then alkylated, digested, and labeled with iTRAQ reagents, and proteins identified by LC-MS/MS on a LTQ Orbitrap Velos Pro. Proteins were defined as BCEM resident if they were consistently depleted from the BCEM fraction following MβCD treatment. Selective activation of α-, β1-, and β2-AR prior to preparation of BCEMs was achieved by application of agonist/antagonist pairs for 10 min in populations of field-stimulated myocytes. We typically identified 600-850 proteins per experiment, of which, 249 were defined as high-confidence BCEM residents. Functional annotation clustering indicates cardiac BCEMs are enriched in integrin signaling, guanine nucleotide binding, ion transport, and insulin signaling clusters. Proteins possessing a caveolin binding motif were poorly enriched in BCEMs, suggesting this is not the only mechanism that targets proteins to caveolae. With the notable exception of the cavin family, very few proteins show

  6. Identification of Caveolar Resident Proteins in Ventricular Myocytes Using a Quantitative Proteomic Approach: Dynamic Changes in Caveolar Composition Following Adrenoceptor Activation*

    Science.gov (United States)

    Wypijewski, Krzysztof J.; Tinti, Michele; Chen, Wenzhang; Lamont, Douglas; Ashford, Michael L. J.; Calaghan, Sarah C.; Fuller, William

    2015-01-01

    The lipid raft concept proposes that membrane environments enriched in cholesterol and sphingolipids cluster certain proteins and form platforms to integrate cell signaling. In cardiac muscle, caveolae concentrate signaling molecules and ion transporters, and play a vital role in adrenergic regulation of excitation–contraction coupling, and consequently cardiac contractility. Proteomic analysis of cardiac caveolae is hampered by the presence of contaminants that have sometimes, erroneously, been proposed to be resident in these domains. Here we present the first unbiased analysis of the proteome of cardiac caveolae, and investigate dynamic changes in their protein constituents following adrenoreceptor (AR) stimulation. Rat ventricular myocytes were treated with methyl-β-cyclodextrin (MβCD) to deplete cholesterol and disrupt caveolae. Buoyant caveolin-enriched microdomains (BCEMs) were prepared from MβCD-treated and control cell lysates using a standard discontinuous sucrose gradient. BCEMs were harvested, pelleted, and resolubilized, then alkylated, digested, and labeled with iTRAQ reagents, and proteins identified by LC-MS/MS on a LTQ Orbitrap Velos Pro. Proteins were defined as BCEM resident if they were consistently depleted from the BCEM fraction following MβCD treatment. Selective activation of α-, β1-, and β2-AR prior to preparation of BCEMs was achieved by application of agonist/antagonist pairs for 10 min in populations of field-stimulated myocytes. We typically identified 600–850 proteins per experiment, of which, 249 were defined as high-confidence BCEM residents. Functional annotation clustering indicates cardiac BCEMs are enriched in integrin signaling, guanine nucleotide binding, ion transport, and insulin signaling clusters. Proteins possessing a caveolin binding motif were poorly enriched in BCEMs, suggesting this is not the only mechanism that targets proteins to caveolae. With the notable exception of the cavin family, very few proteins

  7. Calcium homeostasis in a local/global whole cell model of permeabilized ventricular myocytes with a Langevin description of stochastic calcium release.

    Science.gov (United States)

    Wang, Xiao; Weinberg, Seth H; Hao, Yan; Sobie, Eric A; Smith, Gregory D

    2015-03-01

    Population density approaches to modeling local control of Ca(2+)-induced Ca(2+) release in cardiac myocytes can be used to construct minimal whole cell models that accurately represent heterogeneous local Ca(2+) signals. Unfortunately, the computational complexity of such "local/global" whole cell models scales with the number of Ca(2+) release unit (CaRU) states, which is a rapidly increasing function of the number of ryanodine receptors (RyRs) per CaRU. Here we present an alternative approach based on a Langevin description of the collective gating of RyRs coupled by local Ca(2+) concentration ([Ca(2+)]). The computational efficiency of this approach no longer depends on the number of RyRs per CaRU. When the RyR model is minimal, Langevin equations may be replaced by a single Fokker-Planck equation, yielding an extremely compact and efficient local/global whole cell model that reproduces and helps interpret recent experiments that investigate Ca(2+) homeostasis in permeabilized ventricular myocytes. Our calculations show that elevated myoplasmic [Ca(2+)] promotes elevated network sarcoplasmic reticulum (SR) [Ca(2+)] via SR Ca(2+)-ATPase-mediated Ca(2+) uptake. However, elevated myoplasmic [Ca(2+)] may also activate RyRs and promote stochastic SR Ca(2+) release, which can in turn decrease SR [Ca(2+)]. Increasing myoplasmic [Ca(2+)] results in an exponential increase in spark-mediated release and a linear increase in nonspark-mediated release, consistent with recent experiments. The model exhibits two steady-state release fluxes for the same network SR [Ca(2+)] depending on whether myoplasmic [Ca(2+)] is low or high. In the later case, spontaneous release decreases SR [Ca(2+)] in a manner that maintains robust Ca(2+) sparks. PMID:25485896

  8. A Study on the Relationship between Hypertensive Left VentricularHypertrophy and Ventricular Premature Beat%高血压左心室肥厚与室性过早搏动关系的研究

    Institute of Scientific and Technical Information of China (English)

    罗明; 宋浩明; 邓南伟

    2001-01-01

    Objective To study the relationship between hypertensive left ventricular hypertrophy (LVH) and ventricular premature beat. Methods The relationship between LVH and ventricular premature beat in 87 hypertensive patients was analyzed by the data of echocadiography and dynamic electrocardiography examinations. Results Ventricular premature beat and couples ventricular premature beat occurred more frequently in LVH than in non-LVH (P<0.05 and P<0.01 respectively).Linear correlation was found between wall thickness of left ventricle and ventricular premature beat grades (r=0.781,P<0.01). Conclusion It is concluded that the incidence of premature beat not only correlates with LVH but also its ventricular premature beat grade correlates with the wall thickness of left ventricle.%-01)。结论高血压病人室性过早搏动的发生与左室肥厚有关,而且其严重程度与左室厚度有关。

  9. 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

  10. Thallium myocardial perfusion scans for the assessment of right ventricular hypertrophy in patients with cystic fibrosis. A comparison with other noninvasive techniques

    Energy Technology Data Exchange (ETDEWEB)

    Newth, C.J.; Corey, M.L.; Fowler, R.S.; Gilday, D.L.; Gross, D.; Mitchell, I.

    1981-01-01

    The incidence of right ventricular hypertrophy in 32 patients with cystic fibrosis was studied using thallium 201 (TI-201) myocardial perfusion scans, and compared with other noninvasive techniques including electrocardiography, vectorcardiography, and M-mode echocardiography. The patients (mean age, 17.3 yr; range, 7 to 33) had a wide range of clinical and pulmonary abnormalities (mean Shwachman-Kulczycki score, 66.6). In the total study group, TI-201 scans, like the vectorcardiograms and the M-mode echocardiograms, gave a surprisingly high proportion of positive predictions for right ventricular hypertrophy (RVH) (44%). The correlations with all other noninvasive methods were uniformly poor, so caution must be exercised in using this technique to predict early RVH in order to follow the natural history of cor pulmonale in cystic fibrosis. At the time of the study, 6 patients had clinical evidence of right ventricular failure, and in this disease setting must have had RVH. In 3 patients, RVH was confirmed at autopsy, and it was successfully predicted by TI-201 scans in 5 of the 6 patients. The false negative scan may have been due to regional myocardial ischemia secondary to severe right ventricular failure. In contrast, the vectorcardiogram, using Fowler's new criteria, made a successful prediction of RVH in all 6 patients, and the electro cardiogram in only 3. Although the M-mode echocardiogram was abnormal in all patients, it would have predicted RVH (with increased right ventricular anterior wall thickness) in only 1 patient. We concluded that TI-201 myocardial perfusion cans are good at confirming RVH in cases with established right ventricular failure, but have no advantage over vectorcardiographic assessments, which are logistically easier to perform and carry no radiation risks.

  11. Thallium myocardial perfusion scans for the assessment of right ventricular hypertrophy in patients with cystic fibrosis. A comparison with other noninvasive techniques

    International Nuclear Information System (INIS)

    The incidence of right ventricular hypertrophy in 32 patients with cystic fibrosis was studied using thallium 201 (TI-201) myocardial perfusion scans, and compared with other noninvasive techniques including electrocardiography, vectorcardiography, and M-mode echocardiography. The patients (mean age, 17.3 yr; range, 7 to 33) had a wide range of clinical and pulmonary abnormalities (mean Shwachman-Kulczycki score, 66.6). In the total study group, TI-201 scans, like the vectorcardiograms and the M-mode echocardiograms, gave a surprisingly high proportion of positive predictions for right ventricular hypertrophy (RVH) (44%). The correlations with all other noninvasive methods were uniformly poor, so caution must be exercised in using this technique to predict early RVH in order to follow the natural history of cor pulmonale in cystic fibrosis. At the time of the study, 6 patients had clinical evidence of right ventricular failure, and in this disease setting must have had RVH. In 3 patients, RVH was confirmed at autopsy, and it was successfully predicted by TI-201 scans in 5 of the 6 patients. The false negative scan may have been due to regional myocardial ischemia secondary to severe right ventricular failure. In contrast, the vectorcardiogram, using Fowler's new criteria, made a successful prediction of RVH in all 6 patients, and the electro cardiogram in only 3. Although the M-mode echocardiogram was abnormal in all patients, it would have predicted RVH (with increased right ventricular anterior wall thickness) in only 1 patient. We concluded that TI-201 myocardial perfusion cans are good at confirming RVH in cases with established right ventricular failure, but have no advantage over vectorcardiographic assessments, which are logistically easier to perform and carry no radiation risks

  12. The importance of trabecular hypertrophy in right ventricular adaptation to chronic pressure overload.

    Science.gov (United States)

    van de Veerdonk, Mariëlle C; Dusoswa, Sophie A; Marcus, J Tim; Bogaard, Harm-Jan; Spruijt, Onno; Kind, Taco; Westerhof, Nico; Vonk-Noordegraaf, Anton

    2014-02-01

    To assess the contribution of right ventricular (RV) trabeculae and papillary muscles (TPM) to RV mass and volumes in controls and patients with pulmonary arterial hypertension (PAH). Furthermore, to evaluate whether TPM shows a similar response as the RV free wall (RVFW) to changes in pulmonary artery pressure (PAP) during follow-up. 50 patients underwent cardiac magnetic resonance (CMR) and right heart catheterization at baseline and after one-year follow-up. Furthermore 20 controls underwent CMR. RV masses were assessed with and without TPM. TPM constituted a larger proportion of total RV mass and RV end-diastolic volume (RVEDV) in PAH than in controls (Mass: 35 ± 7 vs. 25 ± 5 %; p TPM mass was related to the RVFW mass in patients (baseline: R = 0.65; p TPM from the assessment resulted in altered RV mass, volumes and function than when included (all p TPM mass (β = 0.44; p = 0.004) but not the changes in RVFW mass (p = 0.095) were independently related to changes in PAP during follow-up. RV TPM showed a larger contribution to total RV mass in PAH (~35 %) compared to controls (~25 %). Inclusion of TPM in the analyses significantly influenced the magnitude of the RV volumes and mass. Furthermore, TPM mass was stronger related to changes in PAP than RVFW mass. Our results implicate that TPM are important contributors to RV adaptation during pressure overload and cannot be neglected from the RV assessment.

  13. Urocortin 2 stimulates nitric oxide production in ventricular myocytes via Akt- and PKA-mediated phosphorylation of eNOS at serine 1177

    Science.gov (United States)

    Walther, Stefanie; Pluteanu, Florentina; Renz, Susanne; Nikonova, Yulia; Maxwell, Joshua T.; Yang, Li-Zhen; Schmidt, Kurt; Edwards, Joshua N.; Wakula, Paulina; Groschner, Klaus; Maier, Lars S.; Spiess, Joachim; Blatter, Lothar A.; Pieske, Burkert

    2014-01-01

    Urocortin 2 (Ucn2) is a cardioactive peptide exhibiting beneficial effects in normal and failing heart. In cardiomyocytes, it elicits cAMP- and Ca2+-dependent positive inotropic and lusitropic effects. We tested the hypothesis that, in addition, Ucn2 activates cardiac nitric oxide (NO) signaling and elucidated the underlying signaling pathways and mechanisms. In isolated rabbit ventricular myocytes, Ucn2 caused concentration- and time-dependent increases in phosphorylation of Akt (Ser473, Thr308), endothelial NO synthase (eNOS) (Ser1177), and ERK1/2 (Thr202/Tyr204). ERK1/2 phosphorylation, but not Akt and eNOS phosphorylation, was suppressed by inhibition of MEK1/2. Increased Akt phosphorylation resulted in increased Akt kinase activity and was mediated by corticotropin-releasing factor 2 (CRF2) receptors (astressin-2B sensitive). Inhibition of phosphatidylinositol 3-kinase (PI3K) diminished both Akt as well as eNOS phosphorylation mediated by Ucn2. Inhibition of protein kinase A (PKA) reduced Ucn2-induced phosphorylation of eNOS but did not affect the increase in phosphorylation of Akt. Conversely, direct receptor-independent elevation of cAMP via forskolin increased phosphorylation of eNOS but not of Akt. Ucn2 increased intracellular NO concentration ([NO]i), [cGMP], [cAMP], and cell shortening. Inhibition of eNOS suppressed the increases in [NO]i and cell shortening. When both PI3K-Akt and cAMP-PKA signaling were inhibited, the Ucn2-induced increases in [NO]i and cell shortening were attenuated. Thus, in rabbit ventricular myocytes, Ucn2 causes activation of cAMP-PKA, PI3K-Akt, and MEK1/2-ERK1/2 signaling. The MEK1/2-ERK1/2 pathway is not required for stimulation of NO signaling in these cells. The other two pathways, cAMP-PKA and PI3K-Akt, converge on eNOS phosphorylation at Ser1177 and result in pronounced and sustained cellular NO production with subsequent stimulation of cGMP signaling. PMID:25015964

  14. Calcium-sensing receptor activation contributed to apoptosis stimulates TRPC6 channel in rat neonatal ventricular myocytes

    International Nuclear Information System (INIS)

    Capacitative calcium entry (CCE) refers to the influx of calcium through plasma membrane channels activated on depletion of endoplasmic sarcoplasmic/reticulum (ER/SR) Ca2+ stores, which is performed mainly by the transient receptor potential (TRP) channels. TRP channels are expressed in cardiomyocytes. Calcium-sensing receptor (CaR) is also expressed in rat cardiac tissue and plays an important role in mediating cardiomyocyte apoptosis. However, there are no data regarding the link between CaR and TRP channels in rat heart. In this study, in rat neonatal myocytes, by Ca2+ imaging, we found that the depletion of ER/SR Ca2+ stores by thapsigargin (TG) elicited a transient rise in cytoplasmic Ca2+ ([Ca2+]i), followed by sustained increase depending on extracellular Ca2+. But, TRP channels inhibitor (SKF96365), not L-type channels or the Na+/Ca2+ exchanger inhibitors, inhibited [Ca2+]i relatively high. Then, we found that the stimulation of CaR with its activator gadolinium chloride (GdCl3) or by an increased extracellular Ca2+([Ca2+]o) increased the concentration of intracelluar Ca2+, whereas, the sustained elevation of [Ca2+]i was reduced in the presence of SKF96365. Similarly, the duration of [Ca2+]i increase was also shortened in the absence of extracellular Ca2+. Western blot analysis showed that GdCl3 increased the expression of TRPC6, which was reversed by SKF96365. Additionally, SKF96365 reduced cardiomyocyte apoptosis induced by GdCl3. Our results suggested that CCE exhibited in rat neonatal myocytes and CaR activation induced Ca2+-permeable cationic channels TRPCs to gate the CCE, for which TRPC6 was one of the most likely candidates. TRPC6 channel was functionally coupled with CaR to enhance the cardiomyocyte apoptosis.

  15. The metabolic syndrome and ECG detected left ventricular hypertrophy--influences from IGF-1 and IGF-binding protein-1.

    Directory of Open Access Journals (Sweden)

    Mats Halldin

    Full Text Available BACKGROUND AND AIMS: The metabolic syndrome (MetS is associated with an increased risk for left ventricular hypertrophy (LVH and cardiovascular mortality. The aim of this study was to investigate potential influences from insulin-like growth factor-1 (IGF-1 and IGF binding protein-1 (IGFBP-1 on the relationship between the MetS and LVH, also taking into account the role of physical activity (PA, use of oestrogen and gender. METHODS AND RESULTS: In a population-based cross-sectional study of 60-year-old men (n = 1822 and women (n = 2049 participants underwent physical examination and laboratory tests, including electrocardiography (ECG, and completed an extensive questionnaire. Women showed higher levels of IGFBP-1 than men (37.0 vs. 28.0 µg/l, p < 0.001, and women with LVH had lower levels of IGFBP-1 than women without LVH (31.0 µg/l vs. 37.0 µg/l, p < 0.001. Furthermore, women with low levels of IGFBP-1 had a significantly increased risk of having LVH (crude OR ≈ 2.5. When stratifying for PA and oestrogen, respectively, a weaker association between IGFBP-1 and LVH was demonstrated in physically active men and women, compared to inactive individuals, as well as in women using oestrogen, compared to non-users. CONCLUSION: In a representative sample of 60-year-old Swedish men and women, the main findings were higher levels of IGFBP-1 in women than in men; lower levels of IGFBP-1 in women with LVH, compared to women without LVH; and an increased risk of having LVH in women with low levels of IGFBP-1. The association between IGFBP-1 and LVH was diminished in physically active men and women, as well as in women using oestrogen.

  16. Left ventricular hypertrophy in relation to systolic blood pressure and the angiotensin converting enzyme I/D polymorphism in Chinese

    Institute of Scientific and Technical Information of China (English)

    Alexander P. Headley; Yan Li; Yi Zhang; Ji-Yong Ge; Qi-Fang Huang; Ji-Guang Wang

    2009-01-01

    Objective There is little population-based data on the prevalence and the environmental or genetic determinants of left ventricular hypertrophy (LVH) in China. The purpose of this paper is to study LVH in relation to systolic blood pressure and the angiotensin converting enzyme (ACE) insertion/deletion(I/D) polymorphism in Chinese. Methods We recorded 12-lead ECG (CardioSoft, v4.2) in 1365 residents in the Jingning County, Zhejiang Province, China. LVH was defined according to the gender-specific Sokolow-Lyon and Comell product ECG criteria. Results Regardless of whether the Sokolow-Lyon or Comell product ECG criteria was used, the prevalence of LVH (20.7% and 4.8%, respectively) significantly (P<0.0001) increased with male gender (odds ratio [OR] 2.33 and 7.15) and systolic blood pressure (per 10 mm Hg increase, OR 1.46 and 1.33). If the Sokolow-Lyon criteria was used, the prevalence of LVH was also influenced by alcohol intake (OR 1.44, P=0.03) and body mass index (OR 0.83, P=0.0005). The association between the Sokolow-Lyon voltage amplitude and the ACE I/D polymorphism was dependent on antihypertensive therapy (P=0.01). In 1262 untreated subjects, but not 103 patients on antihypertensive medication, the ACE DD compared with Ⅱ subjects had significantly higher Sokolow-Lyon voltage amplitudes (29.8±0.6 vs. 28.0±20.5 mV, P=0.02) and higher risk of LVH (OR 1.74, 95% CI: 1. 12-2.69, P=0.01). Conclusion LVH is prevalent in Chinese, and is associated with systolic blood pressure and the ACE D allele. The genetic association might be modulated by antihypertensive therapy.

  17. The occurrence of left ventricular hypertrophy in normotensive individuals in a community setting in North-East Trinidad

    Directory of Open Access Journals (Sweden)

    Bacchus R

    2011-07-01

    Full Text Available Romel Bacchus, Kristianna Singh, Ijaz Ogeer, Kameel MungrueDepartment Paraclinical Sciences, Public Health and Primary Care Unit, Faculty of Medical Sciences, University of the West Indies, EWMSC, Mt Hope TrinidadObjective: The purpose of this study is to determine primarily the occurrence of left ventricular hypertrophy (LVH in normotensive Trinidadians.Design and methods: Enrolment into the study required participants to have normal blood pressure (≤140/90 using the JNC 7 (The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure classification, free of type 2 diabetes, as well as no existing LVH. Upon entry into the study, participants were first screened for LVH using a standard 12-lead electrocardiogram (ECG, using the Sokolow–Lyon index and the Cornell index. ECHO was used to confirm or refute the diagnosis of LVH.Results: A total of 209 patients met the criteria for entry into the study. Of these, 63.6% had LVH using Cornell criteria and 68.2% using LVH by Sokolow–Lyon criteria. Subsequently, ECHO confirmed the diagnosis in 2.9% using American Society of Echocardiography criteria and 1.5% using World Health Organization criteria. Thus the estimated prevalence of LVH in normotensive individuals was approximately 3%.Conclusion: The estimated prevalence of LVH in normotensive individuals appears to be relatively high if an ECG is the single investigation performed, which is common in our setting and may also be common in the developing world. However, using ECHO, the prevalence of LVH approaches a value similarly reported in the literature. Therefore, these findings raise two important issues: 1 the use of criteria such as the Cornell and Sokolow–Lyon voltage criteria established in the developed world from populations of vastly different ethnic backgrounds may not be widely applicable, and 2 all individuals suspected of having LVH should have an ECHO

  18. The effect of obesity on electrocardiographic detection of hypertensive left ventricular hypertrophy: recalibration against cardiac magnetic resonance.

    Science.gov (United States)

    Rodrigues, J C L; McIntyre, B; Dastidar, A G; Lyen, S M; Ratcliffe, L E; Burchell, A E; Hart, E C; Bucciarelli-Ducci, C; Hamilton, M C K; Paton, J F R; Nightingale, A K; Manghat, N E

    2016-03-01

    Electrocardiograph (ECG) criteria for left ventricular hypertrophy (LVH) are a widely used clinical tool. We recalibrated six ECG criteria for LVH against gold-standard cardiac magnetic resonance (CMR) and assessed the impact of obesity. One hundred and fifty consecutive tertiary hypertension clinic referrals for CMR (1.5 T) were reviewed. Patients with cardiac pathology potentially confounding hypertensive LVH were excluded (n=22). The final sample size was 128 (age: 51.0±15.2 years, 48% male). LVH was defined by CMR. From a 12-lead ECG, Sokolow-Lyon voltage and product, Cornell voltage and product, Gubner-Ungerleidger voltage and Romhilt-Estes score were evaluated, blinded to the CMR. ECG diagnostic performance was calculated. LVH by CMR was present in 37% and obesity in 51%. Obesity significantly reduced ECG sensitivity, because of significant attenuation in mean ECG values for Cornell voltage (22.2±5.7 vs 26.4±9.4 mm, PECG specificity, because of significantly higher prevalence of LV remodeling (no LVH but increased mass-to-volume ratio) in obese subjects without LVH (36% vs 16%, PECG LVH criteria values. Obesity-specific partition values were generated at fixed 95% specificity; Cornell voltage had highest sensitivity in non-obese (56%) and Sokolow-Lyon product in obese patients (24%). Obesity significantly lowers ECG sensitivity at detecting LVH, by attenuating ECG LVH values, and lowers ECG specificity through changes associated with LV remodeling. Our obesity-specific ECG partition values could improve the diagnostic performance in obese patients with hypertension. PMID:26040440

  19. Severe Left Ventricular Hypertrophy, Small Pericardial Effusion, and Diffuse Late Gadolinium Enhancement by Cardiac Magnetic Resonance Suspecting Cardiac Amyloidosis: Endomyocardial Biopsy Reveals an Unexpected Diagnosis

    Directory of Open Access Journals (Sweden)

    Nina P. Hofmann

    2016-01-01

    Full Text Available Left ventricular (LV hypertrophy can be related to a multitude of cardiac disorders, such as hypertrophic cardiomyopathy (HCM, cardiac amyloidosis, and hypertensive heart disease. Although the presence of LV hypertrophy is generally associated with poorer cardiac outcomes, the early differentiation between these pathologies is crucial due to the presence of specific treatment options. The diagnostic process with LV hypertrophy requires the integration of clinical evaluation, electrocardiography (ECG, echocardiography, biochemical markers, and if required CMR and endomyocardial biopsy in order to reach the correct diagnosis. Here, we present a case of a patient with severe LV hypertrophy (septal wall thickness of 23 mm, LV mass of 264 g, and LV mass index of 147 g/m2, severely impaired longitudinal function, and preserved radial contractility (ejection fraction = 55%, accompanied by small pericardial effusion and diffuse late gadolinium enhancement (LGE by cardiac magnetic resonance (CMR. Due to the imaging findings, an infiltrative cardiomyopathy, such as cardiac amyloidosis, was suspected. However, amyloid accumulation was excluded by endomyocardial biopsy, which revealed the presence of diffuse myocardial fibrosis in an advanced hypertensive heart disease.

  20. Pressure-overload hypertrophy of the developing heart reveals activation of divergent gene and protein pathways in the left and right ventricular myocardium.

    Science.gov (United States)

    Friehs, Ingeborg; Cowan, Douglas B; Choi, Yeong-Hoon; Black, Kendra M; Barnett, Reanne; Bhasin, Manoj K; Daly, Christian; Dillon, Simon J; Libermann, Towia A; McGowan, Francis X; del Nido, Pedro J; Levitsky, Sidney; McCully, James D

    2013-03-01

    Right ventricular (RV) and left ventricular (LV) myocardium differ in their pathophysiological response to pressure-overload hypertrophy. In this report we use microarray and proteomic analyses to identify pathways modulated by LV-aortic banding (AOB) and RV-pulmonary artery banding (PAB) in the immature heart. Newborn New Zealand White rabbits underwent banding of the descending thoracic aorta [LV-AOB; n = 6]. RV-PAB was achieved by banding the pulmonary artery (n = 6). Controls (n = 6 each) were sham-manipulated. After 4 (LV-AOB) and 6 (RV-PAB) wk recovery, the hearts were removed and matched RNA and proteins samples were isolated for microarray and proteomic analysis. Microarray and proteomic data demonstrate that in LV-AOB there is increased transcript expression levels for oxidative phosphorylation, mitochondria energy pathways, actin, ILK, hypoxia, calcium, and protein kinase-A signaling and increased protein expression levels of proteins for cellular macromolecular complex assembly and oxidative phosphorylation. In RV-PAB there is also an increased transcript expression levels for cardiac oxidative phosphorylation but increased protein expression levels for structural constituents of muscle, cardiac muscle tissue development, and calcium handling. These results identify divergent transcript and protein expression profiles in LV-AOB and RV-PAB and provide new insight into the biological basis of ventricular specific hypertrophy. The identification of these pathways should allow for the development of specific therapeutic interventions for targeted treatment and amelioration of LV-AOB and RV-PAB to ameliorate morbidity and mortality.

  1. Carbon Nanohorns Promote Maturation of Neonatal Rat Ventricular Myocytes and Inhibit Proliferation of Cardiac Fibroblasts: a Promising Scaffold for Cardiac Tissue Engineering

    Science.gov (United States)

    Wu, Yujing; Shi, Xiaoli; Li, Yi; Tian, Lei; Bai, Rui; Wei, Yujie; Han, Dong; Liu, Huiliang; Xu, Jianxun

    2016-06-01

    Cardiac tissue engineering (CTE) has developed rapidly, but a great challenge remains in finding practical scaffold materials for the construction of engineered cardiac tissues. Carbon nanohorns (CNHs) may be a potential candidate due to their special structure and properties. The purpose of this study was to assess the effect of CNHs on the biological behavior of neonatal rat ventricular myocytes (NRVMs) for CTE applications. CNHs were incorporated into collagen to form growth substrates for NRVMs. Transmission electron microscopy (TEM) observations demonstrated that CNHs exhibited a good affinity to collagen. Moreover, it was found that CNH-embedded substrates enhanced adhesion and proliferation of NRVMs. Immunohistochemical staining, western blot analysis, and intracellular calcium transient measurements indicated that the addition of CNHs significantly increased the expression and maturation of electrical and mechanical proteins (connexin-43 and N-cadherin). Bromodeoxyuridine staining and a Cell Counting Kit-8 assay showed that CNHs have the ability to inhibit the proliferation of cardiac fibroblasts. These findings suggest that CNHs can have a valuable effect on the construction of engineered cardiac tissues and may be a promising scaffold for CTE.

  2. Three-dimensional geometric modeling of membrane-bound organelles in ventricular myocytes: bridging the gap between microscopic imaging and mathematical simulation.

    Science.gov (United States)

    Yu, Zeyun; Holst, Michael J; Hayashi, Takeharu; Bajaj, Chandrajit L; Ellisman, Mark H; McCammon, J Andrew; Hoshijima, Masahiko

    2008-12-01

    A general framework of image-based geometric processing is presented to bridge the gap between three-dimensional (3D) imaging that provides structural details of a biological system and mathematical simulation where high-quality surface or volumetric meshes are required. A 3D density map is processed in the order of image pre-processing (contrast enhancement and anisotropic filtering), feature extraction (boundary segmentation and skeletonization), and high-quality and realistic surface (triangular) and volumetric (tetrahedral) mesh generation. While the tool-chain described is applicable to general types of 3D imaging data, the performance is demonstrated specifically on membrane-bound organelles in ventricular myocytes that are imaged and reconstructed with electron microscopic (EM) tomography and two-photon microscopy (T-PM). Of particular interest in this study are two types of membrane-bound Ca(2+)-handling organelles, namely, transverse tubules (T-tubules) and junctional sarcoplasmic reticulum (jSR), both of which play an important role in regulating the excitation-contraction (E-C) coupling through dynamic Ca(2+) mobilization in cardiomyocytes. PMID:18835449

  3. Effects of Arecoline on Calcium Channel Currents and Caffeine-induced Calcium Release in Isolated Single Ventricular Myocyte of Guinea Pig

    Institute of Scientific and Technical Information of China (English)

    林先明; 李真; 胡本容; 夏国瑾; 姚伟星; 向继洲

    2002-01-01

    Summary: The effects of Arecoline (Are) on calcium mobilization were investigated. In isolatedsingle ventricular myocyte of guinea pig, patch clamp whole cell recording techniques were used torecord the current of L-type calcium channel and cytosolic Ca2+ level ([Ca2+]i) labeled with fluo-rescence probe Fluo-3/AM was measured under a laser scanning confocal microscope. Results re-vealed that Are (3-100 μmol/L) could inhibit L-type calcium current in a concentration-depen-dent manner and the value of IC50 was 33. 73μmol/L (n= 5). In the absence of extracellular calci-um, the resting levels of [Ca2+]i was not affected by Are (n=6, P>0. 05), but pretreatmentwith Are (30 μmol/L) could significantly inhibit the [Ca2+]i elevation induced by caffeine (10mmol/L, n = 6, P < 0. 01). It was concluded that Are could inhibit not only calcium influxthrough L-type calcium channel but also calcium release from sarcoplasmic reticulum.

  4. Carbon Nanohorns Promote Maturation of Neonatal Rat Ventricular Myocytes and Inhibit Proliferation of Cardiac Fibroblasts: a Promising Scaffold for Cardiac Tissue Engineering.

    Science.gov (United States)

    Wu, Yujing; Shi, Xiaoli; Li, Yi; Tian, Lei; Bai, Rui; Wei, Yujie; Han, Dong; Liu, Huiliang; Xu, Jianxun

    2016-12-01

    Cardiac tissue engineering (CTE) has developed rapidly, but a great challenge remains in finding practical scaffold materials for the construction of engineered cardiac tissues. Carbon nanohorns (CNHs) may be a potential candidate due to their special structure and properties. The purpose of this study was to assess the effect of CNHs on the biological behavior of neonatal rat ventricular myocytes (NRVMs) for CTE applications. CNHs were incorporated into collagen to form growth substrates for NRVMs. Transmission electron microscopy (TEM) observations demonstrated that CNHs exhibited a good affinity to collagen. Moreover, it was found that CNH-embedded substrates enhanced adhesion and proliferation of NRVMs. Immunohistochemical staining, western blot analysis, and intracellular calcium transient measurements indicated that the addition of CNHs significantly increased the expression and maturation of electrical and mechanical proteins (connexin-43 and N-cadherin). Bromodeoxyuridine staining and a Cell Counting Kit-8 assay showed that CNHs have the ability to inhibit the proliferation of cardiac fibroblasts. These findings suggest that CNHs can have a valuable effect on the construction of engineered cardiac tissues and may be a promising scaffold for CTE. PMID:27263018

  5. The relation between left ventricular hypertrophy and QT dispersion in patients with primary hypertension%原发性高血压患者左心室肥厚与QT离散度的关系

    Institute of Scientific and Technical Information of China (English)

    蔡录

    2014-01-01

    目的:探讨原发性高血压患者左心室肥厚与QT离散度(QTd)的关系,阐明在高血压治疗中逆转心肌肥厚的意义。方法:选取原发性高血压患者160例,根据有无左心室肥厚分为两组,其中左心室肥厚者78例为LVH组;无左心室肥厚者82例为对照组。比较两组之间左心室改变及QTd差异。结果:LVH组与观察组QTd比较差异有统计学意义(P<0.01)。结论:高血压伴有左室肥厚者的复极离散度明显大于无左室肥厚者。%Objective:To explore the relation between left ventricular hypertrophy and QT dispersion in patients with primary hypertension,and clarify the significance of reversing myocardial hypertrophy in the treatment of hypertension.Methods:160 cases with primary hypertension were selected.They were divided into two groups according to the presence of left ventricular hypertrophy.78 cases had left ventricular hypertrophy as the LVH group.82 cases had non left ventricular hypertrophy as the observation group.The left ventricle changes and QTd differences of two groups were compared.Results:The QTd of the LVH group and the observation group were compared,and the difference was statistically significant(P<0.05).Conclusion:The dispersion of repolarization in hypertension patients with left ventricular hypertrophy is significantly higher than that of non left ventricular hypertrophy.

  6. ROLE OF ALPHA-ADRENERGIC BLOCKING AGENT IN HYPERTROPHY OF CARDIAC MYOCYTE CARDIAC MYOCYTE%α受体阻滞剂对心肌细胞肥大的作用

    Institute of Scientific and Technical Information of China (English)

    谢协驹; 吉丽敏; 符史干

    2001-01-01

    objective:The present study was to investigate the role of alphal-adrenergic receptor blocking agent(phentolamine) in the hypertrophy of cardiaomyocyte induced by adrenaline.Methods:The measurement of cell surface area and[3H]-Leucine incorporation judged the hypertrophy of cardiaomyocyte in cultured neonatal rat myocardal cells,Results:The results showed that adrenaline could significantly increase cell.surface area promote[3H]-Leucine incorporation.Alphal-adrenergic blocking agent could markedly block effects of adrenaline increasing cell surface area and promoting [3H]-Leucine incorporation, Conclusions:These results suggest that alpha-adrenergic blocking agent can prevent the hypertrophy of cardiomyocytes induced by adrenaline in cultured neontal rat myocardal cells.%目的:观察α受体阻滞剂酚妥拉明对肾上腺素诱导的心肌细胞肥大的作用。方法:在培养新生大鼠心肌细胞上。通过测量心肌细胞表面积和[3H]-Leu的掺入量来判断心肌细胞肥大。结果:肾上腺素要明显增加心肌细胞表面和[3H]-亮氨酸([3H-Leu]的掺入量,α受体阻滞剂酚妥拉明能阻断肾上腺素增加心肌细胞表面积和[3H]-Leu掺入量的作用。结论:α受体阻滞有减轻肾上腺素诱导心肌细胞肥大的作用。

  7. Impact of alcohol habits and smoking on the risk of new-onset atrial fibrillation in hypertensive patients with ECG left ventricular hypertrophy: The LIFE Study

    DEFF Research Database (Denmark)

    Ariansen, Inger; Reims, Henrik M; Gjesdal, Knut;

    2012-01-01

    . Methods. In the Losartan Intervention For Endpoint reduction in Hypertension (LIFE) study, a double-blinded, randomized, parallel-group study, 9193 hypertensive patients with electrocardiogram (ECG)-documented left ventricular hypertrophy (LVH), randomized to once-daily losartan- or atenolol......-based antihypertensive therapy were followed for a mean of 4.8 years. At baseline, 8831 patients (54% women, mean age 67 years, mean blood pressure 174/98 mmHg after placebo run-in) had neither a history of AF nor AF on ECG, and they were thus at risk of developing this condition during the study. Results. New-onset AF...

  8. Determinants of Discrepancies in Detection and Comparison of the Prognostic Significance of Left Ventricular Hypertrophy by Electrocardiogram and Cardiac Magnetic Resonance Imaging

    OpenAIRE

    Bacharova, Ljuba; Chen, Haiying; Estes, E. Harvey; Mateasik, Anton; Bluemke, David A.; Lima, Joao A. C.; Burke, Gregory L; Soliman, Elsayed Z

    2014-01-01

    Despite the low sensitivity of the electrocardiogram (ECG) in detecting left ventricular hypertrophy (LVH), ECG-LVH is known to be a strong predictor of cardiovascular risk. Understanding reasons for the discrepancies in detection of LVH by ECG versus imaging could help improve the diagnostic ability of ECG. We examined factors associated with false-positive and false-negative ECG-LVH, using cardiac MRI as the gold standard. We also compared the prognostic significance of ECG-LVH and MRI-LVH ...

  9. Altered ventricular torsion and transmural patterns of myocyte relaxation precede heart failure in aging F344 rats.

    Science.gov (United States)

    Campbell, Stuart G; Haynes, Premi; Kelsey Snapp, W; Nava, Kristofer E; Campbell, Kenneth S

    2013-09-01

    The purpose of this study was to identify and explain changes in ventricular and cellular function that contribute to aging-associated cardiovascular disease in aging F344 rats. Three groups of female F344 rats, aged 6, 18, and 22 mo, were studied. Echocardiographic measurements in isoflurane-anesthetized animals showed an increase in peak left ventricular torsion between the 6- and the 18-mo-old groups that was partially reversed in the 22-mo-old animals (P 75 cells for each of the nine age-region groups). The decay time of the Ca(2+) transient and the time required for 50% length relaxation both increased with age but not uniformly across the three regions (P 50% reduction in troponin I phosphoprotein content in 22-mo-old epicardium relative to the other regions. These data suggest that between 18 and 22 mo of age (before the onset of heart failure), F344 rats display epicardial-specific myofilament-level modifications that 1) break from the progression observed between 6 and 18 mo and 2) coincide with aberrant patterns of cardiac torsion.

  10. Implementation of Contraction to Electrophysiological Ventricular Myocyte Models, and Their Quantitative Characterization via Post-Extrasystolic Potentiation.

    Directory of Open Access Journals (Sweden)

    Yanyan Claire Ji

    Full Text Available Heart failure (HF affects over 5 million Americans and is characterized by impairment of cellular cardiac contractile function resulting in reduced ejection fraction in patients. Electrical stimulation such as cardiac resynchronization therapy (CRT and cardiac contractility modulation (CCM have shown some success in treating patients with HF. Computer simulations have the potential to help improve such therapy (e.g. suggest optimal lead placement as well as provide insight into the underlying mechanisms which could be beneficial. However, these myocyte models require a quantitatively accurate excitation-contraction coupling such that the electrical and contraction predictions are correct. While currently there are close to a hundred models describing the detailed electrophysiology of cardiac cells, the majority of cell models do not include the equations to reproduce contractile force or they have been added ad hoc. Here we present a systematic methodology to couple first generation contraction models into electrophysiological models via intracellular calcium and then compare the resulting model predictions to experimental data. This is done by using a post-extrasystolic pacing protocol, which captures essential dynamics of contractile forces. We found that modeling the dynamic intracellular calcium buffers is necessary in order to reproduce the experimental data. Furthermore, we demonstrate that in models the mechanism of the post-extrasystolic potentiation is highly dependent on the calcium released from the Sarcoplasmic Reticulum. Overall this study provides new insights into both specific and general determinants of cellular contractile force and provides a framework for incorporating contraction into electrophysiological models, both of which will be necessary to develop reliable simulations to optimize electrical therapies for HF.

  11. Implementation of Contraction to Electrophysiological Ventricular Myocyte Models, and Their Quantitative Characterization via Post-Extrasystolic Potentiation.

    Science.gov (United States)

    Ji, Yanyan Claire; Gray, Richard A; Fenton, Flavio H

    2015-01-01

    Heart failure (HF) affects over 5 million Americans and is characterized by impairment of cellular cardiac contractile function resulting in reduced ejection fraction in patients. Electrical stimulation such as cardiac resynchronization therapy (CRT) and cardiac contractility modulation (CCM) have shown some success in treating patients with HF. Computer simulations have the potential to help improve such therapy (e.g. suggest optimal lead placement) as well as provide insight into the underlying mechanisms which could be beneficial. However, these myocyte models require a quantitatively accurate excitation-contraction coupling such that the electrical and contraction predictions are correct. While currently there are close to a hundred models describing the detailed electrophysiology of cardiac cells, the majority of cell models do not include the equations to reproduce contractile force or they have been added ad hoc. Here we present a systematic methodology to couple first generation contraction models into electrophysiological models via intracellular calcium and then compare the resulting model predictions to experimental data. This is done by using a post-extrasystolic pacing protocol, which captures essential dynamics of contractile forces. We found that modeling the dynamic intracellular calcium buffers is necessary in order to reproduce the experimental data. Furthermore, we demonstrate that in models the mechanism of the post-extrasystolic potentiation is highly dependent on the calcium released from the Sarcoplasmic Reticulum. Overall this study provides new insights into both specific and general determinants of cellular contractile force and provides a framework for incorporating contraction into electrophysiological models, both of which will be necessary to develop reliable simulations to optimize electrical therapies for HF. PMID:26317204

  12. Remodeling of the sarcomeric cytoskeleton in cardiac ventricular myocytes during heart failure and after cardiac resynchronization therapy.

    Science.gov (United States)

    Lichter, Justin G; Carruth, Eric; Mitchell, Chelsea; Barth, Andreas S; Aiba, Takeshi; Kass, David A; Tomaselli, Gordon F; Bridge, John H; Sachse, Frank B

    2014-07-01

    Sarcomeres are the basic contractile units of cardiac myocytes. Recent studies demonstrated remodeling of sarcomeric proteins in several diseases, including genetic defects and heart failure. Here we investigated remodeling of sarcomeric α-actinin in two models of heart failure, synchronous (SHF) and dyssynchronous heart failure (DHF), as well as a model of cardiac resynchronization therapy (CRT). We applied three-dimensional confocal microscopy and quantitative methods of image analysis to study isolated cells from our animal models. 3D Fourier analysis revealed a decrease of the spatial regularity of the α-actinin distribution in both SHF and DHF versus control cells. The spatial regularity of α-actinin in DHF cells was reduced when compared with SHF cells. The spatial regularity of α-actinin was partially restored after CRT. We found longitudinal depositions of α-actinin in SHF, DHF and CRT cells. These depositions spanned adjacent Z-disks and exhibited a lower density of α-actinin than in the Z-disk. Differences in the occurrence of depositions between the SHF, CRT and DHF models versus control were significant. Also, CRT cells exhibited a higher occurrence of depositions versus SHF, but not DHF cells. Other sarcomeric proteins did not accumulate in the depositions to the same extent as α-actinin. We did not find differences in the expression of α-actinin protein and its encoding gene in our animal models. In summary, our studies indicate that HF is associated with two different types of remodeling of α-actinin and only one of those was reversed after CRT. We suggest that these results can guide us to an understanding of remodeling of structures and function associated with sarcomeres.

