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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. Activation of Mst1 causes dilated cardiomyopathy by stimulating apoptosis without compensatory ventricular myocyte hypertrophy

    OpenAIRE

    Yamamoto, Shimako; Yang, Guiping; Zablocki, Daniela; Liu, Jing; Hong, Chull; Kim, Song-jung; Soler, Sandra; Odashima, Mari; Thaisz, Jill; Yehia, Ghassan; Molina, Carlos A.; Yatani, Atsuko; Vatner, Dorothy E.; Vatner, Stephen F.; Sadoshima, Junichi

    2003-01-01

    Activation of mammalian sterile 20–like kinase 1 (Mst1) by genotoxic compounds is known to stimulate apoptosis in some cell types. The importance of Mst1 in cell death caused by clinically relevant pathologic stimuli is unknown, however. In this study, we show that Mst1 is a prominent myelin basic protein kinase activated by proapoptotic stimuli in cardiac myocytes and that Mst1 causes cardiac myocyte apoptosis in vitro in a kinase activity–dependent manner. In vivo, cardiac-specific over...

  3. Impaired beta-adrenergic response and decreased L-type calcium current of hypertrophied left ventricular myocytes in postinfarction heart failure

    Scientific Electronic Library Online (English)

    R.M., Saraiva; N.G.B., Chedid; C.C., Quintero H.; L.E., Díaz G.; M.O., Masuda.

    2003-05-01

    Full Text Available Infarct-induced heart failure is usually associated with cardiac hypertrophy and decreased ß-adrenergic responsiveness. However, conflicting results have been reported concerning the density of L-type calcium current (I Ca(L)), and the mechanisms underlying the decreased ß-adrenergic inotropic respo [...] nse. We determined I Ca(L) density, cytoplasmic calcium ([Ca2+]i) transients, and the effects of ß-adrenergic stimulation (isoproterenol) in a model of postinfarction heart failure in rats. Left ventricular myocytes were obtained by enzymatic digestion 8-10 weeks after infarction. Electrophysiological recordings were obtained using the patch-clamp technique. [Ca2+]i transients were investigated via fura-2 fluorescence. ß-Adrenergic receptor density was determined by [³H]-dihydroalprenolol binding to left ventricle homogenates. Postinfarction myocytes showed a significant 25% reduction in mean I Ca(L) density (5.7 ± 0.28 vs 7.6 ± 0.32 pA/pF) and a 19% reduction in mean peak [Ca2+]i transients (0.13 ± 0.007 vs 0.16 ± 0.009) compared to sham myocytes. The isoproterenol-stimulated increase in I Ca(L) was significantly smaller in postinfarction myocytes (Emax: 63.6 ± 4.3 vs 123.3 ± 0.9% in sham myocytes), but EC50 was not altered. The isoproterenol-stimulated peak amplitude of [Ca2+]i transients was also blunted in postinfarction myocytes. Adenylate cyclase activation through forskolin produced similar I Ca(L) increases in both groups. ß-Adrenergic receptor density was significantly reduced in homogenates from infarcted hearts (Bmax: 93.89 ± 20.22 vs 271.5 ± 31.43 fmol/mg protein in sham myocytes), while Kd values were similar. We conclude that postinfarction myocytes from large infarcts display reduced I Ca(L) density and peak [Ca2+]i transients. The response to ß-adrenergic stimulation was also reduced and was probably related to ß-adrenergic receptor down-regulation and not to changes in adenylate cyclase activity.

  4. Automated microscopy of cardiac myocyte hypertrophy: a case study on the role of intracellular ?-adrenergic receptors.

    Science.gov (United States)

    Ryall, Karen A; Saucerman, Jeffrey J

    2015-01-01

    Traditional approaches for measuring cardiac myocyte hypertrophy have been of low throughput and subjective, limiting the scope of experimental studies designed to understand it. Here, we describe an automated image acquisition and analysis platform for studying the dynamics of cardiac myocyte hypertrophy in vitro. Image acquisition scripts record 5?×?5 mosaic images of fluorescent protein-labeled neonatal rat ventricular myocytes from each well of a 96-well plate using the microscope's automated stage and focus. Image analysis algorithms automatically segment myocyte boundaries, track myocytes, and quantify changes in shape. We describe each step of the image acquisition and analysis algorithms and provide specific examples of how to implement them using Metamorph and CellProfiler software. With this system, shape dynamics of thousands of individual cardiac myocytes can be tracked for up to a week. This imaging platform was recently applied to study reversal of cardiac myocyte hypertrophy following withdrawal of the ?-adrenergic agonist phenylephrine. Hypertrophy readily reversed at low but not high levels of ?-adrenergic signaling, leading to identification of an intracellular population of ?-adrenergic receptors responsible for this reversibility delay. PMID:25304353

  5. Contractile reserve and intracellular calcium regulation in mouse myocytes from normal and hypertrophied failing hearts

    Science.gov (United States)

    Ito, K.; Yan, X.; Tajima, M.; Su, Z.; Barry, W. H.; Lorell, B. H.; Schneider, M. (Principal Investigator)

    2000-01-01

    Mouse myocyte contractility and the changes induced by pressure overload are not fully understood. We studied contractile reserve in isolated left ventricular myocytes from mice with ascending aortic stenosis (AS) during compensatory hypertrophy (4-week AS) and the later stage of early failure (7-week AS) and from control mice. Myocyte contraction and [Ca(2+)](i) transients with fluo-3 were measured simultaneously. At baseline (0.5 Hz, 1.5 mmol/L [Ca(2+)](o), 25 degrees C), the amplitude of myocyte shortening and peak-systolic [Ca(2+)](i) in 7-week AS were not different from those of controls, whereas contraction, relaxation, and the decline of [Ca(2+)](i) transients were slower. In response to the challenge of high [Ca(2+)](o), fractional cell shortening was severely depressed with reduced peak-systolic [Ca(2+)](i) in 7-week AS compared with controls. In response to rapid pacing stimulation, cell shortening and peak-systolic [Ca(2+)](i) increased in controls, but this response was depressed in 7-week AS. In contrast, the responses to both challenge with high [Ca(2+)](o) and rapid pacing in 4-week AS were similar to those of controls. Although protein levels of Na(+)-Ca(2+) exchanger were increased in both 4-week and 7-week AS, the ratio of SR Ca(2+)-ATPase to phospholamban protein levels was depressed in 7-week AS compared with controls but not in 4-week AS. This was associated with an impaired capacity to increase sarcoplasmic reticulum Ca(2+) load during high work states in 7-week AS myocytes. In hypertrophied failing mouse myocytes, depressed contractile reserve is related to an impaired augmentation of systolic [Ca(2+)](i) and SR Ca(2+) load and simulates findings in human failing myocytes.

  6. Phenotypic screen quantifying differential regulation of cardiac myocyte hypertrophy identifies CITED4 regulation of myocyte elongation.

    Science.gov (United States)

    Ryall, Karen A; Bezzerides, Vassilios J; Rosenzweig, Anthony; Saucerman, Jeffrey J

    2014-07-01

    Cardiac hypertrophy is controlled by a highly connected signaling network with many effectors of cardiac myocyte size. Quantification of the contribution of individual pathways to specific changes in shape and transcript abundance is needed to better understand hypertrophy signaling and to improve heart failure therapies. We stimulated cardiac myocytes with 15 hypertrophic agonists and quantitatively characterized differential regulation of 5 shape features using high-throughput microscopy and transcript levels of 12 genes using qPCR. Transcripts measured were associated with phenotypes including fibrosis, cell death, contractility, proliferation, angiogenesis, inflammation, and the fetal cardiac gene program. While hypertrophy pathways are highly connected, the agonist screen revealed distinct hypertrophy phenotypic signatures for the 15 receptor agonists. We then used k-means clustering of inputs and outputs to identify a network map linking input modules to output modules. Five modules were identified within inputs and outputs with many maladaptive outputs grouping together in one module: Bax, C/EBP?, Serca2a, TNF?, and CTGF. Subsequently, we identified mechanisms underlying two correlations revealed in the agonist screen: correlation between regulators of fibrosis and cell death signaling (CTGF and Bax mRNA) caused by AngII; and myocyte proliferation (CITED4 mRNA) and elongation caused by Nrg1. Follow-up experiments revealed positive regulation of Bax mRNA level by CTGF and an incoherent feedforward loop linking Nrg1, CITED4 and elongation. With this agonist screen, we identified the most influential inputs in the cardiac hypertrophy signaling network for a variety of features related to pathological and protective hypertrophy signaling and shared regulation among cardiac myocyte phenotypes. PMID:24613264

  7. Effect of fosinopril on the transient outward potassium current of hypertrophied left ventricular myocardium in the spontaneously hypertensive rat.

    Science.gov (United States)

    Huang, Zhi-Bin; Fang, Chang; Lin, Mao-Huan; Yuan, Gui-Yi; Zhou, Shu-Xian; Wu, Wei

    2014-05-01

    To investigate fosinopril's effect on the transient outward potassium current (Ito) of differing degrees of hypertrophied myocytes in the spontaneously hypertensive rat (SHR). Ten- and 24-week-old SHRs were used as models for cardiac hypertrophy. Hypertrophied ventricular myocytes were exposed to 1, 10, and 100 ?mol/L fosinopril; the whole-cell patch-clamp technique was used to study the effects on the transient outward potassium current. Ito current density was decreased in SHR myocytes relative to controls (14.17?±?0.31 and 11.62?±?0.08 pA/pF in 10- and 24-week-old SHR versus 16.73?±?0.15 pA/pF, p?fosinopril (10 and 100 ?mol/L) increased Ito peak current density in 10-week-old SHR myocytes compared with controls (14.92?±?0.14 and 15.27?±?0.13 pA/pF versus 14.17?±?0.31 pA/pF, p?Fosinopril increased Ito peak current density in 24-week-old SHR myocytes at all doses (12.70?±?0.07, 13.74?±?0.10, and 14.53?±?0.13 versus 11.62?±?0.08 pA/pF for controls, p?Fosinopril had a greater Ito elevation potential on hypertrophied myocytes in 24-week-old compared with 10-week-old SHR for each dose (1.08?±?0.09 versus 0.37?±?0.26 pA/pF, p?Fosinopril increased Ito current density in hypertrophied myocytes. This effect was more pronounced in myocytes with a greater degree of hypertrophy. PMID:24441766

  8. 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...

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

    Science.gov (United States)

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

    2010-10-01

    Histone deacetylase inhibitors represent a new class of anticancer therapeutics and the expectation is that they will be most effective when used in combination with conventional cancer therapies, such as the anthracycline, doxorubicin. The dose-limiting side effect of doxorubicin is severe cardiotoxicity and evaluation of the effects of combinations of the anthracycline with histone deacetylase inhibitors in relevant models is important. We used a well-established in vitro model of doxorubicin-induced hypertrophy to examine the effects of the prototypical histone deacetylase inhibitor, Trichostatin A. Our findings indicate that doxorubicin modulates the expression of the hypertrophy-associated genes, ventricular myosin light chain-2, the alpha isoform of myosin heavy chain and atrial natriuretic peptide, an effect which is augmented by Trichostatin A. Furthermore, we show that Trichostatin A amplifies doxorubicin-induced DNA double strand breaks, as assessed by ?H2AX formation. More generally, our findings highlight the importance of investigating potential side effects that may be associated with emerging combination therapies for cancer. PMID:20930262

  10. Hypoadiponectinemia, cardiometabolic comorbidities and left ventricular hypertrophy.

    Science.gov (United States)

    Di Chiara, Tiziana; Argano, Christiano; Scaglione, Alessandra; Duro, Giovanni; Corrao, Salvatore; Scaglione, Rosario; Licata, Giuseppe

    2015-02-01

    This study was designed to evaluate the prevalence of cardiometabolic comorbidities and the changes in left ventricular geometry and function in 135 subjects subgrouped according to low or normal total adiponectin plasma (ADPN) levels. Left ventricular (LV) internal diameter/height, total LV mass (LVM) and LVM index (LVMI), relative wall thickness (RWT), LV ejection fraction by echocardiography and diastolic parameters by pulsed-wave Doppler were calculated. Body mass index (BMI) (p < 0.0001), waist-to-hip ratio (p < 0.03), triglycerides (p < 0,001), prevalence of obesity (p < 0.005), visceral obesity (p < 0.003), left ventricular hypertrophy (LVH) (p < 0.001), metabolic syndrome (p < 0.0003) and coronary artery disease (CAD) (p < 0.003) were significantly increased and high-density lipoprotein-cholesterol (p < 0.001) was significantly reduced in hypo-ADPN than normal-ADPN subjects. LVM, LVMI, interventricular septum thickness and RWT were significantly (p < 0.0001) higher and left ventricular ejection fraction was significantly (p < 0.0002) lower in hypo-ADPN than normal-ADPN patients. LVMI correlated directly with BMI (p < 0.001), mean blood pressure (p < 0.001), metabolic syndrome (MetS) (p < 0.001) and inversely with ADPN (p < 0.0001). The prevalence of LVH (p < 0.001) and CAD (p < 0.01) was higher in subjects with normal-ADPN and MetS, while the presence of MetS did not change this finding in hypo ADPN group. Both models of regression analysis indicated that ADPN and BMI resulted independently associated with LVMI. In conclusion, our data seem to indicate that hypoadiponectinemia might be associated with an increased prevalence both of clinical comorbidities and increased LVMI. In this subset of subjects, ADPN and BMI, more than MetS, are able to explain cardiac damage. Accordingly, ADPN might become a new target in the management of cardiometabolic risk. PMID:25034520

  11. Inhibition of angiotensin-converting enzyme reduces susceptibility of hypertrophied rat myocardium to ventricular fibrillation.

    Science.gov (United States)

    Shimada, Yasuyuki; Gunasegaram, Suba; Yokoyama, Hiroyuki; Avkiran, Metin

    2002-11-01

    Left ventricular (LV) hypertrophy increases susceptibility to reperfusion arrhythmias and the angiotensin-converting enzyme inhibitor, ramipril, may reduce that susceptibility via regression of LV hypertrophy. Rats (n=12 per group) were subjected to abdominal aortic constriction (AC) or sham-operation (SH) and from 3 to 6 weeks after surgery, 3 AC groups received ramipril (0.01, 0.1, or 1 mg/kg per day p.o.) while the SH and 1 AC group received vehicle. Six weeks after surgery (ie after 3 weeks of treatment), the hearts were excised and subjected to independent Langendorf perfusion of left and right coronary beds. The left coronary bed was then subjected to ischemia (7 min) and reperfusion (5 min). Hypertrophied hearts from the vehicle AC group showed a significant increase in the incidence of reperfusion-induced ventricular fibrillation (VF) compared with control hearts from the SH group (92%* vs 33%: *p<0.05); this difference was abolished by ramipril (42%, 50%, and 42%, at 0.01, 0.1, or 1 mg/kg per day, respectively). The LV weight/body weight ratio was significantly increased in all AC groups (regardless of ramipril treatment) relative to the SH group. At the cellular level, myocyte length was significantly increased in the vehicle AC group, but was normalized by ramipril treatment (1 mg/kg per day). At the molecular level, atrial natriuretic factor (ANF) mRNA expression was also significantly increased in the vehicle AC group, but was again normalized by ramipril treatment (1 mg/kg per day). In conclusion, short-term treatment with ramipril reduced susceptibility to severe ventricular arrhythmias in hypertrophied rat hearts. This protection was achieved in the absence of a significant reduction in LV weight, but was accompanied by regression of myocyte hypertrophy, as reflected by reductions in cell size and ANF expression. PMID:12419938

  12. Left ventricular diastolic performance of left ventricular hypertrophy

    International Nuclear Information System (INIS)

    To study left ventricular diastolic performance in different forms of left ventricular hypertrophy, ECG gated cardiac blood pool scan was performed in 11 patients with hypertrophic nonobstructive cardiomyopathy (HCM) and in 19 patients with hypertension (HT), and left ventricular volume curve (LVVC) was analyzed and compared with those of 13 normal subjects (N). Ejection fraction (EF) and early filling volume ratio (the ratio of volume increment of 100 msec later than the zero point in the first derivative of LVVC to the end diastolic volume) (%EFV) were computed from LVVC. Peak ejection rate (PER) and peak filling rate (PFR) were obtained from the first derivative of LVVC. Peak ejection acceleration (PEA) and peak filling acceleration (PFA) were calculated from the second derivative of LVVC. EF, PER and PEA did not show any difference between these 3 groups. PFR was lower in HT (2.6 ± 0.5) compared with those in HCM (3.0 ± 0.5) (p < 0.05) and in N (3.4 ± 0.5) (p < 0.001), but the %EFV in HCM (4.9 ± 1.8) was lower than those in HT (6.9 ± 1.9) (p < 0.01) and in N (11.4 ± 1.4) (p < 0.001). Moreover, PFA in HCM (27.9 ± 7.2) was increased than those in HT (20.2 ± 5.4) (p < 0.01) with no differences between HCM and N (29.4 ± 8.1). Significant correlation was observed between PFR and PFA (Y = 0.06X + 1.4. r = 0.856. p < 0.001). These result indicate that, in HCM, reduced increase in early left ventricular volume is compensated by a greater filling acceleration. In greater filling acceleration. In contrast, there is no compensation by filling acceleration in HT. (author)

  13. Bioenergetic abnormalities associated with severe left ventricular hypertrophy.

    OpenAIRE

    Zhang, J.; Merkle, H.; Hendrich, K.; Garwood, M.; From, A. H.; Ugurbil, K.; Bache, R. J.

    1993-01-01

    Transmurally localized 31P-nuclear magnetic resonance spectroscopy (NMR) was used to study the effect of severe pressure overload left ventricular hypertrophy (LVH) on myocardial high energy phosphate content. Studies were performed on 8 normal dogs and 12 dogs with severe left ventricular hypertrophy produced by banding the ascending aorta at 8 wk of age. Spatially localized 31P-NMR spectroscopy provided measurements of the transmural distribution of myocardial ATP, phosphocreatine (CP), and...

  14. Stochastic Simulation of Cardiac Ventricular Myocyte Calcium Dynamics and Waves

    OpenAIRE

    Tuan, Hoang-trong Minh; Williams, George S. B.; Chikando, Aristide C.; Sobie, Eric A.; Lederer, W. Jonathan; Jafri, M. Saleet

    2011-01-01

    A three dimensional model of calcium dynamics in the rat ventricular myocyte was developed to study the mechanism of calcium homeostasis and pathological calcium dynamics during calcium overload. The model contains 20,000 calcium release units (CRUs) each containing 49 ryanodine receptors. The model simulates calcium sparks with a realistic spontaneous calcium spark rate. It suggests that in addition to the calcium spark-based leak, there is an invisible calcium leak caused by the stochastic ...

  15. Cyclin D2 induces proliferation of cardiac myocytes and represses hypertrophy

    International Nuclear Information System (INIS)

    The myocytes of the adult mammalian heart are considered unable to divide. Instead, mitogens induce cardiomyocyte hypertrophy. We have investigated the effect of adenoviral overexpression of cyclin D2 on myocyte proliferation and morphology. Cardiomyocytes in culture were identified by established markers. Cyclin D2 induced DNA synthesis and proliferation of cardiomyocytes and impaired hypertrophy induced by angiotensin II and serum. At the molecular level, cyclin D2 activated CDK4/6 and lead to pRB phosphorylation and downregulation of the cell cycle inhibitors p21Waf1/Cip1 and p27Kip1. Expression of the CDK4/6 inhibitor p16 inhibited proliferation and cyclin D2 overexpressing myocytes became hypertrophic under such conditions. Inhibition of hypertrophy by cyclin D2 correlated with downregulation of p27Kip1. These data show that hypertrophy and proliferation are highly related processes and suggest that cardiomyocyte hypertrophy is due to low amounts of cell cycle activators unable to overcome the block imposed by cell cycle inhibitors. Cell cycle entry upon hypertrophy may be converted to cell division by increased expression of activators such as cyclin D2

  16. [Validity of electrocardiographic indices of left ventricular hypertrophy in athletes].

    Science.gov (United States)

    Cottini, E; Lisi, M; Maria, N; Martelli, V; Corsini, M; Raspagliesi, M; Tamburino, C

    1989-09-01

    The Authors have evaluated the reliability of the most important electrocardiographic criteria for left ventricular hypertrophy in a group of 95 athletes. An ECG and a M- and B-mode echocardiogram have been performed in each subject; the criteria by Sokolow and Lyon, by Cornell, by Gubner, by Romhilt and Estes and by Casale have been employed to evaluate left ventricular hypertrophy. Left ventricular mass has been evaluated by the echocardiogram according to Devereux and coll. The electrocardiographic method by Casale and coll., proposed only for a few years, is based on the valuation of R wave and on the study of ventricular repolarization depending on sex and age. By this method, still now not much used in the study of athletes, a good correlation with the echocardiographic data was expected, in relation to the young age of the population. The athletes have been divided into three groups, practising aerobic sports, aerobic-anaerobic sports and power sports, according to the physiologic classification of the sports activities of Dal Monte. Using the chi-squared test, for the whole population and separately for the three groups, no significant statistical correlation has been observed. In conclusion, the results demonstrate that not only the "classic" criteria, but also the most recent ECG criteria of left ventricular hypertrophy are not reliable in evaluating left ventricular hypertrophy in trained athletes, leaving the final assessment of the real state of the cardiac chambers to echocardiography. PMID:2532715

  17. Hemodynamic versus adrenergic control of cat right ventricular hypertrophy.

    OpenAIRE

    Cooper, G.; Kent, R. L.; Uboh, C. E.; Thompson, E. W.; Marino, T. A.

    1985-01-01

    The purpose of this study was to determine whether cardiac hypertrophy in response to hemodynamic overloading is a primary result of the increased load or is instead a secondary result of such other factors as concurrent sympathetic activation. To make this distinction, four experiments were done; the major experimental result, cardiac hypertrophy, was assessed in terms of ventricular mass and cardiocyte cross-sectional area. In the first experiment, the cat right ventricle was loaded differe...

  18. Transcription Factor CHF1/Hey2 Regulates Specific Pathways in Serum Stimulated Primary Cardiac Myocytes: Implications for Cardiac Hypertrophy

    OpenAIRE

    Yu, Man; Xiang, Fan; Beyer, Richard P.; Farin, Federico M.; Bammler, Theo K.; Chin, Michael T.

    2010-01-01

    We have previously found that overexpression of CHF1/Hey2 in the myocardium prevents the development of phenylephrine-induced hypertrophy. To identify transcriptional pathways regulated by CHF1/Hey2, we cultured primary neonatal mouse cardiac myocytes from wild type and transgenic mice overexpressing CHF1/Hey2 and treated them with serum, a potent hypertrophic stimulus. We verified that overexpression of CHF1/Hey2 suppressed cardiac myocyte hypertrophy induced by serum and then determined tra...

  19. Focal Adhesion Kinase and p130Cas Mediate Both Sarcomeric Organization and Activation of Genes Associated with Cardiac Myocyte Hypertrophy

    OpenAIRE

    Kovac?ic?-milivojevic?, Branka; Roediger, Frederick; Almeida, Eduardo A. C.; Damsky, Caroline H.; Gardner, David G.; Ilic?, Dus?ko

    2001-01-01

    Hypertrophic terminally differentiated cardiac myocytes show increased sarcomeric organization and altered gene expression. Previously, we established a role for the nonreceptor tyrosine kinase Src in signaling cardiac myocyte hypertrophy. Here we report evidence that p130Cas (Cas) and focal adhesion kinase (FAK) regulate this process. In neonatal cardiac myocytes, tyrosine phosphorylation of Cas and FAK increased upon endothelin (ET) stimulation. FAK, Cas, and pax...

  20. Eosinophilic Myocarditis-An Unusual Cause of Left Ventricular Hypertrophy.

    Science.gov (United States)

    Coffin, Samuel T; Benton, Stewart M; Lenihan, Daniel J; Naftilan, Allen J; Mendes, Lisa A

    2014-10-16

    : Eosinophilic myocarditis is a rare condition in which inflammation of the heart results in an infiltrative cardiomyopathy that is often difficult to diagnose in the acute setting. It sometimes presents as left ventricular hypertrophy. The authors present a case of a 79-year-old woman with a history of Non-Hodgkin's lymphoma who presented with acute heart failure with marked left ventricular hypertrophy. Echocardiography demonstrated abnormalities consistent with an infiltrative cardiomyopathy, and endomyocardial biopsy showed findings consistent with eosinophilic myocarditis. The patient was managed with diuresis and glucocorticoid therapy, and within 4 weeks of her admission, her clinical status had improved and her echocardiogram normalized. The prompt diagnosis and treatment of this patient's myocarditis likely resulted in her favorable outcome. This illustrates the need for a broad consideration of all the potential causes of hypertrophy and the necessary diagnostic strategies and therapeutic options. PMID:25325192

  1. Activated human platelet products induce proarrhythmic effects in ventricular myocytes.

    Science.gov (United States)

    de Jong, Jonas S S G; Verkerk, Arie O; van Borren, Marcel M G J; Zakhrabova-Zwiauer, Olga M; Nieuwland, Rienk; Meijers, Joost C M; Akkerman, Jan-Willem N; Wilde, Arthur A M; Tan, Hanno L; Dekker, Lukas R C

    2011-09-01

    Sudden cardiac death remains one of the most prevalent modes of death and is mainly caused by ventricular fibrillation (VF) in the setting of acute ischemia resulting from coronary thrombi. Animal experiments have shown that platelet activation may increase susceptibility of ischemic myocardium to VF, but the mechanism is unknown. In the present study, we evaluated the effects of activated blood platelet products (ABPPs) on electrophysiological properties and intracellular Ca(2+) (Ca(2+)(i)) homeostasis. Platelets were collected from healthy volunteers. After activation, their secreted ABPPs were added to superfusion solutions. Rabbit ventricular myocytes were freshly isolated, and membrane potentials and Ca(2+)(i) were recorded using patch-clamp methodology and indo-1 fluorescence measurements, respectively. ABPPs prolonged action potential duration and induced early and delayed afterdepolarizations. ABPPs increased L-type Ca(2+) current (I(Ca,L)) density, but left densities of sodium current, inward rectifier K(+) current, transient outward K(+) current, and rapid component of the delayed rectifier K(+) current unchanged. ABPPs did not affect kinetics or (in)activation properties of membrane currents. ABPPs increased systolic Ca(2+)(i), Ca(2+)(i) transient amplitude, and sarcoplasmic reticulum Ca(2+) content. ABPPs did not affect the Na(+)-Ca(2+) exchange current (I(NCX)) in Ca(2+)-buffered conditions. Products secreted from activated human platelets induce changes in I(Ca,L) and Ca(2+)(i), which result in action potential prolongation and the occurrence of early and delayed afterdepolarizations in rabbit myocytes. These changes may trigger and support reentrant arrhythmias in ischemia models of coronary thrombosis. PMID:21651913

  2. Chronotropic Response of Cultured Neonatal Rat Ventricular Myocytes to Short-Term Fluid Shear

    OpenAIRE

    Lorenzen-schmidt, Ilka; Schmid-scho?nbein, Geert W.; Giles, Wayne R.; Mcculloch, Andrew D.; Chien, Shu; Omens, Jeffrey H.

    2006-01-01

    Ventricular myocytes are continuously exposed to fluid shear in vivo by relative movement of laminar sheets and adjacent cells. Preliminary observations have shown that neonatal myocytes respond to fluid shear by increasing their beating rate, which could have an arrhythmogenic effect under elevated shear conditions. The objective of this study is to investigate the characteristics of the fluid shear response in cultured myocytes and to study selected potential mechanisms. Cultured neonatal r...

  3. Left ventricular hypertrophy in ascending aortic stenosis mice: anoikis and the progression to early failure

    Science.gov (United States)

    Ding, B.; Price, R. L.; Goldsmith, E. C.; Borg, T. K.; Yan, X.; Douglas, P. S.; Weinberg, E. O.; Bartunek, J.; Thielen, T.; Didenko, V. V.; Lorell, B. H.; Schneider, M. (Principal Investigator)

    2000-01-01

    BACKGROUND: To determine potential mechanisms of the transition from hypertrophy to very early failure, we examined apoptosis in a model of ascending aortic stenosis (AS) in male FVB/n mice. METHODS AND RESULTS: Compared with age-matched controls, 4-week and 7-week AS animals (n=12 to 16 per group) had increased ratios of left ventricular weight to body weight (4.7+/-0.7 versus 3.1+/-0.2 and 5. 7+/-0.4 versus 2.7+/-0.1 mg/g, respectively, Phypertrophy to early failure in mice with chronic biomechanical stress and support the hypothesis that the disruption of normal myocyte anchorage to adjacent extracellular matrix and cells, a process called anoikis, may signal apoptosis.

  4. Left Ventricular Hypertrophy and Microalbuminuria in Patients With Essential Hypertension

    OpenAIRE

    Ali Monfared; Arsalan Salari; Fardin Mirbolok; Maryam Momeni; Shora Shafighnia; Maryam Shakiba; Amir Sheikholeslami

    2013-01-01

    Introduction. Microalbuminuria and left ventricular hypertrophy (LVH) have both been shown to predict increased cardiovascular morbidity and mortality, especially in diabetic patients. The present study investigated the relationship between microalbuminuria and LVH in patients with essential hypertension. Materials and Methods. After a primary workup to rule out secondary hypertension, 110 essential hypertensive patients with LVH (mean age, 62.97 ± 11.02 years) and 10 essential hyperte...

  5. Skeletal myocyte hypertrophy requires mTOR kinase activity and S6K1

    International Nuclear Information System (INIS)

    The protein kinase mammalian target of rapamycin (mTOR) is a central regulator of cell proliferation and growth, with the ribosomal subunit S6 kinase 1 (S6K1) as one of the key downstream signaling effectors. A critical role of mTOR signaling in skeletal muscle differentiation has been identified recently, and an unusual regulatory mechanism independent of mTOR kinase activity and S6K1 is revealed. An mTOR pathway has also been reported to regulate skeletal muscle hypertrophy, but the regulatory mechanism is not completely understood. Here, we report the investigation of mTOR's function in insulin growth factor I (IGF-I)-induced C2C12 myotube hypertrophy. Added at a later stage when rapamycin no longer had any effect on normal myocyte differentiation, rapamycin completely blocked myocyte hypertrophy as measured by myotube diameter. Importantly, a concerted increase of average myonuclei per myotube was observed in IGF-I-stimulated myotubes, which was also inhibited by rapamycin added at a time when it no longer affected normal differentiation. The mTOR protein level, its catalytic activity, its phosphorylation on Ser2448, and the activity of S6K1 were all found increased in IGF-I-stimulated myotubes compared to unstimulated myotubes. Using C2C12 cells stably expressing rapamycin-resistant forms of mTOR and S6K1, we provide genetic evidence for the requirement of mTOR and its downstream effector S6K1 in the regulation of myotube hypertrophy. Our results suggest distinct hypertrophy. Our results suggest distinct mTOR signaling mechanisms in different stages of skeletal muscle development: While mTOR regulates the initial myoblast differentiation in a kinase-independent and S6K1-independent manner, the hypertrophic function of mTOR requires its kinase activity and employs S6K1 as a downstream effector

  6. Effects of neuropeptide Y on L-type calcium current in guinea-pig ventricular myocytes.

    OpenAIRE

    Bryant, S. M.; Hart, G.

    1996-01-01

    1. Neuropeptide Y (NPY) reduces cell shortening at high concentrations in guinea-pig ventricular myocytes. We have studied the effects of the peptide on calcium current in cardiac myocytes. 2. We have recorded L-type calcium current in guinea-pig ventricular myocytes under conditions in which the effects of other overlapping currents have been minimised by using Na(+)-free, K(+)-free external solution and patch-clamp electrodes containing Cs+. 3. Peak inward calcium current is reduced by NPY ...

  7. Tonic block of the Na+ current in single atrial and ventricular guinea-pig myocytes, by a new antiarrhythmic drug, Ro 22-9194.

    Science.gov (United States)

    Hiroe, K; Hisatome, I; Tanaka, Y; Ahmmed, G U; Sasaki, N; Shimoyama, M; Tsuboi, M; Inoue, Y; Manabe, I; Yamamoto, Y; Ohtahata, A; Kinugawa, T; Ogino, K; Igawa, O; Yoshida, A; Shigemasa, C; Sato, R

    1997-01-01

    Ro 22-9194 reduced the Na+ current in the atrial myocytes as well as ventricular myocytes in a tonic block fashion. Ro 22-9194 had a higher affinity to the inactivated state Na+ channels (KdI = 3.3 microM in atrial myocytes, KdI = 10.3 microM in ventricular myocytes) than to those in the rested state (KdR = 91 microM in atrial myocytes, KdR = 180 microM in ventricular myocytes), which indicated that Ro 22-9194 had a higher affinity to the Na+ channels in atrial myocytes than in ventricular myocytes. Ro 22-9194 shifted the inactivation curve in the hyperpolarized direction in both atrial and ventricular myocytes. These findings suggest that Ro 22-9194 more strongly inhibited the Na+ channel of the atrial myocytes of the diseased hearts with the depolarized membranes potentials than the Na+ channels in ventricular myocytes. PMID:9342593

  8. L-Arginine currents in rat cardiac ventricular myocytes.

    Science.gov (United States)

    Peluffo, R Daniel

    2007-05-01

    L-Arginine (L-Arg) is a basic amino acid that plays a central role in the biosynthesis of nitric oxide, creatine, agmantine, polyamines, proline and glutamate. Most tissues, including myocardium, must import L-Arg from the circulation to ensure adequate intracellular levels of this amino acid. This study reports novel L-Arg-activated inward currents in whole-cell voltage-clamped rat ventricular cardiomyocytes. Ion-substitution experiments identified extracellular L-Arg as the charge-carrying cationic species responsible for these currents, which, thus, represent L-Arg import into cardiac myocytes. This result was independently confirmed by an increase in myocyte nitric oxide production upon extracellular application of L-Arg. The inward movement of Arg molecules was found to be passive and independent of Na(2+), K(2+), Ca(2+) and Mg(2+). The process displayed saturation and membrane potential (V(m))-dependent kinetics, with a K(0.5) for l-Arg that increased from 5 mm at hyperpolarizing V(m) to 20 mm at +40 mV. L-Lysine and L-ornithine but not D-Arg produced currents with characteristics similar to that activated by L-Arg indicating that the transport process is stereospecific for cationic L-amino acids. L-Arg current was fully blocked after brief incubation with 0.2 mm N-ethylmaleimide. These features suggest that the activity of the low-affinity, high-capacity CAT-2A member of the y(2+) family of transporters is responsible for L-Arg currents in acutely isolated cardiomyocytes. Regardless of the mechanism, we hypothesize that a low-affinity arginine transport process in heart, by ensuring substrate availability for sustained NO production, might play a cardio-protective role during catabolic states known to increase Arg plasma levels severalfold. PMID:17303641

  9. Physiological pathway of magnesium influx in rat ventricular myocytes.

    Science.gov (United States)

    Tashiro, Michiko; Inoue, Hana; Konishi, Masato

    2014-11-01

    Cytoplasmic free Mg(2+) concentration ([Mg(2+)]i) was measured in rat ventricular myocytes with a fluorescent indicator furaptra (mag-fura-2) introduced by AM-loading. By incubation of the cells in a high-K(+) (Ca(2+)- and Mg(2+)-free) solution, [Mg(2+)]i decreased from ? 0.9 mM to 0.2 to 0.5 mM. The lowered [Mg(2+)]i was recovered by perfusion with Ca(2+)-free Tyrode's solution containing 1 mM Mg(2+). The time course of the [Mg(2+)]i recovery was fitted by a single exponential function, and the first derivative at time 0 was analyzed as being proportional to the initial Mg(2+) influx rate. The Mg(2+) influx rate was inversely related to [Mg(2+)]i, being higher at low [Mg(2+)]i. The Mg(2+) influx rate was augmented by the high extracellular Mg(2+) concentration (5 mM), whereas it was greatly reduced by cell membrane depolarization caused by high K(+). Known inhibitors of TRPM7 channels, 2-aminoethoxydiphenyl borate (2-APB), NS8593, and spermine reduced the Mg(2+) influx rate with half inhibitory concentrations (IC50) of, respectively, 17 ?M, 2.0 ?M, and 22 ?M. We also studied Ni(2+) influx by fluorescence quenching of intracellular furaptra by Ni(2+). The Ni(2+) influx was activated by lowering intra- and extracellular Mg(2+) concentrations, and it was inhibited by 2-APB and NS8593 with IC50 values comparable with those for the Mg(2+) influx. Intracellular alkalization (caused by pulse application of NH4Cl) enhanced, whereas intracellular acidification (induced after the removal of NH4Cl) slowed the Mg(2+) influx. Under the whole-cell patch-clamp configuration, the removal of intracellular and extracellular divalent cations induced large inward and outward currents, MIC (Mg-inhibited cation) currents or IMIC, carried by monovalent cations likely via TRPM7 channels. IMIC measured at -120 mV was diminished to ? 50% by 100 ?M 2-APB or 10 ?M NS8593. These results suggest that TRPM7/MIC channels serve as a major physiological pathway of Mg(2+) influx in rat ventricular myocytes. PMID:25418090

  10. Cell contact as an independent factor modulating cardiac myocyte hypertrophy and survival in long-term primary culture

    Science.gov (United States)

    Clark, W. A.; Decker, M. L.; Behnke-Barclay, M.; Janes, D. M.; Decker, R. S.

    1998-01-01

    Cardiac myocytes maintained in cell culture develop hypertrophy both in response to mechanical loading as well as to receptor-mediated signaling mechanisms. However, it has been shown that the hypertrophic response to these stimuli may be modulated through effects of intercellular contact achieved by maintaining cells at different plating densities. In this study, we show that the myocyte plating density affects not only the hypertrophic response and features of the differentiated phenotype of isolated adult myocytes, but also plays a significant role influencing myocyte survival in vitro. The native rod-shaped phenotype of freshly isolated adult myocytes persists in an environment which minimizes myocyte attachment and spreading on the substratum. However, these conditions are not optimal for long-term maintenance of cultured adult cardiac myocytes. Conditions which promote myocyte attachment and spreading on the substratum, on the other hand, also promote the re-establishment of new intercellular contacts between myocytes. These contacts appear to play a significant role in the development of spontaneous activity, which enhances the redevelopment of highly differentiated contractile, junctional, and sarcoplasmic reticulum structures in the cultured adult cardiomyocyte. Although it has previously been shown that adult cardiac myocytes are typically quiescent in culture, the addition of beta-adrenergic agonists stimulates beating and myocyte hypertrophy, and thereby serves to increase the level of intercellular contact as well. However, in densely-plated cultures with intrinsically high levels of intercellular contact, spontaneous contractile activity develops without the addition of beta-adrenergic agonists. In this study, we compare the function, morphology, and natural history of adult feline cardiomyocytes which have been maintained in cultures with different levels of intercellular contact, with and without the addition of beta-adrenergic agonists. Intercellular contact, communication, and transmission of contractile forces between myocytes appears to play a primary role in remodeling the 2-dimensional cell layer into a parallel alignment of elongated myocytes with highly developed intercalated disk-like junctions. This highly differentiated state is very stable, and cultures which achieve this state exhibit significantly greater longevity than more sparsely plated myocytes. These myocytes typically continue beating, and survive from 6 to more than 12 weeks in culture. When this level of contact and differentiation are not achieved, even among beta-adrenergic stimulated myocytes, contractile activity is not sustained, myofibrils atrophy, there is little or no development of junctional complexes, and the period of myocyte viability is typically no more than 5 weeks in vitro.

  11. An analysis of electrocardiographic criteria for determining left ventricular hypertrophy

    Scientific Electronic Library Online (English)

    Carlos Alberto, Gasperin; Helio, Germiniani; Carlos Roberto, Facin; Admar Moraes de, Souza; Cláudio Leinig Pereira da, Cunha.

    2002-01-01

    Full Text Available OBJECTIVE: To determine the most sensitive criterion for the detection of left ventricular hypertrophy according to echocardiographically defined left ventricular mass. METHODS: The Sokolow-Lyon voltage, Sokolow-Lyon-Rappaport, Cornell voltage duration product, White-Bock, and Romhilt-Estes point sc [...] oring criteria were compared with left ventricular mass index, corrected for body surface, obtained from the echocardiograms of 306 outpatients (176 females, 130 males), of all age groups. RESULTS: The Cornell voltage duration product criteria index had the greatest sensitivity in women (54.90%), and the Sokolow-Lyon-Rappaport index was most sensitive in men (73.53%). When applied to men at the same voltage amplitude (20mm) as that in women, the Cornell index showed increased sensitivity relative to the conventional index (28mm) of 67.65% (P

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

    International Nuclear Information System (INIS)

    For 15 normotensive patients with asymmetric septal hypertrophy (ASH), 10 hypertensive patients with concentric hypertrophy (CH), and five normal subjects (N), we examined changes in myocardial T1 and T2 values related to the cardiac cycle. The usefulness of those values in differentiating diseases with left ventricular hypertrophy was evaluated. Left ventricular (LV) short-axis spin echo images and inversion recovery images were obtained at endsystolic and diastolic cardiac phases, and T1 and T2 images were calculated. The regional wall thickness (WT) and T1 and T2 values were measured in the anterior septum, anterior wall, lateral wall, posterior wall and posterior septum. Myocardial T1 and T2 values were significantly decreased in systole (T1: 185.6±37.9 msec, T2: 24.4±6.3 msec, mean±SD) compared to those in diastole (T1: 249.2±56.7 msec, T2: 31.7±9.4 msec). In both the ASH and CH groups, significant correlations were observed between diastolic T1 values and WT (ASH: r = 0.80, p 2 values and WT (ASH: r = 0.58, p 1 values in the ASH group (343.4±40.5 msec) were significantly higher than those of the CH group (247.3±21.4 msec), although the mean wall thic msec), although the mean wall thickness values were similar in both groups. The T1/WT and T2/WT were significantly lower in the CH group than those in the ASH and N groups. In conclusion, myocardial T1 and T2 values were related not only to the cardiac cycle, but to wall thickness and to types of hypertrophy. The T1 and T2 values may be useful for distinguishing hypertrophic cardiomyopathy from hypertrophy due to hypertension. (author)

  13. Dual effect of ethanol on inward rectifier potassium current IK1 in rat ventricular myocytes.

    Czech Academy of Sciences Publication Activity Database

    Bébarová, M.; Matejovi?, P.; Pásek, Michal; Šimurdová, M.; Šimurda, J.

    2014-01-01

    Ro?. 65, ?. 4 (2014), s. 497-509. ISSN 0867-5910 Grant ostatní: GA MZd NT14301 Institutional support: RVO:61388998 Keywords : ethanol * rat ventricular myocyte * rat ventricular action potential model Subject RIV: BO - Biophysics Impact factor: 2.720, year: 2013

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

    Directory of Open Access Journals (Sweden)

    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 refractory characteristics mediated by the luminal SR Ca2+ sensor. Proper functioning of the DCU, sodium-calcium exchangers and SERCA pump are important in achieving negative feedback control and hence Ca2+ homeostasis. Conclusions We examine the role of the above Ca2+ regulating mechanisms in handling various types of induced disturbances in Ca2+ levels by quantifying cellular Ca2+ balance. Our model provides biophysically-based explanations of phenomena associated with CICR generating useful and testable hypotheses.

  15. Bone marrow mesenchymal stem cells upregulate transient outward potassium currents in postnatal rat ventricular myocytes.

    Science.gov (United States)

    Benzhi, Cai; Limei, Zhao; Ning, Wang; Jiaqi, Liu; Songling, Zhu; Fanyu, Meng; Hongyu, Zhou; Yanjie, Lu; Jing, Ai; Baofeng, Yang

    2009-07-01

    Bone marrow mesenchymal stem cell (BMSC) transplantation has been shown to effectively improve cardiac function in experimental animals and patients with myocardial infarction and heart hypertrophy. BMSCs exert potent effects on cardiomyocytes through the inhibition of cardiac apoptosis, the attenuation of cardiac inflammation, etc. However, novel biological actions of BMSCs on cardiomyocytes remain to be explored. The present study was designed to investigate whether BMSCs affect electrophysiological features of neonatal rat ventricular myocytes (NRVMs). BMSCs and NRVMs were indirectly co-cultured at a ratio of 1:10 with a semi-permeable membrane. We found that compared with mono-cultured NRVMs, co-cultured NRVMs exhibited an obvious increase of transient outward potassium current (I(to)), accompanied by significant changes in activation, inactivation and recovery of I(to). Meanwhile, K(V)4.2 mRNA which encodes the channel carrying I(to) was more abundant in co-cultured NRVMs than mono-cultured NRVMs. The increases in basic fibroblast growth factor (bFGF) and insulin growth factor-1 (IGF-1) levels were observed in culture medium of BMSCs. bFGF but not IGF-1 upregulated the K(V)4.2 mRNA expression and enhanced I(to) currents. Taken together, we conclude that BMSCs upregulate I(to) of NRVMs, at least partially, by secreting bFGF that in turn upregulates K(V)4.2 expression and alters the kinetics of I(to). PMID:19285983

  16. Measurement of Cardiac Mechanical Function in Isolated Ventricular Myocytes from Rats and Mice by Computerized Video-Based Imaging

    Directory of Open Access Journals (Sweden)

    Ren Jun

    2001-01-01

    Full Text Available Isolated adult cardiac ventricular myocytes have been a useful model for cardiovascular research for more than 20 years. With the recent advances in cellular physiology and transgenic techniques, direct measurement of isolated ventricular myocyte mechanics is becoming an increasingly important technique in cardiac physiology that provides fundamental information on excitation-contraction coupling of the heart, either in drug intervention or pathological states. The goal of this article is to describe the isolation of ventricular myocytes from both rats and mice, and the use of real-time beat-to-beat simultaneous recording of both myocyte contraction and intracellular Ca2+ transient.

  17. Left Ventricular Hypertrophy and Microalbuminuria in Patients With Essential Hypertension

    Directory of Open Access Journals (Sweden)

    Ali Monfared

    2013-05-01

    Full Text Available Introduction. Microalbuminuria and left ventricular hypertrophy (LVH have both been shown to predict increased cardiovascular morbidity and mortality, especially in diabetic patients. The present study investigated the relationship between microalbuminuria and LVH in patients with essential hypertension. Materials and Methods. After a primary workup to rule out secondary hypertension, 110 essential hypertensive patients with LVH (mean age, 62.97 ± 11.02 years and 10 essential hypertensive patients without LVH (mean age, 65.13 ± 10.15 years were enrolled in this case-control study. Spot urine sample was collected for the assessment of microalbuminuria and creatinine concentrations in the two groups. Smoking status, blood pressure, and serum levels of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and creatinine were evaluated.  Results. Patients with LVH had significantly higher microalbuminuria level compared with those without LVH (mean urine albumin-creatinine ratio, 54.4 ± 39.48 ?g/mg versus 33.56 ± 21.73 ?g/mg; P P Conclusions. Left ventricular hypertrophy is associated with microalbuminuria in patients with essential hypertension. These data are strengthening the role of microalbuminuria as an indicator of high cardiovascular risk.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1988-06-01

    For 15 normotensive patients with asymmetric septal hypertrophy (ASH), 10 hypertensive patients with concentric hypertrophy (CH), and five normal subjects (N), we examined changes in myocardial T/sub 1/ and T/sub 2/ values related to the cardiac cycle. The usefulness of those values in differentiating diseases with left ventricular hypertrophy was evaluated. Left ventricular (LV) short-axis spin echo images and inversion recovery images were obtained at endsystolic and diastolic cardiac phases, and T/sub 1/ and T/sub 2/ images were calculated. The regional wall thickness (WT) and T/sub 1/ and T/sub 2/ values were measured in the anterior septum, anterior wall, lateral wall, posterior wall and posterior septum. Myocardial T/sub 1/ and T/sub 2/ values were significantly decreased in systole (T/sub 1/: 185.6+-37.9 msec, T/sub 2/: 24.4+-6.3 msec, mean+-SD) compared to those in diastole (T/sub 1/: 249.2+-56.7 msec, T/sub 2/: 31.7+-9.4 msec). In both the ASH and CH groups, significant correlations were observed between diastolic T/sub 1/ values and WT (ASH: r = 0.80, p < 0.01, CH: r = 0.45, p < 0.01), and between diastolic T/sub 2/ values and WT (ASH: r = 0.58, p < 0.01, CH: r = 0.60, p < 0.01). In the regions where diastolic WT were more than 17 mm, T/sub 1/ values in the ASH group (343.4+-40.5 msec) were significantly higher than those of the CH group (247.3+-21.4 msec), although the mean wall thickness values were similar in both groups. The T/sub 1//WT and T/sub 2//WT were significantly lower in the CH group than those in the ASH and N groups. In conclusion, myocardial T/sub 1/ and T/sub 2/ values were related not only to the cardiac cycle, but to wall thickness and to types of hypertrophy. The T/sub 1/ and T/sub 2/ values may be useful for distinguishing hypertrophic cardiomyopathy from hypertrophy due to hypertension.

  19. 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.

  20. Effects of tanshinone VI on the hypertrophy of cardiac myocytes and fibrosis of cardiac fibroblasts of neonatal rats.

    Science.gov (United States)

    Maki, Toshiyuki; Kawahara, Yuji; Tanonaka, Kouichi; Yagi, Akira; Takeo, Satoshi

    2002-12-01

    The possible effects of tanshinone VI (tsh), a diterpene from the root of Tan-Shen (Salvia miltiorrhiza, Bunge (Labiatae)) on hypertrophy and fibrosis in cultured neonatal rat cardiac myocytes and fibroblasts were examined. Tsh had no significant effect on protein synthesis, which was evaluated by [3H]-leucine incorporation into the acid insoluble fraction in the cells, in the absence of stimulatory factors in cardiac myocytes. The amount of protein produced in cardiac myocytes was increased by 10(-8) M endothelin-1 (ET-1), 10(-6) M phenylephrine (PE), or 10(-8) M insulin-like growth factor-1 (IGF-1), suggesting that hypertrophy of cardiac myocytes in vitro was induced by these factors. The ET-1-, PE-, or IGF-1-induced increase in protein synthesis was attenuated by treatment with 10(-5) M tsh. Treatment with 10(-5) M tsh significantly decreased the synthesis of collagen by cardiac fibroblasts, which was evaluated by [3H]-proline incorpolation into acid-insoluble fraction of the fiblobrasts, in the absence of stimulatory factors for the production. Fetal bovine serum (FBS) or IGF-1 increased collagen synthesis in a concentration-dependent manner. The increase at 5% FBS or 10(-8) M IGF-1 was inhibited by 10(-5) M tsh. Fibroblast-conditioned medium (FB-CM) increased protein synthesis in cardiac myocytes in a concentration-dependent manner (10; - 100 %). Tsh attenuated the FB-CM-induced increase in protein synthesis by cardiac myocytes. These results show that tsh may attenuate the humoral factor-induced hypertrophy of cardiac myocytes and fibrosis of cardiac fibroblasts. The findings suggest that tsh may improve the development of cardiac remodeling under pathophysiological conditions. Abbreviations. ANP:atrial natriuretic peptide DMEM:Dulbecco-modified Eagle's medium ET-1:endothelin-1 FB-CM:fibroblast-conditioned medium FBS:fetal bovine serum IGF-1:insulin-like growth factor-1 PE:phenylephrine tsh:tanshinone VI PMID:12494338

  1. Non-gated computed tomography of left ventricular hypertrophy

    International Nuclear Information System (INIS)

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

  2. Arritmias ventriculares e hipertrofia ventricular esquerda na cardiomiopatia hipertrófica / Ventricular arrhythmias and left ventricular hypertrophy in hypertrophic cardiomyopathy

    Scientific Electronic Library Online (English)

    Beatriz Piva e, Mattos; Marco Antonio Rodrigues, Torres; Valéria Centeno de, Freitas; Fernando Luís, Scolari; Melina Silva de, Loreto.

    2013-05-01

    Full Text Available SciELO Brazil | Languages: English, Portuguese Abstract in portuguese FUNDAMENTO: Na Cardiomiopatia Hipertrófica (CMH), o grau de Hipertrofia Ventricular Esquerda (HVE) poderia influenciar o desenvolvimento de arritmias ventriculares. OBJETIVO: Analisar, na CMH, a associação entre a ocorrência de arritmias ventriculares no eletrocardiograma-Holter (ECG-Holter) e o gra [...] u de HVE determinado ao ecocardiograma pela espessura parietal máxima (EPM) e Índice de Massa (IM). MÉTODOS: Cinquenta e quatro pacientes consecutivos com CMH realizaram ECG-Holter de 24 horas e ecocardiograma para avaliação do grau de HVE através da EPM e IM. Foram estabelecidos dois níveis para a ocorrência de arritmias ventriculares: I - extrassístoles isoladas ou pareadas e II - Taquicardia Ventricular Não Sustentada (TVNS). RESULTADOS: Nos 13 pacientes (24%) com TVNS (nível II), houve maior frequência de EPM do ventrículo esquerdo (VE) > 21 mm (n = 10, 77%; 25 ± 4 mm) e IMVE > 144 g/m² (n = 10, 77%; 200 ± 30 g/m²), em relação àqueles que apresentavam apenas arritmia extrassistólica (nível I) (n = 41, 76%), em que essas medidas foram identificadas em, respectivamente, 37% (n = 15, 23 ± 1 mm), p = 0,023, e 39% (n = 16, 192 ± 53 g/m²) dos casos, p = 0,026. Os citados valores de corte foram determinados por curva ROC com intervalo de confiança de 95%. O registro de TVNS foi mais comum em pacientes com EPMVE > 21 mm e IMVE > 144 g/m² (8 de 13; 62%), do que naqueles com uma (4 de 13; 31%) ou nenhuma (1 de 13; 8%) variável ecocardiográfica acima dos valores de corte, p = 0,04. CONCLUSÃO: A ocorrência de arritmias ventriculares no Holter associou-se, na CMH, ao grau de HVE, avaliado pelo ecocardiograma através da respectiva EPM e IM. Abstract in english BACKGROUND: In hypertrophic cardiomyopathy (HCM), the degree of left ventricular hypertrophy (LVH) could influence the development of ventricular arrhythmias. OBJECTIVE: In HCM, analyze the association between the occurrence of ventricular arrhythmias determined by Holter electrocardiogram (ECG-Holt [...] er) and the degree of LVH determined by maximum wall thickness (MWT) in echocardiography and body mass index (BMI). METHODS: Fifty-four consecutive patients with HCM underwent 24-hour ECG-Holter and echocardiography for assessment of level of LVH through MWT and BMI. Two levels were established for the occurrence of Ventricular Arrhythmias: I - alone or paired extrasystoles and II - Non- Sustained Ventricular Tachycardia (NSVT). RESULTS: In 13 patients (24%) with NSVT (level II), there was a higher frequency of MWT of the left ventricle (LV) > 21 mm (n = 10, 77%, 25 ± 4 mm) and LLLV = 144 g/m² (n = 10, 77%, 200 ± 30 g/m²), in comparison with those presenting with extrasystole arrhythmias (level I) (n = 41, 76%), in which these measures were identified in, respectively, 37 % (n= 15, 23 ± 1 mm), p = 0.023, and 39% (n = 16, 192 ± 53 g / m²) of the cases (p = 0.026). The cut-off values mentioned were determined by the ROC curve with a confidence interval of 95%. NSVT was more common in patients with MWTLV > 21 mm and LLLV > 144 g/m² (8 of 13, 62%) than in those with (4 of 13, 31%) or without (1 of 13; 8%) echocardiographic variables above cut-off values (p = 0.04). CONCLUSION: In HCM, occurrence of ventricular arrhythmias by Holter was associated with the degree of LVH assessed by echocardiography through MWT and BMI.

  3. Electrophysiological effects of bimoclomol in canine ventricular myocytes.

    Science.gov (United States)

    Magyar, J; Bányász, T; Szigligeti, P; Körtvély, A; Jednákovits, A; Nánási, P P

    2000-03-01

    Concentration-dependent effects of bimoclomol, a novel heat shock protein (HSP) coinducer, were studied on the parameters of action potential and transmembrane ionic currents in enzymatically dispersed canine ventricular cardiomyocytes using conventional microelectrode and whole cell voltage clamp techniques. Bimoclomol (10-100 microM) decreased the maximum velocity of depolarization (Vmax) and amplitude of action potentials in a concentration-dependent manner. These effects were fully reversible after a 5-min period of washout in drug-free medium. Action potential duration measured at 50% or 90% level of repolarization (APD-50 and APD-90, respectively) was markedly shortened by bimoclomol. Both APD-50 and APD-90 were decreased, but the reduction in APD-50 was more pronounced. The APD-shortening effect of bimoclomol was significantly reduced in the presence of 20 nM charybdotoxin (inhibitor of the Ca-dependent K current) or 0.5 mM anthracene-9-carboxylic acid (inhibitor of the Ca-dependent Cl current) or 1 microM glibenclamide (inhibitor of the ATP-sensitive K current). In the presence of anthracene-9-carboxylic acid, APD-90 was lengthened by bimoclomol. The APD-shortening effect of bimoclomol was also partially antagonized by chelation of intracellular Ca2+ by application of the cell permeant form of BAPTA, or when using 10 mM EGTA-containing patch pipettes to record action potentials. The Vmax-depressant effect of bimoclomol was not affected by charybdotoxin, anthracene-9-carboxylic acid, glibenclamide, or BAPTA load. In voltage clamped cardiomyocytes bimoclomol (100 microM) had no effect on the amplitude of I(Ca), but decreased significantly the inactivation time constant of I(Ca) (from 19.8+/-1.6 ms to 16.8+/-1.2 ms at 0 mV). Bimoclomol also decreased significantly the amplitude of I(K1) (from -20.5+/-1.1 pA/pF to -16.6+/-0.8 pA/pF at -135 mV), causing reduction in slope of the negative branch of the I-V curve. At positive potentials, however, bimoclomol increased outward current. The bimoclomol-induced current, therefore, was studied in the presence of BaCl2, when I(K1) current was blocked. The bimoclomol-induced current had a reversal potential close to -90 mV. Bimoclomol (100 microM) had no effect on the amplitude or kinetic properties of the transient outward K current (I(to)) and the delayed rectifier K current (I(K)). It is concluded that bimoclomol exerts both Ca-independent (inhibition of I(Na) and I(K1), activation of the ATP-sensitive K current) and Ca-dependent effects (mediated by Ca-activated Cl and probably K currents) in canine ventricular myocytes. PMID:10731044

  4. Obesity and left ventricular hypertrophy: the hypertension connection.

    Science.gov (United States)

    Woodiwiss, Angela J; Norton, Gavin R

    2015-04-01

    The detection of left ventricular hypertrophy (LVH) is recommended for risk prediction, and changes in LV geometry may provide further prognostic information. Obesity is a major determinant of LVH, but the approach to LVH detection in obese hypertensives remains a challenge. In the present review, we discuss evidence leading to the recent acceptance of the use of LV mass indexed to height(2.7) or height(1.7) rather than body surface area, for LVH detection and its regression in obesity. We also review recent findings which indicate that obesity-induced LVH may be associated with concentric LV remodeling, and hence, that the presence of concentric LVH in obesity should not be assumed to indicate a cause of LVH other than obesity. We also discuss recent evidence for obesity and blood pressure producing additive and interactive effects on LV mass, and hence, that weight loss and blood pressure reduction are required to achieve appropriate regression. PMID:25794954

  5. Calcium signaling regulates ventricular hypertrophy during development independent of contraction or blood flow.

    Science.gov (United States)

    Andersen, Nicholas D; Ramachandran, Kapil V; Bao, Michelle M; Kirby, Margaret L; Pitt, Geoffrey S; Hutson, Mary R

    2015-03-01

    In utero interventions aimed at restoring left ventricular hemodynamic forces in fetuses with prenatally diagnosed hypoplastic left heart syndrome failed to stimulate ventricular myocardial growth during gestation, suggesting chamber growth during development may not rely upon fluid forces. We therefore hypothesized that ventricular hypertrophy during development may depend upon fundamental Ca(2+)-dependent growth pathways that function independent of hemodynamic forces. To test this hypothesis, zebrafish embryos were treated with inhibitors or activators of Ca(2+) signaling in the presence or absence of contraction during the period of chamber development. Abolishment of contractile function alone in the setting of preserved Ca(2+) signaling did not impair ventricular hypertrophy. In contrast, inhibition of L-type voltage-gated Ca(2+) influx abolished contraction and led to reduced ventricular hypertrophy, whereas increasing L-type voltage-gated Ca(2+) influx led to enhanced ventricular hypertrophy in either the presence or absence of contraction. Similarly, inhibition of the downstream Ca(2+)-sensitive phosphatase calcineurin, a known regulator of adult cardiac hypertrophy, led to reduced ventricular hypertrophy in the presence or absence of contraction, whereas hypertrophy was rescued in the absence of L-type voltage-gated Ca(2+) influx and contraction by expression of a constitutively active calcineurin. These data suggest that ventricular cardiomyocyte hypertrophy during chamber formation is dependent upon Ca(2+) signaling pathways that are unaffected by heart function or hemodynamic forces. Disruption of Ca(2+)-dependent hypertrophy during heart development may therefore represent one mechanism for impaired chamber formation that is not related to impaired blood flow. PMID:25536179

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

    International Nuclear Information System (INIS)

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

  7. The morphological patterns of left ventricular hypertrophy and left ventricular performance in essential hypertensives

    International Nuclear Information System (INIS)

    Magnetic resonance imaging (MRI) was performed in 27 patients with essential hypertension (EHT), in whom the ventricular septum or left ventricular free wall or both was 12 mm or more in thickness on two-dimensional echocardiograms, and four healthy volunteers to determine the morphology of left ventricular hypertrophy (LVH). The morphological appearances of LVH were divided into four types: (1) diffuse (D) type in which the entire left ventricle was diffusely thickened (n = 11); (2) free wall (F) type in which the free wall was much more thickened than the other sites (n = 8); (3) apical (A) type in which the thickness was limited to the apical site (n = 5); (4) septal (S) type in which the ventricular septum was asymmetrically thickened (n = 3). Ejection fraction (EF), 1/3 filling fraction, and time to peak filling rate, as determined by blood pool scintigraphy, were used as systolic and diastolic function indices. Groups of both D-type and F-type patients had normal systolic function, depressed diastolic function, and decreased cardiac reserve. The group of A-type patients had a marked decrease in both systolic and diastolic functions, and normal cardiac reserve. In the last group of S-type patients, systolic function was hyperkinetic, diastolic function was decreased, and cardiac reserve was normal. In cases or LVH, left ventricular performance was found to vary according to the morphology of LVH. (Namekawa, K.)