  13. Impact of Left Ventricular Hypertrophy on Troponin Release During Acute Myocardial Infarction: New Insights From a Comprehensive Translational Study

    Science.gov (United States)

    Fernández‐Jiménez, Rodrigo; Silva, Jacobo; Martínez‐Martínez, Sara; López‐Maderuelo, Mª Dolores; Nuno‐Ayala, Mario; García‐Ruiz, José Manuel; García‐Álvarez, Ana; Fernández‐Friera, Leticia; Pizarro, Tech Gonzalo; García‐Prieto, Jaime; Sanz‐Rosa, David; López‐Martin, Gonzalo; Fernández‐Ortiz, Antonio; Macaya, Carlos; Fuster, Valentin; Redondo, Juan Miguel; Ibanez, Borja

    2015-01-01

    Background Biomarkers are frequently used to estimate infarct size (IS) as an endpoint in experimental and clinical studies. Here, we prospectively studied the impact of left ventricular (LV) hypertrophy (LVH) on biomarker release in clinical and experimental myocardial infarction (MI). Methods and Results ST‐segment elevation myocardial infarction (STEMI) patients (n=140) were monitored for total creatine kinase (CK) and cardiac troponin I (cTnI) over 72 hours postinfarction and were examined by cardiac magnetic resonance (CMR) at 1 week and 6 months postinfarction. MI was generated in pigs with induced LVH (n=10) and in sham‐operated pigs (n=8), and serial total CK and cTnI measurements were performed and CMR scans conducted at 7 days postinfarction. Regression analysis was used to study the influence of LVH on total CK and cTnI release and IS estimated by CMR (gold standard). Receiver operating characteristic (ROC) curve analysis was performed to study the discriminatory capacity of the area under the curve (AUC) of cTnI and total CK in predicting LV dysfunction. Cardiomyocyte cTnI expression was quantified in myocardial sections from LVH and sham‐operated pigs. In both the clinical and experimental studies, LVH was associated with significantly higher peak and AUC of cTnI, but not with differences in total CK. ROC curves showed that the discriminatory capacity of AUC of cTnI to predict LV dysfunction was significantly worse for patients with LVH. LVH did not affect the capacity of total CK to estimate IS or LV dysfunction. Immunofluorescence analysis revealed significantly higher cTnI content in hypertrophic cardiomyocytes. Conclusions Peak and AUC of cTnI both significantly overestimate IS in the presence of LVH, owing to the higher troponin content per cardiomyocyte. In the setting of LVH, cTnI release during STEMI poorly predicts postinfarction LV dysfunction. LV mass should be taken into consideration when IS or LV function are estimated by troponin

  14. Cardiac-specific genetic inhibition of nuclear factor-κB prevents right ventricular hypertrophy induced by monocrotaline.

    Science.gov (United States)

    Kumar, Sandeep; Wei, Chuanyu; Thomas, Candice M; Kim, Il-Kwon; Seqqat, Rachid; Kumar, Rajesh; Baker, Kenneth M; Jones, W Keith; Gupta, Sudhiranjan

    2012-04-15

    Uncontrolled pulmonary arterial hypertension (PAH) results in right ventricular (RV) hypertrophy (RVH), progressive RV failure, and low cardiac output leading to increased morbidity and mortality (McLaughlin VV, Archer SL, Badesch DB, Barst RJ, Farber HW, Lindner JR, Mathier MA, McGoon MD, Park MH, Rosenson RS, Rubin LJ, Tapson VF, Varga J. J Am Coll Cardiol 53: 1573-1619, 2009). Although the exact figures of its prevalence are difficult to obtain because of the diversity of identifiable causes, it is estimated that the incidence of pulmonary hypertension is seven to nine cases per million persons in the general population and is most prevalent in the age group of 20-40, occurring more commonly in women than in men (ratio: 1.7 to 1; Rubin LJ. N Engl J Med 336: 111-117, 1997). PAH is characterized by dyspnea, chest pain, and syncope. Unfortunately, there is no cure for this disease and medical regimens are limited (Simon MA. Curr Opin Crit Care 16: 237-243, 2010). PAH leads to adverse remodeling that results in RVH, progressive right heart failure, low cardiac output, and ultimately death if left untreated (Humbert M, Morrell NW, Archer SL, Stenmark KR, MacLean MR, Lang IM, Christman BW, Weir EK, Eickelberg O, Voelkel NF, Rabinovitch M. J Am Coll Cardiol 43: 13S-24S, 2004; Humbert M, Sitbon O, Simonneau G. N Engl J Med 351: 1425-1436, 2004. LaRaia AV, Waxman AB. South Med J 100: 393-399, 2007). As there are no direct tools to assess the onset and progression of PAH and RVH, the disease is often detected in later stages marked by full-blown RVH, with the outcome predominantly determined by the level of increased afterload (D'Alonzo GE, Barst RJ, Ayres SM, Bergofsky EH, Brundage BH, Detre KM, Fishman AP, Goldring RM, Groves BM, Kernis JT, et al. Ann Intern Med 115: 343-349, 1991; Sandoval J, Bauerle O, Palomar A, Gomez A, Martinez-Guerra ML, Beltran M, Guerrero ML. Validation of a prognostic equation Circulation 89: 1733-1744, 1994). Various studies have been

  15. Effect of temperature on the activation of myocardial KATP channel in guinea pig ventricular myocytes: a pilot study by whole cell patch clamp recording

    Institute of Scientific and Technical Information of China (English)

    JIN San-qing; NIU Li-jun; DENG Chun-yu; YAO Zhi-bin; ZHOU Ying-jie

    2006-01-01

    Background The myocardial ATP sensitive potassium channel (KATP channel) has been known for more than two decades, the properties of this channel have been intensively investigated, especially the myocardial protection effect by opening this channel. Numerous studies, including hypothermic, using KATP agonists to achieve a hyperpolarizing cardioplegic arrest, have shown a better myocardial protection than potassium arrest.However, there is no evidence showing that KATP channel could be opened by its agonists under profound hypothermia. We investigated the effect of temperature on activation of myocardial KATP channel by nicorandil.Methods Isolated ventricular myocytes were obtained by collagenase digestion of the hearts of guinea pigs and stored in KB solution at 4℃. With a steady ground current, the myocytes were perfused with 1 mmol/L nicorandil until a steady IKATP occurred. Then the cells were perfused with 1 mmol/L nicorandil plus 1 μmol/L glybenclamide. Currents signals were recorded on whole cells using patch clamp technique at several temperatures. The temperature of the bath solution around myocytes was monitored and was controlled at 4℃,10℃, 20℃, 25℃ and 35℃ respectively. About 10 cells were tested at each temperature, the cells were considered useful only when the outward current could be induced by nicorandil and blocked by glybenclamide.All data were analyzed using Graphpad PRISM 3.0 (Graphpad, San Diego, CA, USA). Nonlinear curve fitting was done in Clampfit (Axon) or Sigmaplot (SPSS).Results At 4℃, 10℃, 20℃, 25℃ and 35℃, the time needed to open the myocardial KATP channel was (81.0±0)minutes, (50.5±11.7) minutes, (28.8±2.3) minutes, (9.4±10.2) minutes and (2.3± 1.0) minutes respectively (P=0.003). The linear relationship between temperature and time needed to open the channel was y (min) =(4348.790-124.277x)/60, where y (min) is time needed to open KATP channel, x is temperature, correlation coefficient r =-0.942 (P=0

  16. Cardiac hypertrophy, arrhythmogenicity and the new myocardial phenotype. II. The cellular adaptational process.

    Science.gov (United States)

    Swynghedauw, B; Chevalier, B; Charlemagne, D; Mansier, P; Carré, F

    1997-07-01

    Ventricular fibrosis is not the only structural determinant of arrhythmias in left ventricular hypertrophy. In an experimental model of compensatory cardiac hypertrophy (CCH) the degree of cardiac hypertrophy is also independently linked to ventricular arrhythmias. Cardiac hypertrophy reflects the level of adaptation, and matches the adaptational modifications of the myocardial phenotype. We suggest that these modifications have detrimental aspects. The increased action potential (AP) and QT duration and the prolonged calcium transient both favour spontaneous calcium oscillations, and both are potentially arrhythmogenic and linked to phenotypic changes in membrane proteins. To date, only two ionic currents have been studied in detail: Ito is depressed (likely the main determinant in AP durations), and If, the pacemaker current, is induced in the overloaded ventricular myocytes. In rat CCH, the two components of the sarcoplasmic reticulum, namely Ca(2+)-ATPase and ryanodine receptors, are down-regulated in parallel. Nevertheless, while the inward calcium current is unchanged, the functionally linked duo composed of the Na+/Ca2+ exchanged and (Na+, K+)-ATPase, is less active. Such an imbalance may explain the prolonged calcium transient. The changes in heart rate variability provide information about the state of the autonomic nervous system and has prognostic value even in CCH. Transgenic studies have demonstrated that the myocardial adrenergic and muscarinic receptor content is also a determining factor. During CCH, several phenotypic membrane changes participate in the slowing of contraction velocity and are thus adaptational. They also have a detrimental counterpart and, together with fibrosis, favour arrhythmias. PMID:9302342

  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. Calpain inhibition reduces amplitude and accelerates decay of the late sodium current in ventricular myocytes from dogs with chronic heart failure.

    Directory of Open Access Journals (Sweden)

    Albertas Undrovinas

    Full Text Available Calpain is an intracellular Ca²⁺-activated protease that is involved in numerous Ca²⁺ dependent regulation of protein function in many cell types. This paper tests a hypothesis that calpains are involved in Ca²⁺-dependent increase of the late sodium current (INaL in failing heart. Chronic heart failure (HF was induced in 2 dogs by multiple coronary artery embolization. Using a conventional patch-clamp technique, the whole-cell INaL was recorded in enzymatically isolated ventricular cardiomyocytes (VCMs in which INaL was activated by the presence of a higher (1 μM intracellular [Ca²⁺] in the patch pipette. Cell suspensions were exposed to a cell- permeant calpain inhibitor MDL-28170 for 1-2 h before INaL recordings. The numerical excitation-contraction coupling (ECC model was used to evaluate electrophysiological effects of calpain inhibition in silico. MDL caused acceleration of INaL decay evaluated by the two-exponential fit (τ₁ = 42±3.0 ms τ₂ = 435±27 ms, n = 6, in MDL vs. τ₁ = 52±2.1 ms τ₂ = 605±26 control no vehicle, n = 11, and vs. τ₁ = 52±2.8 ms τ₂ = 583±37 ms n = 7, control with vehicle, P<0.05 ANOVA. MDL significantly reduced INaL density recorded at -30 mV (0.488±0.03, n = 12, in control no vehicle, 0.4502±0.0210, n = 9 in vehicle vs. 0.166±0.05pA/pF, n = 5, in MDL. Our measurements of current-voltage relationships demonstrated that the INaL density was decreased by MDL in a wide range of potentials, including that for the action potential plateau. At the same time the membrane potential dependency of the steady-state activation and inactivation remained unchanged in the MDL-treated VCMs. Our ECC model predicted that calpain inhibition greatly improves myocyte function by reducing the action potential duration and intracellular diastolic Ca²⁺ accumulation in the pulse train.Calpain inhibition reverses INaL changes in failing dog ventricular

  19. Effect of angiotensin converting enzyme inhibitor on the calcium transients and calcium handling proteins in ventricular myocytes from rats with heart failure

    Institute of Scientific and Technical Information of China (English)

    WANG Li-chun; ZENG Wu-tao; LIU Jun; DONG Yu-gang; TANG An-li; FENG Chong; MA Hong; HE Jian-gui; LIAO Xin-xue; CHEN Wen-fang; LENG Xiu-yu; MA Li; MAI Wei-yi; TAO Jun

    2005-01-01

    Background Chronic heart failure (CHF) is associated with calcium transients and calcium handling proteins. Angiotensin converting enzyme (ACE) inhibitor has been demonstrated to have beneficial effect on CHF. Yet studies addressed to the relationship between ACE inhibitor and calcium transients in CHF are rare. The aim of this study was to investigate the influence of ACE inhibitor (perindopril) on the contractility and calcium transients and calcium handling proteins in ventricular myocytes from rats with experimental heart failure.Results The fraction of cell shortening (FS%) and [Ca2+]imax (nmol/L) were significantly reduced in group CHF-C compared with group PS (FS%: 7.51±1.15 vs 13.21±1.49;[Ca2+]imax:330.85±50.05 vs 498.16±14.07; both P<0.01), and restored at least partially in CHF-T group. In CHF-C group, the left ventricular mRNA of NCX1 and PLB were significantly upregulated in comparing with PS group (RNCX1/β-Actin: 0.51±0.12 vs 0.19±0.06, P<0.01; RPLB/β-Actin: 0.26±0.12 vs 0.20±0.08, P<0.05), while SERCA2 mRNA was downregulated (0.48±0.10 vs 0.80±0.11, P<0.01). The mRNA levels of NCX1 and SERCA2 in CHF-T group were between the CHF-C and PS group, and the differences of the latter two groups were significant (all P<0.05). In CHF-C and CHF-T groups, the protein expression of NCX1 were 1.141±0.047 and 1.074±0.081 times of that in PS group respectively (both P<0.05), and SERCA2 protein levels were 0.803±0.100 and 0.893±0.084 times of that in PS group respectively (both P<0.05). The protein expression of NCX1 and SERCA2 in the CHF-C and CHF-T groups is significantly different (both P<0.05).Conclusion ACE inhibitor could improve cardiac function of failing heart through directly enhancing the contractility of single cardiomyocyte, and these effects are probably mediated by its roles in preventing the deleterious changes of calcium transients and calcium handling proteins in CHF.

  20. 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

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

    International Nuclear Information System (INIS)

    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. The H{sub 1}–H{sub 2} domain of the α{sub 1} isoform of Na{sup +}–K{sup +}–ATPase is involved in ouabain toxicity in rat ventricular myocytes

    Energy Technology Data Exchange (ETDEWEB)

    Xiong, Chen; Li, Jun-xia; Guo, Hui-cai; Zhang, Li-nan; Guo, Wei; Meng, Jing; Wang, Yong-li, E-mail: wangyongli@gmail.com

    2012-07-01

    The composition of different isoforms of Na{sup +}-K{sup +}-ATPase (NKA, Na/K pump) in ventricular myocytes is an important factor in determining the therapeutic effect and toxicity of cardiac glycosides (CGs) on heart failure. The mechanism whereby CGs cause these effects is still not completely clear. In the present study, we prepared two site-specific antibodies (SSA78 and WJS) against the H{sub 1}–H{sub 2} domain of α{sub 1} and α{sub 2} isoforms of NKA in rat heart, respectively, and compared their influences on the effect of ouabain (OUA) in isolated rat ventricular myocytes. SSA78 or WJS, which can specifically bind with the α{sub 1} or α{sub 2} isoform, were assessed with enzyme linked immunosorbent assay (ELISA), Western blot and immunofluorescent staining methods. Preincubation of myocytes with SSA78 inhibited low OUA affinity pump current but not high OUA affinity pump current, reduced the rise in cytosolic calcium concentration ([Ca{sup 2+}]{sub i}), attenuated mitochondrial Ca{sup 2+} overload, restored mitochondrial membrane potential reduction, and delayed the decrease of the myocardial contractile force as well as the occurrence of arrhythmic contraction induced by high concentrations (1 mM) but not low concentrations (1 μM) of OUA. Similarly, preincubation of myocytes with WJS inhibited high OUA affinity pump current, reduced the increase of [Ca{sup 2+}]{sub i} and the contractility induced by 1 μM but not that induced by 1 mM OUA. These results indicate that the H{sub 1}–H{sub 2} domain of the NKA α{sub 1} isoform mediates OUA-induced cardiac toxicity in rat ventricular myocytes, and inhibitors for this binding site may be used as an adjunct to CGs treatment for cardiovascular disease. -- Highlights: ► We prepared two antibodies against the H{sub 1}-H{sub 2} domain of α{sub 1} and α{sub 2} isoforms of NKA. ► The H{sub 1}-H{sub 2} domain of the NKA α{sub 1} isoform mediates OUA-induced cardiac toxicity. ► The H{sub 1}-H{sub 2

  3. Simultaneous recording of ATP-sensitive K+ current and intracellular Ca2+ in anoxic rat ventricular myocytes. Effects of glibenclamide.

    Science.gov (United States)

    Russ, U; Englert, H; Schölkens, B A; Gögelein, H

    1996-05-01

    We investigated the temporal relationship between the adenosine triphosphate-sensitive K current (KATP current), hypoxic shortening and Ca accumulation in cardiomyocytes exposed to anoxia or metabolic inhibition. Whole-cell, patch-clamp experiments were performed with nonstimulated isolated rat heart ventricular muscle cells loaded with the Ca-sensitive fluorescent dye 1-[2-(5-carboxyoxazol-2-yl)-6-aminobenzofuran-5-oxy]-2-(2'- amino-5'-methylphenoxy) ethane-N,N,N',N'-tetraacetic acid (fura-2) via the patch pipette. After approximately 8 min anoxia, the KATP current started to rise and reached a maximum of 21.3 +/- 3.7 nA (n = 5, recorded at 0 mV clamp potential) within 1-3 min. At that time hypoxic contracture also occurred. Resting cytoplasmic free calcium (Cai) did not change significantly before hypoxic shortening. After hypoxic contracture, the KATP current decreased and Cai started to rise, reaching about 1 micromol/l. The presence of glibenclamide (10 micromol/l) in the bath reduced the anoxia-induced KATP current by more than 50%, but did not significantly influence the time dependence of current, hypoxic shortening and Cai, or the magnitude of Cai. Metabolic inhibition with 1.5 mmol/l CN resulted in KATP current increase and hypoxic shortening, occurring somewhat earlier than under anoxia, but all other parameters were comparable. In non-patch-clamped cells loaded with fura-2 AM ester and field-stimulated with 1 Hz, 1 micronol/l glibenclamide had no significant effect on the magnitude of the Cai increase caused by exposure of the cells to 1.5 mmol/l CN-. After CN- wash-out in non-patch-clamped cells, Cai declined, oscillated and finally returned to control values. It can be concluded that glibenclamide inhibits anoxia-induced KATP currents only partially and has no significant effect on anoxia-induced rise in resting Cai.

  4. 血清素抑制大鼠心室肌细胞瞬时外向钾电流%Inhibitory effects of serotonin on transient outward potassimn current in rat ventricular myocytes

    Institute of Scientific and Technical Information of China (English)

    招明高; 梅其炳; 张延凤; 邢斌; 李小强; 崔毅

    2002-01-01

    目的:观察血清素(5-HT)对大鼠心室肌细胞瞬时外向钾电流Ito的影响并探讨其作用机制.方法:全细胞膜片箝技术记录Ito.结果:Ito电流密度在正常心肌和肥厚心肌细胞无明显差异.在实验电压为+70mV时,5-HT浓度依赖性抑制Ito,在正常和肥厚心肌细胞,其半数抑制浓度分别为(40±5)μmol/L和(38±7)μmol/L. 5-HT2受体阻断剂米胺舍林和磷脂酶C抑制剂Compound 48/80均可逆转5-HT抑制Ito的作用;蛋白激酶激动剂醋酸佛波酯显著加强5-HT的抑制作用,而蛋白激酶抑制剂白屈菜季铵碱则逆转5-HT抑制Ito的作用.结论:5-HT具有抑制心肌细胞Ito的作用.此作用是通过激动5-HT2受体,启动磷脂酶C信号转导途径,进一步激活蛋白激酶从而抑制心肌Ito.%AIM: To study the effects of serotonin (5-hydroxytryptamine, 5-HT) on transient outward potassium current (Ito) and elucidate its mechanism in mt ventricular myocytes. METHODS: Ito was recorded using the conventional whole cell patch-clamp techniques. RESULTS:Ito density in normal myocytes was similar to that in norepinephrine-induced hypertrophic myocytes. 5-HT depressed Ito in a concentration-dependent manner with the half-maximal inhibitory concentration of ( 40 ± 5)μmol/L and (38 ± 7) μtmoL/L in normal and hypertrophic ventricular myocytes respectively. Mianserin (5-HT2 receptor antagonist), compound 48/80 (phospholipase C antagonist), and chelerythrine chloride (protein kinase C antagonist) reversed the inhibitory effects of 5-HT on Ito,while phorbol 12-myristate 13-acetate (protein kinase C agonist) enhanced the inhibitory effect of 5-HT on Ito in normal myocytes. CONCLUSION: 5-HT markedly inhibits Ito in rat ventricular myocytes. The putative signal pathway is that 5-HT activates phospholipase C,which causes inositol phospholipid hydrolysis. The activation of downstream signal molecule, protein kinase C, phosphorates substrate target proteins, which leads to inhibition of Ito in

  5. Phenotyping of Left and Right Ventricular Function in Mouse Models of Compensated Hypertrophy and Heart Failure with Cardiac MRI

    NARCIS (Netherlands)

    B.J. van Nierop (Bastiaan); H.C. van Assen (Hans); E.D. van Deel (Elza); L.B.P. Niesen (Leonie); D.J.G.M. Duncker (Dirk); G.J. Strijkers (Gustav); K. Nicolay (Klaas)

    2013-01-01

    textabstractBackground: 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 aorti

  6. Effect of Salvia Miltiorrhiza Bge on Left Ventricular Hypertrophy and the Expression of Tumor Necrosis Factor-α in Spontaneously Hypertensive Rats

    Institute of Scientific and Technical Information of China (English)

    SUN Lianping; ZHENG Zhi

    2007-01-01

    The effects of salvia miltiorrhiza Bge (SMB) on left ventricular hypertrophy (LVH) and the expression of tumor necrosis factor-α (TNF-α) in the left ventricle of spontaneously hypertensive rats and the action mechanism were investigated. Normal Wistar-kyoto (WKY) rats were used as negative control, and spontaneously hypertensive rats (SHR) were randomly assigned to receive placebo or SMB. SMB (1 g/kg·d) was injected intraperitoneally for 12 weeks. Systolic blood pressure (SBP) and left ventricular mass index (LVMI) were measured. HE, VG and immunohistochemical staining combined with computed morphometry were employed to evaluate the cardiomyocyte size,diameter, the collagen volume fraction (CVF), perivascular circumferential area (PVCA), and tumor necrosis factor-α (TNF-α) expression in the left ventricular tissue. The results showed, as compared with WKY rats, the SBP, LVMI, cardiomyocyte size, diameter, CVF, PCVA, and TNF-α expression were increased markedly in the 20-week-old spontaneously hypertensive rats. SMB decreased LVMI (P<0.01), size of cardiomyocytes (P<0.01), collagen volume fraction (P<0.01), perivascular circumferential area (P<0.01), and TNF-α expression (P<0.01), but had no effect on SBP (P>0.05). It was suggested that chronic administration of SMB could inhibit and reverse the development of LVH in spontaneously hypertensive rats independent of BP. TNF-α may be involved in the reversal mechanism of LVH by SMB.

  7. Polymorphisms of angiotensin-converting enzyme 2 gene associated with magnitude of left ventricular hypertrophy in male patients with hypertrophic cardiomyopathy

    Institute of Scientific and Technical Information of China (English)

    WANG Shu-xia; HUI Ru-tai; FU Chun-yan; ZOU Yu-bao; WANG Hu; SHI Yi; XU Xi-qi; CHEN Jing-zhou; SONG Xiao-dong; HUAN Tu-jun

    2008-01-01

    Background Even carrying an identicai gene mutation, inter- and intra-family variations have been noticed worldwide in the presence and the severity of left ventricular hypertrophy and sudden death in patients with hypertrophic cardiomyopathy (HCM). Modifier genes may contribute to the diversity. Angiotensin-converting enzyme 2 (ACE2) gene has been established to be associated with parameters of left ventricular hypertrophy in Community based male subjects.The objective of the present study was to investigate the association of ACE2 gene polymorphisms with the phenotype of HCM.Methods A total of 261 consecutive HCM patients and 609 healthy controls were enrolled into this study. The polymorphism of rs2106809 and rs6632677 were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and confirmed by sequencing. Logistic regression model and multivariate analysis were used to determine the odds ratio (OR) and 95% confidence intervals (CI) of variations of ACE2 for HCM.Results The T allele of rs2106809 and C allele of rs6632677 conferred increasing risk for HCM (OR 1.34, 95% CI 1.01-1.77, P=0.04; OR 1.11, 95% CI 1.03-1.21, P=0.002, respectively), and the 2 single nucleotide polymorphisms (SNPs) were in strong linkage disequilibrium (LD), the TC haplotype was independently associated with a higher OR for HCM (OR=1.59, 95% CI 1.21-1.87) after adjusted for conventional risk factors. And the risk alleles were associated with thicker interventricular septal thickness of HCM ((20.0±6.3) mm vs (17.9±5.5) mm, P=0.03 and (21.3±5.9) mm vs (17.9±5.8) mm, P=O.04, respectively). No association was found between the two polymorphisms with female patients with HCM.Conclusion Minor alleles of ACE2 gene might be the genetic modifier for the magnitude of left ventricular hypertrophy in male patients with HCM.

  8. Phosphatidylinositol-bisphosphate regulates intercellular coupling in cardiac myocytes

    DEFF Research Database (Denmark)

    Hofgaard, Johannes P; Banach, Kathrin; Mollerup, Sarah;

    2008-01-01

    Changes in the lipid composition of cardiac myocytes have been reported during cardiac hypertrophy, cardiomyopathy, and infarction. Because a recent study indicates a relation between low phosphatidylinositol-bisphosphate (PIP(2)) levels and reduced intercellular coupling, we tested the hypothesis...

  9. 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

  10. Clinical Implications of Electrocardiographic Left Ventricular Strain and Hypertrophy in Asymptomatic Patients with Aortic Stenosis: The Simvastatin and Ezetimibe in Aortic Stenosis Study

    DEFF Research Database (Denmark)

    Greve, Anders M; Boman, Kurt; Gohlke-Baerwolf, Christa;

    2012-01-01

    in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Primary endpoint was the first of myocardial infarction, non-hemorrhagic stroke, heart failure, aortic valve replacement (AVR) or cardiovascular death. Predictive value of electrocardiographic LV strain (defined as T-wave inversion in leads V(4.......1, both p=0.001) and 2.5-fold higher risk of a combined endpoint of myocardial infarction, heart failure or cardiovascular death (95% CI, 1.3 to 4.9, p=0.008). CONCLUSIONS: Electrocardiographic LV strain and LVH were independently predictive of poor prognosis in asymptomatic AS. CLINICAL TRIAL......BACKGROUND: The prognostic impact of electrocardiographic left ventricular (LV) strain and hypertrophy (LVH) in asymptomatic aortic stenosis (AS) is not well described. METHODS AND RESULTS: Data were obtained in asymptomatic patients randomized to simvastatin/ezetimibe combination vs. placebo...

  11. The value of the different indexes of electrocardiogram in diagnosing high blood pressure with left ventricular hypertrophy%心电图不同指标对高血压病左室肥厚的诊断价值

    Institute of Scientific and Technical Information of China (English)

    严国平; 颜玉芳

    2009-01-01

    目的 探讨心电图(ECG)各指标对诊断高血压病左室肥厚(LVH)的价值.方法 根据超声心动图(UCG)报告,确定观察组(A组)高血压病伴LVH 55例及对照组(B组)高血压病不伴LVH 50例;测定ECG各指标数据并计算其敏感性.结果 ECG不同指标对诊断高血压病LVH的价值存在较大差异,其中QRS波群电压指标敏感性最高,肢体导联室壁激动时间(VAT)次之,余指标敏感性较低.结论 ECG不同指标在诊断高血压病LVH时的价值不同.%Objective To investigate the value of the different indexes of electrocardiogram (ECG) in diagnosing high blood pressure with left ventricular hypertrophy. Methods 55 cases of high blood pressure with left ventricular hy-pertrophy and 50 cases of high blood pressure without left ventricular hypertrophy by the investigation of ultrasonic cardio-gram(UCG) were studied. The figure and sensitivity of the different indexes of ECG were determined. Results There was obvious difference among each ECG index in the diagnosing value of high blood pressure with left ventricular hypertro-phy, QRS wave amplitude had the most sensitive value compared with others. Conclusion It was different for each ECG index in the value of diagnosing high blood pressure with left ventricular hypertrophy. In order to improve the diagnosing ac-curacy, it is important to understand the different diagnosing value of each ECG index.

  12. 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.

  13. Localization of Kv4.2 and KChIP2 in lipid rafts and modulation of outward K+ currents by membrane cholesterol content in rat left ventricular myocytes.

    Science.gov (United States)

    Rudakova, Elena; Wagner, Michael; Frank, Magdalena; Volk, Tilmann

    2015-02-01

    Lipid rafts are cholesterol-enriched microdomains of the cell membrane. Here we investigate the localization of the pore forming K(+)-channel α-subunit Kv4.2 and the β-subunit KChIP2, underlying the transient outward K(+) current (I to), in lipid rafts in left ventricular myocytes. Furthermore, we explored the impact of membrane cholesterol depletion (using 20 mM methyl-beta-cyclodextrin (MBCD)) on K(+) outward currents. Cholesterol-saturated MBCD (20 mM) served as control. Myocytes were isolated from the left ventricular free wall of Wistar rats. The Triton X-100 (4 °C) insoluble fraction of whole cell protein was analyzed by sucrose density gradient centrifugation followed by Western blot. Kv4.2 and KChIP2 were partially detected in low-density fractions (lipid rafts). MBCD treatment (5 min) resulted in a shift of Kv4.2 and KChIP2 towards high-density fractions. K(+) currents were assessed by whole-cell patch-clamp. MBCD treatment resulted in a 29 ± 3 % decrease in I to (20.0 ± 1.6pApF(-1) vs. 28.5 ± 2.0pApF(-1), n = 15, p lipid rafts. Membrane cholesterol depletion results in ~12 % net reduction of I to, a redistribution of the channel proteins Kv4.2 and KChIP2 and an increased delayed rectifier current.

  14. Reduction of prohibitin expression contributes to left ventricular hypertrophy via enhancement of mitochondrial reactive oxygen species formation in spontaneous hypertensive rats.

    Science.gov (United States)

    Zheng, H; Lu, G M

    2015-02-01

    Left ventricular hypertrophy (LVH) in hypertension is characterized by thickening of myocardium and decrease in heart chamber volume in response to mechanical or pathological stress, but the underlying molecular mechanisms remain to be defined. In this work, we investigate whether mitochondrial prohibitin (PHB) was involved in the progression of LVH in spontaneous hypertensive rats (SHR). First, it was found that mitochondrial dysfunction occurred in left ventricles of SHR. Through analysis using quantitative reverse transcription polymerase chain reaction and Western blotting, it was found that PHB mRNA and mitochondrial PHB levels in left ventricles of SHR were significantly lower than that in Wistar-Kyoto rats. Furthermore, PHB mRNA levels were negatively correlated to left ventricles weight-to-body weight ratio in SHR. Knockdown of PHB led to increased formation of mitochondrial reactive oxygen species (ROS) and reduced activities of complex I, mitochondrial adenosine triphosphate generation and mitochondrial membrane potential in cultured cardiomyocytes. Knockdown of PHB contributed to the cardiomyocyte hypertrophy, which could be attenuated by treatment with the Tempol. Angiotensin II (AngII) was increased in plasma and left ventricles of SHR. Incubation with AngII reduced mitochondrial PHB expression in cardiomyocytes, which was reversed when pretreated with losartan. In conclusion, reduction of PHB expression in left ventricles in SHR contributed to LVH, at least in part, through promoting mitochondrial ROS formation.

  15. Cardiac MRI in a Patient with Coincident Left Ventricular Non-Compaction and Hypertrophic Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Zahra Alizadeh-Sani

    2011-12-01

    Full Text Available Left ventricular non-compaction cardiomyopathy is a rare congenital cardiomyopathy that affects both children and adults. Since the clinical manifestations are not sufficient to establish diagnosis, echocardiography is the diagnostic tool that makes it possible to document ventricular non-compaction and establish prognostic factors. We report a 47-year-old woman with a history of dilated cardiomyopathy with unknown etiology. Echocardiography showed mild left ventricular enlargement with severe systolic dysfunction (EF = 20-25%. According to cardiac magnetic resonance imaging findings non-compaction left ventricle with hypertrophic cardiomyopathy was considered, and right ventricular septal biopsy was recommended. Right ventricular endomyocardial biopsy showed moderate hypertrophy of cardiac myocytes with foci of myocytolysis and moderate interstitial fibrosis. No evidence of infiltrative deposition was seen.

  16. EFFECT OF ANGIOTENSIN-II RECEPTOR ANTAGONIST LOSARTAN AND ITS COMBINATION WITH DIURETICS ON MYOCARDIAL MORPHO-FUNCTIONAL CONDITIONS IN HYPERTENSIVE PATIENTS WITH LEFT VENTRICULAR HYPERTROPHY

    Directory of Open Access Journals (Sweden)

    S. N. Tolpygina

    2008-01-01

    Full Text Available Aim. To compare the effects of long-term therapy with angiotensin-II receptor antagonist losartan, alone or in combination with hydrochlorothiazide, and amlodipine treatment on left ventricular morpho-functional variables and blood pressure (BP in hypertensive patients.Material and methods. 25 women and 27 men (average age 52,7±1,2 y.o. with essential hypertension (1-2 grade and left ventricular hypertrophy (LVH were included into the study. After 3 week washout period the patients were randomized in 2:1 fashion to receive either losartan (n=34 or amlodipine (n=17. In 17 patients with insufficient response to losartan monotherapy (50-100mg/day hydrochlorothiazide (12,5mg was added to losartan (50mg 4 weeks later. The daily dose of amlodipine was increased from 5 to 10 mg in 10 patients. At baseline and after 24 weeks of treatment 24-h BP monitoring and echocardiography (with evaluation of cardiac chamber dimensions, inter-ventricular septal and posterior wall thickness, left ventricular mass index -LVMI were performed.Results. 4-week losartan treatment significantly decreased clinic BP (-14,1±2,2/8,2±1,4 mm Hg, p<0,01, mean daily systolic and diastolic BP (-15,1±2,4 mm Hg and -8,9±1,7 mm Hg , p<0,001, mean day-time and night-time BP and systolic and diastolic BP load in 34 patients. Addition of hydrochlorothiazide induced a further decrease of mean night-time BP, pulse BP, improved circadian rhythm and normalized BP in 75% of patients compared with 50% in losartan alone. Significant decrease of clinic BP (-24,1±3,6/15,2±2,3, p<0,01, mean daily systolic and diastolic BP and BP load were noticed at 24 week of amlodipine treatment. Circadian BP rhythm didn’t change; night-time decrease of BP was insufficient. Antihypertensive efficacy was similar in both groups. Losartan, alone or combined with hydrochlorothiazide, caused regression of LVH in all patients, normalized geometry of left ventricle in 33% of patients and improved left

  17. Tissue Doppler Imaging can be useful to distinguish pathological from physiological left ventricular hypertrophy: a study in master athletes and mild hypertensive subjects

    Directory of Open Access Journals (Sweden)

    De Luca Alessio

    2009-10-01

    Full Text Available Abstract Background Transthoracic echocardiography left ventricular wall thickness is often increased in master athletes and it results by intense physical training. Left Ventricular Hypertrophy can also be due to a constant pressure overload. Conventional Pulsed Wave (PW Doppler analysis of diastolic function sometimes fails to distinguish physiological from pathological LVH. The aim of this study is to evaluate the role of Pulsed Wave Tissue Doppler Imaging in differentiating pathological from physiological LVH in the middle-aged population. Methods we selected a group of 80 master athletes, a group of 80 sedentary subjects with essential hypertension and an apparent normal diastolic function at standard PW Doppler analysis. The two groups were comparable for increased left ventricular wall thickness and mass index (134.4 ± 19.7 vs 134.5 ± 22.1 gr/m2; p > .05. Diastolic function indexes using the PW technique were in the normal range for both. Results Pulsed Wave TDI study of diastolic function immediately distinguished the two groups. While in master athletes the diastolic TDI-derived parameters remained within normal range (E' 9.4 ± 3.1 cm/sec; E/E' 7.8 ± 2.1, in the hypertensive group these parameters were found to be constantly altered, with mean values and variation ranges always outside normal validated limits (E' 7.2 ± 2.4 cm/sec; E/E' 10.6 ± 3.2, and with E' and E/E' statistically different in the two groups (p Conclusion Our study showed that the TDI technique can be an easy and validated method to assess diastolic function in differentiating normal from pseudonormal diastolic patterns and it can distinguish physiological from pathological LVH emphasizing the eligibility certification required by legal medical legislation as in Italy.

  18. Generation of PP2A CαKnockout Model in Neonatal Mouse Ventricular Myocytes%PP2A Cα敲除小鼠心肌细胞模型的构建

    Institute of Scientific and Technical Information of China (English)

    陈文; 温明达; 董大川; 高艳红; 张朝

    2013-01-01

    To generate PP2A Cαknockout model in neonatal mouse ventricular myocytes. Male PP2A Cαfl/fl,Cre/-were se-lectively mated with female PP2A Cαfl/fl,Cre/- mice to obtain abundant offsprings with the same genotype. The neonatal mouse ventricular myocytes were digested by trypsinization and subsequently infected with Cre-adenovirus. The effects of adenovirus infection were observed by fluorescence microscope and identified by western blot analysis. The offsprings in aboundance were obtained by seting up a mating between male and female of PP2A Cαfl/fl,Cre/-mice, as a result, an abundance of neonatal mouse ventricular myocytes with the genotype of PP2A Cαfl/fl,Cre/-were available for Ad-Cre infection. Green fluorescence was observed after GFP labeled Cre-adenovirus( Cre-Ad) infection for 48 h. The expression level of PP2A Cα protein in Cre-Ad infected myocytes was 60% ~80% lower than control. The PP2A Cα knockout model in neonatal mouse ventricular myocytes was successfully generated.%体外构建PP2A Cα敲除的原代小鼠心室肌细胞模型。选择性地将雄性PP2A Cαfl/fl,Cre/-小鼠与雌性PP2A Cαfl/fl,Cre/-小鼠交配。新生小鼠心脏经胰酶消化后差速贴壁获得原代小鼠心室肌细胞,用带有Cre的腺病毒侵染心肌细胞,经荧光显微镜观察和Western-blot检测,分析PP2A Cα的敲除效果。将基因型为PP2A Cαfl/fl,Cre/-的雌雄小鼠进行交配,得到其同样基因型的后代,进而可获得足量基因型为PP2A Cαfl/fl,Cre/-的原代小鼠心肌细胞。用带有重组酶Cre的腺病毒侵染细胞48 h后,可见带有绿色荧光的心肌细胞;Western-blot检测显示,PP2A Cα在Cre腺病毒侵染的心肌细胞可下调60%~80%。本研究成功建立了PP2A Cα敲除的原代小鼠心肌细胞模型。

  19. 乙酰胆碱对离体豚鼠心室肌的直接作用机制探讨%The mechanisms underlying the effects of acetylcholine on isolated guinea-pig ventricular myocytes

    Institute of Scientific and Technical Information of China (English)

    方萍; 张晓东; 等

    2001-01-01

    To investigate the mechanisms underlying the effects of ACh on isolated guinea-pig ventricular myocytes. METHODS: Using standard microelectrodes and force transducer we recorded the effects of ACh (10-5 mol/L) and various blockers such as atropine, CsCl and CdCl2 on the action potential and force contraction in isolated ventricular myocytes of guinea-pig. RESULTS: ACh(10-5 mol/L) reduced the duration of action potential and twitch tensions by 7.31% and 37.57% respectively (P<0.05),which could be blocked by atropine, CsCl, but not by CdCl2. CONCLUSION: ACh (10-5 mol/L) could cause a negative chronotropic and inotropic effects on guinea-pig ventricular myocytes. These effects are related to the muscarinic receptor and the potassium channel and may not related to the calcium channel.%目的: 研究乙酰胆碱(ACh)对离体豚鼠心室肌的直接负性作用及机制。方法: 采用标准玻璃微电极细胞内记录技术记录动作电位(AP)及肌力换能器记录心肌收缩力(FC)的方法观察ACh对离体豚鼠心室肌的作用,并观察几种受体或通道水平的阻断剂阿托品、氯化铯(CsCl)、氯化镉(CdCl2)对ACh直接作用的影响。结果: 10-5mol/L ACh对心室肌动作电位持续时间(APD)及FC的抑制率分别为7.31%和37.57%(P<0.05),10-5 mol/L阿托品和20 mmol/L CsCl可阻断该作用,0.1 mmol/L CdCl2对该作用无影响。结论: 10-5mol/L ACh 对离体豚鼠心室肌有直接负性作用,ACh的作用与毒蕈碱型胆碱受体及K+电流有关,而与Ca2+电流的关系可能不大。

  20. Vitamin D therapy to reduce blood pressure and left ventricular hypertrophy in resistant hypertension: randomized, controlled trial.

    Science.gov (United States)

    Witham, Miles D; Ireland, Sheila; Houston, J Graeme; Gandy, Stephen J; Waugh, Shelley; Macdonald, Thomas M; Mackenzie, Isla S; Struthers, Allan D

    2014-04-01

    Low 25-hydroxyvitamin D levels are associated with higher prevalent blood pressure. We tested whether high-dose intermittent oral vitamin D therapy could reduce blood pressure and left ventricular mass in patients with hypertension resistant to conventional treatment. We conducted a parallel-group, double-blind, randomized placebo-controlled trial. Patients with supine office blood pressure >140/90 mm Hg on ≥3 antihypertensive agents received 100 000 U oral vitamin D3 or matching placebo every 2 months. Office and 24-hour ambulatory blood pressure, glucose, and cholesterol were measured at baseline, 2, 4, and 6 months; left ventricular mass index was measured by cardiac MRI on a subgroup at baseline and 6 months. The primary outcome was mean 24-hour ambulatory blood pressure at 6 months. A total of 68 participants were randomized, 34 in each group. Mean age was 63 (SD 11) years, mean baseline office blood pressure was 154/84 (13/10) mm Hg, and mean baseline 25-hydroxyvitamin D level was 42 (16) nmol/L. Treatment with vitamin D did not reduce 24-hour ambulatory blood pressure (adjusted treatment effects: systolic, +3 mm Hg; 95% confidence interval, -4 to +11; P=0.33; diastolic, -2 mm Hg; 95% confidence interval, -6 to +2; P=0.29); similar results were seen for office blood pressure. Left ventricular mass index was measured in a subgroup (n=25); no reduction was seen with vitamin D treatment (adjusted treatment effect, +4 g/m(2); 95% confidence interval, 0 to +7; P=0.04). There was no significant change in cholesterol or glucose levels. Thus, 6 months of intermittent, high-dose oral vitamin D3 did not reduce blood pressure or left ventricular mass in patients with resistant hypertension.

  1. A Rare Case of Lipomatous Hypertrophy of the Interventricular Septum

    OpenAIRE

    Papadopoulos, Christodoulos E; Matsiras, Sotirios; Vassilikos, Vassilios

    2016-01-01

    Asymmetrical left ventricular hypertrophy secondary to interventricular septum hypertrophy is usually considered a typical phenotype of hypertrophic cardiomyopathy. In rare cases other conditions such as tumors or lipomatous hypertrophy of the interventricular septum may have a similar presentation. We present a case of a male patient who presented for routine cardiology work up and was diagnosed of having ventricular septal hypertrophy secondary to localized lipomatous hypertrophy.

  2. Negative association of endothelial nitric oxide gene polymorphism with hypertension in Turkish patients: effect of ecNOS polymorphism on left ventricular hypertrophy

    Directory of Open Access Journals (Sweden)

    Arslan Erol

    2006-08-01

    Full Text Available Abstract Background Endothelial nitric oxide synthase produces nitric oxide which is involved in many physiologic regulatory functions. Variable number of tandem repeats in intron 4 of endothelial nitric oxide synthase gene are reported to be associated with blood pressure regulation. Nitric oxide is involved in regulation of cardiomyocyte genes but it is not known If endothelial nitric oxide synthase 4 gene polymorphisms are related with left ventricular hypertrophy. We studied endothelial nitric oxide synthase 4a/b allele status in hypertensive and normotensive patients and echocardiographic parameters in a subgroup of hypertensive group. Methods We performed a case-control study involving 110 Turkish hypertensive patients and 87 controls. All subjects were genotyped for endothelial nitric oxide synthase 4a/b polymorphism. Echocardiographic measurements were obtained in 94 of the hypertensive patients. Results Endothelial nitric oxide synthase 4a/b genotype frequencies were 6.4%, 23.6%, 70% in hypertensives and 1.1%, 18.4%, 80.5% in controls for a/a, a/b, b/b, respectively. Left ventricular dimensions, mass and diastolic indices were not different across endothelial nitric oxide synthase 4 genotypes. Patients with 4a/a genotype had higher interventricular septal thickness than the other group; 14.83(1.6, 11.91(1.51, 12.21(1.56 for a/a, a/b, b/b, respectively and p = 0.0001. Conclusion Endothelial nitric oxide synthase 4a/b gene polymorphism is not associated with hypertension in Turkish patients. 4a/a genotype was associated with higher interventricular septal thickness in hypertensive patients.

  3. The diagnostic performance of mid-regional portion of pro-atrial natriuretic peptide for the detection of left ventricular hypertrophy in Caucasian hypertensive patients.

    Science.gov (United States)

    Bhandari, S S; Davies, J E; Struck, J; Ng, L L

    2012-12-01

    Left ventricular hypertrophy (LVH) is predictive of cardiovascular disease. The vasodilator, natriuretic and diuretic actions of atrial natriuretic peptide (ANP) support a role in the pathophysiology of hypertension. Measuring the redundant precursor fragment mid-regional portion of pro-atrial natriuretic peptide (MRproANP) overcomes the technical difficulties of quantifying the bioactive ANP. This study sought to investigate the diagnostic and prognostic utility of MRproANP in a hypertensive Caucasian patient population. A total of 194 hypertensive patients (39 patients with LVH, 69±7.82 years of age, 74% female vs 155 patients without LVH, 68±6.51 years of age, 71% female) were derived from a screening study. Plasma MRproANP concentrations were quantified using immunoluminometric assays. Hypertensive patients with LVH had higher MRproANP concentrations than those without LVH (103.04 (50.58) vs 84.11 pmol l(-1) (44.82); P=0.014). Independent predictors of left ventricular mass index were LogMRproANP (P=0.022), male gender (Pdetection of LVH was limited, yielding an area under the curve of only 0.628 (confidence interval 0.523-0.733; P=0.014). Therefore, the role of MRproANP may not lie in the diagnosis of LVH but in monitoring the response to therapy. A nonsignificant trend towards greater mortality in patients with above-median MRproANP levels compared with below-median levels (P=0.167) was observed. Larger studies are required to assess its prognostic utility further. PMID:22113442

  4. THE ROLE OF THE MATRIX METALLOPROTEINASES IN THE DEVELOPMENT OF LEFT VENTRICULAR HYPERTROPHY IN PATIENTS WITH ARTERIAL HYPERTENSION AND METABOLIC SYNDROME

    Directory of Open Access Journals (Sweden)

    A. N. Zakirova

    2015-09-01

    Full Text Available Aim. To assess the role of the activation of matrix metalloproteinase-1 zymogen (ProMMP-1 and tissue inhibitor of metalloproteinase-1 (TIMP-1 in the development of left ventricular (LV hypertrophy in patients with arterial hypertension (HT and metabolic syndrome (MS with varying degree of obesity.Material and methods. 108 patients with HT and MS divided into 3 groups according to body mass index, and 28 healthy women were studied. Intracardiac blood flow and ProMMP-1 and TIMP-1 levels were assessed.Results. Disbalance in the ProMMP-1 and TIMP-1 systems  is associated with the severity of left ventricular remodeling and grade of obesity. The changes in LV structure and geometry and activation ProMMP-1 with a deficit of TIMP-1 were most significant in patients with HT and grade 3 obesity (respectively 7.7±0.61 and 183.6±17.2 ng/ml in grade 3 obesity vs 3.5±0.3 and 291.7±22.4 ng/ml in grade 1 obesity; p<0.05. Associations between hemodynamic parameters and levels of ProMMP-1 [withLVmass index (LVMI: r=0.47; p<0.05] and TIMP-1 (with LVMI: r=-0.39;  p<0.05 were determined.Conclusion. Changes in the ProMMP-1 and TIMP-1 system in women with HT and MS are associated with the severity ofLVhypertrophy.

  5. Concomitant coronary and renal revascularization improves left ventricular hypertrophy more than coronary stenting alone in patients with ischemic heart and renal disease.

    Science.gov (United States)

    Dong, Hao-jian; Huang, Cheng; Luo, De-mou; Ye, Jing-guang; Yang, Jun-qing; Li, Guang; Luo, Jian-fang; Zhou, Ying-ling

    2016-01-01

    Percutaneous transluminal renal artery stenting (PTRAS) has been proved to have no more benefit than medication alone in treating atherosclerotic renal artery stenosis (ARAS). Whether PTRAS could improve left ventricular hypertrophy (LVH) and reduce adverse events when based on percutaneous coronary intervention (PCI) for patients with coronary artery disease (CAD) and ARAS is still unclear. A retrospective study was conducted, which explored the effect of concomitant PCI and PTRAS versus PCI alone for patients with CAD and ARAS complicated by heart failure with preserved ejection fraction (HFpEF). A total of 228 patients meeting inclusion criteria were divided into two groups: (1) the HFpEF-I group, with PCI and PTRAS; (2) the HFpEF-II group, with PCI alone. Both groups had a two-year follow-up. The left ventricular mass index (LVMI) and other clinical characteristics were compared between groups. During the follow-up period, a substantial decrease in systolic blood pressure (SBP) was observed in the HFpEF-I group, but not in the HFpEF-II group. There was marked decrease in LVMI in both groups, but the HFpEF-I group showed a greater decrease than the HFpEF-II group. Regression analysis demonstrated that PTRAS was significantly associated with LVMI reduction and fewer adverse events after adjusting for other factors. In HFpEF patients with both CAD and ARAS, concomitant PCI and PTRAS can improve LVH and decrease the incidence of adverse events more than PCI alone. This study highlights the beneficial effect of ARAS revascularization, as a new and more aggressive revascularization strategy for such high-risk patients.

  6. [EFFICACY OF STANDARD TWO-YEAR COMPREHENSIVE THERAPY TO ACHIEVE TARGET BLOOD PRESSURE AND REGRESSION DEGREES OF REMODELING OF THE LEFT VENTRICULAR HYPERTROPHY IN PATIENTS AFTER ACUTE MYOCARDIAL INFARCTION WITH COMORBID HYPERTENSION].

    Science.gov (United States)

    Denesiuk, E V

    2015-01-01

    The study involved 23 men after acute myocardial infarction (AMI) with comorbid arterial hypertension (AH). Mean age of patients was 56.7 years. Recurrent myocardial infarction was determined in 38.4%, cardiac failure I-III functional classes--100% of the cases. All patients underwent clinical examination, electrocardiography and echocardiography, blood lipid profile. Standard comprehensive treatment for two years included an perindopril 5-10 mg/day, beta-blocker bisoprolol--5-10 mg/day, antisclerotic drug atorvastatin--20 mg/day and aspirin--75 mg/day. The patients after treatment was determined by a gradual increase towards the target of AT at 3, 6 and 12 to 24 months. Concentric left ventricular hypertrophy (LVH) before treatment was determined in 47.8%, eccentric--in 52.2% of patients. In the study of degrees of LVH I (initial) the extent to treatment was determined by 4.3%, II (moderate)--26.1%, III (large)--at 69.6%, indicating the development of cardiac remodeling. After the treatment was determined by marked reduction III (large) degree and transfer it in the II (moderate) and I (small) degree of left ventricular hypertrophy due to more or less pronounced changes remodeling left ventricular. The obtained data allow a more detailed and adequately assess the structural and functional outcome variables and determine the regression of myocardial hypertrophy in the background to achieve target blood pressure, which is important in practical cardiology.

  7. [EFFICACY OF STANDARD TWO-YEAR COMPREHENSIVE THERAPY TO ACHIEVE TARGET BLOOD PRESSURE AND REGRESSION DEGREES OF REMODELING OF THE LEFT VENTRICULAR HYPERTROPHY IN PATIENTS AFTER ACUTE MYOCARDIAL INFARCTION WITH COMORBID HYPERTENSION].

    Science.gov (United States)

    Denesiuk, E V

    2015-01-01

    The study involved 23 men after acute myocardial infarction (AMI) with comorbid arterial hypertension (AH). Mean age of patients was 56.7 years. Recurrent myocardial infarction was determined in 38.4%, cardiac failure I-III functional classes--100% of the cases. All patients underwent clinical examination, electrocardiography and echocardiography, blood lipid profile. Standard comprehensive treatment for two years included an perindopril 5-10 mg/day, beta-blocker bisoprolol--5-10 mg/day, antisclerotic drug atorvastatin--20 mg/day and aspirin--75 mg/day. The patients after treatment was determined by a gradual increase towards the target of AT at 3, 6 and 12 to 24 months. Concentric left ventricular hypertrophy (LVH) before treatment was determined in 47.8%, eccentric--in 52.2% of patients. In the study of degrees of LVH I (initial) the extent to treatment was determined by 4.3%, II (moderate)--26.1%, III (large)--at 69.6%, indicating the development of cardiac remodeling. After the treatment was determined by marked reduction III (large) degree and transfer it in the II (moderate) and I (small) degree of left ventricular hypertrophy due to more or less pronounced changes remodeling left ventricular. The obtained data allow a more detailed and adequately assess the structural and functional outcome variables and determine the regression of myocardial hypertrophy in the background to achieve target blood pressure, which is important in practical cardiology. PMID:27491146

  8. Effect of fosinopril on progression of the asymptomatic carotid atherosclerosis and left ventricular hypertrophy in hypertensive patients

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    Tasić Ivan

    2006-01-01

    Full Text Available INTRODUCTION The cardiovascular changes (vascular structure changes, hypertrophy of the left ventricle contribute to both the increased cardiovascular morbidity and the mortality of essential hypertension. Therefore, modern treatment strategies should not only target blood pressure (BP reduction but also normalize cardiovascular structure and function. OBJECTIVE Aim of the study was to determine the effect of the ACE inhibitor Fosinopril on the Intima-media thickness of the common carotid artery and on the left ventricle mass after 9-month treatment of hypertensive patients. METHOD The study included 40 patients with the arterial hypertension and the left ventricle hypertrophy verified by echocardiography. The patients were randomized on A ACE-inhibitor - Fosinopril and 6 without ACE inhibitor - atenolol, and they were followed up 9 months. The groups were not different by age, sex, and metabolic status. Color Duplex ultrasonography of the carotid arteries was performed by Acuson Sequia C236 with high-frequency linear probe of 8 MHz. The Intima-media thickness of the common carotids on the left and the right was measured in diastole at 1.5. cm from the highest point of bifurcation under maximal magnification. Using the same device, the left ventricle mass and other parameters of the left ventricle were determined in M-mode and by means of 2D image. RESULTS After 9 months, BP In both groups Was reduced In similar range (group A: systolic BP from 158 to 137 mmHg, and diastolic BP from 94 to 85 mmHg, and group B; systolic BP from 164 to 137 mmHg, and diastolic BP from 87 to 84 mmHg. The thickness of the intimomedial complex in patients using Fosinopril was decreased by 0.0278 ± 0.03 mm, while in the group of patients that did not use the ACE-inhibitor, it was increased by 0.078 ±0.13 mm. The left ventricle mass in patients using Fosinopril was decreased by 5 grams (312 ± 72 g vs. 307 ± 77 g, while in group B patients, it was increased by 15

  9. Left ventricular hypertrophy index based on a combination of frontal and transverse planes in the ECG and VCG: Diagnostic utility of cardiac vectors

    Science.gov (United States)

    Bonomini, Maria Paula; Juan Ingallina, Fernando; Barone, Valeria; Antonucci, Ricardo; Valentinuzzi, Max; Arini, Pedro David

    2016-04-01

    The changes that left ventricular hypertrophy (LVH) induces in depolarization and repolarization vectors are well known. We analyzed the performance of the electrocardiographic and vectorcardiographic transverse planes (TP in the ECG and XZ in the VCG) and frontal planes (FP in the ECG and XY in the VCG) to discriminate LVH patients from control subjects. In an age-balanced set of 58 patients, the directions and amplitudes of QRS-complexes and T-wave vectors were studied. The repolarization vector significantly decreased in modulus from controls to LVH in the transverse plane (TP: 0.45±0.17mV vs. 0.24±0.13mV, pECG and VCG spaces. A subset of all those indexes with AUC values greater than 0.7 was further studied. This subset comprised four indexes, with three of them belonging to the ECG space. Two out of the four indexes presented the best ROC curves (AUC values: 0.78 and 0.75, respectively). One index belonged to the ECG space and the other one to the VCG space. Both indexes showed a sensitivity of 86% and a specificity of 70%. In conclusion, the proposed indexes can favorably complement LVH diagnosis

  10. Effects of Yixin Jiangya Capsules on Insulin Resistance and Tumor Necrosis Factor-α in Cases of Primary Hypertension with Left Ventricular Hypertrophy

    Institute of Scientific and Technical Information of China (English)

    Duan Xuezhong; Zhong Shenqing; Sun Xiqing; Cai Xinji

    2007-01-01

    Objectives:To observe the effects of Yixin Jiangya Capsules (益心降压胶囊 capsules for nourishing the heart and lowering blood pressure) on insulin resistance (IR) and tumor necrosis factor-α (TNF-α) in patients with primary hypertension with left ventricular hypertrophy (LVH). Methods: Totally 93cases were randomly divided into a control group of 31 cases taking Enalapril and a treatment group of 62cases taking Enalapril and Yixin Jiangya Capsules. Results: Fasting serum insulin (FSI) and TNF-α obviously increased and insulin sensitive index (ISI) significantly decreased in both groups before treatment as compared to those of a healthy group. After treatment, FSI, TNF-α and fasting blood glucose (FBG) obviously decreased and ISI remarkably increased in the treatment group, while ISI significantly increased and TNF-α obviously decreased in the control group. The curative effect in the treatment group was remarkably superior to that in the control group. FSI was positively related to TNF-α before treatment in both groups. Conclusion: FSI and TNF-α obviously increase and ISI significantly decreases in patients with primary hypertension with LVH. FSI and TNF-α influencing each other are involved in the generation and development of hypertension. Yixin Jiangya Capsules can improve IR and decrease TNF-α.

  11. Effects of losartan compared with atenolol on lipids in patients with hypertension and left ventricular hypertrophy: the Losartan Intervention For Endpoint reduction in hypertension study

    DEFF Research Database (Denmark)

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

    2009-01-01

    OBJECTIVE: Beta-blockers and angiotensin II receptor blockers have different effects on lipids. METHODS: We examined lipid levels in the Losartan Intervention For Endpoint reduction in hypertension study and their impact on the primary composite endpoint of cardiovascular death, myocardial...... infarction, or stroke. We measured total and high-density lipoprotein cholesterol at baseline and annually during 4.8 years of losartan-based compared with atenolol-based treatment in 8611 patients with hypertension and left ventricular hypertrophy. RESULTS: Patients randomized to losartan-based or atenolol...... decreased less during the first 2 years in patients randomized to losartan compared with atenolol (-0.13 +/- 0.24 vs. -0.19 +/- 0.25 mmol/l) and remained higher each year (1.38, 1.37, 1.42, 1.47, and 1.48 mmol/l vs. 1.32, 1.30, 1.36, 1.40, and 1.42 mmol/l, all P

  12. 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 Markers of collagen synthesis is related to blood pressure and vascular hypertrophy: a LIFE substudy

    DEFF Research Database (Denmark)

    Olsen, M H; Christensen, M K; Wachtell, K;

    2005-01-01

    Cardiac fibrosis and high levels of circulating collagen markers has been associated with left ventricular (LV) hypertrophy. However, the relationship to vascular hypertrophy and blood pressure (BP) load is unclear. In 204 patients with essential hypertension and electrocardiographic LV hypertrophy...

  13. Hipertrofia ventricular esquerda em pacientes com doença renal crônica em tratamento conservador Left ventricular hypertrophy in patients with chronic kidney disease under conservative treatment

    Directory of Open Access Journals (Sweden)

    Rachel Bregman

    2010-03-01

    Full Text Available A doença cardiovascular (DCV permanece sendo uma das maiores causas de morte em pacientes com doença renal crônica (DRC. A hipertrofia ventricular esquerda (HVE está presente em 75% dos pacientes ao iniciarem diálise, sugerindo que esta deve estar presente precocemente no curso da DRC. Poucos estudos avaliaram a prevalência de HVE na pré-diálise. Foram avaliados 309 pacientes clinicamente estáveis em acompanhamento por pelo menos três meses em cinco Centros no Brasil. Perfil bioquímico e marcadores inflamatórios foram avaliados. Dados são apresentados como media ± DP. Observamos que a HVE esteve presente em 53% dos pacientes, idade = 60 ± 13 anos, e 55 ± 14 anos para aqueles sem HVE. Diabetes mellitus como doença de base esteve presente em 35% dos pacientes em ambos os grupos. Filtração glomerular estimada foi 30 ± 11 e 32 ± 12 mL/min para pacientes com HVE e sem, respectivamente (p = 0,19. A distribuição de pacientes mostrou que 60% com HVE se encontravam no estágio 4. Análise logística multivariada mostrou que eram determinantes independentes para HVE: idade (p Cardiovascular disease (CVD remains the major cause of death in patients with chronic kidney disease (CKD. Left ventricular hypertrophy (LVH is present in 75% of patients starting dialysis, suggesting that LVH might be present from an early stage of CKD. Few studies have addressed the predialysis prevalence of LVH. This study evaluated 309 clinically stable patients under treatment for at least three months at five Brazilian centers. Biochemical profile and inflammatory markers were assessed. Data were shown as mean ± SD. Left ventricular hypertrophy was present in 53% of the patients, whose mean age was 60 ± 13years. The mean age of those without LVH was 55 ± 14 years. Diabetes mellitus was the underlying disease in 35% of the patients in both groups. Estimated glomerular filtration rate was 30 ± 11 and 32 ± 12 mL/min for patients with and without LVH

  14. [THE EFFECTIVENESS OF THE CORRECTION OF ENDOTHELIAL DYSFUNCTION AND REMODELING OF THE BRACHIAL ARTERY WITH CONCENTRIC AND ECCENTRIC LEFT VENTRICULAR HYPERTROPHY IN PATIENTS WITH UNSTABLE ANGINA WITH COMORBID HYPERTENSION].

    Science.gov (United States)

    Denesiuk, E V

    2015-01-01

    The study involved patients with unstable angina (UA), comorbid hypertension (AH), myocardial infarction in 55.5% of cases. Systolic blood pressure was (163.2 ± 1.5) mm Hg. Art., diastolic blood pressure--(101.10 ± 0.67) mm Hg. Art., pulse pressure--(61.1 ± 17.0) mm Hg. Art. Examined patients underwent clinical studies, ECG in 12 conventional leads, echocardiography in M and B modes, Doppler ultrasonography of the brachial artery. To correct the detected change using standard combined therapy: perindopril 5-10 mg/day, bisoprolol--5-10 mg/day, atorvastatin--20 mg/day, acetylsalicylic acid--75-100 mg/day. Monitoring the treatment was carried out at 3; 6 and 12 months. Standard one-year comprehensive treatment of patients with UA with comorbid AH resulted in significant improvement of effective endothelial dysfunction in concentric and eccentric left ventricular hypertrophy in 3; 6 and 12 months, however, regression of hypertrophy brachial artery advancing much less mainly in concentric left ventricular hypertrophy. PMID:27089719

  15. False-positive defects in technetium-99m sestamibi myocardial single-photon emission tomography in healthy athletes with left ventricular hypertrophy

    International Nuclear Information System (INIS)

    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.)

  16. Short-term beat-to-beat variability of the QT interval is increased and correlates with parameters of left ventricular hypertrophy in patients with hypertrophic cardiomyopathy.

    Science.gov (United States)

    Orosz, Andrea; Baczkó, István; Nagy, Viktória; Gavallér, Henriette; Csanády, Miklós; Forster, Tamás; Papp, Julius Gy; Varró, András; Lengyel, Csaba; Sepp, Róbert

    2015-09-01

    Stratification models for the prediction of sudden cardiac death (SCD) are inappropriate in patients with hypertrophic cardiomyopathy (HCM). We investigated conventional electrocardiogram (ECG) repolarization parameters and the beat-to-beat short-term QT interval variability (QT-STV), a new parameter of proarrhythmic risk, in 37 patients with HCM (21 males, average age 48 ± 15 years). Resting ECGs were recorded for 5 min and the frequency corrected QT interval (QTc), QT dispersion (QTd), beat-to-beat short-term variability of QT interval (QT-STV), and the duration of terminal part of T waves (Tpeak-Tend) were calculated. While all repolarization parameters were significantly increased in patients with HCM compared with the controls (QTc, 488 ± 61 vs. 434 ± 23 ms, p < 0.0001; QT-STV, 4.5 ± 2 vs. 3.2 ± 1 ms, p = 0.0002; Tpeak-Tend duration, 107 ± 27 vs. 91 ± 10 ms, p = 0.0015; QTd, 47 ± 17 vs. 34 ± 9 ms, p = 0.0002), QT-STV had the highest relative increase (+41%). QT-STV also showed the best correlation with indices of left ventricular (LV) hypertrophy, i.e., maximal LV wall thickness normalized for body surface area (BSA; r = 0.461, p = 0.004) or LV mass (determined by cardiac magnetic resonance imaging) normalized for BSA (r = 0.455, p = 0.015). In summary, beat-to-beat QT-STV showed the most marked increase in patients with HCM and may represent a novel marker that merits further testing for increased SCD risk in HCM. PMID:26313025

  17. Management of high-risk patients with hypertension and left ventricular hypertrophy in Germany: differences between cardiac specialists in the inpatient and outpatient setting

    Directory of Open Access Journals (Sweden)

    Wegscheider Karl

    2006-10-01

    Full Text Available Abstract Background Among patients with hypertension, those with established left ventricular hypertrophy (LVH represent a high risk cohort with poor prognosis. We aimed to investigate differences in characteristics and health care management of such patients treated as inpatients or outpatients by cardiac specialists. Methods Prospective cross-sectional study in patients with hypertension and LVH who were referred to either inpatient care (rehabilitation hospitals or to outpatient care (cardiology practices. Results A total of 6358 inpatients (59.6% males; mean age 66.6 years and 2246 outpatients (59.5% males; mean age 63.2 years were followed up for a mean of 23 vs. 52 days, respectively. Inpatients compared to outpatients had a significantly higher prevalence of coronary heart disease, history of stroke, renal failure or diabetes. Mean blood pressure of inpatients compared to outpatients was significantly lower both at entry (150/84 vs. 161/93 mmHg and at end of follow-up (129/75 vs. 139/83 mmHg. After adjustment for baseline blood pressure and a propensity score, differences between out- and inpatients at end of follow-up were 8.0/5.1 mmHg in favour of inpatients. Blood pressure goals as specified by guidelines were not met by 32% of inpatients and 55% of outpatients. Conclusion Inpatients had a higher rate of comorbidities and more advanced atherosclerotic disease than outpatients. Control of hypertension of inpatients was already better on admission than in outpatients, and treatment intensity in this group was also higher during the observation period. While blood pressure lowering was substantial in both groups, there were still a high proportion of patients who did not achieve treatment goals at discharge.

  18. False-positive defects in technetium-99m sestamibi myocardial single-photon emission tomography in healthy athletes with left ventricular hypertrophy

    Energy Technology Data Exchange (ETDEWEB)

    Bartram, P.; Hanel, B.; Gustafsson, F.; Mortensen, J.; Hesse, B. [Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital (Denmark); Toft, J. [Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital (Denmark)]|[Copenhagen City Heart Study, Epidemiological Research Unit (Denmark); Ali, S. [Dept. of Cardiology, Copenhagen University Hospital (Denmark)

    1998-09-01

    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.) With 1 fig., 26 tabs., 22 refs.

  19. Effects of the combinations of amlodipine/valsartan versus losartan/hydrochlorothiazide on left ventricular hypertrophy as determined with magnetic resonance imaging in patients with hypertension

    Science.gov (United States)

    Bruder, Oliver; Jensen, Christoph J.; Bell, Michael; Rummel, Reinhard; Boehm, Guenter; Klebs, Sven; Sieder, Christian; Senges, Jochen

    2012-01-01

    Background Left ventricular hypertrophy (LVH), a marker of cardiac end-organ damage, is frequently found in patients with arterial hypertension and is associated with cardiovascular and cerebrovascular morbidity and mortality. Therefore, LVH regression is an important treatment goal. For amlodipine plus valsartan (A/V) no specific study on LVH has been reported to date. Methods Prospective, open-label, randomized parallel-group study. Patients with essential hypertension and LVH were randomized to 52-week treatment with A/V 10/160 mg (n = 43) or the active comparator losartan/HCT 100/25 mg (L/H, n = 47). Add-on medication was allowed in case of inadequate blood pressure control. LV parameters were measured by cardiovascular magnetic resonance imaging (MRI), and adjudicated in a blinded manner. Study identifiers were NCT00446563 and EudraCT 2006-001977-17. Results In addition to the study treatment, 35% of patients in the A/V group and 49% in the L/H group received additional antihypertensive medication. Compared to baseline, both treatments reduced measures of LVH significantly after 52 weeks (e.g. LV mass index in the A/V group from 64.7 g/m2 by −3.5 g/m2, in the L/H group from 69.1 g/m2 by −4.4 g/m2, p < 0.01 for both). LV ejection fraction and LV volumes were not significantly changed by any regimen. A/V and L/H treatments were well tolerated. Conclusions Both regimen were effective in reducing LV mass compared to baseline and were well tolerated.

  1. Expression of mitochondrial regulatory genes parallels respiratory capacity and contractile function in a rat model of hypoxia-induced right ventricular hypertrophy

    Science.gov (United States)

    Chronic hypobaric hypoxia (CHH) increases load on the right ventricle (RV) resulting in RV hypertrophy. We hypothesized that CHH elicits distinct responses, i.e., the hypertrophied RV, unlike the left ventricle (LV), displaying enhanced mitochondrial respiratory and contractile function. Wistar rats...

  2. Molecular mechanism of carvedilol in attenuating the reversion to fetal energy metabolism during cardiac hypertrophy development

    Institute of Scientific and Technical Information of China (English)

    胡琴; 李隆贵

    2003-01-01

    Objective: To explore the molecular regulation mechanism of carvedilol in attenuating the reversion back towards fetal energy metabolism during the development of cardiac hypertrophy induced by coarctation of abdominal aorta (CAA) in male Wistar rats. Methods: Hemodynamic and ventricular remodeling parameters, free fatty acid content in the serum were measured in the experimental animals at 16 weeks after the surgical CAA, the rats receiving carvedilol intervention (CAR) after CAA, and those with sham operation (SH). The expressions of muscle carnitine palmitoyltransferaseⅠ (M-CPTⅠ) and medium chain acyl-CoA dehydrogenase (MCAD) mRNA in the cardiac myocytes from every group were studied with RT-PCR. Results: Significant left ventricular hypertrophy were observed in the rats 16 weeks after coarctation operation (P<0.05), together with significant free fatty acids accumulation and downregulation of M-CPTⅠ and MCAD mRNA (P<0.05) in CAA group. Carvedilol at a dose of 30 mg/kg/d for 12 weeks inhibited the left ventricular hypertrophy induced by pressure overload and enhanced the gene expressions of rate-limiting enzyme (M-CPTⅠ) and key enzyme of fatty acid (MCAD) in the CAR group compared with CAA group (P<0.05). Conclusion: Pressure overload-induced hypertrophy in CAA rats causes the reversion back towards fetal enery metabolism, that is, downregulates the expressions of rate-limiting enzyme and key enzyme of fatty acid oxidation. The intervention therapy with carvedilol, a vasodilating alpha- and beta-adrenoreceptor antagonist, attenuates the reversion of the metabolic gene expression to fetal type through upregulating M-CPTⅠ and MCAD mRNA expressions. Thus, carvedilol may exert cardioprotective effects on heart failure by the mechanism of preserving the adult metabolic gene regulation.

  3. Regulation of myoglobin in hypertrophied rat cardiomyocytes in experimental pulmonary hypertension.

    Science.gov (United States)

    Peters, E L; Offringa, C; Kos, D; Van der Laarse, W J; Jaspers, R T

    2016-10-01

    A major problem in chronic heart failure is the inability of hypertrophied cardiomyocytes to maintain the required power output. A Hill-type oxygen diffusion model predicts that oxygen supply is limiting in hypertrophied cardiomyocytes at maximal rates of oxygen consumption and that this limitation can be reduced by increasing the myoglobin (Mb) concentration. We explored how cardiac hypertrophy, oxidative capacity, and Mb expression in right ventricular cardiomyocytes are regulated at the transcriptional and translational levels in an early stage of experimental pulmonary hypertension, in order to identify targets to improve the oxygen supply/demand ratio. Male Wistar rats were injected with monocrotaline to induce pulmonary hypertension (PH) and right ventricular heart failure. The messenger RNA (mRNA) expression levels per nucleus of growth factors insulin-like growth factor-1Ea (IGF-1Ea) and mechano growth factor (MGF) were higher in PH than in healthy controls, consistent with a doubling in cardiomyocyte cross-sectional area (CSA). Succinate dehydrogenase (SDH) activity was unaltered, indicating that oxidative capacity per cell increased. Although the Mb protein concentration was unchanged, Mb mRNA concentration was reduced. However, total RNA per nucleus was about threefold higher in PH rats versus controls, and Mb mRNA content expressed per nucleus was similar in the two groups. The increase in oxidative capacity without an increase in oxygen supply via Mb-facilitated diffusion caused a doubling of the critical extracellular oxygen tension required to prevent hypoxia (PO2crit). We conclude that Mb mRNA expression is not increased during pressure overload-induced right ventricular hypertrophy and that the increase in myoglobin content per myocyte is likely due to increased translation. We conclude that increasing Mb mRNA expression may be beneficial in the treatment of experimental PH.

  4. 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

  5. Up Regulation of cystathione γ lyase and Hydrogen Sulphide in the Myocardium Inhibits the Progression of Isoproterenol-Caffeine Induced Left Ventricular Hypertrophy in Wistar Kyoto Rats.

    Directory of Open Access Journals (Sweden)

    Ashfaq Ahmad

    Full Text Available Hydrogen sulphide (H2S is an emerging molecule in many cardiovascular complications but its role in left ventricular hypertrophy (LVH is unknown. The present study explored the effect of exogenous H2S administration in the regression of LVH by modulating oxidative stress, arterial stiffness and expression of cystathione γ lyase (CSE in the myocardium. Animals were divided into four groups: Control, LVH, Control-H2S and LVH-H2S. LVH was induced by administering isoprenaline (5mg/kg, every 72 hours, S/C and caffeine in drinking water (62mg/L for 2 weeks. Intraperitoneal NaHS, 56μM/kg/day for 5 weeks, was given as an H2S donor. Myocardial expression of Cystathione γ lyase (CSE mRNA was quantified using real time polymerase chain reaction (qPCR.There was a 3 fold reduction in the expression of myocardial CSE mRNA in LVH but it was up regulated by 7 and 4 fold in the Control-H2S and LVH-H2S myocardium, respectively. Systolic blood pressure, mean arterial pressure, pulse wave velocity were reduced (all P<0.05 in LVH-H2S when compared to the LVH group. Heart, LV weight, myocardial thickness were reduced while LV internal diameter was increased (all P<0.05 in the LVH-H2S when compared to the LVH group. Exogenous administration of H2S in LVH increased superoxide dismutase, glutathione and total antioxidant capacity but significantly reduced (all P<0.05 plasma malanodialdehyde in the LVH-H2S compared to the LVH group. The renal cortical blood perfusion increased by 40% in LVH-H2S as compared to the LVH group. Exogenous administration of H2S suppressed the progression of LVH which was associated with an up regulation of myocardial CSE mRNA/ H2S and a reduction in pulse wave velocity with a blunting of systemic hemodynamic. This CSE/H2S pathway exhibits an antihypertrophic role by antagonizing the hypertrophic actions of angiotensin II(Ang II and noradrenaline (NA but attenuates oxidative stress and improves pulse wave velocity which helps to suppress

  6. 儿童左心室肥厚的临床病因分析%Etiological analysis of left ventricular hypertrophy in children

    Institute of Scientific and Technical Information of China (English)

    李淑华; 黄萍; 张丽; 刘特长; 虢艳

    2011-01-01

    目的 了解儿童左心室肥厚(LVH)的病因分布.方法 对2005年3月至2008年3月在广州市儿童医院二维超声诊断LVH的27例患儿(男19例、女8例,年龄平均2.66岁)行病因诊断分析.结果 27例LVH中主动脉病变所致4例(14.8%),糖原累积病Ⅱ型所致2例(7.4%),肢端肥大症所致1例(3.7%),黏多糖蓄积症所致1例(3.7%);6例(22.2%)有家族史且无明显临床症状者考虑为肥厚型心肌病(HCM);病因未明占13例(48.1%),须进一步跟踪分析.结论 心脏影像学检查提示LVH的患儿病因复杂多样,不能简单根据影像学的结果诊断HCM,进一步完善LVH病因的诊断程序,区分儿童期及成人期LVH病因分布是必要的.%Objective Left ventricular hypertrophy (LVH), especially in children, is associated with a series of disorder including cardiac and systemic diseases. The etiological diagnosis should be evaluated in pediatric LVH patients. Methods From March 2005 to March 2008, clinical data from 27 patients (19 males and 8 females, mean age 2.66 years) with LVH diagnosed by two-dimensional ultrasound were analyzed. Results Among 27 patients, the prinary disease were aortic disease in 4 (14.8%) patients, glycogen-storage disease in 2 (7.4%) patients, acromegaly in one (3.7%) patient, and glycosaminoglycan disease in one (3.7%) patient. Six (22.2%) patients with positive family history of LVH were considered to have hypertrophic cardiomyopathy. The primary diseases were unclear in another 13 (48.1%) patients. Conclusions The primary diseases were complicated in LVH patients diagnosed by imaging examination. The diagnosis of LVH should be not only based on imping examination, but also relied on etiological diagnosis.

  7. Relation of electrocardiographic left ventricular hypertrophy to blood pressure, body mass index, serum lipids and blood sugar levels in adult Nigerians.

    Science.gov (United States)

    Opadijo, O G; Omotoso, A B O; Akande, A A

    2003-12-01

    Left ventricular hypertrophy (LVH) is considered an independent risk factor even in the absence of systemic hypertension. Electrocardiographic (ECG) LVH with repolarisation changes has been found in some countries to carry more coronary risk than LVH alone. How far this observation is true among adult Nigerians is not known. We therefore decided to study adult Nigerians with ECG-LVH with or without ST-T waves changes and compare them with normal age matched controls (without ECG-LVH) in relation with established modifiable risk factors such as systemic hypertension (BP), body mass index (BMI), fasting blood sugar (FBS) and serum lipids such as total cholesterol (Tc), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and triglyceride (TG). Adult Nigerians who were consecutively referred to the ECG laboratory were randomly recruited. Three hundred patients were studied. Their blood pressures (BP) as well as body mass indices were recorded after recording their resting 12 read ECG using portable Seward 9953 ECG machine. Their waist-hip ratio (WHR) was also recorded. Blood samples were taken to determine their fasting blood sugar and serum lipids. Their ECG tracings were read by the cardiologists involved in the study while the blood samples were analysed by the chemical pathologist also involved in the study. At the end of the ECG reading, the patients were divided into 3 groups according to whether there was no ECG-LVH (control group A), ECG-LVH alone (group B), and ECG-LVH with ST-T waves changes (group C). One hundred and fifty (50%) patients belonged to group A, 100 (33.3%) patients to group B and 50 (16.7%) group C. Group B patients were found to have higher modifiable risk factors in form of systemic BP. Tc, LDL-C, and WHR compared to group A. However, the group C patients had increased load of these coronary risk factors in terms of BP elevation, higher BMI, FBS, and scrum cholesterol compared to group B. In addition

  8. Determinants of discrepancies in detection and comparison of the prognostic significance of left ventricular hypertrophy by electrocardiogram and cardiac magnetic resonance imaging.

    Science.gov (United States)

    Bacharova, Ljuba; Chen, Haiying; Estes, E Harvey; Mateasik, Anton; Bluemke, David A; Lima, Joao A C; Burke, Gregory L; Soliman, Elsayed Z

    2015-02-15

    Despite the low sensitivity of the electrocardiogram (ECG) in detecting left ventricular hypertrophy (LVH), ECG-LVH is known to be a strong predictor of cardiovascular risk. Understanding reasons for the discrepancies in detection of LVH by ECG versus imaging could help improve the diagnostic ability of ECG. We examined factors associated with false-positive and false-negative ECG-LVH, using cardiac magnetic resonance imaging (MRI) as the gold standard. We also compared the prognostic significance of ECG-LVH and MRI-LVH as predictors of cardiovascular events. This analysis included 4,748 participants (mean age 61.9 years, 53.5% females, 61.7% nonwhites). Logistic regression with stepwise selection was used to identify factors associated with false-positive (n = 208) and false-negative (n = 387), compared with true-positive (n = 208) and true-negative (n = 4,041) ECG-LVH, respectively. A false-negative ECG-LVH status was associated with increased odds of Hispanic race/ethnicity, current smoking, hypertension, increased systolic blood pressure, prolongation of QRS duration, and higher body mass index and with lower odds of increased ejection fraction (model-generalized R(2) = 0.20). A false-positive ECG-LVH status was associated with lower odds of black race, Hispanic race/ethnicity, minor ST-T abnormalities, increased systolic blood pressure, and presence of any major electrocardiographic abnormalities (model-generalized R(2) = 0.29). Both ECG-LVH and MRI-LVH were associated with an increased risk of cardiovascular disease events (hazard ratio 1.51, 95% confidence interval 1.03 to 2.20 and hazard ratio 1.81, 95% confidence interval 1.33 to 2.46, respectively). In conclusion, discrepancy in LVH detection by ECG and MRI can be relatively improved by considering certain participant characteristics. Discrepancy in diagnostic performance, yet agreement on predictive ability, suggests that LVH by ECG and LVH by imaging are likely to be two distinct but somehow related

  9. Crocin, a carotenoid component of Crocus cativus, exerts inhibitory effects on L-type Ca(2+) current, Ca(2+) transient, and contractility in rat ventricular myocytes.

    Science.gov (United States)

    Liu, Tao; Chu, Xi; Wang, Hua; Zhang, Xuan; Zhang, Yuanyuan; Guo, Hui; Liu, Zhenyi; Dong, Yongsheng; Liu, Hongying; Liu, Yang; Chu, Li; Zhang, Jianping

    2016-03-01

    Crocin, a carotenoid component of Crocus sativus L. belonging to the Iridaceae family, has demonstrated cardioprotective effects. To investigate the cellular mechanisms of these cardioprotective effects, here we studied the influence of crocin on L-type Ca(2+)current (I(Ca-L)), intracellular Ca(2+) ([Ca(2+)]i), and contraction of isolated rat cardiomyocytes by using the whole-cell patch-clamp technique and video-based edge detection and dual excitation fluorescence photomultiplier systems. Crocin inhibited I(Ca-L) in a concentration-dependent manner with the half-maximal inhibitory concentration (IC50) of 45 μmol/L and the maximal inhibitory effect of 72.195% ± 1.54%. Neither current-voltage relationship of I(Ca-L), reversal potential of I(Ca-L), nor the activation/inactivation of I(Ca-L) was significantly changed. Crocin at 1 μmol/L reduced cell shortening by 44.64% ± 2.12% and the peak value of the Ca(2+) transient by 23.66% ± 4.52%. Crocin significantly reduced amplitudes of myocyte shortening and [Ca(2+)]i with an increase in the time to reach 10% of the peak (Tp) and a decrease in the time to 10% of the baseline (Tr). Thus, the cardioprotective effects of crocin may be attributed to the attenuation of [Ca(2+)]i through the inhibition of I(Ca-L) in rat cardiomyocytes and negative inotropic effects on myocardial contractility.

  10. 美托洛尔联合缬沙坦对高血压左室肥厚及左室舒张功能的影响%Effect of metoprolol combined with valsartan on hypertensive left ventricular hypertrophy and left ventricular diastolic function

    Institute of Scientific and Technical Information of China (English)

    韩艳华; 杨春梅; 宋忠海; 栗玉斌; 徐斌; 李秋颖

    2015-01-01

    目的 观察美托洛尔联合缬沙坦治疗高血压对左室肥厚及左室舒张功能的影响. 方法 选择经超声心动图检查有左室肥厚( LVH)的高血压患者180例,随机分为A、B、C 3组,A组给予美托洛尔+缬沙坦治疗;B组给予缬沙坦治疗;C组给予美托洛尔治疗;疗程均为1年. 检查心脏超声并计算左室肌重量和左室肌重量指数( LVMI)、24 h动态血压、心电图等,并进行治疗前后对比及组间对比. 结果 所有病例治疗后,血压下降、左室肥厚、左室舒张功能都显示有效(P<0.01),但A组的疗效优于B、C组(P<0.01),特别是A组LVMI明显降低,由(136.8 ±7.3)g/m2 降至(127.7 ±4.6)g/m2,左室舒张功能提高. 结论 美托洛尔联合缬沙坦治疗高血压,可以降低血压、减轻左室肥厚、提高左室舒张功能.%Objective Effect of metoprolol combined with valsartan for treatment of hypertensive patients with left ventricular hypertrophy and left ventricular diastolic function was observed .Methods In this study , we recruited 180 patients diagnosed as hav-ing hypertension and left ventricular hypertrophy ( LVH ) by echocardiographic examination and randomly divided them into three groups, A, B and C.The treatment of the patients in group A was given metoprolol and valsartan;the group B was given valsartan;the group C was given metoprolol;all treatment courses were one year .Echocardiography , 24-hour ambulatory blood pressure , and electro-cardiogram were checked , and left ventricular muscle weight and left ventricular mass index were measured .The effects and group differences after and before treatment were compared .Results After treatment , in all patients , blood pressure was well-controlled , left ventricular hypertrophy , left ventricular diastolic function were improved (P<0.01).But group A obtained better efficacy than group B and group C (P<0.01), especially the left ventricular mass index in group A dropped clearly from (136.8 ±7.3)g/m2

  11. 脉压与冠心病患者左室肥厚的关系探讨%The relationship between pulse pressure and left ventricular hypertrophy in patients with coronary heart disease

    Institute of Scientific and Technical Information of China (English)

    宋文东

    2011-01-01

    Objective To investigate the relationship between pulse pressure and left ventricular hypertrophy in patients with coronary heart disease. Methods Ninety - six patients admitted to hospital with coronary heart disease were divided into three groups according to the size of pulse pressure: group A, 30 patients, pulse pressure ≤ 45 mmHg; group B, 35 patients, 55 mmHg ≥ pulse pressure> 45 mmHg; group C, 31 patients, pulse pressure> 55 mmHg. Interven-tricular septal thickness (IVST), left ventricular posterior wall thickness (PWT), left ventricular end - diastolic diameter (LVDd), left ventricular ejection fraction (LVEF) and left ventricular mass index (LVMI) were measured with the help of color ultrasound diagnostic cardiac diastolic. Results LVEF of Group was significantly lower than that of group A and group B . LVMI and IVST were significantly higher. Conclusion Increased pulse pressure can make left ventricular hypertrophy more obvious and heart function in patients with coronary heart disease significantly worsened.%目的 探讨冠心病患者左室肥厚与脉压的关系.方法 将本院收治的96例冠心病患者根据脉压大小分为3组:A组30例,脉压≤45 mmHg;B组35例,55 mmHg≥脉压>45 mmHg;C组31例,脉压>55 mmHg.采用彩色超声心脏诊断仪测定舒张期室间隔厚度(IVST)、左室后壁厚度(PWT)、左室舒张末期内径(LVDd)、左室射血分数(LVEF)及左心室质量指数(LVMI).结果 C组患者LVEF明显低于A、13组;LVMI、IVST明显高于A、B组.结论 脉压增高使冠心病患者左室肥厚更加明显,且心功能下降明显.