  8. Prevalencia de hipertrofia ventricular izquierda en pacientes hipertensos / Prevalence of left ventricular hypertrophy in hypertensive patients

    Scientific Electronic Library Online (English)

    Fred Gustavo, Manrique; Juan Manuel, Ospina; Giomar Maritza, Herrera-Amaya.

    2014-07-01

    Full Text Available SciELO Colombia | Language: Spanish Abstract in spanish Antecedentes: se ha documentado a la hipertrofia ventricular izquierda como una de las manifestaciones tempranas de afectación cardiaca en la enfermedad hipertensiva. Objetivo: evaluar la prevalencia de hipertrofia ventricular izquierda en los pacientes hipertensos que asisten a los programas de con [...] trol en instituciones de salud de Boyacá. Material y métodos: mediante muestreo secuencial aleatorio se ensambló una muestra de 1275 pacientes a quienes se realizó valoración de la presión arterial y electrocardiograma. Se evaluaron criterios de Cornell, Romhilt-Estest y Rodríguez-Padial para determinar la presencia de hipertrofia ventricular izquierda. Resultados: se encontró prevalencia global de 17.9% de HVI en los pacientes analizados, con marcadas diferencias por municipio. La HVI se encontró asociada con edad mayor de 65 años, sexo femenino, índice de masa corporal aumentado y cifras elevadas de presión sistólica y diastólica. Conclusión: estos resultados sugieren la necesidad de incrementar los programas de tamizaje y control de la presión arterial, así como de incluir capacitación a los agentes de salud en la valoración de evidencia sugestiva de HVI como alteraciones electrocardiográficas y diferencias en las presionesentre las dos extremidades superiores. Abstract in english Background: left ventricular hypertrophy has been documented as one of the early manifestations of cardiac involvement in hypertensive disease. Objectives: to assess the prevalence of left ventricular hypertrophy in hypertensive patients attending control programs in health institutions of Boyacá. M [...] aterials and methods: by sequential random sampling, a sample of 1275 patients for whom assessment of blood pressure and electrocardiogram was performed, was assembled. Cornell, Romhilt-ESTest and Rodriguez-Padial criteria were evaluated to determine the presence of left ventricular hypertrophy. Results: overall prevalence of LVH in the patients studied was 17.9%, with marked differences respect to the village of origin. LVH was found associated with age over 65, female gender, increased body mass index and high levels of systolic and diastolic pressure. Conclusion: these results suggest the need for increased screening programs and control of blood pressure as well as include training to health workers in assessing suggestive evidence of LVH as electrocardiographic changes and differences in pressure between the two upper limbs.

  9. Symptomatic and silent myocardial ischaemia in hypertensive patients with left ventricular hypertrophy.

    OpenAIRE

    Pringle, S. D.; Dunn, F. G.; Tweddel, A. C.; Martin, W.; Macfarlane, P. W.; Mckillop, J. H.; Lorimer, A. R.; Cobbe, S. M.

    1992-01-01

    OBJECTIVE--To assess the prevalence of symptomatic and silent myocardial ischaemia in patients with hypertensive left ventricular hypertrophy. DESIGN--Cross sectional study. SETTING--University department of medical cardiology. PATIENTS--90 patients (68 men and 22 women; mean age 57 (range 25 to 79)) with left ventricular hypertrophy due to essential hypertension. INTERVENTIONS--48 hour ambulatory ST segment monitoring (all patients), exercise electrocardiography (n = 79), stress thallium sci...

  10. Asymmetric left ventricular hypertrophy associated with morbid obesity mimicking familial hypertrophic cardiomyopathy.

    Science.gov (United States)

    Wong, Raymond Ching-Chiew; Tan, Kong Bing

    2014-12-01

    Asymmetric septal hypertrophy with systolic anterior motion of the mitral valve is frequently a phenotypic, but not pathognomonic, expression of genetic hypertrophic cardiomyopathy (HCM) with or without obstruction. It can, however, be associated nonspecifically with other forms of increased left ventricular (LV) afterload. We herein report the case of a young man with obesity cardiomyopathy and heart failure who presented with asymmetric septal hypertrophy and marked LV hypertrophy, and endomyocardial biopsy ruled out genetic HCM. PMID:25630327

  11. 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

  12. Exercise body surface mapping in patients with left ventricular hypertrophy

    International Nuclear Information System (INIS)

    To evaluate exercise-induced myocardial ischemia in patients with electrocardiographic evidence of left ventricular hypertrophy (LVH), including ST·T changes, body surface maps (QRST area maps) were recorded using 87 lead points before and after exercise. The patterns of the subtraction QRST area maps (S-maps) were compared with the findings of stress thallium (Tl) scans in 31 patients with hypertrophic cardiomyopathy and in five with essential hypertension. All 18 patients whose S-maps revealed changes less than -40 ?VS or only an increase over the anterior chest region showed no positive findings on the stress Tl scans. However, there were clearly positive findings on stress Tl scans in eight (89%) of nine patients whose S-maps revealed changes greater than -40 ?VS over a wide precordial region or in six (67%) of nine patients whose S-maps revealed increases over the anterior chest region and had accompanying changes greater than -40 ?VS somewhere over the precordial region. These results suggested that exercise QRST area maps could differentiate exercise-induced myocardial ischemia from LVH with ST·T changes. (author)

  13. Distribution of proteins implicated in excitation-contraction coupling in rat ventricular myocytes.

    OpenAIRE

    Scriven, D. R.; Dan, P.; Moore, E. D.

    2000-01-01

    We have examined the distribution of ryanodine receptors, L-type Ca(2+) channels, calsequestrin, Na(+)/Ca(2+) exchangers, and voltage-gated Na(+) channels in adult rat ventricular myocytes. Enzymatically dissociated cells were fixed and dual-labeled with specific antibodies using standard immunocytochemistry protocols. Images were deconvolved to reverse the optical distortion produced by wide-field microscopes equipped with high numerical aperture objectives. Every image showed a well-ordered...

  14. Swelling-activated Gd3+-sensitive Cation Current and Cell Volume Regulation in Rabbit Ventricular Myocytes

    OpenAIRE

    Clemo, Henry F.; Baumgarten, Clive M.

    1997-01-01

    The role of swelling-activated currents in cell volume regulation is unclear. Currents elicited by swelling rabbit ventricular myocytes in solutions with 0.6–0.9× normal osmolarity were studied using amphotericin perforated patch clamp techniques, and cell volume was examined concurrently by digital video microscopy. Graded swelling caused graded activation of an inwardly rectifying, time-independent cation current (ICir,swell) that was reversibly blocked by Gd3+, but ICir,swell was not...

  15. Overexpression of a human potassium channel suppresses cardiac hyperexcitability in rabbit ventricular myocytes

    OpenAIRE

    Nuss, H. Bradley; Marba?n, Eduardo; Johns, David C.

    1999-01-01

    The high incidence of sudden death in heart failure may reflect abnormalities of repolarization and heightened susceptibility to arrhythmogenic early afterdepolarizations (EADs). We hypothesized that overexpression of the human K+ channel HERG (human ether-a-go-go-related gene) could enhance repolarization and suppress EADs. Adult rabbit ventricular myocytes were maintained in primary culture, which suffices to prolong action potentials and predisposes to EADs. To achieve efficient gene trans...

  16. Time-dependent outward current in guinea pig ventricular myocytes. Gating kinetics of the delayed rectifier

    OpenAIRE

    1990-01-01

    Several conflicting models have been used to characterize the gating behavior of the cardiac delayed rectifier. In this study, whole-cell delayed rectifier currents were measured in voltage-clamped guinea pig ventricular myocytes, and a minimal model which reproduced the observed kinetic behavior was identified. First, whole-cell potassium currents between -10 and +70 mV were recorded using external solutions designed to eliminate Na and Ca currents and two components of time-dependent outwar...

  17. Platelet-activating factor stimulates sodium-hydrogen exchange in ventricular myocytes

    OpenAIRE

    Ajiro, Yoichi; Saegusa, Noriko; Giles, Wayne R.; Stafforini, Diana M.; Spitzer, Kenneth W.

    2011-01-01

    Sodium-hydrogen exchanger (NHE), the principal sarcolemmal acid extruder in ventricular myocytes, is stimulated by a variety of autocrine/paracrine factors and contributes to myocardial injury and arrhythmias during ischemia-reperfusion. Platelet-activating factor (PAF; 1-o-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a potent proinflammatory phospholipid that is released in the heart in response to oxidative stress and promotes myocardial ischemia-reperfusion injury. PAF stimulates NHE in ...

  18. Effect of ethanol on action potential and ionic membrane currents in rat ventricular myocytes.

    Czech Academy of Sciences Publication Activity Database

    Bébarová, M.; Matejovi?, P.; Pásek, Michal; Ohlídalová, D.; Jansová, D.; Šimurdová, M.; Šimurda, J.

    2010-01-01

    Ro?. 200, ?. 4 (2010), s. 301-314. ISSN 1748-1708 Institutional research plan: CEZ:AV0Z20760514 Keywords : action potential * ethanol * rat ventricular myocyte Subject RIV: BO - Biophysics Impact factor: 3.138, year: 2010 http:// apps .isiknowledge.com/full_record.do?product=UA&search_mode=GeneralSearch&qid=15&SID=Y1pmpi@7k2HPEc8ehEE&page=1&doc=1&colname=WOS

  19. Stimulation of Single Isolated Adult Ventricular Myocytes within a Low Volume Using a Planar Microelectrode Array

    OpenAIRE

    Klauke, Norbert; Smith, Godfrey L.; Cooper, Jon

    2003-01-01

    Microchannels (40-?m wide, 10-?m high, 10-mm long, 70-?m pitch) were patterned in the silicone elastomer, polydimethylsiloxane on a microscope coverslip base. Integrated within each microchamber were individually addressable stimulation electrodes (40-?m wide, 20-?m long, 100-nm thick) and a common central pseudo-reference electrode (60-?m wide, 500-?m long, 100-nm thick). Isolated rabbit ventricular myocytes were introduced into the chamber by micropipetting and subsequently capped wi...

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

    OpenAIRE

    Chiranjivi Potu; Edwin Tulloch-Reid; Dainia Baugh; Ismail, Olusegun A.; Madu, Ernest C.

    2012-01-01

    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 ...

  1. A new electrocardiographic left ventricular hypertrophy prognostic score.

    Science.gov (United States)

    Jindal, Akash; Singla, Varun; Pargaonkar, Vedant; Froelicher, Victor

    2015-04-01

    This report determines if the classic Romhilt-Estes score would predict better if points for its components were determined using a Cox hazard model and if the Cornell voltage criteria should replace the original criteria. Of the 20,903 subjects, the mean age was 43 ± 10 years and 90.6% were men. The mean follow-up for the population was 17 years, with 881 cardiovascular deaths; they were tested from 1987 to 1999 and followed until 2013. The new score was created with multipliers based on the Cox hazards of its elements with age bracket and gender included. The Cornell criteria were analyzed individually using Cox hazards with and without adjustments for age, gender, and African-American ethnicity and subsequently incorporated into the new score for analysis. For the new score, all 7 components were significant predictors of cardiovascular mortality with gender producing the greatest hazard ratio (HR) and left axis deviation and QRS duration >110 ms producing the lowest. For the original Romhilt-Estes score, 367 patients (1.8%) met the "definite" cutoff and had an HR of 5.6 (95% confidence interval 4.3 to 7.1). For the new score, 208 patients (1.0%) met the "definite" left ventricular hypertrophy cutoff and had an HR of 13.6 (95% confidence interval 10.8 to 17.3). The Romhilt-Estes had an area under the curve of 0.63, whereas the new score and new score with Cornell voltage both had an area under the curve of 0.7. In conclusion, our modified Romhilt-Estes score with new multipliers and without voltage criteria outperformed the original score. PMID:25700803

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

    Scientific Electronic Library Online (English)

    Diego, Valarezo-Sevilla; Armín, Pazmiño-Martínez; Nidya, Morales-Mora.

    2013-03-01

    Full Text Available SciELO Public Health | Language: Spanish Abstract in spanish 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 pres [...] encia 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 diagnóstico Abstract in english In 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 t [...] rans-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

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

    Scientific Electronic Library Online (English)

    Diego, Valarezo-Sevilla; Armín, Pazmiño-Martínez; Nidya, Morales-Mora.

    2013-01-01

    Full Text Available SciELO Peru | Language: Spanish Abstract in spanish 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 pres [...] encia 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 diagnóstico Abstract in english In 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 t [...] rans-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

  4. Dynamic left ventricular outflow tract obstruction due to concentric left ventricular hypertrophy: effect of pacing with a short AV interval.

    Science.gov (United States)

    Krahn, A D; Geddes, J S

    1994-10-01

    Dual chamber pacing with a short atrioventricular (AV) interval has emerged as a novel therapeutic approach in dynamic left ventricular outflow tract obstruction. A morbidly obese 65-year-old man with previous borderline hypertension and documented normal coronary arteries and concentric left ventricular hypertrophy who underwent uneventful elective hip replacement is reported. Eight hours postoperatively the patient developed junctional tachycardiac and hypotension. Echocardiogram revealed concentric left ventricular hypertrophy with dynamic left ventricular outflow tract obstruction and peak gradient of 262 mmHg. The patient improved with intravenous fluid replacement. The gradient fell to 112 mmHg 14 days later. Twelve days later the patient developed symptomatic sinus pauses and a dual chamber pacemaker was implanted. After testing various AV intervals, the lowest gradient of 138 mmHg was associated with an AV interval of 100 ms. One year later the gradient was 37 mmHg at the same AV interval, with a higher gradient at shorter and longer AV intervals. Dual chamber pacing with a short AV interval has been associated with improvement in hypertrophic obstructive cardiomyopathy. This case suggests the benefit of this therapy may extend to acquired forms of dynamic left ventricular outflow tract obstruction such as concentric left ventricular hypertrophy. PMID:7954021

  5. Effects of cannabidiol on contractions and calcium signaling in rat ventricular myocytes.

    Science.gov (United States)

    Ali, Ramez M; Al Kury, Lina T; Yang, Keun-Hang Susan; Qureshi, Anwar; Rajesh, Mohanraj; Galadari, Sehamuddin; Shuba, Yaroslav M; Howarth, Frank Christopher; Oz, Murat

    2015-04-01

    Cannabidiol (CBD), a major nonpsychotropic cannabinoid found in Cannabis plant, has been shown to influence cardiovascular functions under various physiological and pathological conditions. In the present study, the effects of CBD on contractility and electrophysiological properties of rat ventricular myocytes were investigated. Video edge detection was used to measure myocyte shortening. Intracellular Ca(2+) was measured in cells loaded with the Ca(2+) sensitive fluorescent indicator fura-2 AM. Whole-cell patch clamp was used to measure action potential and Ca(2+) currents. Radioligand binding was employed to study pharmacological characteristics of CBD binding. CBD (1?M) caused a significant decrease in the amplitudes of electrically evoked myocyte shortening and Ca(2+) transients. However, the amplitudes of caffeine-evoked Ca(2+) transients and the rate of recovery of electrically evoked Ca(2+) transients following caffeine application were not altered. CBD (1?M) significantly decreased the duration of APs. Further studies on L-type Ca(2+) channels indicated that CBD inhibits these channels with IC50 of 0.1?M in a voltage-independent manner. Radioligand studies indicated that the specific binding of [(3)H]Isradipine, was not altered significantly by CBD. The results suggest that CBD depresses myocyte contractility by suppressing L-type Ca(2+) channels at a site different than dihydropyridine binding site and inhibits excitation-contraction coupling in cardiomyocytes. PMID:25711828

  6. A localized meshless approach for modeling spatial-temporal calcium dynamics in ventricular myocytes.

    Science.gov (United States)

    Yao, Guangming; Yu, Zeyun

    2012-02-01

    Spatial–temporal calcium dynamics due to calcium release, buffering and re-uptaking plays a central role in studying excitation–contraction (E–C) coupling in both normal and diseased cardiac myocytes. In this paper, we employ a meshless method, namely, the local radial basis function collocation method (LRBFCM), to model such calcium behaviors by solving a nonlinear system of reaction–diffusion partial differential equations. In particular, a simplified structural unit containing a single transverse tubule (T-tubule) and its surrounding half sarcomeres is investigated using the meshless method. Numerical results are compared with those generated by finite element methods, showing the capability and efficiency of the LRBFCM in modeling calcium dynamics in ventricular myocytes. The single T-tubule model is also extended to the whole-cell scale with T-tubules excluded to demonstrate the scalability of the proposed meshless method in handling very large domains. The experiments have shown that the LRBFCM is suitable to multiscale modeling of calcium dynamics in ventricular myocytes with high accuracy and efficiency. PMID:22408720

  7. Presence of a calcium-activated chloride current in mouse ventricular myocytes.

    Science.gov (United States)

    Xu, Yanfang; Dong, Pei Hong; Zhang, Zhao; Ahmmed, Gias Uddin; Chiamvimonvat, Nipavan

    2002-07-01

    The properties of several components of outward K(+) currents, including the pharmacological and kinetics profiles as well as the respective molecular correlates, have been identified in mouse cardiac myocytes. Surprisingly little is known with regard to the Ca(2+)-activated ionic currents. We studied the Ca(2+)-activated transient outward currents in mouse ventricular myocytes. We have identified a 4-aminopyridine (4-AP)- and tetraethyl ammonium-resistant transient outward current that is Ca(2+) dependent. The current is carried by Cl(-) and is critically dependent on Ca(2+) influx via voltage-gated Ca(2+) channels and the sarcoplasmic reticulum Ca(2+) store. The current can be blocked by the anion transport blockers niflumic acid and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid. Single channel recordings reveal small conductance channels (approximately 1 pS in 140 mM Cl(-)) that can be blocked by anion transport blockers. Ensemble-averaged current faithfully mirrors the transient kinetics observed at the whole level. Niflumic acid (in the presence of 4-AP) leads to prolongation of the early repolarization. Thus this current may contribute to early repolarization of action potentials in mouse ventricular myocytes. PMID:12063303

  8. Diagnosis of cardiac amyloidosis based on the myocardial velocity profile in the hypertrophied left ventricular wall.

    Science.gov (United States)

    Oki, Takashi; Tanaka, Hideji; Yamada, Hirotsugu; Tabata, Tomotsugu; Oishi, Yoshifumi; Ishimoto, Takeo; Nagase, Norio; Shinohara, Hisanori; Sakabe, Koichi; Fukuda, Nobuo

    2004-04-01

    The myocardial velocity profile (MVP), derived from color-coded tissue Doppler imaging (TDI), can identify transmural heterogeneity based on the physiology and pathology of the myocardium. This study sought to clarify whether the MVP can differentiate cardiac amyloidosis from other causes of left ventricular hypertrophy. We recorded the MVP and determined its myocardial velocity gradient (MVG) in the ventricular septum and left ventricular posterior wall using color-coded TDI in 10 patients with cardiac amyloidosis, in 25 patients with hypertensive hypertrophied left ventricular wall, in 25 patients with asymmetric septal hypertrophy of hypertrophic cardiomyopathy, and in 20 clinically normal controls. End-diastolic ventricular septal thickness was similar among the cardiac amyloidosis, hypertension, and hypertrophic cardiomyopathy groups. Percent systolic thickening of the ventricular septum and left ventricular posterior wall calculated from M-mode left ventricular echocardiograms was lower in the cardiac amyloidosis group than in the hypertension, hypertrophic cardiomyopathy, or control group. Peak MVGs during systole and early diastole were lowest in the cardiac amyloidosis group, followed, in order, by the control, hypertension, and hypertrophic cardiomyopathy groups. The systolic and early diastolic MVPs in the ventricular septum and left ventricular posterior wall showed a characteristic serrated pattern in all patients with cardiac amyloidosis, but not in any other patient groups. In conclusion, MVPs in the ventricular septum and left ventricular posterior wall show a distinctive serrated pattern that may be related to amyloid deposition in the myocardium. Myocardial tissue characterization using color-coded TDI provides diagnostic information in patients with cardiac amyloidosis. PMID:15050490

  9. Intracellular calcium activates a chloride current in canine ventricular myocytes.

    Science.gov (United States)

    Zygmunt, A C

    1994-11-01

    The contribution of chloride and potassium to the 4-aminopyridine (4-AP)-resistant transient outward current was investigated in dog cardiac myocytes. Whole cell currents were recorded at 37 degrees C in single cells dissociated from epicardial and midmyocardial regions of the canine ventricle. Sodium-calcium exchange current and voltage-dependent transient outward potassium current (IA) were blocked in sodium-free solutions containing 2 mM 4-AP; sodium channels were inactivated by the -50-mV holding potential. When patch pipettes contained 0.4-0.8 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, voltage-clamp steps over the range -20 to +50 mV activated an inward calcium current (ICa) and a Ca(2+)-activated chloride current [ICl(Ca)]. ICl(Ca) was blocked by 200 microM 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, 1 mM 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS), or reduction of external chloride. Independent of the presence of potassium, the reversal potential of the SITS-sensitive current varied with extracellular chloride, as predicted for a chloride-selective conductance. The bell-shaped current-voltage relation of ICl(Ca) has a threshold of -20 mV and a peak at +40 mV. No evidence could be found for a Ca(2+)-activated potassium current or a Ca(2+)-activated nonspecific cation current under these conditions. ICl(Ca) contributed to oscillatory inward currents at diastolic potentials in cells superfused by isoproterenol and high Ca2+, suggesting a role for this current in triggered arrhythmias associated with delayed afterdepolarizations. In the normal heart, ICl(Ca) is likely to contribute to rate- and rhythm-dependent repolarization of the cardiac action potential. PMID:7977830

  10. Multiscale modeling of calcium dynamics in ventricular myocytes with realistic transverse tubules.

    Science.gov (United States)

    Yu, Zeyun; Yao, Guangming; Hoshijima, Masahiko; Michailova, Anushka; Holst, Michael

    2011-10-01

    Spatial-temporal Ca(2+) dynamics due to Ca(2+) release, buffering, and reuptaking plays a central role in studying excitation-contraction (E-C) coupling in both normal and diseased cardiac myocytes. In this paper, we employ two numerical methods, namely, the meshless method and the finite element method, to model such Ca(2+) behaviors by solving a nonlinear system of reaction-diffusion partial differential equations at two scales. In particular, a subcellular model containing several realistic transverse tubules (or t-tubules) is investigated and assumed to reside at different locations relative to the cell membrane. To this end, the Ca(2+) concentration calculated from the whole-cell modeling is adopted as part of the boundary constraint in the subcellular model. The preliminary simulations show that Ca(2+) concentration changes in ventricular myocytes are mainly influenced by calcium release from t-tubules. PMID:21632291

  11. Phytoestrogenic isoflavones daidzein and genistein reduce glucose-toxicity-induced cardiac contractile dysfunction in ventricular myocytes.

    Science.gov (United States)

    Hintz, Kadon K; Ren, Jun

    2004-05-01

    Epidemiological evidence suggests a reduction in the incidence of coronary heart disease, cancer and osteoporosis in populations with a high dietary intake of plant estrogen or phytoestrogen. The clinical benefit of phytoestrogens in cereals, vegetables and medicinal plants is attracting increasing attention for the general public. In the present study, we examined the effect of phytoestrogenic isoflavones daidzein and genistein on glucose toxicity-induced cardiac mechanical malfunction simulating diabetic cardiomyopathy. Adult rat ventricular myocytes were isolated and maintained for 24 hours in normal (NG, 5.5 mM) or high glucose (HG, 25.5 mM) medium in the absence or presence of isoflavones daidzein (50 microM) or genistein (20 microM). Cardiac contractile indices were evaluated using an IonOptix MyoCam system including peak shortening (PS), maximal velocity of shortening/relengthening (+/- dL/dt), time-to-PS (TPS) and time-to-90% relengthening (TR90). Myocytes maintained in HG medium displayed altered mechanical function simulating in vivo diabetes including reduced PS, +/- dL/dt and prolonged TR90 associated with normal TPS compared to those from NG myocytes. Interestingly, these HG-induced mechanical dysfunctions were abolished by co-incubation of daidzein or genistein. However, daidzein but not genistein itself depressed PS in NG myocytes. Neither daidzein nor genistein affected any other mechanical parameters tested in NG myocytes. Collectively, these data suggest that the phytoestrogenic isoflavones daidzein and genistein may reduce glucose toxicity-induced cardiac mechanical dysfunction and thus possess therapeutic potential against diabetes-associated cardiac defects. PMID:15473131

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

    Energy Technology Data Exchange (ETDEWEB)

    Harmer, A.R., E-mail: alex.harmer@astrazeneca.com; Abi-Gerges, N.; Morton, M.J.; Pullen, G.F.; Valentin, J.P.; Pollard, C.E.

    2012-04-15

    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.

  13. Aliskiren limits abdominal aortic aneurysm, ventricular hypertrophy and atherosclerosis in an apolipoprotein-E-deficient mouse model.

    Science.gov (United States)

    Seto, Sai-Wang; Krishna, Smriti M; Moran, Corey S; Liu, David; Golledge, Jonathan

    2014-07-01

    Aliskiren is a direct renin inhibitor developed to treat hypertension. Several clinical studies have suggested that aliskiren has beneficial effects on cardiovascular diseases beyond its antihypertensive effect. In the present study, we examined whether aliskiren limits the progression of AAA (abdominal aortic aneurysm), VH (ventricular hypertrophy) and atherosclerosis in an AngII (angiotensin II)-infused mouse model. ApoE-/- (apolipoprotein-E-deficient) mice were infused subcutaneously with AngII (1000 ng/kg of body weight per day; 4 weeks) to induce AAA and VH. At the completion of the AngII infusion, mice were randomly allocated to three groups to receive vehicle control, low-dose aliskiren (10 mg/kg of body weight per day) or high-dose aliskiren (50 mg/kg of body weight per day) for 4 weeks. Suprarenal aortic diameter assessed by ultrasound was significantly smaller in mice administered aliskiren at days 42 and 56. Aliskiren also significantly reduced the normalized heart weight, ventricular myocyte cell width and aortic arch atherosclerosis. Aliskiren lowered PRR (pro-renin receptor) expression and MAPK (mitogen-activated protein kinase) activity in the suprarenal aorta and heart. Aortic infiltration of T-lymphocytes and macrophages was reduced by aliskiren. In conclusion, aliskiren limits the progression of AAA, VH and atherosclerosis in an AngII-infused mouse model. PMID:24476071

  14. 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. PMID:20718730

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

    DEFF Research Database (Denmark)

    Gerdts, E.; Cramariuc, D.

    2008-01-01

    AIMS: Less is known about the relation between in-treatment left ventricular (LV) geometry and risk of cardiovascular events. We assessed LV geometric patterns on baseline and annual echocardiograms as time-varying predictors of the primary composite endpoint (cardiovascular death, stroke, and myocardial infarction) in 937 hypertensive patients with LV hypertrophy during 4.8 years losartan- or atenolol-based treatment in the Losartan Intervention for Endpoint reduction in hypertension (LIFE) echocardiography substudy. METHODS AND RESULTS: LV geometry was determined from LV mass/body surface area and relative wall thickness in combination. At end of the study, 52% of patients with initial LV hypertrophy had normal geometry (P < 0.001). In particular, concentric remodelling was reduced by 82% and concentric LV hypertrophy by 84%. Development of LV hypertrophy was seen in <5%. In Cox regression analyses including LV geometric patterns as time-varying variables and adjusting for treatment, Framingham risk score, race, and time-varying systolic blood pressure, the patterns independently predicted higher risk of primary composite endpoints [HR 2.99 (1.16-7.71) for concentric remodelling, HR 1.79 (1.17-2.73) for eccentric hypertrophy, and HR 2.71 (1.13-6.45) for concentric hypertrophy; all P < 0.05]. CONCLUSION: In hypertensive patients with ECG LV hypertrophy, in-treatment LV geometry by echocardiography adds information on risk of cardiovascular events Udgivelsesdato: 2008/11

  16. Beta-adrenoceptor subtypes in young and old rat ventricular myocytes: a combined patch-clamp and binding study.

    OpenAIRE

    Cerbai, E.; Guerra, L.; Varani, K.; Barbieri, M.; Borea, P. A.; Mugelli, A.

    1995-01-01

    1. We used electrophysiological and binding techniques to assess the presence of beta 1- and beta 2-adrenoceptors (beta 1AR and beta 2AR) in rat cardiac myocytes and to determine their ratio during aging. Experiments were performed in left ventricular myocytes enzymatically dissociated from the heart of 3-(young) or 22-month-old (old) Wistar Kyoto rats. 2. In patch-clamp experiments, myocytes from old rats showed a prolonged action potential duration (at -20 mV: 41.7 +/- 3.6 vs 26.2 +/- 3.1 m...

  17. Effects of external protons on single cardiac sodium channels from guinea pig ventricular myocytes

    OpenAIRE

    1991-01-01

    The effects of external protons on single sodium channel currents recorded from cell-attached patches on guinea pig ventricular myocytes were investigated. Extracellular protons reduce single channel current amplitude in a dose-dependent manner, consistent with a simple rapid channel block model where protons bind to a site within the channel with an apparent pKH of 5.10. The reduction in single channel current amplitude by protons is voltage independent between -70 and -20 mV. Increasing ext...

  18. Bimodal regulation of Na+–Ca2+ exchanger by ?-adrenergic signaling pathway in shark ventricular myocytes

    OpenAIRE

    Woo, Sun-hee; Morad, Martin

    2001-01-01

    In shark heart, the Na+–Ca2+ exchanger serves as a major pathway for both Ca2+ influx and efflux, as there is only rudimentary sarcoplasmic reticulum in these hearts. The modulation of the exchanger by a ?-adrenergic agonist in whole-cell clamped ventricular myocytes was compared with that of the Na+–Ca2+ exchanger blocker KB-R7943. Application of 5 ?M isoproterenol and 10 ?M KB-R7943 suppressed both the inward and the outward Na+–Ca2+ exchanger curren...

  19. Action of nicorandil on ATP-sensitive K+ channel in guinea-pig ventricular myocytes.

    OpenAIRE

    Nakayama, K.; Fan, Z.; Marumo, F.; Sawanobori, T.; Hiraoka, M.

    1991-01-01

    1. Patch-clamp techniques were used to study the effects of nicorandil (2-nicotinamiodethyl nitrate) on the adenosine 5'-triphosphate (ATP)-sensitive K+ channel current (IK.ATP) in guinea-pig ventricular myocytes. 2. Nicorandil activated the time-independent outward current. This effect was dependent on intracellular ATP concentration ([ATP]i) showing a larger effect at 2 mM than at 10 mM [ATP]i. The nicorandil-induced outward current was inhibited by application of 0.3 microM glibenclamide. ...

  20. QT interval dispersion in chronic heart failure and left ventricular hypertrophy: relation to autonomic nervous system and Holter tape abnormalities.

    OpenAIRE

    Davey, P. P.; Bateman, J.; Mulligan, I. P.; Forfar, C.; Barlow, C.; Hart, G.

    1994-01-01

    OBJECTIVE--To study QT dispersion in left ventricular hypertrophy and chronic heart failure and to determine the relation to ventricular arrhythmias. SETTING--Investigational laboratory of a tertiary referral centre. STUDY DESIGN--Patients with left ventricular hypertrophy and normal systolic function (n = 14) and patients with chronic heart failure (n = 18) were matched with controls (n = 17). The QT dispersion was examined in relation to abnormalities in resting mechanical and autonomic fun...

  1. Relationship between serum leptin levels and left ventricular hypertrophy

    Directory of Open Access Journals (Sweden)

    Ozgur Kartal

    2008-10-01

    Full Text Available Objective: Previous studies showed relation between elevated serum leptin levels (SLL and hypertension. The aim of this study was to evaluate relationship between SLL and left ventricular hypertrophy (LVH and body mass index (BMI in obese hypertensive patients.Methods: Eighty patients with newly diagnosed essential hypertension were included in this cross-sectional, case-controlled study. Hypertensive patients were classified as; level-I or level-II according to JNC-VII classification and as normal weighted (18-24.99 kg/m2, over weighted (25-26.99 kg/m2 and obese (27 kg/m2 and above according to BMI’s. All the patients were evaluated by echocardiography and blood samples were withdrawn for determination SLL. Statistical analysis was performed using Wilcoxon sign rank, Mann Whitney U and Kruskal Wallis tests. Logistic regression analysis was applied for the evaluation of relationship between SLL and clinical variables.Results: Mean levels of arterial blood pressure (ABP of total 80 patients (36 males and 44 females was 155±1.1/95.1±0.7 mmHg and the mean age was 48.9±1.3 years. Patients with level I hypertension (n=32 had mean ABP of 149.7±0.5/90.9±0.6 mmHg and with level-II hypertension (n=48 - mean ABP 168.5±1.6/102.9±0.9 mmHg. The mean BMI in normal weighted group (n=26 was 22.7±0.3 kg/m2, over weighted group (n=19-26.1±0.2 kg/m2 and obese group (n=35-30.9±0.5 kg/m2. There were no differences in LVH incidence between hypertension level groups and BMI groups (p>0.05. Serum leptin levels were similar in patients with level I and level II hypertension (33.5±2.9 ng/ml and 37.3±3.6ng/ml, respectively, p>0.05. However, leptin levels were higher in obese patients as compared with normal and over weighted patients (40.9±3.2 ng/ml versus 28.5±3.6 ng/ml and 32.8 ± 4.9 ng/ml, p<0.01. Patients with LVH had significantly higher levels of leptin as compared with patients without LVH (51.40±5.1 ng/ml versus 28.30±4.20 ng/ml, p<0.05. Logistic regression analysis demonstrated that SLL independently of blood pressure and BMI is related with LVH (OR - 1.7, %95 CI - 1.2-1.9, p<0.05.Conclusion: Our study showed that elevated serum leptin levels are significantly related with LVH independently of body mass index and level of blood pressure. Thus, elevated SLLs, independently of hypertension level and BMI classification, coexist with LVH. Sympathetic activation or direct cardiac receptor activation or proliferative effects of leptin may be responsible for this coexistence.

  2. Effects of sleep deprivation on action potential and transient outward potassium current in ventricular myocytes in rats.

    Science.gov (United States)

    Fang, Zhou; Ren, Yi-Peng; Lu, Cai-Yi; Li, Yang; Xu, Qiang; Peng, Li; Fan, Yong-Yan

    2015-01-01

    Background Sleep deprivation contributes to the development and recurrence of ventricular arrhythmias. However, the electrophysiological changes in ventricular myocytes in sleep deprivation are still unknown. Material and Methods Sleep deprivation was induced by modified multiple platform technique. Fifty rats were assigned to control and sleep deprivation 1, 3, 5, and 7 days groups, and single ventricular myocytes were enzymatically dissociated from rat hearts. Action potential duration (APD) and transient outward current (Ito) were recorded using whole-cell patch clamp technique. Results Compared with the control group, the phases of APD of ventricular myocytes in 3, 5, and 7 days groups were prolonged and APD at 20% and 50% level of repolarization (APD20 and APD50) was significantly elongated (The APD20 values of control, 1, 3, 5, and 7 days groups: 5.66±0.16 ms, 5.77±0.20 ms, 8.28±0.30 ms, 11.56±0.32 ms, 13.24±0.56 ms. The APD50 values: 50.66±2.16 ms, 52.77±3.20 ms, 65.28±5.30 ms, 83.56±7.32 ms, 89.24±5.56 ms. Psleep deprivation rats. The inactivation recovery time of Ito was markedly retarded and the time of closed-state inactivation was markedly accelerated in 3, 5, and 7 days groups. Conclusions APD of ventricular myocytes in sleep deprivation rats was significantly prolonged, which could be attributed to decreased activation and accelerated inactivation of Ito. PMID:25694200

  3. Quantification of Ca2+ uptake in the sarcoplasmic reticulum of trout ventricular myocytes.

    Science.gov (United States)

    Hove-Madsen, L; Llach, A; Tort, L

    1998-12-01

    We measured Ca2+ uptake by the sarcoplasmic reticulum (SR) in trout ventricular myocytes, measuring indo 1 fluorescence in permeabilized cells or ionic currents in single myocytes subjected to voltage clamp. Titration of the SR Ca2+ pumps with thapsigargin gave a pump site density of 454 pmol/mg cell protein. Lowering the temperature from 20 degreesC to 10 or 5 degreesC reduced the SR Ca2+ uptake rate in permeabilized myocytes by 50 and 63%, respectively. Surprisingly, Ca2+ leak from the SR also decreased with decreasing temperatures. Exposure of single myocytes to 10 mM caffeine (Caf) induced a cell contracture and an inward ionic current. Neither contracture nor current decreased significantly after rest periods of 120 and 320 s. The inward current was due to Ca2+ extrusion by the Na+/Ca2+ exchanger (NCX), and the time integral of the exchange current (INCX) was used to calculate the SR Ca2+ content. This gave a steady-state SR Ca2+ content of 22.5 +/- 2.8 amol Ca2+/pF or 750 microM. When the SR was loaded by depolarizing the cell to +50 mV, the Ca2+ content increased with increasing length of the depolarization, reaching a maximum of 52.0 +/- 5.9 amol Ca2+/pF. When the cell was depolarized to different voltages for 3 s, a subsequent Caf-induced INCX increased with increasing voltage. At +100 mV, the Ca2+ content was 36.6 +/- 3.8 amol/pF, giving a maximal SR Ca2+ uptake rate of 12.2 +/- 1.2 amol Ca2+. pF-1. s-1 or 417 microM/s. We conclude that maximal SR Ca2+ content and Ca2+ uptake rates can be estimated using specific SR Ca2+ loading protocols. Contrary to the general assumption that contraction in lower vertebrates depends largely on transsarcolemmal Ca2+ fluxes, we found that although the L-type Ca2+ current is insufficient to fully activate contraction, the SR is capable of participating in the regulation of the cytosolic Ca2+ during the excitation-contraction coupling in trout ventricular myocytes. PMID:9843899

  4. 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

    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 patients with electrocardiographic LV hypertrophy. M-mode, 2-dimensional, and pulsed Doppler echocardiographic recordings of mitral inflow velocity and isovolumetric relaxation time (IVRT) were obtained in 750 patients with stage I to III hypertension and LV hypertrophy determined by electrocardiography (sex-adjusted Cornell voltage duration criteria or Sokolow-Lyon voltage criteria) after 14 days of placebo treatment. The patients' mean age was 67+/-7 years and 44% were women. One hundred forty patients (19%) had normal LV geometric pattern, 79 (11%) had concentric remodeling, 342 (45%) had eccentric LV hypertrophy, and 189 (25%) had concentric LV hypertrophy. A normal LV filling pattern was found in 116 patients (16%),abnormal relaxation in 519 (69%), "pseudonormal" filling was found in 83 (11%), and a restrictive filling pattern in 32 (4%). Prolonged IVRT was associated with LV hypertrophy (p

  5. Ovariectomy enhances SR Ca²? release and increases Ca²? spark amplitudes in isolated ventricular myocytes.

    Science.gov (United States)

    Fares, Elias; Parks, Randi J; Macdonald, Jennifer K; Egar, Jeanne M S; Howlett, Susan E

    2012-01-01

    This study compared Ca(2+) homeostasis in ventricular myocytes from 8-month-old female C57BL/6J mice that had either a bilateral ovariectomy (OVX) or a sham surgery at 3 weeks of age. Cells were loaded with fura-2 and field-stimulated or voltage-clamped with steps to membrane potentials between -40 and +80 mV (37°C). Peak Ca(2+) transients increased by two-fold in OVX myocytes when compared to sham, and Ca(2+) transient rates of rise and decay were faster in OVX cells. In contrast, Ca(2+) current densities were similar in sham and OVX cells. Sarcoplasmic reticulum (SR) Ca(2+) content, assessed by caffeine, also was higher in OVX compared to sham cells (111.7 ± 11.9 vs. 61.2 ± 10.4 nM; p<0.05). Furthermore, the gain of Ca(2+) release (Ca(2+) release/Ca(2+) current) was significantly greater in OVX than in sham cells (16.3 ± 2.5 vs. 7.7 ± 2.0 nM/pApF(-1) at 0 mV; p<0.05). As changes in unitary Ca(2+) release might account for the increased gain in OVX cells, spontaneous Ca(2+) sparks were compared in fluo-4-loaded myocytes (37°C). Spark frequency was higher in OVX cells than in sham cells. In addition, spark amplitudes were greater in OVX than in sham myocytes (?F/F(0)=0.379 ± 0.006 vs. 0.342 ± 0.006; p<0.05). However, spark widths and time courses were similar in the two groups. These data suggest that the size of individual SR Ca(2+) release units is larger and the SR Ca(2+) content is greater in myocytes of OVX mice, producing augmented gain and SR Ca(2+) release. These observations show that OVX disrupts intracellular Ca(2+) homeostasis and suggest that sex steroid hormones modulate unitary Ca(2+) release in individual cardiac myocytes. PMID:21939666

  6. Functional cross-talk between aldosterone and angiotensin-(1-7) in ventricular myocytes.

    Science.gov (United States)

    de Almeida, Pedro W Machado; de Freitas Lima, Ricardo; de Morais Gomes, Enéas Ricardo; Rocha-Resende, Cibele; Roman-Campos, Danilo; Gondim, Antonio Nei S; Gavioli, Mariana; Lara, Aline; Parreira, Amanda; de Azevedo Nunes, Sasha Luísa; Alves, Márcia N M; Santos, Sandra Lauton; Alenina, Natalia; Bader, Michael; Resende, Rodrigo Ribeiro; dos Santos Cruz, Jader; Souza dos Santos, Robson Augusto; Guatimosim, Silvia

    2013-02-01

    High serum levels of aldosterone have been linked to the development of cardiac disease. In contrast, angiotensin (Ang)-(1-7) was extensively shown to possess cardioprotective effects, including the attenuation of cardiac dysfunction induced by excessive mineralocorticoid activation in vivo, suggesting possible interactions between these 2 molecules. Here, we investigated whether there is cross-talk between aldosterone and Ang-(1-7) and its functional consequences for calcium (Ca(2+)) signaling in ventricular myocytes. Short-term effects of aldosterone on Ca(2+) transient were assessed in Fluo-4/AM-loaded myocytes. Confocal images showed that Ang-(1-7) had no effect on Ca(2+) transient parameters, whereas aldosterone increased the magnitude of the Ca(2+) transient. Quite unexpectedly, addition of Ang-(1-7) to aldosterone-treated myocytes further enhanced the amplitude of the Ca(2+) transient suggesting a synergistic effect of these molecules. Aldosterone action on Ca(2+) transient amplitude was mediated by protein kinase A, and was related to an increase in Ca(2+) current (I(Ca)) density. Both changes were not altered by Ang-(1-7). When cardiomyocytes were exposed to aldosterone, increased Ca(2+) spark rate was measured. Ang-(1-7) prevented this change. In addition, a NO synthase inhibitor restored the effect of aldosterone on Ca(2+) spark rate in Ang-(1-7)-treated myocytes and attenuated the synergistic effect of these 2 molecules on Ca(2+) transient. These results indicate that NO plays an important role in this cross-talk. Our results bring new perspectives in the understanding of how 2 prominent molecules with supposedly antagonist cardiac actions cross-talk to synergistically amplify Ca(2+) signals in cardiomyocytes. PMID:23232646

  7. Inositol 1, 4, 5-Triphosphate Receptors and Human Left Ventricular Myocytes

    Science.gov (United States)

    Signore, Sergio; Sorrentino, Andrea; Ferreira-Martins, João; Kannappan, Ramaswamy; Shafaie, Mehrdad; Ben, Fabio Del; Isobe, Kazuya; Arranto, Christian; Wybieralska, Ewa; Webster, Andrew; Sanada, Fumihiro; Ogórek, Barbara; Zheng, Hanqiao; Liu, Xiaoxia; del Monte, Federica; D’Alessandro, David A.; Wunimenghe, Oriyanhan; Michler, Robert E.; Hosoda, Toru; Goichberg, Polina; Leri, Annarosa; Kajstura, Jan; Anversa, Piero; Rota, Marcello

    2013-01-01

    Background Little is known concerning the function of inositol 1,4,5-triphosphate receptors (IP3Rs) in the adult heart experimentally. Moreover, whether these Ca2+ release channels are present and play a critical role in human cardiomyocytes remains to be defined. IP3Rs may be activated following G?q-protein-coupled receptors (GPCR) stimulation affecting Ca2+ cycling, enhancing myocyte performance and, potentially, favoring an increase in the incidence of arrhythmias. Methods and Results IP3R function was determined in human left ventricular (LV) myocytes and this analysis was integrated with assays in mouse myocytes to identify the mechanisms by which IP3Rs influence the electrical and mechanical properties of the myocardium. We report that IP3Rs are expressed and operative in human LV myocytes. Following GPCR activation, Ca2+ mobilized from the sarcoplasmic reticulum via IP3Rs contributes to the decrease in resting membrane potential, prolongation of the action-potential, and occurrence of early after-depolarizations. Ca2+ transient amplitude and cell shortening are enhanced, and extra-systolic and dysregulated Ca2+ elevations and contractions become apparent. These alterations in the electromechanical behavior of human cardiomyocytes are coupled with increased isometric twitch of the myocardium and arrhythmic events, suggesting that GPCR activation provide inotropic reserve, which is hampered by electrical instability and contractile abnormalities. Additionally, our findings support the notion that increases in Ca2+ load by IP3Rs promote Ca2+ extrusion by forward mode Na+/Ca2+ exchange, an important mechanism of arrhythmic events. Conclusions Thus, the GPCR/IP3R axis modulates the electromechanical properties of the human myocardium and its propensity to develop arrhythmias. PMID:23983250

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

    DEFF Research Database (Denmark)

    Chinali, M.; Simone, G. de

    2008-01-01

    In hypertensive patients without prevalent cardiovascular disease, enhanced left atrial systolic force is associated with left ventricular hypertrophy and increased preload. It also predicts cardiovascular events in a population with high prevalence of obesity. Relations between left atrial systolic force and left ventricular geometry and function have not been investigated in high-risk hypertrophic hypertensive patients. Participants in the Losartan Intervention For Endpoint reduction in hypertension echocardiography substudy without prevalent cardiovascular disease or atrial fibrillation (n = 567) underwent standard Doppler echocardiography. Left atrial systolic force was obtained from the mitral orifice area and Doppler mitral peak A velocity. Patients were divided into groups with normal or increased left atrial systolic force (>14.33 kdyn). Left atrial systolic force was high in 297 patients (52.3%), who were older and had higher body mass index and heart rate (all P < 0.01) but similar systolic and diastolic blood pressure, in comparison with patients with normal left atrial systolic force. After controlling for confounders, increased left atrial systolic force was associated with larger left ventricular diameter and higher left ventricular mass index (both P < 0.01). Prevalence of left ventricular hypertrophy was greater (84 vs. 64%; P < 0.001). Participants with increased left atrial systolic force exhibited normal ejection fraction; higher stroke volume, cardiac output, transmitral peak E velocities and peak A velocities; and lower E/A ratio (all P < 0.01). Enhanced left atrial systolic force identifies hypertensive patients with greater left ventricular mass and prevalence of left ventricular hypertrophy, but normal left ventricular chamber systolic function with increased transmitral flow gradient occurring during early filling, consistent with increased preload Udgivelsesdato: 2008/7

  9. Left ventricular hypertrophy in Turner syndrome : a prospective echocardiographic study

    DEFF Research Database (Denmark)

    Mortensen, Kristian Havmand; Gravholt, Claus HØjbjerg

    2012-01-01

    Cardiovascular risk stratification in Turner syndrome (TS) is difficult. Increased left ventricular mass associates with an adverse prognosis in several settings, and this study aimed to elucidate this risk marker in relation to metabolic and cardiovascular status in TS.

  10. Does Contractile Ca2+ Control Calcineurin-NFAT Signaling and Pathological Hypertrophy in Cardiac Myocytes?

    Science.gov (United States)

    Steven R. Houser (Temple University School of Medicine; Department of Physiology REV)

    2008-06-24

    In noncontractile cells, a sustained increase in total cytoplasmic Ca2+ concentration is typically needed to activate the intracellular protein phosphatase calcineurin, leading to dephosphorylation of the transcription factor nuclear factor of activated T cells (NFAT), its nuclear translocation, and induction of gene expression. It remains a mystery exactly how Ca2+-dependent signaling pathways, such as that mediated by calcineurin-NFAT, are regulated in contracting cardiac myocytes given the highly specialized manner in which Ca2+ concentration rhythmically cycles in excitation-contraction coupling. Here, we critically review evidence that supports the hypothesis that calcineurin-NFAT signaling is regulated by contractile Ca2+ transients in cardiac myocytes.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1989-05-01

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

  12. 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.

  13. Resting tension participates in the modulation of active tension in isolated guinea pig ventricular myocytes.

    Science.gov (United States)

    Cazorla, O; Pascarel, C; Garnier, D; Le Guennec, J Y

    1997-06-01

    We studied active and passive properties of intact isolated guinea-pig ventricular myocytes in auxotonic conditions. Cells were attached using carbon fibres. The passive properties of the myocytes, in the presence of the stretch-activated channel blocker streptomycin sulphate, could be separated into two groups: stiff cells (stiffness slope = 2.88 +/- 0.93 nN/micron3, n = 63 cells) and compliant cells (stiffness slope = 0.91 +/- 0.35 nN/micron3, n = 52 cells). The study and the localization of the different kind of cells indicated that endocardium is mainly constituted of stiff cells (80%) while the epicardium contained more compliant cells (60%). When a longitudinal strain was applied to compliant cells, an increase in resting tension, diastolic sarcomere length and active tension were observed. On the other hand, in stiff cells, it induced an increase in resting tension and active tension with little change of diastolic sarcomere length. In both kinds of cells, strain had no effect on Ca2+ transient amplitude and shape. Plotting active tension v diastolic sarcomere length also clearly showed two separated populations of cells, corresponding to stiff and compliant cells. The results of the two groups of cells when plotting active tension v resting tension could not be distinguished. We conclude that resting tension is an important factor in the modulation of active tension by stretch in addition to interfilament lattice spacing or sarcomere length. PMID:9220348

  14. T-tubule disruption promotes calcium alternans in failing ventricular myocytes: mechanistic insights from computational modeling.

    Science.gov (United States)

    Nivala, Michael; Song, Zhen; Weiss, James N; Qu, Zhilin

    2015-02-01

    In heart failure (HF), T-tubule (TT) disruption contributes to dyssynchronous calcium (Ca) release and impaired contraction, but its role in arrhythmogenesis remains unclear. In this study, we investigate the effects of TT disruption and other HF remodeling factors on Ca alternans in ventricular myocytes using computer modeling. A ventricular myocyte model with detailed spatiotemporal Ca cycling modeled by a coupled Ca release unit (CRU) network was used, in which the L-type Ca channels and the ryanodine receptor (RyR) channels were simulated by random Markov transitions. TT disruption, which removes the L-type Ca channels from the associated CRUs, results in "orphaned" RyR clusters and thus provides increased opportunity for spark-induced Ca sparks to occur. This effect combined with other HF remodeling factors promoted alternans by two distinct mechanisms: 1) for normal sarco-endoplasmic reticulum Ca ATPase (SERCA) activity, alternans was caused by both CRU refractoriness and coupling. The increased opportunity for spark-induced sparks by TT disruption combined with the enhanced CRU coupling by Ca elevation in the presence or absence of increased RyR leakiness facilitated spark synchronization on alternate beats to promote Ca alternans; 2) for down-regulated SERCA, alternans was caused by the sarcoplasmic reticulum (SR) Ca load-dependent mechanism, independent of CRU refractoriness. TT disruption and increased RyR leakiness shifted and steepened the SR Ca release-load relationship, which combines with down-regulated SERCA to promote Ca alternans. In conclusion, the mechanisms of Ca alternans for normal and down-regulated SERCA are different, and TT disruption promotes Ca alternans by both mechanisms, which may contribute to alternans at different stages of HF. PMID:25450613

  15. Enhancing effects of diethyldithiocarbamate on increase of sodium channel by sulfur dioxide derivatives in ventricular myocytes.

    Science.gov (United States)

    Wei, Haiying; Meng, Ziqiang

    2008-09-01

    The enhancing effects of diethyldithiocarbamate (DDC) on increase of sodium channel by sulfur dioxide derivatives in ventricular myocytes were studied using the whole cell patch-clamp technique to probe the mechanism of SO2 on the cardiovascular system in this study. Firstly, the effects of DDC and/or sulfur dioxide (SO2) derivatives on the activities of superoxide dismutase (SOD) were studied. The results showed that DDC decreased SOD activities significantly and SO2 derivatives had no significant effect on SOD activities; however, DDC and SO2 derivatives combined led to a significant decrease of SOD activities. In the electrophysiological test, DDC (1-100 mM) increased sodium current (INa) in a concentration-dependent manner and the concentration for half-maximum increase (EC50) was 20 mM. Addition of 20 mM DDC to the SO2 derivatives-containing medium significantly shifted the voltage-dependent activation curve of INa toward the hyperpolarizing direction (Vh are -51 mV, -53 mV and -54 mV, respectively) and shifted the steady-state inactivation curve to more positive potentials (Vh are -74 mV, -71 mV and -65 mV, respectively) compared with the control and 10 microM SO2 derivatives exposure. These results indicated that DDC could enhance the increasing effects on Na+ channels induced by SO2 derivatives, and suggested that the toxicity of SO2 on ventricular myocytes of rats was realized by free radical, especially O2-. PMID:18606235

  16. Adrenaline and extracellular ATP switch between two modes of acid extrusion in the guinea-pig ventricular myocyte.

    OpenAIRE

    Lagadic-gossmann, D.; Vaughan-jones, Rd; Buckler, KJ

    1992-01-01

    1. Intracellular pH (pHi) was recorded in isolated guinea-pig ventricular myocytes using the pH-sensitive fluoroprobe, carboxy-SNARF-1 (carboxy-seminaphthorhodafluor). 2. Addition and removal of 10 mM NH4Cl was used to induce an intracellular acid load in a myocyte perfused with HCO3(-)-buffered solution containing amiloride. Under these conditions, subsequent pHi recovery is known to rely upon Na(+)-HCO3- co-transport into the cell. The application of 0.5-5 microM adrenaline resulted in an i...

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

    International Nuclear Information System (INIS)

    Objective: Based on coronary angiography, thallium-201 myocardial scintigraphy was evaluated in hypertensive patients with and without left ventricular hypertrophy, and the causes of its perfusion abnormalities were discussed. Methods: Thallium-201 myocardial scintigraphy was performed on 85 patients with clinically suspected coronary artery disease. Coronary angiography was performed on patients with perfusion abnormalities in one month after scintigraphy. Results: The rate of 201Tl perfusion abnormalities in hypertensive patients with hypertrophy (85.7%) was higher than normal blood pressure (39.3%, P201Tl perfusion abnormalities occur in hypertensive patients with hypertrophy. The perfusion abnormalities may be caused not only by coronary large vessel disease, but also by coronary microvascular disease

  18. 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)

  19. Therapeutic inhibition of fatty acid oxidation in right ventricular hypertrophy: exploiting Randle’s cycle

    OpenAIRE

    Fang, Yong-hu; Piao, Lin; Hong, Zhigang; Toth, Peter T.; Marsboom, Glenn; Bache-wiig, Peter; Rehman, Jalees; Archer, Stephen L.

    2011-01-01

    Right ventricular hypertrophy (RVH) and RV failure are major determinants of prognosis in pulmonary hypertension and congenital heart disease. In RVH, there is a metabolic shift from glucose oxidation (GO) to glycolysis. Directly increasing GO improves RV function, demonstrating the susceptibility of RVH to metabolic intervention. However, the effects of RVH on fatty acid oxidation (FAO), the main energy source in adult myocardium, are unknown. We hypothesized that partial inhibitors of FAO (...

  20. Increased prevalence of left ventricular hypertrophy in hypertensive women with type 2 diabetes mellitus

    OpenAIRE

    Adler Yehuda; Schwammenthal Ehud; Fisman Enrique Z; Tenenbaum Alexander; Benderly Michal; Motro Michael; Shemesh Joseph

    2003-01-01

    Abstract Background Left ventricular hypertrophy (LVH) is a powerful independent risk factor for cardiovascular morbidity and mortality among hypertensive patients. Data regarding relationships between diabetes and LVH are controversial and inconclusive, whereas possible gender differences were not specifically investigated. The goal of this work was to investigate whether gender differences in left heart structure and mass are present in hypertensive patients with type 2 diabetes. Methods Fi...

  1. Thymosin Beta 4 Protects Mice from Monocrotaline-Induced Pulmonary Hypertension and Right Ventricular Hypertrophy

    OpenAIRE

    Wei, Chuanyu; Kim, Il-kwon; Li, Li; Wu, Liling; Gupta, Sudhiranjan

    2014-01-01

    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 therapi...

  2. 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 ?1 receptor antagonist with respect to LVH regression. CONCLUSION: The anti-hypertensive drugs induced various degrees of hypertrophic regression.

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

    Scientific Electronic Library Online (English)

    Celso, Ferreira Filho; Luiz Carlos de, Abreu; Vitor E., Valenti; Marcelo, Ferreira; Adriano, Meneghini; José Alexandre, Silveira; Andrés R. Pérez, Riera; Eduardo, Colombari; Neif, Murad; Paulo Roberto, Santos-Silva; Lovian José Henrique Pereira da, Silva; Luiz Carlos Marques, Vanderlei; Tatiana D., Carvalho; Celso, Ferreira.

    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 Medlin [...] e (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 ?1 receptor antagonist) with respect to LVH regression. CONCLUSION: The anti-hypertensive drugs induced various degrees of hypertrophic regression.

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Isobe, Naoki; Toyama, Takuji; Hoshizaki, Hiroshi [Gunma Prefectural Cardiovascular Center (Japan)] (and others)

    1999-09-01

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

  6. Protection from the effects of metabolic inhibition and reperfusion in contracting isolated ventricular myocytes via protein kinase C activation.

    Science.gov (United States)

    Hudman, D; Standen, N B

    2004-08-01

    The protective effects of the PKC activator Phorbol 12-myristate 13-acetate (PMA) were investigated in electrically field stimulated (EFS) rat isolated ventricular myocytes following 7 min of metabolic inhibition induced by cyanide, iodoacetic acid and substrate removal, followed by reperfusion. PMA reduced reperfusion damage and increased functional recovery (response to EFS) following 10 min reperfusion from 20.0 +/- 10.7% of control myocytes to 90.0 +/- 7.2% following 5 min PMA pre-treatment (p<0.001). PMA significantly increased the time from the onset of MI before the myocytes failed to respond to EFS from 135 +/- 19s in control cells to 200 +/- 14s in PMA pre-treated cells (p<0.05). Additionally, there was an increase in the time to rigor with PMA pre-treated cells entering rigor 255 +/- 17s after MI compared to 174 +/-15s in control cell (p<0.05), indicating a delay in ATP depletion. During MI PMA pre-treated cells showed a significantly smaller increase in [Ca(2+)]i compared to control myocytes. Following reperfusion the majority of PMA pre-treated myocytes recovered calcium transients in response to EFS and diastolic Ca(2+) levels not significantly different to those seen prior to metabolic inhibition. Activation of PKC is thought to involve translocation to the particulate fraction. Our results demonstrate the presence of PKC-alpha, beta, gamma, delta, iota, lambda/zeta in rat ventricular myocytes, all of which translocate to the membrane in response to PMA. PMID:15276027

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

    International Nuclear Information System (INIS)

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

  8. 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 hypertAR reflects the degree of pulmonary hypertension and anatomical right ventricular hypertrophy and is a useful non-invasive method to detect right ventricular hypertrophy in chronic pulmonary disease. (J.P.N.)