  12. Hypertrophied hearts: what of sevoflurane cardioprotection?

    DEFF Research Database (Denmark)

    Larsen, Jens Kjærgaard Rolighed; Smerup, Morten Holdgaard; Hasenkam, John Michael;

    2009-01-01

    cardioprotection with anaesthetics remain controversial--in contrast to solid experimental evidence. Concomitant left ventricular hypertrophy is found in some cardiac surgery patients and could change cardioprotection efficacy. Hypertrophy could potentially render the heart less susceptible to sevoflurane...... cardioprotection and more susceptible to ischaemic injury. We investigated whether hypertrophy blocks sevoflurane cardioprotection, and whether tolerance to ischaemia is altered by left ventricular hypertrophy, in an established experimental animal model of ischaemia-reperfusion. METHODS: Anaesthetized juvenile...... left ventricular hypertrophy development in two further groups and these animals underwent identical ischaemia-reperfusion protocols, with or without sevoflurane cardioprotection. Myocardial infarct sizes were compared post-mortem. RESULTS: The mean myocardial infarct size (% of area-at-risk) was...

  13. 培哚普利联合非洛地平缓释片对高血压患者左室结构及功能的影响%Effect of Combined Treatment by Perindopril and Plendil on Left Ventricular Hypertrophy and Left Ventricular Function in Hypertensive Patients

    Institute of Scientific and Technical Information of China (English)

    左起禧

    2001-01-01

    目的 了解培哚普利联合非洛地平缓释片对高血压患者左室结构及功能的影响。方法 观察38例高血压患者口服培哚普利与非洛地平缓释片6个月后左室结构和功能改变。结果 治疗后降压效果显著,心率无变化,室间隔厚度,左室后壁厚度及左室重量指数明显降低。结论 培哚普利联合非洛地平治疗高血压病可安全有效降压,同时逆转左室肥厚,改变左室舒张功能。%Objective To study effect of combined treatment by perindopriland plendil on left ventricular hypertrophy and left ventricualr function in hypertensive patients. Method 38 hypertensive patients were given perindopril and plendil for an average of 6 months. Left ventriculars structure and cardiac function were observed. Result Both SBP and DBP decreased, HR didn't change, LVMI, IVST, PWT became thinner. Conclusion The perindopril combined with plendil treatment has good effects on hypertension, it could decrease blood pressure, regress left ventricular hypertrophy and improve cardiac function.

  14. Asymmetric septal hypertrophy and hypothyroidism in children.

    OpenAIRE

    Altman, D I; Murray, J.; Milner, S.; Dansky, R; Levin, S. E.

    1985-01-01

    Any echocardiographic study of two children with hypothyroidism demonstrated the presence of asymmetric septal hypertrophy. One child died aged 11 months, and pronounced thickening of the interventricular septum was confirmed at necropsy. There was also hypertrophy of the left ventricular free wall. Histological examination showed only slight muscle fibre disarray, but there was striking vacuolation and hypertrophy of muscle fibres. In the second case, a child aged five years, the asymmetric ...

  15. 阿米洛利对豚鼠心肌细胞钾电流及钙电流的作用%Effects of amiloride on potassium and calcium currents in guinea pig ventricular myocytes

    Institute of Scientific and Technical Information of China (English)

    程岚; 王芳; 周红义; 姚伟星; 夏国瑾; 江明性

    2004-01-01

    目的研究阿米洛利(amiloride)对豚鼠心肌细胞钾电流及钙电流的作用.方法采用全细胞膜片钳技术记录豚鼠心室肌细胞钾通道及钙通道电流.结果阿米洛利在10~100μmol·L-1抑制L型及T型钙电流,不改变钙电流I-V曲线的形状,仅抑制这两型电流的幅度.当累积浓度达l00μmol·L-1时,阿米洛利轻微抑制快激活延迟整流钾电流(IKr),对慢激活延迟整流钾电流(IKs)无影响.阿米洛利在1~100μmol·L-1浓度依赖性地抑制内向整流钾电流(IK1).结论阿米洛利抑制电压依赖性的钾、钙电流,为其抗心律失常作用提供了离子基础.%Aim To elucidate the possible mechanisms underlying antiarrhythmia of the non-selective Na*/H + exchanger inhibitor- amiloride. Methods Single ventricular cells were isolated using a double-enzyme method. Effects of amiloride on voltage-dependent potassium and calcium currents in isolated guinea pig ventricular myocyte were recorded by using whole-cell patch clamp techniques. Results Amiloride resulted in a concentration-dependent inhibition of peak ICa,L, But amiloride did not change the shape of their I - V curves. It only decreased the amplitudes of the currents of the two types. When Amiloride depressed potassium and calcium currents, which may give support to its uses in some diseases of the cardiovascular system.

  16. 白藜芦醇降低大鼠心室肌细胞内游离钙浓度%Resveratrol reduces intracellular free calcium concentration in rat ventricular myocytes

    Institute of Scientific and Technical Information of China (English)

    刘政; 张利萍; 马会杰; 王川; 李明; 王庆山

    2005-01-01

    Resveratrol (trans-3,4',5-trihydroxy stilbene), a phytoalexin found in grape skins and red wine, has been reported to have a wide range of biological and pharmacological properties. It has been speculated that resveratrol may have cardioprotective activity.The objective of our study was to investigate the effects of resveratrol on intracellular calcium concentratoin ([Ca2+]i) in rat ventricular myocytes. [Ca2+]i was detected by laser scanning confocal microscopy. The results showed that resveratrol (15~60 μmol/L) reduced [Ca2+]i in normal and Ca2+-free Tyrode's solution in a concentration-dependent manner. The effects of resveratrol on [Ca2+]i in normal Tyrode's solution was partially inhibited by pretreatment with sodium orthovanadate (Na3VO4, 1.0 mmol/L, P<0.01), an inhibitor of protein tyrosine phosphatase, or L-type Ca2+ channel agonist Bay K8644 (10 μmol/L, P<0.05), but could not be antagonized by NO synthase inhibitor L-NAME (1.0 mmol/L). Resveratrol also markedly inhibited the ryanodine-induced [Ca2+]i increase in Ca2+-free Tyrode's solution (P<0.01). When Ca2+ waves were produced by increasing extracellular Ca2+ concentration from 1 to 10 mmol/L,resveratrol (60 μmol/L) could reduce the velocity and duration of propagating waves, and block the propagating waves of elevated [Ca2+]i. These results suggest that resveratrol may reduce the [Ca2+]i in isolated rat ventricular myocytes. The inhibition of voltagedependent Ca2+ channel and tyrosine kinase, and alleviation of Ca2+ release from sarcoplasmic reticulum (SR) are possibly involved in the effects of resveratrol on rat ventricular myocytes. These findings could help explain the protective activity of resveratrol against cardiovascular disease.%实验旨在研究白藜芦醇(resveratrol)对大鼠心室肌细胞内钙浓度(intracellular calcium concentratoin,[Ca2+]i)的影响.应用激光共聚焦显微镜技术记录心室肌细胞内的钙荧光强度.结果表明:在正常台氏液和

  17. 神经介素 B 对大鼠心室肌细胞 L 型钙离子通道调节及机制研究%Modulation of L-type Ca2 + channels by neuromedin B in adult rat ventricular myocytes and the underlying mechanisms

    Institute of Scientific and Technical Information of China (English)

    应娇茜; 张园; 孙玉芳; 张国强; 常志刚

    2016-01-01

    Objective Toinvestigagte the effects of neuromedin B (NeuroB) on L-type Ca2 +channel currents ( IL ) and clarify the relevant signal pathway in adult rat ventricular myocytes.Methods RT-PCR and western blotting analysis were used todetect the expression ofNeuroB receptors in adult rat ventricular myocytes. The content of cAM P was detected by ELISA. The whole-cell patch clamp recording was used to investigate the effect of NeuroB on IL in adult rat ventricular myocytes. Further transduction pathway was studied by pharmacological methods.Results The NeuroB receptorwas endogenouly expressed in adult rat ventricular myocytes. NeuroB enhanced IL in a concentration-dependent manner. NeuroB-mediated increasement of IL was blocked by phosphokinase A ( PKA ) antagonist KT-5720 ,while the antagonist of phosphokinase C (PKC ) GF109203X elicited no such effects. NeuroB induced significant increase of cAM P level in adult rat ventricular myocytes.Conclusions NeuroB enhanced IL in adult rat ventricular myocytes through a NeuroB receptor-denpendent PKA signalling pathway ,whereas PKC was not involved.%目的:研究神经介素 B(NeuroB)对成年大鼠心室肌细胞 L 型钙离子通道的调节及信号转导机制。方法应用 RT-PCR 及 Western blot 方法研究 NeuroB 受体 mRNA 及蛋白在成年大鼠心室肌细胞中的表达。应用 ELISA 方法检测 NeuroB 对心室肌细胞中 cAMP 含量的影响。应用全细胞膜片钳技术研究 NeuroB 对成年大鼠心室肌细胞 L 型钙离子通道电流(IL )的作用,并应用药理学方法阐明其信号转导机制。结果 NeuroB 受体在成年大鼠心室肌细胞中呈高表达。 NeuroB 对大鼠心室肌细胞 IL 具有量效依赖性的增加作用。蛋白激酶 A(PKA)阻断剂 KT-5720能够抑制 NeuroB对该 IL 的增强作用,但蛋白激酶 C(PKC)阻断剂 GF109203X 却无任何效应。 NeuroB 可浓度依赖性增加心室肌细胞中 cAMP 含量水平。结论 NeuroB

  18. Propranolol and verapamil inhibit mRNA expression of RyR2 and SERCA in L-thyroxin-induced rat ventricular hypertrophy

    Institute of Scientific and Technical Information of China (English)

    Xiao-dong WU; De-zai DAI; Qiu-pin ZHANG; Feng GAO

    2004-01-01

    AIM: To study the alteration in the mRNA level of cardiac ryanodine receptor 2 (RyR2) and sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) in L-thyroxin-induced hypertrophy. METHODS: L-thyroxin (500 g/kg) daily was injected for 10 d. RT-PCR was used to determine mRNA expression. RESULTS: An increase in the relative amount of RyR2 (111%) and SERCA mRNA (65 %) expression was observed in the hypertrophied rats (RyR2:77± 11; SERCA: 87± 10, n=9) compared with the normal rats (RyR2: 36± 10; SERCA: 53± 10, n=9). Propranolol was effective to inhibit the increase in RyR2 (51±7) and SERCA (63±13) mRNA expression in hypertrophied rats,respectively. Verapamil also reduced RyR2 (62±5) and SERCA (75±8) mRNA expression. CONCLUSION: Both RyR2 and SERCA mRNA level in L-thyroxin-induced cardiac hypertrophy was over-expressed and propranolol or verapamil inhibited the alteration.

  19. Temporal patterns of electrical remodeling in canine ventricular hypertrophy: Focus on I-Ks downregulation and blunted beta-adrenergic activation

    NARCIS (Netherlands)

    M. Stengl; C. Ramakers; D.W. Donker; A. Nabar; A.V. Rybin; R.L.H.M.G. Spatjens; T. van der Nagel; W.K.W.H. Wodzig; K.R. Sipido; G. Antoons; A.F.M. Moorman; M.A. Vos; P.G.A. Volders

    2006-01-01

    Objectives: Electrical remodeling in cardiac hypertrophy often involves the downregulation of K+ currents, including beta-adrenergic (beta-A)-sensitive I-Ks. Temporal patterns of ion-channel downregulation are poorly resolved. In dogs with complete atrioventricular block (AVB), we examined (1) the t

  20. 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 dilatatio...

  1. Non-hypertrophic cardiomyopathy presenting as left ventricular hypertrophy in 4 cases%左心室肥厚而非肥厚型心肌病的病例分析

    Institute of Scientific and Technical Information of China (English)

    吴鸿谊; 钱菊英; 崔洁; 聂振宁; 彭娟; 葛均波

    2012-01-01

    目的 探讨以左心室肥厚为临床表征而非肥厚型心肌病的诊疗经验.方法 分析临床上遇到的4例初步诊断为肥厚型心肌病最终考虑为其他相对少见心肌病患者的临床表现特点、辅助检查结果和诊断方法.结果 4例均为由超声心动图检查出的不可解释的心肌肥厚患者.1例17岁男性,心肌极度肥厚合并预激的心电图图形、伴有近端肌肉萎缩和智力发育迟缓,肌酶升高,骨骼肌病理为边缘存在肌膜蛋白的自噬空泡性肌病,诊断为Danon病.1例老年女性,表现为梗阻性肥厚型心肌病,其姐姐明确诊断为Fabry病,诊断为晚发的轻型Fabry病.1例青年男性,表现为心肌肥厚和A型预激,但无其他异常,有明确的家族史,考虑为编码AMP激活蛋白激酶y2亚单位(PRKAG2)心脏综合征可能.1例44岁男性,心肌肥厚程度与心电图电压不匹配,肾穿刺活组织病理检查发现淀粉样变性,诊断为原发性淀粉样变浸润心肌.结论 除原发性遗传性的肥厚型心肌病外,尚有少见的代谢性遗传性肥厚型心肌病和系统疾病浸润心肌导致的心肌肥厚,值得引起重视.%Objective To summarize the diagnosis experience for non-hypertrophic myocardiopathy presenting as left ventricular hypertrophy. Methods The clinical characteristics, auxiliary examinations and diagnostic methods of 4 patients with rare diseases presenting as hypertrophic myocardiopathy were retrospectively investigated. Results All patients had unexplainable myocardial hypertrophy. A 17-years-old male patient with clinical features of extreme myocardial hypertrophy, ventricular pre-excitation, proximal muscle weakness, slow intelligence development, high creatase level and intracytoplasmic autophagic vacuoles in muscle cells was diagnosed as having Danon disease. An old female patient was diagnosed as delayed mild Fabry disease presenting as obstructive hypertrophic cardiomyopathys her elder sister had been

  2. Changes of potassium ion currents in ventricular myocytes with chronic heart failure%压力超负荷慢性心力衰竭大鼠心室肌钾电流变化的研究

    Institute of Scientific and Technical Information of China (English)

    吴钢; 程冕; 黄从新; 江洪; 黄鹤; 杨波; 蒋学俊

    2012-01-01

    目的:检测慢性心力衰竭(CHF)大鼠心室肌钾电流的变化,探讨CHF时心律失常发生的可能机制.方法:建立腹主动脉缩窄大鼠CHF模型,采用全细胞膜片钳技术记录心室肌细胞短暂外向钾电流(Ito)、延迟整流性钾电流(IK)及内向整流性钾电流(IK1),并进行对照分析.结果:CHF组大鼠左心室收缩末压(LVSP)、左心室内压上升最大速率(+ dp/dtmax)及左心室内压下降最大速率(-dp/dtmax)显著低于假手术组,左心室舒张末压(LVEDP)显著高于假手术组(均P<0.01),提示CHF模型制作成功.假手术组Ito的电流密度为(7.41±0.51)pA/pF,CHF组为(5.22±0.61)pA/pF,后者显著小于前者(P<0.01),Ⅰ~Ⅴ曲线显著下移;假手术组IK-tail的电流密度为(0.63±0.05) pA/pF,CHF组为(0.48±0.04)pA/pF,后者显著小于前者(P<0.01),Ⅰ~Ⅴ曲线显著下移;假手术组IK1内向电流密度为-(9.61±1.04)pA/pF,CHF组为-(6.33±0.71)pA/pF,后者显著小于前者(P<0.01),CHF组Ⅰ~Ⅴ曲线较假手术组显著上移.结论:CHF时,Ito、IK与IK1电流密度均显著减小,而IK和IK1减小可能是导致室性心律失常的重要原因.%Objective: To explore the changes of potassium ion currents in ventricular myocytes with chronic heart failure (CHF). Method: Rat model of CHF of abdominal aortic banding was established. Whole cell patch clamp technique was used to record transient outward potassium current (Ito), delayed rectifying potassium current (IK), inward rectifying potassium current (IK1), and compared with pseudo-surgery group. Result; The left ventricular end-systolic pressure (LVSP), the maximum increase rate of left ventricular pressure ( + dp/dtmax), the maximum decrease rate of left ventricular pressure ( — dp/dtmax) of CHF group were significant lower than those of pseudo-surgery group (all P<0. 01) , the left ventricular end-diastolic pressure (LVEDP) of CHF group was significant higher than that of pseudo-surgery group (P<0. 01

  3. Right Ventricular Dysfunction in Chronic Lung Disease

    OpenAIRE

    Kolb, Todd M.; Hassoun, Paul M.

    2012-01-01

    Right ventricular dysfunction arises in chronic lung disease when chronic hypoxemia and disruption of pulmonary vascular beds contribute to increase ventricular afterload, and is generally defined by hypertrophy with preserved myocardial contractility and cardiac output. Although the exact prevalence is unknown, right ventricular hypertrophy appears to be a common complication of chronic lung disease, and more frequently complicates advanced lung disease. Right ventricular failure is rare, ex...

  4. Hypertrophy signaling pathways in experimental chronic aortic regurgitation

    DEFF Research Database (Denmark)

    Olsen, Niels Thue; Dimaano, Veronica L; Fritz-Hansen, Thomas;

    2013-01-01

    The development of left ventricular hypertrophy and dysfunction in aortic regurgitation (AR) has only been sparsely studied experimentally. In a new model of chronic AR in rats, we examined activation of molecular pathways involved in myocardial hypertrophy. Chronic AR was produced by damaging on...... of activation of intracellular pathways different from that seen with pathological hypertrophy in pressure overload, and more similar to that associated with benign physiological hypertrophy....

  5. Metformin and its effects on myocardial dimension and left ventricular hypertrophy in normotensive patients with coronary heart disease (the MET-REMODEL study): rationale and design of the MET-REMODEL study.

    Science.gov (United States)

    Mohan, Mohapradeep; McSwiggan, Stephen; Baig, Fatima; Rutherford, Lynn; Lang, Chim C

    2015-02-01

    Left ventricular hypertrophy (LVH) is a common and independent risk factor for cardiovascular events in patients with coronary artery disease (CAD). Controlling blood pressure is the standard approach to the management of LVH, but this is only partially effective as LVH also persists in normotensive patients. Apart from blood pressure (BP), other main risk factors associated with LVH are insulin resistance (IR) and central obesity. The diabetic medication, Metformin, reduces IR and aids weight loss and may therefore regress LVH. The MET REMODEL study will investigate the ability of Metformin to regress LVH in 64 patients with CAD. The MET-REMODEL trial is a single-center, phase IV, double blind, randomized, placebo-controlled trial to investigate the efficacy of Metformin in regression of the independent cardiac risk factor of LVH in patients with CAD who are insulin resistant. A minimum of 64 adults with a history of CAD with LVH and IR will be randomized into two groups to receive, either Metformin XL or placebo. The primary endpoint of this trial is to investigate any change in left ventricular mass index. Secondary endpoints include changes to insulin resistance measured using fasting insulin resistance index (FIRI), obesity, LV size, and function and improvement in endothelial function. A positive result will assist clinicians to identify a new mechanism for LVH regression by administering Metformin XL. This may also lead to investigating the mortality benefit of Metformin in patients with CAD and LVH.

  6. Effect of hypercholesterolemia on the ionic currents in cardiac ventricular myocytes of rats%高胆固醇血症对大鼠心室肌细胞离子电流的作用

    Institute of Scientific and Technical Information of China (English)

    周宇宏; 王玲; 单宏丽; 张妍; 孙宏丽; 杨宝峰

    2007-01-01

    AIM: To determine whether chronic hypercholesterolemia affects ionic currents on cardiac ventricular myocytes of rats. METHODS: Whole - cell patch - clamp technique was used to record the ionic currents in single cardiac myocytes isolated from normal cholesterolemia and hypercholesterolemia rats. RESULTS: In the hypercholesterol group (group Ⅱ ), serum total - cholesterol level was significantly higher than that of normal group (group Ⅰ) [ (3. 10 ±tricular myocytes of rats, 50% repolarization of action potential duration (APD50) prolonged from (70. 86 ± 8.12) ms (group Ⅰ) to (116.16±6.90)ms (group Ⅱ) (n=10 in each group, P<0.01); APD90 prolonged from (95.10±7. 27)ms (group Ⅰ ) to (144. 04 ± 7.39)ms (group Ⅱ ) (n = 10 in each group, P < 0. 01 ); at the test potential of - 120 mV, Ik1 increased from ( - 16. 98 ±4. 54) pA/pF(group Ⅰ ) to ( - 19.92 ±4.08) pA/pF (group Ⅱ ) (n = 12 in each group, P < 0. 05 ); at the test potential of 0 mV, ICa- L decreased from ( - 8.56 ± 1.29) pA/pF ( group Ⅰ ) to ( -5. 24 ± 0. 90) pA/pF ( group Ⅱ ) ( n = 10 in each group, P < 0. 01 ); at the test potential of + 60 mV, Ito decreased from (13.20±1.97) pA/pF (group Ⅰ) to (10.30±1.97) pA/pF (group Ⅱ) (n=8 in each group, P<0. 05). CON-CLUSION: Hypercholesterolemia affects the ionic currents on cardiomyocytes of rats greatly, which may be the ionic mechanism of cardiac toxicity induced by hypercholesterolemia.%目的:观察高胆固醇血症对大鼠心室肌细胞离子电流的作用.方法:通过全细胞膜片钳技术记录用酶解法分离的正常和高胆固醇饮食的大鼠心室肌细胞离子电流.结果:高胆固醇组(组Ⅱ)血清总胆固醇水平明显高于正常组(组Ⅰ)[(3.10±0.62)mmol·L-1vs(1.18±0.37)mmol·L-1,P<0.01,n=20].组Ⅱ血清甘油三酯也明显高于组Ⅰ[(1.51±0.30)mmol·L-1vs(0.43±0.15)mmol·L-1,P<0.01,n=20].组Ⅱ大鼠心室肌细胞动作电位时程(APD)与组Ⅰ相比明显延长,APD50从(70

  7. Changes in ECG features and clinical prognosis of ventricular electrical storm in patients with left ventricular hypertrophy and acute myocardial infarction%左心室肥厚并急性心肌梗死室性电风暴心电图对预后的影响

    Institute of Scientific and Technical Information of China (English)

    于文江; 王为民

    2009-01-01

    目的 探讨沿海居民高血压性左室肥厚(left ventricular hypertrophy,LNH)并急性心肌梗死(acute myocardial infarction,AMI)后心电图特征性改变,评估室性电风暴与临床预后危险分层.方法 选择急诊住院有高皿压性LVH并AMI室性电风暴(室速或室颤)317例(Ⅱ组),另选无高血压性LVH室性电风暴AMI 109例(Ⅰ组)进行心电图检查和持续心电监护,分析心电图特征与临床高危特点.结果 室性电风暴组以高血压LVH并AMI患者心电图指标心房终末电势异常、∑ST段抬高振幅、ST段抬高导联数、QTc间期延长、对应导联ST段振幅下移等特征,梗死部位以前壁或复合前壁,并以左前降支合并回旋支或/和右冠脉完全闭塞多支病变为主,与Ⅰ组比较差异有统计学意义(P<0.05或P<0.01),临床并发泵衰竭、AMI扩展、住院病死率、室性电风暴AMI发病后6 h内发生率明显增多(P<0.01).结论 高血压性LVH并AMI室性电风暴患者,心电图多项指标异常对临床预后有预测作用.%Objective To investigate changes in ECG feature and clinical prognosis of ventricular electrical storm (VES) in patients with left ventricular hypertrophy (LVH) and acute myocardial infarction (AMI). Methods Three hundred and seventeen cases of left ventricular hypertrophy induced by hypertension and combined with AMI (Group Ⅱ) from emergency inpatients, and another 109 patients without LVH induced by hypertension and accompanied with AMI (Group Ⅰ) were chosen to have sustained ECG monitoring, analyze ECG features and clinical high risks. Results Clinical features, such as abnormality in PTFvl,ΣST segment elevation amplitude, ST segment elevation leads, ST segment reduction amplitude leads, QTc interval prolongation could be noted in the VES group. Infarction could be seen at sites of anterior and complex anterior walls, and dominant clinical signs were mainly at left descending branches accompanied by circumflex arteries and

  8. Alteration of ion channel currents in hypertrophic ventricular myocytes 2 months after myocardial infarction%兔心肌梗死后2个月肥大心室肌细胞的电生理研究

    Institute of Scientific and Technical Information of China (English)

    丁超; 何振山; 崔俊玉; 石巧; 杨丽; 胡丽叶

    2004-01-01

    <0.01).Nevertheless, there was a significant increase in REM compared with MI ( t =2. 429, P < 0.05).CONCLUSION: Exaggeration of cell captiance is found in the myocytes remote from infracted area, indicating myocardial hypertrophy. There is an increase in ICa-L, but the current density of Ito is significantly reduced in REM. These changes may underlie the abnormally long transmembrane action potentials in myocytes of region remote from infarction zone, thus contributing to reentrant arrhymias in the healed infarcted heart.%背景:心肌梗死后电重构与梗死后时间和区域相关.目的:研究陈旧性心肌梗死非梗死区肥大心室肌细胞离子通道电流的变化,探讨心肌梗死后肥大心肌发生心律失常的可能的离子机制.设计:随机对照实验研究.地点、材料和干预:所有实验过程在石家庄市白求恩国际和平医院心内科中心实验室完成.新西兰纯种大耳白兔20只,按随机抽签法分为两组:心肌梗死动物模型组和正常对照组.采用结扎兔冠状动脉左前降支的方法建立急性心肌梗死动物模型,应用膜片钳全细胞记录方法.主要观察指标:梗死后2个月心外膜远离梗死区组与梗死区组及正常对照组心室肌细胞L-钙通道电流(L-calcium current,ICa-L)、瞬间外向钾电流(transient outward current,Ito)的变化.结果:①远离梗死区组细胞电容[(155.7±5.8)pF,n=41]明显大于对照组[(120.3±6.2)pF,n=35]和梗死区组[(130.4±7.8)pF,n=38](t=2.642,2.613,P均<0.01).②ICa-L:远离梗死区组ICa-L电流峰值(0 mV)为[(826.12±121.31)pA,n=21],较对照组[(670.21±183.32)pA,n=10]和梗死区组[(629.43±172.12)pA,n=11]明显增大(t=2.451,2.732,P均<0.05).但远离梗死区组电流密度峰值为(5.32±0.78)pA/pF,较对照组[(5.58±1.53)pA/pF]略下降,与梗死区组[(4.84±1.48)pA/pF]和对照组比较无显著性意义(P均>0.05).③Ito:远离梗死区组[(13.21±4.13)pA/pF,n=23]和梗死区组[(10.61±4.12)p

  9. Evaluation of Left Ventricular Function in Patients with Apex-hypertrophy Using Speckle Tracking Imaging%斑点追踪显像对心尖肥厚型心肌病左室功能的评价分析

    Institute of Scientific and Technical Information of China (English)

    王春梅; 唐琪; 穆玉明; 李艳红

    2011-01-01

    Objective To evaluate the left ventricular function in patients with apex - hypertrophy using speckle tracking imaging.Methods A total of 18 patinents with apex - hypertrophy ( HCM ) and 20 normal controls were enrolled in this study.Images of apacial 4-chamber, 2 - chamber and ventricular short - axises ( anular, papillary - muscle, apex ) were obtained ; the peak - systolic longitudinal strain ( SL ), circumfrencial strain ( SC ) and radial strain ( SR ) of all segments were analyzed.Results SL, SC, and SR of all segments in the HCM group were lower than those in normal controls ( P <0.05 ).Compared with normal controls, SL was lower in all segments in HCM group.SR was lower in most segments in the angular and the papillary - muscle views; SC was lower in several segments in the angular and the papillary - muscle views.Conclusion The longitudinal and radial systolic function among HCM patients is decreased, especially for the longitudinal systolic function.Changes of regional SL, SR and SC are promising indices that reflect these changes.%目的 探讨斑点追踪显像评价心尖肥厚型心肌病左室收缩功能的改变.方法 记录18例心尖肥厚型心肌病患者(HCM组)和20例健康对照者(对照组),获取二维灰阶图像,分析各个心肌节段收缩期峰值的纵向应变(SL)、径向应变(SR)和周向应变(SC).结果 HCM组心肌整体SL、SR及SC收缩期峰值应变均明显低于对照组(P<0.05).HCM组所有节段的收缩期峰值SL均明显低于对照组;与对照组相比,左房室瓣及乳头肌水平大多数节段的SR降低,左房室瓣及乳头肌水平个别节段的SC降低,心尖水平所有节段的SC及SR均明显降低(P<0.05).结论 HCM患者左室长轴和短轴收缩功能均降低,以长轴功能减弱明显,局部心肌SL、SR及SC的变化可反映心肌的功能改变.

  10. Effects of Zhenwu decoction on rats with pressure-overloaded left ventricular myocardial hypertrophy XIE%真武汤冲剂对压力负荷性心肌肥厚的影响

    Institute of Scientific and Technical Information of China (English)

    谢志翔; 王舒茵; 梁子敬; 曾量波

    2010-01-01

    Objective To investigate the effects of Zhenwu decoction (a herbal preparation made in a form of instant granules readily soluble into decoction to administer) on rats with chronic pressure-overloaded left ven-tricular hypertrophy. Method All the male SD rats were randomly(random number) divided into 3 groups: sham operation group (n= 8), operation group (n= 15) and herbal medicine group (n= 15). The model of myocar-dial hypertrophy was made by gradually constricting the abdominal aorta. After 16 weeks, cardiac ultrasonography was used in rats of all groups to ascertain the post-operational left ventricular (LV) hypertrophy established. And the Zhenwu decoction was added in the herbal medicine group in a dose of 12 g/kg mixed in feedstuff fed for 8 weeks. After 24 weeks, the weight and structure as well as function of the heart of rats in each group were mea-sured by high-frequency ultrasonography, and Massion stain was performed on cardiac muscles. Meanwhile, both the total collagen volume fraction (CVF-T) and non-coronary vessel collagen volume fraction (CVF-NV) were ana-lyzed. Results There was an increase in the weight of the heart with a predominance of the left ventricle in the operation group (P < 0.05) . The heart was enlarged with diastolic interventricular septum thickness (IVSt) and left ventricular posterior wall thickness (LVPWt) increased predominantly (P < 0.01). There was a significant decrease in cardiac function (P < 0.05). In herbal medicine group, both the weight and volume of heart were lower than those in operation group with predominance of IVSt and systolic left ventricular wall (P < 0.01 both).And the cardiac function of rats in herbal group was better (P < 0.05). Interstitial and collagen hyperplasia increased significantly in the rats of operation group found by pathological analysis. In herbal medicine group, the pathological changes were blunted in varied magnitude with significant decrease in CVF-T and CVF-NV in compari

  11. Signaling Pathways Involved in Cardiac Hypertrophy

    Institute of Scientific and Technical Information of China (English)

    Tao Zewei; Li Longgui

    2006-01-01

    Cardiac hypertrophy is the heart's response to a variety of extrinsic and intrinsic stimuli that impose increased biomechanical stress.Traditionally, it has been considered a beneficial mechanism; however, sustained hypertrophy has been associated with a significant increase in the risk of cardiovascular disease and mortality. Delineating intracellular signaling pathways involved in the different aspects of cardiac hypertrophy will permit future improvements in potential targets for therapeutic intervention. Generally, there are two types of cardiac hypertrophies, adaptive hypertrophy, including eutrophy (normal growth) and physiological hypertrophy (growth induced by physical conditioning), and maladaptive hypertrophy, including pathologic or reactive hypertrophy (growth induced by pathologic stimuli) and hypertrophic growth caused by genetic mutations affecting sarcomeric or cytoskeletal proteins. Accumulating observations from animal models and human patients have identified a number of intracellular signaling pathways that characterized as important transducers of the hypertrophic response,including calcineurin/nuclear factor of activated Tcells, phosphoinositide 3-kinases/Akt (PI3Ks/Akt),G protein-coupled receptors, small G proteins,MAPK, PKCs, Gp130/STAT'3, Na+/H+ exchanger,peroxisome proliferator-activated receptors, myocyte enhancer factor 2/histone deacetylases, and many others. Furthermore, recent evidence suggests that adaptive cardiac hypertrophy is regulated in large part by the growth hormone/insulin-like growth factors axis via signaling through the PI3K/Akt pathway. In contrast, pathological or reactive hypertrophy is triggered by autocrine and paracrine neurohormonal factors released during biomechanical stress that signal through the Gq/phosphorlipase C pathway, leading to an increase in cytosolic calcium and activation of PKC.

  12. Effects of acute cooling/rewarming on membrane potential and K+ currents in rat ventricular myocytes%急性低温/再复温对大鼠心室肌膜电位和钾电流的影响

    Institute of Scientific and Technical Information of China (English)

    李龙天; 张利彬; 司艳丽; 肖付诚; 李达; 高姗; 李东亮; 周士胜

    2008-01-01

    The effects of acute cooling/rewarming on cardiac K+ currents and membrane potential were investigated. Membrane potential and current were assessed with whole-cell patch-clamp technique in current-and voltage-clamp modes. When the temperature of bath solution was decreased from 25℃ to 4℃, the transient outward current (Ito) was completely abolished, the sustained outward K+ current (Iss) at +60mV and the inward rectifier K+ current (IK1) at-120mV were depressed by (48.5±14.1)% and (35.7±18.2)%, respectively, and the membrane potential became more positive. After the temperature of bath solution was raised from 4℃ to 36℃, the membrane potential exhibited a transient hyperpolarization and then was maintained at a stable level. In some myocytes (36 out of 58), activation of the ATP-sensitive K+ (KATP) channels after rewarming was observed. The rewarming-induced change in the membrane potential was inhibited by the Na+/K+-ATPase inhibitor ouabain (100μmol/L), and the rewarming-elicited activation of KATP channels was inhibited by the protein kinase A inhibitor H-89 (100μmol/L). Moreover, decrease of the temperature from 25℃ to 4℃ did not induce any significant change in cell volume when the cell membrane potential was clamped at O mV. However, significant ceil shrinkage with spots was observed soon after rewarming-induced activation of KATP channels. These data demonstrate that acute cooling/rewarming has a profound influence on the membrane potential and K+ currents of ventricular myocytes, and suggest that activation of KATP channels may play a role in cardiac cooling/rewarming injury.%本文旨在研究急性低温/再复温对大鼠心室肌膜电位和钾电流的影响.膜电位和膜电流分别在全细胞膜片钳的电压钳和电流钳模式下记录.当细胞外灌流液从25℃降低到4℃后,一过性外向电流(transient outward current, Ito)完全消失,膜电位为+60mV时的稳态外向K+电流(sustained outward K+ current, Iss

  13. Effect of melittin on potassium currents and action potential in ventricular myocytes of guinea pig%蜂毒肽对豚鼠心室肌细胞钾电流和动作电位的影响

    Institute of Scientific and Technical Information of China (English)

    张雪梅; 杨申; 何晓静; 郑平; 江明华

    2000-01-01

    AIM: To examine the effects of melittin (Mel) , the major component of bee venom, on delayed rectifier K + current (Ik), inward rectifier K+ current (Ik1) and action potential (AP) in guinea pig ventricular myocytes. METHODS: Ik, Ikl, and AP were recorded using the whole-cell patch-clamp technique. RESULTS: The action potential duration (APD) was shortened by Mel in a concentration-dependent manner. Mel 0.05, 0.1, 0.2 μmol· L- 1 shortened APD5o from ( 520 ± 55) to (459±91) (n=5, P>0.05), (385±102) (n=5, P<0.01), and (281±81) ms (n=5, P<0.01), respectively; and APD9o from (613±96) to (536±93) (n =5, P>0.05), (467±96)ms (n=5, P<0.01), and (354±95) ms (n=5, P <0.01), respectively. Mel increased the amplitude of Ik alSo in a concentration-dependent manner. Mel 0.05, 0.1, 0.2 μmol· L- 1 increased Ik from (295 ± 109) to (371 ± 142) ( n = 5, P <0.05), (467±180) (n=5, P<0.05), (552±248) pA ( n = 5, P < 0.05), respectively at testing potential of + 40 rmV. But no significant effect of Mci on Ikl was observed at these concentrations. CONCLUSION: Mel significantly increased Ik in a concentration-dependent manner which contributed to shortening of APD.%目的:研究蜂毒肽(Melittin,Mel)对豚鼠心室肌细胞钾电流和动作电位的影响.方法:全细胞膜片箝记录.结果:蜂毒肽可呈浓度依赖性促进延迟整流钾电流(Ik),在测定电压为40mv时,0.05,0.1,0.2μmol·L-1蜂毒肽分别使Ik从(295±109)增大到(371±142)(n=5 P<0.05),(467±180)(n=5,P<0.05),(552±248)pA(n=5,P<0.05).但药物在三个浓度时对内向整流钾电流(Ikl)均无显著影响.蜂毒肽0.05,0.1,0.2 μmol·L-1分别使动作电位APD5o由(520±55)减小到(459±91)(n=5,P>0.05),(385±102)(n=5,P<0.01),(281±81)ms(n=5,P<0.01),使APD9o由(613±96)减小到(536±93)(n=5,P>0.05),(467±96)(n=5,P<0.01),(354±95)ms(n=5,P<0.01).结论:蜂毒肽促进延迟整流钾电流,缩短动作电位时程.

  14. 牛磺酸对低氧条件下豚鼠心室肌细胞内向整流钾电流的影响%Effects of taurine on the inwardly rectified potassium current in guinea pig ventricular myocytes under hypoxia

    Institute of Scientific and Technical Information of China (English)

    祝芬; 董晓雁

    2012-01-01

    目的:研究牛磺酸对低氧条件下豚鼠心室肌细胞内向整流钾电流(Ik1)的影响.方法:酶解法分离单个豚鼠心室肌细胞和建立离体低氧模型,采用全细胞膜片钳记录技术记录牛磺酸对急性低氧条件下豚鼠心室肌细胞Ik1的作用.结果:在钳制电压一40 mV下,给予20 mmol/L牛磺酸使Ik1的电流峰值降低,抑制率(45.61±10.70)%;洗脱后,Ik1能够部分恢复(P<0.05).牛磺酸影响了Ik1的电流-电压曲线.结论:牛磺酸可明显阻滞低氧条件下豚鼠心室肌细胞膜上Ik1电流,这可能是其抗心律失常作用的电生理机制之一.%Objective:To study the effect of taurine on the inwardly rectified potassium current (Ik1 ) in isolated guinea pig ventricular myocytes under hypoxia conditions. Method: Single guinea pig ventricular myocytes were isolated enzymatically and the vitro hypoxia model was established. With treatment of taurine , the alterations of Ik1 during hypoxia were recorded using the whole-cell patch clamp recording technique. Result: After 10 minutes acute hypoxia, the peak value of Iki was decreased by (45. 61±10. 70)\\% with the supply of taurine (20 mmol/L) at the clamp voltage of —40 mV (P<0. 05). After elution, Ik1 could be partially restored. Moreover, taurine altered Ik1 and it's current-voltage curve. Conclusion: Taurine inhibit significantly Ik1 in guinea pig ventricular myocytes under hypoxia. This may be one of the electrophysiological mechanisms of its antiarrhythmic effects.

  15. 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.

  16. Role of Bradykinin on Left Ventricular Remodeling and Cardiac Function after Myocardial Infarction in Rats

    Institute of Scientific and Technical Information of China (English)

    Hai-zhu ZHANG; Li-quan LEI; Chang-cong CUI; Jian LIU

    2009-01-01

    Objectives To investigate the influences of bradykinin (BK) on hemodynamics, left ventricular hypertrophy and interstitial collagen metabolism after myocardial infarction (MI) in rats and the contribution of BK in angiotensin-con-verting enzyme (ACE) inhibition therapy. Methods By means of hemodynamic measurements, morphometric study of myocyte hypertrophy and SDS-PAGE technique ,the effects of enalapril pressure (500μg·kg-1·day-1) ,enalapril(500μg·kg-1·day-1) with BK B2 receptor antagonist Hoe-140 (500μg·kg-1·day-1),angiotensin Ⅱ (AgII) type 1 (AT1) receptor antagonist losartan(3mg·kg-1·day-1)on mean arterial pressure (MAP) ,left ventricular end-dias-tolic pressure (LVEDP), as well as maximum positive left ventricular pressure change (+ dp/dtmax), Ⅴ(m) n, col-lagen content and the ratio of type Ⅰ to type Ⅲ collagen (Ⅰ / Ⅲ) of noninfarcted area were observed in rats after MI. Treatments were started on the 3rd day after MI and continued for another 28 days. Results Enalapril reduced LV-EDP, Ⅴ(m) n and collagen content as well as collagen Ⅰ/Ⅲ compared with the untreated MI group (P < 0. 05), and all of these effects of enalapril were partly blunted by concomitant treatment with hoe-140 (P < 0. 05). Losartan was less effective than enalapril (P < 0. 05). However, three treatment groups had no significant differences in + dp/dtmax and had similar reductions in MAP compared with untreated MI group. Conclusions BK can improve cardiac function and prevent left ventricular hypertrophy with myocardial fibrosis independent of blood pressure. The mechanisms of ACEI are both blockade of Ang Ⅱ formation and inhibition of BK degradation.

  17. 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.

  18. Cardiac pressure overload hypertrophy is differentially regulated by β-adrenergic receptor subtypes

    OpenAIRE

    Zhao, Mingming; Fajardo, Giovanni; Urashima, Takashi; Spin, Joshua M; Poorfarahani, Sara; Rajagopalan, Viswanathan; Huynh, Diem; Connolly, Andrew; Quertermous, Thomas; Bernstein, Daniel

    2011-01-01

    In isolated myocytes, hypertrophy induced by norepinephrine is mediated via α1-adrenergic receptors (ARs) and not β-ARs. However, mice with deletions of both major cardiac α1-ARs still develop hypertrophy in response to pressure overload. Our purpose was to better define the role of β-AR subtypes in regulating cardiac hypertrophy in vivo, important given the widespread clinical use of β-AR antagonists and the likelihood that patients treated with these agents could develop conditions of furth...

  19. Akt activation induces hypertrophy without contractile phenotypic maturation in airway smooth muscle

    OpenAIRE

    Ma, Lan; Brown, Melanie; Kogut, Paul; Serban, Karina; Li, Xiaojing; McConville, John; Chen, Bohao; Bentley, J. Kelley; Hershenson, Marc B.; Dulin, Nickolai; Solway, Julian; Camoretti-Mercado, Blanca

    2011-01-01

    Airway smooth muscle (ASM) hypertrophy is a cardinal feature of severe asthma, but the underlying molecular mechanisms remain uncertain. Forced protein kinase B/Akt 1 activation is known to induce myocyte hypertrophy in other muscle types, and, since a number of mediators present in asthmatic airways can activate Akt signaling, we hypothesized that Akt activation could contribute to ASM hypertrophy in asthma. To test this hypothesis, we evaluated whether Akt activation occurs naturally within...

  20. Extracellular matrix remodelling in myocardial hypertrophy and failure : focus on osteopontin.

    Science.gov (United States)

    Francia, Pietro; Uccellini, Arianna; Frattari, Alessandra; Modestino, Anna; Ricotta, Agnese; Balla, Cristina; Scialla, Ludovica; Volpe, Massimo

    2009-12-01

    Cardiac remodelling refers to molecular and cellular changes of the myocardium, as well as adapting alterations in size, shape and function of the heart in response to changing loading conditions. It represents the final common pathway of different heart diseases, and is recognized as a crucial aspect of cardiac and myocardial dysfunction and a well established determinant of the clinical course of heart failure.Osteopontin is an extracellular matrix glycoprotein secreted by osteoblasts, osteoclasts, macrophages, T cells, vascular smooth muscle cells, fibroblasts and cardiomyocytes. Osteopontin is not expressed in healthy cardiac tissue, although its expression can be triggered by pressure or volume overload, hypoxia and angiotensin II. Indeed, osteopontin has been reported in macrophages and interstitial tissues early after myocardial infarction and in cardiac macrophage-like cells of inflammatory lesions in experimental models of cardiomyopathy. Pressure overload is associated with osteopontin overexpression as well. Indeed, myocardial osteopontin messenger RNA is upregulated in rats following renovascular hypertension or aortic banding. In humans, a significant correlation exists between increased osteopontin immunoreactivity in cardiac myocytes and impaired left ventricular function or cardiomyocyte hypertrophy in patients with dilated cardiomyopathy.The present article focuses on the role of osteopontin in myocardial hypertrophy and remodelling. In general, evidence supports the concept that osteopontin plays a crucial role in extracellular matrix remodelling following myocardial adaptation to hypertrophic, inflammatory and neurohormonal stimuli in the overloaded heart.

  1. Hypertrophic cardiomyopathy and hypertensive left ventricular hypertrophy by Beckoning figure analysis%肥厚性心肌病与高血压性左心室肥厚超声心动图对比分析

    Institute of Scientific and Technical Information of China (English)

    舒娜

    2016-01-01

    Objective The hypertrophic cardiomyopathy and hypertensive left ventricular hypertrophy Beckon-ing ultrasound results were analyzed, and the clinical features were summarized. Methods Selection of hypertrophic cardiomyopathy from April to 2014 in 2013 May in our hospital and patients with hypertensive left ventricular hyper-trophy 30 cases as LVH group and HCM group, 30 cases in healthy people for physical examination in our hospital as control group, to compare the three groups of patients with Heartbeat ultrasound graph, after analysis, three groups of ultrasound patients were analyzed and Heartbeat map between QT dispersion. Results Control group cardiac index map and QT dispersion and LVH group and HCM groups exist obvious differences and LVH group and the HCM group left ventricular myocardial weight (LVmass), interventricular septal thickness (LVST), diastolic interventricular septum thickness (LVSTd), diastolic late left ventricular posterior wall thickness (LVPWTd) and QT dispersion were lower than the control group (P<0.05), and the difference is statistically significant; LVH group and HCM groups be-tween lvmass, LVST, LVSTd / LVPWTd and QT dispersion difference significantly(P<0.05), the difference is signifi-cant. Conclusion Hypertrophic cardiomyopathy and hypertensive left ventricular hypertrophy echocardiography has obvious difference, echocardiography showed significant diagnostic value of more than two diseases, the diagnosis model is worth in the clinical practice, to reference and promotion, the other group of patients with HCM QT disper-sion is large, so in the course of treatment. Prevention efforts should be strengthened to malignant arrhythmia.%目的:探讨肥厚性心肌病与高血压性左心室肥厚超声心动图结果的异同点。方法选择2013年4月至2014年5月该院收治的肥厚性心肌病和高血压性左心室肥厚患者各30例分别作为左心室肥厚(LVH)组和非对称性室间隔肥厚(HCM)组

  2. Effects of recombinant human erythropoietin on left ventricular hypertrophy in anemic patients on maintenance hemodialysis%纠正维持性血液透析患者贫血对逆转左心室肥厚的作用

    Institute of Scientific and Technical Information of China (English)

    梁军; 范宝英

    2011-01-01

    Objective To investigate the efficacy of recombinant human erythropoietin(rHuEPO) on reversing left ventricular hypertrophy(LVH) by improving anemia in patients on maintenance hemodialysis(MHD). Methods Forty patients on MHD were randomly divided into two groups: treatment group(group A) and control group B. In Group A ( =20), the patients were given rHuEPO 80 - 120 u / kg / w through hypodermic injection to begin with. When hemoglobin(Hb) reached 110 - 120 g/L and the hematocdt(Hct) was 0. 33 ~0. 36, the dose of rHuEPO was decreased to the maintenance dose. In Group B( = 20), the patients did not receive rHuEPO therapy. The blood pressure of all the patients in the two groups were normal or near normal during the treatment. Hb,Hct, left ventricular mass index ( LVMI), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were compared between the two groups. Results There were no significant changes in SBP or DBP in the two groups after treatment( P >0.05 ). Hb and Hct increased significantly in Group A after treatment(P <0.01 ). LVMI in Group A declined after treatment(P <0.01 ). Conclusions rHuEPO therapy reverses LVH by correcting anemia in patients on MHD.%目的 观察应用重组人促红细胞生成素(recombinant human erythropoietin,rHuEPO)纠正维持性血液透析(maintenance hemodialysis,MHD)患者贫血对逆转左心室肥厚(left ventricular hypertrophy,LVH)的作用.方法 选择我院血透中心40例MHD患者随机分为两组:治疗组20例予rHuEPO皮下注射治疗,起始量每周80~120 U/kg;当血红蛋白(Hb)110~120 g/L、血细胞比容(Hct)033~036时rHuEPO减为维持量.对照组20例不使用rHuEPO治疗.两组在治疗过程中均积极控制血压在正常或接近正常水平.观察并比较两组Hb、Hct、左心室重量指数(LVMI)、收缩压(SBP)、舒张压(DBP)情况.结果 治疗前后两组SBP、DBP差异无统计学意义(P>0.05),治疗后治疗组较对照组Hb、Hct明显升高(P<0.01),LVMI

  3. Mid-ventricular hypertrophy complicated with the lengthy of mitral valve leaflets lead to dynamic left ventricular outflow tract obstruction: A case report and literature review%左心室中部肥厚合并二尖瓣冗长致左室流出道梗阻——病例报告与文献复习

    Institute of Scientific and Technical Information of China (English)

    洪李锋; 罗松辉; 夏璐; 范莹; 胡良焱; 项金洲

    2013-01-01

    Objective:To investigate the etiology,manifestations and the progress regarding the diagnosis and treatment for left ventricular outflow tract obstruction.Methods:Diagnosis and treatment of one case with mid-ventricular hypertrophy complicated with the lengthy of mitral valve leaflets lead to dynamic left ventricnlar outflow tract obstruction was followed up and reviewed with related literatures.Resuhs:The etiology of ventricular outflow tract obstruction was complex and the incidence was rather high.Transthoracic two-dimensional exercise echocardiography with transesophageal echocardiography analysis is the most effective non-invasive screening and prognostic predictive tool for left ventricular outflow tract obstruction.Conclusions:It is mandatory to selectively conduct multiple imaging examinations which mainly include exercise echocardiography and selectively left ventriculography in order to successfully improve the diagnosis of left ventricular outflow tract obstruction.%目的:探讨左室流出道梗阻的病因分类、临床表现和诊治进展.方法:对1例左心室中部肥厚合并二尖瓣前叶冗长致隐匿性左室流出道梗阻患者的诊治过程进行全程追踪随访,结合复习相关文献.结果:左室流出道梗阻病因复杂,发生率较高;超声心动图运动试验结合经食道超声探查是左室流出道梗阻最有效的无创筛查和随访评价手段,必要时左心室造影和测压可进一步明确诊断.结论:对左心室肥厚患者常规开展运动超声心动图、必要时左心室造影等多种影像学检查可以有效提高左室流出道梗阻及其病因的诊断正确率.

  4. Value of 4D-strain imaging echocardiography in detecting left ventricular systolic dysfunction in patients with aortic stenosis

    Institute of Scientific and Technical Information of China (English)

    ZHENG Zhi-chao; LI He-zhi; LI Chang-mao; CHEN Ou-di; FEI Hong-wen; LIN Qiong-wen

    2016-01-01

    Background The myocyte dysfunction may be present in aortic stenosis (AS) patients with preserved left ventricular ejection fraction (LVEF).Early aortic valve replacement (AVR) can reverse the LV hypertrophy and improve LV systolic performance and clinical outcome.Strain imaging has demonstrated to be the most appropriate method to evaluate LV myocardial contractility.However,4D-strain imaging echocardiography for the detection of subclinical left ventricular dysfunction in AS patients with preserved LVEF is seldom studied.Methods We prospectively enrolled 30 consecutive moderate to severe AS patients with preserved LVEF,and 30 healthy controls.Conventional echocardiography and 4D-strain imaging echocardiography were undergone in two groups.The 4D strain echocardiographic analyses were undertaken by using 4D Auto LVQ software.Results Compared with the healthy controls,the moderate to severe AS patients with preserved LVEF had significantly decreased global radial strain (GRS),global longitudinal strain (GLS),global area strain (GAS) and 4D strain (P < 0.05),had significantly increased left ventricular end-diastolic volume index (LVEDVI) and left ventricular mass index (LVMI) (P < 0.05),and had lower global circumferential strain (GCS) (P > 0.05).Conclusions Impaired LV myocardial contractility exists in moderate to severe AS patients,although LVEF is preserved.4D-strain imaging echocardiography can detect early left ventricular dysfunction in AS patients with preserved LVEF.

  5. 初诊狼疮肾炎患者左心室肥厚的相关因素%Influence Factors of Left Ventricular Hypertrophy in Incipient Lupus Nephritis Patients

    Institute of Scientific and Technical Information of China (English)

    沈晓琦; 陈伟钱; 陈江华

    2015-01-01

    目的 探讨初诊系统性红斑狼疮狼疮肾炎(lupus nephritis, LN)患者左心室肥厚的发生率及可能的相关因素.方法 选取初诊狼疮肾炎患者,共210例,采用横断面调查分析方法. 采集患者一般情况、血生化检验结果及同时期心脏彩色多普勒超声检测结果,按左心室心肌质量指数(left ventricular mass index, LVMI)分为两组:左心室肥厚组(n=89)和左心室正常组( n=121) ,比较两组生化指标的差异. 使用Spearman秩相关和多元线性回归分析评价左心室肥厚的相关因素. 结果 左心室肥厚组LN患者血尿酸、超敏C反应蛋白( hyper-sensitive C-reactive protein , hs-CRP)高于对照组,血红蛋白、估算的肾小球滤过率(estimated glomerular filtration rate , eGFR)低于对照组,差异有统计学意义(P<0.05). Spearman秩相关分析提示LVMI与尿酸、hs-CRP呈正相关(r=0.283、0.327,P<0.05),与血红蛋白,eGFR呈负相关(r=-0.232、-0.186,P<0.05). 多元线性回归分析提示hs-CRP、血红蛋白与狼疮肾炎患者左心室肥厚相关(r=0.235、-0.206,P<0.05). 结论 炎症状态、贫血是初诊狼疮肾炎患者左心室肥厚的独立危险因素. 改善患者炎症状态、纠正贫血可能利于减少左心室肥厚的发生.%Objective To investigate the influence factors of left ventricular hypertrophy ( LVH) in incipient systemic lupus erythe-matosus (SLE) patients with lupus nephritis (LN).Methods A total of 210 LN patients in the authors′centre were enrolled in this cross-section study .General information , laboratory measurements , examinations of left ventricular hypertrophy by ultrasonography were col -lected.Patients were divided into two groups according to left ventricular mass index (LVMI):left ventricle thickening (LVT) group (n=89) and left ventricle normal group (n=121).General information and laboratory results of two groups were statistically analyzed .In-fluence factors of the patients were analyzed with Spearman

  6. The Obesity Associated Peptide Leptin Induces Hypertrophy in Neonatal Rat Ventricular Myocytes%瘦素(leptin)诱导新生大鼠心室肌细胞的肥厚

    Institute of Scientific and Technical Information of China (English)

    张震; 惠汝太

    2003-01-01

    肥胖的一个主要表现是来源于脂肪细胞的大小为16kDa的leptin增加,leptin在心脏疾病如充血性心衰中也会增加.然而,leptin能否直接改变心脏表型还未明确.因此,我们利用1~4d的新生大鼠心室肌细胞来研究leptin作为潜在的肥厚因子的作用.利用RT-PCR,我们发现这些细胞可以表达短型(OB-Ra)leptin受体.用leptin(0.31~31.3nmol/L)处理细胞24h后,发现细胞表面积明显增大,达到最大表面积时的leptin浓度为0.63nmol/L.随后的实验使用3.1nmol/L的leptin处理细胞,发现细胞表面积增加42%,蛋白合成增加32%,α-骨骼肌肌动蛋白和肌球蛋白轻链-2表达分别增加250%和300%.这些事件发生并不伴随着细胞死亡的增加.包括p38和p44/42在内的丝裂原激活蛋白激酶系统(MAPK)的快速激活发生在肥厚反应之前,在leptin处理后的5min就被激活.用p38的抑制剂SB203580能够抑制leptin引起的肥厚,但是用p44/42的抑制剂PD98059却不能抑制这种肥厚.我们的实验结果证明,leptin是一个直接的肥厚因素,可能在肥厚和高浓度的leptin环境如肥胖之间提供了一个生物学上的关联.

  7. Evidence for angiotensin II type 2 receptor–mediated cardiac myocyte enlargement during in vivo pressure overload

    OpenAIRE

    Senbonmatsu, Takaaki; Ichihara, Sahoko; Price, Edward; Gaffney, F.Andrew; Inagami, Tadashi

    2000-01-01

    The pathophysiological roles of the angiotensin II type 2 receptor (AT2) in cardiac hypertrophy remain unclear. By the targeted deletion of mouse AT2 we were able to prevent the left ventricular hypertrophy resulting from pressure overload, while cardiac contractile functions remained normal. This implies that AT2 is a mediator of cardiac hypertrophy in response to increased blood pressure. The effects of AT2 deletion were independent of activation of embryonic genes for cardiac hypertrophy. ...

  8. Right ventricular collagen and fibronectin levels in patients with pulmonary atresia and ventricular septal defect

    NARCIS (Netherlands)

    Peters, Theodorus H F; de Jong, Peter L; Klompe, Lennart; Berger, Rolf M F; Saxena, Pramod R; Sharma, Hari S; Bogers, Ad J J C; Berger, Rudolphus

    2003-01-01

    Pulmonary atresia (PA) with ventricular septal defect (VSD) is an extreme form of tetralogy of Fallot with characteristic right ventricular hypertrophy. To reduce the right ventricular overload, these children have to undergo staged corrective surgery to restore physiological pulmonary perfusion. We

  9. The Akt-mTOR axis is a pivotal regulator of eccentric hypertrophy during volume overload

    OpenAIRE

    Masataka Ikeda; Tomomi Ide; Takeo Fujino; Yuka Matsuo; Shinobu Arai; Keita Saku; Takamori Kakino; Yasuhiro Oga; Akiko Nishizaki; Kenji Sunagawa

    2015-01-01

    The heart has two major modalities of hypertrophy in response to hemodynamic loads: concentric and eccentric hypertrophy caused by pressure and volume overload (VO), respectively. However, the molecular mechanism of eccentric hypertrophy remains poorly understood. Here we demonstrate that the Akt-mammalian target of rapamycin (mTOR) axis is a pivotal regulator of eccentric hypertrophy during VO. While mTOR in the heart was activated in a left ventricular end-diastolic pressure (LVEDP)-depende...

  10. Long pentraxin PTX3 exacerbates pressure overload-induced left ventricular dysfunction.

    Directory of Open Access Journals (Sweden)

    Satoshi Suzuki

    Full Text Available BACKGROUND: Left ventricular hypertrophy is enhanced by an inflammatory state and stimulation of various cytokines. Pentraxin 3 (PTX3 is rapidly produced in response to inflammatory signals, and high plasma PTX3 levels are seen in patients with heart failure. This study aimed to examine the influence of PTX3 on cardiac hypertrophy and left ventricular dysfunction with respect to pressure overload. METHODS AND RESULTS: PTX3 systemic knockout (PTX3-KO mice, transgenic mice with cardiac-specific overexpression of PTX3 (PTX3-TG, and the respective wild-type (WT littermate mice were subjected to transverse aortic constriction (TAC or a sham operation. Cardiac PTX3 expression increased after TAC in WT mice. In vitro, hydrogen peroxide induced the expression of PTX3 in both cardiac myocytes and cardiac fibroblasts. Recombinant PTX3 phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2 in cardiac fibroblasts. Phosphorylation of cardiac ERK1/2 and nuclear factor kappa-B after TAC was attenuated in the PTX3-KO mice but was enhanced in the PTX3-TG mice compared with WT mice. Interleukin-6 and connective tissue growth factor production was lower in the PTX3-KO mice than in the WT mice, but this was augmented in the PTX3-TG mice than in the WT mice. Echocardiography revealed that adverse remodeling with left ventricular dysfunction, as well as with increased interstitial fibrosis, was enhanced in PTX3-TG mice, while these responses were suppressed in PTX3-KO mice. CONCLUSION: The local inflammatory mediator PTX3 directly modulates the hypertrophic response and ventricular dysfunction following an increased afterload.

  11. Influence of losartan combined with perindopril on older hypertensive left ventricular hypertrophy and plasma fibrinogen%氯沙坦与培哚普利联用对老年高血压左室肥厚及血浆纤维蛋白原的影响

    Institute of Scientific and Technical Information of China (English)

    李淑兰; 丁召兴; 薄其美; 耿花娥

    2014-01-01

    目的:探讨氯沙坦与培哚普利联合应用对老年高血压患者左室肥厚及纤维蛋白原的影响。方法:2012年-2013年收治高血压合并左室肥厚老年患者90例,所有患者均采用氯沙坦联合培哚普利治疗,治疗前及治疗后6个月,对患者进行心脏超声检查,测定左心室质量指数(LVMI),同时进行血浆纤维蛋白原(Fg)检测,观察患者治疗前后两者变化。结果:治疗后与治疗前比较,LVMI及Fg含量均明显降低,差异有统计学意义(P<0.05)。结论:氯沙坦与培哚普利联合用药治疗老年性高血压,能逆转左心室肥厚,降低Fg含量,值得在临床推广。%Objective:To explore the influence of losartan combined with perindopril on older hypertensive left ventricular hypertrophy and plasma fibrinogen.Methods:90 elderly cases with essential hypertension and left ventricular hypertrophy were selected from 2012 to 2013.All cases were treated with losartan and perindopril treatment.Before treatment and at 6 months after the treatment,they received cardiac ultrasound examination to determinate the left ventricular mass index(LVMI).At the same time, they received the plasma fibrinogen(Fg) detection.We observed the changes of left ventricular mass index and the content of fibrinogen of all patients before and after treatment.Results:Compared before and after treatment,LVMI and Fg content were decreased.The difference was statistically significant(P<0.05).Conclusion:The application of losartan combined with perindopril in the treatment of hypertension in the elderly,can reverse left ventricular hypertrophy,and decrease the content of Fg.It is worthy of clinical application.

  12. Cystathione gamma lyase/Hydrogen Sulphide Pathway Up Regulation Enhances the Responsiveness of α1A and α1B-Adrenoreceptors in the Kidney of Rats with Left Ventricular Hypertrophy

    Science.gov (United States)

    Ahmad, Ashfaq; Sattar, Munavvar A.; Azam, Maleeha; Abdulla, Mohammed H.; Khan, Safia A.; Hashmi, Fayyaz; Abdullah, Nor A.; Johns, Edward J.

    2016-01-01

    The purpose of the present study was to investigate the interaction between H2S and NO (nitric oxide) in the kidney and to evaluate its impact on the functional contribution of α1A and α1B-adrenoreceptors subtypes mediating the renal vasoconstriction in the kidney of rats with left ventricular hypertrophy (LVH). In rats the LVH induction was by isoprenaline administration and caffeine in the drinking water together with intraperitoneal administration of H2S. The responsiveness of α1A and α1B to exogenous noradrenaline, phenylephrine and methoxaminein the absence and presence of 5-methylurapidil (5-MeU) and chloroethylclonidine (CEC) was studied. Cystathione gamma lyase (CSE), cystathione β synthase (CBS), 3-mercaptopyruvate sulphar transferase (3-MST) and endothelial nitric oxide synthase (eNOS) were quantified. There was significant up regulation of CSE and eNOS in the LVH-H2S compared to the LVH group (P<0.05). Baseline renal cortical blood perfusion (RCBP) was increased (P<0.05) in the LVH-H2S compared to the LVH group. The responsiveness of α1A-adrenergic receptors to adrenergic agonists was increased (P<0.05) after administration of low dose 5-Methylurapidil in the LVH-H2S group while α1B-adrenergic receptors responsiveness to adrenergic agonists were increased (P<0.05) by both low and high dose chloroethylclonidine in the LVH-H2S group. Treatment of LVH with H2S resulted in up-regulation of CSE/H2S, CBS, and 3-MST and eNOS/NO/cGMP pathways in the kidney. These up regulation of CSE/H2S, CBS, and 3-MST and eNOS/NO/cGMP pathways enhanced the responsiveness of α1A and α1B-adrenoreceptors subtypes to adrenergic agonists in LVH-H2S. These findings indicate an important role for H2S in modulating deranged signalling in the renal vasculature resulting from LVH development. PMID:27191852

  13. Physiologic Limits of Left Ventricular Hypertrophy in Elite Junior Football Athletes%青少年足球运动员左室肥厚的生理极限研究

    Institute of Scientific and Technical Information of China (English)

    冯爱民

    2014-01-01

    Objectives:This study was undertaken to define physiologic limits of left ventricular hypertrophy in elite football athletes. Methods: 60 elite football athletes and 60 healthy sedentary controls and 40 sundry items of similar age and gender underwent echocardiography. Results:Compared with controls, football athletes had greater absolute LVWT (9.5±1.7mm vs. 8.4±1.4mm;). Maximal LVWT exceeded predicted upper limits in 5 athletes (8.3%);however, only one trained male athletes had absolute LVWT>12 mm (1.7%). Each of the 5 athletes with a LVWT exceeding predicted limits also showed enlarged left ventricular cavity dimension (54.4±2.1 mm;range 52 to 60 mm). Female athlete had a LVWT>11 mm. Conclusions:Trained adolescent football athletes demonstrated greater absolute LVWT compared with nonathletes. Only a small proportion of athletes exhibited a LVWT exceeding upper limits, very rarely>12 mm, and then always with chamber enlargement. Hypertrophic cardiomyopathy should be considered strongly in any trained football male athlete with LVWT>12 mm(females>11mm).%目的:确定青少年足球运动员左室肥厚的生理极限值,预防运动员运动性猝死的发生风险。方法:采用超声心动仪检测60名优秀青少年足球运动员和60名年龄、性别类似的健康对照者及40名其他项目运动员的左心室厚度。结果:与对照组相比,青少年足球运动员的左心室壁厚度(LVWT)较大,为9.5±1.7 mm,对照组为8.4±1.4mm。其中5名运动员(8.3%)的最大LVWT超过了预测值的上限;只有1名男运动员的绝对LVWT值大于12mm(1.7%)。5名运动员的LVWT超过了预测限度,提示左心腔扩大(54.4±2.1mm;范围为52~60mm)。而女运动员LVWT值均小于11 mm。结论:与非运动员相比,有训练的青少年足球运动员的LVWT值更大。只有一小部分运动员的LVWT超过了上限,但少有大于12mm,而腔室一般都有扩大现象。提示,当有训练

  14. Participação do estado contrátil e do relaxamento miocárdico na disfunção ventricular durante a transição hipertrofia-falência cardíaca Myocardial function during the transition from compensated left ventricular hypertrophy to failure

    Directory of Open Access Journals (Sweden)

    Antonio Carlos Cicogna

    1997-12-01

    Full Text Available OBJETIVO: Avaliar a participação do estado contrátil e do relaxamento miocárdico na disfunção do músculo cardíaco durante a transição hipertrofia-falência cardíaca em ratos espontaneamente hipertensos (SHR. MÉTODOS: Músculos papilares isolados do ventrículo esquerdo de SHR com insuficiência cardíaca (SHR-IC e sem falência cardíaca (SHR e de ratos normotensos controle Wistar-Kyoto (WKY foram estudados em contrações isométrica e isotônica, em solução de Krebs-Henseleit (1,25 mM Ca2+, 28ºC. RESULTADOS: Os valores da tensão máxima desenvolvida (TD e da velocidade máxima de encurtamento (Vmáx foram menores nos SHR-IC e SHR, em relação aos WKY (p0,05. A rigidez passiva do músculo aumentou significantemente nos SHR-IC (p0,05. CONCLUSÃO: Os dados obtidos mostram que a transição da fase de hipertrofia estável para insuficiência cardíaca nos ratos espontaneamente hipertensos está associada ao aumento da rigidez passiva do miocárdio e não à piora da função contrátil do músculo cardíaco.PURPOSE: To investigate the participation of contractile state and relaxation in cardiac muscle dysfunction during the transition from stable hypertrophy to cardiac decompensation in aging spontaneously hypertensive rats (SHR. METHODS: Isolated left ventricular papillary muscle function was studied in SHR with heart failure (SHR-F, in age-matched SHR without evidence of heart failure (SHR-NF, and in nonhypertensive controls Wistar-Kyoto rats (WKY. Muscles were analised in isometric and isotonic contractions in Krebs-Henseleit solution with calcium concentration of 1.25mM at 28ºC. RESULTS: Papillary muscles from SHR-F and SHR-NF demonstrated decreased active tension development and shortening velocity relative to normotensive WKY (p0.05. CONCLUSION: These data suggest that the progression from stable hypertrophy to heart failure is associated with changes in the passive stiffness and is not related to depression of myocardial

  15. The Effect of Losartan Combined with Perindopril on Elderly Hypertensive Left Ventricular Hypertrophy and Plasma Fibrinogen%氯沙坦与培哚普利联用对老年高血压左室肥厚及血浆纤维蛋白原的影响

    Institute of Scientific and Technical Information of China (English)

    王正斌

    2014-01-01

    Objective To investigate the effect of losartan combined with perindopril on left ventricular hypertrophy and plasma fibrinogen of patients with senile hypertension. Methods The data of 90 cases of patients with senile hypertension complicated by left ventricular hypertrophy admitted in our hospital from May, 2012 to May, 2013 were divided into observation group and control group with 45 cases in each according to the randomized, controlled, double-blind principles. Both groups were given perindopril for treatment;in addition, the observation group were given losartan for treatment. Color Doppler echocardiography and plasma fib-rinogen detection were performed in the patients before and after the treatment. And the changes of indexes related to left ventric-ular hypertrophy before and after treatment and plasma fibrinogen levels were compared between the two groups. Results The im-provement in left ventricular hypertrophy IVST, PWT, LVDd of the observation group was obviously better than that of the control group, the difference was statistically significant (P<0.05);compared with the control group, the plasma fibrinogen of the observa-tion group decreased significantly, the difference was statistically significant (P<0.05). Conclusion Losartan combined with perindopril for patients with senile hypertension can reverse left ventricular hypertrophy and reduce plasma fibrinogen with satis-factory effect, and it is worthy of clinical promotion.%目的:探讨氯沙坦联合培哚普利治疗老年高血压对左室肥厚及血浆纤维蛋白原的影响。方法回顾性分析该院2012年5月-2013年5月收治的90例老年高血压合并左室肥厚患者的资料,按照随机、对照、双盲原则将患者分为观察组及对照组,各45例,两组患者均应用培哚普利治疗,观察组患者加用氯沙坦,患者治疗前后均行彩色多普勒超声心动图检查和血浆纤维蛋白原检查,比较两组患者治疗前后左室肥厚相关

  16. ErbB4 localization to cardiac myocyte nuclei, and its role in myocyte DNA damage response

    Energy Technology Data Exchange (ETDEWEB)

    Icli, Basak [Department of Medicine, Cardiovascular Division, Brigham and Women' s Hospital, Harvard Medical School, Boston, MA 02115 (United States); Bharti, Ajit [Center of Molecular Stress Response Whitaker Cardiovascular Institute, Department of Medicine, Boston University Medical Center, Boston, MA 02118 (United States); Pentassuglia, Laura; Peng, Xuyang [Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (United States); Sawyer, Douglas B., E-mail: douglas.b.sawyer@vanderbilt.edu [Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (United States)

    2012-02-03

    Highlights: Black-Right-Pointing-Pointer ErbB4 localizes to cardiac myocyte nuclei as a full-length receptor. Black-Right-Pointing-Pointer Cardiac myocytes express predominantly JM-a/CYT-1 ErbB4. Black-Right-Pointing-Pointer Myocyte p53 activation in response to doxorubicin requires ErbB4 activity. -- Abstract: The intracellular domain of ErbB4 receptor tyrosine kinase is known to translocate to the nucleus of cells where it can regulate p53 transcriptional activity. The purpose of this study was to examine whether ErbB4 can localize to the nucleus of adult rat ventricular myocytes (ARVM), and regulate p53 in these cells. We demonstrate that ErbB4 does locate to the nucleus of cardiac myocytes as a full-length protein, although nuclear location occurs as a full-length protein that does not require Protein Kinase C or {gamma}-secretase activity. Consistent with this we found that only the non-cleavable JM-b isoform of ErbB4 is expressed in ARVM. Doxorubicin was used to examine ErbB4 role in regulation of a DNA damage response in ARVM. Doxorubicin induced p53 and p21 was suppressed by treatment with AG1478, an EGFR and ErbB4 kinase inhibitor, or suppression of ErbB4 expression with small interfering RNA. Thus ErbB4 localizes to the nucleus as a full-length protein, and plays a role in the DNA damage response induced by doxorubicin in cardiac myocytes.

  17. Status and risk factors of chronic kidney disease complicated by left ventricular hypertrophy%慢性肾脏病并发左室肥厚现况及其危险因素

    Institute of Scientific and Technical Information of China (English)

    彭道有; 岳华; 何卫; 关彦军; 赵龙

    2011-01-01

    Objective: To explore the prevalence of left ventricular hypertrophy (LVH) and risk factors among patients with chronic kidney disease (CKD) at ages 40-75years.Methods: The medical records of 210 patients with CKD at the stage of 2-5, who were nephrology inpatients in our hospital and 40-75 years old, were analyzed retrospectively.Results: (1) The incidence of diastolic dysfunction was significantly higher than systolic dysfunction (79.1% VS 20.3% P=0.000); The detection rate of left atrial enlargement was significantly higher than that of left ventricular enlargement (46.5% VS 19.8% P=0.000); The detection rate of interventricular septum thickening(IVSH) was significantly higher than that of left ventricular posterior wall thickening(LVPWH) (43.0% VS 21.1% P=0.000); LVH prevalence (according to the formula) was significantly higher than IVSH prevalence (47.9% VS 35% P=0.001), LVH in females had significantly difference than that in male (73.2% VS 31.0% P=0.000).However, if applying a different diagnostic criteria for LVH, no significant differences (50% VS 34.5% P=0.068).(2) The systolic blood pressure(SBP), pulse pressure(PP), serum creatinine (Scr) in IVSH group were higher than those in non-IVSH.The serum phosphate in LVPWH group in addition to the above factors was still higher than those non-LVPWH group, but by subgroup analysis in CKD5 ,only the SBP compared with the control group was significantly different.In LVH group SBP, PP were higher than those non-LVH, and hemoglobin(Hb), body mass index(BMI) were lower than the control group.Logistic regression analysis indicated that only gender, BMI were statistically significant.Conclusion:(1) 40-75 years old CKD patients with high risk of cardiovascular disease, diagnosed by echocardiography with different diagnostic criteria, different conclusions of LVH may be drawn,but the highest positive rate of LVH is from the formula.(2) 40-75 years CKD patients, SBP, PP, anemia, BMI, female are

  18. Role of inositol 1,4,5-trisphosphate receptors in α1-adrenergic receptor-induced cardiomyocyte hypertrophy

    Institute of Scientific and Technical Information of China (English)

    Da-li LUO; Jian GAO; Xiao-mei LAN; Gang WANG; Sheng WEI; Rui-ping XIAO; Qi-de HAN

    2006-01-01

    Aim: Intracellular Ca2+ plays pivotal roles in diverse cellular functions, including gene transcription that underlies cardiac remodeling during stress responses. However, the role of inositol 1,4,5-trisphosphate receptors (IP3Rs) in the mediation of cardiac intracellular Ca2+ and hypertrophic growth remains elusive. Prior work with neonatal rat ventricular myocytes suggests that activation of IP3Rs may be linked to α1 adrenergic receptor (α1AR) increased stereotyped Ca2+ spark occurrence and global Ca2+ oscillations. Thus, we hypothesized that Ca2+ release through IP3Rs was necessary for α1AR-stimulated cardiac hypertrophy. Methods: We used myoinositol 1,4,5-trisphosphate hexakis (butyryloxymethyl) ester (IP3BM), a membrane-permeant ester of IP3, to activate IP3Rs directly, and Fluo 4/AM to measure intracellular Ca2+ signaling. Results: IP3BM (10μmol·L-1) mimicked the effects of phenylephrine, a selective agonist of α1AR, in increments in local Ca2+ spark release (especially in the perinuclear area) and global Ca2+ transient frequencies. More importantly, IP3R inhibitors, 2-aminoethoxydiphenyl borate and Xestospongin C, abolished the IP3BM-induced Ca2+ responses, and significantly suppressed α1AR-induced cardiomyocyte hypertrophy assayed by cell size, [3H] leucine incorporation and atrial natriuretic factor gene expression, during sustained (48 h) phenylephrine stimulation. Conclusion: These results, therefore, provide cellular mechanisms that link IP3R signaling to α1AR-stimulated gene expression and cardiomyocyte hypertrophy.

  19. Myofibril growth during cardiac hypertrophy is regulated through dual phosphorylation and acetylation of the actin capping protein CapZ.

    Science.gov (United States)

    Lin, Ying-Hsi; Warren, Chad M; Li, Jieli; McKinsey, Timothy A; Russell, Brenda

    2016-08-01

    The mechanotransduction signaling pathways initiated in heart muscle by increased mechanical loading are known to lead to long-term transcriptional changes and hypertrophy, but the rapid events for adaptation at the sarcomeric level are not fully understood. The goal of this study was to test the hypothesis that actin filament assembly during cardiomyocyte growth is regulated by post-translational modifications (PTMs) of CapZβ1. In rapidly hypertrophying neonatal rat ventricular myocytes (NRVMs) stimulated by phenylephrine (PE), two-dimensional gel electrophoresis (2DGE) of CapZβ1 revealed a shift toward more negative charge. Consistent with this, mass spectrometry identified CapZβ1 phosphorylation on serine-204 and acetylation on lysine-199, two residues which are near the actin binding surface of CapZβ1. Ectopic expression of dominant negative PKCɛ (dnPKCɛ) in NRVMs blunted the PE-induced increase in CapZ dynamics, as evidenced by the kinetic constant (Kfrap) of fluorescence recovery after photobleaching (FRAP), and concomitantly reduced phosphorylation and acetylation of CapZβ1. Furthermore, inhibition of class I histone deacetylases (HDACs) increased lysine-199 acetylation on CapZβ1, which increased Kfrap of CapZ and stimulated actin dynamics. Finally, we show that PE treatment of NRVMs results in decreased binding of HDAC3 to myofibrils, suggesting a signal-dependent mechanism for the regulation of sarcomere-associated CapZβ1 acetylation. Taken together, this dual regulation through phosphorylation and acetylation of CapZβ1 provides a novel model for the regulation of myofibril growth during cardiac hypertrophy. PMID:27185186

  20. Modulation of membrane potential by an acetylcholine-activated potassium current in trout atrial myocytes

    DEFF Research Database (Denmark)

    Molina, C.E.; Gesser, Hans; Llach, A.;

    2007-01-01

    mV from 4.3 pA/pF to 27 pA/pF with an EC50 of 45 nM in atrial myocytes. Moreover, 3 nM ACh increased the slope conductance of Im fourfold, shifted its reversal potential from -78 ± 3 to -84 ± 3 mV, and stabilized the resting membrane potential at -92 ± 4 mV. ACh also shortened the action potential...... hypothesized that this is at least partly due to a small slope conductance of Im around the resting membrane potential in atrial myocytes. In accordance with this hypothesis, the slope conductance of Im was about sevenfold smaller in atrial than in ventricular myocytes. Interestingly, ACh increased Im at -120...... of an inwardly rectifying K+ current can modulate the membrane potential in the trout atrial myocytes and stabilize the resting membrane potential. teleost heart; IK,ACh; cholinergic modulation; action potential...

  1. Postexertional Supraventricular Tachycardia in Children with Catecholaminergic Polymorphic Ventricular Tachycardia

    Directory of Open Access Journals (Sweden)

    Scott D. N. Else

    2012-01-01

    Full Text Available Catecholaminergic polymorphic ventricular tachycardia (CPVT is a severe arrhythmia associated with sudden death in the young. It is caused by defective calcium handling in ventricular myocytes. The association of supraventricular tachycardia (SVT with CPVT is described in the literature, occurring in the lead-up to ventricular tachycardia during exercise testing. We describe three cases of SVT that were initiated in the recovery period of exercise testing in children with CPVT.

  2. Sex Difference in the Repolarization Currents of Rabbit Ventricular Cells

    Institute of Scientific and Technical Information of China (English)

    RUAN Yanfei; LIU Nian; ZHOU Qiang; LI Yang; WANG Lin

    2005-01-01

    Summary: The current difference between male and female rabbit ventricular myocytes was investigated for elucidating the mechanism of longer QT interval and higher incidence of drug-associated torsade de pointes in female rabbits than in male rabbits. Whole cell patch clamp technique was used to record APD, Ito, IK,tail, IK1 and ICa,L of myocytes from left ventricular apex. There was no difference in the membrane capacitance between male and female rabbit myocytes. APD90 was longer in female rabbits (560.4±26.5 ms, n=15) than in male ones (489.0±20.7 ms, n=14), P0.05). The lower IK,tail of female rabbit myocytes may contribute to the longer repolarization and the higher incidence of drug-associated torsade de pointes.

  3. 厄贝沙坦联合氢氯噻嗪对原发性高血压患者左心室肥厚的影响%Effect of Irbesartan and Hydrochlorothiazide on Blood Pressure in Patients with Essential Hypertension and Left Ventricular Hypertrophy

    Institute of Scientific and Technical Information of China (English)

    张云; 梅松柳; 郭红霞

    2011-01-01

    目的 观察厄贝沙坦联合氢氯噻嗪对原发性高血压患者左心室肥厚的逆转效果.方法 56例原发性高血压伴左心室肥厚患者随机分成两组,各28例.对照组给予厄贝沙坦150 mg/d,观察组在此基础上加氢氯噻嗪12.5 mg/d,治疗6个月后,观察治疗前后两组患者血压变化,并计算左心室心肌重量(LVM)、左心室重量指数(LVMI).结果 两组患者治疗后收缩压及舒张压与对照组比较差异有统计学意义(P<0.05).两组患者治疗后LVM、LVMI与对照组比较差异有统计学意义(P<0.05).两组治疗后血钾水平分别与本组治疗前比较,差异均无统计学意义(P>0.05).结论 厄贝沙坦联合氢氯噻嗪降压以及逆转左心室肥厚的临床效果比单用厄贝沙坦更好.%Objective To observe the reversal effect of irbesartan and hydrochlorothiazide on blood pressure in patients with essential hypertension and left ventricular hypertrophy.Methods 56 cases of essential hypertension with left ventricular hypertrophy were randomly divided into two groups, treated with irbesartan 150 mg/d, plus hydrogenation chlorothiazide 12.5 mg/d in the observation group,for 6 months,observed before and after treatment of blood pressure change and calculate left ventricular myocardial weight measurement( LVM ),left ventricular mass index( LVMI ).Results The two groups after treatment compared with those before treatment significantly reduced SBP and DBP, and the observation group was lower than the control group after treatment ( P < 0.05 ).LVM, LVMI were significantly lower in both groups of patients after treatment,and the observation group was lower than the control group( P < 0.05 ).No significant difference was observed in serum potassium levels after treatment( P > 0.05 ).Conclusion Irbesartan combined with hydrochlorothiazide effect on lowering the blood pressure and reversing of left ventricular hypertrophy is better than the single - use.

  4. Valsartan in the treatment of heart failure or left ventricular dysfunction after myocardial infarction

    Directory of Open Access Journals (Sweden)

    Naylin Bissessor

    2007-09-01

    Full Text Available Naylin Bissessor1, Harvey White21Cardiology Research Fellow, 2Director of Coronary Care and Green Lane, Cardiovascular Research Unit, Green Lane Cardiovascular Research Unit, Auckland City Hospital, Auckland, New ZealandAbstract: The physiological role of the renin angiotensin aldosterone system (RAAS is to maintain the integrity of the cardiovascular system. The effect of angiotensin II is mediated via the angiotensin type I receptor (AT1 resulting in vasoconstriction, sodium retention and myocyte growth changes. This causes myocardial remodeling which eventually leads to left ventricular hypertrophy, dilation and dysfunction. Inhibition of the RAAS with angiotensin converting enzyme (ACE inhibitors after acute myocardial infarction has been shown to reduce cardiovascular morbidity and mortality. Angiotensin receptor blockers (ARBs specifically inhibit the AT1 receptor. It has not been known until the performance of the VALIANT (valsartan in acute myocardial infarction trial whether blockade of the angiotensin receptor with an ARB or combination of an ACE inhibitor and ARB leads to similar outcomes as an ACE inhibitor. The VALIANT trial demonstrated equal efficacy and non-inferiority of the ARB valsartan 160 mg bid compared with captopril 50 mg tds, when administered to high risk patients with left ventricular dysfunction or heart failure in the immediate post myocardial infarction period. The combination therapy showed no incremental benefit over ACE inhibition or an ARB alone and resulted in increased adverse effects. This review examines the role of valsartan in left ventricular dysfunction post myocardial infarction. We also discuss pharmacokinetics, dosing, side effects, and usage in the elderly.Keywords: valsartan, heart failure, left ventricular dysfunction, myocardial infarction

  5. Identification of a core set of genes that signifies pathways underlying cardiac hypertrophy

    DEFF Research Database (Denmark)

    Strøm, Claes C; Kruhøffer, Mogens; Knudsen, Steen;

    2004-01-01

    Although the molecular signals underlying cardiac hypertrophy have been the subject of intense investigation, the extent of common and distinct gene regulation between different forms of cardiac hypertrophy remains unclear. We hypothesized that a general and comparative analysis of hypertrophic...... gene expression, using microarray technology in multiple models of cardiac hypertrophy, including aortic banding, myocardial infarction, an arteriovenous shunt and pharmacologically induced hypertrophy, would uncover networks of conserved hypertrophy-specific genes and identify novel genes involved in...... hypertrophic signalling. From gene expression analyses (8740 probe sets, n = 46) of rat ventricular RNA, we identified a core set of 139 genes with consistent differential expression in all hypertrophy models as compared to their controls, including 78 genes not previously associated with hypertrophy and 61...