  9. 123I-MIBG myocardial imaging in hypertensive patients. Abnormality progresses with left ventricular hypertrophy

    International Nuclear Information System (INIS)

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

  10. The evaluation of left ventricular eccentric hypertrophy by 201Tl-myocardial scintigraphy

    International Nuclear Information System (INIS)

    In order to elucidate the mechanism of left ventricular eccentric hypertrophy in conditions of volume overload, Tl-201 myocardial scintigraphy was performed in patients with aortic valve regurgitation and mitral valve regurgitation. There was a good relationship between the severity of Tl-defects, as determined by Tl-201 myocardial scintigraphy, and the changes in the T wave on the ECG on the one hand and the NYHA functional classification of heart diseases. In 17 of 18 patients where LVDd increased with increasing severity of Tl-defects and the defects were moderate to severe, LVDd was 65 mm or larger. There was a significant negative correlation between the washout rate for the whole circumference of the left ventricle, as determined by exercise Tl-201 SPECT, and LVDd (r=-0.603, p<0.01). The phenomenon of redistribution as determined by exercise Tl-201 myocardial scintigraphy was observed relatively early. Our results suggest that mechanical volume overload and ischemic changes are involved in left ventricular wall damage in left ventricular eccentric hypertrophy. For patients with moderate to severe Tl-defects valve replacement is indicated, no matter whether they may have heart failure or arrhythmia. (author)

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

    International Nuclear Information System (INIS)

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

  12. Cardiotoxic effects of fenfluramine hydrochloride on isolated cardiac preparations and ventricular myocytes of guinea-pigs.

    Science.gov (United States)

    Rajamani, S; Studenik, C; Lemmens-Gruber, R; Heistracher, P

    2000-03-01

    The cardiotoxic effects of fenfluramine hydrochloride on mechanical and electrical activity were studied in papillary muscles, Purkinje fibres, left atria and ventricular myocytes of guinea-pigs. Force of contraction (f(c)) was measured isometrically, action potentials and maximum rate of rise of the action potential (V(max)) were recorded by means of the intracellular microelectrode technique and the sodium current (I(Na)) with patch-clamp technique in the cell-attached mode. For kinetic analysis (S)-DPI-201-106-modified Na(+) channels from isolated guinea-pig ventricular heart cells were used. Fenfluramine (1 - 300 microM) produced negative chronotropic and inotropic effects; additional extracellular Ca(2+) competitively antagonized the negative inotropic effect. Fenfluramine concentration-dependently reduced V(max) and showed tonic blockade of sodium channels, shortened the action potential duration in papillary muscles and Purkinje fibres. In cell-attached patches, fenfluramine decreased I(Na) concentration-dependently (10 - 100 microM), frequency-independently (0.1 - 3 Hz; 30 microM). The h(infinity) curve was shifted towards hyperpolarizing direction. At 30 microM, fenfluramine blocked the sodium channel at all test potentials to the same degree, and neither changed the threshold and reversal potentials nor the peak of the curve. No effect on single channel availability, but a significant decrease in mean open times and increase in mean closed times was observed. Mean duration of the bursts decreased and number of openings per record increased with increasing drug concentration. It is concluded that the effect on I(Na) plays an important role in the cardiotoxicity of fenfluramine in addition to primary pulmonary hypertension and valvular disorders. PMID:10696080

  13. Combining stimulus direction and waveform for optimization of threshold stimulation of isolated ventricular myocytes.

    Science.gov (United States)

    Bassani, Rosana A; Lima, Katherine A; Gomes, Paulo A P; Oliveira, Pedro X; Bassani, José W M

    2006-09-01

    Electric field stimulation is widely used for heart pacing and arrhythmia reversion. In this study, we analysed the influence of waveform and direction of external stimulating electric field on the excitation threshold of isolated ventricular myocytes. The threshold field (E(T)) was lower when the field was applied longitudinally (E(T,L)) rather than transversally (E(T,T)) to the cell major axis. Rheobase was greater for transversal stimulation, but chronaxie and estimated membrane polarization were similar for both directions. The calculated maximal variation in membrane potential at the threshold (DeltaV(T) approximately 15 mV) was insensitive to field direction. As DeltaV(T) values were similar, we assumed that the E(T,T)/E(T,L) ratio might be described solely as the ratio of the major and minor cell semi-axes. Accordingly, the ratio thus estimated was comparable to that determined experimentally. Stimulus waveform significantly affected both E(T) and DeltaV(T), which were greater for monophasic versus biphasic stimuli. Direction and waveform effects were independent. We conclude that (a) direction affects E(T) by its influence on the ability of a given field intensity to cause threshold membrane polarization and (b) threshold-lowering effects of longitudinal stimulation and biphasic waveforms apparently depend on different mechanisms, are additive and thus may be combined to decrease the energy requirement for myocardial stimulation. PMID:16868351

  14. Coronary blood flow during the development and regression of left ventricular hypertrophy in renovascular hypertensive rats.

    Science.gov (United States)

    Wicker, P; Tarazi, R C; Kobayashi, K

    1983-06-01

    Left ventricular (LV) coronary flow (CF) was determined by left atrial injection of microspheres in conscious rats during the development and after the reversal of LV hypertrophy in 2-kidney, 1-clip Goldblatt hypertension. Two groups of untreated renal hypertensive rats (RHR) were studied, the first (RHR1, n = 17) at 10 weeks and the second (RHR2, n = 9) at 24 weeks after clipping. Beginning 9 weeks after clipping, 2 other groups were treated either with captopril (40 to 60 mg/kg/day) in drinking water (RHR-C, n = 8) or left nephrectomy (RHR-N, n = 9) and followed for 15 weeks. Sham-operated animals followed for similar periods of time served as controls (Sham-1, n = 12, as a control for RHR1, and Sham-2, n = 11, as a control for RHR2). In all groups, LV mass increased or decreased in close correlation with changes in arterial blood pressure, and minimal total LV coronary resistance remained unchanged. The development of hypertrophy was associated with a tendency toward reduction in CF reserve (defined as maximal CF/unit mass); this flow reserve was restored with reversal of hypertrophy. The importance of the relation between pressure and LV mass as a determinant of CF reserve was investigated in a second study in which this relation was changed by altering the periods of captopril therapy; in these cases, CF reserve correlated significantly with the ratio of arterial pressure to LV mass (r = 0.76, n = 12, p less than 0.01). The results suggest that maintenance of CF reserve in LV hypertrophy depends on an appropriate balance between arterial pressure and LV mass, and might be disturbed by antihypertensive therapy that leaves LV hypertrophy unchanged. PMID:6222644

  15. Adiponectin as an independent predictor of left ventricular hypertrophy in nondiabetic patients with hypertension.

    Science.gov (United States)

    Peer, Maya; Mashavi, Margarita; Matas, Zipora; Harpaz, David; Shargorodsky, Marina

    2015-03-01

    We evaluated novel and traditional biomarkers as well as hemodynamic parameters associated with the development of left ventricular hypertrophy (LVH) in nondiabetic patients with hypertension. Nondiabetic patients with hypertension (n = 86) were evaluated for lipids, glucose, insulin, homeostasis model assessment-insulin resistance (HOMA-IR), adiponectin, aldosterone, renin, matrix metalloproteinase 2, and endothelin. Arterial elasticity was evaluated using pulse wave contour. The LVH parameters were assessed echographically. Adiponectin was significantly and inversely associated with left ventricular mass (LVM; P = .032). The aldosterone-renin ratio (ARR) was significantly, positively associated with LVM (P = .031). Fasting insulin as well as HOMA-IR was significantly, positively associated with LVM (P = .036 and P = .025, respectively). In multiple linear regression analysis, adiponectin and ARR remained a significant predictor of LVM. The present study found that adiponectin and ARR are important independent determinants of LVH in nondiabetic patients with hypertension. PMID:24576986

  16. Gene Deletion of VIP Leads to Increased Mortality Associated with Progressive Right Ventricular Hypertrophy.

    Science.gov (United States)

    Szema, Anthony M; Hamidi, Sayyed A

    2014-04-01

    Vasoactive Intestinal Peptide (VIP) knockout mice exhibit asthma, pulmonary hypertension, and left ventricular wall thinning. Humans with these disorders have premature death. We show here that VIP KO mice have reduced survival (100% mortality at 20 months), vs. 100% survival among WT C57BL/6 mice. Moreover, the ratios of weights of right ventricle divided by left ventricle plus septum were progressively increased in VIP KO mice with age. Core temperatures were lower in VIP KO mice when compared to WT littermates, with an associated pro-inflammatory cytokine milieu. Overall, our results indicate that VIP is important for survival in mice. Its absence leads to increased mortality, with progressive right ventricular hypertrophy as a surrogate of pulmonary hypertension, lower body weight, hypothermia, and pro-inflammatory milieu. These studies support VIP as a novel therapeutic agent in pulmonary hypertension. PMID:24860842

  17. Reduction of Left Ventricular Hypertrophy by Sirolimus in Kidney Transplant Recipients: A Nonrandomized Clinical Trial

    Directory of Open Access Journals (Sweden)

    Ghorbani Yekta B

    2012-02-01

    Full Text Available Background: Persistence of left ventricular hypertrophy (LVH in renal transplant recipients is associated with unfavorable outcomes. Calcineurin-inhibitor (CNI nephrotoxicity is a major cause of morbidity and mortality after kidney transplantation. In this study we compared sirolimus (SRL with calcineurin-inhibitor as primary immunosuppressants for the attenuation of left ventricular hypertrophy in renal transplantation recipients. Methods: In this prospective cohort study done in Shariati Hospital in 2010, we evaluated the effects of sirolimus and CNI on LVH of 55 renal transplant recipients. The cases (19 received sirolimus while the controls (36 received CNI while being matched for age and duration of transplantation. Data regarding blood pressure (BP, hemoglobin, serum creatinine, uric acid and lipid concentrations were assessed and changes in left ventricular (LV mass were evaluated by echocardiography over a one-year follow-up. Results: Left ventricular mass significantly decreased (P=0.0001 in the SRL group but blood pressure did not differ between the two groups. LV mass and LV mass index both decreased significantly (P?0.05 but the difference was not associated with changes in BP. The difference in interventricular septal thickness at end diastole (IVSD and posterior wall diameter (PWD were significant (P?0.05 in the SRL group but the difference in end diastolic diameter (EDD was not significant. Conclusion: Conversion from CNI to SRL-based immunosuppressive therapy in RTRs is safe and SRL may decrease LVH. SRL seems to be safe and improve renal function without cardiac compromise in kidney transplant recipients.

  18. Effect of spironolactone on diastolic function in hypertensive left ventricular hypertrophy.

    Science.gov (United States)

    Gupta, A; Schiros, C G; Gaddam, K K; Aban, I; Denney, T S; Lloyd, S G; Oparil, S; Dell'Italia, L J; Calhoun, D A; Gupta, H

    2015-04-01

    We have previously shown rapid reversal of left ventricular hypertrophy (LVH) with 6 months of spironolactone therapy in patients with resistant hypertension (HTN), preserved left ventricular ejection fraction and no history of heart failure. In this substudy, we investigated the effect of mineralocorticoid receptor blockade with spironolactone on pre-clinical diastolic dysfunction. Thirty-four patients (19 with high and 15 with normal aldosterone levels) were treated with spironolactone and followed with cardiac magnetic resonance with tissue tagging at baseline, 3 and 6 months of treatment. Serum markers of collagen turnover (C-propeptide of type-I procollagen and carboxy-terminal telopeptide of type-I collagen) were measured at baseline and at 6 months. At baseline, patients demonstrated reduced E/A ratio (volumetric normalized peak early filling rate/late filling rate, normalized to left ventricular end-diastolic volume), lower peak early-diastolic mitral annular velocity and lower peak early-diastolic circumferential strain rates compared to the reference values obtained from 45 normal controls without HTN or cardiac disease (all comparisons, P<0.01). No significant change occurred in diastolic filling, relaxation parameters or collagen markers with spironolactone therapy at 6 months irrespective of aldosterone status despite significant reduction in left ventricular mass index in both high- and normal-aldosterone groups. In conclusion, resistant HTN patients with LVH demonstrate significant pre-clinical diastolic dysfunction. Short-term spironolactone therapy may not lead to improvement in diastolic function despite rapid reversal of LVH. PMID:25231508

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

    International Nuclear Information System (INIS)

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

  20. Left ventricular hypertrophy are associated with increased ostial pulmonary vein diameter

    Directory of Open Access Journals (Sweden)

    Yoga Yuniadi

    2006-08-01

    Full Text Available Atrial fibrillation (AF, which is called as a global epidemic disease, frequently found in hypertensive patients with left ventricular hypertrophy (LVH. Pulmonary vein (PV, which is known to have an important role in AF initiation and maintenance, increases in its diameter during AF. We sought to investigate PVs diameter changes in LVH with sinus rhythm. Of 70 hypertensive patients with sinus rhythm, 42 subjects demonstrated LVH. The mean ostial diameter of patient with and without LVH, assessed by doing spiral multisliced CT scan in the axial plane, were as follow: right superior (RSPV of 19.6±2.78 vs 17.8±1.93 (p = 0.003, right inferior (RIPV of 18.4±3.12 vs 16.0±2.19 (p < 0.001, left superior (LSPV of 18.1±2.62 vs 16.0±2.16 (p < 0.001, and left inferior (LIPV of 15.9±1.93 vs 15.4±1.85 mm (p = 0.284, respectively. Even during sinus rhythm, LVH causes PV dilation. This result might give an explanation of frequent AF prevalence in hypertensive patients. (Med J Indones 2006; 15:173-6 Keywords: Pulmonary veins, Left ventricular hypertrophy

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

    DEFF Research Database (Denmark)

    Mehlsen, J; Fornitz, Gitte Gleerup

    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 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 with isradipine (254 +/- 55 g). The results indicate that antihypertensive treatment with isradipine as monotherapy may preventthe development of left ventricular hypertrophy whereas treatment with atenolol as monotherapy does not appear to offer this possibility.

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

    DEFF Research Database (Denmark)

    Ravn, Nathja; Zois, Nora Elisabeth

    2014-01-01

    Abstract Objectives: We aimed to develop a porcine model for chronic non-ischemic mitral regurgitation (MR) to investigate left ventricular (LV) enlargement and eccentric hypertrophy. Design: Non-ischemic MR was induced in 30 pigs by open chest immobilization of the posterior mitral leaflet by transannular 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 eight weeks follow-up. Results: Eight pigs died and 7 were excluded due to mediastinal infection (n=2) or failure to produce MR (n=5). Thus, 28 pigs were included and were divided into 3 groups: controls (n=12), mild MR (mMR; n=10) and moderate to severe MR (sMR; n=6). The change in LV internal diameter in diastole (LVIDd) from baseline to follow-up was significantly higher in the sMR group compared to the control group (P=0.0017). Furthermore, LV weight was significantly increased in the mMR (P=0.047) and the sMR (P=0.0087) groups compared to the control group. Conclusions: A new model for chronic moderate to severe non-ischemic MR with development of LV enlargement and eccentric hypertrophy within 8 weeks has been established in pigs.

  3. Effects of hypertrophy on left atrial and ventricular compliance and plasma ANF levels in conscious dogs.

    Science.gov (United States)

    Hasebe, N; Hittinger, L; Kohin, S; Shen, Y T; Graham, R M; Vatner, S F

    1995-02-01

    Alterations in left atrial (LA) and left ventricular (LV) compliance and arterial and coronary sinus atrial natriuretic factor (ANF) concentrations at baseline and in response to both volume depletion and expansion were investigated in 15 conscious dogs with aortic banding-induced LV hypertrophy (LVH) (LV/body wt increased by 64%), which also induced LAH (LA/body wt increased by 61%). With volume expansion coronary sinus ANF increased more (P < 0.05) in dogs with LVH (+427 +/- 88 pg/ml) compared with control dogs (+146 +/- 45 pg/ml). Arterial ANF levels also rose more with volume expansion in LVH. In dogs with LVH, the LV end-diastolic pressure-diameter relationship was shifted to the left with a steeper slope with volume expansion, such that at any given diastolic dimension, diastolic pressure was higher. In contrast, the pressure-dimension relationship for the LA appendage was shifted in the opposite direction during both atrial systolic and diastolic phases, with a more shallow slope in hypertrophy compared with control dogs, resulting in an augmented pressure-dimension product during volume loading in LAH. In conclusion, in dogs with LVH and LAH, enhanced ANF was revealed in the coronary sinus and systemic circulation during volume expansion, which could be due, in part, to a more compliant, but hypertrophied, LA, which responded to equivalent volume loading with an augmented pressure-dimension product. PMID:7864205

  4. 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

    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 electrocardiographic LV hypertrophy who underwent echocardiography at baseline and annually thereafter during randomized losartan- or atenolol-based antihypertensive treatment were followed for a mean of 4.6 years. The composite cardiovascular end point was the first occurrence of fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, and cardiovascular mortality. Antihypertensive therapy resulted in an increase in the prevalence of normal transmitral flow pattern from 28% to 46% of patients. Although antihypertensive treatment often resulted in a marked increase in the prevalence of normal mitral 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 into 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 was strongly associated with a reduced risk for hospitalization for heart failure.

  5. Arrhythmogenic substrate in hearts of rats with monocrotaline-induced pulmonary hypertension and right ventricular hypertrophy.

    Science.gov (United States)

    Benoist, David; Stones, Rachel; Drinkhill, Mark; Bernus, Olivier; White, Ed

    2011-06-01

    Mechanisms associated with right ventricular (RV) hypertension and arrhythmias are less understood than those in the left ventricle (LV). The aim of our study was to investigate whether and by what mechanisms a proarrhythmic substrate exists in a rat model of RV hypertension and hypertrophy. Rats were injected with monocrotaline (MCT; 60 mg/kg) to induce pulmonary artery hypertension or with saline (CON). Myocardial levels of mRNA for genes expressing ion channels were measured by real-time RT-PCR. Monophasic action potential duration (MAPD) was recorded in isolated Langendorff-perfused hearts. MAPD restitution was measured, and arrhythmias were induced by burst stimulation. Twenty-two to twenty-six days after treatment, MCT animals had RV hypertension, hypertrophy, and decreased ejection fractions compared with CON. A greater proportion of MCT hearts developed sustained ventricular tachycardias/fibrillation (0.83 MCT vs. 0.14 CON). MAPD was prolonged in RV and less so in the LV of MCT hearts. There were decreased levels of mRNA for K(+) channels. Restitution curves of MCT RV were steeper than CON RV or either LV. Dispersion of MAPD was greater in MCT hearts and was dependent on stimulation frequency. Computer simulations based on ion channel gene expression closely predicted experimental changes in MAPD and restitution. We have identified a proarrhythmic substrate in the hearts of MCT-treated rats. We conclude that steeper RV electrical restitution and rate-dependant RV-LV action potential duration dispersion may be contributing mechanisms and be implicated in the generation of arrhythmias associated with in RV hypertension and hypertrophy. PMID:21398591

  6. The effects of mechanical loading and changes of length on single guinea-pig ventricular myocytes.

    Science.gov (United States)

    White, E; Boyett, M R; Orchard, C H

    1995-01-01

    1. The effects of mechanical loading and changes of length on the contraction of single guinea-pig ventricular myocytes has been investigated. 2. Cell shortening was monitored during isotonic contractions (in which the cell shortened freely) and after attaching carbon fibres of known compliance to the ends of the cell, so that the cell contracted auxotonically (the cell both shortened and developed force). 3. Mechanically loading the cells decreased the amount of shortening during a contraction and abbreviated the contraction. There were, however, no consistent changes in the action potential or the [Ca2+]i transient (measured with the fluorescent dye fura-2). 4. Increasing stimulation rate increased the size of the contraction and the [Ca2+]i transient in both isotonic and auxotonic conditions. The increase in the size of the contraction induced by an increase in stimulation rate was greater in auxotonic conditions but the increase in the size of the [Ca2+]i transient was not. 5. When cells were stretched, there was a step increase in the size of the contraction and a prolongation of its time course. However, neither the size nor the time course of the accompanying [Ca2+]i transient was significantly altered by this intervention. 6. When a stretch was maintained, a further, slow increase in the size of the contraction occurred during the following 3-11 min, in about half the cells studied. The probability of this slow response occurring was increased if the initial degree of activation of the cell was decreased. 7. These data suggest that the mechanisms underlying the responses to mechanical loading and changes of length are the same in both multicellular and single cell preparations of cardiac muscle. PMID:7730993

  7. Calcium-sensitive and insensitive transient outward current in rabbit ventricular myocytes.

    Science.gov (United States)

    Hiraoka, M; Kawano, S

    1989-01-01

    1. A suction pipette whole-cell voltage-clamp technique was used to record membrane currents and potentials of isolated ventricular myocytes from rabbit hearts. 2. Transient outward current (Ito) was activated by voltage steps positive to -20 mV, increasing in amplitude with further depolarization to reach a maximum around +70 mV. The current attained its peak within 10 ms and then it inactivated for 100-200 ms. 3. A large portion of Ito still remained after the calcium current (ICa) was blocked when depolarizing pulses were applied at a frequency of 0.1 Hz or less. Therefore, this current component is referred to as calcium-insensitive Ito or It. 4. It showed voltage- and time-dependent inactivation similar to that observed in Purkinje fibres and other cardiac preparations. 5. The reversal potential of It depended on external K+ concentration, [K+]o, with a slope of 32 mV per 10-fold change in the presence of a normal [Na+]o (143 mM), while the slope was 48 mV per 10-fold change in low [Na+]o (1.0 mM). 6. It was completely inhibited by 2-4 mM-4-aminopyridine. Ito in the presence of ICa was also partially blocked by 4-aminopyridine and the remainder was abolished by 5 mM-caffeine. 7. The calcium-insensitive and caffeine-sensitive Ito differed in their decay rates as well as in their recovery time courses. The former was predominantly available at a slow pulsing rate, while the latter increased its amplitude with high-frequency depolarization. 8. The caffeine-sensitive Ito was inhibited by a blockade of ICa, by replacing Ca2+ with Sr2+, by external application of ryanodine and by internal application of EGTA. This indicates that the current is calcium-sensitive and is dependent on increased myoplasmic Ca2+ through Ca2+ influx via the sarcolemma and Ca2+ release from the sarcoplasmic reticulum. The current is therefore designated as IK, Ca. 9. The physiological functions of IK, Ca and It are indicated by their contribution to ventricular repolarization at fast and slow heart rates, respectively. PMID:2552080

  8. Rosuvastatin provides pleiotropic protection against pulmonary hypertension, right ventricular hypertrophy, and coronary endothelial dysfunction in rats.

    Science.gov (United States)

    Sun, Xiaowei; Ku, David D

    2008-02-01

    We recently reported that increased vascular endothelial nitric oxide production could protect against the development of monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) and right ventricular hypertrophy (RVH) in rats (32). The present study investigated whether the pleiotropic action of 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors in upregulating endothelial function could also protect against the MCT-induced end-organ damages. Rosuvastatin (2 mg kg(-1) day(-1) via oral gavage) or placebo was initiated 1 wk before or 1 wk after MCT (60 mg/kg ip) administration. One month after MCT, significant PAH developed in the placebo rats, which were accompanied by histological evidence of pulmonary vascular thickening and right ventricular hypertrophy. The coronary endothelial vasodilatory function, assessed with endothelial/nitric oxide-dependent responses to acetylcholine and N(G)-nitro-L-arginine methyl ester (L-NAME), was depressed, while the constrictory responses to known coronary constrictors was enhanced. In rats that received rosuvastatin treatment 1 wk before MCT administration, a significantly reduced PAH and RVH was observed, as well as reduced pulmonary vascular and right ventricular remodelings. Rosuvastatin 1-wk posttreatment had no effect on PAH, but inhibited RVH. Right coronary endothelial dysfunction, which was shown in placebo rats, was effectively prevented by both pre- and postrosuvastatin treatment, while this effect was more dramatic in the pretreated group. Left coronary endothelial function, which was not affected by MCT, also showed an upregulation by rosuvastatin. Taken together, our results demonstrated the pleiotropic protection of rosuvastatin against the development of PAH and RVH and confirmed our previous finding that the targeted preservation of coronary endothelial function and vasoactivity may provide a novel approach to protect against cardiac remodeling. PMID:18055512

  9. Effects of levosimendan in patients with left ventricular hypertrophy undergoing aortic valve replacement

    DEFF Research Database (Denmark)

    Juhl-Olsen, P; Jakobsen, C-J

    2014-01-01

    BACKGROUND: Left ventricular hypertrophy is associated with adverse outcomes, including death, during cardiac surgery. This may be facilitated by an increased oxygen demand and diastolic dysfunction. Levosimendan augments haemodynamics without further oxygen consumption and improves echocardiographic indices of diastolic dysfunction. This study aimed to describe the haemodynamic effects of short-term pre- and intra-operative levosimendan infusion including advanced echocardiographic measures of diastolic and systolic heart function. METHODS: The study was randomised, double-blinded and placebo-controlled performed at a single-centre university hospital. Patients with left ventricular hypertrophy and ejection fraction >?45% scheduled for single procedure aortic valve replacement were included and randomised to infusion of either levosimendan 0.1??g/kg/min or placebo from 4?h before anaesthesia to the end of surgery. Outcome measures were echocardiographic indices of left ventricular diastolic function: E/e' (primary endpoint), e', e'/a' and indices of systolic function: longitudinal strain, ejection fraction and s'. Patients were followed until 6 months after surgery. In addition, invasive haemodynamic measures were obtained perioperatively. RESULTS: The trial was prematurely terminated due to an overall high incidence of post-operative atrial fibrillation (15/20, P?=?0.002) after inclusion of 20 patients. The relative decrease in perioperative cardiac index was lower (P?=?0.016) in the levosimendan group. There was no difference in E/e', and similar results were found for all measures of systolic function. CONCLUSION: Short-term levosimendan caused a transient relative increase in cardiac index, but no effect was seen on the first post-operative day and up to 6 months post-operatively with indices of systolic and diastolic heart function.

  10. Differentiation of hypertrophic cardiomyopathy from left ventricular hypertrophy induced by essential hypertension using magnetic resonance imaging

    International Nuclear Information System (INIS)

    To examine the efficacy of magnetic resonance imaging (MRI) in diagnosing hypertrophic cardiomyopathy (HCM), 16 patients with HCM and 14 hypertensives with left ventricular hypertrophy (LDH) were studied using a 0.5 Tesla Siemens MRI apparatus equipped with cardiac gating. In HCM, left ventricular hypertrophy was localized to the septal wall in four, to the apical wall in two, to both the septal and apical walls in two, and to the apical and inferior walls in one, and it was diffuse in seven patients. In hypertensives, LVH was localized to the septal wall in three, to both the septal and anterior walls in two, to the free wall in one, and it was diffuse in eight patients. The distribution of the hypertrophic portion was nearly equal in both groups. The thickest portion of the left ventricular wall was 24.6 ± 4.8 mm in HCM and 21.6 ± 5.4 mm in hypertension, and there was no significant difference between them. The T2 relaxation time of the hypertrophic portion was 52.2 ± 4.8 msec in HCM and 45.3 ± 6.1 msec in hypertension, and there was a significant difference between them (p 2 relaxation times of the hypertrophic and non-hypertrophic protions in both groups. In conclusion, it may be difficult to differentiate HCM from hypertension based on the distribution of hypertrophic portions, but measurements of the T2 relaxation times may be useful for making the differentmay be useful for making the differential diagnosis. (author)

  11. The effects of implanted valve sizes on ventricular hypertrophy in aortic stenosis

    Directory of Open Access Journals (Sweden)

    Hikmet Selçuk Gedik

    2012-02-01

    Full Text Available Objective: We aimed to study the effects of the valve sizes according to body surface area on aortic gradient and ventricular hypertrophy in the cases of aortic valve replacement due to isolated aortic stenosis.Methods: Between January 2006 and April 2007, patients (12 men, 15 women; totally 27 followed up prospectively with echocardiography fourth and sixth month postoperatively. The patients were divided into two groups according to the prosthetic aortic valve diameters (19-21 mm vs 23-25 mm. The primary endpoints between the two groups (aortic regurgitation, left ventricular mass index and transvalvular gradient measured by color and continuous wave Doppler were compared. Fischer exact test and Mann-Whitney U test were used for intergroup comparison whereas intragroup analysis was done with Freidman test.Results: Mean systolic gradient and left ventricular mass index were significantly reduced in 23 mm and 25 mm valves (p<0.01 in the postoperative follow-up. In addition, especially, decline in the values of left ventricular mass, left ventricular mass index, peak systolic gradient and the mean systolic gradient were found to be significant. These values associated with regression were detectable at the postoperative 4th month, but actual significant regression was observed at the postoperative 6th month (p<0.01. On the other hand, the values obtained for 19 mm and 21 mm valves also showed significant progress (p<0.05.Conclusion: Factors such as age, gender and activity are important in the selection of appropriate valve sizes in aortic valve replacement. However, the patient's body surface is the most important prognostic factor compared to others.

  12. Cross-signaling between L-type Ca2+ channels and ryanodine receptors in rat ventricular myocytes

    OpenAIRE

    1996-01-01

    Calcium-mediated cross-signaling between the dihydropyridine (DHP) receptor, ryanodine receptor, and Na(+)-Ca2+ exchanger was examined in single rat ventricular myocytes where the diffusion distance of Ca2+ was limited to < 50 nm by dialysis with high concentrations of Ca2+ buffers. Dialysis of the cell with 2 mM Ca(2+)- indicator dye, Fura-2, or 2 mM Fura-2 plus 14 mM EGTA decreased the magnitude of ICa-triggered intracellular Ca2+ transients (Cai-transients) from 500 to 20-100 nM and comple...

  13. The cell cycle factor E2F-1 activates Bnip3 and the intrinsic death pathway in ventricular myocytes.

    Science.gov (United States)

    Yurkova, Natalia; Shaw, James; Blackie, Karen; Weidman, Danielle; Jayas, Ravi; Flynn, Bryan; Kirshenbaum, Lorrie A

    2008-02-29

    The cell cycle factor E2F-1 is known to regulate a variety of cellular processes including apoptosis. Previously we showed that disruption of Rb-E2F-1 complexes provoked apoptosis of postmitotic adult and neonatal ventricular myocytes; however, the underlying mechanism was undetermined. In this report, we show that E2F-1 provokes cell death of ventricular myocytes through a mechanism that directly impinges on the intrinsic death pathway. Furthermore, we show mechanistically that the hypoxia-inducible death factor Bnip3 is a direct transcriptional target of E2F-1 that is necessary and sufficient for E2F-1-induced cell death. Expression of E2F-1 resulted in a 4.9-fold increase (P<0.001) in nucleosomal DNA fragmentation and cell death by Hoechst 33258 dye and vital staining. E2F-1 provoked mitochondrial perturbations that were consistent with permeability transition pore opening. As determined by quantitative real-time PCR analysis, a 6.2-fold increase (P<0.001) in endogenous Bnip3 gene transcription was observed in cells expressing wild-type E2F-1 but not in cells expressing a mutation of E2F-1 defective for DNA binding. Rb, the principle regulator of cellular E2F-1 activity, was proteolytically cleaved and inactivated in ventricular myocytes during hypoxia. Consistent with the proteolytic cleavage of Rb, chromatin immunoprecipitation analysis revealed increased binding of E2F-1 to the Bnip3 promoter during hypoxia, a finding concordant with the induction of Bnip3 gene transcription. The Bnip3 homolog Nix/Bnip3L was unaffected in ventricular myocytes by either E2F-1 or hypoxia. Genetic knockdown of E2F-1 or expression of a caspase-resistant form of Rb suppressed basal and hypoxia-inducible Bnip3 gene transcription. Loss-of-function mutations of Bnip3 defective for mitochondrial membrane insertion or small interference RNA directed against Bnip3 suppressed cell death signals elicited by E2F-1. To our knowledge, the data provide the first direct evidence that activation of the intrinsic mitochondrial death pathway by E2F-1 is mutually dependent on and obligatorily linked to the transcriptional activation of Bnip3. PMID:18096822

  14. Iodine-123 phenylpentadecanoic acid myocardial scintigraphy in patients with left ventricular hypertrophy: Alterations in left ventricular distribution and utilization

    International Nuclear Information System (INIS)

    Regional alterations in myocardial substrate uptake and/or utilization have been demonstrated in rats with hypertension. To determine whether alterations in left ventricular fatty acid uptake and/or utilization are present in patients with left ventricular hypertrophy (LVH), we compared the results of rest and exercise iodine-123 phenylpentadecanoic acid (IPPA) myocardial scintigraphy in 10 patients with hypertension who had concentric LVH without evidence of coronary artery disease and in 15 normal subjects. Patients with LVH had more heterogeneous left ventricular activity of IPPA compared to normal subjects after exercise but not at rest. Although IPPA clearance was similar in both patients with LVH and normal subjects, postexercise washout in segments showing decreased initial IPPA uptake was reduced compared to washout at rest in patients with LVH (11.7 +/- 7.5% versus 21.5 +/- 8.4% at 20 minutes after injection, n = 15; p = 0.005). Exercise thallium-201 (TI-201) scintigraphy was normal in all seven patients with LVH tested. Patients with LVH showed significantly greater heterogeneity in IPPA uptake compared to TI-201 uptake immediately after exercise (25 +/- 5% versus 16 +/- 6%; p = 0.013). We conclude that (1) compared to normal subjects, patients with LVH show heterogeneous myocardial IPPA activity after exercise but not at rest; (2) postexercise washout of IPPA was decreased in segments with reduced uptake after exercise in patients with LVH; and (3) the distise in patients with LVH; and (3) the distribution of IPPA is more heterogeneous than that of TI-201 immediately after exercise in patients with concentric LVH. The postexercise heterogeneity in IPPA uptake and delayed washout in segments with reduced initial uptake is consistent with exercise-induced myocardial ischemia in patients with LVH

  15. 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

    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.

  16. [Effects of exercise on coronary circulation in left ventricular hypertrophy caused by hypertension].

    Science.gov (United States)

    Wicker, P; Tarazi, R C

    1986-06-01

    Exercise is known to promote myocardial vascularity. We therefore studied whether it could prevent coronary abnormalities of hypertensive left ventricular (LV) hypertrophy. Female Sprague-Dawley 1 clip-2 kidneys Goldblatt hypertensive rats (RHR) and their appropriate controls (Sham-SH), were either made to swim (RHR-SW, SH-SW) or kept sedentary (RHR-SED, SH-SED) for 9 weeks. Maximal coronary blood flow (LV CBF, ml/min/gm) and minimal coronary resistance after carbochrome (total LVCR/LV mmHg/ml/min), an index of the functional cross sectional area (CSA) of coronary resistance vessels, were determined in conscious rats by microspheres. Results (m +/- SD) (n = 12 in all groups): (Table: see text). Exercise increased functional coronary CSA in normotensive rats only. This beneficial effect did not occur in hypertension, probably because of functional changes in the coronary vessels of RHR. PMID:2948470

  17. 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.

  18. 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 ?-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.

  19. Cardiac morphology in left ventricular hypertrophy using thallium-201 myocardial scintigraphy

    International Nuclear Information System (INIS)

    To evaluate cardiac morphology in the patients with various cases of hypertrophy, we measured left ventricular (LV) size using thallium-201 myocardial scintigraphy in 29 normal subjects and in 90 patients. Cardiac shape and dimension were assessed by measuring the wall thickness and external length in the short and long axis of LV image in LAO projection. In aortic stenosis and hypertensive heart disease the shape was spherical and the wall was thickened. In both mitral (MR) and aortic (AR) regurgitations, LV dilatation were shown; spherical shape in chronic MR but ellipsoid shape in acute MR and AR. Decreased LV size but normal shape was observed in mitral stenosis and cor pulmonale. In hypertrophic cardiomyopathy the LV wall was asymmetrically hypertrophied, while in congestive cardiomyopathy the wall is thin with marked LV dilatation and the shape was spherical. We concluded that the heart had characteristic configuration which might reflect cardiac performance or compensate for the load to the heart, and that thallium-201 myocardial scintigraphy is useful in the evaluation of cardiac morphology as well as in diagnosis of myocardial ischemia. (author)

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

    Scientific Electronic Library Online (English)

    Ljuba, Bacharova; Jan, Kyselovic; Jan, Klimas.

    2002-08-01

    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

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

    International Nuclear Information System (INIS)

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

  2. Inhibition of glycogen synthase kinase 3beta prevents peroxide-induced collapse of mitochondrial membrane potential in rat ventricular myocytes.

    Science.gov (United States)

    Förster, Karina; Richter, Heike; Alexeyev, Mikhail F; Rosskopf, Dieter; Felix, Stephan B; Krieg, Thomas

    2010-07-01

    1. Preconditioning has been proposed to protect the myocardium by inhibiting glycogen-synthase kinase (GSK) 3beta. The aim of the present study was to test whether transfection of ventricular myocytes with inactive GSK3 beta would mimic preconditioning and whether a constitutively active form of GSK3 beta would prevent protection by an opioid receptor agonist. 2. Isolated ventricular myocytes from adult rats were infected with live adenovirus containing either a wild-type (wtGSK), constitutively active (caGSK) or dominant-negative (dnGSK) GSK3 beta plasmid. Cells were loaded with tetramethylrhodamine ethyl ester (TMRE) and exposed to H(2)O(2) (100 micromol/L) for 40 min before mitochondrial membrane potential (Delta Psi(m)) was assessed using flow cytometric analysis. 3. Fluorescence intensity was reduced in H(2)O(2)-treated cells compared with untreated cells, presumably because oxidant injury opened mitochondrial permeability transition pores, causing mitochondria to lose TMRE. The selective GSK3 beta inhibitor SB216763, as well as the delta-opioid receptor agonist [d-Ala(2)-D-Leu(5)]-enkephalin (DADLE) (1 micromol/L), protected cells against peroxide-induced loss of Delta Psi(m). 4. Cells transfected with dnGSK (1 micromol/L) were equally protected against peroxide stress, when given throughout the TMRE and H(2)O(2) treatment, confirming a protective effect of GSK3 beta with a highly selective inhibition. Cells transfected with wtGSK did not show any difference in responses to H(2)O(2), SB216763 or DADLE compared with untransfected cells, suggesting that adenovirus infection itself had no effect. In contrast, caGSK-transfected myocytes could no longer be protected with DADLE, suggesting a role for GSK3 beta between the surface receptor and the mitochondria. 5. These experiments confirm that inhibition of GSK3 beta protects the myocytes, but also that the preconditioning mimetic DADLE loses its protective effect when a constitutively active GSK3 beta is present. PMID:20337662

  3. Sodium current block caused by group IIb cations in calf Purkinje fibres and in guinea-pig ventricular myocytes.

    Science.gov (United States)

    Visentin, S; Zaza, A; Ferroni, A; Tromba, C; DiFrancesco, C

    1990-10-01

    The action of group IIb cations [Cadmium (Cd2+), Zinc (Zn2+), Mercury (Hg2+)] on the cardiac fast sodium current (INa) was investigated in calf Purkinje fibres and in ventricular cells isolated from guinea-pig hearts. In calf Purkinje fibres, INa was depressed by submillimolar concentrations of Zn2+ and Hg2+. With both cations, the current reduction occurred at all voltages in the range of current activation and the voltage dependence of peak current was unchanged. The degree of peak current inhibition depended on the cation concentration but not on voltage. The position of the inactivation curve on the voltage axis was unaltered at cation concentrations giving substantial current inhibition, and moved to the right only with concentration exceeding 1-1.5 mM. These effects can be interpreted as due to INa channel blockade. The action of Zn2+ and Hg2+ was similar to that described earlier of Cd2+ on Purkinje fibres (DiFrancesco et al. 1985b). INa was also inhibited by group IIb cations in isolated guinea-pig ventricular cells. Depression of INa by Cd2+, Zn2+ and Hg2+ was essentially voltage-independent, in agreement with its being caused by channel block. The dependence of INa block by Cd2+ upon external Na concentration [Na+0] was investigated in ventricular myocytes. The fraction of INa block by 0.1 mM CdCl2 was 0.50 at 140 mM, 0.81 at 70 mM and 0.83 at 35 mM [Na+]0. A similar increase of block efficiency at low [Na+0] was observed with 0.05 mM CdCl2. In both the Purkinje fibre and the ventricular cell, the order of potency of INa block by group IIb cations was Hg2+ greater than Zn2+ greater than Cd2+. Manganese (Mn2+, 2-5 mM), an ion of group VIIa, also depressed the INa in Purkinje fibres and ventricular myocytes. This effect was however due mainly to a positive shift on the voltage dependence of current kinetics rather than to a reduction of the conductance of the channel (GNa), and can be accounted for by an ion-screening action of Mn2+ on the external membrane surface. The block by group IIb cations is a typical property of cardiac Na+ channels and characterizes the cardiac as opposed to other types of Na+ channel. PMID:1964724

  4. Metabolic inhibition strongly inhibits Na+-dependent Mg2+ efflux in rat ventricular myocytes.

    Science.gov (United States)

    Tashiro, Michiko; Inoue, Hana; Konishi, Masato

    2009-06-17

    We measured intracellular Mg2+ concentration ([Mg2+]i) in rat ventricular myocytes using the fluorescent indicator furaptra (25 degrees C). In normally energized cells loaded with Mg2+, the introduction of extracellular Na+ induced a rapid decrease in [Mg2+]i: the initial rate of decrease in [Mg2+]i (initial Delta[Mg2+]i/Deltat) is thought to represent the rate of Na+-dependent Mg2+ efflux (putative Na+/Mg2+ exchange). To determine whether Mg2+ efflux depends directly on energy derived from cellular metabolism, in addition to the transmembrane Na+ gradient, we estimated the initial Delta[Mg2+]i/Deltat after metabolic inhibition. In the absence of extracellular Na+ and Ca2+, treatment of the cells with 1 microM carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone, an uncoupler of mitochondria, caused a large increase in [Mg2+]i from approximately 0.9 mM to approximately 2.5 mM in a period of 5-8 min (probably because of breakdown of MgATP and release of Mg2+) and cell shortening to approximately 50% of the initial length (probably because of formation of rigor cross-bridges). Similar increases in [Mg2+]i and cell shortening were observed after application of 5 mM potassium cyanide (KCN) (an inhibitor of respiration) for > or = 90 min. The initial Delta[Mg2+]i/Deltat was diminished, on average, by 90% in carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone-treated cells and 92% in KCN-treated cells. When the cells were treated with 5 mM KCN for shorter times (59-85 min), a significant decrease in the initial Delta[Mg2+]i/Deltat (on average by 59%) was observed with only a slight shortening of the cell length. Intracellular Na+ concentration ([Na+]i) estimated with a Na+ indicator sodium-binding benzofuran isophthalate was, on average, 5.0-10.5 mM during the time required for the initial Delta[Mg2+]i/Deltat measurements, which is well below the [Na+]i level for half inhibition of the Mg2+ efflux (approximately 40 mM). Normalization of intracellular pH using 10 microM nigericin, a H+ ionophore, did not reverse the inhibition of the Mg2+ efflux. From these results, it seems likely that a decrease in ATP below the threshold of rigor cross-bridge formation (approximately 0.4 mM estimated indirectly in the this study), rather than elevation of [Na+]i or intracellular acidosis, inhibits the Mg2+ efflux, suggesting the absolute necessity of ATP for the Na+/Mg2+ exchange. PMID:19527653

  5. Changing pattern of gene expression is associated with ventricular myocyte dysfunction and altered mechanisms of Ca2+ signalling in young type 2 Zucker diabetic fatty rat heart.

    Science.gov (United States)

    Howarth, F C; Qureshi, M A; Hassan, Z; Al Kury, L T; Isaev, D; Parekh, K; Yammahi, S R K D; Oz, M; Adrian, T E; Adeghate, E

    2011-03-01

    The association between type 2 diabetes and obesity is very strong, and cardiovascular complications are the major cause of morbidity and mortality in diabetic patients. The aim of this study was to investigate early changes in the pattern of genes encoding cardiac muscle regulatory proteins and associated changes in ventricular myocyte contraction and Ca(2+) transport in young (9- to 13-week-old) type 2 Zucker diabetic fatty (ZDF) rats. The amplitude of myocyte shortening was unaltered; however, time-to-peak shortening and time to half-relaxation of shortening were prolonged in ZDF myocytes (163 ± 5 and 127 ± 7 ms, respectively) compared with age-matched control rats (136 ± 5 and 103 ± 4 ms, respectively). The amplitude of the Ca(2+) transient was unaltered; however, time-to-peak Ca(2+) transient was prolonged in ZDF myocytes (66.9 ± 2.6 ms) compared with control myocytes (57.6 ± 2.3 ms). The L-type Ca(2+) current was reduced, and inactivation was prolonged over a range of test potentials in ZDF myocytes. At 0 mV, the density of L-type Ca(2+) current was 1.19 ± 0.28 pA pF(-1) in ZDF myocytes compared with 2.42 ± 0.40 pA pF(-1) in control myocytes. Sarcoplasmic reticulum Ca(2+) content, release and uptake and myofilament sensitivity to Ca(2+) were unaltered in ZDF myocytes compared with control myocytes. Expression of genes encoding various L-type Ca(2+) channel proteins (Cacna1c, Cacna1g, Cacna1h and Cacna2d1) and cardiac muscle proteins (Myh7) were upregulated, and genes encoding intracellular Ca(2+) transport regulatory proteins (Atp2a2 and Calm1) and some cardiac muscle proteins (Myh6, Myl2, Actc1, Tnni3, Tnn2, and Tnnc1) were downregulated in ZDF heart compared with control heart. A change in the expression of genes encoding myosin heavy chain and L-type Ca(2+) channel proteins might partly underlie alterations in the time course of contraction and Ca(2+) transients in ventricular myocytes from ZDF rats. PMID:21216827

  6. The aqueous extract, not organic extracts, of Terminalia arjuna bark exerts cardiotonic effect on adult ventricular myocytes.

    Science.gov (United States)

    Oberoi, Lalit; Akiyama, Toshiyuki; Lee, Kuo-Hsiung; Liu, Shi J

    2011-02-15

    The bark of Terminalia arjuna (TA) has been used for centuries in ayurvedic medicine as cardiotonics for treatment of cardiac disorders. It became recently available as over-the-counter supplements marketed for maintaining a healthy heart. However, the cellular mechanism of its cardiotonic effect remains undefined. The present study was designed to investigate the physicochemical property and inotropic effect of the aqueous extract of TA bark (TA(AqE)) on adult rat ventricular myocytes in comparison with extracts prepared sequentially with organic solvents (organic extracts). The kinetics of myocyte contraction and caffeine-induced contraction were analyzed to assess the effect of TA(AqE) on sarcoplasmic reticular (SR) function. The inotropic effect of TA(AqE) was also compared with that of known cardiotonics, isoproterenol (ISO) and ouabain (Ouab). We found that TA(AqE) decoctions exerted positive inotropy, accelerated myocyte relaxation and increased caffeine-induced contraction concentration-dependently. In contrast, TA organic extracts caused interruption of excitability and arrhythmias without consistent inotropic action. In conclusion, TA(AqE)-induced cardiotonic action via enhancing SR function, a unique action minimizing the occurrence of arrhythmias, makes TA(AqE) a promising and relatively safe cardiotonic beneficial to the healthy heart and the treatment for chronic heart disease. The cardiotonic effect of TA(AqE) is consistent with the therapeutic property of TA bark used in ayurvedic medicine. The method of administration and/or selective omission of hydrophobic components from bark powder could be crucial to the efficacy and safety of TA bark in cardiac therapy and uses as over-the-counter supplements. PMID:21315570

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

    OpenAIRE

    Merwe, Lize; Cloete, Ruben; Revera, Miriam; Heradien, Marshall; Goosen, Althea; Corfield, Valerie A.; Brink, Paul A.; 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...

  8. Selective block of swelling-activated Cl- channels over cAMP-dependent Cl- channels in ventricular myocytes.

    Science.gov (United States)

    Shuba, Lesya M; Missan, Sergey; Zhabyeyev, Pavel; Linsdell, Paul; McDonald, Terence F

    2004-05-01

    The objective of this study on guinea-pig and rabbit ventricular myocytes was to evaluate the sensitivities of swelling-activated Cl- current (ICl(swell)) and cAMP-dependent cystic fibrosis transmembrane regulator (CFTR) Cl- current (ICl(CFTR)) to block by dideoxyforskolin and verapamil. The currents were recorded from whole-cell configured myocytes that were dialysed with a Cs+-rich pipette solution and superfused with either isosmotic Na+-, K+-, Ca2+-free solution that contained 140 mM sucrose or hyposmotic sucrose-free solution. Forskolin-activated ICl(CFTR) was inhibited by reference blocker anthracene-9-carboxylic acid but unaffected by < or = 200 microM dideoxyforskolin and verapamil. However, dideoxyforskolin and verapamil had strong inhibitory effects on outwardly-rectifying, inactivating, distilbene-sensitive ICl(swell); IC50 values were approximately 30 microM, and blocks were voltage-independent and reversible. The results establish that dideoxyforskolin and verapamil can be used to distinguish between ICl(CFTR) and ICl(swell) in heart cells, and expand the pharmacological characterization of cardiac ICl(swell). PMID:15140627

  9. Real-time observations of intracellular Mg2+ signaling and waves in a single living ventricular myocyte cell.

    Science.gov (United States)

    Lee, Seungah; Lee, Hee Gu; Kang, Seong Ho

    2009-01-15

    Despite the important regulatory role of Mg(2+) in metabolic pathways, its underlying mechanism is not completely understood at the single-cell level. This study examined the propagation and dynamics of Mg(2+) signaling across the cell membrane by employing the real-time visualization of intracellular Mg(2+) waves in living ventricular myocytes using a combination of total internal reflection fluorescence microscopy and Nomarski differential interference contrast. Real-time Mg(2+) waves and sparks in a living cell membrane were observed using a fluorescent Mg(2+) indicator (mag-fluo-4-AM) in the concentration range of 5 aM-5 muM. The intracellular locations of the fluorescent Mg(2+) indicator were confirmed by adding Na(+)ATP. The Mg(2+) sparks and waves showed random temporal propagation patterns in nonhomogeneous substructures. These results show that spatiotemporal intracellular Mg(2+) signaling information can be obtained for individual living cells. PMID:19086893

  10. 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 groups: CON, control; ENA, treated with enalaprilat (1mg/kg via subcutaneous (sc for 8 days; ISO, treated with isoproterenol (0.3mg via sc for 8 days e ENA+ISO, treated with both drugs simultaneously. Each group had the arterial blood pressure, cardiac rate and the left ventricle (LV weight determined in 10 animals. In 8 animals from each group a small sample was taken from the LV and stained with hematoxyline-eosine and picrosirius for morphometric and ultra-structural studies with optic and transmission electronic microscopy. RESULTS: The ISO group showed that the LV weight increased 47% in comparison with control. On the other hand the ENA+ISO group showed only 22.1% increase (p<0.05. The morphometric and ultra-structural analyses revealed that isoproterenol induced cardiomyocite hypertrophy and augmented the content of the type I collagen in the cardiac interstitium. CONCLUSION: Enalaprilat inhibited the isoproterenol action on the cardiomyocite, avoiding partially the LVH and decreasing the content of collagen fibers.

  11. 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 speci?c 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 ?g/mL venom obviously prolonged APDs. Signi?cantly, 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. PMID:24930961

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

    Scientific Electronic Library Online (English)

    R.B., Randon; L.E., Rohde; L., Comerlato; J.P., Ribeiro; R.C., Manfro.

    1409-14-01

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

  13. Biological, electrical and echocardiographic indices versus cardiac magnetic resonance imaging in diagnosing left ventricular hypertrophy.

    Science.gov (United States)

    Courand, Pierre-Yves; Gaudebout, Nathalie; Mouly-Bertin, Carine; Thomson, Vivien; Fauvel, Jean-Pierre; Bricca, Giampiero; Lantelme, Pierre

    2014-05-01

    The aim of this study was to compare the diagnostic performance of N-terminal pro-brain natriuretic peptide (NT-proBNP), electrocardiographic (ECG) criteria and transthoracic echocardiography (TTE) versus cardiac magnetic resonance imaging in detecting left ventricular hypertrophy (LVH). The study included 42 hypertensive subjects with mean±s.d. age 48.1±12.3 years, 57.1% men, 24-h ambulatory blood pressure 144/89?mm?Hg, left ventricular ejection fraction >50%, without symptoms of heart failure, and not taking any drugs that interfere with hormonal regulation. The accuracies of the methods in detecting LVH were compared at two diagnostic LVH cutoffs: low, 83?g?m(-2) in men and 67?g?m(-2) in women; and high, 96?g?m(-2) in men and 81?g?m(-2) in women. With the low and high LVH cutoffs, the areas under the receiver-operating characteristic curves and the optimal values for NT-proBNP were 0.761, 0.849, 200 and 421?pg?ml(-1), respectively. An NT-proBNP level under 30?pg?ml(-1) ruled out LVH with 100% sensitivity. The optimal values and literature-based values of NT-proBNP allowed a correct classification of 73-81% of the subjects. In 80-90% of the cases, the diagnostic accuracy of NT-proBNP was close to that of ECG criteria but lower than that of TTE criteria. Interestingly, combining ECG criteria and NT-proBNP level improved the diagnostic performance to be at least comparable to that of TTE: the percentages of correctly classified subjects were 73-95% vs. 67-86%, respectively. Of note, the range considers both diagnostic LVH cutoffs. The simultaneous use of ECG criteria and NT-proBNP plasma levels seemed to be powerful enough to detect LVH in most hypertensive subjects. PMID:24132010

  14. Suppression of cardiac myocyte hypertrophy by conjugated linoleic acid: role of peroxisome proliferator-activated receptors alpha and gamma.

    Science.gov (United States)

    Alibin, Caroline P; Kopilas, Melanie A; Anderson, Hope D I

    2008-04-18

    Conjugated linoleic acid (CLA) refers to a naturally occurring mixture of positional and geometric isomers of linoleic acid. Evidence suggests that CLA is a dietary constituent and nutraceutical with anti-cancer, insulin-sensitizing, immunomodulatory, weight-partitioning, and cardioprotective properties. The aim of this study was to evaluate the effects of intervention with CLA on cardiac hypertrophy. In vitro, CLA prevented indicators of cardiomyocyte hypertrophy elicited by endothelin-1, including cell size augmentation, protein synthesis, and fetal gene activation. Similar anti-hypertrophic effects of CLA were observed in hypertrophy induced by angiotensin II, fibroblast growth factor, and mechanical strain. CLA may inhibit hypertrophy through activation of peroxisome proliferator-activated receptors (PPARs). CLA stimulated PPAR activity in cardiomyocytes, and the anti-hypertrophic effects of CLA were blocked by genetic and pharmacological inhibitors of PPAR isoforms alpha and gamma. CLA may disrupt hypertrophic signaling by stimulating diacylglycerol kinase zeta, which decreases availability of diacylglycerol and thereby inhibits the protein kinase Cepsilon pathway. In vivo, dietary CLA supplementation significantly reduced blood pressure and cardiac hypertrophy in spontaneously hypertensive heart failure rats. These data suggest that dietary supplementation with CLA may be a viable strategy to prevent pathological cardiac hypertrophy, a major risk factor for heart failure. PMID:18283099

  15. The impact of left ventricular hypertrophy on survival in candidates for liver transplantation.

    Science.gov (United States)

    Batra, Sachin; Machicao, Victor I; Bynon, John S; Mehta, Shivang; Tanikella, Rajasekhar; Krowka, Michael J; Zacks, Steven; Trotter, James; Roberts, Kari E; Brown, Robert S; Kawut, Steven M; Fallon, Michael B

    2014-06-01

    Left ventricular hypertrophy (LVH) occurs in 12% to 30% of patients with cirrhosis; however, its prognostic significance is not well studied. We assessed the association of LVH with survival in patients undergoing a liver transplantation (LT) evaluation. We performed a multicenter cohort study of patients undergoing an evaluation for LT. LVH was defined with transthoracic echocardiography. The outcome of interest was all-cause mortality. LVH was present in 138 of 485 patients (28%). Patients with LVH were older, more likely to be male and African American, and were more likely to have hypertension. Three hundred forty-five patients did not undergo transplantation (212 declined, and 133 were waiting): 36 of 110 patients with LVH (33%) died, whereas 57 of 235 patients without LVH (24%) died (P?=?0.23). After LT, 8 of 28 patients with LVH (29%) died over the course of 3 years, whereas 9 of 112 patients without LVH (8%) died (P?=?0.007). This finding was independent of conventional risk factors for LVH, and all deaths for patients with LVH occurred within 9 months of LT. No clinical or demographic characteristics were associated with mortality among LVH patients. In conclusion, the presence of LVH is associated with an early increase in mortality after LT, and this is independent of conventional risk factors for LVH. Further studies are needed to confirm these findings and identify factors associated with mortality after transplantation to improve outcomes. PMID:24659368

  16. A Localized Meshless Approach for Modeling Spatial-temporal Calcium Dynamics in Ventricular Myocytes

    OpenAIRE

    Yao, Guangming; Yu, Zeyun

    2012-01-01

    Spatial-temporal calcium dynamics due to calcium release, buffering and re-uptaking plays a central role in studying excitation-contraction (E-C) coupling in both normal and diseased cardiac myocytes. In this paper, we employ a meshless method, namely, the local radial basis function collocation method (LRBFCM) to model such calcium behaviors by solving a nonlinear system of reaction-diffusion partial differential equations. In particular, a simplified structural unit containing a single tran...

  17. Effects of phorbol ester on contraction, intracellular pH and intracellular Ca2+ in isolated mammalian ventricular myocytes.

    Science.gov (United States)

    MacLeod, K T; Harding, S E

    1991-12-01

    1. We have investigated the actions of certain phorbol esters on the intracellular pH, intracellular Ca2+ and contractility of isolated rat and guinea-pig cardiac myocytes. Intracellular pH was measured using 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF) and intracellular Ca2+ was measured using Fura-2. 2. Application of the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (also called phorbol 12-myristate 13-acetate) (TPA) (which activates protein kinase C) to rat cardiac myocytes significantly increased cell shortening by 116 +/- 34% (n = 8) (p less than 0.02). The rate of change of cell length during contraction (i.e. +dL/dt) increased from 67.2 +/- 8.7 microns/s to 127.7 +/- 14.1 microns/s (n = 7). The rate of change of cell length during relaxation (-dL/dt) increased from 55.8 +/- 7.4 microns/s to 118.9 +/- 12.1 microns/s (n = 7). Time to peak shortening was unchanged. 3. Application of 4 alpha-phorbol 12,13-didecanoate, which does not activate protein kinase C, did not affect rat myocyte contractility. An insignificant decrease in contractility (by 7.5 +/- 7.5%) was observed (n = 5). The positive inotropic effect of TPA may therefore be evoked through an activation of protein kinase C. 4. In rat myocytes we have measured the changes of pHi and contractility (cell shortening) during an alkalosis and acidosis induced by exposure to and subsequent removal of NH4Cl both in the presence and absence of TPA. Recovery times from an acid load were significantly (p less than 0.05) enhanced by 15.1 +/- 6.9% (n = 13) in the presence of TPA. Recovery times of cell shortening were also more rapid (p less than 0.05) by an average of 59.1 +/- 10.6% (n = 5) in the presence of TPA. Recovery times were unchanged in the presence of 4-phorbol 12,13-didecanoate (which does not activate protein kinase C). 5. Since pHi recovery of an isolated myocyte from an acid load is partially inhibited by the presence of 1 mM-amiloride and inhibited by removing extracellular Na+ then it is suggested that, like pHi regulation in sheep heart Purkinje fibres, pHi recovery in rat cardiac ventricular myocytes is mainly through sarcolemmal Na(+)-H+ exchange. We suggest that in the presence of TPA the Na(+)-H+ exchange is stimulated. 6. The relationship between pHi and cell shortening is non-linear as has been observed by others in whole tissue preparations. The presence of TPA shifts the relationship upwards such that at any one pHi, cell shortening is greater.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:1822559

  18. Changes in intracellular calcium concentration influence beat-to-beat variability of action potential duration in canine ventricular myocytes.

    Science.gov (United States)

    Kistamas, K; Szentandrassy, N; Hegyi, B; Vaczi, K; Ruzsnavszky, F; Horvath, B; Banyasz, T; Nanasi, P P; Magyar, J

    2015-02-01

    The aim of the present work was to study the influence of changes in intracellular calcium concentration ([Ca(2+)]i) on beat-to-beat variability (short term variability, SV) of action potential duration (APD) in isolated canine ventricular cardiomyocytes. Series of action potentials were recorded from enzymatically isolated canine ventricular cells using conventional microelectrode technique. Drug effects on SV were evaluated as relative SV changes determined by plotting the drug-induced changes in SV against corresponding changes in APD and comparing these data to the exponential SV-APD function obtained with inward and outward current injections. Exposure of myocytes to the Ca(2+) chelator BAPTA-AM (5 ?M) decreased, while Ca(2+) ionophore A23187 (1 ?M) increased the magnitude of relative SV. Both effects were primarily due to the concomitant changes in APD. Relative SV was reduced by BAPTA-AM under various experimental conditions including pretreatment with veratridine, BAY K8644, dofetilide or E-4031. Contribution of transient changes of [Ca(2+)]i due to Ca(2+) released from the sarcoplasmic reticulum (SR) was studied using 10 ?M ryanodine and 1 ?M cyclopiazonic acid: relative SV was reduced by both agents. Inhibition of the Na(+)-Ca(2+) exchanger by 1 ?M SEA0400 increased relative SV. It is concluded that elevation of [Ca(2+)]i increases relative SV significantly. More importantly, Ca(2+) released from the SR is an important component of this effect. PMID:25716967

  19. 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

  20. The H1–H2 domain of the ?1 isoform of Na+–K+–ATPase is involved in ouabain toxicity in rat ventricular myocytes

    International Nuclear Information System (INIS)

    The composition of different isoforms of Na+-K+-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 H1–H2 domain of ?1 and ?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 ?1 or ?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 ([Ca2+]i), attenuated mitochondrial Ca2+ 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 ?M) of OUA. Similarly, preincubation of myocytes with WJS inhibited high OUA affinity pump current, reduced the increase of [Ca2+]i and the contractility induced by 1 ?M but not that induced by 1 mM OUA. These results indicate that the H1–H2 domain of the NKA ?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 H1-H2 domain of ?1 and ?2 isoforms of NKA. ? The H1-H2 domain of the NKA ?1 isoform mediates OUA-induced cardiac toxicity. ? The H1-H2 domain of the NKA ?2 isoform mediates OUA-induced positive inotropic.