  6. Adiponectin Upregulates MiR-133a in Cardiac Hypertrophy through AMPK Activation and Reduced ERK1/2 Phosphorylation.

    Directory of Open Access Journals (Sweden)

    Ying Li

    Full Text Available Adiponectin and miR-133a are key regulators in cardiac hypertrophy. However, whether APN has a potential effect on miR-133a remains unclear. In this study, we aimed to investigate whether APN could regulate miR-133a expression in Angiotensin II (Ang II induced cardiac hypertrophy in vivo and in vitro. Lentiviral-mediated adiponectin treatment attenuated cardiac hypertrophy induced by Ang II infusion in male wistar rats as determined by reduced cell surface area and mRNA levels of atrial natriuretic peptide (ANF and brain natriuretic peptide (BNP, also the reduced left ventricular end-diastolic posterior wall thickness (LVPWd and end-diastolic interventricular septal thickness (IVSd. Meanwhile, APN elevated miR-133a level which was downregulated by Ang II. To further investigate the underlying molecular mechanisms, we treated neonatal rat ventricular myocytes (NRVMs with recombinant rat APN before Ang II stimulation. Pretreating cells with recombinant APN promoted AMP-activated protein kinase (AMPK phosphorylation and inhibited ERK activation. By using the inhibitor of AMPK or a lentiviral vector expressing AMPK short hairpin RNA (shRNA cancelled the positive effect of APN on miR-133a. The ERK inhibitor PD98059 reversed the downregulation of miR-133a induced by Ang II. These results indicated that the AMPK activation and ERK inhibition were responsible for the positive effect of APN on miR-133a. Furthermore, adiponectin receptor 1 (AdipoR1 mRNA expression was inhibited by Ang II stimulation. The positive effects of APN on AMPK activation and miR-133a, and the inhibitory effect on ERK phosphorylation were inhibited in NRVMs transfected with lentiviral AdipoR1shRNA. In addition, APN depressed the elevated expression of connective tissue growth factor (CTGF, a direct target of miR-133a, through the AMPK pathway. Taken together, our data indicated that APN reversed miR-133a levels through AMPK activation, reduced ERK1/2 phosphorylation in

  7. Influence of skeletal muscle satellite cells implanted into infarcted myocardium on remnant myocyte volumes

    Institute of Scientific and Technical Information of China (English)

    钟竑; 朱洪生; 卫洪超; 张臻

    2003-01-01

    Objective To study the effects of skeletal muscle satellite cells implanted into infarcted myocardium on the volume of remnant myocytes.Methods Thirty-six adult mongrel canines were divided randomly into implantation group and control group. In the implantation group, skeletal muscle satellite cells taken from the gluteus maximus muscles of the dogs were cultured, proliferated and labeled with 4', 6-diamidino-2-phenylindone (DAPI) in vitro. In both groups, a model of acute myocardial infarction was established in every dog. In the implantation group, each dog was injected with M199 solution containing autologous skeletal muscle satellite cells. The dogs in the control group received M199 solution without skeletal muscle satellite cells. The dogs of both groups were killed 2, 4 and 8 weeks after implantation (six dogs in a separate group each time). Both infarcted myocardium and normal myocytes distal from the infracted regions isolated were observed under optical and fluorescent microscope. Their volumes were determined using a confocal microscopy image analysis system and analyzed using SAS. A P<0.05 was considered significant.Results A portion of the implanted cells differentiated into muscle fiber with striations and were connected with intercalated discs. Cross-sectional area and cell volume were increased in normal myocardium. Hypertrophy of remnant myocytes in the infarcted site after skeletal muscle cell implantation was much more evident than in the control group. Cross-sectional area, cell area and cell volume differed significantly from those of the control group (P< 0.05). Hypertrophy of the cells occurred predominantly in terms of width and thickness, whereas cell length remained unchanged. Conclusion Skeletal muscle satellite cells implanted into infarct myocardium, could induce the hypertrophy of remnant myocyte cells in the infarcted site and could also aid in the recovery of the contractile force of the infarcted myocardium.

  8. 利多卡因对兔心室肌细胞动作电位的影响及对快钠电流的阻滞作用%Effects of lidocaine on the action potential and the blockade of fast sodium current in rabbit ventricular myocyte

    Institute of Scientific and Technical Information of China (English)

    李晶; 杨震; 赵籥陶; 周刚; 刘德平

    2015-01-01

    目的:探讨利多卡因对心室肌细胞动作电位(AP)的影响以及对快钠电流(INa-T )的张力性阻滞和使用依赖性阻滞作用。方法急性分离新西兰大白兔心脏,并予消化酶消化获得单个心室肌细胞,采用微电极技术检测 AP 相关参数:最大舒张期电位、零相最大上升速率(Vmax)、AP 振幅,以及复极化20%、50%和90%时的 AP 时程(APD20、APD50、APD90)。采用全细胞膜片钳技术检测兔心室肌细胞的 I Na-T。用100μmol/ L 利多卡因溶液灌流干预,观察各参数的变化。结果100μmol/ L 利多卡因灌流后,兔心室肌细胞最大舒张电位无明显变化[(-81±7) mV 比(-80±6)mV,P =0.102], AP 振幅显著降低[(100±12) mV 比(127±9) mV,P =0.002],Vmax 明显减慢[(328±41) V/ s 比(422±45) V/ s, P =0.004],APD90显著缩短[(66±8) ms 比(85±10) ms,P =0.021],峰值钠电流明显降低[(2468±389)pA 比(3223±367)pA,P =0.003]。在5 Hz 频率刺激下,利多卡因灌流前第40个刺激与第1个刺激诱发的电流分别为(3145±323)pA 和(3287±432)pA (P =0.087),灌流后电流分别为(1125±298)pA 和(2365±376)pA(P =0.013)。结论利多卡因降低 AP 振幅,减慢 Vmax,缩短 APD90,对 INa-T不但有张力性阻滞,更有显著的使用依赖性阻滞作用。%Objective To investigate the effects of lidocaine upon the action potential (AP) and its tonic block and use-dependent block of fast sodium current (INa-T ). Methods Hearts of New Zealand white rabbits were acutely separated, digested using enzyme solution, and individual ventricular myocytes were isolated. AP parameters were detected using microelectrode technique including the maximum diastolic potential (MDP), the maximum rate of rise of the action potential upstroke (Vmax), the action potential amplitude (APA) and the action potential duration at 20% , 50% and 90% (APD20 , APD50 and APD90 ) of repolarization. INa-T of rabbit ventricular myocytes was measured using whole cell patch clamp before

  9. Subaortic and midventricular obstructive hypertrophic cardiomyopathy with extreme segmental hypertrophy

    Directory of Open Access Journals (Sweden)

    Karoulas Takis

    2007-03-01

    Full Text Available Abstract Background Subaortic and midventricular hypertrophic cardiomyopathy in a patient with extreme segmental hypertrophy exceeding the usual maximum wall thickness reported in the literature is a rare phenomenon. Case Presentation A 19-year-old man with recently diagnosed hypertrophic cardiomyopathy (HCM was referred for sudden death risk assessment. The patient had mild exertional dyspnea (New York Heart Association functional class II, but without syncope or chest pain. There was no family history of HCM or sudden death. A two dimensional echocardiogram revealed an asymmetric type of LV hypertrophy; anterior ventricular septum = 49 mm; posterior ventricular septum = 20 mm; anterolateral free wall = 12 mm; and posterior free wall = 6 mm. The patient had 2 types of obstruction; a LV outflow obstruction due to systolic anterior motion of both mitral leaflets (Doppler-estimated 38 mm Hg gradient at rest; and a midventricular obstruction (Doppler-estimated 43 mm Hg gradient, but without apical aneurysm or dyskinesia. The patient had a normal blood pressure response on exercise test and no episodes of non-sustained ventricular tachycardia in 24-h ECG recording. Cardiac MRI showed a gross late enhancement at the hypertrophied septum. Based on the extreme degree of LV hypertrophy and the myocardial hyperenhancement, an implantation of a cardioverter-defibrillator was recommended prophylactically for primary prevention of sudden death. Conclusion Midventricular HCM is an infrequent phenotype, but may be associated with an apical aneurysm and progression to systolic dysfunction (end-stage HCM.

  10. 二尖瓣环位移对肥厚性重构患者左室收缩功能的评估作用%Evaluation of left ventricular systolic dysfunction by mitral annular displacement in patients with cardiac hypertrophy and remodeling

    Institute of Scientific and Technical Information of China (English)

    吴卫华; 黄艳; 陆静; 马兰; 魏松霞; 谢晓奕; 刘奇志; 王雷; 杨玲

    2011-01-01

    目的 应用超声二维斑点追踪显像技术测定二尖瓣环位移(MAD),探讨其在评估肥厚性重构所致的早期左室收缩功能减退方面的临床应用价值.方法 选择86例左室射血分数(LVEF)正常(>50%)的各类心肌肥厚(左室壁厚度≥12 mm)患者作为研究对象.采用Philips Sonos iE33超声仪进行检查,先通过M型超声计算出相对室壁厚度(RWT),然后取心尖四腔观分别采集二维和实时三维全容积(RT3D)图像.应用QLAB 6.2在机量化分析软件分别获取MAD相关参数(包括二尖瓣环中点位移和左室长轴缩短率)和经RT3D图像测得左室射血分数(RT3D-LVEF);计算三维心肌重构指标,包括左室舒末容积指数(LVEDVI)和左室质量指数(LVMI).将心肌肥厚患者中RWT<0.45且LVMI在正常范围内的患者归入肥厚正常几何构型组(HNG组),其余归入肥厚重构组(HR组);以46名年龄相匹配的健康志愿者作为正常对照组.结果 HNG组、HR组和正常对照组的RT3D-LVEF均在正常范围内,两两比较差异均无统计学意义(P>0.05).HR组的MAD各值和LVEDVI均显著低于HNG组和正常对照组,差异均有统计学意义(P<0.01或P<0.05);HNG组与正常对照组MAD相关参数值和LVEDVI比较差异均无统计学意义(P>0.05).Bland-Altman分析显示MAD各值的可重复性较高.结论 在心肌肥厚性重构患者中,与LVEF比较,MAD能更早地反映患者的左室收缩功能减退情况.%Objective To investigate the value of mitral annular displacement (MAD) by two-dimensional speckle tracking in evaluating left ventricular systolic dysfunction in patients with cardiac hypertrophy and remodeling.Methods Eightysix patients with cardiac hypertrophy ( left ventricular wall thickness ≥ 12 mm) and normal left ventricular ejection fraction (LVEF) ( > 50% ) were selected.Philips Sonos iE33 ultrasound device was used for examinations.Relative wall thickness (IRWT) was calculated by M mode ultrasound, and two

  11. 应变率成像技术评价左心室心肌肥厚病人左心房功能的价值%THE VALUE OF STRAIN RATE IMAGING IN THE ASSESSMENT OF LEFT ATRIAL FUNCTION IN PATIENTS WITH LEFT VENTRICULAR MYOCARDIAL HYPERTROPHY

    Institute of Scientific and Technical Information of China (English)

    聂晶; 邵倩倩; 王志斌

    2012-01-01

    目的 探讨实时三平面应变率成像检测生理性与病理性左心室肥厚者左心房功能的价值.方法选取原发性高血压病人30例、专业运动员25例、正常人30例,应用实时三平面应变率成像定量检测左心房每个壁在收缩期、舒张早期、舒张晚期的峰值应变率并进行比较.结果 运动员组与对照组的峰值应变率相近,差异无统计学意义(P>0.05),而高血压组峰值应变率明显下降(F=29.54~35.03,q=11.52~19.74,P<0.05).结论实时三平面应变率成像能够敏感地反映高血压早期左心房功能的改变,对于全面评价原发性高血压与生理性左心室心肌肥厚者左心房功能有重要作用.%Objective To investigate the value of real-time tri-plane strain rate imaging in detection of left atrial function in those with physiologic and pathologic left ventricular hypertrophy. Methods Thirty patients with primary hypertension. 25 professional athletes, and 30 normal individuals were enrolled in this study. By using real-time tri-plane strain rate imaging technique, the strain rate peak values of each LA wall in systole period, early diastole and late diastole were detected and compared. Results The peak strain rate in the athletes and normal controls was close to each other, the difference between them was not significant (P>0. 05) , and in hypertension group, the peak strain rate declined obviously (F = 29. 54 —35. 03,q=11. 52 —19. 74,P< 0. 05). Conclusion Real-time tri-plane strain rate imaging technique can sensitively reflect the changes of left atrial function in early hypertension, which is of important role in overall assessment of left atrial function due to left ventricular hypertrophy caused by primary hypertension or physiologic reason.

  12. 老年腹膜透析患者的临床特点及左心室肥厚相关因素分析%Clinical characteristics and correlation analysis between left ventricular hypertrophy and related factors in elderly patients with peritoneal dialysis

    Institute of Scientific and Technical Information of China (English)

    付莎; 徐安平; 梁佩芬; 曾玉纯

    2014-01-01

    Objective To analyze the clinical characteristics of elderly patients with peritoneal dialy-sis and investigate the relationship between left ventricular hypertrophy and related clinical indicators. Methods A retrospective study was performed in 1 1 9 patients undergoing continuous ambulatory peritoneal dialysis. All enrolled subjects were divided into two groups according to age:elderly group (≥60 years)and young group (<60 years). The laboratory and blood pressure parameters were evaluated,echocardiography was performed and LVMI (left ventricular mass index)was calculated. The correlation between LVMI and the above indica-tors was tested by single factor and multiple linear regression analysis. Results The levels of serum albumin, creatinine and urea nitrogen in the elderly group were significantly lower than those in the young group (all P<0.05 ),whereas the incidence of peritonitis,left ventricular hypertrophy and heart failure was significantly higher in the elderly patients (all P<0.05 ). Single factor analysis revealed that LVMI was positively correla-ted with systolic blood pressure,pulse pressure and vascular overload index (VOI)(all P<0.05 )and nega-tively correlated with residual urine volume,prealbumin and KT/V (all P<0.05 ). Multiple linear regression analysis demonstrated that LVMI was positively correlated with pulse pressure (β=0.782,P<0.01 )and VOI (β=0.51 7,P<0.05),and negatively associated with KT/V (β=-0.632,P<0.05). Conclusions The elderly patients with peritoneal dialysis have a significantly higher incidence of hypoproteinemia,malnutrition, peritonitis,left ventricular hypertrophy and heart failure compared with the younger counterparts. The left ven-tricular hypertrophy is closely correlated with pulse pressure,VOI and KT/V.%目的:分析老年腹膜透析患者的临床特点,探讨老年腹膜透析患者左心室肥厚与临床指标的相关性。方法收集119例规律腹膜透析患者,根据年龄

  13. Adiponectin downregulation is associated with volume overload-induced myocyte dysfunction in rats

    OpenAIRE

    Wang, Li-li; Miller, Dori; Wanders, Desiree; Nanayakkara, Gayani; Amin, Rajesh; Judd, Robert; Morrison, Edward E.; Zhong, Ju-ming

    2015-01-01

    Aim: Adiponectin has been reported to exert protective effects during pathological ventricular remodeling, but the role of adiponectin in volume overload-induced heart failure remains unclear. In this study we investigated the effect of adiponectin on cardiac myocyte contractile dysfunction following volume overload in rats. Methods: Volume overload was surgically induced in rats by infrarenal aorta-vena cava fistula. The rats were intravenously administered adenoviral adiponectin at 2-, 6- a...

  14. In-treatment midwall and endocardial fractional shortening predict cardiovascular outcome in hypertensive patients with preserved baseline systolic ventricular function: the Losartan Intervention For Endpoint reduction study

    DEFF Research Database (Denmark)

    Wachtell, Kristian; Gerdts, Eva; Palmieri, Vittorio;

    2010-01-01

    Endocardial fractional shortening (EFS) and midwall shortening (MWS) are impaired in patients with left ventricular hypertrophy. However, it remains unknown whether improvement of left ventricular systolic function during treatment reduces cardiovascular morbidity and mortality in hypertensive pa...

  15. Molecular and cellular biology of the senescent hypertrophied and failing heart.

    Science.gov (United States)

    Swynghedauw, B; Besse, S; Assayag, P; Carré, F; Chevalier, B; Charlemagne, D; Delcayre, C; Hardouin, S; Heymes, C; Moalic, J M

    1995-11-01

    During aging, experimental studies have revealed various cellular changes, principal among which is myocyte hypertrophy, which compensates for the loss of myocytes and is associated with fibrosis. The expression of alpha-myosin heavy chain is replaced by that of the isogene beta-myosin, which leads to decreased myosin adenosine triphosphatase (ATPase) activity. In consequence, contraction is slower and more energetically economical. The Ca(2+)-ATPase of the sarcoplasmic reticulum and Na+/Ca2+ exchange activity are decreased, which probably explains the reduced velocity of relaxation. Membrane receptors are also modified, since the density of both the total beta-adrenergic and muscarinic receptors is decreased. The senescent heart is able to hypertrophy in response to overload and to adapt to the new requirements. Similar alterations are observed both in the senescent heart and in the overloaded heart, in clinical as well as in experimental studies; however, differences do exist, especially in terms of fibrosis and arrhythmias. PMID:7495213

  16. Ataxia telangiectasia-mutated kinase deficiency exacerbates left ventricular dysfunction and remodeling late after myocardial infarction.

    Science.gov (United States)

    Daniel, Laura L; Scofield, Stephanie L C; Thrasher, Patsy; Dalal, Suman; Daniels, Christopher R; Foster, Cerrone R; Singh, Mahipal; Singh, Krishna

    2016-08-01

    Ataxia telangiectasia-mutated kinase (ATM), a cell cycle checkpoint protein, is activated in response to DNA damage and oxidative stress. We have previously shown that ATM deficiency is associated with increased apoptosis and fibrosis and attenuation of cardiac dysfunction early (1-7 days) following myocardial infarction (MI). Here, we tested the hypothesis that enhanced fibrosis and apoptosis, as observed early post-MI during ATM deficiency, exacerbate cardiac dysfunction and remodeling in ATM-deficient mice late post-MI. MIs were induced in wild-type (WT) and ATM heterozygous knockout (hKO) mice by ligation of the left anterior descending artery. Left ventricular (LV) structural and functional parameters were assessed by echocardiography 14 and 28 days post-MI, whereas biochemical parameters were measured 28 days post-MI. hKO-MI mice exhibited exacerbated LV dysfunction as observed by increased LV end-systolic volume and decreased percent fractional shortening and ejection fraction. Infarct size and thickness were not different between the two genotypes. Myocyte cross-sectional area was greater in hKO-MI group. The hKO-MI group exhibited increased fibrosis in the noninfarct and higher expression of α-smooth muscle actin (myofibroblast marker) in the infarct region. Apoptosis and activation of GSK-3β (proapoptotic kinase) were significantly lower in the infarct region of hKO-MI group. Matrix metalloproteinase 2 (MMP-2) expression was not different between the two genotypes. However, MMP-9 expression was significantly lower in the noninfarct region of hKO-MI group. Thus ATM deficiency exacerbates cardiac remodeling late post-MI with effects on cardiac function, fibrosis, apoptosis, and myocyte hypertrophy. PMID:27288435

  17. Model dependent behaviour of pressure hypertrophied myocardium.

    Science.gov (United States)

    Cooper, G; Tomanek, R J

    1987-05-01

    Two animal models with contrasting responses to pressure overloading were used to determine whether cardiac dysfunction is a general property of pressure hypertrophied myocardium or a specific property of a particular model. Chronic progressive cardiac pressure overload was compared in (a) the left ventricle of the adult and aged spontaneously hypertensive rat, in which pressure overloading begins in the pup, and (b) the right ventricle of the adult cat, in which pressure overloading was initiated surgically in the kitten. Nine hypertensive and nine control rats were studied at 1 year of age, when hypertension is stable in this model; five hypertensive and five control rats were then studied at 2 years of age, when both groups of rats are beginning to show appreciable senile mortality. Systolic blood pressure was similarly increased in both hypertensive groups; compared with the normotensive control groups, the ratio of left ventricular to body weight was 36% and 76% higher in the 1 and 2 year old hypertensive groups respectively. During isotonic contractions of left ventricular papillary muscles the extent and velocity of shortening in muscles from the control and hypertensive rats in each group were the same, but shortening and relaxation times were prolonged in muscles from the hypertensive rats in both age groups. During isometric contractions developed tension and the rate of tension rise were the same throughout, but the time integral of active tension was increased in muscles from the hypertensive rats in both age groups. The ratio of oxygen consumption to either external work or developed tension was decreased in muscles from the hypertensive rats. In contrast to these data, previous data from the hypertrophied cat model showed reductions in both the velocity and the extent of isotonic shortening as well as in the rate and amount of isometric tension development, and prolongation of contraction was not observed. A similar but smaller decrease in the oxygen

  18. 急性激活α1和β1肾上腺素能受体对豚鼠心室肌细胞快激活延迟整流钾电流的交叉影响%Cross effects of acute adrenergic stimulation on rapid component of delayed rectifier potassium channel current in guinea-pig left ventricular myocytes

    Institute of Scientific and Technical Information of China (English)

    吴婷婷; 王森; 邹建刚; 曹克将; 许迪

    2014-01-01

    different subtype and both of adrenergic receptors (α1-AR or β1-AR) on the rapidly activating delayed rectifier potassium current ( IKr ) in guinea-pig ventricular myocytes,and the effects of acute stimulation of both α1-AR and β1-AR on IKr current. Methods Single ventricular myocyte was obtained from guinea-pig using enzymatic dissociation technique. Whole-cell patch clamp technique was used to record IKr current. The amplitudes of IKr current before and after stimulation of adrenergic receptors were measured to reflect the effects of acute stimulation of different adrener-gic receptors. The expression level of IKr channel protein after acute stimulation of different subtype of adrenergic receptors was detected by western-blot. Results Phenylephrine( PE) and xamoterol( Xamo) inhibited IKr cur-rent amplitude by a content dependent way,the IC50 was 0. 93 μmol/L and 6. 40 μmol/L respectively. In our study,1 μmol/L PE (PE group) reduced IKr current to 0. 79±0. 02,and shifted the voltage-dependent activa-ting curve to the negative voltage,where U0.5 changed from (-2. 99±1. 44) mV to (-9. 10±1. 74) mV,and k changed a little. 10μmol/L Xamo (Xamo group) reduced IKr current to 0. 72±0. 01,and shifted the voltage-de-pendent activating curve to the negative voltage, where U0. 5 changed from (-4. 54 ± 1. 48 ) mV to (-7. 24 ± 1. 93) mV,and k changed a little. While simultaneously administration of 1 μmol/L PE and 10 μmol/L Xamo (PE+Xamo group) only reduced IKr current to 0. 69±0. 02,and it also shifted the voltage-dependent activating curve to the negative voltage,where U0.5 changed from (-2. 71±1. 95) mV to (-8. 45±1. 97) mV,and k changed a little. In PE group, Xamo group and PE+XAMO group, IKr tail current amplitude decreased by (20. 73±2. 46)%,(27. 99±0. 68)% and (30. 56±1. 80)%,separately. By western-blot,the expression level of IKr channel protein after acute adrenergic stimulation did not show a statistical change. Conclusions Acute stimulation of α1-AR or

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

    Directory of Open Access Journals (Sweden)

    Erling David Kaunang

    2014-09-01

    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. The 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 echocardio-graphy (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 common in male adolescent athletes than in non-athletes. [Paediatr Indones. 2014;54:305-8.].

  20. [Doppler echocardiography of ventricular diastole].

    Science.gov (United States)

    Roudaut, R; Gosse, P; Dallocchio, M

    1988-12-01

    Non-invasive studies of left ventricular relaxation and filling by means of doppler-echocardiography are of considerable interest owing to easy recording and good reproducibility. However, such physiological parameters as site of measurement, heart rate and, chiefly, age may interfere with the curves obtained. The interpretation of tracings must also take into account the presence of mitral valve pathology (stenosis or regurgitation), aortic stenosis, disorders of atrioventricular (prolonged PR complex) or intraventricular (left bundle branch block) conduction and medication (e.g. vasodilators). In clinical practice, one of the main advantages of the technique is that it makes it possible to distinguish between the physiological left ventricular hypertrophy (LVH) of top-class sportsmen (without impaired ventricular filling) and the pathological LVH of hypertrophic cardiomyopathy. The purpose of this study, with a review of the literature, was to take stock of the value and limitations of the doppler indices.

  1. PARM-1 is an endoplasmic reticulum molecule involved in endoplasmic reticulum stress-induced apoptosis in rat cardiac myocytes.

    Directory of Open Access Journals (Sweden)

    Koji Isodono

    Full Text Available To identify novel transmembrane and secretory molecules expressed in cardiac myocytes, signal sequence trap screening was performed in rat neonatal cardiac myocytes. One of the molecules identified was a transmembrane protein, prostatic androgen repressed message-1 (PARM-1. While PARM-1 has been identified as a gene induced in prostate in response to castration, its function is largely unknown. Our expression analysis revealed that PARM-1 was specifically expressed in hearts and skeletal muscles, and in the heart, cardiac myocytes, but not non-myocytes expressed PARM-1. Immunofluorescent staining showed that PARM-1 was predominantly localized in endoplasmic reticulum (ER. In Dahl salt-sensitive rats, high-salt diet resulted in hypertension, cardiac hypertrophy and subsequent heart failure, and significantly stimulated PARM-1 expression in the hearts, with a concomitant increase in ER stress markers such as GRP78 and CHOP. In cultured cardiac myocytes, PARM-1 expression was stimulated by proinflammatory cytokines, but not by hypertrophic stimuli. A marked increase in PARM-1 expression was observed in response to ER stress inducers such as thapsigargin and tunicamycin, which also induced apoptotic cell death. Silencing PARM-1 expression by siRNAs enhanced apoptotic response in cardiac myocytes to ER stresses. PARM-1 silencing also repressed expression of PERK and ATF6, and augmented expression of CHOP without affecting IRE-1 expression and JNK and Caspase-12 activation. Thus, PARM-1 expression is induced by ER stress, which plays a protective role in cardiac myocytes through regulating PERK, ATF6 and CHOP expression. These results suggested that PARM-1 is a novel ER transmembrane molecule involved in cardiac remodeling in hypertensive heart disease.

  2. Resistance training and cardiac hypertrophy: unravelling the training effect.

    Science.gov (United States)

    Haykowsky, Mark J; Dressendorfer, Rudolph; Taylor, Dylan; Mandic, Sandra; Humen, Dennis

    2002-01-01

    Resistance training (RT) is a popular method of conditioning to enhance sport performance as well as an effective form of exercise to attenuate the age-mediated decline in muscle strength and mass. Although the benefits of RT on skeletal muscle morphology and function are well established, its effect on left ventricular (LV) morphology remains equivocal. Some investigations have found that RT is associated with an obligatory increase in LV wall thickness and mass with minimal alteration in LV internal cavity dimension, an effect called concentric hypertrophy. However, others report that short- (18 years) RT does not alter LV morphology, arguing that concentric hypertrophy is not an obligatory adaptation secondary to this form of exertion. This disparity between studies on whether RT consistently results in cardiac hypertrophy could be caused by: (i) acute cardiopulmonary mechanisms that minimise the increase in transmural pressure (i.e. ventricular pressure minus intrathoracic pressure) and LV wall stress during exercise; (ii) the underlying use of anabolic steroids by the athletes; or (iii) the specific type of RT performed. We propose that when LV geometry is altered after RT, the pattern is usually concentric hypertrophy in Olympic weightlifters. However, the pattern of eccentric hypertrophy (increased LV mass secondary to an increase in diastolic internal cavity dimension and wall thickness) is not uncommon in bodybuilders. Of particular interest, nearly 40% of all RT athletes have normal LV geometry, and these athletes are typically powerlifters. RT athletes who use anabolic steroids have been shown to have significantly higher LV mass compared with drug-free sport-matched athletes. This brief review will sort out some of the factors that may affect the acute and chronic outcome of RT on LV morphology. In addition, a conceptual framework is offered to help explain why cardiac hypertrophy is not always found in RT athletes. PMID:12392444

  3. Ventricular assist device

    Science.gov (United States)

    VAD; RVAD; LVAD; BVAD; Right ventricular assist device; Left ventricular assist device; Biventricular assist device; Heart pump; Left ventricular assist system; LVAS; Implantable ventricular assist device

  4. Selumetinib, an Oral Anti-Neoplastic Drug, May Attenuate Cardiac Hypertrophy via Targeting the ERK Pathway.

    Directory of Open Access Journals (Sweden)

    Chen Li

    Full Text Available Although extracellular-regulated kinases (ERK are a well-known central mediator in cardiac hypertrophy, no clinically available ERK antagonist has been tested for preventing cardiac hypertrophy. Selumetinib is a novel oral MEK inhibitor that is currently under Phase II and Phase III clinical investigation for advanced solid tumors. In this study, we investigated whether Selumetinib could inhibit the aberrant ERK activation of the heart in response to stress as well as prevent cardiac hypertrophy.In an in vitro model of PE-induced cardiac hypertrophy, Selumetinib significantly inhibited the ERK activation and prevented enlargement of cardiomyocytes or reactivation of certain fetal genes. In the pathologic cardiac hypertrophy model of ascending aortic constriction, Selumetinib provided significant ERK inhibition in the stressed heart but not in the other organs. This selective ERK inhibition prevented left ventricular (LV wall thickening, LV mass increase, fetal gene reactivation and cardiac fibrosis. In another distinct physiologic cardiac hypertrophy model of a swimming rat, Selumetinib provided a similar anti-hypertrophy effect, except that no significant fetal gene reactivation or cardiac fibrosis was observed.Selumetinib, a novel oral anti-cancer drug with good safety records in a number of Phase II clinical trials, can inhibit ERK activity in the heart and prevent cardiac hypertrophy. These promising results indicate that Selumetinib could potentially be used to treat cardiac hypertrophy. However, this hypothesis needs to be validated in human clinical trials.

  5. Selumetinib, an Oral Anti-Neoplastic Drug, May Attenuate Cardiac Hypertrophy via Targeting the ERK Pathway

    Science.gov (United States)

    Yang, Hao; Luo, Fangbo; Chen, Lihong; Cai, Huawei; Li, Yajiao; You, Guiying; Long, Dan; Li, Shengfu; Zhang, Qiuping; Rao, Li

    2016-01-01

    Aims Although extracellular-regulated kinases (ERK) are a well-known central mediator in cardiac hypertrophy, no clinically available ERK antagonist has been tested for preventing cardiac hypertrophy. Selumetinib is a novel oral MEK inhibitor that is currently under Phase II and Phase III clinical investigation for advanced solid tumors. In this study, we investigated whether Selumetinib could inhibit the aberrant ERK activation of the heart in response to stress as well as prevent cardiac hypertrophy. Methods and Results In an in vitro model of PE-induced cardiac hypertrophy, Selumetinib significantly inhibited the ERK activation and prevented enlargement of cardiomyocytes or reactivation of certain fetal genes. In the pathologic cardiac hypertrophy model of ascending aortic constriction, Selumetinib provided significant ERK inhibition in the stressed heart but not in the other organs. This selective ERK inhibition prevented left ventricular (LV) wall thickening, LV mass increase, fetal gene reactivation and cardiac fibrosis. In another distinct physiologic cardiac hypertrophy model of a swimming rat, Selumetinib provided a similar anti-hypertrophy effect, except that no significant fetal gene reactivation or cardiac fibrosis was observed. Conclusions Selumetinib, a novel oral anti-cancer drug with good safety records in a number of Phase II clinical trials, can inhibit ERK activity in the heart and prevent cardiac hypertrophy. These promising results indicate that Selumetinib could potentially be used to treat cardiac hypertrophy. However, this hypothesis needs to be validated in human clinical trials. PMID:27438013

  6. A dual potassium channel activator improves repolarization reserve and normalizes ventricular action potentials

    DEFF Research Database (Denmark)

    Calloe, Kirstine; Di Diego, José M; Hansen, Rie Schultz;

    2016-01-01

    cultured canine cardiac myocytes and determined whether a dual K(+) current activator can normalize K(+) currents and restore action potential (AP) configuration. METHODS AND RESULTS: Ventricular myocytes were isolated and cultured for up to 48h. Current and voltage clamp recordings were made using patch...... of EADs. Our results suggest a potential benefit of K(+) current activators under conditions of reduced repolarization reserve including heart failure....

  7. Effects of preemptive enoximone on left ventricular diastolic function after valve replacement for aortic stenosis

    NARCIS (Netherlands)

    van der Maaten, Joost M. A. A.; de Vries, Adrianus J.; Rietman, Gerrit W.; Gallandat Huet, Rolf C. G.; De Hert, Stefan G.

    2007-01-01

    Objective: Left ventricular (LV) hypertrophy is associated with increased diastolic chamber stiffness early after aortic valve replacement for valve stenosis. Enoximone, a phosphodiesterase III inhibitor, has been shown to improve myocardial contractility and relaxation when administered as a single

  8. Evaluation of left ventricular strain by real-time three-dimensional speckle tracking echocardiography in patients with hypertension and myocardial hypertrophy%实时三维超声心动图斑点追踪技术测量高血压心肌肥厚患者收缩期左室心肌应变

    Institute of Scientific and Technical Information of China (English)

    汤乔颖; 邓又斌; 黄润青; 刘琨; 孙杰; 邓琪

    2013-01-01

    Objective To investigate left ventricular (LV) strain in patients with hypertension (HT)and myocardial hypertrophy using three-dimensional speckle tracking echocardiography.Methods Myocardial movement was analyzed in 37 primary HT patients with myocardial hypertrophy and 27 healthy volunteers.LV longitudinal,circumferential,radial and area strains were measured.The correlation between each global strain parameter and LV ejection fraction (LVEF) was analyzed.Results LV global longitudinal strain(GSL),global radial strain (GSR) and global area strain (GSA) of HT patients with myocardial hypertrophy were significantly lower than the contrast group,whereas global circumferential strain(GSC) showed no significant difference between the two groups.Longitudinal,radial and area strains were decreased in LV basal and middle levels,while decreased circumferential strain was detected only in basal level.There were significant correlations between LVEF and GSL,GSC,GSR,GSA.Conclusions Impairment of LV regional myocardial contractility can be detected by three-dimensional speckle tracking echocardiography.%目的 采用实时三维超声心动图斑点追踪技术研究原发性高血压心肌肥厚患者的收缩期左室心肌应变特点.方法 采用三维超声心动图斑点追踪技术对37例原发性高血压心肌肥厚患者及27例健康志愿者进行了室壁运动分析,测量左室纵向、圆周向、径向、面积应变,比较两组间各应变参数的差异,并分析各项整体应变参数与左室射血分数(LVEF)的相关性.结果 高血压心肌肥厚患者的左室整体纵向、径向和面积应变较正常对照组明显减低,左室整体圆周向应变与对照组间无明显差异.纵向、径向、圆周向应变在左室基底段、中段明显减低,圆周向应变减低仅见于基底段.左室整体纵向、圆周向、径向、面积应变与LVEF具有相关性.结论 实时三维超声心动图斑点追踪技术可检测到高血压心

  9. Immunoreactive atrial natriuretic peptide and dopamine beta-hydroxylase in myocytes and chromaffin cells of the heart of the African lungfish, Protopterus aethiopicus.

    Science.gov (United States)

    Larsen, T H; Helle, K B; Saetersdal, T

    1994-07-01

    The heart of the African lungfish, Protopterus aethiopicus, was examined for immunoreactive atrial natriuretic peptide (ANP) and dopamine beta-hydroxylase (D beta H) as markers for hormone secreting myocytes and chromaffin cells, respectively. Specific antibodies raised against rat alpha-ANP and rat D beta H were used for immunofluorescence microscopy and immunogold electron microscopy. D beta H-immunoreactive cells were restricted to subendocardial areas of the atrium whereas ANP immunoreactivity occurred throughout both the atrial and the ventricular myocardium, showing particularly strong staining intensity in the atrial myocytes. The granular ANP immunostaining in the atrial myocytes was frequently accumulated in the sarcoplasm. In the ventricular myocytes ANP immunoreactivity occurred as scattered granular staining throughout the sarcoplasm. ANP and D beta H immunofluorescence staining coincided with the presence of immunoreactive specific granules and secretory vesicles in the cardiac myocytes and chromaffin cells, respectively, as revealed by electron microscopy. The number of ANP-containing specific granules was generally high in the atrial myocytes, and they were frequently observed in clusters in subsarcolemmal areas. Granular frequency was considerably lower and the mean granular diameter was smaller (0.142 +/- 0.045 micron versus 0.213 +/- 0.049 micron) in the ventricular than in the atrial myocytes. The present results indicate that ANP and D beta H are phylogenetically highly conserved proteins from the dipnoi to the rat. The large amounts of ANP and of specific granules are consistent with an endocrine myocardium in the Protopterus heart. The presence of D beta H and secretory vesicles in the subendocardial chromaffin cells of the atrium suggests a local production of catecholamines from dopamine in the heart of this dipnoan. PMID:7926645

  10. Cytoskeletal mechanics in pressure-overload cardiac hypertrophy

    Science.gov (United States)

    Tagawa, H.; Wang, N.; Narishige, T.; Ingber, D. E.; Zile, M. R.; Cooper, G. 4th

    1997-01-01

    We have shown that the cellular contractile dysfunction characteristic of pressure-overload cardiac hypertrophy results not from an abnormality intrinsic to the myofilament portion of the cardiocyte cytoskeleton but rather from an increased density of the microtubule component of the extramyofilament portion of the cardiocyte cytoskeleton. To determine how, in physical terms, this increased microtubule density mechanically overloads the contractile apparatus at the cellular level, we measured cytoskeletal stiffness and apparent viscosity in isolated cardiocytes via magnetic twisting cytometry, a technique by which magnetically induced force is applied directly to the cytoskeleton through integrin-coupled ferromagnetic beads coated with Arg-Gly-Asp (RGD) peptide. Measurements were made in two groups of cardiocytes from cats with right ventricular (RV) hypertrophy induced by pulmonary artery banding: (1) those from the pressure-overloaded RV and (2) those from the normally loaded same-animal control left ventricle (LV). Cytoskeletal stiffness increased almost twofold, from 8.53 +/- 0.77 dyne/cm2 in the normally loaded LV cardiocytes to 16.46 +/- 1.32 dyne/cm2 in the hypertrophied RV cardiocytes. Cytoskeletal apparent viscosity increased almost fourfold, from 20.97 +/- 1.92 poise in the normally loaded LV cardiocytes to 87.85 +/- 6.95 poise in the hypertrophied RV cardiocytes. In addition to these baseline data showing differing stiffness and, especially, apparent viscosity in the two groups of cardiocytes, microtubule depolymerization by colchicine was found to return both the stiffness and the apparent viscosity of the pressure overload-hypertrophied RV cells fully to normal. Conversely, microtubule hyperpolymerization by taxol increased the stiffness and apparent viscosity values of normally loaded LV cardiocytes to the abnormal values given above for pressure-hypertrophied RV cardiocytes. Thus, increased microtubule density constitutes primarily a viscous load on

  11. Greater hypertrophy in right than left ventricles is associated with pulmonary vasculopathy in sinoaortic-denervated Wistar-Kyoto rats

    Institute of Scientific and Technical Information of China (English)

    Miao CY; Cai GJ; Tao X; Xie HH; Su DF

    2005-01-01

    1. Biventricular hypertrophy has been described in a high blood pressure variability (BPV) model of sinoaortic-denervated (SAD) rats without systemic hypertension. To explore the possible involvement of the lung in SAD-induced right ventricular hypertrophy (RVH), we examined lung morphology, in addition to systemic haemodynamics and ventricle morphology, in Wistar-Kyoto rats 32 weeks after SAD. 2. In Wistar-Kyoto rats 32 weeks after SAD, there existed a substantial elevation in BPV, with no change in the average level of arterial pressure. Biventricular hypertrophy following SAD was characterized by a greater hypertrophy in right than left ventricles; both absolute and normalized right ventricular weights were significantly increased by 22 and 27%, respectively, and only normalized left ventricular weight was significantly increased by 12%. No infarcts were found in any ventricles examined. 3. In the lung, the most prominent change following SAD was pulmonary vasculopathy, including wall thickening, perivascular fibrosis and cell infiltration. In pulmonary arteries with an internal diameter of 70-130 microm, the external diameter, wall thickness and wall thickness to internal diameter ratio were increased in SAD compared with control rats. 4. There was no correlation between right and left ventricular weights. In contrast with BPV-correlated left ventricular weight, right ventricular weight was correlated with the wall thickness of the pulmonary artery, but not with BPV. 5. These findings suggest that greater RVH following SAD is associated with pulmonary vasculopathy, but is not secondary to the left ventricular problems or high BPV.

  12. 高同型半胱氨酸对高血压大鼠心肌细胞GRP78和CHOP表达及左室肥厚的影响%Influences of hyperhomocysteine on expressions of myocardial GRP78 and CHOP and left ventricular ;hypertrophy in hypertensive rats

    Institute of Scientific and Technical Information of China (English)

    张志敏; 赵连友; 卢凡; 邹青; 李雪; 丁璐; 卫聪颖

    2014-01-01

    Objective To observe the influences of hyperhomocysteine (Hcy) on expressions of myocardial GRP78 and CHOP (relative factors to endoplasmic reticulum stress, ERS), and discuss the relationship between Hcy and left ventricular hypertrophy. Methods The rat model of hypertension was established by using abdominal aortic coarctation and after 2 w, caudal artery pressure was detected with non-invasive caudal artery piezometer and 40 hypertensive rats were randomly divided into control group and homomethionine group (Hmn group, each n=20). Control group was given normal diet and Hmn group was given diet with 2%methionine. According to feeding time after grouping, the two groups were further divided into 4-w Hmn or control subgroups and 8-w Hmn or control subgroups respectively (each n=10). The level of SBP was detected by using non-invasive caudal artery piezometer, concentreation of plasma Hcy was detected by using Hcy detector, and heart weight index (HWI) and left ventricular weight index (LVWI) were calculated after weighing body weight, heart weight and left ventricular weight. The changes of cardiomyocyte morphology were observed after HE staining, and expressions of GRP78 and CHOP were detected by using immunohistochemistry technique. Results ①Hcy level did not increased in control group and increased gradually in Hmn group, and was significantly higher in Hmn group than that in control group (P0.05). The comparison between 8-w Hmn or control subgroups showed that SBP was significantly higher in 8-w Hmn group than that in 8-w control group (P<0.05). ③HWI and LVWI increased significantly in 4-w and 8-w Hmn or control subgroups, which was more significant in 4-w and 8-w Hmn subgroups (P<0.05). ④The expression of GRP78 was significantly higher in Hmn group than that in control group (P<0.05) on the 4th w, and expression of CHOP was much significantly higher in Hmn group than that in control group (P<0.05) on the 8th w. Conclusion Higher level of serum Hcy can

  13. Mitochondria-Targeted Antioxidant Prevents Cardiac Dysfunction Induced by Tafazzin Gene Knockdown in Cardiac Myocytes

    Directory of Open Access Journals (Sweden)

    Quan He

    2014-01-01

    Full Text Available Tafazzin, a mitochondrial acyltransferase, plays an important role in cardiolipin side chain remodeling. Previous studies have shown that dysfunction of tafazzin reduces cardiolipin content, impairs mitochondrial function, and causes dilated cardiomyopathy in Barth syndrome. Reactive oxygen species (ROS have been implicated in the development of cardiomyopathy and are also the obligated byproducts of mitochondria. We hypothesized that tafazzin knockdown increases ROS production from mitochondria, and a mitochondria-targeted antioxidant prevents tafazzin knockdown induced mitochondrial and cardiac dysfunction. We employed cardiac myocytes transduced with an adenovirus containing tafazzin shRNA as a model to investigate the effects of the mitochondrial antioxidant, mito-Tempo. Knocking down tafazzin decreased steady state levels of cardiolipin and increased mitochondrial ROS. Treatment of cardiac myocytes with mito-Tempo normalized tafazzin knockdown enhanced mitochondrial ROS production and cellular ATP decline. Mito-Tempo also significantly abrogated tafazzin knockdown induced cardiac hypertrophy, contractile dysfunction, and cell death. We conclude that mitochondria-targeted antioxidant prevents cardiac dysfunction induced by tafazzin gene knockdown in cardiac myocytes and suggest mito-Tempo as a potential therapeutic for Barth syndrome and other dilated cardiomyopathies resulting from mitochondrial oxidative stress.

  14. 厄贝沙坦氢氯噻嗪对高血压患者血压变异性和左心室肥厚的影响%Effect of irbesartan and hydrochlorothiazide on blood pressure variability and left ventricular hypertrophy in patients with essential hypertension

    Institute of Scientific and Technical Information of China (English)

    荆忱; 李洁; 傅涛; 陈杰; 陈宏

    2014-01-01

    目的 观察厄贝沙坦氢氯噻嗪对原发性高血压患者血压变异性和左心室肥厚的影响.方法 选择2009年12月至2011年12月空军航空医学研究所附属医院门诊及住院治疗的92例原发性高血压患者,口服厄贝沙坦氢氯噻嗪(每片含厄贝沙坦150 mg及氢氯噻嗪12.5 mg),1片/次,1次/d,共 8周,比较治疗前后血压、血压变异性,以收缩压、舒张压标准差(SD)表示血压变异性,24 h 收缩压、24 h 舒张压变异(24 h 收缩压变异、24 h 舒张压变异)及左心室质量的变化.结果治疗前、后24 h 收缩压变异分别为(14.8±3.6)、(9.7±2.8) mmHg(1 mmHg=0.133 kPa),24 h 舒张压变异分别为(12.9±3.1)、(8.6±2.4)mmHg,治疗后24 h收缩压变异、24 h 舒张压变异较治疗前降低,差异有统计学意义(P<0.05);治疗前左心室质量为(242±40)g,治疗后为(223±20)g,左心室质量较治疗前下降,差异有统计学意义(P<0.05).结论 厄贝沙坦氢氯噻嗪在稳定降压的同时可降低血压变异性,改善心室重构.%Objective To observe the effect of irbesartan hydrochlorothiazide tablet on variability of blood pressure and left ventricular hypertrophy in the patients with light and midrange hypertension. Methods Before the therapeutic course with irbesartan hydrochlorothiazide tablet, oral drugs were stopped in all 92 patients with hypertension for two weeks. Variability of blood pressure and left ventricular mass(LVM) with dynamic 24- hour blood pressure and echocardiography were observed in these patients before and therapeutic course. Results After treatment with oral administration of irbesartan hydrochlorothiazide tablet for 8 weeks, 24 h average systolic blood pressure (SPB) [(151±11)mmHg(1 mmHg=0.133 kPa)vs (126±10)mmHg] and 24 h SPB variability[(14.8±3.6)mmHg vs (9.7±2.8) mmHg], 24 h average diastolic blood pressure (DBP) [(96±8)mmHg vs (74±7)mmHg]and 24 h DBP variation[(12.9±3.1)mmHg vs (8.6±2.4)mmHg] were significantly decreased(P<0

  15. Platelet-derived growth factor receptor-β in myocyte was upregulated by angiotensin II

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    To observe the regulation of platelet-derived growth factor (PDGF) receptor-βin myocyte stimulated by angiotensin II (AngII) at both integrated and cellular levels and reveal the signal transduction mechanism in cell, two kidneys, one clip (2K1C) renal hypertension were performed by placing a sliver clip around the left renal artery. Blood pressure and the ratio of left ventricular weight to body weight were measured at 4 and 8 weeks after operation. The content of AngII in heart was detected by radioimmunology assay; the protein level of PDGF receptor-βin heart was measured by Western blot analysis. The alteration of PDGF receptor-βstimulated by AngII and several inhibitors was observed on cultured neonatal rat ventricular myocyte (NRVM). The content of AngII in heart of 2K1C renal hypertensive rat at 4 and 8 weeks after operation was increased. Compared with sham group, 4 and 8 weeks after operation, PDGF receptor-βin heart of 2K1C group was upregulated by 100.3% and 127.1% (P < 0.05), respectively. This upregulation could be inhibited by captopril. For cultured myocyte, PDGF receptor-βwas increased by 47.1% after being stimulated by AngII and this upregulation could be inhibited by losartan which was an inhibitor of AT1 receptor. PLC inhibitor (U73122) and MEK inhibitor (PD98059) could partly inhibit PDGF receptor-βupregulation induced by AngII. These results suggested that AngII could upregulate PDGF receptor-βin myocyte by its AT1 receptor and this effect was at least partly dependent on PLC and extracellular signal-regulated kinase (ERK).

  16. Insulin improves cardiac myocytes contractile function recovery in simulated ischemia-reperfusion: Key role of Akt

    Institute of Scientific and Technical Information of China (English)

    ZHANG Bo; ZHANG Haifeng; FAN Qian; MA Xinliang; GAO Feng

    2003-01-01

    The present study examined cardiac myocyte contractile and Ca2+ transient responses to insulin during simulated ischemia/reperfusion (I/R) and furtherinvestigated the role of protein kinase B (Akt) in the insulin- induced inotropic effect. Ventricular myocytes were enzymatically isolated from adult Sprague-Dawley rats and perfused with Tyrode solution while electrically field-stimulated. Simulated I/R was induced by perfusing the cells with chemical anoxic solution including sodium cyanide-sodium lactate for 15 min followed by reperfusion with normal oxygenated Tyrode solution with or without insulin. It is found that insulin only at concentration as high as 10 IU/L could increase cell shortening (16±5%, P < 0.05) in normal myocytes, whereas it concentration-dependently (0.01-10 IU/L) increased the contraction,the velocity of shortening/releng- theningand Ca2+ transient in I/R myocytes. In addition, insulin treatment (1 IU/L) increased Akt phosphorylation of I/R cardiomyocytes by 2.4-fold compared with that of the control (P < 0.01). Most importantly, pretreatment with LY 294002, a specific inhibitor of phosphatidylinositol 3′-kinase (PI3-kinase), significantly inhibited both Akt phosphorylation and the positive inotropic response to insulin in the I/R cardiomyocytes. These results suggest that insulin exerts direct positive inotropic effect by increasing Ca2+ transient of cardiomyocytes, which is enhanced in the pathological condition of I/R. Akt activation plays an important role in the insulin-induced improvement of myocyte contractile function following I/R.

  17. Abrogation of Nrf2 impairs antioxidant signaling and promotes atrial hypertrophy in response to high-intensity exercise stress

    OpenAIRE

    Kumar, Radhakrishnan Rajesh; Narasimhan, Madhusudhanan; Shanmugam, Gobinath; Hong, Jennifer; Devarajan, Asokan; Palaniappan, Sethu; Zhang, Jianhua; Halade, Ganesh V; Darley-Usmar, Victor M.; Hoidal, John R.; Rajasekaran, Namakkal S.

    2016-01-01

    Background Anomalies in myocardial structure involving myocyte growth, hypertrophy, differentiation, apoptosis, necrosis etc. affects its function and render cardiac tissue more vulnerable to the development of heart failure. Although oxidative stress has a well-established role in cardiac remodeling and dysfunction, the mechanisms linking redox state to atrial cardiomyocyte hypertrophic changes are poorly understood. Here, we investigated the role of nuclear erythroid-2 like factor-2 (Nrf2),...

  18. Ubiquitin-Specific Protease 4 Is an Endogenous Negative Regulator of Pathological Cardiac Hypertrophy.

    Science.gov (United States)

    He, Ben; Zhao, Yi-Chao; Gao, Ling-Chen; Ying, Xiao-Ying; Xu, Long-Wei; Su, Yuan-Yuan; Ji, Qing-Qi; Lin, Nan; Pu, Jun

    2016-06-01

    Dysregulation of the ubiquitin proteasome system components ubiquitin ligases and proteasome plays an important role in the pathogenesis of cardiac hypertrophy. However, little is known about the role of another ubiquitin proteasome system component, the deubiquitinating enzymes, in cardiac hypertrophy. Here, we revealed a crucial role of ubiquitin specific protease 4 (USP4), a deubiquitinating enzyme prominently expressed in the heart, in attenuating pathological cardiac hypertrophy and dysfunction. USP4 levels were consistently decreased in human failing hearts and in murine hypertrophied hearts. Adenovirus-mediated gain- and loss-of-function approaches indicated that deficiency of endogenous USP4 promoted myocyte hypertrophy induced by angiotensin II in vitro, whereas restoration of USP4 significantly attenuated the prohypertrophic effect of angiotensin II. To corroborate the role of USP4 in vivo, we generated USP4 global knockout mice and mice with cardiac-specific overexpression of USP4. Consistent with the in vitro study, USP4 depletion exacerbated the hypertrophic phenotype and cardiac dysfunction in mice subjected to pressure overload, whereas USP4 transgenic mice presented ameliorated pathological cardiac hypertrophy compared with their control littermates. Molecular analysis revealed that USP4 deficiency augmented the activation of the transforming growth factor β-activated kinase 1 (TAK1)-(JNK1/2)/P38 signaling in response to hypertrophic stress, and blockage of TAK1 activation abolished the pathological effects of USP4 deficiency in vivo. These findings provide the first evidence for the involvement of USP4 in cardiac hypertrophy, and shed light on the therapeutic potential of targeting USP4 in the treatment of cardiac hypertrophy.

  19. Genetic and clinical profile of Indian patients of idiopathic restrictive cardiomyopathy with and without hypertrophy

    DEFF Research Database (Denmark)

    Rai, Taranjit Singh; Ahmad, Shamim; Ahluwalia, Tarun Veer Singh;

    2009-01-01

    Both idiopathic restrictive cardiomyopathy (IRCM) and hypertrophic cardiomyopathy (HCM) are part of the same disease spectrum and are due to sarcomeric gene mutations. A patient with restrictive physiology without left ventricular hypertrophy (LVH) would be diagnosed as IRCM, while one with LVH...

  20. 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.

  1. 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.

  2. Left ventricular muscle mass regression after aortic valve replacement.

    OpenAIRE

    Lee, J. W.; Choi, K. J.; Lee, S G; Choo, S. J.; Kim, J.O.; Kang, D H; Song, J.K.; Song, M. G.

    1999-01-01

    Implanting a valve that will reduce left ventricular mass is critical in aortic stenosis. Regression of left ventricular hypertrophy in 46 aortic valve replacement (AVR) patients receiving a St. Jude Medical (SJM) valve was assessed by serial electrocardiographic and echocardiographic studies during the preoperative, immediate, and late postoperative periods. The patients were divided into three groups according to valve size; 19 mm group (n=9), 21 mm group (n=20), and 23+mm group (n=17). The...

  3. Calcium handling by vascular myocytes in hypertension

    Directory of Open Access Journals (Sweden)

    R.C.A. Tostes

    1997-03-01

    Full Text Available Calcium ions (Ca2+ trigger the contraction of vascular myocytes and the level of free intracellular Ca2+ within the myocyte is precisely regulated by sequestration and extrusion mechanisms. Extensive evidence indicates that a defect in the regulation of intracellular Ca2+ plays a role in the augmented vascular reactivity characteristic of clinical and experimental hypertension. For example, arteries from spontaneously hypertensive rats (SHR have an increased contractile sensitivity to extracellular Ca2+ and intracellular Ca2+ levels are elevated in aortic smooth muscle cells of SHR. We hypothesize that these changes are due to an increase in membrane Ca2+ channel density and possibly function in vascular myocytes from hypertensive animals. Several observations using various experimental approaches support this hypothesis: 1 the contractile activity in response to depolarizing stimuli is increased in arteries from hypertensive animals demonstrating increased voltage-dependent Ca2+ channel activity in hypertension; 2 Ca2+ channel agonists such as Bay K 8644 produce contractions in isolated arterial segments from hypertensive rats and minimal contraction in those from normotensive rats; 3 intracellular Ca2+ concentration is abnormally increased in vascular myocytes from hypertensive animals following treatment with Ca2+ channel agonists and depolarizing interventions, and 4 using the voltage-clamp technique, the inward Ca2+ current in arterial myocytes from hypertensive rats is nearly twice as large as that from myocytes of normotensive rats. We suggest that an alteration in Ca2+ channel function and/or an increase in Ca2+ channel density, resulting from increased channel synthesis or reduced turnover, underlies the increased vascular reactivity characteristic of hypertension

  4. Metformin attenuates pressure overload-induced cardiac hypertrophy via AMPK activation

    Institute of Scientific and Technical Information of China (English)

    Yong-nan FU; Han XIAO; Xiao-wei MA; Sheng-yang JIANG; Ming XU; You-yi ZHANG

    2011-01-01

    Aim: To identify the role of metformin in cardiac hypertrophy and investigate the possible mechanism underlying this effect.Methods: Wild type and AMPKα2 knockout (AMPKα2-/-) littermates were subjected to left ventricular pressure overload caused by evaluated using echocardiography and anatomic and histological methods. The antihypertrophic mechanism of metformin was analyzed using Western blotting.Results: Metformin significantly attenuated cardiac hypertrophy induced by pressure overload in wild type mice, but the antihypertrophic actions of metformin were ablated in AMPKx2-/- mice. Furthermore, metformin suppressed the phosphorylation of Akt/protein kinase B (AKT) and mammalian target of rapamycin (mTOR) in response to pressure overload in wild type mice, but not in AMPKα2-/-mice.Conclusion: Long-term administration of metformin may attenuate cardiac hypertrophy induced by pressure overload in nondiabetic mice, and this attenuation is highly dependent on AMPK activation. These findings may provide a potential therapy for patients at risk of developing pathological cardiac hypertrophy.

  5. Myocardial hypertrophy after pulmonary regurgitation and valve implantation in pigs

    DEFF Research Database (Denmark)

    Smith, Julie; Goetze, Jens Peter; Søndergaard, Lars;

    2012-01-01

    BACKGROUND: Patients may suffer from right ventricular (RV) failure and malignant cardiac arrhythmias after late pulmonary valve replacement correcting pulmonary regurgitation (PR). But the underlying mechanisms of the refractory arrhythmias are not well understood. METHODS: The aim of present...... study was to characterize the RV myocardium after percutaneous pulmonary valve implantation (PPVI) in a porcine model after severe PR for 3months. RV histology was evaluated with morphometric methods and RV function was assessed with electrophysiology, echocardiography, and biochemical measures...... and plasma natriuretic peptides were unchanged. CONCLUSIONS: The RV does not completely recover after three months of PR with persistent myocardial hypertrophy one month after PPVI. Future studies should address whether RV chamber and cellular hypertrophy, without fibrosis or interventional scar tissue, may...

  6. BMP type I receptor ALK2 is required for angiotensin II-induced cardiac hypertrophy.

    Science.gov (United States)

    Shahid, Mohd; Spagnolli, Ester; Ernande, Laura; Thoonen, Robrecht; Kolodziej, Starsha A; Leyton, Patricio A; Cheng, Juan; Tainsh, Robert E T; Mayeur, Claire; Rhee, David K; Wu, Mei X; Scherrer-Crosbie, Marielle; Buys, Emmanuel S; Zapol, Warren M; Bloch, Kenneth D; Bloch, Donald B

    2016-04-15

    Bone morphogenetic protein (BMP) signaling contributes to the development of cardiac hypertrophy. However, the identity of the BMP type I receptor involved in cardiac hypertrophy and the underlying molecular mechanisms are poorly understood. By using quantitative PCR and immunoblotting, we demonstrated that BMP signaling increased during phenylephrine-induced hypertrophy in cultured neonatal rat cardiomyocytes (NRCs), as evidenced by increased phosphorylation of Smads 1 and 5 and induction of Id1 gene expression. Inhibition of BMP signaling with LDN193189 or noggin, and silencing of Smad 1 or 4 using small interfering RNA diminished the ability of phenylephrine to induce hypertrophy in NRCs. Conversely, activation of BMP signaling with BMP2 or BMP4 induced hypertrophy in NRCs. Luciferase reporter assay further showed that BMP2 or BMP4 treatment of NRCs repressed atrogin-1 gene expression concomitant with an increase in calcineurin protein levels and enhanced activity of nuclear factor of activated T cells, providing a mechanism by which BMP signaling contributes to cardiac hypertrophy. In a model of cardiac hypertrophy, C57BL/6 mice treated with angiotensin II (A2) had increased BMP signaling in the left ventricle. Treatment with LDN193189 attenuated A2-induced cardiac hypertrophy and collagen deposition in left ventricles. Cardiomyocyte-specific deletion of BMP type I receptor ALK2 (activin-like kinase 2), but not ALK1 or ALK3, inhibited BMP signaling and mitigated A2-induced cardiac hypertrophy and left ventricular fibrosis in mice. The results suggest that BMP signaling upregulates the calcineurin/nuclear factor of activated T cell pathway via BMP type I receptor ALK2, contributing to cardiac hypertrophy and fibrosis. PMID:26873969

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

    OpenAIRE

    Chhabra, Lovely

    2013-01-01

    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...

  8. MicroRNA-1 and-16 inhibit cardiomyocyte hypertrophy by targeting cyclins/Rb pathway

    Institute of Scientific and Technical Information of China (English)

    SHAN Zhi-xin; ZHU Jie-ning; TANG Chun-mei; ZHU Wen-si; LIN Qiu-xiong; HU Zhi-qin; FU Yong-heng; ZHANG Meng-zhen

    2016-01-01

    AIM:MicroRNAs ( miRNAs) were recognized to play significant roles in cardiac hypertrophy .But, it remains unknown whether cyclin/Rb pathway is modulated by miRNAs during cardiac hypertrophy .This study investigates the potential roles of microRNA-1 (miR-1) and microRNA-16 (miR-16) in modulating cyclin/Rb pathway during cardiomyocyte hypertrophy .METHODS:An animal model of hypertrophy was established in a rat with abdominal aortic constriction (AAC).In addition, a cell model of hypertrophy was also achieved based on PE-promoted neonatal rat ventricular cardiomyocyte .RESULTS:miR-1 and-16 expression were markedly de-creased in hypertrophic myocardium and hypertrophic cardiomyocytes in rats .Overexpression of miR-1 and -16 suppressed rat cardiac hypertrophy and hypertrophic phenotype of cultured cardiomyocytes .Expression of cyclins D1, D2 and E1, CDK6 and phosphorylated pRb was increased in hypertrophic myocardium and hypertrophic cardiomyocytes , but could be reversed by enforced expression of miR-1 and -16.CDK6 was validated to be modulated post-transcriptionally by miR-1, and cyclins D1, D2 and E1 were further validated to be modulated post-transcriptionally by miR-16.CONCLUSION: Attenuations of miR-1 and -16 provoke cardiomyocyte hypertrophy via derepressing the cyclins D1, D2, E1 and CDK6, and activating cyclin/Rb pathway.

  9. Simulation methods and validation criteria for modeling cardiac ventricular electrophysiology

    OpenAIRE

    Shankarjee Krishnamoorthi; Luigi E Perotti; Nils P Borgstrom; Ajijola, Olujimi A.; Anna Frid; Ponnaluri, Aditya V.; Weiss, James N.; Zhilin Qu; Klug, William S.; Ennis, Daniel B.; Alan Garfinkel

    2014-01-01

    © 2014 Krishnamoorthi et al. We describe a sequence of methods to produce a partial differential equation model of the electrical activation of the ventricles. In our framework, we incorporate the anatomy and cardiac microstructure obtained from magnetic resonance imaging and diffusion tensor imaging of a New Zealand White rabbit, the Purkinje structure and the Purkinje-muscle junctions, and an electrophysiologically accurate model of the ventricular myocytes and tissue, which includes transm...

  10. A simple nomogram for determination of echocardiographic left ventricular geometry

    NARCIS (Netherlands)

    Heesen, WF; Beltman, FW; Smit, AJ; May, JF

    1998-01-01

    Recent data have shown that left ventricular (I.V) geometry provides additional information on the simple dichotomy of presence or absence of LV hypertrophy with regard to cardiovascular risk of hypertensive patients. A "new" class of concentric remodeling was created, identifying a rather large gro

  11. Regulation of Cardiac Hypertrophy: the nuclear option

    OpenAIRE

    Kuster, Diederik

    2011-01-01

    textabstractCardiac hypertrophy is the response of the heart to an increased workload. After myocardial infarction (MI) the surviving muscle tissue has to work harder to maintain cardiac output. This sustained increase in workload leads to cardiac hypertrophy. Despite its apparent appropriateness, cardiac hypertrophy is an independent risk factor for the development of heart failure and is therefore called pathological hypertrophy. That hypertrophy is not bad per se, is illustrated by the hyp...

  12. Kshara application for turbinate hypertrophy

    OpenAIRE

    Kotrannavar, Vijay Kumar S.; Angadi, Savita S.

    2013-01-01

    Nasapratinaha (nasal obstruction) is a commonly encountered disease in clinical practice. It is one of the nasal disorders, explained in Ayurveda, having nasal obstruction leading to difficulty in breathing as the main cardinal feature. In contemporary science, this condition can be correlated with various diseases such as turbinate hypertrophy, deviated nasal septum, nasal mass, mucosal congestion, allergic rhinitis, and others; among which turbinate hypertrophy is a common cause. Turbinate ...

  13. Kshara application for turbinate hypertrophy.

    Science.gov (United States)

    Kotrannavar, Vijay Kumar S; Angadi, Savita S

    2013-10-01

    Nasapratinaha (nasal obstruction) is a commonly encountered disease in clinical practice. It is one of the nasal disorders, explained in Ayurveda, having nasal obstruction leading to difficulty in breathing as the main cardinal feature. In contemporary science, this condition can be correlated with various diseases such as turbinate hypertrophy, deviated nasal septum, nasal mass, mucosal congestion, allergic rhinitis, and others; among which turbinate hypertrophy is a common cause. Turbinate hypertrophy can be treated with surgical and medical methods. The medical treatment has limitation for prolonged use because of health purpose, surgical approaches too have failed to achieve desired results in turbinate hypertrophy due to complications and high recurrence rate. The medical and surgical managements have their own limitations, merits, and demerits like synechiae formation, rhinitis sicca, severe bleeding, or osteonecrosis of the turbinate bone A parasurgical treatment explained in Ayurveda, known as kshara pratisarana, which is a minimal invasive and precise procedure for this ailment, tried to overcome this problem. 'Kshara Karma' is a popular treatment modality in Ayurveda, which has been advocated in disorders of nose like arbuda (tumor) and adhimamsa (muscular growth). Clinical observation has shown its effectiveness in the management of turbinate hypertrophy. A case report of 45-year-old male who presented with complaints of frequent nasal obstruction, nasal discharge, discomfort in nose, and headache; and diagnosed as turbinate hypertrophy has been presented here. The patient was treated with one application of Kshara over the turbinates. The treatment was effective and no recurrence was noticed in the follow up. PMID:24459392

  14. Physiological and pathological cardiac hypertrophy.

    Science.gov (United States)

    Shimizu, Ippei; Minamino, Tohru

    2016-08-01

    The heart must continuously pump blood to supply the body with oxygen and nutrients. To maintain the high energy consumption required by this role, the heart is equipped with multiple complex biological systems that allow adaptation to changes of systemic demand. The processes of growth (hypertrophy), angiogenesis, and metabolic plasticity are critically involved in maintenance of cardiac homeostasis. Cardiac hypertrophy is classified as physiological when it is associated with normal cardiac function or as pathological when associated with cardiac dysfunction. Physiological hypertrophy of the heart occurs in response to normal growth of children or during pregnancy, as well as in athletes. In contrast, pathological hypertrophy is induced by factors such as prolonged and abnormal hemodynamic stress, due to hypertension, myocardial infarction etc. Pathological hypertrophy is associated with fibrosis, capillary rarefaction, increased production of pro-inflammatory cytokines, and cellular dysfunction (impairment of signaling, suppression of autophagy, and abnormal cardiomyocyte/non-cardiomyocyte interactions), as well as undesirable epigenetic changes, with these complex responses leading to maladaptive cardiac remodeling and heart failure. This review describes the key molecules and cellular responses involved in physiological/pathological cardiac hypertrophy. PMID:27262674

  15. Cardiac hypertrophy and failure--a disease of adaptation. Modifications in membrane proteins provide a molecular basis for arrhythmogenicity.

    Science.gov (United States)

    Moalic, J M; Charlemagne, D; Mansier, P; Chevalier, B; Swynghedauw, B

    1993-05-01

    Cardiac hypertrophy is the physiological adaptation of the heart to chronic mechanical overload. Cardiac failure indicates the limits of the process. Cardiac hypertrophy is only one example of biological adaptation and results from the induction of several changes in gene expression, mostly of the fetal type, including those coding for the myosin heavy chain or the alpha-subunit of the Na+,K(+)-ATPase. From a thermodynamic point of view, the decrease in Vmax allows the heart to produce a normal tension at a lower cost. This process results from changes both in the sarcomere and in the expression of certain membrane proteins. The decrease in calcium transient is determined by several changes in membrane proteins that result in a rather fragile equilibrium in terms of calcium homeostasis. Any abnormal input in calcium will have exaggerated detrimental consequences on a hypertrophied myocyte and may cause automaticity and arrhythmias or an exaggerated response to anoxia in terms of compliance. PMID:8485830

  16. Effects of pressure- or volume-overload hypertrophy on passive stiffness in isolated adult cardiac muscle cells

    Science.gov (United States)

    Kato, S.; Koide, M.; Cooper, G. 4th; Zile, M. R.

    1996-01-01

    It has been hypothesized that the changes in myocardial stiffness induced by chronic hemodynamic overloading are dependent on changes in the passive stiffness of the cardiac muscle cell (cardiocyte). However, no previous studies have examined the passive constitutive properties of cardiocytes isolated from animals with myocardial hypertrophy. Accordingly, changes in relative passive stiffness of cardiocytes isolated from animals with chronic pressure- or volume-overload hypertrophy were determined by examining the effects of anisosmotic stress on cardiocyte size. Anisosmotic stress was produced by altering superfusate osmolarity. Hypertrophied cardiocytes were enzymatically isolated from 16 adult cats with right ventricular (RV) pressure-overload hypertrophy induced by pulmonary artery banding (PAB) and from 6 adult cats with RV volume-overload hypertrophy induced by creating an atrial septal defect (ASD). Left ventricular (LV) cardiocytes from each cat served as nonhypertrophied, normally loaded, same-animal controls. Superfusate osmolarity was decreased from 305 +/- 3 to 135 +/- 5 mosM and increased to 645 +/- 4 mosM. During anisosmotic stress, there were no significant differences between hypertrophied RV and normal LV cardiocytes in pressure overload PAB cats with respect to percent change in cardiocyte area (47 +/- 2% in RV vs. 48 +/- 2% in LV), diameter (46 +/- 3% in RV vs. 48 +/- 2% in LV), or length (2.4 +/- 0.2% in RV vs. 2.0 +/- 0.3% in LV), or sarcomere length (1.5 +/- 0.1% in RV vs. 1.3 +/- 0.3% in LV). Likewise, there were no significant differences in cardiocyte strain between hypertrophied RV and normal LV cardiocytes from ASD cats. In conclusion, chronic pressure-overload hypertrophy and chronic volume-overload hypertrophy did not alter the cardiocyte response to anisosmotic stress. Thus chronic overload hypertrophy did not alter relative passive cardiocyte stiffness.

  17. Ca(2+ release events in cardiac myocytes up close: insights from fast confocal imaging.

    Directory of Open Access Journals (Sweden)

    Vyacheslav M Shkryl

    Full Text Available The spatio-temporal properties of Ca(2+ transients during excitation-contraction coupling and elementary Ca(2+ release events (Ca(2+ sparks were studied in atrial and ventricular myocytes with ultra-fast confocal microscopy using a Zeiss LSM 5 LIVE system that allows sampling rates of up to 60 kHz. Ca(2+ sparks which originated from subsarcolemmal junctional sarcoplasmic reticulum (j-SR release sites in atrial myocytes were anisotropic and elongated in the longitudinal direction of the cell. Ca(2+ sparks in atrial cells originating from non-junctional SR and in ventricular myocytes were symmetrical. Ca(2+ spark recording in line scan mode at 40,000 lines/s uncovered step-like increases of [Ca(2+]i. 2-D imaging of Ca(2+ transients revealed an asynchronous activation of release sites and allowed the sequential recording of Ca(2+ entry through surface membrane Ca(2+ channels and subsequent activation of Ca(2+-induced Ca(2+ release. With a latency of 2.5 ms after application of an electrical stimulus, Ca(2+ entry could be detected that was followed by SR Ca(2+ release after an additional 3 ms delay. Maximum Ca(2+ release was observed 4 ms after the beginning of release. The timing of Ca(2+ entry and release was confirmed by simultaneous [Ca(2+]i and membrane current measurements using the whole cell voltage-clamp technique. In atrial cells activation of discrete individual release sites of the j-SR led to spatially restricted Ca(2+ release events that fused into a peripheral ring of elevated [Ca(2+]i that subsequently propagated in a wave-like fashion towards the center of the cell. In ventricular myocytes asynchronous Ca(2+ release signals from discrete sites with no preferential subcellular location preceded the whole-cell Ca(2+ transient. In summary, ultra-fast confocal imaging allows investigation of Ca(2+ signals with a time resolution similar to patch clamp technique, however in a less invasive fashion.

  18. EGCG inhibits cardiomyocyte apoptosis in pressure overload-induced cardiac hypertrophy and protects cardiomyocytes from oxidative stress in rats

    Institute of Scientific and Technical Information of China (English)

    Rui SHENG; Zhen-lun GU; Mei-lin XIE; Wen-xuan ZHOU; Ci-yi GUO

    2007-01-01

    Aim: To investigate the effects of epigallocatechin gallate (EGCG) on pressure overload and hydrogen peroxide (H2O2) induced cardiac myocyte apoptosis. Methods: Cardiac hypertrophy was established in rats by abdominal aortic constriction. EGCG 25, 50 and 100 mg/kg were administered intragastrically (ig). Cultured newborn rat cardiomyocytes were preincubated with EGCG, and oxidative stress injury was induced by H2O2. Results: In cardiac hypertrophy induced by AC in rats, relative to the model group, EGCG 25, 50 and 100 mg/kg ig for 6weeks dose-dependently reduced systolic blood pressure (SBP) and heart weight indices, decreased malondialdehyde (MDA) content, and increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activity, both in serum and in the myocardium. Also, treatment with EGCG 50 and 100 mg/kg markedly improved cardiac structure and inhibited fibrosis in HE and van Gieson (VG) stain, and reduced apoptotic myocytes in the hypertrophic myocardium detected by terminal transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay. Inthe Western blot analysis, EGCG significantly inhibited pressure overload-inducedp53 increase and bcl-2 decrease. In H2O2-induced cardiomyocyte injury, when preincubated with myocytes for 6-48 h, EGCG 12.5-200 mg/L increased cell viability determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay. EGCG also attenuated H2O2-induced lactate dehydrogenase (LDH) release and MDA formation. Meanwhile, EGCG 50 and 100 mg/L significantly inhibited the cardiomyocyte apoptotic rate in flow cytometry. Conclusion: EGCG inhibits cardiac myocyte apoptosis and oxidative stress in pressure overload in-duced cardiac hypertrophy. Also, EGCG prevented cardiomyocyte apoptosis from oxidative stress in vitro. The mechanism might be related to the inhibitory effects of EGCG on p53 induction and bcl-2 decrease.

  19. Effects of left ventricular hypertrophy on prognosis of kidney in patients with chronic kidney disease of stages 3~4%慢性肾脏病3~4期患者左心室肥厚对肾脏预后的影响

    Institute of Scientific and Technical Information of China (English)

    肖晓芬; 王小琴; 韩四萍

    2016-01-01

    目的 了解慢性肾脏病(chronic kidney disease,CKD) 3~4期患者左心室肥厚(left ventricular hypertrophy,LVH)的发生情况,并探讨其对肾脏预后的影响.方法 选择2012年2月至2016年2月在湖北省中医院肾病内科门诊随访的CKD 3~4期患者61例进行基线访视记录,了解LVH的发生情况并进行规律随访,记录终点事件包括血肌酐(SCr)水平翻倍、估算肾小球滤过率(estimated glomerular filtration rate,eGFR)<15 ml·min-1 ·(1.73 m2)-1或下降大于50%、行肾脏替代治疗及死亡.将进入终点事件定义为肾功能进展组,截尾事件定义为肾功能平稳组,将2组各项指标进行比较,并运用COX风险回归模型对影响肾脏预后的相关因素进行分析.结果61例CKD 3~4期患者平均随访时间为(34.70±9.54)个月,其中1例脱落,22例患者进入终点,包括12例SCr水平翻倍/eGFR下降大于50%或<15 ml·min-1 ·(1.73 m2)-1,8例进入维持性血液透析治疗,2例死亡.CKD 3~4期患者左心室扩大、LVH、左心室舒张功能减退的比例分别为22.95%、37.70%、60.66%.肾功能进展组与肾功能平稳组比较,在收缩压、SCr、eGFR、室间隔厚度、左室舒张末期内径、左心室质量(left ventricular mass,LVM)、左心室质量指数(left ventricular mass index,LVMI)、左心室扩大比例及LVH比例方面,差异有统计学意义(P<0.05).COX回归分析单因素分析:收缩压(P=0.013)、LVM(P=0.003)、LVMI(P=0.001)、LVH (P<0.001)、左心室扩大(P=0.009)是影响CKD 3~4期患者肾脏进展的危险因素;多因素分析:收缩压(偏回归系数b=1.075,HR=2.931,P=0.025)、LVH(偏回归系数b=1.319,HR=3.740,P=0.048)进入回归方程.结论 LVH在CKD 3~4期患者中已普遍存在,尽早对CKD 3~4期患者血压、左心室结构异常进行干预和控制,对延缓病程进展,改善肾脏预后有重要意义.

  20. Calcium binding to cardiac myocytes protected from proteolytic enzyme activity.

    Science.gov (United States)

    Bailey, L E; Fawzi, A B

    1985-04-17

    Excitation-contraction coupling in cardiac muscle is dependent on extracellular calcium and calcium bound to the surface of the myocardial cell. In this study, we examined the physical characteristics of calcium binding to adult guinea pig ventricular myocytes disaggregated mechanically in oxygenated tissue culture medium containing a proteinase inhibitor (aprotinin), and separated from cellular debris by Cytodex beads. Cells prepared in this manner excluded Trypan blue and showed no evidence of spontaneous contraction or contracture. Scatchard plots of calcium binding determined by continuous flow equilibrium dialysis revealed a high-affinity, low-capacity pool, Ka = 65 X 10(3) M-1 and Bt = 1.3 nmol X mg-1 and a low-affinity, high-capacity pool, Ka = 141 M-1 and Bt = 138 nmol X mg-1. The low-affinity pool was not detectable after lanthanum, trypsin or collagenase treatment or in cells prepared without aprotinin in the isolation medium. Both neuraminidase and phospholipase C reduced Bt of the low-affinity pool by one half, but only neuraminidase affected the affinity constant of this pool. Ka was increased to 516.7 M-1, similar to the apparent affinity constant for calcium binding estimated from dP/dtmax measured at several extracellular calcium concentrations (470 M-1). The results suggest that calcium bound to sarcolemmal phospholipids represents the superficial calcium involved in excitation-contraction coupling in the heart.

  1. Left Ventricular Noncompaction: A Distinct Genetic Cardiomyopathy?

    Science.gov (United States)

    Arbustini, Eloisa; Favalli, Valentina; Narula, Nupoor; Serio, Alessandra; Grasso, Maurizia

    2016-08-30

    Left ventricular noncompaction (LVNC) describes a ventricular wall anatomy characterized by prominent left ventricular (LV) trabeculae, a thin compacted layer, and deep intertrabecular recesses. Individual variability is extreme, and trabeculae represent a sort of individual "cardioprinting." By itself, the diagnosis of LVNC does not coincide with that of a "cardiomyopathy" because it can be observed in healthy subjects with normal LV size and function, and it can be acquired and is reversible. Rarely, LVNC is intrinsically part of a cardiomyopathy; the paradigmatic examples are infantile tafazzinopathies. When associated with LV dilation and dysfunction, hypertrophy, or congenital heart disease, the genetic cause may overlap. The prevalence of LVNC in healthy athletes, its possible reversibility, and increasing diagnosis in healthy subjects suggests cautious use of the term LVNC cardiomyopathy, which describes the morphology but not the functional profile of the cardiomyopathy. PMID:27561770

  2. The effects of compensated cardiac hypertrophy on dihydropyridine and ryanodine receptors in rat, ferret and guinea-pig hearts.

    Science.gov (United States)

    Rannou, F; Sainte-Beuve, C; Oliviero, P; Do, E; Trouvé, P; Charlemagne, D

    1995-05-01

    The number of dihydropyridine and ryanodine receptors (DHP-R and RyR) has been measured in control and hypertrophied ventricles from rats, guinea pigs and ferrets to determine whether these two channels contribute to the alterations in excitation-contraction coupling (ECC), and in Ca2+ transient during compensated cardiac hypertrophy. We found that ventricular hypertrophy did not change the density of DHP-R. Mild hypertrophy did not alter the density of RyR in the rat but decreased it in the guinea-pig and in the ferret (30% and 36%, respectively). Severe hypertrophy decreased the density of RyR by 20% in the rat and by 34% in the guinea-pig. Therefore, the decrease is greater in ferret and guinea-pig hearts than in rat heart. We conclude that the sarcoplasmic reticulum (SR) Ca2+ release channels but not the L-type Ca2+ channels could contribute to the slowing of intracellular Ca2+ movements and to the reduced velocity of shortening of the hypertrophied hearts. We suggest that, in the guinea pig and ferret hearts which express only the beta myosin heavy chain (MHC) isoform, the reduced velocity of shortening during hypertrophy is related to the decrease in RyR density, whereas in the rat, it is regulated primarily via a shift in the MHC isoform, except in severe hypertrophy in which the moderate decrease in RyR would also be involved. PMID:7473781

  3. Temperature dependence of intracellular free calcium in cardiac myocytes from rat and ground squirrel measured by confocal microscopy

    Institute of Scientific and Technical Information of China (English)

    王世强; 周曾铨; 钱洪

    1999-01-01

    The temperature-dependence of infraeeliular free caleimn (Ca) was investigated in mdo-1 loaded ventricular myocytes from the ral, a non-hibernator, and from the ground squirrel, a hibernator. The dissociation constant of indo-l at different temperatures was calibrated both al pll-tat and at @-stat . and the result demonstrated that the @-stat ralibration should be prettrred . Analysis of the fluoreseent image showed a striking increase of Ca2 as well as spontaneous caleiuni waves in ral cells, indicating an overloaded cakuum. In contrast, cardiac myocytes of the ground sqnirraf were found to keep a constant (Ca2+) without caleium overload regardless of temperature variation. It is be-lieved that understanding of the mechanisms underlying the interccllular caleima homeostasis of hibrernators may lead to solutions of some medical questions .

  4. Kshara application for turbinate hypertrophy

    Directory of Open Access Journals (Sweden)

    Vijay Kumar S Kotrannavar

    2013-01-01

    Full Text Available Nasapratinaha (nasal obstruction is a commonly encountered disease in clinical practice. It is one of the nasal disorders, explained in Ayurveda, having nasal obstruction leading to difficulty in breathing as the main cardinal feature. In contemporary science, this condition can be correlated with various diseases such as turbinate hypertrophy, deviated nasal septum, nasal mass, mucosal congestion, allergic rhinitis, and others; among which turbinate hypertrophy is a common cause. Turbinate hypertrophy can be treated with surgical and medical methods. The medical treatment has limitation for prolonged use because of health purpose, surgical approaches too have failed to achieve desired results in turbinate hypertrophy due to complications and high recurrence rate. The medical and surgical managements have their own limitations, merits, and demerits like synechiae formation, rhinitis sicca, severe bleeding, or osteonecrosis of the turbinate bone A parasurgical treatment explained in Ayurveda, known as kshara pratisarana, which is a minimal invasive and precise procedure for this ailment, tried to overcome this problem. ′Kshara Karma′ is a popular treatment modality in Ayurveda, which has been advocated in disorders of nose like arbuda (tumor and adhimamsa (muscular growth. Clinical observation has shown its effectiveness in the management of turbinate hypertrophy. A case report of 45-year-old male who presented with complaints of frequent nasal obstruction, nasal discharge, discomfort in nose, and headache; and diagnosed as turbinate hypertrophy has been presented here. The patient was treated with one application of Kshara over the turbinates. The treatment was effective and no recurrence was noticed in the follow up.