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

    Scientific Electronic Library Online (English)

    Eduardo A. S., Costa; Bráulio, Luna Fº; Rui, Póvoa; Celso, Ferreira Fº; Neif, Murad; Marcelo, Ferreira; Celso, Ferreira.

    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. Abstract in english 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 groups: CON, control; ENA, treated with enalaprilat (1mg/kg via su [...] bcutaneous (sc) for 8 days); ISO, treated with isoproterenol (0.3mg via sc for 8 days) e ENA+ISO, treated with both drugs simultaneously. Each group had the arterial blood pressure, cardiac rate and the left ventricle (LV) weight determined in 10 animals. In 8 animals from each group a small sample was taken from the LV and stained with hematoxyline-eosine and picrosirius for morphometric and ultra-structural studies with optic and transmission electronic microscopy. RESULTS: The ISO group showed that the LV weight increased 47% in comparison with control. On the other hand the ENA+ISO group showed only 22.1% increase (p

  2. Exercise-induced subendocardial dysfunction in dogs with left ventricular hypertrophy.

    Science.gov (United States)

    Hittinger, L; Shannon, R P; Kohin, S; Manders, W T; Kelly, P; Vatner, S F

    1990-02-01

    The effects of treadmill exercise on regional myocardial blood flow and function were examined in 10 adult, conscious dogs with left ventricular hypertrophy (LVH) induced by aortic banding in puppies, which resulted in a left ventricular (LV) weight/body weight ratio of 8.5 +/- 0.3. Data were compared with results from eight control dogs with an LV weight/body weight ratio of 4.9 +/- 0.2. At rest, LV systolic and end-diastolic pressures were significantly greater (p less than 0.01), and mean arterial pressure was significantly less (p less than 0.05) in LVH dogs. Mean myocardial blood flow (control dogs, 0.98 +/- 0.11 ml/min/g; LVH dogs, 1.16 +/- 0.06 ml/min/g) and the transmural blood flow distribution at baseline, as assessed by endocardial/epicardial blood flow ratio (control, 1.35 +/- 0.12; LVH, 1.21 +/- 0.09), were similar in the two groups. During exercise to a target heart rate (240 beats/min), LVH dogs demonstrated greater (p less than 0.01) increases in LV systolic and end-diastolic pressures. In control dogs, as expected, exercise augmented velocity of circumferential fiber shortening (16 +/- 9%) and shortening fraction (15 +/- 5%), but in LVH dogs, exercise reduced the velocity of circumferential fiber shortening (-14 +/- 6%) and shortening fraction (-17 +/- 5%). Exercise also increased full wall thickening (35 +/- 5%), subendocardial wall thickening (66 +/- 10%), and subepicardial wall thickening (44 +/- 9%) in control dogs. In LVH dogs, exercise increased subepicardial wall thickening (31 +/- 9%) and reduced subendocardial wall thickening (-40 +/- 7%); full wall thickening did not change (-11 +/- 9%). This was associated with a fall in endocardial/epicardial flow ratio to 0.72 +/- 0.05 (p less than 0.01) in LVH dogs. The subendocardial dysfunction persisted late into recovery, at a time when the transmural blood flow distribution had returned to baseline; this occurrence suggested myocardial stunning. Thus, in dogs with LVH, selective subendocardial hypoperfusion and profound selective depression in subendocardial wall thickening are observed during exercise. The subendocardial dysfunction persisted into recovery despite resolution of the perfusion abnormality. PMID:2137037

  3. Comparison of guinea-pig ventricular myocytes and dog Purkinje fibres for in vitro assessment of drug-induced delayed repolarization.

    OpenAIRE

    Terrar, Da; Wilson, Cm; Graham, Sg; Bryant, Sm; Heath, Bm

    2007-01-01

    INTRODUCTION: QT interval prolongation and Torsade de Pointes (TdP) arrhythmias are recognised as a potential risk with many drugs, most of which delay cardiac repolarization by inhibiting the rapidly activating K(+) current (I(Kr)). The objective of this study was to compare the effects of compounds on cardiac action potentials recorded from guinea-pig ventricular myocytes and dog Purkinje fibres. METHODS AND RESULTS: Effects of dofetilide, sotalol, cisapride, terfenadine, haloperidol and sp...

  4. Gender differences in factors influencing electrocardiographic findings of left ventricular hypertrophy in severe aortic stenosis.

    Science.gov (United States)

    Satoh, Shinji; Omura, Soichiro; Inoue, Hiroko; Ejima, Emiko; Shimozono, Koutatsu; Hayashi, Makiko; Mori, Takahiro; Takenaka, Katsuhiko; Kawamura, Natsumi; Numaguchi, Kotaro; Mori, Etsuo; Asoh, Akemi; Nakamura, Toshihiro; Hiyamuta, Koji

    2014-09-01

    We investigated gender differences in factors influencing the electrocardiographic (ECG) findings of left ventricular hypertrophy (LVH) in patients with severe aortic stenosis (AS). The functional and geometric responses of the left ventricle to chronic pressure overload, such as hypertension and AS, have been reported to be different between men and women. However, gender differences in the factors influencing the ECG findings of LVH in pressure overload remain unknown. We conducted a retrospective observational study in consecutive patients with severe AS (aortic valve area (AVA) assessed by cardiac catheterization <1.0 cm(2)) without concomitant significant aortic regurgitation, mitral stenosis and/or regurgitation, conduction disturbance, or myocardial infarction (n = 35 males, 68 females). The ECG criteria were classified into three categories: (1) high voltage by the Sokolow-Lyon index associated with ST-T wave changes (with no digitalis therapy); (2) high voltage alone; and (3) normal. Groups 1 and 2 were defined as LVH on ECG. We compared the ECG findings in relation to the AS severity between genders. Women were older, but there were no significant differences in the prevalence of hypertension, AVA index (AVAI), mean pressure gradient or peak velocity across the AV, LV mass index (LVMI) derived from echocardiography or the distribution of ECG categories between genders. A multiple logistic regression analysis including age, gender, hypertension, AVAI, mean pressure gradient, and LVMI revealed that the LVMI (P = 0.001) and AVAI (P = 0.0434) were significantly related to the distribution of ECG categories. LVMI significantly predicted LVH on ECG in both genders, but AVAI was a predictive factor in only women. ECG LVH in patients with severe AS may be mainly reflected by LVMI in men and by both LVMI and AVAI in women. Factors other than AVA, such as end-stage disease and/or complicating factors such as hypertension, may underlie the observed differences in ECG findings of LVH between men and women. PMID:23979264

  5. Differential metal content and gene expression in rat left ventricular hypertrophy due to hypertension and hyperactivity.

    Science.gov (United States)

    Subramanian, Meenakumari; Hunt, Adam L; Petrucci, Giuseppe A; Chen, Zengyi; Hendley, Edith D; Palmer, Bradley M

    2014-07-01

    The spontaneously hypertensive rat (SHR) has been studied extensively as a model of left ventricular hypertrophy (LVH) and associated cardiac dysfunction due to hypertension (HT). The SHR also possesses a hyperactive trait (HA). Crossbreeding SHR with Wistar-Kyoto (WKY) control rats, which are nonHT and nonHA, followed by selected inbreeding produced two additional homozygous strains: WKHT and WKHA, in which the traits of HT and HA, respectively, are expressed separately. WKHT, WKHA and SHR all display LVH, but only the SHR exhibits cardiac dysfunction. We hypothesized that cardiac dysfunction in the SHR is uniquely characterized by calcium overload. We measured total cardiac Ca, Cu, Fe, K, Mg and Zn in the four strains. We found elevated Ca and depressed Cu, Mg and Zn with HT, but not unique to SHR. We surmise that HT promotes aberrant regulation of cardiac Ca(2+), Cu(2+), Mg(2+) and Zn(2+), which does not necessarily result in cardiac dysfunction. Interestingly, Cu was elevated in HA strains compared to nonHA counterparts. We then analyzed gene expression as mRNA of Cu-containing proteins, most notably mitochondrial-Cox, Dbh, Lox, Loxl1, Loxl2, Sod1 and Tyr. The gene expression profiles of Lox, Loxl1, Loxl2 and Sod1 were found especially high in the WKHA, which if reflective of protein content could account for the high Cu content in the WKHA. The mRNA of other genes, notably Mb, Fxyd1, Maoa and Maob were also examined. We found that Maoa gene expression and monoamine oxidase-A (MAO-A) protein content were low in the SHR compared to the other strains. The finding that MAO-A protein is low in the SHR and normal in the WKHT and WKHA strains is most consistent with the idea that MAO-A protects against the development of cardiac dysfunction in LVH but not against LVH in these rats. PMID:24629670

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

    Science.gov (United States)

    Bacharova, Ljuba; Ugander, Martin

    2014-11-01

    Conventional assessment of left ventricular hypertrophy (LVH) using the electrocardiogram (ECG), for example, by the Sokolow-Lyon, Romhilt-Estes or Cornell criteria, have relied on assessing changes in the amplitude and/or duration of the QRS complex of the ECG to quantify LV mass. ECG measures of LV mass have typically been validated by imaging with echocardiography or cardiovascular magnetic resonance imaging (CMR). However, LVH can be the result of diverse etiologies, and LVH is also characterized by pathological changes in myocardial tissue characteristics on the genetic, molecular, cellular, and tissue level beyond a pure increase in the number of otherwise normal cardiomyocytes. For example, slowed conduction velocity through the myocardium, which can be due to diffuse myocardial fibrosis, has been shown to be an important determinant of conventional ECG LVH criteria regardless of LV mass. Myocardial tissue characterization by CMR has emerged to not only quantify LV mass, but also detect and quantify the extent and severity of focal or diffuse myocardial fibrosis, edema, inflammation, myocarditis, fatty replacement, myocardial disarray, and myocardial deposition of amyloid proteins (amyloidosis), glycolipids (Fabry disease), or iron (siderosis). This can be undertaken using CMR techniques including late gadolinium enhancement (LGE), T1 mapping, T2 mapping, T2* mapping, extracellular volume fraction (ECV) mapping, fat/water-weighted imaging, and diffusion tensor CMR. This review presents an overview of current and emerging concepts regarding the diagnostic possibilities of both ECG and CMR for LVH in an attempt to narrow gaps in our knowledge regarding the ECG diagnosis of LVH. PMID:25367364

  7. 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

    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 (GUSTO) IV ACS trial had admission electrocardiograms analysed at a core laboratory. LVH [>or=20 mm Cornell voltage (LV voltage) (women) or >or=28 mm (men) plus strain patterns] was observed in 586 (7.9%) patients, and women accounted for 74%. LVH patients were also older and had more co-morbidities, ST-depression >or= 0.5 mm, elevated C-reactive protein and N-terminal pro-brain naturetic peptide (NT-proBNP), and lower troponin T. Invasive procedures occurred less often in LVH patients (cardiac catheterization: 31 vs. 38%, P = 0.001; percutaneous coronary intervention: 12 vs. 20%, P < 0.001). Mortality was significantly higher in patients with LVH (30 day: 5 vs. 3%, P = 0.046; 1 year: 14 vs. 7%, P < 0.001), whereas 30day myocardial infarction (MI) and death/MI did not differ. After baseline adjustment including NT-proBNP, LVH remained associated with increased hazard of 1 year mortality in women, but not in men [P-interaction = 0.033; women: adjusted hazard ratio (LVH vs. no LVH): 1.42 (1.04-1.94), P = 0.029]. CONCLUSION: Electrocardiographic-LVH identifies an important subset of ACS patients with a higher risk of long-term mortality, particularly among women. These novel findings highlight opportunities to improve treatment and outcome among similar ACS patients. Udgivelsesdato: 2007-Sep

  8. High-normal blood pressure is associated with new-onset electrocardiographic left ventricular hypertrophy.

    Science.gov (United States)

    Ueda, H; Miyawaki, M; Hiraoka, H

    2015-01-01

    Whether high-normal blood pressure (BP) is a predictor of new-onset electrocardiographic (ECG)-left ventricular hypertrophy (LVH) is not known. A total of 4112 subjects who underwent physical examinations were enrolled in this study. BP was measured on entry. Standard 12-lead ECG was recorded at initial evaluation and 3 years later. BP categories were defined on the basis of the 2013 European Society of Hypertension/European Society of Cardiology guidelines. Of the 4112 subjects, 133 developed ECG-LVH 3 years later. Crude cumulative prevalence rates of new-onset ECG-LVH were 2.0% for the optimal BP group, 3.2% for the normal BP group, 5.1% for the high-normal BP group and 5.0% for the hypertension group. After adjustment for age, gender, body mass index, smoking, low-density lipoprotein cholesterol, log-transformed high-density lipoprotein cholesterol, log-transformed triglycerides, estimated glomerular filtration rate, haemoglobin A1c, haemoglobin, uric acid and antihypertensive medication use, compared with the optimal BP group, the odds ratios of new-onset ECG-LVH for the normal BP, high-normal BP and hypertension groups were 1.52 (95% confidence interval (CI): 0.93-2.49, P=0.094), 2.38 (95% CI: 1.40-4.03, P=0.001) and 2.44 (95% CI: 1.43-4.18, P=0.001), respectively. Even high-normal BP was significantly associated with the presence of new-onset ECG-LVH. PMID:24694799

  9. Intercoronary connection with bidirectional blood flow and concentric left ventricular hypertrophy

    Scientific Electronic Library Online (English)

    George César Ximenes, Meireles; Luciano Mauricio, Abreu Filho.

    1994-12-01

    Full Text Available Homem de cor branca, 54 anos, com histórias de dor esternal atípica para insuficiência coronária, iniciada há 6 meses. Antecedentes: HAS e tabagismo. O exame do aparelho cardiovascular era normal. PA = 140/100mmHg (ambos os braços). O E.C.G. de repouso revelou onda T negativa em D2, D3 e AVF. O ecoc [...] ardiograma bidimensional demonstrou hipertrofia concêntrica do VE de grau moderado. No TE, protocolo de Ellestad, a frequência cardíaca não atingiu os níveis preconizados e ocorreu aumento acentuado da PA (230/140 mm Hg). Não apresentou alterações expressivas do segmento ST em relação ao repouso. No cateterismo cardíaco, a pressão do VE foi de 170/20 mm HG. O VE apresentava aspecto hipertrófico. Cinecoronariografia esquerda e direita não revelaram lesões obstrutivas. Injeção seletiva de contraste na ACD demonstrou enchimento retrógrado da porção distal da ACX até sua porção média através de conexões intercoronárias. Da mesma forma injeção seletiva na ACE demonstrou enchimento retrógrado da porção distal da ACD por conexões intercoronárias da ACX para a ACD. Revisão da literatura e possíveis mecanismos foram apresentados. Abstract in english Cardiac catheterization in a 55-year-old man, with a 6-month history of atypical chest pain and Q-waves in D1, Dili and AVF, showed concentric left ventricular (LV) hypertrophy and a large intercoronary connection between right coronary artery (RCA) and circumflex artery (CX), with bidirectional blo [...] od flow. Although the RCA and CX were normal, selective injection of CX filled RCA retrogradely and in the same way selective injection of RCA filled CX. Possible mechanisms and literature are reviewed.

  10. Predictors of left ventricular hypertrophy and their cutoffs in peritoneal dialysis patients.

    Science.gov (United States)

    Hassan, Kamal; Hassan, Shadi; Anwar, Saab; Zaher, Armaly; Edgem, Rabia; Hassan, Fadi

    2015-03-20

    Cardiovascular complications are the main cause of morbidity and mortality in peritoneal dialysis (PD) patients. Left ventricular hypertrophy (LVH) is a major predictor of the development of cardiovascular events. This study aimed to identify risk factors that contribute to the development of LVH and to determine their cutoffs in patients on maintenance peritoneal dialysis.In this cross sectional study we evaluated the association of 23 variables including age, PD vintage, ultrafiltration, urine volume, residual renal function, mean daily SBP, mean daily DBP, fasting glucose, HbA1c, peritoneal glucose load index (PGLI), fluid overload (FO), plasma brain natriuretic peptide (BNP), plasma hsCRP and IL-6, serum albumin, white blood cell (WBC) count, hemoglobin, hematocrit, triglycerides, LDL-C (low density lipoprotein cholesterol), HDL-C (high density lipoprotein cholesterol), and PTH with LVH in 38 stable patients on maintenance PD ? 24 months.LVH was detected in 57.9% of patients. Logistic regression and receiver operating characteristics (ROC) analysis revealed that HbA1c, PGLI, FO, plasma BNP, hsCRP and IL-6 seem to be possible predictors of LVH. The cutoffs associated with the presence of LVH were: 7.5%, 3.2 g/kg/day, 1.7 L, 330 pg/mL, 7.5 mg/dL and 3.3 pg/mL for HbA1c, PGLI, FO, plasma BNP, hsCRP and IL-6, respectively (sensitivity 72.8 to 81.8% and specificity 75.0 to 93.8%).The results suggest that efforts should be made to reduce the peritoneal glucose load (PGL), to improve the hydration status, and to attenuate the inflammatory process in order to reduce the risk of the development of LVH among PD patients. PMID:25740398

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

    Science.gov (United States)

    Nivala, Michael; de Lange, Enno; Rovetti, Robert; Qu, Zhilin

    2012-01-01

    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 variant 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 5?×?5?×?5 voxels to maintain proper Ca diffusion. Advanced numerical algorithms implemented on graphical processing units were used for fast computational simulations. For a myocyte containing 100?×?20?×?10 CRUs, a 1-s heart time simulation takes about 10?min 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. PMID:22586402

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

    Directory of Open Access Journals (Sweden)

    MichaelNivala

    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.

  13. Allosteric Activation of Na+-Ca2+ Exchange by L-Type Ca2+ Current Augments the Trigger Flux for SR Ca2+ Release in Ventricular Myocytes

    OpenAIRE

    Sobie, Eric A.; Cannell, Mark B.; Bridge, John H. B.

    2008-01-01

    The possible contribution of Na+-Ca2+ exchange to the triggering of Ca2+ release from the sarcoplasmic reticulum in ventricular cells remains unresolved. To gain insight into this issue, we measured the “trigger flux” of Ca2+ crossing the cell membrane in rabbit ventricular myocytes with Ca2+ release disabled pharmacologically. Under conditions that promote Ca2+ entry via Na+-Ca2+ exchange, internal [Na+] (10 mM), and positive membrane potential, the Ca2+ trigger flux (measured using a fl...

  14. Natakalim improves post-infarction left ventricular remodeling by restoring the coordinated balance between endothelial function and cardiac hypertrophy.

    Science.gov (United States)

    Zhou, Hong-Min; Zhong, Ming-Li; Zhang, Yan-Fang; Cui, Wen-Yu; Long, Chao-Liang; Wang, Hai

    2014-11-01

    Endothelial dysfunction can lead to congestive heart failure and the activation of endothelial ATP-sensitive potassium (K(ATP)) channels may contribute to endothelial protection. Therefore, the present study was carried out to investigate the hypothesis that natakalim, a novel K(ATP) channel opener, ameliorates post-infarction left ventricular remodeling and failure by correcting endothelial dysfunction. The effects of myocardial infarction were assessed 8 weeks following left anterior descending coronary artery occlusion in male Wistar rats. Depressed blood pressure, cardiac dysfunction, evidence of left ventricular remodeling and congestive heart failure were observed in the rats with myocardial infarction. Treatment with natakalim at daily oral doses of 1, 3 or 9 mg/kg/day for 8 weeks prevented these changes. Natakalim also prevented the progression to cardiac failure, which was demonstrated by the increase in right ventricular weight/body weight (RVW/BW) and relative lung weight, signs of cardiac dysfunction, as well as the overexpression of atrial and brain natriuretic peptide mRNAs. Our results also demonstrated that natakalim enhanced the downregulation of endothelium-derived nitric oxide, attenuated the upregulation of inducible nitric oxide synthase-derived nitric oxide (NO), inhibited the upregulated endothelin system and corrected the imbalance between prostacyclin and thromboxane A(2). Overall, our findings suggest that natakalim prevents post-infarction hypertrophy and cardiac failure by restoring the coordinated balance between endothelial function and cardiac hypertrophy. PMID:25215478

  15. Resolution of left ventricular and asymmetric septal hypertrophy after resection of left ventricular outflow obstruction in a patient with troponin-positive hypertrophic obstructive cardiomyopathy: a case report.

    Science.gov (United States)

    Narsupalli, Sreekanth; Castle, Bruce; Veldtman, Gruschen

    2010-10-01

    We report the case of a young woman with a troponin mutation of C to T nucleotide substitution in exon 17 of troponin 2 (TNNT2; c.868C.T; p.Arg288Cys) leading to hypertrophic obstructive cardiomyopathy. Following surgical resection of the outflow obstruction, she had near-complete resolution of her asymmetric left ventricular hypertrophy, such that cardiomyopathy could no longer be diagnosed on echocardiographic grounds. We believe that this unusual case shows important aspects relating to the interplay between genetic and environmental mechanisms and the overlap in the phenotypic spectrum between primary subaortic stenosis and obstructive hypertrophic cardiomyopathy. PMID:20663266

  16. 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.

    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 was superior to atenolol-based treatment for reducing new-onset AF and complications, especially stroke, associated with new-onset or pre-existing AF. Potential mechanisms of AF prevention by angiotensin receptor blockade supported by LIFE results include greater reduction in left atrial size and LV hypertrophy. Differential effects of antihypertensive treatment on the left atrium and left ventricle may help prevent AF and reduce risk of stroke associated with hypertensive heart disease Udgivelsesdato: 2008/12

  17. Distribution of Kir6.0 and SUR2 ATP-sensitive potassium channel subunits in isolated ventricular myocytes.

    Science.gov (United States)

    Singh, H; Hudman, D; Lawrence, C L; Rainbow, R D; Lodwick, D; Norman, R I

    2003-05-01

    The subcellular distribution of ATP-sensitive potassium (K(ATP)) channel subunits in rat-isolated ventricular myocytes was investigated using a panel of subunit-specific antisera. Kir6.1 subunits were associated predominantly with myofibril structures and were co-localized with the mitochondrial marker MitoFluor red (correlation coefficient (cc) = 0.63 +/- 0.05). Anti-Kir6.1 antibodies specifically recognized a polypeptide of 48 kDa in mitochondrial membrane fractions consistent with the presence of Kir6.1 subunits in this organelle. Both Kir6.2 and SUR2A subunits were distributed universally over the sarcolemma. Lower-intensity antibody-associated immunofluorescence was detected intracellularly, which was correlated with the distribution of MitoFluor red in both cases (cc, Kir6.2, 0.56 +/- 0.05; SUR2A, 0.61 +/- 0.06). A polypeptide of 40 kDa was recognized by anti-Kir6.2-subunit antibodies in western blots of both microsomal and mitochondrial membrane fractions consistent with the presence of this subunit in the sarcolemma and mitochondria. Similarly, SUR2A and SUR2B subunits were detected in western blots of microsomal membrane proteins consistent with a sarcolemmal localization for these polypeptides. SUR2B subunits were shown in confocal microscopy to co-localize strongly with t-tubules (cc, 0.81 +/- 0.05). Together, the results indicate that Kir6.2 and SUR2A subunits predominate in the sarcolemma of ventricular myocytes consistent with a Kir6.2/SUR2A-subunit combination in the sarcolemmal K(ATP)channel. Kir6.1, Kir6.2 and SUR2A subunits were demonstrated in mitochondria. Combinations of these subunits would not explain the reported pharmacology of the mitochondrial K(ATP) channel (Mol Pharmacol 59 (2001) 225) suggesting the possibility of further unidentified components of this channel. PMID:12738227

  18. Early regression of left ventricular hypertrophy after treatment with esmolol in an experimental rat model of primary hypertension.

    Science.gov (United States)

    Quintana-Villamandos, Begoña; Delgado-Martos, María Jesús; Sánchez-Hernández, Jose Javier; Gómez de Diego, Jose Juan; Fernández-Criado, María del Carmen; Canillas, Fernando; Martos-Rodríguez, Antonia; Delgado-Baeza, Emilio

    2013-05-01

    Certain ?-adrenergic blockers have proven useful in the regression of ventricular remodeling when administered as long-term treatment. However, early regression of left ventricular hypertrophy (LVH) has not been reported, following short-term administration of these drugs. We tested the hypothesis that short-term administration of the cardioselective ?-blocker esmolol induces early regression of LVH in spontaneously hypertensive rats (SHR). Fourteen-month-old male SHRs were treated i.v. with vehicle (SHR) or esmolol (SHR-E) (300??g?kg(-1)?min(-1)). Age-matched vehicle-treated male Wistar-Kyoto (WKY) rats served as controls. After 48?h, left ventricular morphology and function were assessed using M-mode echocardiograms (left ventricular mass index (LVMI), ejection fraction and transmitral Doppler (early-to-atrial filling velocity ratio (E/A), E-wave deceleration time (Edec time)). The standardized uptake value (SUV) was applied to evaluate FDG (2-deoxy-2[18F]fluoro-D-glucose) uptake by the heart using PET/CT. Left ventricular subendocardial and subepicardial biopsies were taken to analyze changes in cross-sectional area (CSA) of left ventricular cardiomyocytes and the fibrosis was expressed as collagen volume fraction (CVF). LVMI was lower in SHR-E with respect to SHR (P=0.009). There were no significant differences in EF, E/A ratio or Edec time in SHR-E compared with SHR (P=0.17, 0.55 and P=0.80, respectively). PET acquisitions in SHR-E showed lower (18)F-FDG uptake than SHR (P=0.003). Interestingly, there were no significant differences in SUV in either SHR-E or WKY (P=0.63). CSA in subendocardial and subepicardial regions was minor in SHR-E with respect to SHR (PEsmolol reverses early LVH in the SHR model of stable compensated ventricular hypertrophy. This is the first study to associate early regression of LVH with administration of a short-term ?-blocker. PMID:23364336

  19. H2 and H3 relaxin inhibit high glucose-induced apoptosis in neonatal rat ventricular myocytes.

    Science.gov (United States)

    Zhang, Xiaohui; Ma, Xiao; Zhao, Meng; Zhang, Bo; Chi, Jinyu; Liu, Wenxiu; Chen, Wenjia; Fu, Yu; Liu, Yue; Yin, Xinhua

    2015-01-01

    High concentrations of glucose induce cardiomyocyte apoptosis, and contribute to diabetic cardiomyopathy. Relaxin-2 and relaxin-3 are two members of the relaxin peptide family that are cardioprotective. However, it remains unknown whether relaxin-2 or relaxin-3 can regulate apoptosis in high glucose treated-neonatal rat ventricular myocytes (NRVMs). In cultured NRVMs, 33 mmol/l high glucose (HG) increased apoptosis in a time-dependent manner. HG-increased the protein expression of cleaved caspase-8 and -9, two initiators of the extrinsic and intrinsic pathways of apoptosis, Caspase-3 was attenuated by human recombinant relaxin-2 (H2 relaxin) or relaxin-3 (H3 relaxin), indicating that H2 and H3 relaxin inhibited HG-induced apoptosis. Furthermore, endoplasmic reticulum stress (ERS) markers CHOP and caspase-12 were markedly increased in HG-treated NRVMs, leading to apoptosis; this effect was also effectively attenuated by H2 relaxin or H3 relaxin. Treatment of NRVMs with HG reduced autophagy which cannot be adjusted by H2 relaxin or H3 relaxin. In conclusion, HG-induced apoptosis in NRVMs was mediated, in part, by the activation of the extrinsic and intrinsic pathways of apoptosis and ERS, all inhibited by H2 relaxin or H3 relaxin. PMID:25446652

  20. [High intracellular Mg(2+) affects the activities of L-type calcium channel in guinea- pig ventricular myocytes].

    Science.gov (United States)

    Zhao, Mei-Mi; Lian, Wen-Wen; Sun, Rui; Wang, Hong-Mei; Feng, Rui; Hu, Hui-Yuan; Sun, Xue-Fei; Hao, Li-Ying

    2014-12-25

    This study is aimed to investigate the effects of high intracellular Mg(2+) on L-type calcium channel in guinea-pig ventricular myocytes. The cardiomyocytes were acutely isolated with enzyme digestion method. By adopting inside-out configuration of patch clamp technique, single channel currents of the L-type calcium channel were recorded under different intracellular Mg(2+) concentrations ([Mg(2+)]i). In control group, which was treated with 0.9 mmol/L Mg(2+), the relative activity of calcium channel was (176.5 ± 34.1)% (n = 7). When [Mg(2+)]i was increased from 0.9 to 8.1 mmol/L (high Mg(2+) group), the relative activities of calcium channel decreased to (64.8 ± 18.1)% (n = 6, P < 0.05). Moreover, under 8.1 mmol/L Mg(2+), the mean open time of calcium channel was shortened to about 25% of that under control condition (P < 0.05), but the mean close time of calcium channel was not altered. These results suggest that high intracellular Mg(2+) may inhibit the activities of L-type calcium channel, which is mainly due to the shortening of the mean open time of single L-type calcium channel. PMID:25516521

  1. Evaluation of left atrial function in hypertensive patients with and without left ventricular hypertrophy using velocity vector imaging.

    Science.gov (United States)

    Yang, Li; Qiu, Qiong; Fang, Si-hua

    2014-12-01

    To study left atrial deformation characteristics using Velocity vector imaging (VVI) in hypertensive patients with and without left ventricular hypertrophy (LVH), and to explore its value for detection of left atrial dysfunction in these patients. Sixty-four patients with essential hypertension were divided into normal left ventricular geometry (LVN, 37 cases) and LVH (27 cases) groups, according to their left ventricular mass index. Twenty-five age-matched healthy participants were included as control group. Two-dimensional dynamic images of the apical four- and two-chamber echocardiographic views were obtained, and strain/strain rate (SR) curves of eight atrial segments were derived by VVI software. Peak systolic strain (?(sys)), systolic SR (SRs), early and late diastolic SR (SRe, SRa) were measured and calculated. Peak early diastolic mitral inflow and annulus velocities were also measured and their ratio (E/E') calculated. Compared with the control group, SRe decreased and SRa increased significantly in LVH group (P SRs and ?(sys) (P > 0.05). Also, no significant difference was observed in SRe, SRa, SRs and ?(sys) between LVH and LVN groups (P > 0.05). SRe and SRa correlated significantly with E/E' (r = -0.634, r = 0.609; both P < 0.001). Strain/SR parameters derived from VVI may reflect decreased conduit, increased booster pump function of the left atrium in hypertensive patients with LVH and correlate with left ventricular diastolic function. PMID:25005684

  2. Usefulness of NT-proBNP level for diagnosing left ventricular hypertrophy in hypertensive patients. A cardiac magnetic resonance study.

    Science.gov (United States)

    Morillas, Pedro; Castillo, Jesús; Quiles, Juan; Nuñez, Daniel; Guillén, Silvia; Maceira, Alicia; Rivera, Miguel; Bertomeu, Vicente

    2008-09-01

    The presence of left ventricular hypertrophy (LVH) is associated with an increase in cardiovascular morbidity and mortality in hypertensive patients. We investigated the diagnostic value of the N-terminal probrain natriuretic peptide (NT-proBNP) level for detecting LVH in hypertensive patients with a conserved left ventricular ejection fraction. The study involved 27 consecutive patients. Cardiac magnetic resonance imaging was performed to determine left ventricular mass and the plasma NT-proBNP level was measured. A significant correlation was found between the NT-proBNP level and left ventricular mass (r=0.598; P=.001). Use of a cut-off point of 35 pg/mL enabled the presence of LVH to be identified with a sensitivity of 100% (95% confidence interval [CI], 69%-100%) and a specificity of 70.6% (95% CI, 44.1%-89.6%). The area under the receiver operating characteristic (ROC) curve was 0.867 (95% CI, 0.73-1; P< .05). The plasma NT-proBNP level may be useful for identifying patients with LVH. PMID:18775240

  3. 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

    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 Hypertension (LIFE) study included 9193 patients 55 to 80 years of age with essential hypertension and ECG LV hypertrophy by gender-adjusted Cornell product (CP) (RaVL+SV(3) [+6 mm in women]). QRS duration>2440 mm x ms) and/or Sokolow-Lyon voltage (SLV) (SV1+RV(5/6)>38 mm). During follow-up (mean, 4.8 years), 190 patients (2%) experienced SCD. In time-dependent Cox analyses, absence of in-treatment LV hypertrophy was associated with a decreased risk of SCD: every 1-SD-lower in-treatment CP (1050 mm x ms) was associated with a 28% lower risk of SCD (hazard ratio [HR], 0.72; 95% CI, 0.66 to 0.79) and 1-SD-lower SLV (10.5 mm) with a 26% lower risk (HR, 0.74; 95% CI, 0.65 to 0.84). After adjustment for time-varying systolic and diastolic blood pressures, treatment allocation, age, gender, baseline Framingham risk score, ECG strain, heart rate, urine albumin/creatinine ratio, smoking, diabetes, congestive heart failure, coronary heart disease, atrial fibrillation, and occurrence of myocardial infarction, atrial fibrillation, heart failure, and noncardiovascular death, both in-treatment CP and SLV remained predictive of SCD: each 1-SD-lower CP was associated with a 19% lower risk of SCD (HR, 0.81; 95% CI, 0.73 to 0.90) and 1-SD-lower SLV with an 18% lower risk (HR, 0.82; 95% CI, 0.70 to 0.98). Absence of in-treatment LV hypertrophy by both SLV and CP was associated with a 30% lower risk of SCD (HR, 0.70; 95% CI, 0.54 to 0.92). CONCLUSIONS: Absence of in-treatment ECG LV hypertrophy is associated with reduced risk of SCD independently of treatment modality, blood pressure reduction, prevalent coronary heart disease, and other cardiovascular risk factors in hypertensive patients with LV hypertrophy. Udgivelsesdato: 2007-Aug-14

  4. Angiotensin II receptor blockers and cardiovascular protection: Focus on left ventricular hypertrophy regression and atrial fibrillation prevention

    Directory of Open Access Journals (Sweden)

    Cesare Cuspidi

    2008-03-01

    Full Text Available Cesare Cuspidi1,2, Francesca Negri2, Alberto Zanchetti31Department of Clinical Medicine and Prevention, University of Milano-Bicocca, Milan, Italy; 2Policlinico di Monza; 3Centro Interuniversitario di Fisiologia Clinica e Ipertensione, Università di Milano, and Istituto Auxologico Italiano, Milan, ItalyAbstract: Left ventricular hypertrophy (LVH and atrial fibrillation (AF are strong predictors of cardiovascular (CV morbidity and mortality, independently of blood pressure levels and other modifiable and nonmodifiable risk factors. The actions of circulating and tissue angiotensin II, mediated by AT1 receptors, play an important role in the development of a wide spectrum of cardiovascular alterations, including LVH, atrial enlargement and AF. Growing experimental and clinical evidence suggests that antihypertensive drugs may exert different effects on LVH regression and new onset AF in the setting of arterial hypertension. Since a number of large and adequately designed studies have found angiotensin II receptor blockers (ARBs to be more effective in reducing LVH than beta-blockers and data are also available showing their effectiveness in preventing new or recurrent AF, it is reasonable to consider this class of drugs among first line therapies in patients with hypertension and LVH (a very high risk phenotype predisposing to AF and as adjunctive therapy to antiarrhythmic agents in patients undergoing pharmacological or electrical cardioversion of AF.Keywords: angiotensin II receptor blockers, left ventricular hypertrophy, atrial fibrillation

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

    DEFF Research Database (Denmark)

    Diederichsen, SØren Zöga; Gerke, Oke

    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 the presence of CAC, clinical variables and ECG findings was evaluated by means of multivariate logistic regression. RESULTS:: Of 1825 invited individuals, 1226 accepted the screening. The prevalence of hypertension was 50%. Hypertensive patients frequently had LVH and/or strain when compared with nonhypertensive individuals (21 vs. 14%, P?

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

    Science.gov (United States)

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

    2000-01-01

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

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

    International Nuclear Information System (INIS)

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

  8. 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

    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, however, never been investigated. We examined whether 'in- treatment' wall motion abnormalities predicted outcome in the Losartan Intervention For Endpoint ( LIFE) reduction in hypertension echocardiographic substudy. Methods We studied 749 patients without coronary artery disease, myocardial infarction ( MI), or stroke history. Echocardiographic segmental wall motion abnormalities at baseline and annual re-evaluations (' as time- varying covariate') were examined in relation to endpoints ( cardiovascular mortality, MI, stroke, and hospitalized heart failure). Adjusted Cox regression was used 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 pressure lowering, and serial change of left ventricular mass index, ' in-treatment' segmental wall motion abnormalities were associated with subsequent composite endpoint [ hazard ratio =2.1, 95% confidence interval ( CI) 1.1-3.8; P=0.019] and MI [ hazard ratio =3.7 ( 1.5 - 8.9); P=0.004]. Conclusion 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 ventricular mass index Udgivelsesdato: 2008/4

  9. Asynchronous activation of calcium and potassium currents by isoproterenol in canine ventricular myocytes.

    Science.gov (United States)

    Ruzsnavszky, Ferenc; Hegyi, Bence; Kistamás, Kornél; Váczi, Krisztina; Horváth, Balázs; Szentandrássy, Norbert; Bányász, Tamás; Nánási, Péter P; Magyar, János

    2014-05-01

    Adrenergic activation of L-type Ca(2+) and various K(+) currents is a crucial mechanism of cardiac adaptation; however, it may carry a substantial proarrhythmic risk as well. The aim of the present work was to study the timing of activation of Ca(2+) and K(+) currents in isolated canine ventricular cells in response to exposure to isoproterenol (ISO). Whole cell configuration of the patch-clamp technique in either conventional voltage clamp or action potential voltage clamp modes were used to monitor I(Ca), I(Ks), and I(Kr), while action potentials were recorded using sharp microelectrodes. ISO (10 nM) elevated the plateau potential and shortened action potential duration (APD) in subepicardial and mid-myocardial cells, which effects were associated with multifold enhancement of I(Ca) and I(Ks) and moderate stimulation of I(Kr). The ISO-induced plateau shift and I(Ca) increase developed faster than the shortening of APD and stimulation of I(Ks) and I(Kr). Blockade of ?1-adrenoceptors (using 300 nM CGP-20712A) converted the ISO-induced shortening of APD to lengthening, decreased its latency, and reduced the plateau shift. In contrast, blockade of ?2-adrenoceptors (by 50 nM ICI 118,551) augmented the APD-shortening effect and increased the latency of plateau shift without altering its magnitude. All effects of ISO were prevented by simultaneous blockade of both receptor types. Inhibition of phosphodiesterases decreased the differences observed in the turn on of the ISO-induced plateau shift and APD shortening. ISO-induced activation of I(Ca) is turned on faster than the stimulation of I(Ks) and I(Kr) in canine ventricular cells due to the involvement of different adrenergic pathways and compartmentalization. PMID:24566722

  10. Ranolazine attenuates hypoxia- and hydrogen peroxide-induced increases in sodium channel late openings in ventricular myocytes.

    Science.gov (United States)

    Ma, Jihua; Song, Yejia; Shryock, John C; Hu, Liangkun; Wang, Weiping; Yan, Xisheng; Zhang, Peihua; Belardinelli, Luiz

    2014-07-01

    Ranolazine attenuates cardiac arrhythmic activity associated with hypoxia and hydrogen peroxide (H2O2) by inhibition of late sodium current (late INa). The mechanism of ranolazine's action on Na channels was investigated using whole-cell and single-channel recording from guinea pig isolated ventricular myocytes. Hypoxia increased whole-cell late INa from -0.48 ± 0.02 to -3.99 ± 0.07 pA/pF. Ranolazine at 3 and 9 ?mol/L reduced the hypoxia-induced late INa by 16% ± 3% and 55% ± 3%, respectively. Hypoxia increased the mean open probability and open time of Na-channel late openings from 0.016 ± 0.001 to 0.064 ± 0.007 milliseconds and from 0.693 ± 0.043 to 1.081 ± 0.098 milliseconds, respectively. Ranolazine at 3 and 9 ?mol/L attenuated the hypoxia-induced increase of open probability by 19% ± 7% and 61% ± 1%, and increase of open time by 26% ± 19% and 74 ± 21%, respectively. H2O2 increased the mean open probability and open time of Na-channel late openings from 0.013 ± 0.002 to 0.107 ± 0.015 milliseconds and from 0.689 ± 0.075 to 1.487 ± 0.072 milliseconds, respectively. Ranolazine at 3 and 6 ?mol/L reduced the H2O2-induced increase of mean open probability by 60% ± 7% and 95% ± 2%, and the increase of mean open time by 31% ± 21% and 82% ± 8%. In conclusion, the inhibition by ranolazine of hypoxia- and H2O2-stimulated late INa is due to reduction of both the open probability and open time of Na-channel late openings. PMID:24705174

  11. Inhibition of sarcoplasmic reticular function by chronic interleukin-6 exposure via iNOS in adult ventricular myocytes.

    Science.gov (United States)

    Yu, Xin-Wen; Chen, Qian; Kennedy, Richard H; Liu, Shi J

    2005-07-15

    Interleukin (IL)-6 has been shown to decrease cardiac contractility via a nitric oxide synthase (NOS)-dependent pathway during acute exposure. We previously reported that IL-6 decreases contractility and increases inducible NOS (iNOS) in adult rat ventricular myocytes (ARVM) after 2 h exposure. The goal of this study was to investigate the cellular mechanism underlying this chronic IL-6-induced negative inotropy and the role of iNOS. Pretreatment for 2 h with 10 ng ml-1 IL-6 decreased the kinetics of cell shortening (CS) and contractile responsiveness to Ca2+o ([Ca2+]o from(0) to 2 mM) in ARVM. We first examined whether IL-6 reduced Ca2+ influx via L-type Ca2+ -channel current (ICa,L). Whole-cell ICa,L in ARVM was measured under conditions similar to those used for CS measurements, and it was found to be unaltered by IL-6. The sarcoplasmic reticular (SR) function was then assessed by examining postrest potentiation (PRP) and caffeine responsiveness of CS. Results showed that treatment with IL-6 for 2 h significantly decreased PRP, which was concomitant with a decrease in the phosphorylation of phospholamban. Following removal of IL-6, PRP and responsiveness to 10 mM caffeine were also reduced. Meanwhile, the IL-6-induced increase in nitric oxide (NO) production after 2 h (but not 1 h) was abolished by NG-monomethyl-l-arginine (l-NMMA) and 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (AMT; a selective inhibitor of iNOS). Furthermore, IL-6-elicited suppressions of PRP and responsiveness to caffeine and Ca2+o were abolished by L-NMMA and AMT. Thus, these results suggest that activation of iNOS mediates IL-6-induced inhibition of SR function in ARVM during chronic exposure. PMID:15845578

  12. A cardiac dihydropyridine receptor II-III loop peptide inhibits resting Ca(2+) sparks in ferret ventricular myocytes.

    Science.gov (United States)

    Li, Y; Bers, D M

    2001-11-15

    1. We studied the effect of a peptide (Ac-10C) on cardiac ryanodine receptor (RyR) opening. This decapeptide (KKERKLARTA) is a fragment of the cardiac dihydropyridine receptor (DHPR) from the cytosolic loop between the second and third transmembrane domains (II-III loop). Studies were carried out in ferret ventricular myocytes by simultaneously applying ruptured-patch voltage clamp and line-scan confocal microscopy with fluo-3 to measure intracellular [Ca(2+)] ([Ca(2+)](i)) and Ca(2+) sparks. 2. Inclusion of Ac-10C in the dialysing pipette solution inhibited resting Ca(2+) spark frequency (due to diastolic RyR openings) by > 50 %. This occurred without changing sarcoplasmic reticulum (SR) Ca(2+) content, which was measured via the caffeine-induced Ca(2+) transient amplitude and the caffeine-induced Na(+)-Ca(2+) exchange current (I(NCX)) integral. Ac-10C also reduced slightly the size of Ca(2+) sparks. 3. Ac-10C did not alter either resting [Ca(2+)](i) (assessed by indo-1 fluorescence) or DHPR gating (measured as L-type Ca(2+) current). 4. The SR Ca(2+) fractional release was depressed by Ac-10C at relatively low SR Ca(2+) content, but not at higher SR Ca(2+) content. 5. A control scrambled peptide (Ac-10CS) did not alter any of the measured parameters (notably Ca(2+) spark frequency or SR Ca(2+) fractional release). Thus, the Ac-10C effects may be sequence or charge distribution specific. 6. Our results suggest an inhibitory regulation of RyRs at rest via the cardiac DHPR II-III loop N-terminus region. The mechanism of the effect and whether this interaction is important in cardiac excitation-contraction coupling (E-C coupling) per se, requires further investigation. PMID:11711557

  13. 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.)

  14. Scintigraphic evaluation of ventricular hypertrophy using Tc-99m methoxyisobutyl isonitrile

    International Nuclear Information System (INIS)

    The usefulness of a newly developed myocardial imaging agent, Tc-99m methoxyisobutylisonitrile (MIBI), was assessed in 15 patients with hypertrophy. The patients underwent myocardial scintigraphy with Tc-99m MIBI at rest 30 minutes after the administration of 925 MBq. The findings were compared with those of concurrently performed myocardial scintigraphy with Tl-201 (111 MBq). Both types of scans showed hypertrophy in 14 patients. Of a total of 75 segments, 42 (56%) and 45 segmetns (61%) were found hypertrophied on Tc-99m MIBI and Tl-201 scans, respectively. In detecting hypertrophy, an overall concurrence rate between Tc-99m MIBI and Tl-201 scans was 50%: it tended to be high in the anterior and lateral segments and low in the apical, septal, and postero-inferior segments. Decrease or defect of uptake was more frequent on Tl-201 scans than on Tc-99m MIBI scans (9 vs 5 segments). When using echographically proven septum thickness, Tc-99m MIBI and Tl-201 scans defined the septum 13 mm or more and 11 mm or more as hypertrophy, respectively. For the septum 12 mm or more, the detection rates of Tc-99m MIBI and Tl-201 scans were 69% and 46%, respectively. On visual assessment, Tc-99m MIBI scans had the same diagnostic sensitivity as Tl-201 scans. In view of the potential of clear imaging and less overestimation, Tc-99m MIBI scans seemed to be useful in the diagnosis of hypertrophic heart. (N.K.)

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

    Scientific Electronic Library Online (English)

    Yu-luan, Xiang; Li, He; Jun, Xiao; Shuang, Xia; Song-bai, Deng; Yun, Xiu; Qiang, She.

    2012-03-01

    Full Text Available SciELO Brazil | Language: English Abstract in english 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.

  16. 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

    Full Text Available FUNDAMENTO: A hipertrofia ventricular esquerda é potente preditor de mortalidade em renais crônicos. Estudo prévio de nosso grupo mostrou que renais crônicos com menor escolaridade têm hipertrofia ventricular mais intensa. OBJETIVO: Ampliar estudo prévio e verificar se a hipertrofia ventricular esquerda pode justificar a associação entre escolaridade e mortalidade cardiovascular de pacientes em hemodiálise. MÉTODOS: Foram avaliados 113 pacientes entre janeiro de 2005 e março de 2008 e seguidos até outubro de 2010. Foram traçadas curvas de sobrevida comparando a mortalidade cardiovascular, e por todas as causas dos pacientes com escolaridade de até três anos (mediana da escolaridade e pacientes com escolaridade igual ou superior a quatro anos. Foram construídos modelos múltiplos de Cox ajustados para as variáveis de confusão. RESULTADOS: Observou-se associação entre nível de escolaridade e hipertrofia ventricular. A diferença estatística de mortalidade de origem cardiovascular e por todas as causas entre os diferentes níveis de escolaridade ocorreu aos cinco anos e meio de seguimento. No modelo de Cox, a hipertrofia ventricular e a proteína-C reativa associaram-se à mortalidade por todas as causas e de origem cardiovascular. A etiologia da insuficiência renal associou-se à mortalidade por todas as causas e a creatinina associou-se à mortalidade de origem cardiovascular. A associação entre escolaridade e mortalidade perdeu significância estatística no modelo ajustado. CONCLUSÃO: Os resultados do presente trabalho confirmam estudo prévio e demonstram, ademais, que a maior mortalidade cardiovascular observada nos pacientes com menor escolaridade pôde ser explicada por fatores de risco de ordem bioquímica e de morfologia cardíaca.FUNDAMENTO: La hipertrofia ventricular izquierda es potente predictor de mortalidad en renales crónicos. Estudio previo de nuestro grupo mostró que renales crónicos con menor 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 association between schooling and cardiovascular mortality in hemodialysis patients. METHODS: This stud

  17. Sensibilidade do eletrocardiograma na hipertrofia ventricular de acordo com gênero e massa cardíaca Electrocardiogram sensitivity in left ventricular hypertrophy according to gender and cardiac mass

    Directory of Open Access Journals (Sweden)

    Ana P. Colossimo

    2011-09-01

    Full Text Available FUNDAMENTO: Sabe-se que vários fatores interferem na sensibilidade do Eletrocardiograma (ECG no diagnóstico da Hipertrofia Ventricular Esquerda (HVE, sendo o gênero e a massa cardíaca alguns dos principais. OBJETIVO: Avaliar a influência do sexo na sensibilidade de alguns dos critérios utilizados para a detecção de HVE, de acordo com a progressão do grau de hipertrofia ventricular. MÉTODOS: De acordo com o gênero e com o grau de HVE ao ecocardiograma, os pacientes foram divididos em três grupos: HVE leve, moderada e severa. Avaliou-se a sensibilidade do ECG para detectar HVE entre homens e mulheres, conforme o grau de HVE. RESULTADOS: Dos 874 pacientes, 265 eram homens (30,3% e 609, mulheres (69,7%. Os critérios [(S + R X QRS], Sokolow-Lyon, Romhilt-Estes, Perúgia e padrão strain mostraram alto poder discriminatório no diagnóstico de HVE entre homens e mulheres nos três grupos de HVE, com desempenho superior na população masculina e destaque para os escores [(S + R X QRS] e Perúgia. CONCLUSÃO: A sensibilidade diagnóstica do ECG é maior com o aumento da massa cardíaca. O exame é mais sensível entre homens, destacando-se os escores [(S + R X QRS] e Perúgia.BACKGROUND: Several factors are known to interfere with electrocardiogram (ECG sensitivity when diagnosing Left Ventricular Hypertrophy (LVH, with gender and cardiac mass being two of the most important ones OBJECTIVE: To evaluate the influence of gender on the sensitivity of some of the criteria used to detect LVH, according to the progression of ventricular hypertrophy degree. METHODS: According to gender and the degree of LVH at the echocardiogram, the patients were divided in three groups: mild, moderate and severe LVH. ECG sensitivity to detect LVH was assessed between men and women, according to the LVH degree. RESULTS: Of the 874 patients, 265 were males (30.3% and 609, females (69.7%. The [(S + R X QRS], Sokolow-Lyon, Romhilt-Estes, Perugia and strain criteria showed high discriminatory power in the diagnosis of LVH between men and women in the three groups with LVH, with a superior performance in the male population and highlighting the importance of the [(S + R X QRS] and Perugia scores. Conclusion: The diagnostic sensitivity of the ECG increases with the cardiac mass. The examination is more sensitive in men, highlighting the importance of the [(S + R X QRS] and Perugia scores. CONCLUSION: The diagnostic sensitivity of the ECG increases with the cardiac mass. The examination is more sensitive in men, highlighting the importance of the [(S + R X QRS] and Perugia scores.

  18. Sensibilidade do eletrocardiograma na hipertrofia ventricular de acordo com gênero e massa cardíaca / Electrocardiogram sensitivity in left ventricular hypertrophy according to gender and cardiac mass

    Scientific Electronic Library Online (English)

    Ana P., Colossimo; Francisco de Assis, Costa; Andrés R. P., Riera; Maria T. N., Bombig; Valter C., Lima; Francisco A. H., Fonseca; Maria C. O., Izar; Bráulio, L. Filho; Dilma, Souza; Rui M. S., Povoa.

    2011-09-01

    Full Text Available SciELO Brazil | Languages: English, Portuguese Abstract in portuguese FUNDAMENTO: Sabe-se que vários fatores interferem na sensibilidade do Eletrocardiograma (ECG) no diagnóstico da Hipertrofia Ventricular Esquerda (HVE), sendo o gênero e a massa cardíaca alguns dos principais. OBJETIVO: Avaliar a influência do sexo na sensibilidade de alguns dos critérios utilizados [...] para a detecção de HVE, de acordo com a progressão do grau de hipertrofia ventricular. MÉTODOS: De acordo com o gênero e com o grau de HVE ao ecocardiograma, os pacientes foram divididos em três grupos: HVE leve, moderada e severa. Avaliou-se a sensibilidade do ECG para detectar HVE entre homens e mulheres, conforme o grau de HVE. RESULTADOS: Dos 874 pacientes, 265 eram homens (30,3%) e 609, mulheres (69,7%). Os critérios [(S + R) X QRS], Sokolow-Lyon, Romhilt-Estes, Perúgia e padrão strain mostraram alto poder discriminatório no diagnóstico de HVE entre homens e mulheres nos três grupos de HVE, com desempenho superior na população masculina e destaque para os escores [(S + R) X QRS] e Perúgia. CONCLUSÃO: A sensibilidade diagnóstica do ECG é maior com o aumento da massa cardíaca. O exame é mais sensível entre homens, destacando-se os escores [(S + R) X QRS] e Perúgia. Abstract in english BACKGROUND: Several factors are known to interfere with electrocardiogram (ECG) sensitivity when diagnosing Left Ventricular Hypertrophy (LVH), with gender and cardiac mass being two of the most important ones OBJECTIVE: To evaluate the influence of gender on the sensitivity of some of the criteria [...] used to detect LVH, according to the progression of ventricular hypertrophy degree. METHODS: According to gender and the degree of LVH at the echocardiogram, the patients were divided in three groups: mild, moderate and severe LVH. ECG sensitivity to detect LVH was assessed between men and women, according to the LVH degree. RESULTS: Of the 874 patients, 265 were males (30.3%) and 609, females (69.7%). The [(S + R) X QRS], Sokolow-Lyon, Romhilt-Estes, Perugia and strain criteria showed high discriminatory power in the diagnosis of LVH between men and women in the three groups with LVH, with a superior performance in the male population and highlighting the importance of the [(S + R) X QRS] and Perugia scores. Conclusion: The diagnostic sensitivity of the ECG increases with the cardiac mass. The examination is more sensitive in men, highlighting the importance of the [(S + R) X QRS] and Perugia scores. CONCLUSION: The diagnostic sensitivity of the ECG increases with the cardiac mass. The examination is more sensitive in men, highlighting the importance of the [(S + R) X QRS] and Perugia scores.

  19. Modified septal myectomy using a curved knife for left ventricular septal hypertrophy.

    Science.gov (United States)

    Takahashi, Shinya; Takasaki, Taiichi; Tadehara, Futoshi; Taguchi, Takahiro; Katayama, Keijiro; Kurosaki, Tatsuya; Imai, Katsuhiko; Sueda, Taijiro

    2014-10-01

    An 86-year-old woman presented with chest pain and discomfort. Echocardiography revealed severe aortic valve stenosis and asymmetric septal hypertrophy. Aortic valve replacement and myectomy were performed using a curved knife. The blade was U-shaped in cross-section, and was curved upward along the long axis. Hypertrophic septal myocardium was removed along the long axis of the left ventricle (LV), and a groove for blood flow was constructed. The patient was discharged uneventfully without recurrence of her chest discomfort. Our result suggested that a curved knife is a reasonable option for transaortic septal myectomy in patients with obstructive LV hypertrophy. PMID:25367241

  20. Voltage dependence of intracellular [Ca2+]i transients in guinea pig ventricular myocytes.

    Science.gov (United States)

    Barcenas-Ruiz, L; Wier, W G

    1987-07-01

    [Ca2+]i transients, elicited by voltage-clamp depolarization of single guinea pig cardiac ventricular cells, were observed through use of the fluorescent Ca2+ indicator, fura-2. Individual cells, loaded with fura-2 either by internal perfusion or by exposure to fura-2/AM, were studied with the use of an inverted microscope that was equipped with ultraviolet epifluorescence illumination, an intensified silicon intensifier target camera, and a photomultiplier tube. Variation of membrane voltage and exposure of cells to verapamil (a Ca2+ channel blocker) and ryanodine (which was assumed to abolish selectively the release of Ca2+ from the sarcoplasmic reticulum) were used to investigate the cellular processes that determine the [Ca2+]i transient. The principal results of the study are: When appropriate methods are used, the properties of cytosolic fura-2 inside guinea pig cells are similar to those of fura-2 in solution, irrespective of the method of loading. The amplitude (at 100 msec) of verapamil-sensitive fluorescence transients elicited by pulse depolarization (range -30 to 80 mV) has a bell-shaped dependence on membrane voltage (maximum at 10 mV). Rapid, ryanodine-sensitive and verapamil-sensitive "tail transients" are elicited on repolarization from membrane potentials greater than 30 mV; their amplitude increases as the amplitude of the preceding pulse increases. The amplitude of slow fluorescence transients that are insensitive to verapamil and ryanodine increases continuously with membrane potential throughout the range -20 to 80 mV. The voltage dependence and pharmacology of the rapid transients elicited by pulse depolarization or by repolarization are consistent with their having arisen from Ca2+ released from the sarcoplasmic reticulum, via Ca2+-induced Ca2+ release.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2440616

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

    International Nuclear Information System (INIS)

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

  2. Transient asymmetric ventricular septal hypertrophy in the newborn unassociated with maternal diabetes.

    OpenAIRE

    Cecchi, F.; Zuppiroli, A.; Manetti, A.

    1984-01-01

    Severe hypertrophy of the interventricular septum was found by echocardiography in a 15 day old infant without symptoms whose mother was not diabetic. The electrocardiogram showed pronounced intraventricular conduction disturbances. Both echocardiographic and electrocardiographic findings showed no abnormality after 27 months, the explanation for which could be the spontaneous regression of an intracardiac rhabdomyoma.

  3. 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 inflammatory response, fibrin deposition and RVH, and stimulates alveolarization. Initiation of sildenafil treatment after hyperoxic lung injury and continued during room air recovery improves alveolarization and restores pulmonary angiogenesis and RVH in experimental BPD.

  4. Diagnosis of apical hypertrophic cardiomyopathy: T-wave inversion and relative but not absolute apical left ventricular hypertrophy?

    Science.gov (United States)

    Flett, Andrew S.; Maestrini, Viviana; Milliken, Don; Fontana, Mariana; Treibel, Thomas A.; Harb, Rami; Sado, Daniel M.; Quarta, Giovanni; Herrey, Anna; Sneddon, James; Elliott, Perry; McKenna, William; Moon, James C.

    2015-01-01

    Background Diagnosis of apical HCM utilizes conventional wall thickness criteria. The normal left ventricular wall thins towards the apex such that normal values are lower in the apical versus the basal segments. The impact of this on the diagnosis of apical hypertrophic cardiomyopathy has not been evaluated. Methods We performed a retrospective review of 2662 consecutive CMR referrals, of which 75 patients were identified in whom there was abnormal T-wave inversion on ECG and a clinical suspicion of hypertrophic cardiomyopathy. These were retrospectively analyzed for imaging features consistent with cardiomyopathy, specifically: relative apical hypertrophy, left atrial dilatation, scar, apical cavity obliteration or apical aneurysm. For comparison, the same evaluation was performed in 60 healthy volunteers and 50 hypertensive patients. Results Of the 75 patients, 48 met conventional HCM diagnostic criteria and went on to act as another comparator group. Twenty-seven did not meet criteria for HCM and of these 5 had no relative apical hypertrophy and were not analyzed further. The remaining 22 patients had relative apical thickening with an apical:basal wall thickness ratio > 1 and a higher prevalence of features consistent with a cardiomyopathy than in the control groups with 54% having 2 or more of the 4 features. No individual in the healthy volunteer group had more than one feature and no hypertension patient had more than 2. Conclusion A cohort of individuals exist with T wave inversion, relative apical hypertrophy and additional imaging features of HCM suggesting an apical HCM phenotype not captured by existing diagnostic criteria. PMID:25666123

  5. Diverse effects of renal denervation on ventricular hypertrophy and blood pressure in DOCA-salt hypertensive rats

    Directory of Open Access Journals (Sweden)

    Cabral A.M.

    1998-01-01

    Full Text Available Cardiac hypertrophy that accompanies hypertension seems to be a phenomenon of multifactorial origin whose development does not seem to depend on an increased pressure load alone, but also on local growth factors and cardioadrenergic activity. The aim of the present study was to determine if sympathetic renal denervation and its effects on arterial pressure level can prevent cardiac hypertrophy and if it can also delay the onset and attenuate the severity of deoxycorticosterone acetate (DOCA-salt hypertension. DOCA-salt treatment was initiated in rats seven days after uninephrectomy and contralateral renal denervation or sham renal denervation. DOCA (15 mg/kg, sc or vehicle (soybean oil, 0.25 ml per animal was administered twice a week for two weeks. Rats treated with DOCA or vehicle (control were provided drinking water containing 1% NaCl and 0.03% KCl. At the end of the treatment period, mean arterial pressure (MAP and heart rate measurements were made in conscious animals. Under ether anesthesia, the heart was removed and the right and left ventricles (including the septum were separated and weighed. DOCA-salt treatment produced a significant increase in left ventricular weight/body weight (LVW/BW ratio (2.44 ± 0.09 mg/g and right ventricular weight/body weight (RVW/BW ratio (0.53 ± 0.01 mg/g compared to control (1.92 ± 0.04 and 0.48 ± 0.01 mg/g, respectively rats. MAP was significantly higher (39% in DOCA-salt rats. Renal denervation prevented (P>0.05 the development of hypertension in DOCA-salt rats but did not prevent the increase in LVW/BW (2.27 ± 0.03 mg/g and RVW/BW (0.52 ± 0.01 mg/g. We have shown that the increase in arterial pressure level is not responsible for cardiac hypertrophy, which may be more related to other events associated with DOCA-salt hypertension, such as an increase in cardiac sympathetic activity

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

    OpenAIRE

    Costa, Eduardo A. S.; Fº, Bra?ulio Luna; Rui Póvoa; Fº, Celso Ferreira; Neif Murad; Marcelo Ferreira; Celso Ferreira

    1997-01-01

    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 ...

  7. delta-Opioid receptor stimulation enhances the growth of neonatal rat ventricular myocytes via the extracellular signal-regulated kinase pathway.

    Science.gov (United States)

    Zhao, Min; Wang, Hong-Xin; Yang, Jing; Su, Yu-Hong; Su, Rong-Jian; Wong, Tak Ming

    2008-01-01

    1. The aims of the present study were to determine whether delta-opioid receptor stimulation enhanced proliferation of and to investigate the role of the extracellular signal-regulated kinase (ERK) pathway in ventricular myocytes from neonatal rats. 2. At concentratins ranging from 10 nmol/L to 10 micromol/L, [D-Ala2,D-Leu5]enkephalin (DADLE) concentration-dependently promoted myocardial growth and DNA synthesis and altered the cytoskeleton. 3. At 1 micromol/L, DADLE also increased the expression and phosphorylation of ERK. 4. These effects of 1 micromol/L DADLE were abolished by 10 micromol/L naltrindole, a selective delta-opioid receptor antagonist, 10 nmol/L U0126, a selective ERK antagonist, 1 micromol/L staurosporine, an inhibitor of protein kinase (PK) C, and 100 micromol/L Rp-adenosine 3',5'-cyclic monophosphorothioate triethylammonium salt hydrate (Rp-cAMPS), an inhibitor of PKA. 5. In conclusion, delta-opioid receptor stimulation enhances the proliferation and development of the ventricular myocytes of neonatal rats. The ERK pathway and related signalling mechanisms, namely PKC and PKA, are involved. PMID:18047635

  8. Stoichiometry of Na+-Ca2+ exchange is 3:1 in guinea-pig ventricular myocytes.

    Science.gov (United States)

    Hinata, Masamitsu; Yamamura, Hisao; Li, Libing; Watanabe, Yasuhide; Watano, Tomokazu; Imaizumi, Yuji; Kimura, Junko

    2002-12-01

    In single guinea-pig ventricular myocytes, we examined the stoichiometry of Na(+)-Ca(2+) exchange (NCX) by measuring the reversal potential (E(NCX)) of NCX current (I(NCX)) and intracellular Ca(2+) concentration ([Ca(2+)](i)) with the whole-cell voltage-clamp technique and confocal microscopy, respectively. With given ionic concentrations in the external and pipette solutions, the predicted E(NCX) were -73 and -11 mV at 3:1 and 4:1 stoichiometries, respectively. E(NCX) measured were -69 +/- 2 mV (n = 11), -47 +/- 1 mV (n = 14) and -15 +/- 1 mV (n = 15) at holding potentials (HP) of -73, -42 and -11 mV, respectively. Thus, E(NCX) almost coincided with HP, indicating that [Ca(2+)](i) and/or [Na(+)](i) changed due to I(NCX) flow. Shifts of E(NCX) (deltaE(NCX)) were measured by changing [Ca(2+)](o) or [Na(+)](o). The measured values of deltaE(NCX) were almost always smaller than those expected theoretically at a stoichiometry of either 3:1 or 4:1. Using indo-1 fluorescence, [Ca(2+)](i) measured under the whole-cell voltage-clamp supported a 3:1 but not 4:1 stoichiometry. To prevent Ca(2+) accumulation, we inhibited I(NCX) with Ni(2+) and re-examined E(NCX) during washing out Ni(2+). With HP at predicted E(NCX) at a 3:1 stoichiometry, E(NCX) developed was close to predicted E(NCX) and did not change with time. However, with HP at predicted E(NCX) for a 4:1 stoichiometry, E(NCX) developed initially near a predicted E(NCX) for a 3:1 stoichiometry and shifted toward E(NCX) for a 4:1 stoichiometry with time. We conclude that the stoichiometry of cardiac NCX is 3:1. PMID:12456825

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

    OpenAIRE

    Tillmanns Harald H; Goldenberg Anna; Faulhammer Petra; von Lilien Anna-Laura; Stieger Philipp; Paddenberg Renate; Kummer Wolfgang; Braun-Dullaeus Ruediger C

    2007-01-01

    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,...

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

    Scientific Electronic Library Online (English)

    T.A., Uggere; G.R., Abreu; K.N., Sampaio; A.M., Cabral; N.S., Bissoli.

    2000-05-01

    Full Text Available SciELO Brazil | Language: English Abstract in english 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 hype [...] rtension 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 chemosensitive, reflex can be restored by treatment of SHR with enalapril. It is possible that by augmenting the gain of the volume-sensitive reflex control of RSNA, enalapril contributed to the reversal of cardiac hypertrophy and normalization of arterial blood pressure in SHR.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2002-12-01

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

  12. 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)

  13. Fetal-Adult Cardiac Transcriptome Analysis in Rats with Contrasting Left Ventricular Mass Reveals New Candidates for Cardiac Hypertrophy

    Science.gov (United States)

    Grabowski, Katja; Riemenschneider, Mona; Schulte, Leonard; Witten, Anika; Schulz, Angela; Stoll, Monika; Kreutz, Reinhold

    2015-01-01

    Reactivation of fetal gene expression patterns has been implicated in common cardiac diseases in adult life including left ventricular (LV) hypertrophy (LVH) in arterial hypertension. Thus, increased wall stress and neurohumoral activation are discussed to induce the return to expression of fetal genes after birth in LVH. We therefore aimed to identify novel potential candidates for LVH by analyzing fetal-adult cardiac gene expression in a genetic rat model of hypertension, i.e. the stroke-prone spontaneously hypertensive rat (SHRSP). To this end we performed genome-wide transcriptome analysis in SHRSP to identify differences in expression patterns between day 20 of fetal development (E20) and adult animals in week 14 in comparison to a normotensive rat strain with contrasting low LV mass, i.e. Fischer (F344). 15232 probes were detected as expressed in LV tissue obtained from rats at E20 and week 14 (p < 0.05) and subsequently screened for differential expression. We identified 24 genes with SHRSP specific up-regulation and 21 genes with down-regulation as compared to F344. Further bioinformatic analysis presented Efcab6 as a new candidate for LVH that showed only in the hypertensive SHRSP rat differential expression during development (logFC = 2.41, p < 0.001) and was significantly higher expressed in adult SHRSP rats compared with adult F344 (+ 76%) and adult normotensive Wistar-Kyoto rats (+ 82%). Thus, it represents an interesting new target for further functional analyses and the elucidation of mechanisms leading to LVH. Here we report a new approach to identify candidate genes for cardiac hypertrophy by combining the analysis of gene expression differences between strains with a contrasting cardiac phenotype with a comparison of fetal-adult cardiac expression patterns. PMID:25646840

  14. Reversal of severe angioproliferative pulmonary arterial hypertension and right ventricular hypertrophy by combined phosphodiesterase-5 and endothelin receptor inhibition.

    Science.gov (United States)

    Cavasin, Maria A; Demos-Davies, Kimberly M; Schuetze, Katherine B; Blakeslee, Weston W; Stratton, Matthew S; Tuder, Rubin M; McKinsey, Timothy A

    2014-11-26

    BackgroundPatients with pulmonary arterial hypertension (PAH) are treated with vasodilators, including endothelin receptor antagonists (ERAs), phosphodiesterase-5 (PDE-5) inhibitors, soluble guanylyl cyclase activators, and prostacyclin. Despite recent advances in pharmacotherapy for individuals with PAH, morbidity and mortality rates in this patient population remain unacceptably high. Here, we tested the hypothesis that combination therapy with two PAH drugs that target distinct biochemical pathways will provide superior efficacy relative to monotherapy in the rat SU5416 plus hypoxia (SU-Hx) model of severe angioproliferative PAH, which closely mimics the human condition.MethodsMale Sprague Dawley rats were injected with a single dose of SU5416, which is a VEGF receptor antagonist, and exposed to hypobaric hypoxia for three weeks. Rats were subsequently housed at Denver altitude and treated daily with the PDE-5 inhibitor, tadalafil (TAD), the type A endothelin receptor (ETA) antagonist, ambrisentan (AMB), or a combination of TAD and AMB for four additional weeks.ResultsMonotherapy with TAD or AMB led to modest reductions in pulmonary arterial pressure (PAP) and right ventricular (RV) hypertrophy. In contrast, echocardiography and invasive hemodynamic measurements revealed that combined TAD/AMB nearly completely reversed pulmonary hemodynamic impairment, RV hypertrophy, and RV functional deficit in SU-Hx rats. Efficacy of TAD/AMB was associated with dramatic reductions in pulmonary vascular remodeling, including suppression of endothelial cell plexiform lesions, which are common in human PAH.ConclusionsCombined therapy with two vasodilators that are approved for the treatment of human PAH provides unprecedented efficacy in the rat SU-Hx preclinical model of severe, angioproliferative PAH. PMID:25425003

  15. Extracellular Superoxide Dismutase Deficiency Exacerbates Pressure Overload–Induced Left Ventricular Hypertrophy and Dysfunction

    OpenAIRE

    Lu, Z.; Xu, X.; Hu, X.; Zhu, G.; Zhang, P.; Deel, E. D.; French, J. P.; Fassett, J. T.; Oury, T. D.; Bache, R. J.; Chen, Y. J.

    2007-01-01

    Extracellular superoxide dismutase (SOD) contributes only a small fraction to total SOD activity in the normal heart but is strategically located to scavenge free radicals in the extracellular compartment. To examine the physiological significance of extracellular SOD in the response of the heart to hemodynamic stress, we studied the effect of extracellular SOD deficiency on transverse aortic constriction (TAC)-induced left ventricular remodeling. Under unstressed conditions extracellular SOD...

  16. Obesidad central y regresión de hipertrofia ventricular izquierda / Central obesity and left ventricular hypertrophy regression / Obesidade central e regressão da hipertrofia esquerda

    Scientific Electronic Library Online (English)

    Daniel, Piskorz; Luciano, Citta; Norberto, Citta; Marcelo, Lanzotti; Roberto, Lanzotti; Horacio, Locatelli; Alicia, Tommasi.

    2007-12-01

    Full Text Available SciELO Argentina | Language: Spanish Abstract in portuguese Em sujeitos hipertensos, os níveis de pressão arterial per se seriam a principal determinante do desenvolvimento de hiperetrofia ventricular esquerda. Por outra parte, o índice de massa corporal e o perímetro de cintura se associaram em forma lineal, contínua e positiva com o índice de massa ventric [...] ular esquerdo ainda em não hipertensos. Um tratamento insuficiente seria a principal causa da falta de regressão do dano no órgão branco. O objetivo do presente trabalho é determinar o impacto da obesidade central sobre a regressão do índice de massa ventricular esquerdo. Material e métodos: incluíram-se 102 pacientes (p) HTA que concorreram por primeira vez a um consultório especializado em forma consecutiva, mediulhes o índice de massa ventricular esquerdo (IMVE) pelo método de Devereux ao início e logo de pelo menos 1 ano de tratamento. Foram divididos em dois grupos: GA: perímetro cintura (PC) esses valores. Para a análise de estatística se aplicou test t de Students para diferenças de médias e proporções, e se considerou significação estatístico p Abstract in spanish En sujetos hipertensos, los niveles de presión arterial per se serían el principal determinante del desarrollo de hipertrofia ventricular izquierda. Por otra parte, el índice de masa corporal y el perímetro de cintura se han asociado en forma lineal, continua y positiva con elíndice de masa ventricu [...] lar izquierdo aún en no hipertensos. Un tratamiento insuficiente sería la principal causa de falta de regresión del daño en órgano blanco. El objetivo del presente trabajo es determinar el impacto de la obesidad central sobre la regresión del índice de masa ventricular izquierdo. Material y métodos: se incluyeron 102 pacientes (p) HTA que concurrieron por primera vez a un consultorio especializado en forma consecutiva, se les midió el índice de masa ventricular izquierdo (IMVI) por método de Devereux al inicio y luego de al menos 1 año de tratamiento. Fueron divididos en dos grupos: GA: perímetro cintura (PC) esos valores. Para el análisis estadístico se aplicó test t de Students para diferencias de medias y proporciones, y se consideró significación estadística p Abstract in english Blood pressure per se may be the main determinant of left ventricle hypertrophy development in hypertensive subjects. On the other side, body mass index and waist circumference are related to left ventricle mass index (LVMI) positively, continuously and linearly even in non hypertensive patients. An [...] insufficient treatment may be the main reason of not achieving regression of target organ damage. The objective of this trial is to establish the impact of central obesity on LVMI regression. Material and methods: 102 consecutive hypertensive patients (p) wich attended for the first time to a specialized consultory room were included. LVMI was measured with the Devereux method at the begining and after at least one year of treatment. The patients were divided into two groups: GA: waist circumference (WC) of those values. The statistic analysis was done with the Students t test for differences in proportions and means and a p value

  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; Gokhan, Ekmekci C.; 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. Left ventricular outflow tract obstruction in the presence of asymmetric septal hypertrophy and accessory mitral valve tissue treated with alcohol septal ablation.

    Science.gov (United States)

    Kim, Michael S; Klein, Andrew J; Groves, Bertron M; Quaife, Robert A; Salcedo, Ernesto E

    2008-09-01

    Redundant or accessory mitral valve tissue (AMVT) is a rare clinical condition. It is an even rarer cause of left ventricular outflow tract obstruction. We report a case of an adult male with medically unresponsive hypertrophic obstructive cardiomyopathy in whom real-time three-dimensional transesophageal echocardiography was used to both diagnose the presence of coexistent asymmetric septal hypertrophy and AMVT as well as confirm the safety and efficacy of treatment with alcohol septal ablation. PMID:18490281

  19. The Effects of Cyclic Guanylate Cyclase Stimulation on Right Ventricular Hypertrophy and Failure Alone and in Combination with Phosphodiesterase-5 Inhibition

    DEFF Research Database (Denmark)

    Andersen, Asger; Nielsen, Jan MØller

    2013-01-01

    BACKGROUND:: We investigated if soluble guanylate cyclase stimulation either alone or in combination with PDE5 inhibition could prevent pressure overload induced right ventricular hypertrophy and failure. METHODS AND RESULTS:: The soluble guanylate cyclase stimulator BAY 41-2272 (BAY, 10 mg/kg/day) either alone or in combination (BAY+SIL) with a PDE5 inhibitor sildenafil (SIL, 100 mg/kg/day) was examined for prevention of right ventricular hypertrophy and failure in Wistar rats (n=73) operated by pulmonary trunk banding (PTB).All treatments failed to inhibit the development of RV hypertrophy and failure. In the BAY and BAY+SIL groups there were an increased mortality. Mean arterial blood pressure was lowered and cardiac output increased in the BAY+SIL group. Systolic RV pressure was increased in the BAY and BAY+SIL group possibly due to an inotropic response and/or increased venous return. CONCLUSIONS:: Stimulation of sGC by BAY 41-2272 alone or in combination with sildenafil failed to prevent the developmentof RV hypertrophy and failure in rats subjected to pulmonary trunk banding. An increased mortality was observed in animals treated by BAY 41-2272 alone and in combination with sildenafil.

  20. Left ventricular diastolic dysfunction is associated with impaired baroreflex at rest and during orthostatic stress in hypertensive patients with left ventricular hypertrophy.

    Science.gov (United States)

    Makowski, K; Gielerak, G; Kramarz, E; Wierzcho?, S; Kami?ski, G; Kowal, J; Krzesi?ski, P; Zegad?o, A; Skrobowski, A

    2013-08-01

    The study aimed to determine the relationship between left ventricular (LV) diastolic function and the heart's spontaneous baroreflex at rest and in response to orthostatic stress during a prospective follow-up of hypertensive patients with LV hypertrophy (LVH+). LV structure and function and baroreflex sensitivity (BRS) during tilt testing were evaluated in 24 LVH+ patients and compared with 25 age-matched healthy controls and 25 hypertensive patients without LVH (LVH-). Clinical status, diastolic function and BRS were then assessed in LVH+ patients during treatment with telmisartan (monotherapy or combined with hydrochlorothiazide and/or amlodipine) at 6- and 18-month follow-ups. LVH+ patients had significantly altered diastolic function indices and decreased BRS as compared with healthy controls and LVH- patients. During the 18-month follow-up, favorable changes in diastolic function were associated with improvement in BRS at rest and during tilting. In multivariate regression models, an index reflecting rate of LV myocardial relaxation (E'sept) where E'sept denotes peak early diastolic velocity at the septal mitral annulus and a surrogate for LV filling pressure (E/E'sept), independently from other clinical and echocardiographic variables related to the low-frequency component of BRS during tilting. In conclusion, the LV diastolic function indices have independent associations with BRS parameters obtained at rest and during orthostatic stress in LVH+ patients receiving long-term pharmacological intervention. PMID:23426068

  1. Shortening and intracellular Ca2+ in ventricular myocytes and expression of genes encoding cardiac muscle proteins in early onset type 2 diabetic Goto-Kakizaki rats.

    Science.gov (United States)

    Salem, K A; Adrian, T E; Qureshi, M A; Parekh, K; Oz, M; Howarth, F C

    2012-12-01

    There has been a spectacular rise in the global prevalence of type 2 diabetes mellitus. Cardiovascular complications are the major cause of morbidity and mortality in diabetic patients. Contractile dysfunction, associated with disturbances in excitation-contraction coupling, has been widely demonstrated in the diabetic heart. The aim of this study was to investigate the pattern of cardiac muscle genes that are involved in the process of excitation-contraction coupling in the hearts of early onset (8-10 weeks of age) type 2 diabetic Goto-Kakizaki (GK) rats. Gene expression was assessed in ventricular muscle with real-time RT-PCR; shortening and intracellular Ca(2+) were measured in ventricular myocytes with video edge detection and fluorescence photometry, respectively. The general characteristics of the GK rats included elevated fasting and non-fasting blood glucose and blood glucose at 120 min following a glucose challenge. Expression of genes encoding cardiac muscle proteins (Myh6/7, Mybpc3, Myl1/3, Actc1, Tnni3, Tnn2, Tpm1/2/4 and Dbi) and intercellular proteins (Gja1/4/5/7, Dsp and Cav1/3) were unaltered in GK ventricle compared with control ventricle. The expression of genes encoding some membrane pumps and exchange proteins was unaltered (Atp1a1/2, Atp1b1 and Slc8a1), whilst others were either upregulated (Atp1a3, relative expression 2.61 ± 0.69 versus 0.84 ± 0.23) or downregulated (Slc9a1, 0.62 ± 0.07 versus 1.08 ± 0.08) in GK ventricle compared with control ventricle. The expression of genes encoding some calcium (Cacna1c/1g, Cacna2d1/2d2 and Cacnb1/b2), sodium (Scn5a) and potassium channels (Kcna3/5, Kcnj3/5/8/11/12, Kchip2, Kcnab1, Kcnb1, Kcnd1/2/3, Kcne1/4, Kcnq1, Kcng2, Kcnh2, Kcnk3 and Kcnn2) were unaltered, whilst others were either upregulated (Cacna1h, 0.95 ± 0.16 versus 0.47 ± 0.09; Scn1b, 1.84 ± 0.16 versus 1.11 ± 0.11; and Hcn2, 1.55 ± 0.15 versus 1.03 ± 0.08) or downregulated (Hcn4, 0.16 ± 0.03 versus 0.37 ± 0.08; Kcna2, 0.35 ± 0.03 versus 0.80 ± 0.11; Kcna4, 0.79 ± 0.25 versus 1.90 ± 0.26; and Kcnj2, 0.52 ± 0.07 versus 0.78 ± 0.08) in GK ventricle compared with control ventricle. The amplitude of ventricular myocyte shortening and the intracellular Ca(2+) transient were unaltered; however, the time-to-peak shortening was prolonged and time-to-half decay of the Ca(2+) transient was shortened in GK myocytes compared with control myocytes. The results of this study demonstrate changes in expression of genes encoding various excitation-contraction coupling proteins that are associated with disturbances in myocyte shortening and intracellular Ca(2+) transport. PMID:22581745

  2. A comparative study of urine albumin ratio to creatinine in hypertensivepatients with or without left ventricular hypertrophy

    Directory of Open Access Journals (Sweden)

    M. Ansari

    2006-01-01

    Full Text Available Background and purpose: Echocardiography and routine E.C.G are standard methods for left ventricular hypertrophy (LVH. However, urine albumin to creatinine ratio (UACR recommended by recent investigations is more available and less expensive than echocardiography for detection of LVH.Materials and Methods: According to inclusion and exclusion criteria, 124 hypertensive patients (62 cases with LVH and 62 cases without LVH were selected and divided into two groups. Eechocardiography and routine E.C.G were done for all patients. Urine albumin (nephlometric methods and creatinine were measured and in patients with urine albumin>100mg/dl, ACR was calculated.Results: No significant differences were observed in mean B.U.N and creatinine, FBS and BMI between two groups. The comparison of UACR between two groups indicates that the frequency of patients with UACR> 100 mg/g in group with LVH, was more than the group without LVH (sensitivity 32.5% and specificity 92%. By combination of these tests a higher sensitivity was obtained (with Cornell criteria 37.1%.Thus, if UACR > 100 is combined with one of the markers of E.C.G for LVH diagnosis, more cases would be detected.Conclusion: Albumin to creatinine ratio in a randomized urine sample, in hypertensive patients. with LVH is higher than patients without LVH and UACR>100 can be applied for diagnosis of LVH More over by combination of E.C.G to ACR a higher sensitivity would be obtained.

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

    DEFF Research Database (Denmark)

    Fyhrquist, Frej; Eriksson, Anders

    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/D genotype with LTL and cardiovascular risk. RESULTS: Mean LTL in DD or ID genotype was shorter (8.15 and 8.14 kb, respectively), than in II genotype (8.27 kb, p=0.0005). This difference was significant in the younger subjects (55-64 years, p=0.02) but not in the older group (65-80 years, p=0.56 ). In DD but not I/D or II genotype, proportion of short telomeres (

  4. Ischemic preconditioning effect of prodromal angina is attenuated in acute myocardial infarction patients with hypertensive left ventricular hypertrophy

    International Nuclear Information System (INIS)

    Several animal experiments on acute myocardial infarction (AMI) have shown that the cardioprotective effects of ischemic preconditioning are more significant in hypertensive subjects. However, because there are no clinical data on the impact of hypertension on ischemic preconditioning in patients with AMI, whether clinical ischemic preconditioning of prodromal angina was beneficial in AMI patients with hypertension was investigated in the present study. 125 patients with a first anterior AMI who had undergone successful reperfusion therapy were divided into 2 groups, with or without hypertension, and into 2 further subgroups based on the presence or absence of prodromal angina. Dual-isotope (thallium-201(TL)/Tc-99m pyrophosphate) single-photon emission computed tomography (SPECT) was performed within 1 week of reperfusion therapy. Left ventricular (LV) function and LV mass index (LVMI) were measured by left ventriculography and echocardiography, respectively. In patients without hypertension, prodromal angina resulted in significantly less myocardial damage on TL-SPECT, better LV ejection fraction and a greater myocardial blush grade compared to patients without prodromal angina. However, these cardioprotective effects of prodromal angina were significantly diminished in hypertensive patients. Importantly, the myocardial salvage effects of prodromal angina showed a significant negative correlation with LVMI, which was significantly greater in hypertensive patients. Thantly greater in hypertensive patients. The cardioprotective effects of prodromal angina were attenuated in patients with hypertension. Hypertensive LV hypertrophy may crucially limit the effects of ischemic preconditioning in AMI. (author)

  5. Hydrogen peroxide-induced stimulation of L-type calcium current in guinea pig ventricular myocytes and its inhibition by adenosine A1 receptor activation.

    Science.gov (United States)

    Thomas, G P; Sims, S M; Cook, M A; Karmazyn, M

    1998-09-01

    Hydrogen peroxide (H2O2) produces complex cardiac effects that may involve altered calcium homeostasis. The cardiotoxic effects of H2O2 can be attenuated by adenosine A1 receptor agonists. The present study examined the effect of H2O2 on L-type Ca++ current (ICa,L) in guinea pig ventricular myocytes under two different recording conditions and the influence of adenosine receptor agonists. H2O2 (100 microM), did not have any significant effect on ICa,L, under conventional whole cell patch configuration. However, when recorded under nystatin perforated patch configuration, H2O2 caused a gradual and significant increase (84 +/- 14%) in ICa,L compared to control values. N6-cyclopentyladenosine (CPA), an adenosine A1 receptor agonist, significantly attenuated the effect of H2O2. The inhibitory effect of N6-cyclopentyladenosine was antagonized by 8cyclopentyl-1, 3-dipropylxanthine, an adenosine A1 receptor antagonist. The A2A and A3 receptor agonists, 2-p-(2-Carboxyethyl)phenethylamino-5'- N - ethylcarboxamidoadenosine (CGS-21680) and 1-deoxy-1-[6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-N-methyl-be ta-D-ribofuranuronamide, respectively, did not modulate the enhancement of ICa,L by H2O2. Moreover the effects of N6-cyclopentyladenosine were mimicked by the protein kinase C inhibitor bisindolylmaleimide. Thus, our results demonstrate a potent stimulatory effect of H2O2 on ICa,L in guinea pig ventricular myocytes. We further demonstrate that adenosine A1 receptor activation attenuates this effect. Our results suggest a potential basis for altered calcium homeostasis in response to H2O2 as well as the salutary effects of A1 receptor activation against H2O2-induced cardiotoxicity. PMID:9732380

  6. Effect of hypertrophy on left ventricular diastolic function in patients with hypertrophic cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Massimo Chiariello

    2006-09-01

    Full Text Available Background. Hypertrophic cardiomyopathy (HCM is characterized by asymmetric LV hypertrophy (LVH and impairment in diastolic function. We assess the relationship between LVH and invasive indexes of diastolic function. Methods. 21 HCM patients underwent cardiac catheterization to assess pulmonary capillary wedge pressure, LV end-diastolic pressure (measured by microtip catheters, and LV volumes (calculated by simultaneous radionuclide angiography. We calculated from LV pressure the time constant of isovolumetric relaxation (?, variable asymptote method, ms, and from LV pressure and volume the constant of chamber stiffness (k, ml-1. LVH was assessed by different indexes: maximal wall thickness, number of hypertrophied LV segments, LVH index, and Wigle’s score. Results. Wigle’s score was directly related to pulmonary capillary Wedge pressure (r=0.436, p=0.048, peak V wave of pulmonary capillary wedge pressure (r=0.503, p=0.024, LV end-diastolic pressure (r=0.643, p=0.002 and k (r=0.564, p=0.015. HCM patients were divided into 2 groups according to Wigle’s score: 10 with mild or moderate LVH (< 8, and 11 with severe LVH (? 8. HCM patients with severe LVH showed a higher pulmonary capillary Wedge pressure (15.1±7.2 vs 9.5±2.4, p=0.033, peak V wave of pulmonary capillary wedge pressure (20.7±4.6 vs 14.6±4.9, p=0.011, LV end-diastolic pressure (23.9±10.9 vs 10.6±2.5, p=0.002, k (0.0465±0.032 vs 0.015±0.007, p=0.022 and LV outflow tract gradient (72±36 mmHg vs 29±30 mmHg, p=0.01. ? was similar in the two groups. Other indexes of LVH were not related to diastolic function. Conclusions. Wigle’s score is the only index of LVH that relates to invasive indices of diastolic function.

  7. Effect of hypertrophy on left ventricular diastolic function in patients with hypertrophic cardiomyopathy

    Science.gov (United States)

    CIAMPI, QUIRINO; BETOCCHI, SANDRO; LOSI, MARIA ANGELA; LOMBARDI, RAFFAELLA; VILLARI, BRUNO; CHIARIELLO, MASSIMO

    2006-01-01

    Background. Hypertrophic cardiomyopathy (HCM) is characterized by asymmetric LV hypertrophy (LVH) and impairment in diastolic function. We assess the relationship between LVH and invasive indexes of diastolic function. Methods. 21 HCM patients underwent cardiac catheterization to assess pulmonary capillary wedge pressure, LV end-diastolic pressure (measured by microtip catheters), and LV volumes (calculated by simultaneous radionuclide angiography). We calculated from LV pressure the time constant of isovolumetric relaxation (?, variable asymptote method, ms), and from LV pressure and volume the constant of chamber stiffness (k, ml?1). LVH was assessed by different indexes: maximal wall thickness, number of hypertrophied LV segments, LVH index, and Wigle’s score. Results. Wigle’s score was directly related to pulmonary capillary Wedge pressure (r=0.436, p=0.048), peak V wave of pulmonary capillary wedge pressure (r=0.503, p=0.024), LV end-diastolic pressure (r=0.643, p=0.002) and k (r=0.564, p=0.015). HCM patients were divided into 2 groups according to Wigle’s score: 10 with mild or moderate LVH (< 8), and 11 with severe LVH (? 8). HCM patients with severe LVH showed a higher pulmonary capillary Wedge pressure (15.1±7.2 vs 9.5±2.4, p=0.033), peak V wave of pulmonary capillary wedge pressure (20.7±4.6 vs 14.6±4.9, p=0.011), LV end-diastolic pressure (23.9±10.9 vs 10.6±2.5, p=0.002), k (0.0465±0.032 vs 0.015±0.007, p=0.022) and LV outflow tract gradient (72±36 mmHg vs 29±30 mmHg, p=0.01).? was similar in the two groups. Other indexes of LVH were not related to diastolic function. Conclusions. Wigle’s score is the only index of LVH that relates to invasive indices of diastolic function. PMID:21977259

  8. Calmodulin kinase II and protein kinase C mediate the effect of increased intracellular calcium to augment late sodium current in rabbit ventricular myocytes.

    Science.gov (United States)

    Ma, Jihua; Luo, Antao; Wu, Lin; Wan, Wei; Zhang, Peihua; Ren, Zhiqiang; Zhang, Shuo; Qian, Chunping; Shryock, John C; Belardinelli, Luiz

    2012-04-15

    An increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) augments late sodium current (I(Na.L)) in cardiomyocytes. This study tests the hypothesis that both Ca(2+)-calmodulin-dependent protein kinase II (CaMKII) and protein kinase C (PKC) mediate the effect of increased [Ca(2+)](i) to increase I(Na.L). Whole cell and open cell-attached patch clamp techniques were used to record I(Na.L) in rabbit ventricular myocytes dialyzed with solutions containing various concentrations of [Ca(2+)](i). Dialysis of cells with [Ca(2+)](i) from 0.1 to 0.3, 0.6, and 1.0 ?M increased I(Na.L) in a concentration-dependent manner from 0.221 ± 0.038 to 0.554 ± 0.045 pA/pF (n = 10, P < 0.01) and was associated with an increase in mean Na(+) channel open probability and prolongation of channel mean open-time (n = 7, P < 0.01). In the presence of 0.6 ?M [Ca(2+)](i), KN-93 (10 ?M) and bisindolylmaleimide (BIM, 2 ?M) decreased I(Na.L) by 45.2 and 54.8%, respectively. The effects of KN-93 and autocamtide-2-related inhibitory peptide II (2 ?M) were not different. A combination of KN-93 and BIM completely reversed the increase in I(Na.L) as well as the Ca(2+)-induced changes in Na(+) channel mean open probability and mean open-time induced by 0.6 ?M [Ca(2+)](i). Phorbol myristoyl acetate increased I(Na.L) in myocytes dialyzed with 0.1 ?M [Ca(2+)](i); the effect was abolished by Gö-6976. In summary, both CaMKII and PKC are involved in [Ca(2+)](i)-mediated augmentation of I(Na.L) in ventricular myocytes. Inhibition of CaMKII and/or PKC pathways may be a therapeutic target to reduce myocardial dysfunction and cardiac arrhythmias caused by calcium overload. PMID:22189558

  9. 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 increas 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

  10. Na-Ca exchange and the trigger for sarcoplasmic reticulum Ca release: studies in adult rabbit ventricular myocytes.

    OpenAIRE

    Litwin, S. E.; Li, J.; Bridge, J. H.

    1998-01-01

    The importance of Na-Ca exchange as a trigger for sarcoplasmic reticulum (SR) Ca release remains controversial. Therefore, we measured whole-cell Ca currents (ICa), Na-Ca exchange currents (INaCa), cellular contractions, and intracellular Ca transients in adult rabbit cardiac myocytes. We found that changing pipette Na concentration markedly affected the relationship between cell shortening (or Ca transients) and voltage, but did not affect the Ca current-voltage relationship. We then inhibit...

  11. The influence of cell dimensions on the vulnerability of ventricular myocytes to lethal injury by high-intensity electrical fields / Influência das dimensões celulares sobre a vulnerabilidade de miócitos ventriculares ao efeito letal de campos elétricos de alta intensidade

    Scientific Electronic Library Online (English)

    Jair Trapé, Goulart; Pedro Xavier de, Oliveira; José Wilson Magalhães, Bassani; Rosana Almada, Bassani.

    2012-12-01

    Full Text Available SciELO Brazil | Language: English Abstract in portuguese Campos elétricos de alta intensidade (HIEF) são aplicados ao miocárdio durante desfibrilação e cardioversão. Embora eficazes na reversão de arritmias potencialmente letais, HIEF podem lesar cardiomiócitos por eletropermeabilização da membrana. Neste estudo, a influência das dimensões celulares sobre [...] o efeito letal de HIEF foi estudada em cardiomiócitos isolados de rato alinhados paralelamente ao campo. A máxima variação do potencial de membrana induzida pelo campo (?Vmax) foi calculada com o modelo de Klee-Plonsey. As células estudadas foram distribuídas em dois pares de grupos de acordo com seu comprimento e largura. A intensidade limiar do campo não dependeu da largura celular, mas sim do comprimento (menor nas células mais longas, p Abstract in english Application of high intensity electric fields (HIEF) to the myocardium is commonly used for cardiac defibrillation/cardioversion. Although effective at reversing life-threatening arrhythmias, HIEF may cause myocyte damage due to membrane electropermeabilization. In this study, the influence of cell [...] length and width on HIEF-induced lethal injury was analyzed in isolated rat cardiomyocytes in parallel alignment with the field. The field-induced maximum variation of membrane potential (?Vmax) was estimated with the Klee-Plonsey model. The studied myocyte population was arranged in two group pairs for comparison: the longest vs. the shortest cells, and the widest vs. narrowest cells. Threshold field intensity was significantly lower in the longest vs. shortest myocytes, whereas cell width influence was not significant. The threshold ?Vmax was comparable in all groups. Likewise, a significant leftward shift of the lethality curve (i.e., relationship of the probability of lethality vs. field intensity) of the longest cells was observed, evidencing greater sensitivity to HIEF-induced damage. However, the lethality curve as a function of ?Vmax was similar in all groups, confirming a prediction of the Klee-Plonsey model. The similar results for excitation and injury at threshold and HIEF stimulation, respectively, indicate that: a) the effect of cell length on the sensitivity to the field would be attributable to differences in field-induced membrane polarization that lead to excitation or lethal electroporation; b) the Klee-Plonsey model seems to be reliable for analysis of cell interaction with HIEF; c) it is possible that increased cell length in hypertrophied hearts enhances myocyte fragility upon defibrillation/cardioversion.

  12. Antihypertensive agents prevent nephrosclerosis and left ventricular hypertrophy induced in rats by prolonged inhibition of nitric oxide synthesis.

    Science.gov (United States)

    Akuzawa, N; Nakamura, T; Kurashina, T; Saito, Y; Hoshino, J; Sakamoto, H; Sumino, H; Ono, Z; Nagai, R

    1998-06-01

    We investigated the ability of the angiotensin converting enzyme (ACE) inhibitor imidapril hydrochloride, and of the calcium channel blocker amlodipine besilate, to prevent nephrosclerosis and left ventricular hypertrophy (LVH) in rats with hypertension induced by chronic inhibition of nitric oxide (NO). Male Wistar rats were given distilled water (control), NG-nitro-L-arginine methyl ester (L-NAME) 500 mg/L, L-NAME plus imidapril 10 mg/L or 100 mg/L, or L-NAME plus amlodipine 50 mg/L or 100 mg/L in the drinking water (n = 10-12). We then collected 24-h urine samples at 2, 4, and 6 weeks, obtained blood samples at 6 weeks, and histologically examined the kidney and heart. L-NAME markedly reduced the levels of NO metabolites in serum and urine while increasing the tail-cuff blood pressure, the urinary albumin level (1.90 +/- 0.65 v 0.05 +/- 0.02 mg/day/100 g in control), and the area of the left ventricular wall (83.3 +/- 3.0 v 69.8 +/- 1.8 mm2 in control). Nephrosclerosis and myocardial interstitial fibrosis were documented histologically. The plasma renin activity was significantly higher in rats treated with L-NAME than in the control rats. The concomitant administration of imidapril (10 mg/L) with L-NAME completely normalized the tail-cuff pressure, the LVH (70.8 +/- 1.8 mm2), the albuminuria (0.05 +/- 0.01 mg/day/100 g), and the histologic changes. Amlodipine (50 mg/L) also ameliorated the L-NAME-induced effects, but to a lesser extent. Thus, the chronic inhibition of NO synthesis in rats produced nephrosclerosis and LVH that were effectively prevented by giving imidapril at a dose lower than that of amlodipine. We conclude that ACE inhibitors can prevent nephrosclerosis and LVH even in the presence of a reduction in NO production, implying that in rats the inhibition of the renin-angiotensin system is more effective than the blockade of calcium channels in preventing hypertensive tissue injury. PMID:9657629

  13. Uncontrolled hypertension is associated with coronary artery calcification and electrocardiographic left ventricular hypertrophy : a case-control study

    DEFF Research Database (Denmark)

    Nielsen, M L; Pareek, Manan

    2015-01-01

    We conducted a 1:2 matched case-control study in order to evaluate whether the prevalence of coronary artery calcium (CAC) and electrocardiographic left ventricular hypertrophy (LVH) or strain was higher in patients with uncontrolled hypertension than in subjects from the general population, and evaluate the association between CAC and LVH in patients with uncontrolled hypertension. Cases were patients with uncontrolled hypertension, whereas the controls were random individuals from the general population without cardiovascular disease. CAC score was assessed using a non-contrast computed tomographic scan. LVH was evaluated using the Sokolow-Lyon voltage combination and Cornell voltage-duration product, respectively. Associations between CAC, LVH and traditional cardiovascular risk factors were tested by means of ordinal, conditional and classic binary logistic regression models. We found that uncontrolled hypertension was independently associated with both an ordinal CAC score category (odds ratio (OR) 3.9 (95% CI, 1.6-9.1), P=0.002), the presence of CAC score>99 (OR 4.5 (95% CI, 1.4-14.7), P=0.01) and electrocardiographic LVH (OR 10.1 (95% CI, 3.4-30.2), P<0.001) on both univariate and multivariable analyses. There was, however, no correlation between CAC and LVH. The lack of an association between CAC and LVH suggests that they are markers of different complications of hypertension and may have independent predictive values. Patients with both CAC and LVH may be at higher risk than those in whom only one of these markers is present.Journal of Human Hypertension advance online publication, 2 October 2014; doi:10.1038/jhh.2014.88.

  14. Effects of valsartan and nebivolol on blood pressure, QT dispersion and left ventricular hypertrophy in hypertensive patients

    Directory of Open Access Journals (Sweden)

    Luminita L??ea

    2010-06-01

    Full Text Available Objectives: The aim of this study was to analyze the antihypertensiveeffect of Valsartan and Nebivolol and their effects on QT dispersion and left ventricular hypertrophy (LVH in the treatment of naive hypertensive patients.Methods: A prospective study with a six-month follow-up was conducted on hypertensive patients with LVH and mild/ moderate essential hypertension. The patients were randomly assigned to Valsartan (80 to 160 mg/day or Nebivolol (5 to 10 mg/day groups. The study group consistedof 108 patients, 55 in the Valsartan group and 53 in the Nebivolol group.Results: The range of mean systolic blood pressure (SBP varied from 152±17 (baseline to 132±17 mmHg (follow-up in the Valsartan group (p<0.001; from 146±13 to 125±14 mmHg in the Nebivolol group (p<0.001. The decrease in mean diastolic blood pressure (DBP was 9.5±2.5 mmHg in the Valsartan group and 12.3±5.0 mmHg in the Nebivolol group. A significant reduction in QT and corrected QT (Bazett’s formula dispersion was observed in both groups, with a slightly higher reduction in the Valsartan group. Echocardiography showed a decreasein the left ventricle mass (LVM indices (p<0.05 in both groups with a greater reduction in the Valsartan group.Conclusion: Valsartan treatment was as effective as Nebivolol in reducing the 24 hour- SBP after a 6 month treatment. Nebivolol treatment proved to be superior to Valsartan in reducing DBP. Both therapies were effective in reducing the LVH; Valsartan proved to be superior to Nebivolol in reducing the QT interval indexes in relation to blood pressure and LVM reduction.

  15. Prolonged corrected QT interval is predictive of future stroke events even in subjects without ECG-diagnosed left ventricular hypertrophy.

    Science.gov (United States)

    Ishikawa, Joji; Ishikawa, Shizukiyo; Kario, Kazuomi

    2015-03-01

    We attempted to evaluate whether subjects who exhibit prolonged corrected QT (QTc) interval (?440 ms in men and ?460 ms in women) on ECG, with and without ECG-diagnosed left ventricular hypertrophy (ECG-LVH; Cornell product, ?244 mV×ms), are at increased risk of stroke. Among the 10 643 subjects, there were a total of 375 stroke events during the follow-up period (128.7±28.1 months; 114 142 person-years). The subjects with prolonged QTc interval (hazard ratio, 2.13; 95% confidence interval, 1.22-3.73) had an increased risk of stroke even after adjustment for ECG-LVH (hazard ratio, 1.71; 95% confidence interval, 1.22-2.40). When we stratified the subjects into those with neither a prolonged QTc interval nor ECG-LVH, those with a prolonged QTc interval but without ECG-LVH, and those with ECG-LVH, multivariate-adjusted Cox proportional hazards analysis demonstrated that the subjects with prolonged QTc intervals but not ECG-LVH (1.2% of all subjects; incidence, 10.7%; hazard ratio, 2.70, 95% confidence interval, 1.48-4.94) and those with ECG-LVH (incidence, 7.9%; hazard ratio, 1.83; 95% confidence interval, 1.31-2.57) had an increased risk of stroke events, compared with those with neither a prolonged QTc interval nor ECG-LVH. In conclusion, prolonged QTc interval was associated with stroke risk even among patients without ECG-LVH in the general population. PMID:25534703

  16. Uncontrolled hypertension is associated with coronary artery calcification and electrocardiographic left ventricular hypertrophy: a case-control study.

    Science.gov (United States)

    Nielsen, M L; Pareek, M; Gerke, O; Diederichsen, S Z; Greve, S V; Blicher, M K; Sand, N P R; Mickley, H; Diederichsen, A C P; Olsen, M H

    2015-05-01

    We conducted a 1:2 matched case-control study in order to evaluate whether the prevalence of coronary artery calcium (CAC) and electrocardiographic left ventricular hypertrophy (LVH) or strain was higher in patients with uncontrolled hypertension than in subjects from the general population, and evaluate the association between CAC and LVH in patients with uncontrolled hypertension. Cases were patients with uncontrolled hypertension, whereas the controls were random individuals from the general population without cardiovascular disease. CAC score was assessed using a non-contrast computed tomographic scan. LVH was evaluated using the Sokolow-Lyon voltage combination and Cornell voltage-duration product, respectively. Associations between CAC, LVH and traditional cardiovascular risk factors were tested by means of ordinal, conditional and classic binary logistic regression models. We found that uncontrolled hypertension was independently associated with both an ordinal CAC score category (odds ratio (OR) 3.9 (95% CI, 1.6-9.1), P=0.002), the presence of CAC score>99 (OR 4.5 (95% CI, 1.4-14.7), P=0.01) and electrocardiographic LVH (OR 10.1 (95% CI, 3.4-30.2), P<0.001) on both univariate and multivariable analyses. There was, however, no correlation between CAC and LVH. The lack of an association between CAC and LVH suggests that they are markers of different complications of hypertension and may have independent predictive values. Patients with both CAC and LVH may be at higher risk than those in whom only one of these markers is present. PMID:25273860

  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.Keywords: hypertension, normotensive, echocardiography, Sokolow–Lyon

  18. 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

    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 <90¿mm¿Hg and ECG-LVH by Cornell voltage-duration product and/or Sokolow–Lyon voltage criteria, randomized to losartan- or atenolol-based treatment with a mean follow-up of 4.8 years. The composite end point of cardiovascular death, non-fatal myocardial infarction (MI) or stroke occurred in 179 (13.6%) patients. In Cox regression models controlling for treatment, Framingham risk score, as well as baseline and in-treatment BP, less severe in-treatment ECG-LVH by Cornell product and Sokolow–Lyon voltage was associated with 17 and 25% risk reduction for the composite end point (adjusted hazard ratio (HR) 0.83, 95% confidence interval (95% CI:) 0.75–0.92, P=0.001 per 1050¿mm × ms (1 s.d.) lower Cornell product; and HR 0.75, 95% CI: 0.65–0.87, P<0.001 per 10.5¿mm (1 s.d.) lower Sokolow–Lyon voltage). In parallel analyses, lower Cornell product and Sokolow–Lyon voltage were associated with lower risks of cardiovascular mortality and MI, and lower Sokolow–Lyon voltage with lower risk of stroke. Lower Cornell product and Sokolow–Lyon voltage during antihypertensive therapy are associated with lower likelihoods of cardiovascular events in patients with ISH.

  19. Tc-99m sestaMIBI SPECT imaging in angina patients with echocardiographic left ventricular hypertrophy (LVH)

    International Nuclear Information System (INIS)

    Left ventricular hypertrophy (LVH) is relatively common, occurring in 15-20% of the general population. LVH were known to exert an adverse influence on the accuracy of myocardial perfusion scintigraphy. However, most studies were done in the patients having hypertension. The diagnostic accuracy of the stress myocardial perfusion scan in the normotensive patients with LVH for the detection of significant coronary artery disease has not been separately examined. This study was prepared to determine the diagnostic accuracy of Tc-99m myocardial perfusion scan in patients with echocardiographic LVH. Tc-99m sestaMIBI myocardial scan was performed with either exercise (n=40) or adenosine (n=44) stress in 84 consecutive anginal patients with normal ECG. Fifty nine patients had significant coronary artery disease (>50%) in coronary angiogram. Overall sensitivity and specificity of the SPECT imaging were 88%, and 84% respectively. The patients were divided into two groups ; 1) LVH= patients with echocardiographic LVH(n=29) and 2) No LVH =patients without echocardiographic LVH(n=55). Sensitivities were 88% in both groups. Specificities were 67% in LVH and 100% in No LVH group ( p < 0.05). Fifty seven patients were normotensive and analyzed separately (LVH group =20, No LVH group = 37). Exercise stress was done in 29 and adenosine in 28 patients. Sensitivities and specificities were not significantly different in LVH and No LVH groups (83% vs 86%, p=NS and 88% vs 100%, p= NS) for% vs 86%, p=NS and 88% vs 100%, p= NS) for the detection of coronary artery disease. Echocardiographic LVH does not appear to affect the diagnostic value of the Tc-99m sestaMIBI SPECT imaging in the normotensive angima patients

  20. Contractility of ventricular myocytes is well preserved despite altered mechanisms of Ca2+ transport and a changing pattern of mRNA in aged type 2 Zucker diabetic fatty rat heart.

    Science.gov (United States)

    Howarth, F C; Qureshi, M A; Hassan, Z; Isaev, D; Parekh, K; John, A; Oz, M; Raza, H; Adeghate, E; Adrian, T E

    2012-02-01

    There has been a spectacular rise in the global prevalence of type 2 diabetes mellitus and cardiovascular complications are the major cause of morbidity and mortality in diabetic patients. The objective of the study was to investigate ventricular myocyte shortening, intracellular Ca(2+) signalling and expression of genes encoding cardiac muscle proteins in the aged Zucker diabetic fatty (ZDF) rat. There was a fourfold elevation in non-fasting blood glucose in ZDF rats (478.43 ± 29.22 mg/dl) compared to controls (108.22 ± 2.52 mg/dl). Amplitude of shortening, time to peak (TPK) and time to half (THALF) relaxation of shortening were unaltered in ZDF myocytes compared to age-matched controls. Amplitude and THALF decay of the Ca(2+) transient were unaltered; however, TPK Ca(2+) transient was prolonged in ZDF myocytes (70.0 ± 3.2 ms) compared to controls (58.4 ± 2.3 ms). Amplitude of the L-type Ca(2+) current was reduced across a wide range of test potentials (-30 to +40 mV) in ZDF myocytes compared to controls. Sarcoplasmic reticulum Ca(2+) content was unaltered in ZDF myocytes compared to controls. Expression of genes encoding cardiac muscle proteins, membrane Ca(2+) channels, and cell membrane ion transport and intracellular Ca(2+) transport proteins were variously altered. Myh6, Tnnt2, Cacna2d3, Slc9a1, and Atp2a2 were downregulated while Myl2, Cacna1g, Cacna1h, and Atp2a1 were upregulated in ZDF ventricle compared to controls. The results of this study have demonstrated that preserved ventricular myocyte shortening is associated with altered mechanisms of Ca(2+) transport and a changing pattern of genes encoding a variety of Ca(2+) signalling and cardiac muscle proteins in aged ZDF rat. PMID:22009485

  1. Massa ventricular e critérios eletrocardiográficos de hipertrofia: avaliação de um novo escore Ventricular mass and electrocardiographic criteria of hypertrophy: evaluation of new score

    Directory of Open Access Journals (Sweden)

    Cléber do Lago Mazzaro

    2008-04-01

    Full Text Available FUNDAMENTO: A hipertrofia ventricular esquerda (HVE é um importante e independente fator de risco cardiovascular. Inexistem, no Brasil, estudos desenhados para testar a eficácia do eletrocardiograma (ECG no diagnóstico desse grave processo patológico. OBJETIVO: Avaliar um novo escore eletrocardiográfico para diagnóstico de HVE pelo ECG: soma da maior amplitude da onda S com a maior da onda R no plano horizontal, multiplicando-se o resultado pela duração do QRS [(S+R X QRS] e comparando-o com os critérios eletrocardiográficos clássicos. MÉTODOS: Foram analisados os ecocardiogramas e ECG de 1.204 pacientes hipertensos em tratamento ambulatorial. Avaliou-se o índice de massa do ventrículo esquerdo (IMVE pelo ecocardiograma, firmando-se o diagnóstico de HVE quando > 96 g/m² para mulheres e > 116 g/m² para homens. No ECG analisaram-se quatro critérios clássicos de HVE, além do novo escore a ser testado. RESULTADOS: Todos os índices estudados tiveram correlação estatisticamente significativa com a massa calculada do ventrículo esquerdo (VE. Porém, o novo escore foi o que apresentou maior correlação (r = 0,564. Os outros critérios apresentaram as seguintes correlações: Romhilt-Estes (r = 0,464; Sokolow-Lyon (r = 0,419; Cornell voltagem (r = 0,377; Cornell duração (r = 0,444. Para avaliação da acurácia do índice testado, utilizou-se o ponto de corte de 2,80 mm.s. Com esse valor foram obtidas as seguintes cifras para sensibilidade e especificidade: 35,2% e 88,7%, respectivamente. CONCLUSÃO: Todos os critérios eletrocardiográficos para avaliação da massa do VE apresentaram baixa sensibilidade. O novo escore foi o que apresentou melhor correlação com o IMVE em relação aos outros avaliados.BACKGROUND: The left ventricular hypertrophy (LVH is an important and independent cardiovascular risk factor. There is a scarcity of studies in Brazil designed to test the efficacy of the electrocardiogram (ECG in the diagnosis of this important pathological process. OBJECTIVE: To evaluate a new electrocardiographic score for the diagnosis of LVH by ECG: the sum of the highest amplitude of the S wave and the highest amplitude of the R wave on the horizontal plane, multiplied by the result of the QRS duration [(S+R X QRS] and comparing it with the classic electrocardiographic criteria. METHODS: The echocardiograms and ECG of 1,204 hypertensive patients receiving outpatient care were evaluated. The left ventricular mass index (LVMI was assessed by the echocardiogram, with a diagnosis of LVH when the LVMI was > 96 g/m² for women and > 116 g/m² for men. Four classic criteria of LVH were analyzed at the ECG, in addition to the new score to be tested. RESULTS: In general, the studied ECG-LVH criteria showed significant statistical correlation to the echocardiographic LVMI. The (R+S X QRS index, using 2.80 mm.s as the cutoff value, provided test accuracy regarding sensibility and specificity of 35.2% and 88.71%, respectively, representing the best correlation to LVMI (r=0.564 when compared to the other indexes: Romhilt-Estes (r=0.464; Sokolow-Lyon (r=0.419; Cornell voltage (r=0.377; Cornell product r=0.444. CONCLUSION: All the electrocardiographic criteria used for the assessment of the LV mass presented low sensitivity. The new score presented the best correlation with LVMI when compared to the other indexes.

  2. Calmodulin mutations associated with long QT syndrome prevent inactivation of cardiac L-type Ca(2+) currents and promote proarrhythmic behavior in ventricular myocytes.

    Science.gov (United States)

    Limpitikul, Worawan B; Dick, Ivy E; Joshi-Mukherjee, Rosy; Overgaard, Michael T; George, Alfred L; Yue, David T

    2014-09-01

    Recent work has identified missense mutations in calmodulin (CaM) that are associated with severe early-onset long-QT syndrome (LQTS), leading to the proposition that altered CaM function may contribute to the molecular etiology of this subset of LQTS. To date, however, no experimental evidence has established these mutations as directly causative of LQTS substrates, nor have the molecular targets of CaM mutants been identified. Here, therefore, we test whether expression of CaM mutants in adult guinea-pig ventricular myocytes (aGPVM) induces action-potential prolongation, and whether affiliated alterations in the Ca(2+) regulation of L-type Ca(2+) channels (LTCC) might contribute to such prolongation. In particular, we first overexpressed CaM mutants in aGPVMs, and observed both increased action potential duration (APD) and heightened Ca(2+) transients. Next, we demonstrated that all LQTS CaM mutants have the potential to strongly suppress Ca(2+)/CaM-dependent inactivation (CDI) of LTCCs, whether channels were heterologously expressed in HEK293 cells, or present in native form within myocytes. This attenuation of CDI is predicted to promote action-potential prolongation and boost Ca(2+) influx. Finally, we demonstrated how a small fraction of LQTS CaM mutants (as in heterozygous patients) would nonetheless suffice to substantially diminish CDI, and derange electrical and Ca(2+) profiles. In all, these results highlight LTCCs as a molecular locus for understanding and treating CaM-related LQTS in this group of patients. PMID:24816216

  3. 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-?-cyclodextrin (M?CD) to deplete cholesterol and disrupt caveolae. Buoyant caveolin-enriched microdomains (BCEMs) were prepared from M?CD-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 M?CD treatment. Selective activation of ?-, ?1-, and ?2-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 altered abundance in BCEMs following AR activation, suggesting signaling complexes are preformed in BCEMs to ensure a rapid and high fidelity response to adrenergic stimulation in cardiac muscle. PMID:25561500

  4. SEA0400, a novel Na+/Ca2+ exchanger inhibitor, reduces calcium overload induced by ischemia and reperfusion in mouse ventricular myocytes.

    Science.gov (United States)

    Wang, J; Zhang, Z; Hu, Y; Hou, X; Cui, Q; Zang, Y; Wang, C

    2007-01-01

    Given the potential clinical benefit of inhibiting Na+/Ca2+ exchanger (NCX) activity during myocardial ischemia reperfusion (I/R), pharmacological approaches have been pursued to both inhibit and clarify the importance of this exchanger. SEA0400 was reported to have a potent NCX selectivity. Thus, we examined the effect of SEA0400 on NCX currents and I/R induced intracellular Ca2+ overload in mouse ventricular myocytes using patch clamp techniques and fluorescence measurements. Ischemia significantly inhibited inward and outward NCX current (from -0.04+/-0.01 nA to 0 nA at -100 mV; from 0.23+/-0.08 nA to 0.11+/-0.03 nA at +50 mV, n=7), Subsequent reperfusion not only restored the current rapidly but enhanced the current amplitude obviously, especially the outward currents (from 0.23+/-0.08 nA to 0.49+/-0.12 nA at +50 mV, n=7). [Ca2+]i, expressed as the ratio of Fura-2 fluorescence intensity, increased to 138+/-7% (PNCX current and the increase of [Ca2+]i during I/R can be blocked by SEA0400 in a dose-dependent manner with an EC50 value of 31 nM and 28 nM for the inward and outward NCX current, respectively. The results suggested that SEA0400 is a potent NCX inhibitor, which can protect mouse cardiac myocytes from Ca2+ overload during I/R injuries. PMID:16497099

  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-?-cyclodextrin (M?CD) to deplete cholesterol and disrupt caveolae. Buoyant caveolin-enriched microdomains (BCEMs) were prepared from M?CD-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 M?CD treatment. Selective activation of ?-, ?1-, and ?2-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 altered abundance in BCEMs following AR activation, suggesting signaling complexes are preformed in BCEMs to ensure a rapid and high fidelity response to adrenergic stimulation in cardiac muscle. PMID:25561500

  6. Electrocardiographic left ventricular hypertrophy in type 1 diabetes. Prevalence and relation to coronary heart disease and cardiovascular risk factors: The Eurodiab IDDM Complications Study

    OpenAIRE

    Cavallo Perin, Paolo; Bruno, Graziella; Gruden, Gabriella

    2005-01-01

    Objective: An excess of cardiovascular morbidity and mortality has been reported in subjects with left ventricular hypertrophy (LVH). We evaluated prevalence of ECG-LVH and associations with coronary heart disease, microvascular complications, QTc and QTd in people with type 1 diabetes. Research Design and Methods: 3113 type 1 diabetic patients across Europe were studied. LVH was defined by ECG Cornell voltage-duration product [(RaVL+SV3)xQRS duration] >2623 mm.ms in men and >1558.7 mm.ms in ...

  7. Effects of fixed combination of lisinopril plus hydrochlorothiazide on regression of left ventricular hypertrophy in patients with essential hypertension: an opened, multi-centre, prospective clinical trial.

    Science.gov (United States)

    Gerc, Vjekoslav; Begovi?, Begler; Vehabovi?, Midhat; Georgievich Voronkov, Leonid; Vataman, Eleonora; Musi?, Ljiljana; Buksa, Marko; Kusljugi?, Zumreta; Barakovi?, Fahir; Iosifovna Tchelujko, Vera; Ivanovich Dyaduk, Alexander; Alekseevna Andrievskaja, Svetlana; Eduardovich Bagrij, Andrey; Nikolaevich Polivoda, Sergey; Lazarevi?, Aleksandar; Knezevi?, Bozidarka; Hima, Faik

    2008-08-01

    The aim of this trial was to examine the effects of antihypertensive fixed combination of lisinopril plus hydrochlorothiazide (Lopril H, Bosnalijek dd, Bosnia and Herzegovina) on regression of left ventricular hypertrophy in patients with essential arterial hypertension. We included 297 patients in our trial, aged 54.65+/-9.6 years, with treated or untreated hypertension and with high risk of cardiac events, in an opened trial of therapy based on lisinopril plus hydrochlorothiazide. Patients from five European countries were followed up for a period of 12 weeks. Duration of treatment was 12 weeks. We adjusted daily doses of lisinopril plus hydrochlorothiazide after every clinical examination and recorded adverse effects of drugs. In the beginning and after 12 weeks of treatment, 277 patients (93.2%) underwent 2-dimensional echocardiography and there were 186 patients evaluated for efficacy of treatment on left ventricular hypertrophy (LVH). We recorded a regression of index mass LVH (168.56 vs 161.51 g/m2, P<0.0001), and regression was something more in women vs men. We recorded average reduction of left ventricular mass index for patients with LVH (N=186) by 7.05 g/m2 (4.18%) in all patients, by 6.73 g/m2 (3.93%) in men and 7.27 g/m2 (4,37%) in women. The proportion of patients who attained a regression of left ventricular mass tended to be greater in men (54.55% vs 53.21%). This research has proved regression of LVH in more than 53% patients after using fixed combination of lisinopril plus hydrochlorothiazide. PMID:18816251

  8. 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.