  5. Concomitant coronary and renal revascularization improves left ventricular hypertrophy more than coronary stenting alone in patients with ischemic heart and renal disease%冠脉合并肾动脉狭窄同期血运重建术比单纯冠脉介入更能减轻左室肥厚

    Institute of Scientific and Technical Information of China (English)

    Hao-jian DONG; Cheng HUANG; De-mou LUO; Jing-guang YE; Jun-qing YANG; Guang LI; Jian-fang LUO; Ying-ling ZHOU‡

    2016-01-01

    Percutaneous transluminal renal artery stenting (PTRAS) has been proved to have no more benefit than medication alone in treating atherosclerotic renal artery stenosis (ARAS). Whether PTRAS could improve left ven-tricular hypertrophy (LVH) and reduce adverse events when based on percutaneous coronary intervention (PCI) for patients with coronary artery disease (CAD) and ARAS is stil unclear. A retrospective study was conducted, which explored the effect of concomitant PCI and PTRAS versus PCI alone for patients with CAD and ARAS complicated by heart failure with preserved ejection fraction (HFpEF). A total of 228 patients meeting inclusion criteria were divided into two groups: (1) the HFpEF-I group, with PCI and PTRAS; (2) the HFpEF-II group, with PCI alone. Both groups had a two-year folow-up. The left ventricular mass index (LVMI) and other clinical characteristics were compared between groups. During the folow-up period, a substantial decrease in systolic blood pressure (SBP) was observed in the HFpEF-I group, but not in the HFpEF-II group. There was marked decrease in LVMI in both groups, but the HFpEF-I group showed a greater decrease than the HFpEF-II group. Regression analysis demonstrated that PTRAS was significantly associated with LVMI reduction and fewer adverse events after adjusting for other factors. In HFpEF patients with both CAD and ARAS, concomitant PCI and PTRAS can improve LVH and decrease the incidence of adverse events more than PCI alone. This study highlights the beneficial effect of ARAS revascularization, as a new and more aggressive revascularization strategy for such high-risk patients.%目的:研究经皮肾动脉支架术(PTRAS)能否在冠脉介入(PCI)基础上进一步改善冠心病合并肾动脉狭窄患者的左室肥厚(LVH)及减少主要心血管不良事件的发生。  创新点:本研究对集中入选全身动脉粥样硬化这类高危患者(冠心病合并肾动脉狭窄(CAD & ARAS))临床

  6. AT1 receptor A/C1166 polymorphism contributes to cardiac hypertrophy in subjects with hypertrophic cardiomyopathy

    NARCIS (Netherlands)

    A.P. Osterop; M.J.M. Kofflard (Marcel); L.A. Sandkuijl (Lodewijk); M.A.D.H. Schalekamp (Maarten); A.H.J. Danser (Jan); R. Krams (Rob); F.J. ten Cate (Folkert)

    1998-01-01

    textabstractThe development of left ventricular hypertrophy (LVH) in subjects with hypertrophic cardiomyopathy (HCM) is variable, suggesting a role for modifying factors such as angiotensin II. We investigated whether the angiotensin II type 1 receptor (AT1-R) A/C1166 p

  7. Mitochondria in cardiac hypertrophy and heart failure

    OpenAIRE

    Rosca, Mariana G.; Tandler, Bernard; Hoppel, Charles L.

    2012-01-01

    Heart failure (HF) frequently is the unfavorable outcome of pathological heart hypertrophy. In contrast to physiological cardiac hypertrophy, which occurs in response to exercise and leads to full adaptation of contractility to the increased wall stress, pathological hypertrophy occurs in response to volume or pressure overload, ultimately leading to contractile dysfunction and HF. Because cardiac hypertrophy impairs the relationship between ATP demand and production, mitochondrial bioenerget...

  8. Expression and protective effects of urocortin in cardiac myocytes.

    Science.gov (United States)

    Okosi, A; Brar, B K; Chan, M; D'Souza, L; Smith, E; Stephanou, A; Latchman, D S; Chowdrey, H S; Knight, R A

    1998-04-01

    Reverse transcription PCR showed that mRNA encoding the CRH-like molecule, urocortin, is expressed in a rat cardiac myocyte cell line and in primary cultures of cardiac myocytes. Identity of the amplified with the published sequence was established by restriction mapping and direct sequencing. Expression of urocortin mRNA was increased 12-18 h after thermal injury. Urocortin peptide protected cardiac myocytes from cell death induced by hypoxia. The data suggest that urocortin is an endogenous cardiac myocyte peptide which modulates the cellular response to stress. PMID:9639256

  9. Effects of imidapril on heterogeneity of action potential and calcium current of ventriclar myocytes in infarcted rabbits

    Institute of Scientific and Technical Information of China (English)

    YangLI; QiaoXUE; JieMA; Cun-taiZHANG; PingQIU; LinWANG; WeiGAO; ReiCHENG; Zai-yinLU; Shi-wenWANG

    2004-01-01

    AIM: To investigate the effects of chronic treatment with imidapril on the electrophysiologic heterogeneous change of the noninfarcted myocardium of rabbits after myocardial infarction and the mechanism of its antiarrhythmic efficacy. METHODS: Rabbits with left coronary artery ligation were prepared and allowed to recover for 8 weeks. Myocytes were isolated from subendocardial, midmyocardial, and subepicardial regions of the noninfarcted left ventricular wall. Action potentials and calcium current were recorded using whole-cell patch clamp technique. RESULTS: The action potential duration of repolarization 90 % (APD90) was more prolonged in midmyocardium rather than in subepicardium and subendocardium with healed myocardial infarction. The transmural dispersion of repolarization (TDR) was increased in the three ventricular regions. The amplitude of/Ca-L was enhanced but its density was decreased in noninfarcted ventricular myocytes due to increased cell membrane capacitance. The increased differences of calcium currents among subepicardium, midmyocardium, and subendocardium were also discovered. Normalization of heterogeneous changes in repolarization after treatment with imidapril was observed and decrease of TDR in noninfarcted area was measured. Early after depolarization (EAD) events of noninfarcted midmyocardium were markedly decreased by imidapril. CONCLUSION: Imidapril reduced the electrophysiologic heterogeneities in noninfarcted area in rabbits after myocardial infarction. This ability of imidapril may contribute to its antiarrhythmic efficacy.

  10. Effects of imidapril on heterogeneity of action potential and calcium current of ventriclar myocytes in infarcted rabbits

    Institute of Scientific and Technical Information of China (English)

    Yang LI; Shi-wen WANG; Qiao XUE; Jie MA; Cun-tai ZHANG; Ping QIU; Lin WANG; Wei GAO; Rei CHENG; Zai-ying LU

    2004-01-01

    AIM: To investigate the effects of chronic treatment with imidapril on the electrophysiologic heterogeneous change of the noninfarcted myocardium of rabbits after myocardial infarction and the mechanism of its antiarrhythmic efficacy. METHODS: Rabbits with left coronary artery ligation were prepared and allowed to recover for 8 weeks.Myocytes were isolated from subendocardial, midmyocardial, and subepicardial regions of the noninfarcted left ventricular wall. Action potentials and calcium current were recorded using whole-cell patch clamp technique.RESULTS: The action potential duration of repolarization 90 % (APD90)was more prolonged in midmyocardium rather than in subepicardium and subendocardium with healed myocardial infarction. The transmural dispersion of repolarization (TDR) was increased in the three ventricular regions. The amplitude of ICa-L was enhanced but its density was decreased in noninfarcted ventricular myocytes due to increased cell membrane capacitance. The increased differences of calcium currents among subepicardium, midmyocardium, and subendocardium were also discovered. Normalization of heterogeneous changes in repolarization after treatment with imidapril was observed and decrease of TDR in noninfarcted area was measvred. Early after depolarization (EAD) events of noninfarcted midmyocardium were markedly decreased by imidapril. CONCLUSION: Imidapril reduced the electrophysiologic heterogeneities in noninfarcted area in rabbits after myocardial infarction. This ability of imidapril may contribute to its antiarrhythmic efficacy.

  11. 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…

  12. Moderate ischemic mitral regurgitation after postero-lateral myocardial infarction in sheep alters left ventricular shear but not normal strain in the infarct and infarct borderzone

    Science.gov (United States)

    Ge, Liang; Wu, Yife; Soleimani, Mehrdad; Khazalpour, Michael; Takaba, Kiyoaki; Tartibi, Mehrzad; Zhang, Zhihong; Acevedo-Bolton, Gabriel; Saloner, David A.; Wallace, Arthur W.; Mishra, Rakesh; Grossi, Eugene A.; Guccione, Julius M.; Ratcliffe, Mark B.

    2016-01-01

    Background Chronic ischemic mitral regurgitation (CIMR: MR) is associated with poor outcome. Left ventricular (LV) strain after postero-lateral myocardial infarction (MI) may drive LV remodeling. Although moderate CIMR has been previously shown to effect LV remodeling, the effect of CIMR on LV strain after postero-lateral MI remains unknown. We tested the hypothesis that moderate CIMR alters LV strain after postero-lateral MI. Methods/Results Postero-lateral MI was created in 10 sheep. Cardiac MRI with tags was performed 2 weeks before and 2, 8 and 16 weeks after MI. LV and right ventricular (RV) volumes were measured and regurgitant volume indexed to body surface area (BSA; RegurgVolume Index) calculated as the difference between LV and RV stroke volumes / BSA. Three-dimensional strain was calculated. Circumferential (Ecc)and longitudinal (Ell) strains were reduced in the infarct proper, MI borderzone (BZ) and remote myocardium 16 weeks after MI. In addition, radial circumferential (Erc) and radial longitudinal (Erl) shear strains were reduced in remote myocardium but increased in the infarct and BZ 16 weeks after MI. Of all strain components, however, only Erc was effected by RegurgVolume Index (p=0.0005). There was no statistically significant effect of RegurgVolume Index on Ecc, Ell, Erl, or circumferential longitudinal shear strain (Ecl). Conclusions Moderate CIMR alters radial circumferential shear strain after postero-lateral MI in the sheep. Further studies are needed to determine the effect of shear strain on myocyte hypertrophy and the effect of mitral repair on myocardial strain. PMID:26857634

  13. Arrhythmogenic Right Ventricular Dysplasia

    Science.gov (United States)

    MENU Return to Web version Arrhythmogenic Right Ventricular Dysplasia Overview What is arrhythmogenic right ventricular dysplasia? Arrhythmogenic right ventricular dysplasia (say: “uh-rith-mo-jen-ic right ven-trick- ...

  14. DETRAINING-RELATED CHANGES IN LEFT VENTRICULAR WALL THICKNESS AND LONGITUDINAL STRAIN IN A YOUNG ATHLETE LIKELY TO HAVE HYPERTROPHIC CARDIOMYOPATHY

    Directory of Open Access Journals (Sweden)

    Cesare de Gregorio

    2012-09-01

    Full Text Available One of the diagnostic criteria in order to differentiate between physiological and pathological left ventricular hypertrophy is the wall thickness reduction after at least 3-month detraining period, which is considered a marker of the athlete's heart. This report describes detraining-related regression of LV hypertrophy and improvement in myocardial deformation in a junior athlete likely to have hypertrophic cardiomyopathy

  15. 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

    In hypertensive patients with left ventricular hypertrophy, antihypertensive treatment induces changes in left ventricular structure and function. However, less is known about gender differences in this response. Baseline and annual echocardiograms until the end of study or a primary end point...... occurred were assessed in 863 hypertensive patients with electrocardiographic left ventricular hypertrophy aged 55 to 80 years (mean: 66 years) during 4.8 years of randomized losartan- or atenolol-based treatment in the Losartan Intervention for Endpoint Reduction in Hypertension Echocardiography substudy...... (47% versus 32%; Ptreatment reduction in mean blood pressure. In logistic regression, left ventricular hypertrophy at study end was more common in women (odds ratio: 1.61; 95% CI: 1.16 to 2.26; P

  16. Cardiac Hypertrophy and Fibrosis in the Metabolic Syndrome: A Role for Aldosterone and the Mineralocorticoid Receptor

    Directory of Open Access Journals (Sweden)

    Eric E. Essick

    2011-01-01

    Full Text Available Obesity and hypertension, major risk factors for the metabolic syndrome, render individuals susceptible to an increased risk of cardiovascular complications, such as adverse cardiac remodeling and heart failure. There has been much investigation into the role that an increase in the renin-angiotensin-aldosterone system (RAAS plays in the pathogenesis of metabolic syndrome and in particular, how aldosterone mediates left ventricular hypertrophy and increased cardiac fibrosis via its interaction with the mineralocorticoid receptor (MR. Here, we review the pertinent findings that link obesity with elevated aldosterone and the development of cardiac hypertrophy and fibrosis associated with the metabolic syndrome. These studies illustrate a complex cross-talk between adipose tissue, the heart, and the adrenal cortex. Furthermore, we discuss findings from our laboratory that suggest that cardiac hypertrophy and fibrosis in the metabolic syndrome may involve cross-talk between aldosterone and adipokines (such as adiponectin.

  17. 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.)

  18. Urocortin2 prolongs action potential duration and modulates potassium currents in guinea pig myocytes and HEK293 cells.

    Science.gov (United States)

    Yang, Li-Zhen; Zhu, Yi-Chun

    2015-07-01

    We previously reported that activation of corticotropin releasing factor receptor type 2 by urocortin2 up-regulates both L-type Ca(2+) channels and intracellular Ca(2+) concentration in ventricular myocytes and plays an important role in cardiac contractility and arrhythmogenesis. This study goal was to further test the hypothesis that urocortin2 may modulate action potentials as well as rapidly and slowly activating delayed rectifier potassium currents. With whole cell patch-clamp techniques, action potentials and slowly activating delayed rectifier potassium currents were recorded in isolated guinea pig ventricular myocytes, respectively. And rapidly activating delayed rectifier potassium currents were tested in hERG-HEK293 cells. Urocortin2 produced a time- and concentration-dependent prolongation of action potential duration. The EC50 values of action potential duration and action potential duration at 90% of repolarization were 14.73 and 24.3nM respectively. The prolongation of action potential duration of urocortin2 was almost completely or partly abolished by H-89 (protein kinase A inhibitor) or KB-R7943 (Na(+)/Ca(2+) exchange inhibitor) pretreatment respectively. And urocortin2 caused reduction of rapidly activating delayed rectifier potassium currents in hERG-HEK293 cells. In addition, urocortin2 slowed the rate of slowly activating delayed rectifier potassium channel activation, and rightward shifted the threshold of slowly activating delayed rectifier potassium currents to more positive potentials. Urocortin2 prolonged action potential duration via activation of protein kinase A and Na(+)/ Ca(2+) exchange in isolated guinea pig ventricular myocytes in a time- and concentration- dependent manner. In hERG-HEK293 cells, urocortin2 reduced rapidly activating delayed rectifier potassium current density which may contribute to action potential duration prolongation.

  19. Adult cardiac fibroblast proliferation is modulated by calcium/calmodulin-dependent protein kinase II in normal and hypertrophied hearts.

    Science.gov (United States)

    Martin, Tamara P; Lawan, Ahmed; Robinson, Emma; Grieve, David J; Plevin, Robin; Paul, Andrew; Currie, Susan

    2014-02-01

    Increased adult cardiac fibroblast proliferation results in an increased collagen deposition responsible for the fibrosis accompanying pathological remodelling of the heart. The mechanisms regulating cardiac fibroblast proliferation remain poorly understood. Using a minimally invasive transverse aortic banding (MTAB) mouse model of cardiac hypertrophy, we have assessed fibrosis and cardiac fibroblast proliferation. We have investigated whether calcium/calmodulin-dependent protein kinase IIδ (CaMKIIδ) regulates proliferation in fibroblasts isolated from normal and hypertrophied hearts. It is known that CaMKIIδ plays a central role in cardiac myocyte contractility, but nothing is known of its role in adult cardiac fibroblast function. The MTAB model used here produces extensive hypertrophy and fibrosis. CaMKIIδ protein expression and activity is upregulated in MTAB hearts and, specifically, in cardiac fibroblasts isolated from hypertrophied hearts. In response to angiotensin II, cardiac fibroblasts isolated from MTAB hearts show increased proliferation rates. Inhibition of CaMKII with autocamtide inhibitory peptide inhibits proliferation in cells isolated from both sham and MTAB hearts, with a significantly greater effect evident in MTAB cells. These results are the first to show selective upregulation of CaMKIIδ in adult cardiac fibroblasts following cardiac hypertrophy and to assign a previously unrecognised role to CaMKII in regulating adult cardiac fibroblast function in normal and diseased hearts. PMID:23881186

  20. Non invasive Measurements of Myocardial Hypertrophy in Patients with Essential Hypertension Treated with Eprosartan: Contribution of the Physics

    Science.gov (United States)

    Cabrera Solé, Ricardo

    2007-04-01

    Objective: The main objective of this study was to evaluate the effects of the treatment with eprosartan on cardiac hypertrophy in hypertensive patients using the echocardiogram to measure the hypertrophy of left ventricle. We studied 60 untreated patients diagnosed of mild to moderate hypertension which received after the diagnosis 600 mg/day of eprosartan, a novel direct angiotensin inhibitor recently introduced to treat hypertension. All patients were submitted to a standard echocardiographic study before the treatment and after 6 months of it We evaluated by echocardiogram the following parameters: left ventricular septum and posterior wall thickness, left ventricular mass, E/A index of mitral flow considering abnormal when this index was less than 1, and left ventricular ejection fraction. Results: at the beginning we found a systolic/diastolic pressures of 165±9/ 96±4 mmHg compared with the end of study of 124±2/79±3 mmHg (ptreatment (pblood pressure but also left ventricular hypertrophy and improve left ventricular diastolic function in patients with essential hypertension according with parameters measured with non invasive methods.

  1. 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.

  2. Stargazing microRNA maps a new miR-21 star for cardiac hypertrophy

    OpenAIRE

    Indolfi, Ciro; Curcio, Antonio

    2014-01-01

    Left ventricular hypertrophy is an initial compensatory mechanism in response to cardiac stress that can degenerate into heart failure and sudden cardiac death. Recent studies have shown that microRNAs (miRs) regulate several aspects of cardiovascular diseases. In this issue of the JCI, Bang and colleagues identified an exosome-mediated communication mechanism between cardiac fibroblasts and cardiomyocytes. Specifically, cardiac fibroblasts secrete miR-enriched exosomes, which are subsequentl...

  3. Hypoxia and glucose independently regulate the beta-adrenergic receptor-adenylate cyclase system in cardiac myocytes.

    OpenAIRE

    Rocha-Singh, K J; Honbo, N Y; Karliner, J S

    1991-01-01

    We explored the effects of two components of ischemia, hypoxia and glucose deprivation, on the beta-adrenergic receptor (beta AR)-adenylate cyclase system in a model of hypoxic injury in cultured neonatal rat ventricular myocytes. After 2 h of hypoxia in the presence of 5 mM glucose, cell surface beta AR density (3H-CGP-12177) decreased from 54.8 +/- 8.4 to 39 +/- 6.3 (SE) fmol/mg protein (n = 10, P less than 0.025), while cytosolic beta AR density (125I-iodocyanopindolol [ICYP]) increased by...

  4. 二维应变技术对未重构高血压患者心肌收缩功能的研究%Assessment of non-left ventricular hypertrophy systolic function in patients with hypertension using two-dimensional strain in echocardiography

    Institute of Scientific and Technical Information of China (English)

    郭显峰; 李益林; 吴筱辉; 王珊珊

    2011-01-01

    Objective To evaluate the non-left ventricular hypertrophy ( NLVH )longitudinal systolic function in patients with primary hypertension using two-dimensional strain in echocardiography. Methods According to the left ventricular mass index( LVMI )and relative wall thick( RWT ),30 patients with hypertension were chosen and 30 normal control subjects,who were determined by transthoracic echocardiography in routine parameters. Height frame rate two-dimensional images were recorded from the apical four-chamber view,two-chamber view and long-axis of the left ventricle. The peak systolic longitudinal strain of 18 segments and 3 whole views were measured using two-dimensional strain software,and eventually the strain of 18 segments were showed in a Bull s eye,and compared wall strain gradient with classification. Results No significant difference in the peak systolic longitudinal strain of 3 whole views were found between the control group and NLVH group. However, the average peak systolic longitudinal strain of base segments were significantly different in the NLVH group compared with the control group [( - 16. 98 ± 5. 60 )% , ( - 19. 29 ± 2. 68 )% , t = - 4. 072, P = 0. 000 J,The peak systolic longitudinal strain of some segments and walls in the NLVH group were significantly lower than those in the control group, for example, the basal segment of septal and anterior[( - 14. 30 ±3. 54 )% ,( - 18.40 ±2. 30 )% ,t = -4. 341, P =0. 000 );the basal segment of[( -14.60 ±4. 35 )% ,( -19.15 ±2.37)% ,t= -4.112, P =0.000); the middle segment of side[( 17.45 ±4. 86)%,( -20.25 ± 2. 94 )% , t = -2.205,P = 0. 034 )]; the middle segment of anterior[( - 17. 95 ± 3. 00 )% , ( -21.70 ± 2. 96 )% ,t = - 3. 981, P = 0. 000]; side[( - 19. 15 ± 6. 68 )% , ( -21.47 ±4. 05 )% ,t = -2. 298, P =0. 024]; Anterior[( - 19. 37 ±6. 10 )% , ( -22.58 ±4.41 )% ,t = -3. 312,P =0.001 ). The part of counter-gradient and completely counter-gradient of the wall ratio in NLVH group were

  5. Correlation between brachial-ankle pulse wave velocity and left ventricular hypertrophy in hypertensive patients%高血压患者肱踝动脉脉搏波传导速度与左心室肥厚的相关性

    Institute of Scientific and Technical Information of China (English)

    2013-01-01

      目的分析高血压患者肱踝动脉脉搏波传导速度(brachial-ankle pulse wave velocity,baPWV)与左心室肥厚的关系。方法入选2009年9月-2012年6月本院969例原发性高血压患者,按照左心室肥厚定义将其分为高血压伴左心室肥厚(n=380)、高血压不伴左心室肥厚(n=589)两组。应用全自动动脉硬化测定仪测定双侧baPWV,取双侧baPWV平均值。结果高血压伴左心室肥厚组baPWV水平明显高于高血压不伴左心室肥厚组(P<0.05)。线性相关分析表明高血压患者baPWV水平与室间隔厚度(r=0.139,P<0.01)、左心室后壁厚度(r=0.124,P<0.01)以及左心室重量指数呈正相关(r=0.312,P<0.01)。进一步应用多元线性回归分析调整了年龄、性别、体重指数、收缩压、舒张压、血糖、血清胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、甘油三酯等心血管危险因素的影响后,baPWV与室间隔厚度(标化的相关系数β=0.125,P<0.05)、左心室后壁厚度(标化的相关系数β=0.131,P<0.05)以及左心室重量指数(标化的相关系数β=0.027,P<0.01)仍然相关。结论高血压患者baPWV与左心室肥厚密切相关。%Objective To analyze the correlation between brachial-ankle pulse wave velocity (baPWV) and left ventricular hypertrophy (LVH) in hypertensive patients. Methods A total 969 primary hypertensive patients admitted to our hospital from September 2009 to June 2012 were divided into hypertension with LVH group (n=380) and hypertension without LVH group (n=589). Their bilateral baPWV was measured with automatic arteriosclerosis detector and its average value was calculated. Results The baPWV value was significantly higher in hypertension with LVH group than in hypertension without LVH group (P < 0.05). Linear correlation analysis showed that the baPW value was positively correlated with the interventricular septal thickness (r=0.139;P <0.01), LV posterior wall

  6. Modeling beta-adrenergic control of cardiac myocyte contractility in silico

    Science.gov (United States)

    Saucerman, Jeffrey J.; Brunton, Laurence L.; Michailova, Anushka P.; McCulloch, Andrew D.; McCullough, A. D. (Principal Investigator)

    2003-01-01

    The beta-adrenergic signaling pathway regulates cardiac myocyte contractility through a combination of feedforward and feedback mechanisms. We used systems analysis to investigate how the components and topology of this signaling network permit neurohormonal control of excitation-contraction coupling in the rat ventricular myocyte. A kinetic model integrating beta-adrenergic signaling with excitation-contraction coupling was formulated, and each subsystem was validated with independent biochemical and physiological measurements. Model analysis was used to investigate quantitatively the effects of specific molecular perturbations. 3-Fold overexpression of adenylyl cyclase in the model allowed an 85% higher rate of cyclic AMP synthesis than an equivalent overexpression of beta 1-adrenergic receptor, and manipulating the affinity of Gs alpha for adenylyl cyclase was a more potent regulator of cyclic AMP production. The model predicted that less than 40% of adenylyl cyclase molecules may be stimulated under maximal receptor activation, and an experimental protocol is suggested for validating this prediction. The model also predicted that the endogenous heat-stable protein kinase inhibitor may enhance basal cyclic AMP buffering by 68% and increasing the apparent Hill coefficient of protein kinase A activation from 1.0 to 2.0. Finally, phosphorylation of the L-type calcium channel and phospholamban were found sufficient to predict the dominant changes in myocyte contractility, including a 2.6x increase in systolic calcium (inotropy) and a 28% decrease in calcium half-relaxation time (lusitropy). By performing systems analysis, the consequences of molecular perturbations in the beta-adrenergic signaling network may be understood within the context of integrative cellular physiology.

  7. Inorganic polyphosphate in cardiac myocytes: from bioenergetics to the permeability transition pore and cell survival.

    Science.gov (United States)

    Dedkova, Elena N

    2016-02-01

    Inorganic polyphosphate (polyP) is a linear polymer of Pi residues linked together by high-energy phosphoanhydride bonds as in ATP. PolyP is present in all living organisms ranging from bacteria to human and possibly even predating life of this planet. The length of polyP chain can vary from just a few phosphates to several thousand phosphate units long, depending on the organism and the tissue in which it is synthesized. PolyP was extensively studied in prokaryotes and unicellular eukaryotes by Kulaev's group in the Russian Academy of Sciences and by the Nobel Prize Laureate Arthur Kornberg at Stanford University. Recently, we reported that mitochondria of cardiac ventricular myocytes contain significant amounts (280±60 pmol/mg of protein) of polyP with an average length of 25 Pi and that polyP is involved in Ca(2+)-dependent activation of the mitochondrial permeability transition pore (mPTP). Enzymatic polyP depletion prevented Ca(2+)-induced mPTP opening during ischaemia; however, it did not affect reactive oxygen species (ROS)-mediated mPTP opening during reperfusion and even enhanced cell death in cardiac myocytes. We found that ROS generation was actually enhanced in polyP-depleted cells demonstrating that polyP protects cardiac myocytes against enhanced ROS formation. Furthermore, polyP concentration was dynamically changed during activation of the mitochondrial respiratory chain and stress conditions such as ischaemia/reperfusion (I/R) and heart failure (HF) indicating that polyP is required for the normal heart metabolism. This review discusses the current literature on the roles of polyP in cardiovascular health and disease. PMID:26862184

  8. 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.

  9. : AMPK and skeletal muscle hypertrophy

    OpenAIRE

    Mounier, Rémi; Lantier, Louise; Leclerc, Jocelyne; Sotiropoulos, Athanassia; Pende, Mario; Daegelen, Dominique; Sakamoto, Kei; Foretz, Marc; Viollet, Benoit

    2009-01-01

    10 pages; 6 figures; 49 références bibliographiques International audience Activation of AMP-activated protein kinase (AMPK) inhibits protein synthesis through the suppression of the mammalian target of rapamycin complex 1 (mTORC1), a critical regulator of muscle growth. The purpose of this investigation was to determine the role of the AMPKalpha1 catalytic subunit on muscle cell size control and adaptation to muscle hypertrophy. We found that AMPKalpha1(-/-) primary cultured myotubes a...

  10. 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.

  11. INTRACELLULAR REDISTRIBUTION OF CARDIAC ENDOTHELIN-1 RECEPTOR IN RAT DURING MYOCARDIAL HYPERTROPHY

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective. In a model of rat cardiac hypertrophy, the changes in the distribution of ET-1 receptors in two subcellular fractions, the sarcolemma and the light vesicles during myocardial hypertrophy were studied. Methods. Cardiac hypertrophy was produced by placing a constricting clip around the suprarenal abdominal aorta of rats, and ET-1 receptor was assayed with radioactive analysis method. Results. It was found that plasma and ventricular ET-1 levels increased significantly on week 2 and week 4 of pressure overload. ET-1 binding studies showed that during myocardial hypertrophy, the maximum binding capacity (Bmax) was increased by 41% (P<0.01) and 65% (P< 0.01) in sarcolemma in H-2 week and H-4 week groups, but was decreased by 24% (P< 0.01) and 21% (P< 0.01) in light vesicles. The sum of Bmax of sarcolemmal and light vesicle fractions was increased by 33% (P< 0.01) and 57% (P< 0.01) in group H-2 week and H-4 week, respectively. ? Conclusion. ET-1 receptors in rat heart were externalized from light vesicles to sarcolemma, which may contribute to the development of myocardial hypertrophy.

  12. Mid-ventricular obstructive hypertrophic cardiomyopathy with apical aneurysm and sustained ventricular tachycardia: a case report and literature review

    Institute of Scientific and Technical Information of China (English)

    GAO Xiao-jin; KANG Lian-ming; ZHANG Jian; DOU Ke-fei; YUAN Jian-song; YANG Yue-jin

    2011-01-01

    The case is a 54-year-old man with hypertrophic cardiomyopathy, mid-ventricular obstruction, apical aneurysm, and recurrence sustained monomorphic ventricular tachycardia (VT). A coronary angiogram revealed myocardial bridging located in the middle of the left anterior descending coronary artery (LAD), and the left ventriculogram showed an hour-glass appearance of the left ventricular cavity. There was a significant pressure gradient of 60 mmHg across the mid-ventricular obliteration at rest. A successful myectomy of the inappropriate hypertrophy myocardium and excision of the apical aneurysm were performed. Pathologic analysis demonstrated fibrosis in the apical aneurysm and thickened and narrowed vessels in the adjacent area. During the follow-up of eighteen months, the patient remained clinically stable and free from arrhythmic recurrence.

  13. Sevoflurane postconditioning alleviates action potential duration shortening and L-type calcium current suppression induced by ischemia/reperfusion injury in rat epicardial myocytes

    Institute of Scientific and Technical Information of China (English)

    GONG Jun-song; YAO Yun-tai; FANG Neng-xin; HUANG Jian; LI Li-huan

    2012-01-01

    Background It has been proved that sevoflurane postconditioning (SpostC) could protect the heart against myocardial ischemia/reperfusion injury,however,there has been few research focused on the electrophysiological effects of SpostC.The objective of the study was to investigate the effects of SpostC on action potential duration (APD) and L-type calcium current (ICa,L) in isolated cardiomyocytes.Methods Langendorff perfused SD rat hearts were randomly assigned to one of the time control (TC),ischemia/reperfusion (I/R,25 minutes of ischemia followed by 30 minutes of reperfusion),and SpostC (postconditioned with 3% sevoflurane) groups.At the end of reperfusion,epicardial myocytes were dissociated enzymatically for patch clamp studies.Results Sevoflurane directly prolonged APD and decreased peak Ica,L densities in epicardial myocytes of the TC group (P<0.05).I/R injury shortened APD and decreased peak Ica,L densities in epicardial myocytes of the I/R group (P<0.05).SpostC prolonged APD and increased peak Ica,L densities in epicardial myocytes exposed to I/R injury (P<0.05).SpostC decreased intracellular reactive oxygen species (ROS) levels,reduced the incidence of ventricular tachycardia and ventricular fibrillation,and decreased reperfusion arrhythmia scores compared with the I/R group (all P<0.05).Conclusions SpostC attenuates APDshortening and ICa,L suppression induced by I/R injury.The regulation of APD and Ica,L by SpostC might be related with intracellular ROS modulation,which contributes to the alleviation of reperfusion ventricular arrhythmia.Chin Med J 2012;125(19):3485-3491

  14. Positive T wave overshoot as a sign of ventricular enlargement.

    Science.gov (United States)

    Short, D; Weir, J

    1984-03-01

    A consecutive series of 86 patients with an inverted T wave showing terminal positivity (overshoot) of a specific pattern in the resting electrocardiogram were studied. Patients with bundle branch block or electrocardiographic evidence of acute infarction and those taking digoxin or a similar drug were excluded. In 67 patients the heart was examined by echocardiography and in a further two by direct inspection. Sixty six of the 69 patients had an abnormal thickness of the left (or right) ventricle or a calculated left ventricular mass greater than 200 g. Seven of the patients examined by echocardiography had clinically pure ischaemic heart disease; all showed evidence of left ventricular enlargement. In only 39 of the 63 patients with anatomical evidence of left ventricular hypertrophy or dilatation did the electrocardiogram satisfy the standard voltage criterion of left ventricular hypertrophy. In the absence of acute infarction, bundle branch block, or digitalisation positive T wave overshoot of the pattern described is a sign of increased ventricular mass. PMID:6230092

  15. Arrhythmogenic right ventricular dysplasia

    OpenAIRE

    Bockeria O.L.; Lе T.G.

    2015-01-01

    Arrhythmogenic right ventricular dysplasia is a hereditary cardiomyopathy characterized by structural and functional disorders in the right ventricle, which results in ventricular arrhythmias. Arrhythmogenic right ventricular dysplasia is one of the important causes of sudden cardiac death in young people and athletes. Structural disorders in arrhythmogenic right ventricular dysplasia are associated with fibrosis and fatty infiltration of the right ventricular myocardium. These changes lead t...

  16. Management of arrhythmogenic right ventricular cardiomyopathy.

    Science.gov (United States)

    Silvano, Maria; Mastella, Giulio; Zorzi, Alessandro; Migliore, Federico; Pilichou, Kalliopi; Bauce, Barbara; Rigato, Ilaria; Perazzolo Marra, Martina; Iliceto, Sabino; Thiene, Gaetano; Basso, Cristina; Corrado, Domenico

    2016-08-01

    Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetically determined heart muscle disorder, predisposing to sudden cardiac death (SCD), particularly in young patients and athletes. Pathological features include loss of myocytes and fibrofatty replacement of right ventricular myocardium; a biventricular involvement is often observed. The diagnosis of ARVC (prevalence 1:5.000 in the general population) does not rely on a single gold standard test but is achieved using a scoring system, proposed in 2010 by an International Task Force, which encompasses familial and genetic factors, ECG abnormalities, arrhythmias, and structural/functional ventricular alterations. The main goal of treatment is the prevention of SCD. Implantable cardioverter defibrillator (ICD) is the only proven "lifesaving" therapy; however, it is associated with a significant morbidity due to device-related complications and inappropriate ICD interventions. Other treatment options such as life style changes, antiarrhythmic drugs, beta-blockers and catheter ablation may reduce the arrhythmic burden and alleviate symptoms, without evident impact on prevention of SCD. Selection of patient candidates to ICD implantation is the most challenging issue in the clinical management of ARVC. This article reviews the current perspective on management of ARVC, focusing on clinical manifestations, diagnostic criteria, risk stratification and therapeutic strategies of affected patients. PMID:27186923

  17. Simvastatin inhibits leptin-induced hypertrophy in cultured neonatal rat cardiomyocytes

    Institute of Scientific and Technical Information of China (English)

    Tai-ping HU; Fang-ping XU; Yuan-jian LI; Jian-dong LUO

    2006-01-01

    Aim:To test the hypothesis that statins inhibit leptin-induced hypertrophy in cultured neonatal rat cardiomyocytes.Methods:Cultured neonatal rat cardiomyocytes were used to evaluate the effects of simvastatin on leptininduced hypertrophy.Intracellular reactive oxygen species (ROS) levels were determined by using 2',7'-dichlorofluorescein diacetate (DCF-DA) fluorescence.Total intracellular RNA and cell protein content,which serve as cell proliferative markers,were assayed by using propidium iodide (PI) fluorescence and the Bio-Rad DC protein assay.respectively.The cell surface area,an indicator of cell hypertrophy,was quantified by using Leica image analysis software.Results:After 72 h treatment,1eptin markedly increased RNA 1evels,cell surface area,and total cell protein levels in cardiomyocytes,which were significantly inhibited by simvastatin or catalase treatment.ROS levels were significantly elevated in cardiomyocytes treated with leptin for 4 h compared with those cells without leptin treatment.The increase in ROS levels in cardiomyocytes induced by leptin was reversed by treatment with simvastatin and catalase.Conclusion:Simvastatin inhibits leptin-induced ROS-mediated hyperophy in cultured neonatal rat cardiac myocytes.Statin therapy may provide an effective means of improving cardiac dysfunction in obese humans.

  18. Toward an integrative computational model of the Guinea pig cardiac myocyte.

    Science.gov (United States)

    Gauthier, Laura Doyle; Greenstein, Joseph L; Winslow, Raimond L

    2012-01-01

    The local control theory of excitation-contraction (EC) coupling asserts that regulation of calcium (Ca(2+)) release occurs at the nanodomain level, where openings of single L-type Ca(2+) channels (LCCs) trigger openings of small clusters of ryanodine receptors (RyRs) co-localized within the dyad. A consequence of local control is that the whole-cell Ca(2+) transient is a smooth continuous function of influx of Ca(2+) through LCCs. While this so-called graded release property has been known for some time, its functional importance to the integrated behavior of the cardiac ventricular myocyte has not been fully appreciated. We previously formulated a biophysically based model, in which LCCs and RyRs interact via a coarse-grained representation of the dyadic space. The model captures key features of local control using a low-dimensional system of ordinary differential equations. Voltage-dependent gain and graded Ca(2+) release are emergent properties of this model by virtue of the fact that model formulation is closely based on the sub-cellular basis of local control. In this current work, we have incorporated this graded release model into a prior model of guinea pig ventricular myocyte electrophysiology, metabolism, and isometric force production. The resulting integrative model predicts the experimentally observed causal relationship between action potential (AP) shape and timing of Ca(2+) and force transients, a relationship that is not explained by models lacking the graded release property. Model results suggest that even relatively subtle changes in AP morphology that may result, for example, from remodeling of membrane transporter expression in disease or spatial variation in cell properties, may have major impact on the temporal waveform of Ca(2+) transients, thus influencing tissue level electromechanical function. PMID:22783206

  19. Towards an integrative computational model of the guinea pig cardiac myocyte

    Directory of Open Access Journals (Sweden)

    Laura Doyle Gauthier

    2012-07-01

    Full Text Available The local control theory of excitation-contraction (EC coupling asserts that regulation of calcium (Ca2+ release occurs at the nanodomain level, where openings of single L-type Ca2+ channels (LCCs trigger openings of small clusters of ryanodine receptors (RyRs co-localized within the dyad. A consequence of local control is that the whole-cell Ca2+ transient is a smooth continuous function of influx of Ca2+ through LCCs. While this so-called graded release property has been known for some time, it’s functional importance to the integrated behavior of the cardiac ventricular myocyte has not been fully appreciated. We previously formulated a biophysically-based model, in which LCCs and RyRs interact via a coarse-grained representation of the dyadic space. The model captures key features of local control using a low-dimensional system of ordinary differential equations. Voltage-dependent gain and graded Ca2+ release are emergent properties of this model by virtue of the fact that model formulation is closely based on the sub-cellular basis of local control. In this current work, we have incorporated this graded release model into a prior model of guinea pig ventricular myocyte electrophysiology, metabolism, and isometric force production. The resulting integrative model predicts the experimentally-observed causal relationship between action potential (AP shape and timing of Ca2+ and force transients, a relationship that is not explained by models lacking the graded release property. Model results suggest that even relatively subtle changes in AP morphology that may result, for example, from remodeling of membrane transporter expression in disease or spatial variation in cell properties, may have major impact on the temporal waveform of Ca2+ transients, thus influencing tissue-level electro-mechanical function.

  20. Impact of the endurance exercise training on structure and function of left ventricular myocardium

    OpenAIRE

    Bisikirskas, Valdas

    2006-01-01

    Key-words: echocardiography, cardiac hypertrophy, aerobic capacity. Subject of the study. Endurance athletes' left ventricular morphofunction. Background. Whether left ventricular structure and function depend on the mode of the regularly performed endurance exercise is not conclusive. If it depended indeed, specialists in sports medicine, exercise physiologist, as well as athletic coaches would have a great possibility to design the architecture and predict the function of athletes' an...

  1. Allopurinol Benefits Left Ventricular Mass and Endothelial Dysfunction in Chronic Kidney Disease

    OpenAIRE

    Kao, Michelle P.; Ang, Donald S.; Gandy, Stephen J.; Nadir, M. Adnan; Houston, J. Graeme; Lang, Chim C; Struthers, Allan D

    2011-01-01

    Allopurinol ameliorates endothelial dysfunction and arterial stiffness among patients without chronic kidney disease (CKD), but it is unknown if it has similar effects among patients with CKD. Furthermore, because arterial stiffness increases left ventricular afterload, any allopurinol-induced improvement in arterial compliance might also regress left ventricular hypertrophy (LVH). We conducted a randomized, double-blind, placebo-controlled, parallel-group study in patients with stage 3 CKD a...

  2. Neurogenic muscle hypertrophy: a case report

    Science.gov (United States)

    Shin, Hyun Ho; Jeon, Young Hoon; Jang, Seung Won

    2016-01-01

    Muscular hypertrophy is caused mainly due to myopathic disorder. But, it is also rarely produced by neurogenic disorder. A 74-year-old woman complained of right calf pain with hypertrophy for several years. Recent lumbar spine magnetic resonance imaging (MRI) showed central and lateral canal narrowing at the L4-L5 intervertebral space. Lower extremity MRI revealed fatty change of right medial head of the gastrocnemius and soleus, causing right calf hypertrophy. Electrodiagnostic examinations including electromyography and nerve conduction velocity testing demonstrated 5th lumbar and 1st sacral polyradiculopathy. Integrating all the results, the diagnosis was neurogenic muscle hypertrophy. Neurogenic muscle hypertrophy is very rare, but we recommend that clinicians consider this problem when a patient complains of lower limb hypertrophy and pain.

  3. Non invasive Measurements of Myocardial Hypertrophy in Patients with Essential Hypertension Treated with Eprosartan: Contribution of the Physics

    International Nuclear Information System (INIS)

    Objective: The main objective of this study was to evaluate the effects of the treatment with eprosartan on cardiac hypertrophy in hypertensive patients using the echocardiogram to measure the hypertrophy of left ventricle. We studied 60 untreated patients diagnosed of mild to moderate hypertension which received after the diagnosis 600 mg/day of eprosartan, a novel direct angiotensin inhibitor recently introduced to treat hypertension. All patients were submitted to a standard echocardiographic study before the treatment and after 6 months of it We evaluated by echocardiogram the following parameters: left ventricular septum and posterior wall thickness, left ventricular mass, E/A index of mitral flow considering abnormal when this index was less than 1, and left ventricular ejection fraction. Results: at the beginning we found a systolic/diastolic pressures of 165±9/ 96±4 mmHg compared with the end of study of 124±2/79±3 mmHg (p<0.05). Septum and posterior wall thickness were respectively at baseline 13.2±2 and 12.1±1.1 mmHg and at the end 11.5±1.2 and 10.5±1.3 mmHg (p<0.05 for both of them). The E/A mitral flow index was less than 1 at baseline in 45 patients compared with 19 patients after treatment (p<0.05). Respect to left ventricular mass we found at the beginning 232±7.5 gr., compared to 194±9 gr., at the end of this study (p<0.05). We did not find any significant differences regarding left ventricular ejection fraction between both groups. Conclusions: we can remark that eprosartan is a very useful drug to reduce not only blood pressure but also left ventricular hypertrophy and improve left ventricular diastolic function in patients with essential hypertension according with parameters measured with non invasive methods

  4. Vitamin D levels and left ventricular diastolic function

    OpenAIRE

    Pandit, Anil; Mookadam, Farouk; Boddu, Sailaja; Aryal Pandit, Aashrayata; Tandar, Anwar; Chaliki, Hari; Cha, Stephen; Lee, Howard R.

    2014-01-01

    Objective To determine the association between serum vitamin D level and left ventricular (LV) diastolic dysfunction. Background Vitamin D deficiency has been shown in observational and prospective studies to be associated with cardiovascular diseases including coronary artery disease, LV hypertrophy and systolic heart failure. Even though diastolic LV dysfunction is an early manifestation of cardiac disease, there is no study that examines whether a deficiency of vitamin D is associated with...