  9. Effects of streptomycin sulphate on I(CaL), I(Kr) and I(Ks) in guinea-pig ventricular myocytes.

    Science.gov (United States)

    Belus, Alexandra; White, Ed

    2002-06-12

    In single guinea pig ventricular myocytes, streptomycin sulphate (streptomycin) reduced intracellular Ca(2+) transients (IC(50) 1.9 mM) and contractility (IC(50) 1.0 mM), 2 mM streptomycin prolonged the action potential. Under switch voltage clamp, 2 mM streptomycin reduced the L-type Ca(2+) current (I(CaL)) amplitude and (Ca(2+)-dependent) relative inactivation at positive membrane potentials and reduced the rapid and slow components of the delayed rectifier current (I(K)). This latter effect seemed Ca(2+)-dependent, not being seen when nifedipine and BAPTA were used to reduce intracellular Ca(2+). Fifty micromolars of streptomycin had no significant effects on any parameter studied. We conclude that the negative inotropic effect of streptomycin results from blockade of I(CaL), and thus, a reduction of intracellular Ca(2+) transients, while prolongation of the action potential is more consistent with effects on I(K). These observations link mechanical and electrical effects of streptomycin that may be important, for example, when streptomycin is used to block stretch-activated events in cardiac muscle. PMID:12079681

  10. Association of pulse pressure with new-onset atrial fibrillation in patients with hypertension and left ventricular hypertrophy : the Losartan Intervention For Endpoint (LIFE) reduction in hypertension study

    DEFF Research Database (Denmark)

    Larstorp, Anne Cecilie K; Ariansen, Inger

    2012-01-01

    Previous studies have found pulse pressure (PP), a marker of arterial stiffness, to be an independent predictor of atrial fibrillation (AF) in general and hypertensive populations. We examined whether PP predicted new-onset AF in comparison with other blood pressure components in the Losartan Intervention For Endpoint reduction in hypertension study, a double-blind, randomized (losartan versus atenolol), parallel-group study, including 9193 patients with hypertension and electrocardiographic left ventricular hypertrophy. In 8810 patients with neither a history of AF nor AF at baseline, Minnesota coding of electrocardiograms confirmed new-onset AF in 353 patients (4.0%) during mean 4.9 years of follow-up. In multivariate Cox regression analyses, baseline and in-treatment PP and baseline and in-treatment systolic blood pressure predicted new-onset AF, independent of baseline age, height, weight, and Framingham Risk Score; sex, race, and treatment allocation; and in-treatment heart rate and Cornell product. PP was the strongest single blood pressure predictor of new-onset AF determined by the decrease in the -2 Log likelihood statistic, in comparison with systolic blood pressure, diastolic blood pressure, and mean arterial pressure. When evaluated in the same model, the predictive effect of systolic and diastolic blood pressures together was similar to that of PP. In this population of patients with hypertension and left ventricular hypertrophy, PP was the strongest single blood pressure predictor of new-onset AF, independent of other risk factors.

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

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Yi-hua [Department of Clinical Laboratory, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086 (China); Li, Yong-quan [Harbin Medical University, Harbin 150086 (China); Feng, Shan-li [Department of Clinical Laboratory, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086 (China); Li, Bao-xin; Pan, Zhen-wei [Department of Pharmacology, Harbin Medical University, Harbin 150086 (China); Xu, Chang-qing [Department of Pathophysiology, Harbin Medical University, Harbin 150086 (China); Li, Ting-ting [Department of Clinical Laboratory, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086 (China); Yang, Bao-feng, E-mail: syh200415@yahoo.com.cn [Department of Pharmacology, Harbin Medical University, Harbin 150086 (China)

    2010-04-16

    Capacitative calcium entry (CCE) refers to the influx of calcium through plasma membrane channels activated on depletion of endoplasmic sarcoplasmic/reticulum (ER/SR) Ca{sup 2+} 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 Ca{sup 2+} imaging, we found that the depletion of ER/SR Ca{sup 2+} stores by thapsigargin (TG) elicited a transient rise in cytoplasmic Ca{sup 2+} ([Ca{sup 2+}]{sub i}), followed by sustained increase depending on extracellular Ca{sup 2+}. But, TRP channels inhibitor (SKF96365), not L-type channels or the Na{sup +}/Ca{sup 2+} exchanger inhibitors, inhibited [Ca{sup 2+}]{sub i} relatively high. Then, we found that the stimulation of CaR with its activator gadolinium chloride (GdCl{sub 3}) or by an increased extracellular Ca{sup 2+}([Ca{sup 2+}]{sub o}) increased the concentration of intracelluar Ca{sup 2+}, whereas, the sustained elevation of [Ca{sup 2+}]{sub i} was reduced in the presence of SKF96365. Similarly, the duration of [Ca{sup 2+}]{sub i} increase was also shortened in the absence of extracellular Ca{sup 2+}. Western blot analysis showed that GdCl{sub 3} increased the expression of TRPC6, which was reversed by SKF96365. Additionally, SKF96365 reduced cardiomyocyte apoptosis induced by GdCl{sub 3}. Our results suggested that CCE exhibited in rat neonatal myocytes and CaR activation induced Ca{sup 2+}-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.

  12. Inositol 1,4,5-trisphosphate supports the arrhythmogenic action of endothelin-1 on ventricular cardiac myocytes.

    OpenAIRE

    Proven, A.; Roderick, Hl; Conway, Sj; Berridge, Mj; Horton, Jk; Capper, Sj; Bootman, Md

    2006-01-01

    Although ventricular cardiomyocytes express inositol 1,4,5-trisphosphate [Ins(1,4,5)?3] receptors, it is unclear how these Ca2+ channels contribute to the effects of Gq-coupled agonists. Endothelin-1 augmented the amplitude of pacing-evoked Ca2+ signals (positive inotropy), and caused an increasing frequency of spontaneous diastolic Ca2+-release transients. Both effects of endothelin-1 were blocked by an antagonist of phospholipase C, suggesting that Ins(1,4,5)?3 and/or diacylglycerol produ...

  13. Phenomenological modeling of cell-to-cell and beat-to-beat variability in isolated Guinea Pig ventricular myocytes.

    Science.gov (United States)

    Walmsley, John; Mirams, Gary; Bahoshy, Maya; Bollensdorff, Christian; Rodriguez, Blanca; Burrage, Kevin

    2010-01-01

    Experimental action potential (AP) recordings in isolated ventricular myoctes display significant temporal beat-to-beat variability in morphology and duration. Furthermore, significant cell-to-cell differences in AP also exist even for isolated cells originating from the same region of the same heart. However, current mathematical models of ventricular AP fail to replicate the temporal and cell-to-cell variability in AP observed experimentally. In this study, we propose a novel mathematical framework for the development of phenomenological AP models capable of capturing cell-to-cell and temporal variabilty in cardiac APs. A novel stochastic phenomenological model of the AP is developed, based on the deterministic Bueno-Orovio/Fentonmodel. Experimental recordings of AP are fit to the model to produce AP models of individual cells from the apex and the base of the guinea-pig ventricles. Our results show that the phenomenological model is able to capture the considerable differences in AP recorded from isolated cells originating from the location. We demonstrate the closeness of fit to the available experimental data which may be achieved using a phenomenological model, and also demonstrate the ability of the stochastic form of the model to capture the observed beat-to-beat variablity in action potential duration. PMID:21096356

  14. Increase in cardiac myosin heavy-chain (MyHC) alpha protein isoform in hibernating ground squirrels, with echocardiographic visualization of ventricular wall hypertrophy and prolonged contraction.

    Science.gov (United States)

    Nelson, O Lynne; Rourke, Bryan C

    2013-12-15

    Deep hibernators such as golden-mantled ground squirrels (Callospermophilus lateralis) have multiple challenges to cardiac function during low temperature torpor and subsequent arousals. As heart rates fall from over 300 beats min(-1) to less than 10, chamber dilation and reduced cardiac output could lead to congestive myopathy. We performed echocardiography on a cohort of individuals prior to and after several months of hibernation. The left ventricular chamber exhibited eccentric and concentric hypertrophy during hibernation and thus calculated ventricular mass was ~30% greater. Ventricular ejection fraction was mildly reduced during hibernation but stroke volumes were greater due to the eccentric hypertrophy and dramatically increased diastolic filling volumes. Globally, the systolic phase in hibernation was ~9.5 times longer, and the diastolic phase was 28× longer. Left atrial ejection generally was not observed during hibernation. Atrial ejection returned weakly during early arousal. Strain echocardiography assessed the velocity and total movement distance of contraction and relaxation for regional ventricular segments in active and early arousal states. Myocardial systolic strain during early arousal was significantly greater than the active state, indicating greater total contractile movement. This mirrored the increased ventricular ejection fraction noted with early arousal. However, strain rates were slower during early arousal than during the active period, particularly systolic strain, which was 33% of active, compared with the rate of diastolic strain, which was 67% of active. As heart rate rose during the arousal period, myocardial velocities and strain rates also increased; this was matched closely by cardiac output. Curiously, though heart rates were only 26% of active heart rates during early arousal, the cardiac output was nearly 40% of the active state, suggesting an efficient pumping system. We further analyzed proportions of cardiac myosin heavy-chain (MyHC) isoforms in a separate cohort of squirrels over 5 months, including time points before hibernation, during hibernation and just prior to emergence. Hibernating individuals were maintained in both a 4°C cold room and a 20°C warm room. Measured by SDS-PAGE, relative percentages of cardiac MyHC alpha were increased during hibernation, at both hibernacula temperatures. A potential increase in contractile speed, and power, from more abundant MyHC alpha may aid force generation at low temperature and at low heart rates. Unlike many models of cardiomyopathies where the alpha isoform is replaced by the beta isoform in order to reduce oxygen consumption, ground squirrels demonstrate a potential cardioprotective mechanism to maintain cardiac output during torpor. PMID:24072796

  15. Diagnóstico electrocardiográfico de la Hipertrofia Ventricular Izquierda en pacientes hipertensos. Utilidad del producto duración por voltaje del QRS / Electrocardiography Diagnosis of the Left Ventricular Hypertrophy in hypertensive patients. Usefulness of the product of the duration of voltage of QRS

    Scientific Electronic Library Online (English)

    Juan Lázaro, González Moreno; Belkis, Martínez Martínez; Olga María, Rivero González; Adys H, Salgado Friol; Pablo José, Díaz San Jorge.

    2013-09-01

    Full Text Available Introducción: las enfermedades cardiovasculares provocan la muerte de uno de cada tres cubanos. La Hipertensión arterial (HTA) y consecuentemente la Hipertrofia Ventricular Izquierda (HVI) constituye un factor de riesgo prevalente y capaz de desencadenar serias complicaciones. Objetivo: identificar [...] el comportamiento de los criterios electrocardiográficos de Sokolow, Cornell y el Producto de la Duración por el Voltaje (PDV) del QRS en pacientes con HVI ecocardiográfica. Material y Método: la muestra seleccionada coincide con el universo y consta de 76 pacientes portadores de hipertensión arterial (HTA) atendidos en la consulta de Cardiología. Se les realizó una encuesta sobre la presencia de factores de riesgo, determinación del índice de masa corporal, realización de electrocardiograma y ecocardiograma para establecer la HVI. Resultados: el 61% de los pacientes eran portadores del HVI ecocardiográfica (Prueba de Oro diagnóstica). Para los índices electrocardiográficos de Sokolow y Cornell la sensibilidad (S) fue respectivamente de 22%, y 24%, existiendo en ambos una especificidad (E) de 93%. La (S) para el PDV-Sokolow alcanzó 33%, 22% entre los hombres y 11% entre las mujeres con una (E) total de 97%, mientras el PDV-Cornell tuvo una (S) de 35%, 11% entre los hombres y 24% entre las mujeres, con una (E) total para este índice de 93%. Conclusiones: el ECG es indispensable para el diagnóstico de HVI; el PDV-C y el PDV-S son de mayor sensibilidad diagnóstica que los índices de voltaje aislados; el primero es más útil en mujeres con características epidemiológicas bien definidas. Abstract in english Introduction: cardiovascular diseases cause the death of one out of three Cubans. High Blood Pressure and consequently Left Ventricular Hyperthrophty constitutes a prevalent risk factor able to trigger serious complications. Objective: to identify the behavior of the electrocardiographic approaches [...] of Sokolow, Cornell and the Product of the Duration of Voltage of QRS in patients with Echocardiography Left Ventricular Hypertrophy. Material and Method: the sample coincides with the universe which consists of 76 patients suffering from High Blood Pressure and treated at the Consultation of Cardiology. The patients were surveyed about the presence of risk factors, body mass index and records of electrocardiogram and echocardiogram to confirm their left ventricular hypertrophy. Results: 61% of the patients had echocardiograph left ventricular hypertrophy. For the electrocardiographic indexes of Sokolow and Cornell the sensitivity was 26% and 24% respectively, both tests showed a specificity of 93%. The sensitivity for the Product of the Duration of Voltage for Sokolow reached 33% with a specificity of 97% while the Product of the Duration of Voltage for Cornell had a sensitivity of 35% and a specificity of 93%. Conclusions: ECG is essential in the diagnosis of Left Ventricular Hypertrophy, the Product of the Duration of Voltage for Cornell and the Product of the Duration of Voltage for Sokolow have a higher diagnostic sensitivity than isolated voltage indexes, the former is more useful in women with well defined epidemiological features.

  16. Endogenous endothelin 1 mediates angiotensin II-induced hypertrophy in electrically paced cardiac myocytes through EGFR transactivation, reactive oxygen species and NHE-1.

    Science.gov (United States)

    Correa, María V; Nolly, Mariela B; Caldiz, Claudia I; de Cingolani, Gladys E Chiappe; Cingolani, Horacio E; Ennis, Irene L

    2014-09-01

    Emerging evidence supports a key role for endothelin-1 (ET-1) and the transactivation of the epidermal growth factor receptor (EGFR) in angiotensin II (Ang II) action. We aim to determine the potential role played by endogenous ET-1, EGFR transactivation and redox-dependent sodium hydrogen exchanger-1 (NHE-1) activation in the hypertrophic response to Ang II of cardiac myocytes. Electrically paced adult cat cardiomyocytes were placed in culture and stimulated with 1 nmol l(-1) Ang II or 5 nmol l(-1) ET-1. Ang II increased ~45 % cell surface area (CSA) and ~37 % [(3)H]-phenylalanine incorporation, effects that were blocked not only by losartan (Los) but also by BQ123 (AT1 and ETA receptor antagonists, respectively). Moreover, Ang II significantly increased ET-1 messenger RNA (mRNA) expression. ET-1 similarly increased myocyte CSA and protein synthesis, actions prevented by the reactive oxygen species scavenger MPG or the NHE-1 inhibitor cariporide (carip). ET-1 increased the phosphorylation of the redox-sensitive ERK1/2-p90(RSK) kinases, main activators of the NHE-1. This effect was prevented by MPG and the antagonist of EGFR, AG1478. Ang II, ET-1 and EGF increased myocardial superoxide production (187?±?9 %, 149?±?8 % and 163.7?±?6 % of control, respectively) and AG1478 inhibited these effects. Interestingly, Los inhibited only Ang II whilst BQ123 cancelled both Ang II and ET-1 actions, supporting the sequential and unidirectional activation of AT1, ETA and EGFR. Based on the present evidence, we propose that endogenous ET-1 mediates the hypertrophic response to Ang II by a mechanism that involves EGFR transactivation and redox-dependent activation of the ERK1/2-p90(RSK) and NHE-1 in adult cardiomyocytes. PMID:24327206

  17. Inhibition of the sarcoplasmic reticulum Ca2+ pump with thapsigargin to estimate the contribution of Na+-Ca2+ exchange to ventricular myocyte relaxation

    Scientific Electronic Library Online (English)

    R.A., Bassani; J.W.M., Bassani.

    1717-17-01

    Full Text Available SciELO Brazil | Language: English Abstract in english Relaxation in the mammalian ventricle is initiated by Ca2+ removal from the cytosol, which is performed by three main transport systems: sarcoplasmic reticulum Ca2+-ATPase (SR-A), Na+-Ca2+ exchanger (NCX) and the so-called slow mechanisms (sarcolemmal Ca2+-ATPase and mitochondrial Ca2+ uptake). To e [...] stimate the relative contribution of each system to twitch relaxation, SR Ca2+ accumulation must be selectively inhibited, usually by the application of high caffeine concentrations. However, caffeine has been reported to often cause changes in membrane potential due to NCX-generated inward current, which compromises the reliability of its use. In the present study, we estimated integrated Ca2+ fluxes carried by SR-A, NCX and slow mechanisms during twitch relaxation, and compared the results when using caffeine application (Cf-NT) and an electrically evoked twitch after inhibition of SR-A with thapsigargin (TG-TW). Ca2+ transients were measured in 20 isolated adult rat ventricular myocytes with indo-1. For transients in which one or more transporters were inhibited, Ca2+ fluxes were estimated from the measured free Ca2+ concentration and myocardial Ca2+ buffering characteristics. NCX-mediated integrated Ca2+ flux was significantly higher with TG-TW than with Cf-NT (12 vs 7 µM), whereas SR-dependent flux was lower with TG-TW (77 vs 81 µM). The relative participations of NCX (12.5 vs 8% with TG-TW and Cf-NT, respectively) and SR-A (85 vs 89.5% with TG-TW and Cf-NT, respectively) in total relaxation-associated Ca2+ flux were also significantly different. We thus propose TG-TW as a reliable alternative to estimate NCX contribution to twitch relaxation in this kind of analysis.

  18. Outcomes in atrial fibrillation patients with and without left ventricular hypertrophy when treated with a lenient rate-control or rhythm-control strategy.

    Science.gov (United States)

    Badheka, Apurva O; Shah, Neeraj; Grover, Peeyush M; Patel, Nileshkumar J; Chothani, Ankit; Mehta, Kathan; Singh, Vikas; Deshmukh, Abhishek; Savani, Ghanshyambhai T; Rathod, Ankit; Panaich, Sidakpal S; Patel, Nilay; Arora, Shilpkumar; Bhalara, Vipulkumar; Coffey, James O; Mitrani, Raul D; Halperin, Jonathan L; Viles-Gonzalez, Juan F

    2014-04-01

    Although left ventricular (LV) hypertrophy has been proposed as a factor predisposing to atrial fibrillation (AF), its relevance to prognosis and selection of therapeutic strategies is unclear. We identified 2,105 patients with echocardiographic data on LV mass enrolled in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial. LV hypertrophy was defined as increased LV mass, stratified by American Society of Echocardiography criteria. The primary end point was all-cause mortality, secondary end point was as per AFFIRM trial definition, and tertiary end point was cardiovascular hospitalizations. We compared "strict" versus "lenient" rate control in patients with increased LV mass, and studied association of heart failure (HF) with preserved and decreased systolic function in patients with increased LV mass. Over 6 years, 332 deaths (15.7%) were reported. Adjusted hazard ratio (HR) of severely increased LV mass for all-cause mortality was 1.34 (95% confidence interval [CI] 1.01 to 1.79, p=0.045) for the overall population and 1.61 (95% CI 1.09 to 2.37, p=0.016) for the rhythm-control arm. Increased LV mass was a predictor of cardiovascular hospitalizations in the lenient rate-control group (HR 1.72, 95% CI 1.05 to 2.82, p=0.03) but not in the strict rate-control group. Severely increased LV mass was predictive of cardiovascular hospitalizations in patients with HF with preserved (HR 1.8, 95% CI 1.0 to 3.2, p=0.03) and decreased LV systolic function (HR 2.4, 95% CI 1.1 to 5.2, p=0.02). Thus, LV hypertrophy is a significant independent predictor of mortality in patients with AF, especially those managed with rhythm control. In patients with LV hypertrophy, strict rate control may be associated with better outcomes than lenient rate control. LV hypertrophy portends higher cardiovascular morbidity in patients with AF and HF. PMID:24507168

  19. Exercise training and PI3K?-induced electrical remodeling is independent of cellular hypertrophy and Akt signaling.

    Science.gov (United States)

    Yang, Kai-Chien; Tseng, Yi-Tang; Nerbonne, Jeanne M

    2012-10-01

    In contrast with pathological hypertrophy, exercise-induced physiological hypertrophy is not associated with electrical abnormalities or increased arrhythmia risk. Recent studies have shown that increased cardiac-specific expression of phosphoinositide-3-kinase-? (PI3K?), the key mediator of physiological hypertrophy, results in transcriptional upregulation of ion channel subunits in parallel with the increase in myocyte size (cellular hypertrophy) and the maintenance of myocardial excitability. The experiments here were undertaken to test the hypothesis that Akt1, which underlies PI3K?-induced cellular hypertrophy, mediates the effects of augmented PI3K? signaling on the transcriptional regulation of cardiac ion channels. In contrast to wild-type animals, chronic exercise (swim) training of mice (Akt1(-/-)) lacking Akt1 did not result in ventricular myocyte hypertrophy. Ventricular K(+) current amplitudes and the expression of K(+) channel subunits, however, were increased markedly in Akt1(-/-) animals with exercise training. Expression of the transcripts encoding inward (Na(+) and Ca(2+)) channel subunits were also increased in Akt1(-/-) ventricles following swim training. Additional experiments in a transgenic mouse model of inducible cardiac-specific expression of constitutively active PI3K? (icaPI3K?) revealed that short-term activation of PI3K? signaling in the myocardium also led to the transcriptional upregulation of ion channel subunits. Inhibition of cardiac Akt activation with triciribine in this (inducible caPI3K? expression) model did not prevent the upregulation of myocardial ion channel subunits. These combined observations demonstrate that chronic exercise training and enhanced PI3K? expression/activity result in transcriptional upregulation of myocardial ion channel subunits independent of cellular hypertrophy and Akt signaling. PMID:22824041

  20. La disfunción diastólica en pacientes hipertensos no es debida a hipertrofia ventricular izquierda / Diastolic dysfunction in hypertensive patients is not due to left ventricular hypertrophy / A disfunção diastólica em pacientes hipertensos não é devida à hipertrofia ventricular esquerda

    Scientific Electronic Library Online (English)

    Daniel, Piskorz; Alicia, Tommasi.

    2011-03-01

    Full Text Available SciELO Argentina | Language: Spanish Abstract in portuguese Introdução. .A hipertrofia ventricular esquerda (HVE) é uma complicação comum da hipertensão e pode estar associada com disfunção diastólica (DD). Objetivos. Determinar a prevalência de DD em pacientes hipertensos (HT) sem HVE. Material e métodos. Foram incluídos 98 pacientes HT, 66 pacientes sem HV [...] E e 32 pacientes com HVE medida pelo método de Devereux, considerando HVE um índice de massa ventricular esquerda >110 g/m2 em mulheres e 125 g/m2 em homens. Foi realizado Doppler pulsado do orifício da válvula mitral, e foi medida a razão velocidade instantânea pico E / velocidade instantânea pico A (VE/VA) e tempo de relaxamento isovolumétrico (TRIV), ambos foram corrigidos pela idade; e Doppler tecidual do septo interventricular, e foi medida a taxa de pico de velocidade instantânea E'/ pico de velocidade instantânea A' (VE'/VA') e de pico e velocidade instantânea E / pico de velocidade instantânea E' (VE/VE'). Resultados. A média de idade 60,3 ± 36,7 anos, 45 pacientes do sexo masculino (45,9%), 8 pacientes diabéticos (8,2%). A tabela apresenta os resultados da avaliação da função diastólica Conclusões. 1) Alta freqüência de DD em pacientes com hipertensão sem HVE; 2) A única diferença na função diastólica entre pacientes com hipertensão sem e com HVE é maior a pressão diastólica ventricular esquerda expressa por VE/VE'; 3) HVE não é causa do DD em pacientes com hipertensão. Abstract in spanish Introducción. La hipertrofia ventricular izquierda (HVI) es una complicación frecuente en hipertensión arterial y se puede acompañar de disfunción diastólica (DD). Objetivos. Determinar la prevalencia de DD en pacientes hipertensos (HT) sin HVI. Material y métodos. Se incluyeron 98 pacientes con HT, [...] 66 pacientes sin HVI y 32 pacientes con HVI medida por método de Devereux, considerándose HVI un índice de masa ventricular izquierda >110 g/m2 en mujeres y 125 g/m2 en hombres. Se efectuó Doppler pulsado del orificio valvular mitral y se midió la relación velocidad instantánea pico E/velocidad instantánea pico A (VE/VA) y el tiempo de relajación isovolumétrica (TRIV), ambos fueron corregidos por edad, y Doppler tisular del septum interventricular, midiéndose la relación velocidad instantánea pico E´/velocidad instantánea pico A´ (VE´/VA´) y velocidad instantánea pico E/velocidad instantánea pico E´ (VE/VE´). Resultados. Edad media: 60,3±36,7 años; sexo masculino: 45 pacientes (45,9 %); 8 pacientes diabéticos (8,2%). La tabla presenta los resultados de la evaluación de función diastólica. Conclusiones. 1) Alta frecuencia de DD en pacientes HT sin HVI. 2) La única diferencia en la función diastólica entre pacientes HT sin y con HVI es la mayor presión de fin de diástole del ventrículo izquierdo expresada por VE/VE´. 3) La HVI no es la causa de DD en pacientes HT. Abstract in english Background. Left ventricular hypertrophy (LVH) is a common complication of hypertension and may be associated with diastolic dysfunction (DD). Objectives. To determine the prevalence of DD in hypertensive (HT) patients without LVH. Methods and material. 98 HT patients were included, 66 with LVH and [...] 32 without LVH measured by the method ofDevereux, LVH was considered a left ventricular mass index >110 g/m2 in women and 125 g/m2 in men. Mitral valve orifice pulsed Doppler was performed and it was measured the peak instantaneous velocity ratio E/A (VE/VA) and isovolumetric relaxation time (IVRT), both were corrected by age; and tissue Doppler of the interventricular septum was also preformed, and it was measured the peak instantaneous velocity ratio E'/A' (VE'/ VA') and instantaneous velocity peak E/E' (VE/VE'). Results. Mean age 60.3±36.7 years, male 45 patients (45,9%), 8 diabetic patients (8.2%). The table presents the results of the assessment of diastolic function. Conclusions. 1) High frequency of DD in HT patients without LVH, 2) The only one difference between patients

  1. 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 (?1AR 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 ?1AR 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, however, since it does not appear to exist among diabetic AMI survivors.

  2. Comparison of the effects of an ACE inhibitor and alphabeta blocker on the progression of renal failure with left ventricular hypertrophy: preliminary report.

    Science.gov (United States)

    Suzuki, H; Moriwaki, K; Kanno, Y; Nakamoto, H; Okada, H; Chen, X M

    2001-03-01

    The aim of this study was to compare the effects of an angiotensin-converting enzyme (ACE) inhibitor and alphabeta blocker in combination with a calcium antagonist on the progression of renal function and left ventricular hypertrophy (LVH) in patients with chronic renal insufficiency and hypertension. The 65 subjects in this study were recruited from a cohort of 316 patients. The main criteria for inclusion were echocardiographic diagnosis of LVH (posterior wall thickness >12 mm) and serum creatinine of more than 1.5 mg/dl. Antihypertensive treatments were switched to the combination of amlodipine at a dose of 5 mg and benazepril at a dose of 2.5 mg daily or the combination of amlodipine at a dose of 5 mg and arotinolol at a dose of 20 mg daily at random irrespective of whether or not patients had been previously treated. The follow-up period was 2 years. Systolic and diastolic blood pressure were significantly reduced from 150/90 +/- 15/11 mmHg to 130/75 +/- 11/9 mmHg (ACE) and the levels of serum creatinine were increased significantly from 1.8 +/- 0.3 to 2.0 +/- 0.4 mg/dl (ACE). In the alphabeta-blocker group, these two values were similar and no significant changes were found. PWT was decreased from 14.2 +/- 0.6 to 12.9 +/- 0.3 cm in alphabeta blocker but was not significantly decreased in the ACE inhibitor group. In conclusion, combination therapy with a calcium antagonist and abeta blocker might be effective treatment for hypertensive patients with chronic renal insufficiency and left ventricular hypertrophy. PMID:11325074

  3. Degree and distribution of left ventricular hypertrophy as a determining factor for elevated natriuretic peptide levels in patients with hypertrophic cardiomyopathy: insights from cardiac magnetic resonance imaging.

    Science.gov (United States)

    Park, Jeong Rang; Choi, Jin-Oh; Han, Hye Jin; Chang, Sung-A; Park, Sung-Ji; Lee, Sang-Chol; Choe, Yeon Hyeon; Park, Seung Woo; Oh, Jae K

    2012-04-01

    Whether the left ventricular (LV) mass index (LVMI) and LV volumetric parameters are associated independently with natriuretic peptide levels is unclear in hypertrophic cardiomyopathy (HCM). Therefore, we investigated which parameters have an independent relationship with N-terminal pro-B type natriuretic peptide (NT-proBNP) levels in HCM patients using echocardiography and cardiac magnetic resonance imaging (CMR). A total of 103 patients with HCM (82 men, age 53 ± 12 years) were evaluated. Echocardiographic evaluations included left atrial volume index (LAVI) and early diastolic mitral inflow E velocity to early annular Ea velocity ratio (E/Ea). LVMI, maximal wall thickness and LV volumetric parameters were measured using CMR. The median value of NT-proBNP level was 387.0 pg/ml. The mean NT-proBNP level in patients with non-apical HCM (n = 69; 36 patients with asymmetric septal hypertrophy, 11 with diffuse, and 22 with mixed type) was significantly higher than in those with apical HCM (n = 34, P hypertrophy and diastolic parameters might be important in the elevation of NT-proBNP level in HCM. Therefore, further evaluation of these parameters in HCM might be warranted. PMID:21516440

  4. Contribution of ion currents to beat-to-beat variability of action potential duration in canine ventricular myocytes.

    Science.gov (United States)

    Szentandrássy, Norbert; Kistamás, Kornél; Hegyi, Bence; Horváth, Balázs; Ruzsnavszky, Ferenc; Váczi, Krisztina; Magyar, János; Bányász, Tamás; Varró, András; Nánási, Péter P

    2014-08-01

    Although beat-to-beat variability (short-term variability, SV) of action potential duration (APD) is considered as a predictor of imminent cardiac arrhythmias, the underlying mechanisms are still not clear. In the present study, therefore, we aimed to determine the role of the major cardiac ion currents, APD, stimulation frequency, and changes in the intracellular Ca(2+) concentration ([Ca(2+)]i) on the magnitude of SV. Action potentials were recorded from isolated canine ventricular cardiomyocytes using conventional microelectrode techniques. SV was an exponential function of APD, when APD was modified by current injections. Drug effects were characterized as relative SV changes by comparing the drug-induced changes in SV to those in APD according to the exponential function obtained with current pulses. Relative SV was increased by dofetilide, HMR 1556, nisoldipine, and veratridine, while it was reduced by BAY K8644, tetrodotoxin, lidocaine, and isoproterenol. Relative SV was also increased by increasing the stimulation frequency and [Ca(2+)]i. In summary, relative SV is decreased by ion currents involved in the negative feedback regulation of APD (I Ca, I Ks, and I Kr), while it is increased by I Na and I to. We conclude that drug-induced effects on SV should be evaluated in relation with the concomitant changes in APD. Since relative SV was decreased by ion currents playing critical role in the negative feedback regulation of APD, blockade of these currents, or the beta-adrenergic pathway, may carry also some additional proarrhythmic risk in addition to their well-known antiarrhythmic action. PMID:25081243

  5. Detection of incipient left ventricular hypertrophy in mild to moderate arterial hypertension with normal electrocardiogram and echocardiogram: a new use for signal-averaged electrocardiography

    Scientific Electronic Library Online (English)

    Paulo, Ginefra; Eduardo C., Barbosa; P. R., Benchimol-Barbosa; Alfredo S., Bomfim; Sílvia H., Boghossian; Angelo A., Salgado; Flávia G., Brasil; Elizabete A., Freitas; Francisco M., Albanesi Filho.

    2003-07-01

    Full Text Available SciELO Brazil | Language: English Abstract in english OBJECTIVE: To assess signal-averaged electrocardiogram (SAECG) for diagnosing incipient left ventricular hypertrophy (LVH). METHODS: A study with 115 individuals was carried out. The individuals were divided as follows: GI - 38 healthy individuals; GII - 47 individuals with mild to moderate hyperten [...] sion and normal findings on echocardiogram and ECG; and GIII - 30 individuals with hypertension and documented LVH. The magnitude vector of the SAECG was analyzed with the high-pass cutoff frequency of 40 Hz through the bidirectional four-pole Butterworth high-pass digital filter. The mean quadratic root of the total QRS voltage (RMST) and the two-dimensional integral of the QRS area of the spectro-temporal map were analyzed between 0 and 30 Hz for the frequency domain (Int FD), and between 40 and 250 Hz for the time domain (Int TD). The electrocardiographic criterion for LVH was based on the Cornell Product. Left ventricular mass was calculated with the Devereux formula. RESULTS: All parameters analyzed increased from GI to GIII, except for Int FD (GII vs GIII) and RMST log (GII vs GIII). Int TD showed greater accuracy for detecting LVH with an appropriate cutoff > 8 (sensitivity of 55%, specificity of 81%). Positive values (> 8) were found in 56.5% of the G II patients and in 18.4% of the GI patients (p

  6. Detection of incipient left ventricular hypertrophy in mild to moderate arterial hypertension with normal electrocardiogram and echocardiogram: a new use for signal-averaged electrocardiography

    Directory of Open Access Journals (Sweden)

    Paulo Ginefra

    2003-07-01

    Full Text Available OBJECTIVE: To assess signal-averaged electrocardiogram (SAECG for diagnosing incipient left ventricular hypertrophy (LVH. METHODS: A study with 115 individuals was carried out. The individuals were divided as follows: GI - 38 healthy individuals; GII - 47 individuals with mild to moderate hypertension and normal findings on echocardiogram and ECG; and GIII - 30 individuals with hypertension and documented LVH. The magnitude vector of the SAECG was analyzed with the high-pass cutoff frequency of 40 Hz through the bidirectional four-pole Butterworth high-pass digital filter. The mean quadratic root of the total QRS voltage (RMST and the two-dimensional integral of the QRS area of the spectro-temporal map were analyzed between 0 and 30 Hz for the frequency domain (Int FD, and between 40 and 250 Hz for the time domain (Int TD. The electrocardiographic criterion for LVH was based on the Cornell Product. Left ventricular mass was calculated with the Devereux formula. RESULTS: All parameters analyzed increased from GI to GIII, except for Int FD (GII vs GIII and RMST log (GII vs GIII. Int TD showed greater accuracy for detecting LVH with an appropriate cutoff > 8 (sensitivity of 55%, specificity of 81%. Positive values (> 8 were found in 56.5% of the G II patients and in 18.4% of the GI patients (p< 0.0005. CONCLUSION: SAECG can be used in the early diagnosis of LVH in hypertensive patients with normal ECG and echocardiogram.

  7. Left ventricular function and cardiac hypertrophy in the cases of mild hypertension with marked ST-T changes in electrocardiogram

    International Nuclear Information System (INIS)

    The characteristics of the hemodynamic pattern and cardiac hypertrophy of mild hypertensive patients with giant negative T waves in electrocardiogram (ECG) (group I, 12 patients) were examined by the radionuclide methods, the cardiac catheterization and the echocardiogram. As control groups, the patients of essential hypertension (EH) with high voltage in ECG (group II, 36 patients), those with high voltage and mild ST-T changes in ECG (group III, 9 patients), and the patients with normotensive hypertrophic cardiomyopathy (group IV, 8 patients) were studied. Ejection fraction and cardiac index in group I were increased compared with those in group II (p 201Tl) myocardial images was significantly lower than in group II and III (p 201Tl-uptake index in cardiac apex determined by apical/total counts was increased in group I compared with other groups. These results suggest that group I is hyperkinetic state and has marked apical hypertrophy. The possibility exists that the increased afterload might be a trigger of apical hypertropoad might be a trigger of apical hypertrophy in predisposed individuals. (author)

  8. Effect of Ca2+ Efflux Pathway Distribution and Exogenous Ca2+ Buffers on Intracellular Ca2+ Dynamics in the Rat Ventricular Myocyte: A Simulation Study.

    Czech Academy of Sciences Publication Activity Database

    Pásek, Michal; Šimurda, J.; Orchard, C.

    2014-01-01

    Ro?. 2014, ?. 2014 (2014), s. 920208. ISSN 2314-6133 R&D Projects: GA MZd(CZ) NT14301-3/2013 Institutional support: RVO:61388998 Keywords : calcium efflux * calcium buffers * cardiac myocyte * computer model Subject RIV: BO - Biophysics

  9. Left ventricular hypertrophy with exercise and ACE gene insertion/deletion polymorphism: a randomized controlled trial with losartan.

    OpenAIRE

    Myerson, Sg; Montgomery, He; Whittingham, M.; Jubb, M.; World, Mj; Humphries, Se; Pennell, Dj

    2001-01-01

    BACKGROUND: Local cardiac renin-angiotensin systems may regulate left ventricular (LV) hypertrophic responses. The absence (deletion [D]) of a 287-bp marker in the ACE gene is associated with greater myocardial ACE levels and exercise-related LV growth than is its presence (insertion [I]), an effect potentially mediated through either increased activity of the cellular growth factor angiotensin II on the angiotensin type 1 (AT(1)) receptor or increased degradation of growth-inhibiting kinins....

  10. Índice tornozelo-braquial e hipertrofia ventricular na hipertensão arterial Índice tobillo-braquial y hipertrofia ventricular en la hipertensión arterial Ankle-brachial index and ventricular hypertrophy in arterial hypertension

    Directory of Open Access Journals (Sweden)

    Pedro Ferreira de Albuquerque

    2012-01-01

    Full Text Available O Índice Tornozelo-Braquial (ITB é marcador de doença arterial obstrutiva periférica. Raros relatos correlacionam esse índice com hipertrofia ventricular esquerda (HVE, capacidade funcional (CF e escore de risco coronariano de Framingham (ERCF. O objetivo do trabalho foi verificar a correlação entre ITB, HVE, CF e ERCF em homens com hipertensão arterial (HA. Estudo prospectivo e transversal de pacientes do sexo masculino (n = 40, com idade média de 57,92 ± 7,61 anos, sem complicações cardiovasculares. Essa população foi submetida às medidas de ITB, ecocardiograma (ECO, teste ergométrico (TE e exames laboratoriais. O ITB (direito e esquerdo foi considerado anormal quando a relação entre a maior média das pressões sistólicas dos tornozelos e dos braços foi inferior ou igual a 0,9 ou superior a 1,3 mmHg. A HVE foi identificada pelo ECO transtorácico; e a CF, pelo TE. Amostras sanguíneas periféricas foram colhidas para o cálculo do ERCF. Valores normais de ITB foram encontrados em 33 pacientes (82,5%, os quais foram incluídos no Grupo I; sete pacientes (17,5% com ITB anormal constituíram o Grupo II. Os índices de massa do índice de massa do ventrículo esquerdo (IMVE ao ECO foram de 111,18 ± 34,34 g/m² (Grupo I e de 150,29 ± 34,06 g/m2 (Grupo II (p = 0,009. A prevalência de HVE foi de 4% (Grupo I e de 35,3% (Grupo II (p = 0,01, constatando-se diferenças significativas entre os grupos. Quanto à CF no TE, não se registrou diferença entre os grupos. Em relação ao ERCF, a média do Grupo I foi inferior à média do Grupo II: 13,18 ± 2,11 versus 15,28±1,79 (p = 0,019. Em HA, a presença de HVE definida pelo IMVE esteve mais presente nos casos com ITB anormal, identificando maior risco cardiovascular.El Índice Tobillo-Braquial (ITB es un marcador de enfermedad arterial obstructiva periférica. Raros relatos correlacionan ese índice con la hipertrofia ventricular izquierda (HVI, capacidad funcional (CF y puntación de riesgo coronario de Framingham (PRCF. El objetivo de este estudio fue verificar la correlación entre ITB, HVI, CF y PRCF en hombres con hipertensión arterial (HA. Estudio prospectivo y transversal de pacientes del sexo masculino (n = 40, con edad promedio de 57,92 ± 7,61 años, sin complicaciones cardiovasculares. Esa población fue sometida a las medidas de ITB, ecocardiograma (ECO, test ergométrico (TE y exámenes de laboratorio. El ITB (derecho e izquierdo, se consideró anormal cuando la relación entre la mayor media de las presiones sistólicas de los tobillos y de los brazos fue inferior o igual a 0,9 o superior a 1,3 mmHg. La HVI fue identificada por el ECO transtorácico; y la CF por el TE. Muestras sanguíneas periféricas se recogieron para el cálculo del PRCF. Valores normales de ITB fueron encontrados en 33 pacientes (82,5%, los cuales se incluyeron en el Grupo I; siete pacientes (17,5% con ITB anormal formaron el Grupo II. Los índices de masa del índice de masa del ventrículo izquierdo (IMVI al ECO fueron de 111,18 ± 34,34 g/m² (Grupo I y de 150,29 ± 34,06 g/m² (Grupo II (p = 0,009. La prevalencia de HVI fue de 4% (Grupo I y de 35,3% (Grupo II (p = 0,01, siendo comprobadas las diferencias significativas entre los grupos. En cuanto a la CF en el TE, no se registró ninguna diferencia entre los grupos. Con relación al PRCF, el promedio del Grupo I quedó por debajo del promedio del Grupo II: 13,18 ± 2,11 versus 15,28±1,79 (p = 0,019. En HA, la presencia de HVI definida por el IMVI estuvo más presente en los casos con ITB anormal, identificando un mayor riesgo cardiovascular.The ankle-brachial index (ABI is a marker of peripheral arterial disease. Very few reports have correlated this index with left ventricular hypertrophy (LVH, functional capacity (FC and Framingham risk score (FRS. The objective of this study was to verify the correlation between ABI, LVH, FC and FRS in men with arterial hypertension (AH. Prospective and cross-sectional study of male patients (n = 40 with a mean age of 57.92 ± 7.61 years and no cardiovascula

  11. [Effects of perindopril on left ventricular hypertrophy, coronary reserve and mechanical properties of the papillary muscle of the rat with renovascular arterial hypertension].

    Science.gov (United States)

    Gosse, P; Grellet, J; Bonoron, S; Tariosse, L; Besse, P; Dallocchio, M

    1987-06-01

    We investigate the effect of a new angiotensin-converting enzyme inhibitor: Perindopril (IRIS) on regression of left ventricular hypertrophy (LVH), coronary blood flow and mechanical performance of isolated papillary muscle in renovascular hypertensive (Goldblatt 2 kidneys-1 clip) Sprague-Dawley male rats. Sham operated rats (G1) and half of hypertensive rats (G2) were studied after 8 weeks. The other half of 8 weeks long hypertensive rats (G3) were treated during 8 weeks with Perindopril in drinking water at a dosage adjusted to maintain blood pressure (BP) measured with tail cuff method under 140 mmHg. The study of each rat included 1) coronary blood flow and resistance measurements under resting conditions and after coronary dilation by carbochrome infusion (9 mg/kg) using left atrial injection of radioactive microspheres (method of Wicker and Tarazi) 2) the study of mechanical performance of the isolated papillary muscle 3) weight of left ventricle after separation of septum and free wall whose subendocardial and subepicardial layers were counted separately. Results (mean +/- SD): (table; see text) MAP: mean pressure. LV/BW: left ventricular mass (mg) per gram of body weight; CR (C): minimal coronary resistance after carbochrome (mmHg/ml/min/100 mg); DL/Dt: peak velocity of shortening at L max preload; Vrelax: peak velocity of relaxation; THR: time of half relaxation; p less than 0.05; p less than 0.01 compared to SHAM. In this model, hypertension induced a 50 p. 100 LVH whose regression was nearly complete after 8 weeks of treatment with Perindopril. Minimal coronary resistance after carbochrome were higher in hypertensive rats compared to sham and return to normal after regression of LVH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2959235

  12. Ventricular Arrhythmias in Hypertrophic Cardiomyopathy- Can We Ever Predict Them?

    Directory of Open Access Journals (Sweden)

    Narayanan Namboodiri

    2010-03-01

    Full Text Available Hypertrophic cardiomyopathy (HCM is characterized by gross cardiac and myocyte hypertrophy, myocyte disarray, and interstitial fibrosis. This condition is relatively common, with a prevalence of about 1:500 in the general population. Most patients with HCM are either asymptomatic or have only minimal symptoms. In general, HCM is a relatively benign disease with an annual mortality rate of slightly less than 1% in unselected HCM populations [1,2]. However, sudden cardiac death (SCD may be the first manifestation of the disease. Approximately 60% to 70% of all patients with HCM die suddenly [3], and the fatal event is generally assumed, though not proven so far, due to ventricular arrhythmias.

  13. Fixed combination of valsartan and amlodipine: effects on the left ventricular hypertrophy regression, albuminuria reduction and endothelium function in hypertensive patients with metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Ye.I. Tarlovskaya

    2010-01-01

    Full Text Available Aim. To study effects of fixed combination of valsartan and amlodipine on of left ventricular hypertrophy (LVH regression, microalbuminuria reduction and endothelium function in hypertensive patients with metabolic syndrome (MS.Materials and methods. 20 hypertensive patients (15 females and 5 males with metabolic syndrome and a history of previous ineffective antihypertensive therapy were studied. Combined antihypertensive therapy was applied during 12-24 weeks. Amlodipine and valsartan dose was 5/160 or 10/160 mg/day depending on blood pressure level. Endothelial function, blood pressure level, urinary albumin excretion and LVH regression were estimated.Results. Blood pressure reduction to the target level was revealed. There was a significant reduction in microalbuminuria by -55.3±39.2% (?=0.022 in comparison with the baseline. Endothelium-dependent vasodilation increased in 3.6±7.2% (?=0.05 in comparison with baseline, LVH decreased by -9.1±12.4 g/m2 (?=0.021.Conclusion. Therapy with fixed combination of valsartan and amlodipine results in blood pressure and microalbuminuria reduction, endothelium-dependent vasodilation improvement, LVH regression in hypertensive patients with MS. These findings show that the fixed combination of these antihypertensives has a multifaceted impact on cardiovascular risk.

  14. Long-term plasma catecholamines in patients with hypertension and left ventricular hypertrophy treated with losartan or atenolol: ICARUS, a LIFE substudy.

    Science.gov (United States)

    Fossum, E; Olsen, M H; Høieggen, A; Wachtell, K; Reims, H M; Ibsen, H; Julius, S; Kjeldsen, S E

    2004-06-01

    Hypertension is a major risk factor for morbidity and mortality. Plasma catecholamines are linked to the pathogenesis of hypertension. Pharmacological intervention, including treatment with beta-blockers, reduces cardiovascular mortality and morbidity. In the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, the angiotensin receptor blocker losartan significantly reduced cardiovascular end points compared to the beta-blocker atenolol. Thus, for the first time, one drug was shown to be superior to another in hypertension. The present substudy examined the effects of atenolol vs losartan treatment on plasma catecholamines at rest and during hyperinsulinaemia in a cohort of 86 LIFE patients. Plasma adrenaline increased significantly from placebo treatment at baseline to year 1 of treatment (P<0.0001), and also during hyperinsulinaemia (P<0.0001). Plasma noradrenaline did not change significantly from placebo treatment at baseline to year 1, but increased significantly during hyperinsulinaemia both at baseline and at year 1 (P<0.0001 for both). There were no differences in plasma catecholamines or the relative changes between the two treatment arms at any stage. In a subset of 42 patients examined also at years 2 and 3, these findings were confirmed during long-term treatment. Thus, losartan had an effect on plasma catecholamines comparable to that with the beta-blocker atenolol in patients with hypertension and left ventricular hypertrophy at rest and during hyperinsulinaemia. We find it unlikely that a difference in sympathetic activity explains the outcome benefits of losartan over atenolol in the LIFE study. PMID:15057253

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

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    Tasi? 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 grams (323 ± 79 g vs. 328 ± 58 g. Diastolic function expressed through relation E/A was improved minimally in the group A, while it worsened by 0.1 in the group B. After 9 months, serious cardiovascular events were recorded (one infarction of myocardium and one hospitalization due to the unstable angina pectoris in two patients of the group A, while four patients of the group B. had serious CV events (1 cerebrovascular stroke and 3 hospitalizations due to unstable angina pectoris. CONCLUSION The results of our study showed that the application of Fosinopril in patients with the arterial hypertension and the left ventricle hypertrophy could efficiently block further progression of the intima-medial thickness of the common carotid artery, reduce the left ventricle mass, and improve. diastolic function of the left ventricle.

  16. 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 less than  0.04 in the F group, the difference was not significant for mitral regurgitation (p=0.7. Stroke prone NVAF patients have a higher rate of hypertension, coronary artery disease, with and without AMI, LVH and left ventricular diastolic dysfunction, but not left atrial dilatation. M-B mode echocardiography and PWD examination help to identify high-risk stroke patients among NVAF subjects; therefore, they may help in the selection of appropriate therapy for each patient.

  17. Role of t-tubules in the control of trans-sarcolemmal ion flux and intracellular Ca2+ in a model of the rat cardiac ventricular myocyte.

    Czech Academy of Sciences Publication Activity Database

    Pásek, Michal; Šimurda, J.; Orchard, C.

    2012-01-01

    Ro?. 41, ?. 6 (2012), s. 491-503. ISSN 0175-7571 Institutional research plan: CEZ:AV0Z20760514 Keywords : t-tubules * rat * cardiac myocyte * computer model * calcium Subject RIV: BO - Biophysics Impact factor: 2.274, year: 2012

  18. Alterações morfológicas e funcionais cardíacas e análise dos fatores determinantes de hipertrofia ventricular esquerda em 40 pacientes com acromegalia Cardiac morphology and performance alterations and analysis of determinant factors of left ventricular hypertrophy in 40 patients with acromegaly

    Directory of Open Access Journals (Sweden)

    Alessandra Ferri Casini

    2006-02-01

    Full Text Available A acromegalia é uma doença de alta mortalidade, especialmente em razão de complicações cardiovasculares. Com o objetivo de avaliar os fatores determinantes da hipertrofia ventricular esquerda (HVE e as alterações cardíacas na acromegalia, analisamos 40 acromegálicos submetidos a exames clínico-laboratoriais e ao ecocardiograma. As variáveis analisadas foram idade, sexo, duração de doença, hipertensão arterial (HA, intolerância à glicose/DM, uso ou não de octreotide, GH e %IGF-I. Na análise univariada, pacientes com HVE foram mais idosos (p= 0,031, apresentaram maior prevalência de HA (p= 0,009 e maiores valores da %IGF-I (p= 0,002, comparados aos sem HVE. Na análise multivariada, HA e %IGF-I foram determinantes de HVE (p= 0,035 e p= 0,016. Após a dicotomização da %IGF-I, foi criado um escore e a freqüência de HVE foi 9%, 65%, 92% x 0, 1, 2; pAcromegaly has a high mortality rate due mainly to cardiovascular complications. The aim was to evaluate the determinant factors of left ventricular hypertrophy (LVH and cardiac alterations in 40 acromegalic patients submitted to clinical-laboratorial studies and echocardiogram. The variables analyzed were age, sex, disease duration, arterial hypertension (AH, impaired glucose tolerance/DM, previous treatment with octreotide, GH and %IGF-I. Univaried analysis showed that patients with LVH were older (p= 0.031, had higher prevalence of AH (p= 0.009 and higher %IGF-I (p= 0.002, than those without LVH. Multivaried analysis showed AH and %IGF-I as determinants of LVH (p= 0.035 and p= 0.016. After dichotomizing of %IGF-I, a score was created and the frequency of LVH was 9%, 65%, 92% x 0, 1, 2; p< 0.0001. Prevalence of aortic ectasia was higher and valvar disease was smaller than reported in the literature. We conclude that AH and %IGF-I were determinants of LVH.

  19. Alterações morfológicas e funcionais cardíacas e análise dos fatores determinantes de hipertrofia ventricular esquerda em 40 pacientes com acromegalia / Cardiac morphology and performance alterations and analysis of determinant factors of left ventricular hypertrophy in 40 patients with acromegaly

    Scientific Electronic Library Online (English)

    Alessandra Ferri, Casini; Paula Bruna, Araújo; Rosita, Fontes; Sérgio Salles, Xavier; Mônica R., Gadelha.

    2006-02-01

    Full Text Available A acromegalia é uma doença de alta mortalidade, especialmente em razão de complicações cardiovasculares. Com o objetivo de avaliar os fatores determinantes da hipertrofia ventricular esquerda (HVE) e as alterações cardíacas na acromegalia, analisamos 40 acromegálicos submetidos a exames clínico-labo [...] ratoriais e ao ecocardiograma. As variáveis analisadas foram idade, sexo, duração de doença, hipertensão arterial (HA), intolerância à glicose/DM, uso ou não de octreotide, GH e %IGF-I. Na análise univariada, pacientes com HVE foram mais idosos (p= 0,031), apresentaram maior prevalência de HA (p= 0,009) e maiores valores da %IGF-I (p= 0,002), comparados aos sem HVE. Na análise multivariada, HA e %IGF-I foram determinantes de HVE (p= 0,035 e p= 0,016). Após a dicotomização da %IGF-I, foi criado um escore e a freqüência de HVE foi 9%, 65%, 92% x 0, 1, 2; p Abstract in english Acromegaly has a high mortality rate due mainly to cardiovascular complications. The aim was to evaluate the determinant factors of left ventricular hypertrophy (LVH) and cardiac alterations in 40 acromegalic patients submitted to clinical-laboratorial studies and echocardiogram. The variables analy [...] zed were age, sex, disease duration, arterial hypertension (AH), impaired glucose tolerance/DM, previous treatment with octreotide, GH and %IGF-I. Univaried analysis showed that patients with LVH were older (p= 0.031), had higher prevalence of AH (p= 0.009) and higher %IGF-I (p= 0.002), than those without LVH. Multivaried analysis showed AH and %IGF-I as determinants of LVH (p= 0.035 and p= 0.016). After dichotomizing of %IGF-I, a score was created and the frequency of LVH was 9%, 65%, 92% x 0, 1, 2; p

  20. Mechanical load-dependent regulation of gene expression in monocrotaline-induced right ventricular hypertrophy in the rat.

    Science.gov (United States)

    Kögler, Harald; Hartmann, Oliver; Leineweber, Kirsten; Nguyen van, Phuc; Schott, Peter; Brodde, Otto-Erich; Hasenfuss, Gerd

    2003-08-01

    Rats treated with monocrotaline (MCT) develop pulmonary hypertension. Their right ventricles (RVs) exhibit severe pressure overload-induced hypertrophy, whereas the left ventricles (LVs) are normally loaded. In contrast, enhanced neuroendocrine stimulation during the transition to heart failure affects both ventricles. We assessed gene expression levels of Ca2+-regulating proteins in RVs and LVs of control and MCT rats in transition to heart failure to identify biomechanical load-regulated genes. In MCT RVs, both mRNA and protein levels of the Ca2+-ATPase of the sarcoplasmic/endoplasmic reticulum (SERCA2a) were reduced by 36% (P=0.001) and 17% (P=0.016), respectively, compared with control RVs. Phospholamban and ryanodine receptor mRNA levels likewise were reduced (by 27% [P=0.05] and 21% [P=0.011], respectively) in MCT RVs, whereas sarcolemmal Na+-Ca2+ exchanger expression was not altered. MCT LVs exhibited no significant expression changes compared with control LVs. Isometrically contracting MCT intact RV trabeculae showed enhanced baseline force development. Although control RV preparations exhibited a positive force-frequency relationship, MCT RVs showed a negative force-frequency relationship and blunted postrest potentiation. Contractile function of MCT LV trabeculae was normal. Maximum Ca2+-activated tension was enhanced by 64% in permeabilized RV MCT preparations (P=0.013). beta-Myosin heavy chain protein was upregulated in MCT RVs (P<0.001) but unaltered in MCT LVs. Degradation of troponin T was prominent in MCT RVs, a phenomenon not observed in the LV. Enhanced biomechanical load is necessary to induce the gene expression changes associated with the hypertrophic phenotype of the pressure-overloaded RV. Neuroendocrine factors, which equally affect both chambers, are not sufficient to alter the expression of Ca2+-cycling proteins. PMID:12842921

  1. 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 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.)

  2. 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 ?-subunit Kv4.2 and the ?-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 < 0.001, V Pip = 40 mV) within 5 min. Control solution resulted in a significantly smaller reduction in I to (17 ± 3 %, p < 0.001, p < 0.01 compared with MBCD). MBCD induced a 38 ± 9 % increase in the non-inactivating current component (I sus) (10.1 ± 0.6pApF(-1) vs. 7.6 ± 0.4pApF(-1), n = 15, p < 0.001). This effect was absent in control solution. The increase in I sus was not sensitive to 100 ?M 4-aminopyridine or 20 mM tetraethylammonium, making a contribution of Kv1.5 or Kv2.1 unlikely. In conclusion, in rat ventricular cardiomyocytes, a fraction of Kv4.2 and KChIP2 is localized in 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. PMID:24793047

  3. Coronary reserve is depressed in postmyocardial infarction reactive cardiac hypertrophy.

    Science.gov (United States)

    Karam, R; Healy, B P; Wicker, P

    1990-01-01

    After a myocardial infarction (MI), the remaining myocardium undergoes a compensatory reactive hypertrophy. Although coronary perfusion to the surviving myocardium can be an important determinant of cardiac function in this setting, there are no available data regarding myocardial blood flow in reactive hypertrophy. Accordingly, we measured coronary blood flow and reserve using radioactive microspheres in rats 4 weeks after induction of an MI by ligation of the left coronary artery. Maximal coronary dilation was induced by Carbochrome, a potent coronary vasodilator, infused at a rate of 0.45 mg/kg/min up to a total dose of 12 mg/kg. Sham-operated rats served as controls. All animals in the infarct group had a large MI affecting 30-51% (average, 41%) of the left ventricle. Left ventricular end-diastolic pressure was significantly elevated (30 +/- 6.5 vs. 8.0 +/- 2.5 mm Hg in sham-operated rats, p less than 0.01) and baseline hemodynamic indexes of cardiac performance were significantly (p less than 0.01) reduced in this group. Myocyte cross-sectional area measurements were used as an index to quantify the degree of reactive hypertrophy and indicated that the infarcted animals had, on average, a 30% hypertrophic response of the surviving left ventricular myocardium. In the infarcted animals, both coronary flow and vasodilator reserve in the surviving myocardium were depressed. Maximal coronary blood flow in the remaining myocardium was significantly lower than that measured in the sham-operated animals (839 and 1,479 ml/min/100 g, respectively; p less than 0.001). Similarly, minimal coronary resistance was significantly higher in the MI group as compared with the sham group (0.12 vs. 0.07 mm Hg/ml/min/100 g, respectively; p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2137045

  4. 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

    2012-01-01

    Abstract Background. The incidence of new-onset atrial fibrillation (AF) is increased by uncontrolled hypertension, and antihypertensive treatment reduces new-onset AF. However, it is unclear whether alcohol intake and smoking influence the risk of new-onset AF during antihypertensive treatment. 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 occurred in 353 (4%) patients. Univariate Cox analyses showed that intake of alcohol > 10 units/week compared with less or no alcohol intake predicted new-onset AF (Hazard ratio, HR = 1.60 [95% CI 1.02-2.51], p = 0.043). Multivariate Cox regression analysis showed that intake of alcohol > 10 units/week predicted new-onset AF (p = 0.010) independently of most other univariate predictors, except when also baseline serum cholesterol, serum potassium and urinary albumin/creatinine ratio were included in the model (HR = 1.60 [95% CI 0.94-2.72], p = 0.081). Impact of smoking was not significant in Cox univariate or multivariate analyses, and there were no significant interactions between high alcohol intake and either smoking or gender on the risk of getting AF. Conclusions. Up to 10 drinks of alcohol per week appears to be safe with respect to the risk for AF in hypertensive patients with LVH. Our data suggest that alcohol intake above this level may be marginally deleterious, while no effect of smoking on risk of AF was detected in hypertensive patients with LVH.

  5. 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; Boman, Kurt

    2012-01-01

    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 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(4-6)) and LVH (assessed by Sokolow-Lyon voltage criterion (R(V5-6)+S(V1) ?35 mV) and Cornell voltage-duration criteria ((RaVL+S(V3)+[6 mV in women]) × QRS-duration ?2440 mV msec), was evaluated by adjusting for other prognostic covariates. 1,533 patients were followed 4.3±0.8 years (6,592 patient-years of follow-up), 627 cardiovascular events occurred. Electrocardiographic strain was present in 340 (23.6%) patients; LVH by Sokolow-Lyon voltage in 260 (17.1%) and in 220 (14.6%) by Cornell voltage-duration product. In multivariable analyses, electrocardiographic LV strain was associated with 3.1-fold higher risk of in-study myocardial infarction (95% confidence interval [CI], 1.4 to 6.8, p=0.004). Similarly, electrocardiographic LVH by both criteria predicted, compared to no electrocardiographic LVH, 5.8-fold higher risk of heart failure (95% CI, 2.0 to 16.8), 2.0-fold higher risk of AVR (95% CI, 1.3 to 3.1, 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 REGISTRATION: http://www.ClinicalTrials.gov; NCT00092677.

  6. Stimulation of gene expression in neonatal rat ventricular myocytes by Ras is mediated by Ral guanine nucleotide dissociation stimulator (Ral.GDS) and phosphatidylinositol 3-kinase in addition to Raf.

    Science.gov (United States)

    Fuller, S J; Finn, S G; Downward, J; Sugden, P H

    1998-10-15

    Treatment of cultured neonatal ventricular myocytes with oncogenic Ras increases their size and stimulates the re-expression of genes which are normally restricted to the fetal stage of ventricular development, including atrial natriuretic factor (ANF) and skeletal muscle (SkM)-alpha-actin. To determine which signalling pathways mediate these responses, myocytes were transfected with oncogenic (V12) Ras mutants which interact selectively with different effectors and their effects on luciferase (LUX) reporter plasmids were examined. V12 human Ras (V12HRas), itself, activated ANF-LUX 9. 6-fold, whereas mutants of V12HRas, which selectively stimulate Ral guanine nucleotide dissociation stimulator (Ral.GDS) (E37G), c-Raf (D38E) and phosphatidylinositol 3-kinase (PI-3-K; Y40C) enhanced ANF-LUX expression 3.0-, 3.7- and 1.7-fold respectively. The full response of ANF-LUX to V12HRas was restored by using a combination of the individual effector domain mutants. Likewise, SkM-alpha-actin-LUX expression was activated 12.0-, 3.5-, 4.5- and 3. 0-fold by V12HRas, E37G, D38E and Y40C respectively, and a similar pattern of activation was also observed using a c-fos serum-response element-LUX reporter gene. Cell size was also increased by each of the mutants, but simultaneous expression of all three mutant constructs was needed to reconstitute the full effect of V12HRas on cell size (50% increase). Transfection with a constitutively active mutant of PI-3-K (p110K227E) stimulated ANF-LUX, SkM-alpha-actin-LUX, c-fos-serum-response element-LUX and Rous sarcoma virus-LUX by 3.1-, 3.2-, 2.1- and 2.9-fold respectively, but the co-transfected cytomegalovirus-beta-galactosidase reporter gene was activated to a similar extent (1.9-fold). These results suggest that Raf, Ral.GDS and PI-3-K can all transduce transcriptional responses to V12HRas, but that the specific induction of genes associated with the hypertrophic response is not mediated through PI-3-K. PMID:9761720

  7. Descenso espontáneo de la frecuencia cardíaca y regresión de la hipertrofia ventricular izquierda / Spontaneous decrease of heart rate and left ventricular hypertrophy regression / Descenso espontâneo da frequência cardíaca e regressão da hipertrofia ventricular esquerda

    Scientific Electronic Library Online (English)

    Daniel, Piskorz; Luciano, Citta; Norberto, Citta; Marcelo, Lanzotti; Roberto, Lanzotti; Horacio, Locatelli; Alicia, Tommasi.

    2009-03-01

    Full Text Available SciELO Argentina | Language: Spanish Abstract in portuguese Antecedentes. A análise da frequência cardíaca demonstrou ter impacto prognóstico em sujeitos sãos, pacientes hipertensos, e portadores de insuficiência cardíaca ou cardiopatia isquêmica. O objetivo do presente trabalho é determinar se existe uma relação, e de que tipo, entre as mudanças espontâneas [...] na frequência cardíaca durante o tratamento de pacientes hipertensos e o índice de massa ventricular esquerda. Material e métodos. Incluíram-se 40 pacientes hipertensos tratados durante 1 ano sem drogas que interferissem na frequência e no ritmo cardíaco. Análise estatística. Aplicou-se test de correlação, e considerou-se de significação estatístico um valor de p Abstract in spanish Antecedentes. El análisis de la frecuencia cardíaca ha demostrado tener impacto pronóstico en sujetos sanos, pacientes hipertensos, y portadores de insuficiencia cardíaca o cardiopatía isquémica. El objetivo del presente trabajo es determinar si existe una relación, y de qué tipo, entre los cambios [...] espontáneos en la frecuencia cardíaca durante el tratamiento en pacientes hipertensos y el índice de masa ventricular izquierda. Material y métodos. Se incluyeron 40 pacientes hipertensos tratados 1 año sin drogas que interfieran sobre la frecuencia ni el ritmo cardíaco. Análisis estadístico. Se aplicó test de correlación, y se consideró significación estadística un valor de p Abstract in english Background. The analysis of heart rate has been shown to have prognostic impact in healthy subjects, and in hypertensive, heart failure or ischemic heart disease patients. The aim of this study is to determine if a relationship exists, and what kind, between the spontaneous changes in heart rate dur [...] ing treatment in patients with hypertension and left ventricular mass index. Material and methods. We included 40 hypertensive patients treated during 1 year without drugs that interfere on heart rate. Statistical analysis. Correlation test was applied, and statistical significance was considered p

  8. AdipoR1/APPL1 Potentiates the Protective Effects of Globular Adiponectin on Angiotensin II-Induced Cardiac Hypertrophy and Fibrosis in Neonatal Rat Atrial Myocytes and Fibroblasts

    OpenAIRE

    Cao, Tengwei; Gao, Zhen; Gu, Lingyun; Chen, Minglong; Yang, Bing; Cao, Kejiang; Huang, He; Li, Mingfang

    2014-01-01

    Atrial hypertrophy and fibrosis are essential pathological features of atrial fibrillation. Recently, adiponectin has become a protein of interest due to its beneficial effects on cardiovascular diseases. However, the molecular mechanism of atrial structural remodeling and signaling pathways evoked by adiponectin remain unclear. In the present study, we investigated the cardioprotective effect of globular adiponectin (gAcrp) on angiotensin II-induced atrial hypertrophy and fibrosis in neonata...

  9. Visualization of hypertrophied papillary muscle mimicking left ventricular mass on gated blood pool and T1-201 myocardial perfusion imaging

    International Nuclear Information System (INIS)

    A sixty-year old man with acute myocardial infarction was incidentally found to have a hypertrophied anterolateral papillary muscle (ALPPM) of the left ventricle on gated blood pool (GBP) and T1-201 myocardial perfusion images. Hypertrophy of the ALPPM was visualized as a movable defect in the lateral basal area on GBP imaging throughout the cardiac cycle and on the TI-201 study as a radionuclide accumulating structure, consistent with the defect in the GBP. A combination of these findings may suggest the presence of a hypertrophied papillary muscle of the left ventricle

  10. 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 ...

  11. Cardiac hypertrophy, hypertrophic cardiomyopathy, and hyperparathyroidism--an association.

    OpenAIRE

    Symons, C.; Fortune, F.; Greenbaum, R. A.; Dandona, P.

    1985-01-01

    Left ventricular hypertrophy (symmetric, asymmetric, or hypertrophic cardiomyopathy) is an almost invariable accompaniment of primary hyperparathyroidism. Five of 18 patients with hypertrophic cardiomyopathy had raised serum concentrations of parathyroid hormone with normal serum calcium concentrations. Left ventricular hypertrophy did not occur in any of the six patients with hypercalcaemia alone. These relations suggest that parathyroid hormone rather than a rise in the extracellular calciu...

  12. Effect of dobutamine stress on basal septal tissue dynamics in hypertensive patients with basal septal hypertrophy.

    Science.gov (United States)

    Yalçin, F; Yigit, F; Erol, T; Baltali, M; Korkmaz, M E; Müderrisoglu, H

    2006-08-01

    Left ventricular outflow tract (LVOT) obstruction has been classically observed in hypertrophic cardiomyopathy in which the LVOT obstruction is associated with asymmetric septal hypertrophy producing a systolic pressure gradient across the LVOT. Basal septal hypertrophy (BSH) with hypertension may result in dynamic LVOT obstruction as well. It was suggested that regional hypertrophy may be related to enhanced ventricular dynamics. PMID:16761028

  13. N-n-butyl haloperidol iodide inhibits H2O2-induced Na+/Ca2+-exchanger activation via the Na+/H+ exchanger in rat ventricular myocytes

    Science.gov (United States)

    Huang, Yong-Pan; Gao, Fen-Fei; Wang, Bin; Zheng, Fu-Chun; Zhang, Yan-Mei; Chen, Yi-Cun; Huang, Zhan-Qin; Zheng, Yan-Shan; Zhong, Shu-Ping; Shi, Gang-Gang

    2014-01-01

    N-n-butyl haloperidol iodide (F2), a novel compound, has shown palliative effects in myocardial ischemia/reperfusion (I/R) injury. In this study, we investigated the effects of F2 on the extracellular signal-regulated kinase kinase (MEK)/extracellular signal-regulated kinase (ERK)/Na+/H+ exchanger (NHE)/Na+/Ca2+ exchanger (NCX) signal-transduction pathway involved in H2O2-induced Ca2+ overload, in order to probe the underlying molecular mechanism by which F2 antagonizes myocardial I/R injury. Acute exposure of rat cardiac myocytes to 100 ?M H2O2 increased both NHE and NCX activities, as well as levels of phosphorylated MEK and ERK. The H2O2-induced increase in NCX current (INCX) was nearly completely inhibited by the MEK inhibitor U0126 (1,4-diamino-2,3-dicyano-1,4-bis[o-aminophenylmercapto] butadiene), but only partly by the NHE inhibitor 5-(N,N-dimethyl)-amiloride (DMA), indicating the INCX increase was primarily mediated by the MEK/mitogen-activated protein kinase (MAPK) pathway, and partially through activation of NHE. F2 attenuated the H2O2-induced INCX increase in a concentration-dependent manner. To determine whether pathway inhibition was H2O2-specific, we examined the ability of F2 to inhibit MEK/ERK activation by epidermal growth factor (EGF), and NHE activation by angiotensin II. F2 not only inhibited H2O2-induced and EGF-induced MEK/ERK activation, but also completely blocked both H2O2-induced and angiotensin II-induced increases in NHE activity, suggesting that F2 directly inhibits MEK/ERK and NHE activation. These results show that F2 exerts multiple inhibitions on the signal-transduction pathway involved in H2O2-induced INCX increase, providing an additional mechanism for F2 alleviating intracellular Ca2+ overload to protect against myocardial I/R injury. PMID:25246767

  14. Asymmetric septal hypertrophy complicated by dynamic left ventricular obstruction after intra-aortic balloon counterpulsation placement in the setting of anterior myocardial infarction.

    Science.gov (United States)

    Cohen, Rémy; Rivagorda, Joel; Elhadad, Simon

    2006-07-01

    We report the case of a 74-year-old patient admitted for acute anterior myocardial infarction and treated by intravenous thrombolysis. Because of hemodynamic instability, an intra-aortic balloon pump (IABP) was inserted. However, the patient's systolic blood pressure deteriorated early after IABP placement. Echocardiography revealed a dynamic left ventricular outflow tract obstruction occurring only during assisted ventricular systoles. Interruption of counterpulsation allowed complete resolution of the dynamic obstruction and improvement of hemodynamic status. PMID:16816450

  15. Electrophysiological properties of the propafenone-analogue GE 68 (1-[3-(phenylethyl)-2-benzofuryl]-2-(propylamino)-ethanol) in isolated preparations and ventricular myocytes of guinea-pig hearts.

    Science.gov (United States)

    Lemmens-Gruber, R; Marei, H; Heistracher, P

    1997-02-01

    GE 68 ((Rac.)-1-[3-(Phenylethyl)-2-benzofuryl]-2-(propylamino)-ethanol hydrochloride) is structurally related to propafenone, and exerts negative inotropic and negative chronotropic effects similar to the parent drug, but lacks any beta-adrenoceptor blocking activity contrary to propafenone. Thus, the electrophysiological effects of GE 68 were studied in papillary muscles, left atria, Purkinje fibres, sinoatrial nodes and ventricular myocytes of the guinea-pig heart with the intracellular microelectrode technique and the patch-clamp technique in the cell-attached mode. The decrease of the maximum upstroke velocity (Vmax) by GE 68 (1 to 10 microM) was use- and frequency-dependent. Vmax recovered from the use-dependent block with a time constant of 4.1 +/- 0.6 s. In papillary muscles and Purkinje fibres action potential duration was shortened, while it was prolonged in left atria and sinoatrial nodes. Half-maximal steady-state inactivation of the sodium channels was shifted to more negative membrane potentials (control: -91.5 +/- 0.8 mV, 10 microM GE 68: -97.9 +/- 2.5 mV). The peak of the current-voltage relationship and the reversal potential were not changed by GE 68. The amplitude of the unitary current remained unaltered, while open state probability was decreased. The most striking effect of GE 68 was an increase of the number of sweeps without single channel openings (1 microM: 2fold, 10 microM: 6fold). GE 68 also caused a decrease of the mean open times, and an increase of the mean closed times in unmodified and pronase-modified sodium channels. Besides the lack of beta-adrenoceptor blocking activity, data present a faster recovery from the use-dependent block by GE 68 and a lower affinity to inactivated sodium channels compared to the reference drug propafenone, as well as differences in the effect on single channel kinetics. PMID:9050017

  16. The FOXO3a Transcription Factor Regulates Cardiac Myocyte Size Downstream of AKT Signaling*

    OpenAIRE

    Skurk, Carsten; Izumiya, Yasuhiro; Maatz, Henrike; Razeghi, Peter; Shiojima, Ichiro; Sandri, Marco; Sato, Kaori; Zeng, Ling; Schiekofer, Stephan; Pimentel, David; Lecker, Stewart; Taegtmeyer, Heinrich; Goldberg, Alfred L.; Walsh, Kenneth

    2005-01-01

    Although signaling mechanisms inducing cardiac hypertrophy have been extensively studied, little is known about the mechanisms that reverse cardiac hypertrophy. Here, we describe the existence of a similar Akt/forkhead signaling axis in cardiac myocytes in vitro and in vivo, which is regulated by insulin, insulin-like growth factor (IGF), stretch, pressure overload, and angiotensin II stimulation. FOXO3a gene transfer prevented both IGF and stretch-induced hypertrophy in rat neonatal cardiac ...

  17. Tratamiento con eritropoyetina recombinante humana, hipertrofia ventricular izquierda y balance beneficio riesgo en la ERC-3b / Treatment with recombinant erythropoietin, left ventricular hypertrophy and balance benefit-risk in CKD-3b

    Scientific Electronic Library Online (English)

    Jorge F, Pérez-Oliva Díaz; Martha, Casanova González; Orosmán, Cuesta Panaco; Osniel, Bencomo Rodríguez; Beatriz, López Tórres; Claudio, González; Liván, Cruz Benítez; Idrian, García García; Ángela D, Tuero Iglesias; Carmen M, Valenzuela Silva; Pedro A, López Saura.

    2013-09-01

    Full Text Available SciELO Cuba | Language: Spanish Abstract in spanish Introducción: la anemia renal es frecuente en la enfermedad renal crónica avanzada (ERC 3b-4) y el tratamiento con eritropoyetina recombinante humana la mejora pero aún está a debate cual meta de hemoglobina alcanzar y cuál es su repercusión sobre las funciones cardíacas. Objetivo de este trabajo fu [...] e evaluar la mejoría de la anemia tratada con EPOrHu sobre parámetros de la función cardiovascular ventricular izquierda en la ERC 3b-4 y el riesgo beneficio. Material y métodos: ensayo clínico abierto, no controlado, no aleatorizado, multicéntrico, prospectivo, seguimiento durante 56 semanas de seguimiento. Se evalúan los cambios en la Tasa de Filtración Glomerular por la fórmula del MDRD y por ecocardiografía en relación al nivel basal, al final del seguimiento estimada la variación al año de la HVI. Resultados: se observó un incremento significativo del hematócrito en todos los pacientes al final del estudio (n = 33, 0.29 ± 0,02 (V%) versus 0.38 ± 0.03, P (Wilcoxon)= 0.000. Al eco inicial el 90,9% tenían HVI y al final solo el 78.8% con una disminución de 2.2 mm (14 a 11.8 mm), y una correlación inversa lineal entre la HVI y la mejoría de la hemoglobina (r = -0.379; p = 0.030). La progresión del daño renal fue lenta (mL/min). En los pacientes diabéticos de 37.2 ± 8.4 versus 34.7 ± 6.7, (p Wilcoxon=0.119) y en los no diabéticos de 35.1 ± 7.833.6 ± 7.7 (p Wilcoxon= 0.119). El 48.5% de los pacientes presentaron algún tipo de evento adverso, ninguno falleció o comenzó hemodiálisis durante el seguimiento. El Balance Beneficio- Riesgo (EA moderados o graves) estimados por el cálculo del Factor de Bayes fue a favor del Beneficio (FB=1,5). Conclusiones: la corrección de la anemia renal en pacientes con ERC-3b con EPOrHu cubana mejora la HVI sin provocar otros daños Este trabajo apoya el tratamiento de la anemia severa con EPOrHU. Abstract in english Introduction: renal anemia is a frequent complication among patients with chronic kidney disease (CKD). The introduction of recombinant erythropoietin (rhuEpo) treatment has changed anemia management, but the therapeutic hemoglobin (Hb) target is still under debate, and clinical evidence for its eff [...] ect on cardiac functions is in discussion. Objective: this study aimed to explore the effect of pre-dialysis erythropoiesis-stimulating agent (ESA) use on the left ventricular hypertrophy (LVH) or general and renal function protective effect in CKD3b-4 patients. Different than in introducción in Spanish. Patients and methods: open multicentric assay. A 56-week follow-Up dose-response study. The change from baseline to the end of treatment was calculated for glomerular filtration rate by MDRD (GFR,) and, LVH by echocardiography at 24 months. Results: the treatment significantly increased hematocrit (Htc) in all patients who completed the study (n = 33, 0.29 ± 0.02(V%) versus 0.38 ± 0.03, P (Wilcoxon)= 0.000. In the beginning 90,9% At the end only the 78.8% the patients had LVH, it was decreased 2.2 mm (14 a 11.8 mm), and significant reverse lineal correlation between the change in the LVH and Hb concentration was noted (r = -0.379; p = 0.030). Progression of the CKD was slow (mL/min). Diabetics 37.2 ± 8.4 versus 34.7 ± 6.7 (p Wilcoxon=0.119) non diabetics 35.1 ± 7.833.6 ± 7.7 (p Wilcoxon= 0.119). 48.5% of the patients had Adverse effects (AE). No patients died or started in dialysis. The Balance Benefit- Risk (AE moderate or severe) estimated from the Bayes Factor was evidence to the benefit (BF=1, 64). Conclusion: we observed that correction of anemia with rhuEpo in patients with CKD 3b seems to improve the LVH without another problems and it is beneficial. The results of this study support the treatment of severe anemia with EPO.

  18. AdipoR1/APPL1 potentiates the protective effects of globular adiponectin on angiotensin II-induced cardiac hypertrophy and fibrosis in neonatal rat atrial myocytes and fibroblasts.

    Science.gov (United States)

    Cao, Tengwei; Gao, Zhen; Gu, Lingyun; Chen, Minglong; Yang, Bing; Cao, Kejiang; Huang, He; Li, Mingfang

    2014-01-01

    Atrial hypertrophy and fibrosis are essential pathological features of atrial fibrillation. Recently, adiponectin has become a protein of interest due to its beneficial effects on cardiovascular diseases. However, the molecular mechanism of atrial structural remodeling and signaling pathways evoked by adiponectin remain unclear. In the present study, we investigated the cardioprotective effect of globular adiponectin (gAcrp) on angiotensin II-induced atrial hypertrophy and fibrosis in neonatal Sprague-Dawley rat. To further investigate the molecular mechanisms underlying the preventive effect of gAcrp, transfection of cells with siRNA was used to suppress the mRNA expression of adiponectin receptor 1 (AdipoR1) and its downstream adaptor protein APPL1. Non-silencing-Cy-3 labelled siRNA was used to determine transfection efficiency using fluorescence microscopy. The expression of atrial natriuretic peptide and procollagen type1 ?-1, hypertrophy marker and fibrosis one, respectively, was detected by real-time PCR. Furthermore, the expression of adenosine monophosphate-activated protein kinase (AMPK), phosphatidylinositol 3-kinase (PI3K) and Akt was detected by western blotting. In addition, nuclear p65 translocation activity was analyzed by EMSA supershift assay. Our results showed that AdipoR1 and the adaptor protein APPL1 mediated the protective effects of gAcrp. In addition, the function of adiponectin and phosphorylation of AMPK were prominently diminished by inhibition of PI3K. Furthermore, nuclear factor-?B (NF-?B) transcription was diminished by the specific inhibition of AMPK. Taken together, AMPK pivotally interacts with NF-?B and PI3K, mediating the cardioprotective effect of adiponectin, and may serve as a therapeutic target for preventing atrial hypertrophy and fibrosis. Our present study suggests that gAcrp could ameliorate AngII-induced cardiac hypertrophy and fibrosis in rat atrial cells, which is mediated by the activation of AMPK signaling pathways. APPL1 and AdipoR1 are the key factors involved in the downstream of gAcrp approach. PMID:25099270

  19. N-n-butyl haloperidol iodide inhibits H2O2- induced Na+/Ca2+-exchanger activation via the Na+/H+ exchanger in rat ventricular myocytes

    Directory of Open Access Journals (Sweden)

    Huang YP

    2014-09-01

    Full Text Available Yong-Pan Huang,1,* Fen-Fei Gao,1,* Bin Wang,1 Fu-Chun Zheng,2 Yan-Mei Zhang,1 Yi-Cun Chen,1 Zhan-Qin Huang,1 Yan-Shan Zheng,1 Shu-Ping Zhong,3 Gang-Gang Shi1,4 1Department of Pharmacology, 2Department of Pharmacy, First Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong, People's Republic of China; 3Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, CA, USA; 4Department of Cardiovascular Diseases, First Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong, People's Republic of China *These authors contributed equally to this work Abstract: N-n-butyl haloperidol iodide (F2, a novel compound, has shown palliative effects in myocardial ischemia/reperfusion (I/R injury. In this study, we investigated the effects of F2 on the extracellular signal-regulated kinase kinase (MEK/extracellular signal-regulated kinase (ERK/Na+/H+ exchanger (NHE/Na+/Ca2+ exchanger (NCX signal-transduction pathway involved in H2O2-induced Ca2+ overload, in order to probe the underlying molecular mechanism by which F2 antagonizes myocardial I/R injury. Acute exposure of rat cardiac myocytes to 100 µM H2O2 increased both NHE and NCX activities, as well as levels of phosphorylated MEK and ERK. The H2O2-induced increase in NCX current (INCX was nearly completely inhibited by the MEK inhibitor U0126 (1,4-diamino-2,3-dicyano-1,4-bis[o-aminophenylmercapto]butadiene, but only partly by the NHE inhibitor 5-(N,N-dimethyl-amiloride (DMA, indicating the INCX increase was primarily mediated by the MEK/mitogen-activated protein kinase (MAPK pathway, and partially through activation of NHE. F2 attenuated the H2O2-induced INCX increase in a concentration-dependent manner. To determine whether pathway inhibition was H2O2-specific, we examined the ability of F2 to inhibit MEK/ERK activation by epidermal growth factor (EGF, and NHE activation by angiotensin II. F2 not only inhibited H2O2-induced and EGF-induced MEK/ERK activation, but also completely blocked both H2O2-induced and angiotensin II-induced increases in NHE activity, suggesting that F2 directly inhibits MEK/ERK and NHE activation. These results show that F2 exerts multiple inhibitions on the signal-transduction pathway involved in H2O2-induced INCX increase, providing an additional mechanism for F2 alleviating intracellular Ca2+ overload to protect against myocardial I/R injury. Keywords: N-n-butyl haloperidol, hydrogen peroxide, Na+/Ca2+ exchanger, Na+/H+ exchanger

  20. The clinical value of apex beat and electrocardiography for the detection of left ventricular hypertrophy from the standpoint of the distance factors from the heart to the chest wall. A multislice CT study

    International Nuclear Information System (INIS)

    The aim of this study was to investigate the clinical value of the apex beat and two electrocardiographic (ECG) voltage criteria in the detection of left ventricular hypertrophy (LVH) while considering two distances, from the heart to the inner chest wall and to the chest surface, measured by using multislice CT (MSCT). The study population consisted of 151 patients clinically judged as requiring MSCT angiography. The apex beat was palpated with patients in the supine. Sokolow-Lyon voltage and Cornell voltage to detect LVH were determined. The pattern of sustained or double apical impulse and Cornell voltage had higher specificity as an indicator of LVH than Sokolow-Lyon voltage. Furthermore, the distance to the inner chest wall was negatively correlated with left ventricular end-diastolic volume and mass. Contrarily, the distance to the chest surface was correlated with the body mass index. Multivariate analyses revealed that the pattern of sustained or double apical impulse showed a stronger association with the distance to the inner chest wall than to the chest surface, but Sokolow-Lyon voltage was associated with the distance to the chest surface. Among the screening tests for excluding patients with LVH, Cornell voltage or the apex beat would be better than Sokolow-Lyon voltage because these are less dependent on body size and have higher specificity. (author)

  1. Effect of renal denervation procedure on left ventricular hypertrophy of hypertensive rats and its mechanisms / Efeito da denervação renal na hipertrofia do ventrículo esquerdo de ratos hipertensos e seu mecanismo

    Scientific Electronic Library Online (English)

    Weihong, Jiang; Lihua, Tan; Yunzhong, Guo; Xiaogang, Li; Xiaohong, Tang; Kan, Yang.

    2012-11-01

    Full Text Available OBJETIVO: Investigar o efeito da denervação renal na pressão sanguínea, na hipertrofia do ventrículo esquerdo e a expressão miocárdica de TLR4/NF-kB em ratos espontaneamente hipertensos. MÉTODOS: Trinta e seis SHR ratos foram aleatoriamente distribuídos em grupo controle, grupo denervação renal (D) [...] e grupo sham(S). 12 WKY ratos de mesma idade serviram de controle. Os ratos controles foram sacrificados, mas os ratos com denervação renal e sham foram sacrificados uma semana e seis semanas após a cirurgia. O coração foi retirado e o ventrículo esquerdo pesado seguido pelo cálculo da massa ventricular (LVMI). RESULTADOS: No grupo DO, a pressão sanguínea, LVMI e a expressão proteica de TLR4, NF-?B, TNF-? e IL-6, no miocárdio foram marcadamente maiores do que o grupo WKY (p Abstract in english PURPOSE: To investigate the effect of renal denervation (RDN) on the blood pressure, left ventricular hypertrophy and myocardial expression of TLR4/NF-?B in spontaneously hypertensive rats (SHR). METHODS: A total of 36 SHR were randomly assigned into control group (D0), RDN group (D) and sham group [...] (S). 12 WKY rats of same age served as controls (WKY group). Rats in the D0 and WKY groups were sacrificed, but rats in the D and S group were sacrificed at one week and six weeks after surgery. The heart was collected and the left ventricle weighted followed by calculation of left ventricular mass index (LVMI). RESULTS: In the D0 group, the blood pressure, LVMI and protein expression of TLR4, NF-?B, TNF-? and IL-6 in the myocardium were markedly higher than that in the WKY group (p

  2. Astragaloside IV Protects against Isoproterenol-Induced Cardiac Hypertrophy by Regulating NF-?B/PGC-1? Signaling Mediated Energy Biosynthesis.

    Science.gov (United States)

    Zhang, Suping; Tang, Futian; Yang, Yuhong; Lu, Meili; Luan, Aina; Zhang, Jing; Yang, Juan; Wang, Hongxin

    2015-01-01

    We previously reported that Astragaloside IV (ASIV), a major active constituent of Astragalus membranaceus (Fisch) Bge protects against cardiac hypertrophy in rats induced by isoproterenol (Iso), however the mechanism underlying the protection remains unknown. Dysfunction of cardiac energy biosynthesis contributes to the hypertrophy and Nuclear Factor ?B (NF-?B)/Peroxisome Proliferator-Activated Receptor-? Coactivator 1? (PGC-1?) signaling gets involved in the dysfunction. The present study was designed to investigate the mechanism by which ASIV improves the cardiac hypertrophy with focuses on the NF-?B/PGC-1? signaling mediated energy biosynthesis. Sprague-Dawley (SD) rats or Neonatal Rat Ventricular Myocytes (NRVMs) were treated with Iso alone or in combination with ASIV. The results showed that combination with ASIV significantly attenuated the pathological changes, reduced the ratios of heart weight/body weight and Left ventricular weight/body weight, improved the cardiac hemodynamics, down-regulated mRNA expression of Atrial Natriuretic Peptide (ANP) and Brain Natriuretic Peptide (BNP), increased the ratio of ATP/AMP, and decreased the content of Free Fat Acid (FFA) in heart tissue of rats compared with Iso alone. In addition, pretreatment with ASIV significantly decreased the surface area and protein content, down-regulated mRNA expression of ANP and BNP, increased the ratio of ATP/AMP, and decreased the content of FFA in NRVMs compared with Iso alone. Furthermore, ASIV increased the protein expression of ATP5D, subunit of ATP synthase and PGC-1?, inhibited translocation of p65, subunit of NF-?B into nuclear fraction in both rats and NRVMs compared with Iso alone. Parthenolide (Par), the specific inhibitor of p65, exerted similar effects as ASIV in NRVMs. Knockdown of p65 with siRNA decreased the surface areas and increased PGC-1? expression of NRVMs compared with Iso alone. The results suggested that ASIV protects against Iso-induced cardiac hypertrophy through regulating NF-?B/PGC-1? signaling mediated energy biosynthesis. PMID:25738576

  3. Astragaloside IV Protects against Isoproterenol-Induced Cardiac Hypertrophy by Regulating NF-?B/PGC-1? Signaling Mediated Energy Biosynthesis

    Science.gov (United States)

    Yang, Yuhong; Lu, Meili; Luan, Aina; Zhang, Jing; Yang, Juan; Wang, Hongxin

    2015-01-01

    We previously reported that Astragaloside IV (ASIV), a major active constituent of Astragalus membranaceus (Fisch) Bge protects against cardiac hypertrophy in rats induced by isoproterenol (Iso), however the mechanism underlying the protection remains unknown. Dysfunction of cardiac energy biosynthesis contributes to the hypertrophy and Nuclear Factor ?B (NF-?B)/Peroxisome Proliferator-Activated Receptor-? Coactivator 1? (PGC-1?) signaling gets involved in the dysfunction. The present study was designed to investigate the mechanism by which ASIV improves the cardiac hypertrophy with focuses on the NF-?B/PGC-1? signaling mediated energy biosynthesis. Sprague-Dawley (SD) rats or Neonatal Rat Ventricular Myocytes (NRVMs) were treated with Iso alone or in combination with ASIV. The results showed that combination with ASIV significantly attenuated the pathological changes, reduced the ratios of heart weight/body weight and Left ventricular weight/body weight, improved the cardiac hemodynamics, down-regulated mRNA expression of Atrial Natriuretic Peptide (ANP) and Brain Natriuretic Peptide (BNP), increased the ratio of ATP/AMP, and decreased the content of Free Fat Acid (FFA) in heart tissue of rats compared with Iso alone. In addition, pretreatment with ASIV significantly decreased the surface area and protein content, down-regulated mRNA expression of ANP and BNP, increased the ratio of ATP/AMP, and decreased the content of FFA in NRVMs compared with Iso alone. Furthermore, ASIV increased the protein expression of ATP5D, subunit of ATP synthase and PGC-1?, inhibited translocation of p65, subunit of NF-?B into nuclear fraction in both rats and NRVMs compared with Iso alone. Parthenolide (Par), the specific inhibitor of p65, exerted similar effects as ASIV in NRVMs. Knockdown of p65 with siRNA decreased the surface areas and increased PGC-1? expression of NRVMs compared with Iso alone. The results suggested that ASIV protects against Iso-induced cardiac hypertrophy through regulating NF-?B/PGC-1? signaling mediated energy biosynthesis. PMID:25738576

  4. Effect of renal denervation procedure on left ventricular hypertrophy of hypertensive rats and its mechanisms Efeito da denervação renal na hipertrofia do ventrículo esquerdo de ratos hipertensos e seu mecanismo

    Directory of Open Access Journals (Sweden)

    Weihong Jiang

    2012-11-01

    Full Text Available PURPOSE: To investigate the effect of renal denervation (RDN on the blood pressure, left ventricular hypertrophy and myocardial expression of TLR4/NF-?B in spontaneously hypertensive rats (SHR. METHODS: A total of 36 SHR were randomly assigned into control group (D0, RDN group (D and sham group (S. 12 WKY rats of same age served as controls (WKY group. Rats in the D0 and WKY groups were sacrificed, but rats in the D and S group were sacrificed at one week and six weeks after surgery. The heart was collected and the left ventricle weighted followed by calculation of left ventricular mass index (LVMI. RESULTS: In the D0 group, the blood pressure, LVMI and protein expression of TLR4, NF-?B, TNF-? and IL-6 in the myocardium were markedly higher than that in the WKY group (pOBJETIVO: Investigar o efeito da denervação renal na pressão sanguínea, na hipertrofia do ventrículo esquerdo e a expressão miocárdica de TLR4/NF-kB em ratos espontaneamente hipertensos. MÉTODOS: Trinta e seis SHR ratos foram aleatoriamente distribuídos em grupo controle, grupo denervação renal (D e grupo sham(S. 12 WKY ratos de mesma idade serviram de controle. Os ratos controles foram sacrificados, mas os ratos com denervação renal e sham foram sacrificados uma semana e seis semanas após a cirurgia. O coração foi retirado e o ventrículo esquerdo pesado seguido pelo cálculo da massa ventricular (LVMI. RESULTADOS: No grupo DO, a pressão sanguínea, LVMI e a expressão proteica de TLR4, NF-?B, TNF-? e IL-6, no miocárdio foram marcadamente maiores do que o grupo WKY (p<0,05. Nos grupos D1 e D2, o LVMI, NE e a expressão proteica de TLR4, NF-?B, TNF-? e IL-6 no miocárdio foi significantemente reduzido (p<0,05. CONCLUSÃO: A denervação renal pode significantemente retardar a progressão da hipertrofia ventricular esquerda em ratos espontaneamente hipertensos, o que pode ser atribuído não apenas pela supressão da atividade simpática e atenuação da pressão, mas pela melhora na imunoinflamação miocárdica.

  5. O eletrocardiograma no diagnóstico da hipertrofia ventricular de pacientes com doença renal crônica / Electrocardiography in the diagnosis of ventricular hypertrophy in patients with chronic renal disease / El electrocardiograma en el diagnóstico de la hipertrofia ventricular de pacientes con enfermedad renal crónica

    Scientific Electronic Library Online (English)

    Francisco de Assis, Costa; Ivan Romero, Rivera; Mirian Lira Castro de, Vasconcelos; André Falcão Pedrosa, Costa; Rui Manoel dos Santos, Póvoa; Maria Tereza Nogueira, Bombig; Bráulio, Luna Filho; Valter Correia de, Lima.

    2009-10-01

    Full Text Available SciELO Brazil | Languages: English, Portuguese, Spanish Abstract in portuguese FUNDAMENTO: A hipertrofia ventricular esquerda (HVE) é um fator preditor independente de risco cardiovascular e sua caracterização e prevalência na doença renal crônica (DRC) carecem de melhor estudo. OBJETIVO: Estabelecer o diagnóstico de HVE em pacientes com DRC em estágio 5 por seis diferentes cr [...] itérios eletrocardiográficos, correlacionando-os com o índice de massa do ventrículo esquerdo (IMVE) obtido pelo ecocardiograma. MÉTODOS: Estudo transversal que incluiu 100 pacientes (58 homens e 42 mulheres, idade de 46,2 ± 14,0 anos) com DRC de todas as etiologias, há pelo menos seis meses em hemodiálise (HD). Foram obtidos eletrocardiograma (ECG) e ecocardiograma dos pacientes, sempre até uma hora após o término das sessões de HD. RESULTADOS: A HVE foi detectada em 83 pacientes (83%), dos quais 56 (67,4%) apresentavam o padrão concêntrico e 27 (32,6%) o padrão excêntrico de HVE. Todos os métodos eletrocardiográficos estudados tiveram sensibilidade, especificidade e acurácia diagnósticas acima de 50%. Pela correlação linear de Pearson com o IMVE, apenas o critério de Sokolow-Lyon voltagem não apresentou coeficiente > 0,50. Já o cálculo da razão de verossimilhança mostrou que o ECG possui poder discriminatório para diagnóstico de HVE na população estudada, com ênfase para os critérios de Cornell produto e Romhilt-Estes. Não houve correlação entre IMVE com o QTc e sua dispersão. CONCLUSÃO: O ECG é um método útil, eficaz e de alta reprodutibilidade no diagnóstico de HVE dos pacientes em HD. Nessa população, o critério de Cornell produto mostrou-se o mais fidedigno para a detecção de HVE. Abstract in spanish FUNDAMENTO: La hipertrofia ventricular izquierda (HVI) es un factor predictor independiente de riesgo cardiovascular y su caracterización y prevalencia en la enfermedad renal crónica (ERC) carecen de mejor estudio. OBJETIVO: Establecer el diagnóstico de HVI en pacientes con ERC en estadio 5 por seis [...] diferentes criterios electrocardiográficos, correlacionándolos al índice de masa del ventrículo izquierdo (IMVI) que se obtuvo mediante el ecocardiograma. MÉTODOS: Estudio transversal que incluyó a 100 pacientes (58 varones y 42 mujeres, edad de 46,2 ± 14,0 años) con ERC de todas las etiologías, desde hace al menos 6 meses en hemodiálisis (HD). Se obtuvieron electrocardiograma (ECG) y ecocardiograma de los pacientes, siempre hasta una hora tras el término de las sesiones de HD. RESULTADOS: La HVI se detectó en 83 pacientes (83%), de los que 56 (67,4%) presentaban el estándar concéntrico y 27 (32,6%) el estándar excéntrico de HVI. Todos los métodos electrocardiográficos estudiados tuvieron sensibilidad, especificidad y exactitud diagnósticas superiores al 50%. Mediante la correlación lineal de Pearson con el IMVI, solamente el criterio de Sokolow-Lyon voltaje no presentó coeficiente > 0,50. Sin embargo, el cálculo de la razón de verosimilitud evidenció que el ECG tiene poder discriminatorio para diagnóstico de HVI en la población estudiada, con énfasis para los criterios de Producto de Cornell y Romhilt-Estes. No hubo correlación entre IMVI con el QTc y su dispersión. CONCLUSIÓN: El ECG es un método útil, eficaz y de alta reproductibilidad en el diagnóstico de HVI de los pacientes en HD. En esa población, el criterio de Producto de Cornell fue más fiable para la detección de HVI. Abstract in english BACKGROUND: Left ventricular hypertrophy (LVH) is an independent predictor of cardiovascular risk, and its characterization and prevalence in chronic renal disease (CRD) should be further studied. OBJECTIVE: To establish the diagnosis of LVH in patients with stage-5 CRD using six different electroca [...] rdiographic criteria, and to correlate them with left ventricular mass index (LVMI) as obtained by echocardiography. METHODS: Cross-sectional study including 100 patients (58 men and 42 women, mean age 46.2 ± 14.0 years) with CRD

  6. Increase in cardiac myosin heavy-chain (MyHC) alpha protein isoform in hibernating ground squirrels, with echocardiographic visualization of ventricular wall hypertrophy and prolonged contraction

    OpenAIRE

    Nelson, O. Lynne; Rourke, Bryan C.

    2013-01-01

    Deep hibernators such as golden-mantled ground squirrels (Callospermophilus lateralis) have multiple challenges to cardiac function during low temperature torpor and subsequent arousals. As heart rates fall from over 300 beats min?1 to less than 10, chamber dilation and reduced cardiac output could lead to congestive myopathy. We performed echocardiography on a cohort of individuals prior to and after several months of hibernation. The left ventricular chamber exhibited eccentric and concen...

  7. Myocardial hypertrophy after pulmonary regurgitation and valve implantation in pigs

    DEFF Research Database (Denmark)

    Smith, Julie; Goetze, Jens Peter

    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: The results were compared with age-matched sham-operated animals. RESULTS: At euthanasia, RV weight was increased compared to sham-animals, median 127g (115-137) vs. 71g (69.5-76.5), p=0.0007. RV myocyte diameters corrected for individual variation with the RV/LV ratio were enlarged, 1.06 (1.02-1.13) vs. 0.84 (0.80-0.91), p=0.0006. There were no excess collagen tissue (RV/LV ratio), p=0.77. Electrophysiological stimulation resulted in RV arrhythmia in 67% of the animals compared to 25% in the sham-operated animals, but this difference was not statistically significant, p=0.28. Echocardiography revealed geometrical dilation in end-systolic RV area, mean±SD, 11.8±4.9cm(2) vs. 6.0±3.5cm(2), p=0.05, and end-diastolic area, 23.3±10.4cm(2) vs. 12.7±2.5cm(2), p=0.08. RV anterior free wall thickness was not increased, 0.7±0.2cm vs. 0.7±0.1cm, p=0.66. Echocardiographic functional parameters 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 be substrate for arrhythmia.

  8. Downregulation of survival signalling pathways and increased apoptosis in the transition of pressure overload-induced cardiac hypertrophy to heart failure.

    Science.gov (United States)

    Li, Xiao-Mei; Ma, Yi-Tong; Yang, Yi-Ning; Liu, Fen; Chen, Bang-Dang; Han, Wei; Zhang, Jian-Fa; Gao, Xiao-Ming

    2009-11-01

    1. Transition from compensated left ventricular (LV) hypertrophy to decompensated heart failure was characterized using a pressure-overload induced model to elucidate the temporal relationship between cardiomyocyte apoptosis and survival signalling in this transition. 2. Mice were subjected to transverse aortic constriction (TAC) or sham operation for 1-16 weeks and were studied by echocardiography, catheterization and histology. Relevant gene expression and phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, Akt and glycogen synthase kinase (GSK)-3beta were determined. 3. Transverse aortic constriction resulted in myocyte hypertrophy and fibrosis from Week 4 and a progressive increase in left ventricular (LV) dimensions and wall thicknesses with maintained contractile function by Week 12. However, a sharp decline in contractile function and elevated LV end-diastolic pressure from 12 to 16 weeks were observed after TAC, indicating functional decompensation. 4. Following TAC, mRNA levels of atrial natriuretic peptide, B-type natriuretic peptide, beta-myosin heavy chain (MHC) and transforming growth factor-beta1 were increased time dependently, whereas mRNA expression of alpha-MHC, sarcoplasmic/endoplasmic reticulum calcium ATPase 2a and Bcl-2 were decreased. The ratio of Bcl-2/Bax was decreased and this was consistent with progressively increased myocyte apoptosis demonstrated by terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling staining. Phosphorylation of ERK1/2 was increased by Week 4, but decreased thereafter. Levels of phosphorylated Akt declined from Week 8, whereas GSK3beta phosphorylation increased from 1 to 8 weeks, then decreased from Week 12 after TAC. 5. In conclusion, TAC resulted in early concentric and late eccentric hypertrophy with eventual development of LV dysfunction. This transition was temporally associated with a progressive increase in cell size, fibrosis and myocyte apoptosis. Downregulation of ERK1/2, Akt and GSK3beta and enhanced cardiomyocyte apoptosis are implicated as important mechanisms in the transition from compensated hypertrophy to heart failure. PMID:19566828

  9. Echocardiographic assessment of subclinical left ventricular eccentric hypertrophy in adult-onset GHD patients by geometric remodeling: an observational case-control study

    OpenAIRE

    Trimarchi Francesco; Narbone Maria; Cento Domenico; Venturino Marilena; Almoto Barbara; Grimaldi Patrizia; Recupero Antonino; Curtò Lorenzo; de Gregorio Cesare; Coglitore Sebastiano; Cannavò Salvatore

    2006-01-01

    Abstract Background Most patients with growth hormone deficiency (GHD) show high body mass index. Overweight subjects, but GHD patients, were demonstrated to have high left ventricular mass index (LVMi) and abnormal LV geometric remodeling. We sought to study these characteristics in a group of GHD patients, in an attempt to establish the BMI-independent role of GHD. Methods Fifty-four patients, 28 F and 26 M, aged 45.9 ± 13.1, with adult-onset GHD (pituitary adenomas 48.2%, empty sella 27.8...

  10. 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...

  11. Estudio de la función ventricular y su correlación con la morfometría en pacientes con estenosis aórtica grave sintomática / Relationship of Ventricular Function and Morphometry in Patients with Symptomatic Aortic Stenosis

    Scientific Electronic Library Online (English)

    Alejandro, Hita; Martín, Donato; Sergio, Baratta; Demián, Chejtman; Ricardo A., Costantini; Juan M., Telayna; Mirian, Matoso; Celina, Morales; Ricardo J., Gelpi; José, Navia.

    2011-08-01

    Full Text Available SciELO Argentina | Language: Spanish Abstract in spanish Introducción En la estenosis aórtica, el mecanismo de adaptación miocárdica a la sobrecarga de presión es la hipertrofia ventricular. Diferentes trabajos han planteado la correlación entre estructura y función en la sobrecarga de presión por estenosis aórtica y su posible asociación con la evolución [...] de la patología ventricular. Sin embargo, son escasos los trabajos en los que se evalúan estas variables en corazones con hipertrofia ventricular compensada (sin incremento significativo del estrés parietal) y con fracción de eyección conservada. Objetivos Evaluar la función ventricular sistólica y diastólica en pacientes con estenosis aórtica grave sintomática con fracción de eyección conservada y correlacionarla con el volumen de colágeno y el área miocitaria. Material y métodos Se estudiaron 12 pacientes, edad 65 ± 13 años, sexo masculino 58%, con estenosis aórtica grave sintomática y 6 pacientes sin patología valvular. En todos se realizaron Doppler tisular y cateterismo cardíaco; asimismo, se efectuaron biopsias intraoperatorias para determinar el volumen de colágeno y el área miocitaria (µm²). Resultados La media ± error estándar del volumen de colágeno fue del 6,1% ± 0,7%, la del área miocitaria fue de 388,4 ± 15,8 µm² y la mediana del strain tisular del septum basal fue del 14% (IIC 6,9-19). Se observó una correlación significativa entre el strain tisular del septum y el volumen de colágeno (coeficiente de correlación de -0,79; p = 0,03). No se observó correlación entre el strain tisular del septum y el área miocitaria (R² = 0,15; p = 0,8). La +dP/dt máx normalizada por presión de fin de diástole del ventrículo izquierdo obtenida en estudio hemodinámico se correlacionó en forma negativa con el área miocitaria (R -0,94; p = 0,005). La constante de caída de la presión (tau) se incrementó el 55% ± 3,5% (p Abstract in english Background Ventricular hypertrophy is an adaptive mechanism of the myocardium to pressure overload in aortic stenosis. Different studies have postulated a correlation between structure and function in pressure overload due to aortic stenosis and the possible association with the development of patho [...] logical ventricular growth. However, there are a few studies evaluat-ing these variables in hearts with compensated ventricular hypertrophy (without a significant increase in wall stress) and preserved ejection fraction. Objectives To evaluate systolic and diastolic ventricular function in patients with symptomatic severe aortic stenosis with preserved ejection fraction and its correlation with collagen volume fraction and myocyte cross-sectional area. Material and Methods A total of 12 patients with symptomatic severe aortic stenosis were evaluated and compared with 6 patients without valvular heart disease; mean age was 65±13 years and 58% were men. All patients underwent tissue Doppler imaging and cardiac catheterization. Endomyocardial biopsies were obtained to determine collagen volume fraction and myocyte cross-sectional area (µm²). Results Mean collagen volume was 6.1±0.7%; mean myocyte cross-sectional area was 388.4±15.8 µm² and median strain in the basal septum was 14% (IIC 6.9-19). There was a significant correlation between septal strain measured by tissue Doppler imaging and collagen volume fraction (correlation coefficient -0.79; p = 0.03). We found no correlation between septal strain and myocyte cross-sectional area (R² = 0.15; p = 0.8). The max positive dP/dt normalized for left ventricular end-diastolic pressure obtained during cardiac catheterization had a negative correlation with the myocyte cross-sectional area (R -0.94; p = 0.005).The time constant of pressure decay (tau) increased by 55%±3,5% (p

  12. pH regulation in adult cardiac myocytes

    International Nuclear Information System (INIS)

    The purpose of this study is to examine the pHi regulatory mechanisms of adult ventricular myocytes, the cells that perform the pumping work of the heart. The cell system for this study was the ventricular myocyte, isolated by enzymatic dissociation from adult rate heart. In agreement with the findings on other cardiac model cells, I demonstrated the existence of a Cl-/HCO3- exchanger and a Na+/H+ exchanger in ventricular myocytes. The existence of the anion exchanger was demonstrated in 36Cl- flux experiments and as stilbene disulfonate-inhibitable and Cl- gradient-dependent intracellular pH shifts in the presence of bicarbonate. The fluorescein derivative BCECF served as a fluorescent probe of intracellular pH in the these experiments. The existence of the Na+/H+ exchanger was demonstrated in pHi experiments using BCECF. Further experiments characterized the kinetics of the Na+/H+ exchanger and its regulation. The steady-state pHi of ventricular myocytes was 7.16 ± 0.11 at pH0 = 7.4. Several agonists caused a rise in steady-state pHi: the protein kinase stimulator phorbol myristate acetate (PMA), the ?1-adrenergic agonist 6-fluoro-norepinephrine (6F-NE) and the ?-agonist UK14304, and ATP

  13. Efectividad del uso combinado de un inhibidor de Rho Kinasa y de un antagonista del receptor de angiotensina II en la prevención de hipertrofia ventricular en ratas hipertensas Effectiveness of the combined use of a Rho-kinase inhibitor and an Angiotensin II receptor antagonist in the prevention of left ventricular hypertrophy in hypertensive rats

    Directory of Open Access Journals (Sweden)

    Ulises Novoa

    2010-08-01

    Full Text Available La actividad de Rho kinasa (ROCK cardíaca en la hipertensión arterial (HTA y el efecto del tratamiento antihipertensivo conjunto han sido poco estudiados. Hemos planteado que la adición de un inhibidor de ROCK al tratamiento antihipertensivo convencional podría tener efectos preventivos adicionales al uso aislado del antihipertensivo. Objetivo: Determinar la actividad de ROCK ventricular y parámetros de remodelamiento cardíaco en ratas hipertensas con y sin tratamiento antihipertensivo, adicionando un inhibidor directo de ROCK. Métodos. Se usaron ratas Sprague Dawley de 150 grs. ( n = 12 - 13/grupo unifrectomizadas tratadas con desoxicorticosterona (DOCA, 100 mg/Kg/sem sbc durante 6 semanas. Como controles se usaron ratas unifrectomizadas. Otros 3 grupos recibieron DOCA y además el antagonista del receptor de angiotensina n, candesartán (10 mg/kg/día o el inhibidor de la vía ROCK fasudil (50 mg/Kg/dia, o la combinación de ambos (5 y 25 mg/Kg/dia, respectivamente, vía gavage desde la tercera semana post cirugía, durante 3 semanas. Al finalizar los tratamientos se determinó la masa corporal (MC, presión arterial sistólica (PAS y la masa cardíaca relativa (MCR. Además se midió en el ventrículo izquierdo la fosforilación de la fosfatasa de la miosina (MYPT-1 como índice de activación de ROCK, la infiltración de macrófagos/ monocitos (células ED1 positivas, la expresión proteica de colágeno I (por Western blot y la expresión génica de la subunidad gp91 de NADPH oxidasa y eNOS por RTPCR. Resultados: Con respecto de las ratas sham, en las ratas hipertensas se observó hipertrofia cardiaca de 63% (p Background: The effect of cardiac Rho-kinase (ROCK on hypertension (HT and cardiac hypertrophy prevention and also the combined anti-hypertensive treatment have been scarcely studied. We hypothesized that the addition of a ROCK inhibitor to conventional anti-hypertensive treatment may have additional beneficial effects. Ainv to determine ventricular ROCK activity and ventricular remodeling in hypertensive rats treated with Angiotensin II inhibition with the addition of a ROCK inhibitor. Methods: Sprague-Dawley rats weighing 150 grams had one kidney removed and received deoxycortisterone acétate (DOCA, 100 mg/kg/week, during 6 weeks. Unilaterally nephrectomized rats were used as controls. The other 3 groups received DOCA along with the Angiotensin II receptor blocker candesartan (10 mg/kg/day or the combination of both agents (5 and 25 mg/kg/day, respectively and ROCK inhibitor fasudil (50 mg/kg/day for 3 weeks starting 3 weeks after surgery. Body mass (BM, systolic blood pressure (SBP and relative cardiac mass (RCM were measured. In addition, myosin phosphatase (MYPT-1 phosphorylation was measured as an indicator of ROCK activation. Cardiac infiltration of macrophages/monocytes (ED1 positive cells, collagen I protein contení (by Western Blot and also cardiac gene expression of NADPH oxydase GP91 subunit and eNOS were determined by RT-PCR. Results: In hypertensive rats we observed cardiac hypertrophy by 63% (p < 0.05, a 300% increase in cardiac MYPT-1 phosphorylation (p< 0.05, 14 times increase in myocardial collagen type 1,270% increase in ED1 cells, a 75% increased gene expression of NADPH oxydase GP91 subunit and a 37% reduction (p< 0.05 in the gene expression of cardiac eNOS. In hypertensive DOCA rats treated during 3 week with candesartan, fasudil or the combination of both, we observed a significant reduction in cardiac hypertrophy and normalization of SBP, MYPT-1 phosphorylation, collagen type I, number of ED1 cells, genic expression of NADPH oxydase GP91 subunit and in the genic expression of cardiac eNOS. Conclusión: The combined use of a ROCK inhibitor and a low dose Angiotensin II receptor blocker was as effective as full doses of both isolated agents in the prevention of cardiac hypertrophy and hypertensive experimental cardiac remodeling (Fondecyt 1085208

  14. Valor clínico de la utilización del strain rate sistólico en el estudio de distintas formas de hipertrofia ventricular izquierda / Clinical Value of Systolic Strain Rate Utilization in the Assessment of Different Types of Left Ventricle Hypertrophy

    Scientific Electronic Library Online (English)

    Sergio, Baratta; Demián, Chejtman; Horacio, Fernández; Fabián E., Ferroni; Jorge, Bilbao; Carol, Kotliar; Norberto, Marani; Domingo, Turri; Alejandro, Hita.

    2007-10-01

    Full Text Available SciELO Argentina | Language: Spanish Abstract in spanish Introducción La hipertrofia del ventrículo izquierdo (HVI) incluye diferentes etiologías, estados evolutivos y pronóstico. El strain rate sistólico (SRS) o estudio de la deformación miocárdica permite analizar la función sistólica regional al evaluar la velocidad de acortamiento miocárdico en funció [...] n del tiempo, con independencia del movimiento traslativo del corazón o del tironeamiento de estructuras vecinas. Objetivo Determinar la utilidad del strain rate sistólico para diferenciar formas de hipertrofia del ventrículo izquierdo. Material y métodos La población del estudio estuvo conformada por cuatro grupos: Grupo 1: (G1, n = 10): voluntarios sanos sedentarios; grupo 2 (G2, n = 21): atletas de alto rendimiento con aumento del índice de masa del ventrículo izquierdo (IMVI) > 125 g/m²; grupo 3 (G3, n = 15): pacientes hipertensos según VII JNC con IMVI > 125 g/m² y grupo 4 (G4, n = 12): pacientes con miocardiopatía hipertrófica (MCH), septum > 15 mm y/o relación septum/pared posterior > 1,5:1, sin causa que lo justifique. Resultados En los grupos con IMVI incrementado no hubo diferencia en la fracción de acortamiento mesoparietal (p = 0,3) o el IMVI (p = 0,6). SRS 01 seg (G1) 0,75 1/s, (G2) 0,87 1/s, (G3) 0,57 1/s, (G4) 0,29 1/s (p Abstract in english Introduction Left ventricular hypertrophy (LVH) includes different etiologies, evolution status and prognosis. Systolic strain rate (SSR) or myocardial deformation assessment allows analyzing the regional systolic function by assessing myocardial shortening velocity throughout time, independently of [...] the translation movement of the heart or pulling of neighboring structures. Objective To determine if the systolic strain rate is a useful resource to differentiate types of left ventricle hypertrophy. Material and methods Study population included four groups: Group 1 (G1, n=10): healthy sedentary volunteers; Group 2 (G2, n=21): highperformance athletes with left ventricle mass index increase (LVMI) >125 g/m²; Group 3 (G3, n=15): hypertensive patients according to VII JNC with LVMI >125 g/m² and Group 4 (G4, n=12): patients with hypertrophic cardiomyopathy (HCM), septum >15 mm and/or posterior septum/wall relation >1,5:1, without any cause. Results There were no differences between groups with increased LVMI in mesoparietal shortening fraction (p=0.3) or LVMI (p=0.6). SRS 01 sec (G1) 0.75 1/s. (G2) 0.87 1/s; (G3) 0.57 1/s; (G4) 0.29 1/s (p

  15. Cardiac-restricted overexpression or deletion of tissue inhibitor of matrix metalloproteinase-4: differential effects on left ventricular structure and function following pressure overload-induced hypertrophy.

    Science.gov (United States)

    Yarbrough, William M; Baicu, Catalin; Mukherjee, Rupak; Van Laer, An; Rivers, William T; McKinney, Richard A; Prescott, Corey B; Stroud, Robert E; Freels, Parker D; Zellars, Kia N; Zile, Michael R; Spinale, Francis G

    2014-09-01

    Historically, the tissue inhibitors of matrix metalloproteinases (TIMPs) were considered monochromatic in function. However, differential TIMP profiles more recently observed with left ventricular (LV) dysfunction and matrix remodeling suggest more diverse biological roles for individual TIMPs. This study tested the hypothesis that cardiac-specific overexpression (TIMP-4OE) or deletion (knockout; TIMP-4KO) would differentially affect LV function and structure following pressure overload (LVPO). LVPO (transverse aortic constriction) was induced in mice (3.5 ± 0.1 mo of age, equal sex distribution) with TIMP-4OE (n = 38), TIMP-4KO (n = 24), as well as age/strain-matched wild type (WT, n = 25), whereby indexes of LV remodeling and function such as LV mass and ejection fraction (LVEF) were determined at 28 days following LVPO. Following LVPO, both early (7 days) and late (28 days) survival was ~25% lower in the TIMP-4KO group (P < 0.05). While LVPO increased LV mass in all groups, the relative hypertrophic response was attenuated with TIMP-4OE. With LVPO, LVEF was similar between WT and TIMP-4KO (48 ± 2% and 45 ± 3%, respectively) but was higher with TIMP-4OE (57 ± 2%, P < 0.05). With LVPO, LV myocardial collagen expression (type I, III) increased by threefold in all groups (P < 0.05), but surprisingly this response was most robust in the TIMP-4KO group. These unique findings suggest that increased myocardial TIMP-4 in the context of a LVPO stimulus may actually provide protective effects with respect to survival, LV function, and extracellular matrix (ECM) remodeling. These findings challenge the canonical belief that increased levels of specific myocardial TIMPs, such as TIMP-4 in and of themselves, contribute to adverse ECM accumulation following a pathological stimulus, such as LVPO. PMID:24993046

  16. Effects of azilsartan compared to other angiotensin receptor blockers on left ventricular hypertrophy and the sympathetic nervous system in hemodialysis patients.

    Science.gov (United States)

    Kusuyama, Takanori; Ogata, Hirohito; Takeshita, Hiroaki; Kohno, Hiroaki; Shimodozono, Shinichi; Iida, Hidetaka; Tsukazaki, Takashi

    2014-10-01

    Hypertension is a major risk factor for cardiovascular and cerebrovascular events, and most patients with hypertension are administered antihypertensive drugs. However, not all patients achieve normal blood pressure levels. The new angiotensin receptor blocker azilsartan (Takeda Pharmaceutical Company Limited, Osaka, Japan) has been reported to have a strong hypotensive effect. Our study investigated the efficacy of azilsartan compared with other angiotensin receptor blockers. This study included 17 hypertensive patients on HD, who had been administered angiotensin receptor blockers, except for azilsartan, for more than 6 months before enrolling, and after enrollment, they were switched to azilsartan. Blood tests, Holter electrocardiogram, ambulatory blood pressure monitoring, and echocardiography were performed at baseline and at the 6-month follow-up. The blood pressure from baseline to 6 months had significantly decreased (24-h systolic blood pressure from 150.9 ± 16.2 mm Hg to 131.3 ± 21.7 mm Hg, P = 0.008), awakening time systolic blood pressure from 152.1 ± 16.9 mm Hg to 131.7 ± 23.2 mm Hg, P = 0.01, sleep-time systolic blood pressure from 148.1 ± 19.7 mm Hg to 130.0 ± 20.1 mm Hg, P = 0.005). There was a significant reduction in serum noradrenaline levels as well as left ventricular mass index after switching to azilsartan (from 550.1 ± 282.9 pg/mL, to 351.7 ± 152.3 pg/mL, P = 0.002; from 117.0 ± 26.4 g/m(2) to 111.3 ± 23.9 g/m(2), P = 0.01, respectively). Azilsartan had a significantly stronger hypotensive effect than other angiotensin receptor blockers. Thus, the switch to azilsartan might improve prognosis of hemodialysis patients. We suggest that the strong anti-hypertensive effect of azilsartan originated from a combination of primary angiotensin receptor blocker class-effect and a stronger suppression of sympathetic nervous system. PMID:24571483

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

    OpenAIRE

    Icli, Basak; Bharti, Ajit; Pentassuglia, Laura; Peng, Xuyang; Sawyer, Douglas B.

    2012-01-01

    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 P...

  18. Varieties of right ventricular diastolic function in patients with non-obstructive hypertrophic cardiomyopathy.

    Science.gov (United States)

    Komaki, Kohtaroh; Sakuma, Masahito; Ishigaki, Hidehiko; Hozawa, Hidenari; Yamamoto, Yoshito; Takahashi, Tohru; Kumasaka, Norihisa; Kagaya, Yutaka; Ikeda, Jun; Watanabe, Jun; Shirato, Kunio

    2003-01-01

    We examined whether differences in the location of myocardial hypertrophy influence the right ventricular diastolic function in patients with non-obstructive hypertrophic cardiomyopathy using cineangiography. Biplane right ventriculography was performed in 34 subjects (normal = 14, asymmetric septal hypertrophy = 9, apical hypertrophy = 11) during cardiac catheterization. In patients with asymmetric septal hypertrophy, compared with apical hypertrophy and normal groups, the indices of the right ventricular diastolic function including right ventricular peak filling rate and filling fraction of rapid filling phase were lower and the time to peak filling rate was prolonged. But in patients with apical hypertrophy, these indices were not significantly different compared with normal. There were no differences in right ventricular ejection fraction and cardiac index among the three groups. These data suggest that the location of the myocardial hypertrophy of the left ventricle is a significant factor affecting the right ventricular diastolic filling in non-obstructive hypertrophic cardiomyopathy. PMID:12688560

  19. Effects of cholesterol depletion on compartmentalized cAMP responses in adult cardiac myocytes

    OpenAIRE

    Agarwal, Shailesh R.; Macdougall, David A.; Tyser, Richard; Pugh, Sara D.; Calaghan, Sarah C.; Harvey, Robert D.

    2011-01-01

    ?1-Adrenergic receptors (?1ARs) and E-type prostaglandin receptors (EPRs) both produce compartmentalized cAMP responses in cardiac myocytes. The role of cholesterol-dependent lipid rafts in producing these compartmentalized responses was investigated in adult rat ventricular myocytes. ?1ARs were found in lipid raft and non-lipid raft containing membrane fractions, while EPRs were only found in non-lipid raft fractions. Furthermore, ?1AR activation enhanced the L-type Ca2+ current, intrace...

  20. Efectividad del uso combinado de un inhibidor de Rho Kinasa y de un antagonista del receptor de angiotensina II en la prevención de hipertrofia ventricular en ratas hipertensas / Effectiveness of the combined use of a Rho-kinase inhibitor and an Angiotensin II receptor antagonist in the prevention of left ventricular hypertrophy in hypertensive rats

    Scientific Electronic Library Online (English)

    Ulises, Novoa; María Paz, Ocaranza; Italo, Mora; Jorge, Jalil.

    2010-08-01

    Full Text Available SciELO Chile | Language: Spanish Abstract in spanish La actividad de Rho kinasa (ROCK) cardíaca en la hipertensión arterial (HTA) y el efecto del tratamiento antihipertensivo conjunto han sido poco estudiados. Hemos planteado que la adición de un inhibidor de ROCK al tratamiento antihipertensivo convencional podría tener efectos preventivos adicionale [...] s al uso aislado del antihipertensivo. Objetivo: Determinar la actividad de ROCK ventricular y parámetros de remodelamiento cardíaco en ratas hipertensas con y sin tratamiento antihipertensivo, adicionando un inhibidor directo de ROCK. Métodos. Se usaron ratas Sprague Dawley de 150 grs. ( n = 12 - 13/grupo) unifrectomizadas tratadas con desoxicorticosterona (DOCA, 100 mg/Kg/sem sbc) durante 6 semanas. Como controles se usaron ratas unifrectomizadas. Otros 3 grupos recibieron DOCA y además el antagonista del receptor de angiotensina n, candesartán (10 mg/kg/día) o el inhibidor de la vía ROCK fasudil (50 mg/Kg/dia), o la combinación de ambos (5 y 25 mg/Kg/dia, respectivamente), vía gavage desde la tercera semana post cirugía, durante 3 semanas. Al finalizar los tratamientos se determinó la masa corporal (MC), presión arterial sistólica (PAS) y la masa cardíaca relativa (MCR). Además se midió en el ventrículo izquierdo la fosforilación de la fosfatasa de la miosina (MYPT-1) como índice de activación de ROCK, la infiltración de macrófagos/ monocitos (células ED1 positivas), la expresión proteica de colágeno I (por Western blot) y la expresión génica de la subunidad gp91 de NADPH oxidasa y eNOS por RTPCR. Resultados: Con respecto de las ratas sham, en las ratas hipertensas se observó hipertrofia cardiaca de 63% (p Abstract in english Background: The effect of cardiac Rho-kinase (ROCK) on hypertension (HT) and cardiac hypertrophy prevention and also the combined anti-hypertensive treatment have been scarcely studied. We hypothesized that the addition of a ROCK inhibitor to conventional anti-hypertensive treatment may have additio [...] nal beneficial effects. Ainv to determine ventricular ROCK activity and ventricular remodeling in hypertensive rats treated with Angiotensin II inhibition with the addition of a ROCK inhibitor. Methods: Sprague-Dawley rats weighing 150 grams had one kidney removed and received deoxycortisterone acétate (DOCA, 100 mg/kg/week, during 6 weeks). Unilaterally nephrectomized rats were used as controls. The other 3 groups received DOCA along with the Angiotensin II receptor blocker candesartan (10 mg/kg/day) or the combination of both agents (5 and 25 mg/kg/day, respectively) and ROCK inhibitor fasudil (50 mg/kg/day) for 3 weeks starting 3 weeks after surgery. Body mass (BM), systolic blood pressure (SBP) and relative cardiac mass (RCM) were measured. In addition, myosin phosphatase (MYPT-1) phosphorylation was measured as an indicator of ROCK activation. Cardiac infiltration of macrophages/monocytes (ED1 positive cells), collagen I protein contení (by Western Blot) and also cardiac gene expression of NADPH oxydase GP91 subunit and eNOS were determined by RT-PCR. Results: In hypertensive rats we observed cardiac hypertrophy by 63% (p

  1. Direct toxic effects of aqueous extract of cigarette smoke on cardiac myocytes at clinically relevant concentrations

    International Nuclear Information System (INIS)

    Aims: Our goal was to determine if clinically relevant concentrations of aqueous extract of cigarette smoke (CSE) have direct deleterious effects on ventricular myocytes during simulated ischemia, and to investigate the mechanisms involved. Methods: CSE was prepared with a smoking chamber. Ischemia was simulated by metabolic inhibition (MI) with cyanide (CN) and 0 glucose. Adult rabbit and mouse ventricular myocyte [Ca2+]i was measured by flow cytometry using fluo-3. Mitochondrial [Ca2+] was measured with confocal microscopy, and Rhod-2 fluorescence. The mitochondrial permeability transition (MPT) was detected by TMRM fluorescence and myocyte contracture. Myocyte oxidative stress was quantified by dichlorofluorescein (DCF) fluorescence with confocal microscopy. Results: CSE 0.1% increased myocyte contracture caused by MI. The nicotine concentration (HPLC) in 0.1% CSE was 15 ng/ml, similar to that in humans after smoking cigarettes. CSE 0.1% increased mitochondrial Ca2+ uptake, and increased the susceptibility of mitochondria to the MPT. CSE 0.1% increased DCF fluorescence in isolated myocytes, and increased [Ca2+]i in paced myocytes exposed to 2.0 mM CN, 0 glucose (P-MI). These effects were inhibited by the superoxide scavenger Tiron. The effect of CSE on [Ca2+]i during P-MI was also prevented by ranolazine. Conclusions: CSE in clinically relevant concentrations increases myocyte [elevant concentrations increases myocyte [Ca2+]i during simulated ischemia, and increases myocyte susceptibility to the MPT. These effects appear to be mediated at least in part by oxidative radicals in CSE, and likely contribute to the effects of cigarette smoke to increase myocardial infarct size, and to decrease angina threshold

  2. Revisão dos critérios de Sokolow-Lyon-Rappaport e cornell para hipertrofia do ventrículo esquerdo / Revision of the Sokolow-Lyon-Rappaport and cornell voltage criteria for left ventricular hypertrophy

    Scientific Electronic Library Online (English)

    Sérgio Lamêgo, Rodrigues; Lílian, D’Angelo; Alexandre Costa, Pereira; José Eduardo, Krieger; José Geraldo, Mill.

    2008-01-01

    Full Text Available FUNDAMENTO: A hipertrofia do ventrículo esquerdo (HVE) detectada pela eletrocardiografia é um forte preditor de morbidade e mortalidade cardiovasculares. OBJETIVO: Analisar o desempenho dos critérios de Sokolow-Lyon-Rappaport (SLR) e de Cornell, em amostra populacional, em relação ao diagnóstico de [...] HVE à ecocardiografia. MÉTODOS: Entre os 682 participantes da segunda fase do Projeto MONICA-OMS/Vitória, 641 foram avaliados por meio de eletrocardiografia e ecocardiografia. O subgrupo de indivíduos saudáveis (n = 269) foi usado para gerar valores de referência da massa do ventrículo esquerdo (MVE). As sensibilidades e especificidades dos critérios eletrocardiográficos foram determinadas pela curva ROC (receptor-operator characteristics) em relação ao diagnóstico de HVE definido pelo critério ecocardiográfico interno (MVE > 48 g/m2,7 e 46 g/m2,7 para homens e mulheres, respectivamente). RESULTADOS: A prevalência de HVE à ecocardiografia foi de 23,7% na amostra global, em que havia 49% de hipertensos. O critério de Cornell apresentou melhor associação com a MVE estimada pela ecocardiografia (r = 0,37; p Abstract in english BACKGROUND: Electrocardiographically-detected left ventricular hypertrophy (LVH) is a strong predictor of cardiovascular morbidity and mortality. OBJECTIVE: To assess the performance of the Sokolow-Lyon-Rappaport (SLR) and Cornell voltage criteria in a population sample regarding the diagnosis of LV [...] H on echocardiogram (ECHO). METHODS: A total of 641 out of the 682 participants of the second phase of the MONICA-Vitória project were assessed using electrocardiogram and echocardiogram. A subgroup of healthy individuals (n=269) was used to generate reference values of LV mass (LVM). Sensitivities and specificities of the electrocardiographic criteria were determined by the ROC (receptor-operator characteristics) curve in relation to the diagnosis of LVH, as defined by the internal echocardiographic criterion (LVM > 48 and 46 g/m2.7 for males and females, respectively). RESULTS: The prevalence of LVH as detected by ECHO was 23.7% in the total sample, in which 49% of the individuals were hypertensive. The Cornell criterion showed a better association with the LVM as estimated by ECHO (r= 0.37, p

  3. Magnesium Homeostasis in Cardiac Myocytes of Mg-Deficient Rats

    OpenAIRE

    Tashiro, Michiko; Inoue, Hana; Konishi, Masato

    2013-01-01

    To study possible modulation of Mg2+ transport in low Mg2+ conditions, we fed either a Mg-deficient diet or a Mg-containing diet (control) to Wistar rats for 1–6 weeks. Total Mg concentrations in serum and cardiac ventricular tissues were measured by atomic absorption spectroscopy. Intracellular free Mg2+ concentration ([Mg2+]i) of ventricular myocytes was measured with the fluorescent indicator furaptra. Mg2+ transport rates, rates of Mg2+ influx and Mg2+ efflux, were estimated from the ra...

  4. Análise da atividade da enzima conversora da angiotensina na hipertrofia aguda do ventrículo direito em modelo experimental de estenose endovascular ajustável do tronco pulmonar / Evaluation of angiotensin converting enzyme activity in acute right ventricular hypertrophy in an experimental model of adjustable endovascular stenosis of the pulmonary trunk

    Scientific Electronic Library Online (English)

    Renato Rocha, RABELLO; Renato Samy, ASSAD; José Eduardo, KRIEGER; Renata, CARMONA; Maria Cristina, ABDUCH; Sérgio Almeida de, OLIVEIRA.

    2001-12-01

    Full Text Available SciELO Brazil | Language: Portuguese Abstract in portuguese INTRODUÇÃO: A bandagem do tronco pulmonar (TP) tem sido aplicada para treinamento do ventrículo esquerdo (VE) em pacientes portadores de transposição das grandes artérias (TGA) com septo íntegro. Este procedimento, além de apresentar alta morbi-mortalidade, pode ocasionar alterações da função ventri [...] cular a longo prazo. Com o objetivo de analisar a hipertrofia aguda do ventrículo direito (VD), foi implantado um cateter balão no TP de seis cabritos jovens. MATERIAL E MÉTODOS: A sobrecarga sistólica foi aplicada através de insuflações progressivas do balão, durante 96 horas. Esta hipertrofia foi acompanhada por medidas hemodinâmicas diárias, através de cateteres implantados na aorta, VD e TP, além de ecocardiogramas seriados a cada 24 horas, com medidas das espessuras do septo interventricular e dos ventrículos. Ao final das 96 horas, os animais foram mortos para remoção dos corações. Os ventrículos e o septo foram pesados separadamente. Foram colhidas biópsias musculares de cada câmara para análise da atividade da enzima conversora da angiotensina (ECA). Oito cabritos (idade e peso semelhantes) foram utilizados como controle para os pesos dos ventrículos e para a atividade da ECA. RESULTADOS: Observou-se um aumento do gradiente VD/TP (p=0,001), com conseqüente aumento da razão VD/VE (p=0,005) durante o tempo de sobrecarga sistólica. Ao fim do protocolo, a parede livre do VD apresentou aumento de espessura (p=0,002) e, conseqüentemente, um aumento do peso indexado (p=0,002). A análise da atividade da ECA revelou aumento somente no músculo do VD hipertrofiado (p=0,002). CONCLUSÃO: O cateter balão foi eficiente em induzir a hipertrofia aguda do VD através do protocolo utilizado. Conseqüentemente, um aumento expressivo da atividade da ECA está associado ao processo de hipertrofia miocárdica induzida por sobrecarga pressórica. Abstract in english INTRODUCTION: The pulmonary trunk (PT) banding has been used to promote rapid left ventricular (LV) hypertrophy in patients with transposition of the great vessels (TGV) with intact septum, treated after the neonatal period. This procedure carries a high morbidity and mortality rates. Genetic altera [...] tions of the cardiomyocytes resulting from acute hypertrophy have not been evaluated in models of variable systolic overload of the subpulmonary ventricle. In order to evaluate the activity of angiotensin converting enzyme (ACE) in acute right ventricular (RV) hypertrophy, a balloon catheter was implanted in the PT of six young goats. MATERIAL AND METHODS: Systolic overload was carried out throughout progressive balloon insufflations for a period of 96 hours. Hypertrophy was followed by daily hemodynamic and echocardiographic evaluations. At the end of the 96 hours, the animals were killed to harvest the heart. The ventricles and septum were weighted separately. Samples of each cardiac muscle were collected for ACE analysis. Eight goats (with similar age and weight) were used as control for weight and ACE activity. RESULTS: At the end of the protocol, the following parameters were increased: RV/PT gradient (p=0.001), RV to LV ratio (p=0.005), thickness of the free wall of RV (p=0.002) and RV weight (p=0.002). The evaluation of ACE activity showed an increase only in the hypertrophied RV muscle (p=0.002), indicating a high correlation with the increase in the RV to LV ratio (r=0.87). CONCLUSION: The progressive systolic overload in the RV of goats induces ventricular hypertrophy. This hypertrophy is related to a significant increase in ACE activity, an important molecular marker of this process.

  5. Effect of PPAR ? activators on hypertrophic cardiac myocytes in vitro

    International Nuclear Information System (INIS)

    Objective: To investigate the effects of peroxisome proliferator-activated receptor ? (PPAR ?) activators pioglitazone and 15-deoxy-?12,14 prostaglandin J2(15d-PGJ2) on hypertrophic cardiac myocytes (MC) of neonatal rats in vitro. Methods; With the stimulation of angiotensin II(Ang II), a model of hypertrophy of MC was established. With the method of reverse transcription-polymerase chain reaction (RT-PCR), mRNA expression of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) was amplified; with the aid of NIH Image J software the surface area of MC was analyzed and with 3H-leucine incorporation, the synthesizing rate of protein in MC was measured. Results: Increases in surface area of MC, mRNA expression of ANP and BNP and 3H-leucine incorporation in MC were observed in the model of cardiac hypertrophy. Pioglitazone and 15d-PGJ2, two kinds of PPAR ? activators, inhibited the above changes in a dose-dependent manner. Conclusion: It is suggested that PPAR ? activators inhibit hypertrophy of cardiac myocytes and PPAR ?-dependent pathway be involved in the inhibitory course

  6. Pharmacological targeting of CDK9 in cardiac hypertrophy.

    Czech Academy of Sciences Publication Activity Database

    Kryštof, Vladimír; Chamrád, Ivo; Jorda, Radek; Kohoutek, J.

    2010-01-01

    Ro?. 30, ?. 4 (2010), s. 646-666. ISSN 0198-6325 R&D Projects: GA ?R GA204/08/0511; GA ?R GA301/09/1832; GA ?R GA301/08/1649 Institutional research plan: CEZ:AV0Z50380511 Keywords : P-TEFb * cardiac myocyte * cardiac hypertrophy Subject RIV: CE - Biochemistry Impact factor: 10.228, year: 2010

  7. Scintigraphic findings in asymmetrical septal hypertrophy with multigated radionuclide angiography

    International Nuclear Information System (INIS)

    Twelve patients with asymmetric septal hypertrophy were studied by mean Multigated Radionuclide Angiography. The ejection fraction, end diastolic volumen, end systolic volumen, and morphological aspects of left ventricle were evaluated. The results were compared with a group of 170 patients (10 normals, 8 aortic valvular stenosis and 152 with coronary artery disease). A significative increase of ejection fraction, a decrease of end systolic volume and abnormal configuration of left ventricular cavity were found in patients with asymmetric septal hypertrophy

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

    OpenAIRE

    Kinnunen, P.; Taskinen, T.; Leppa?luoto, J.; Ruskoaho, H.

    1990-01-01

    1. Ventricular hypertrophy is characterized by stimulation of ventricular synthesis of atrial natriuretic peptide (ANP). To examine the role of ventricular ANP levels in the secretion of ANP into the circulation, atrial and ventricular levels of immunoreactive-ANP (IR-ANP) as well as ANP messenger RNA (mRNA), and the release of IR-ANP from isolated perfused hearts, both before and after atrialectomy, were measured simultaneously in control and minoxidil-treated Wistar-Kyoto (WKY) and spontane...

  9. Papillary muscle hypertrophy as a structural abnormality in patients with asymmetric septal hypertrophy

    Directory of Open Access Journals (Sweden)

    Mehmet Kanada?ý

    2003-09-01

    Full Text Available Introduction: Asymmetric septal hypertrophy (ASH is the most classical abnormality in hypertrophic cardiomy-opathy (HCM. Segmental hypertrophy of the left ventricle is less frequently observed. Some cases with papillary muscle hypertrophy (PMH particularly associated with apical HCM and also ASH has been reported. Aim of the study: The aim of this study was to determine the frequency of PMH in patients with ASH. Material and methods: Two-dimensional echocardiographic examinations were performed in 42 patients with ASH (group I, 32 patients with left ventricular hypertrophy secondary to hypertension (group II and 26 healthy subjects (group III with comparable mean age and sex. The thickness of the papillary muscles was measu-red either the vertical or horizontal diameter of at least one of the two papillary muscles at end-diastole in short axis view. Papillary muscle hypertrophy was defined, if the papillary muscle diameter was more than the mean + 2 standard deviation of the healthy subjects. Results: The mean thickness of anterior papillary muscle (APM and posterior papillary muscle (PPM were 8.1 ±;1.1 mm and 7.9±;1.0mm, respectively, in group III. Both papillary muscles thickness in-group II and I were greater than group III (p<0.001. Ten (24% and 25 (78% patients had APM hypertrophy in group I and II, respectively. PPM hypertrophy was found in 8 (19% and 21 (66% patients in group I and II, respective-ly. A positive correlation was observed between APM hypertrophy and systolic anterior motion in group I (r= 0.522, p=0.003. There was also a positive correlation between APM hypertrophy and the degree of left ventricularoutflowtract obstruction (r=0.478, p=0.004. Conclusion: Our findings show that PMH is an important component of hypertrophic cardiomyopathy as well as ASH in some patients. Patients with PMH may contribute the occurrence of systolic anterior motion and the degree of left ventricle outflow obstruction.

  10. 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.

  11. Combinación de un inhibidor de la enzima convertidora de la angiotensina con un antagonista del calcio versus la monoterapia con el IECA: eficacia terapéutica en hipertensión arterial esencial y regresión de la hipertrofia cardíaca / Combination of a Converting Enzyme Inhibitor (ACEI) with a Calcium Antagonist versus Monotherapy with an ACEI: Therapeutic Efficacy in Essential Hypertension and Regression of Ventricular Hypertrophy

    Scientific Electronic Library Online (English)

    Laura M. J., Brandani; Hugo P., Baglivo; Juan J., Rodríguez-Moncalvo; Fernando, Verra; Ramiro A., Sánchez; Agustín J., Ramírez.

    2006-06-01

    Full Text Available Objetivo Evaluar la eficacia y la tolerancia, así como su acción sobre la regresión de la hipertrofia ventricular izquierda, de la combinación de benazepril más amlodipina (B + A) versus la monoterapia con benazepril (B). Material y métodos Se incluyeron 33 hipertensos esenciales. Durante 6 meses de [...] tratamiento, 18 de ellos recibieron B + A (9 varones, 55 ± 2 años) y los 15 restantes recibieron B (10 varones, 49 ± 2 años). Se realizó una presurometría (MAPA) al comienzo y a los 3 y a los 6 meses de tratamiento. En un subgrupo de 23 pacientes se calculó la masa ventricular izquierda (MVI) y el índice de MVI (IMVI) al inicio y al final del tratamiento. Resultados A los 3 meses de tratamiento, los valores de la presión arterial (PA) fueron significativamente menores (p Abstract in english Objective To evaluate the effectiveness, tolerability and effect on the regression of left ventricular hypertrophy, of a combination therapy of amlodipine and benazepril (B+A), versus monotherapy with benazepril (B). Methods We included 33 patients (p) with essential hypertension. During 6 months of [...] treatment, 18 p received B+A (9 men, 55±2 years) and 15 received B (10 men, 49±2 years). An ambulatory blood pressure monitoring (ABPM) was performed at the beginning and at 3 and 6 months of therapy. In a subgroup of 23 patients, left ventricular mass (LVM) and LVM index (LVMI) were calculated from the two dimensional echocardiogram, at the beginning and the end of treatment. Results At 3 months of treatment, blood pressure (BP) values were significantly (p

  12. Pim-1 kinase antagonizes aspects of myocardial hypertrophy and compensation to pathological pressure overload.

    Science.gov (United States)

    Muraski, John A; Fischer, Kimberlee M; Wu, Weitao; Cottage, Christopher T; Quijada, Pearl; Mason, Matt; Din, Shabana; Gude, Natalie; Alvarez, Roberto; Rota, Marcello; Kajstura, Jan; Wang, Zeping; Schaefer, Erik; Chen, Xiongen; MacDonnel, Scott; Magnuson, Nancy; Houser, Stephen R; Anversa, Piero; Sussman, Mark A

    2008-09-16

    Pim-1 kinase exerts potent cardioprotective effects in the myocardium downstream of AKT, but the participation of Pim-1 in cardiac hypertrophy requires investigation. Cardiac-specific expression of Pim-1 (Pim-WT) or the dominant-negative mutant of Pim-1 (Pim-DN) in transgenic mice together with adenoviral-mediated overexpression of these Pim-1 constructs was used to delineate the role of Pim-1 in hypertrophy. Transgenic overexpression of Pim-1 protects mice from pressure-overload-induced hypertrophy relative to wild-type controls as evidenced by improved hemodynamic function, decreased apoptosis, increases in antihypertrophic proteins, smaller myocyte size, and inhibition of hypertrophic signaling after challenge. Similarly, Pim-1 overexpression in neonatal rat cardiomyocyte cultures inhibits hypertrophy induced by endothelin-1. On the cellular level, hearts of Pim-WT mice show enhanced incorporation of BrdU into myocytes and a hypercellular phenotype compared to wild-type controls after hypertrophic challenge. In comparison, transgenic overexpression of Pim-DN leads to dilated cardiomyopathy characterized by increased apoptosis, fibrosis, and severely depressed cardiac function. Furthermore, overexpression of Pim-DN leads to reduced contractility as evidenced by reduced Ca(2+) transient amplitude and decreased percentage of cell shortening in isolated myocytes. These data support a pivotal role for Pim-1 in modulation of hypertrophy by impacting responses on molecular, cellular, and organ levels. PMID:18784362

  13. Coupling an HCN2-expressing cell to a myocyte creates a two-cell pacing unit

    Science.gov (United States)

    Valiunas, V; Kanaporis, G; Valiuniene, L; Gordon, C; Wang, H Z; Li, L; Robinson, R B; Rosen, M R; Cohen, I S; Brink, P R

    2009-01-01

    We examined whether coupling of a ventricular myocyte to a non-myocyte cell expressing HCN2 could create a two-cell syncytium capable of generating sustained pacing. Three non-myocyte cell types were transfected with the mHCN2 gene and used as sources of mHCN2-induced currents. They were human mesenchymal stem cells and HEK293 cells, both of which express connexin43 (Cx43), and HeLa cells transfected with Cx43. Cell–cell coupling between heterologous pairs increased with time in co-culture, and hyperpolarization of the myocyte induced HCN2 currents, indicating current transfer from the mHCN2-expressing cell to the myocyte via gap junctions. The magnitude of the HCN2 currents recorded in myocytes increased with increasing junctional conductance. Once a critical level of electrical cell–cell coupling between myocytes and mHCN2 transfected cells was exceeded spontaneous action potentials were generated at frequencies of ?0.6 to 1.7 Hz (1.09 ± 0.05 Hz). Addition of carbenoxolone (200 ?m), a gap junction channel blocker, to the media stopped spontaneous activity in heterologous cell pairs. Carbenoxolone washout restored activity. Blockade of HCN2 currents by 100 ?m 9-amino-1,2,3,4-tetrahydroacridine (THA) stopped spontaneous activity and subsequent washout restored it. Neither THA nor carbenoxolone affected electrically stimulated action potentials in isolated single myocytes. In summary, the inward current evoked in the genetically engineered (HCN2-expressing) cell was delivered to the cardiac myocyte via gap junctions and generated action potentials such that the cell pair could function as a pacemaker unit. This finding lays the groundwork for understanding cell-based biological pacemakers in vivo once an understanding of delivery and target cell geometry is defined. PMID:19736302

  14. Influence of extracellular H+ and Ca2+ on Ro 22-9194-induced block of sodium current in cardiac myocytes.

    Science.gov (United States)

    Hisatome, I; Tanaka, Y; Sasaki, N; Hiroe, K; Ahmmed, G U; Tsuboi, M; Manabe, I; Suga, T; Yamamoto, Y; Ohtahara, A; Kinugawa, T; Ogino, K; Igawa, O; Yoshida, A; Saito, M; Sato, R; Shigemasa, C

    1997-10-01

    1. Ro 22-9194 reduced the Na current in ventricular myocytes in either a tonic block or phasic block manner. 2. Ro 22-9194 had a higher affinity to the inactivated state (Kdi = 10.3 microM) than to the rested state (Kdrest = 180 microM). 3. Extracellular acidification enhanced the tonic block but reduced the phasic block. 4. Elevation of extracellular Ca2+ inhibited the enhancing effects of extracellular acidification. 5. These findings suggest that Ro 22-9194 strongly inhibits Na+ channels of the ventricular myocytes of the diseased hearts, characterized by the depolarized cell membranes and by acid conditions. PMID:9352302

  15. Chronic N(G)-nitro-L-arginine methyl ester-induced hypertension : novel molecular adaptation to systolic load in absence of hypertrophy

    Science.gov (United States)

    Bartunek, J.; Weinberg, E. O.; Tajima, M.; Rohrbach, S.; Katz, S. E.; Douglas, P. S.; Lorell, B. H.; Schneider, M. (Principal Investigator)

    2000-01-01

    BACKGROUND: Chronic N(G)-nitro-L-arginine methyl ester (L-NAME), which inhibits nitric oxide synthesis, causes hypertension and would therefore be expected to induce robust cardiac hypertrophy. However, L-NAME has negative metabolic effects on protein synthesis that suppress the increase in left ventricular (LV) mass in response to sustained pressure overload. In the present study, we used L-NAME-induced hypertension to test the hypothesis that adaptation to pressure overload occurs even when hypertrophy is suppressed. METHODS AND RESULTS: Male rats received L-NAME (50 mg. kg(-1). d(-1)) or no drug for 6 weeks. Rats with L-NAME-induced hypertension had levels of systolic wall stress similar to those of rats with aortic stenosis (85+/-19 versus 92+/-16 kdyne/cm). Rats with aortic stenosis developed a nearly 2-fold increase in LV mass compared with controls. In contrast, in the L-NAME rats, no increase in LV mass (1. 00+/-0.03 versus 1.04+/-0.04 g) or hypertrophy of isolated myocytes occurred (3586+/-129 versus 3756+/-135 microm(2)) compared with controls. Nevertheless, chronic pressure overload was not accompanied by the development of heart failure. LV systolic performance was maintained by mechanisms of concentric remodeling (decrease of in vivo LV chamber dimension relative to wall thickness) and augmented myocardial calcium-dependent contractile reserve associated with preserved expression of alpha- and beta-myosin heavy chain isoforms and sarcoplasmic reticulum Ca(2+) ATPase (SERCA-2). CONCLUSIONS: When the expected compensatory hypertrophic response is suppressed during L-NAME-induced hypertension, severe chronic pressure overload is associated with a successful adaptation to maintain systolic performance; this adaptation depends on both LV remodeling and enhanced contractility in response to calcium.

  16. Concentric left ventricular remodeling and aortic stiffness: a comparison of obesity and hypertension.

    OpenAIRE

    Rider, Oj; Nethononda, R.; Petersen, Se; Francis, Jm; Byrne, Jp; Leeson, P.; Clarke, K.; Neubauer, S.

    2013-01-01

    Background: Increased thoracic ascending aortic stiffness is thought to contribute to concentric left ventricular hypertrophy and increased mortality, a pattern seen in hypertension. As such, aortic stiffness and increased left ventricular mass are candidates by which obesity increases cardiovascular risk. However, obesity is characterized predominantly by increased abdominal aortic stiffness and with eccentric left ventricular hypertrophy. Methods: We aimed to establish whether or not, in ad...

  17. ??A-adrenergic receptors regulate cardiac hypertrophy in vivo through interleukin-6 secretion.

    Science.gov (United States)

    Papay, Robert S; Shi, Ting; Piascik, Michael T; Naga Prasad, Sathyamangla V; Perez, Dianne M

    2013-05-01

    The role of ??-adrenergic receptors (ARs) in the regulation of cardiac hypertrophy is still unclear, because transgenic mice demonstrated hypertrophy or the lack of it despite high receptor overexpression. To further address the role of the ??-ARs in cardiac hypertrophy, we analyzed unique transgenic mice that overexpress constitutively active mutation (CAM) ??A-ARs or CAM ??B-ARs under the regulation of large fragments of their native promoters. These constitutively active receptors are expressed in all tissues that endogenously express their wild-type counterparts as opposed to only myocyte-targeted transgenic mice. In this study, we discovered that CAM ??A-AR mice in vivo have cardiac hypertrophy independent of changes in blood pressure, corroborating earlier studies, but in contrast to myocyte-targeted ??A-AR mice. We also found cardiac hypertrophy in CAM ??B-AR mice, in agreement with previous studies, but hypertrophy only developed in older mice. We also discovered unique ??-AR-mediated hypertrophic signaling that was AR subtype-specific with CAM ??A-AR mice secreting atrial naturietic factor and interleukin-6 (IL-6), whereas CAM ??B-AR mice expressed activated nuclear factor-?B (NF-?B). These particular hypertrophic signals were blocked when the other AR subtype was coactivated. We also discovered that crossbreeding the two CAM models (double CAM ??A/B-AR) inhibited the development of hypertrophy and was reversible with single receptor activation, suggesting that coactivation of the receptors can lead to novel antagonistic signal transduction. This was confirmed by demonstrating antagonistic signals that were even lower than normal controls in the double CAM ??A/B-AR mice for p38, NF-?B, and the IL-6/glycoprotein 130/signal transducer and activator of transcription 3 pathway. Because ??A/B double knockout mice fail to develop hypertrophy in response to IL-6, our results suggest that IL-6 is a major mediator of ??A-AR cardiac hypertrophy. PMID:23404509

  18. A mathematical model of the mechanical link between shortening of the cardiomyocytes and systolic deformation of the left ventricular myocardium

    DEFF Research Database (Denmark)

    Smerup, Morten Holdgaard; Partridge, J

    2013-01-01

    Left ventricular myocytes are arranged in a complex three-dimensional mesh. Since all myocytes contract approximately to the same degree, mechanisms must exist to enable force transfer from each of these onto the framework as a whole, despite the transmural differences in deformation strain. This process has hitherto not been clarified in detail.

  19. 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.

  20. Ventricular arrhythmias.

    OpenAIRE

    Kavanagh, K. M.; Wyse, D. G.

    1988-01-01

    Sudden cardiac death claims thousands of Canadians annually. Ventricular tachycardia and fibrillation account for up to 85% of these deaths. Identifying the patients at risk remains a major challenge. Those who have recurrent ventricular tachycardia or have been resuscitated from ventricular fibrillation are generally considered to be at highest risk. Although ventricular premature beats in the absence of previous ventricular tachycardia or fibrillation are not helpful in identifying such pat...

  1. PDE5A suppression of acute ?-adrenergic activation requires modulation of myocyte beta-3 signaling coupled to PKG-mediated troponin I phosphorylation

    OpenAIRE

    Lee, Dong I.; Vahebi, Susan; Tocchetti, Carlo Gabriele; Barouch, Lili A.; Solaro, R. John; Takimoto, Eiki; Kass, David A.

    2010-01-01

    Phosphodiesterase type 5A (PDE5A) inhibitors acutely suppress beta-adrenergic receptor (?-AR) stimulation in left ventricular myocytes and hearts. This modulation requires cyclic GMP synthesis via nitric oxide synthase (NOS)-NO stimulation, but upstream and downstream mechanisms remain un-defined. To determine this, adult cardiac myocytes from genetically engineered mice and controls were studied by video microscopy to assess sarcomere shortening (SS) and fura2-AM fluorescence to measure cal...

  2. Taking the first steps in contraction mechanics of single myocytes from frog heart.

    Science.gov (United States)

    Brandt, P W; Colomo, F; Poggesi, C; Tesi, C

    1993-01-01

    Intact or skinned atrial and ventricular myocytes from frog heart were mounted horizontally between the lever arms of a force transducer and a servo-controlled electromagnetic loud-speaker "motor" in a trough filled with Ringer or relaxing solution. The myocyte length-sarcomere length relation for intact preparations at rest is linear at least in the range from l0 (sarcomere length about 2.1 microns, resting force zero) to 1.6 l0 (resting force about 100 nN). The peak force value for control twitches (21-23 degrees C, stimulus interval 10 s, [Ca2+]o 1 mM) varies from 20 to 100 nN in atrial and ventricular intact myocytes. The effects induced by isoprenaline or changes in [Ca2+]o, stimulation pattern and bath temperature on twitch characteristics are comparable to those observed in multicellular preparations. The steady force produced by maximally Ca(2+)-activated skinned myocytes is much greater than that developed in control twitches and varies from 0.5 to 3.5 microN in different cells. The saturating pCa in the activating solution is around 5.50. The force response of a resting myocyte to slow ramp stretches shows an initial velocity- and length-dependent component during the stretch itself and, after completion of the length change, a gradual recovery towards a steady level which only depends on the stretch extent. The force response of a stimulated myocyte to length steps complete in 2 ms consists of an apparently elastic change during the step itself and then of a rapid partial recovery followed by slowering of recovery. Whether or not the force recovery includes different phases as reported for skeletal muscle remains unclear. PMID:8109374

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

    International Nuclear Information System (INIS)

    The authors have previously shown that the levels of total tissue coenzyme A and carnitine are reduced in hypertrophied hearts of rats subjected to aortic constriction. It was therefore of interest to determine if these changes were associated with alterations in fatty acid oxidation by the hypertrophied myocardium. Hearts were excised from sham-operated and aortic-constricted rats and perfused at 10 cm H2O left atrial filling pressure with a ventricular afterload of 80 cm of H2O with buffer containing 1.2 mM 14C-linoleate. Heart rate and peak systolic pressure were not different in control and hypertrophied hearts. 14CO2 production was linear in both groups of hearts between 10 and 30 minutes of perfusion. The rate of fatty acid oxidation determined by 14CO2 production during this time was 0.728 +/- 0.06 ?moles/min/g dry in control hearts and 0.710 +/- 0.02 ?moles/min/g dry in hypertrophied hearts. Comparable rates of fatty acid oxidation were associated with comparable rates of O2 consumption in the two groups of hearts (39.06 +/- 3.50 and 36.78 +/- 2.39 ?moles/g dry/min for control and hypertrophied hearts, respectively). The data indicate that the ability of the hypertrophied heart to oxidize fatty acids under these perfusion conditions is not impaired in spite of significant reductions in tissue levels of coenzyme A and carnitine

  4. Calcium-calcineurin signaling in the regulation of cardiac hypertrophy

    International Nuclear Information System (INIS)

    Cardiac hypertrophy is a leading predicator of progressive heart disease that often leads to heart failure and a loss of cardiac contractile performance associated with profound alterations in intracellular calcium handling. Recent investigation has centered on identifying the molecular signaling pathways that regulate cardiac myocyte hypertrophy, as well as the mechanisms whereby alterations in calcium handling are associated with progressive heart failure. One potential focal regulator of cardiomyocyte hypertrophy that also responds to altered calcium handling is the calmodulin-activated serine/threonine protein phosphatase calcineurin (PP2B). Once activated by increases in calcium, calcineurin mediates the hypertrophic response through its downstream transcriptional effector nuclear factor of activated T cells (NFAT), which is directly dephosphorylated by calcineurin resulting in nuclear translocation. While previous studies have convincingly demonstrated the sufficiency of calcineurin to mediate cardiac hypertrophy and progressive heart failure, its necessity remains an area of ongoing investigation. Here we weigh an increasing body of literature that suggests a causal link between calcineurin signaling and the cardiac hypertrophic response and heart failure through the use of pharmacologic inhibitors (cyclosporine A and FK506) and genetic approaches. We will also discuss the manner in which calcineurin-NFAT signaling is negatively regulated in the heart through aegatively regulated in the heart through a diverse array of kinases and inhibitory proteins. Finally, we will discuss emerging theories as to the mechanisms whereby alterations in intracellular calcium handling might stimulate calcineurin within the context of a contractile cell continually experiencing calcium flux

  5. 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.].

  6. Resveratrol Inhibits Cardiac Hypertrophy via AMP-activated Protein Kinase and Akt*

    OpenAIRE

    Chan, Anita Y. M.; Dolinsky, Vernon W.; Soltys, Carrie-lynn M.; Viollet, Benoit; Baksh, Shairaz; Light, Peter E.; Dyck, Jason R. B.

    2008-01-01

    Whereas studies involving animal models of cardiovascular disease demonstrated that resveratrol is able to inhibit hypertrophic growth, the mechanisms involved have not been elucidated. Because studies in cells other than cardiomyocytes revealed that AMP-activated protein kinase (AMPK) and Akt are affected by resveratrol, we hypothesized that resveratrol prevents cardiac myocyte hypertrophy via these two kinase systems. Herein, we demonstrate that resveratrol reduces p...

  7. Contractile reserve and calcium regulation are depressed in myocytes from chronically unloaded hearts

    Science.gov (United States)

    Ito, Kenta; Nakayama, Masaharu; Hasan, Faisal; Yan, Xinhua; Schneider, Michael D.; Lorell, Beverly H.

    2003-01-01

    BACKGROUND: Chronic cardiac unloading of the normal heart results in the reduction of left ventricular (LV) mass, but effects on myocyte contractile function are not known. METHODS AND RESULTS: Cardiac unloading and reduction in LV mass were induced by heterotopic heart transplantation to the abdominal aorta in isogenic rats. Contractility and [Ca(2+)](i) regulation in LV myocytes were studied at both 2 and 5 weeks after transplantation. Native in situ hearts from recipient animals were used as the controls for all experiments. Contractile function indices in myocytes from 2-week unloaded and native (control) hearts were similar under baseline conditions (0.5 Hz, 1.2 mmol/L [Ca(2+)](o), and 36 degrees C) and in response to stimulation with high [Ca(2+)](o) (range 2.5 to 4.0 mmol/L). In myocytes from 5-week unloaded hearts, there were no differences in fractional cell shortening and peak-systolic [Ca(2+)](i) at baseline; however, time to 50% relengthening and time to 50% decline in [Ca(2+)](i) were prolonged compared with controls. Severe defects in fractional cell shortening and peak-systolic [Ca(2+)](i) were elicited in myocytes from 5-week unloaded hearts in response to high [Ca(2+)](o). However, there were no differences in the contractile response to isoproterenol between myocytes from unloaded and native hearts. In 5-week unloaded hearts, but not in 2-week unloaded hearts, LV protein levels of phospholamban were increased (345% of native heart values). Protein levels of sarcoplasmic reticulum Ca(2+) ATPase and the Na(+)/Ca(2+) exchanger were not changed. CONCLUSIONS: Chronic unloading of the normal heart caused a time-dependent depression of myocyte contractile function, suggesting the potential for impaired performance in states associated with prolonged cardiac atrophy.

  8. HIV protease inhibitors elicit volume-sensitive Cl? current in cardiac myocytes via mitochondrial ROS

    OpenAIRE

    Deng, Wu; Baki, Lia; Yin, Jun; Zhou, Huiping; Baumgarten, Clive M.

    2010-01-01

    HIV protease inhibitors (HIV PI) reduce morbidity and mortality of HIV infection but cause multiple untoward effects. Because certain HIV PI evoke production of reactive oxygen species (ROS) and volume-sensitive Cl? current (ICl,swell) is activated by ROS, we tested whether HIV PI stimulate ICl,swell in ventricular myocytes. Ritonavir and lopinavir elicited outwardly-rectifying Cl? currents under isosmotic conditions that were abolished by the selective ICl,swell-blocker DCPIB. In contras...

  9. Organization of Ryanodine Receptors, Transverse Tubules, and Sodium-Calcium Exchanger in Rat Myocytes

    OpenAIRE

    Jayasinghe, Isuru D.; Cannell, Mark B.; Soeller, Christian

    2009-01-01

    Confocal and total internal reflection fluorescence imaging was used to examine the distribution of caveolin-3, sodium-calcium exchange (NCX) and ryanodine receptors (RyRs) in rat ventricular myocytes. Transverse and longitudinal optical sectioning shows that NCX is distributed widely along the transverse and longitudinal tubular system (t-system). The NCX labeling consisted of both punctate and distributed components, which partially colocalize with RyRs (27%). Surface membrane labeling show...

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Torii, Yukio (Kyoto Prefectural Univ. of Medicine (Japan))

    1983-09-01

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

  13. 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

  14. Histamine modulates calcium current in guinea pig ventricular myocytes

    OpenAIRE

    Alloatti, Giuseppe; Levi, Renzo

    1988-01-01

    In the present work we have examined the effects of histamine on electrophysiological parameters of isolated cardiocytes acutely dissociated from adult guinea pigs. The whole cell patch clamp technique was used to examine action potential and currents. Stable recordings of calcium current (average peak amplitude of 563 +/- 256 pA per cell, n = 83) were obtained. Application of histamine (5 nM-10 microM) resulted in marked modification of action potentials and calcium current. Calcium current ...

  15. Identification of a core set of genes that signifies pathways underlying cardiac hypertrophy

    DEFF Research Database (Denmark)

    Strom, C.C.; Kruhoffer, M.

    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 genes whose altered expression had previously been reported. We identified a single common gene program underlying hypertrophic remodelling, regardless of how the hypertrophy was induced. These genes constitute the molecular basis for the existence of one main form of cardiac hypertrophy and may be useful for prediction of a common therapeutic approach. Supplementary material for this article can be found at: http://www.interscience.wiley.com/jpages/1531-6912/suppmat.

  16. Identification of a Core Set of Genes That Signifies Pathways Underlying Cardiac Hypertrophy

    Directory of Open Access Journals (Sweden)

    Søren P. Sheikh

    2006-04-01

    Full Text Available 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 genes whose altered expression had previously been reported. We identified a single common gene program underlying hypertrophic remodelling, regardless of how the hypertrophy was induced. These genes constitute the molecular basis for the existence of one main form of cardiac hypertrophy and may be useful for prediction of a common therapeutic approach. Supplementary material for this article can be found at: http://www.interscience.wiley.com/jpages/1531-6912/suppmat

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

    International Nuclear Information System (INIS)

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

  18. Effects of miRNA-455 on cardiac hypertrophy induced by pressure overload.

    Science.gov (United States)

    Wu, Chuntao; Dong, Shimin; Li, Yongjun

    2015-04-01

    microRNAs (miRNAs or miRs) are essential in cardiac hypertrophy and in the development of heart failure. In the present study, we aimed to determine whether the restoration of miRNA-455 (miR-455) gene expression in vivo aggravates hypertrophy, but protects against adverse cardiac remodeling induced by pressure overload. Cardiac hypertrophy was induced by left ventricular pressure overload in male mice subjected to transverse aortic constriction (TAC). The mice were randomly selected to receive a tail vein injection of either miR-455 or green fluorescent protein per animal at 1, 8, 15 and 21 days following surgery. Cardiac hypertrophy, function and remodeling were evaluated by echocardiography, catheterization, histological analysis and the examination of the expression of specific genes and cardiac apoptosis. TAC (2 weeks following surgery) resulted in significant cardiac hypertrophy, which was significantly aggravated by treatment with miR-455. However, miR-455 replacement therapy markedly reduced myocardial fibrosis and inhibited apoptosis, suggesting that this therapy can prevent maladaptive ventricular remodeling. miR-455 was also identified and validated to target calreticulin, a protein that is critical for cardiac development. The restoration of miR-455 gene expression may thus be a potential therapeutic strategy to reverse pressure-induced cardiac hypertrophy and prevent maladaptive cardiac remodeling through the regulation of miR-455 at different time points following hypertrophy. PMID:25695617

  19. Effects of high and low salt intake on left ventricular remodeling after myocardial infarction in normotensive rats.

    Science.gov (United States)

    Forechi, Ludimila; Baldo, Marcelo Perim; de Araujo, Isabela Binotti; Nogueira, Breno Valentim; Mill, José Geraldo

    2015-02-01

    The dietary-sodium restriction is a standard approach following an acute myocardial infarction (MI). We examined the hypothesis in which the use of a high or low-sodium diet would worsen post-infarction left ventricular remodeling in rats and facilitate the development of heart failure. Left coronary artery ligation or sham-operated (SO) was produced in male Wistar rats (250-290 g). After surgery, animals were assigned to one of the three diets: standard amount of sodium (0.3% NaCl, SO and MI groups), a high-sodium diet (0.6% NaCl, SO-High and MI-High groups), or a low-sodium diet (0.03% NaCl, SO-Low and MI-Low groups). Diets were provided for 8 weeks post-surgery. Mortality rate was elevated in high-salt group (MI-Low, 21.4%; MI, 35.3%; MI-High, 47.6%). Contractility parameter was seen to be impaired in MI-Low animals (3195 ± 211 mm Hg/s) compared with MI (3751 ± 200 mm Hg/s). Low-salt diet did not prevent myocardial collagen deposition (MI-Low, 5.2 ± 0.5%; MI, 5.0 ± 0.4%) nor myocyte hypertrophy (MI-Low, 608 ± 41?(2); MI, 712 ± 53 ?m(2)) in left ventricle after MI. High-salt intake increases collagen volume fraction (SO, 3.3 ± 0.4%; SO-High, 4.7 ± 0.4%) in animals sham, but no major changes after MI. Our results show that ventricular remodeling was not altered by immediate introduction of low sodium after MI, and it may be a safe strategy as a therapeutic intervention to avoid volume retention. However, high sodium can be harmful, accelerating the post-infaction ventricular remodeling. PMID:25596013

  20. 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 the cardiocyte contractile apparatus in pressure-overload cardiac hypertrophy.

  1. Hydroxyproline and passive stiffness of pressure-induced hypertrophied kitten myocardium.

    OpenAIRE

    Williams, J. F.; Potter, R. D.; Hern, D. L.; Mathew, B.; Deiss, W. P.

    1982-01-01

    Passive stiffness and hydroxyproline content of myocardium hypertrophied by pressure-loading were determined in kittens 2, 8-16, and 24-52 wk after pulmonary artery banding, which initially elevated right ventricular systolic pressure by 10-15 mm Hg. Right ventricular mass increased by approximately 75%, three-quarters of which occurred during the first 2 wk after banding. Passive stiffness was assessed from resting length-tension relations of isometrically contracting isolated right ventricu...

  2. TGFbeta inducible early gene-1 (TIEG1) and cardiac hypertrophy: Discovery and characterization of a novel signaling pathway.

    Science.gov (United States)

    Rajamannan, Nalini M; Subramaniam, Malayannan; Abraham, Theodore P; Vasile, Vlad C; Ackerman, Michael J; Monroe, David G; Chew, Teng-Leong; Spelsberg, Thomas C

    2007-02-01

    Cellular mechanisms causing cardiac hypertrophy are currently under intense investigation. We report a novel finding in the TGFbeta inducible early gene (TIEG) null mouse implicating TIEG1 in cardiac hypertrophy. The TIEG(-/-) knock-out mouse was studied. Male mice age 4-16 months were characterized (N = 86 total) using echocardiography, transcript profiling by gene microarray, and immunohistochemistry localized upregulated genes for determination of cellular mechanism. The female mice (N = 40) did not develop hypertrophy or fibrosis. The TIEG(-/-) knock-out mouse developed features of cardiac hypertrophy including asymmetric septal hypertrophy, an increase in ventricular size at age 16 months, an increase (214%) in mouse heart/weight body weight ratio TIEG(-/-), and an increase in wall thickness in TIEG(-/-) mice of (1.85 +/- 0.21 mm), compared to the control (1.13 +/- 0.15 mm, P hypertrophy in the TIEG null mouse. PMID:16888812

  3. Papel relativo da remodelação geométrica do ventrículo esquerdo, morfológica e funcional do miocárdio na transição da hipertrofia compensada para a falência cardíaca em ratos com estenose aórtica supravalvar / Relative role of left ventricular geometric remodeling and of morphological and functional myocardial remodeling in the transition from compensated hypertrophy to heart failure in rats with supravalvar aortic stenosis

    Scientific Electronic Library Online (English)

    Edson Antonio, Bregagnollo; Marco Aurélio, Mestrinel; Katashi, Okoshi; Fábio Cardoso, Carvalho; Isamara Fernanda, Bregagnollo; Carlos Roberto, Padovani; Antonio Carlos, Cicogna.

    2007-02-01

    Full Text Available SciELO Brazil | Languages: English, Portuguese Abstract in portuguese OBJETIVO: Avaliar a contribuição relativa da remodelação geométrica do ventrículo esquerdo (VE) e das alterações morfológicas e funcionais do miocárdio, em ratos com estenose aórtica supravalvar (EAS), na fase de transição da hipertrofia compensada para a insuficiência cardíaca congestiva (ICC). MÉT [...] ODOS: Vinte e uma semanas após a indução da EAS os ratos foram classificados como controles (GC,n=13), não portadores (GE,n=11) ou portadores de insuficiência cardíaca congestiva (GE-IC,n=12).Todos os grupos foram avaliados com estudo ecocardiográfico, hemodinâmico e morfológico do miocárdio. RESULTADOS: Vinte e uma semanas após EAS: índice de massa (GE-IC>GE>GC,pGC, pGE>GC, pGE>GC,pGE>GC, pGE>GC, p Abstract in english OBJECTIVE: To evaluate the relative contribution of left ventricular (LV) geometric remodeling and of morphological and functional myocardial changes in rats with induced supravalvar aortic stenosis (SAS), in the transition from compensated hypertrophy to congestive heart failure (CHF). METHODS: Twe [...] nty one weeks after induction of SAS, the rats were classified as controls (CG, n=13), without congestive heart failure (SG, n=11), or with congestive heart failure (SG-HF, n=12). All groups were evaluated with echocardiographic, hemodynamic and morphological study of the myocardium. RESULTS: Twenty one weeks after SAS: mass index (SG-HF>SG>CG, pCG, pSG>CG, pSG>CG, pSG>CG, pSG>CG, p

  4. Ventricular tachycardia

    Science.gov (United States)

    ... used to detect ventricular tachycardia include: Continuous ambulatory electrocardiogram (Holter monitor) ECG Intracardiac electrophysiology study (EPS) Rhythm monitoring with a loop recorder or ...

  5. PPAR gamma agonist normalizes glomerular filtration rate, tissue levels of homocysteine, and attenuates endothelial-myocyte uncoupling in alloxan induced diabetic mice

    OpenAIRE

    Walter E Rodriguez, Utpal Sen

    2008-01-01

    Background: Homocysteine (Hcy) is an independent cardiovascular risk factor; however, in diabetes, the role of tissue Hcy leading to cardiac dysfunction is unclear. Aims: To determine whether tissue Hcy caused endothelial-myocyte uncoupling and ventricular dysfunction in diabetes. Methods: Diabetes was created in C57BL/6J male mice by injecting 65 mg/kg alloxan. To reverse diabetic complications, ciglitazone (CZ) was administered in the drinking water. Plasma glucose, Hcy, left ventricular (L...

  6. A case of hypereosinophilic syndrome presenting mid-ventricular obstruction.

    Science.gov (United States)

    Nakaoka, Yoshikazu; Iwahori, Kota; Kunisada, Keita; Fujio, Yasushi; Izumi, Masahiro; Osugi, Tomoaki; Oshima, Yuichi; Hirota, Hisao; Yamauchi-Takihara, Keiko

    2002-03-01

    A 59-year-old man with hypereosinophilic syndrome (HES) who had been maintained with low-dose prednisolone for 5 years developed the characteristic features of hypertrophic cardiomyopathy. Left ventricular endomyocardial biopsy revealed no eosinophilic infiltration but extensive myocardial fibrosis. Cardiac involvement in HES presents as endocardial fibrosis, resulting in a clinical presentation of restrictive cardiomyopathy. HES heart disease can also present dilated cardiomyopathy, but myocardial hypertrophy has only rarely been noted in conjunction with HES. This report concerns a patient with HES who had clinical and hemodynamic evidence of asymmetric septal hypertrophy with mid-ventricular obstruction. PMID:12027235

  7. El aumento de la expresión del ARNm de la enzima convertidora de angiotensina I homóloga (ECA-2) inducido por atorvastatina se asocia a menor fibrosis e hipertrofia ventricular izquierda en un modelo de cardiomiopatía diabética / Atorvastatin induced increase in homologous angiotensin i converting enzyme (ACE2) mRNA is associated to decreased fibrosis and decreased left ventricular hypertrophy in a rat model of diabetic cardiomyopathy

    Scientific Electronic Library Online (English)

    Cristian, Aguilar; Freddy, Ventura; Luis, Rodríguez-Delfín.

    2011-06-01

    Full Text Available SciELO Peru | Language: Spanish Abstract in spanish Objetivos. Evaluar el efecto de atorvastatina sobre la progresión del remodelado cardiaco y la expresión de ECA-2 en el miocardio de ratas diabéticas. Materiales y métodos. La diabetes fue inducida en ratas Holtzman con una inyección intraperitoneal de estreptozotocina. Los animales fueron divididos [...] en tres grupos: (1) ratas control, (2) ratas diabéticas y (3) ratas diabéticas tratadas con atorvastatina (50 mg/kg/día). Después de ocho semanas de tratamiento, los corazones fueron extraídos para el análisis morfométrico, la cuantificación de colágeno y la determinación de los niveles de ARNm de ECA y ECA-2. Resultados. El índice de hipertrofia ventricular y el depósito de colágeno se incrementaron significativamente en las ratas diabéticas. La administración de atorvastatina previno estos cambios sin modificar los niveles de colesterol. La hiperglicemia produjo un incremento significativo en los niveles del ARNm de ECA y una marcada disminución en la expresión de ECA-2 en el miocardio de ratas diabéticas. La administración de atorvastatina indujo la expresión del ARNm de ECA-2 e inhibió la sobreexpresión del ARNm de ECA en el miocardio de las ratas diabéticas. Conclusiones. Nuestros resultados indican que la atorvastatina, independientemente de su capacidad para disminuir el colesterol, normaliza la relación de la expresión de ECA/ECA-2 y atenúa el desarrollo del remodelado adverso en el corazón diabético. Abstract in english Objectives. This study has investigated the effect of atorvastatin on the progression of cardiac remodelling and ACE- 2 expression in diabetic myocardium in rats. Materials and Methods. Diabetes was induced in Holtzman rats with an intraperitoneal injection of streptozotocin. The animals were divide [...] d into 3 groups: (1) normal control rats, (2) diabetic rats and (3) diabetic rats treated orally with atorvastatin (50 mg/kg/day). After eight weeks of treatment, the hearts were removed for morphometric studies, collagen content assay and genetic expressions of ACE and ACE2 mRNA. Results. Myocardial hypertrophy index and collagen deposition were increased in diabetic rats, but not in the treated-diabetic rats, without producing changes in cholesterol levels. Myocardial ACE mRNA levels were increased while ACE2 mRNA levels were decreased in diabetic rats. Atorvastatin administration attenuated overexpression of ACE mRNA and overexpression of ACE-2 mRNA in diabetic rats. Conclusions. Our results indicate that atorvastatin, independently of its cholesterol-lowering capacity, lowers the ACE/ACE2 ratio to normal values and attenuates the development of adverse remodeling in the diabetic heart.

  8. El aumento de la expresión del ARNm de la enzima convertidora de angiotensina I homóloga (ECA-2) inducido por atorvastatina se asocia a menor fibrosis e hipertrofia ventricular izquierda en un modelo de cardiomiopatía diabética / Atorvastatin induced increase in homologous angiotensin i converting enzyme (ACE2) mRNA is associated to decreased fibrosis and decreased left ventricular hypertrophy in a rat model of diabetic cardiomyopathy

    Scientific Electronic Library Online (English)

    Cristian, Aguilar; Freddy, Ventura; Luis, Rodríguez-Delfín.

    2011-06-01

    Full Text Available SciELO Public Health | Language: Spanish Abstract in spanish Objetivos. Evaluar el efecto de atorvastatina sobre la progresión del remodelado cardiaco y la expresión de ECA-2 en el miocardio de ratas diabéticas. Materiales y métodos. La diabetes fue inducida en ratas Holtzman con una inyección intraperitoneal de estreptozotocina. Los animales fueron divididos [...] en tres grupos: (1) ratas control, (2) ratas diabéticas y (3) ratas diabéticas tratadas con atorvastatina (50 mg/kg/día). Después de ocho semanas de tratamiento, los corazones fueron extraídos para el análisis morfométrico, la cuantificación de colágeno y la determinación de los niveles de ARNm de ECA y ECA-2. Resultados. El índice de hipertrofia ventricular y el depósito de colágeno se incrementaron significativamente en las ratas diabéticas. La administración de atorvastatina previno estos cambios sin modificar los niveles de colesterol. La hiperglicemia produjo un incremento significativo en los niveles del ARNm de ECA y una marcada disminución en la expresión de ECA-2 en el miocardio de ratas diabéticas. La administración de atorvastatina indujo la expresión del ARNm de ECA-2 e inhibió la sobreexpresión del ARNm de ECA en el miocardio de las ratas diabéticas. Conclusiones. Nuestros resultados indican que la atorvastatina, independientemente de su capacidad para disminuir el colesterol, normaliza la relación de la expresión de ECA/ECA-2 y atenúa el desarrollo del remodelado adverso en el corazón diabético. Abstract in english Objectives. This study has investigated the effect of atorvastatin on the progression of cardiac remodelling and ACE- 2 expression in diabetic myocardium in rats. Materials and Methods. Diabetes was induced in Holtzman rats with an intraperitoneal injection of streptozotocin. The animals were divide [...] d into 3 groups: (1) normal control rats, (2) diabetic rats and (3) diabetic rats treated orally with atorvastatin (50 mg/kg/day). After eight weeks of treatment, the hearts were removed for morphometric studies, collagen content assay and genetic expressions of ACE and ACE2 mRNA. Results. Myocardial hypertrophy index and collagen deposition were increased in diabetic rats, but not in the treated-diabetic rats, without producing changes in cholesterol levels. Myocardial ACE mRNA levels were increased while ACE2 mRNA levels were decreased in diabetic rats. Atorvastatin administration attenuated overexpression of ACE mRNA and overexpression of ACE-2 mRNA in diabetic rats. Conclusions. Our results indicate that atorvastatin, independently of its cholesterol-lowering capacity, lowers the ACE/ACE2 ratio to normal values and attenuates the development of adverse remodeling in the diabetic heart.

  9. El aumento de la expresión del ARNm de la enzima convertidora de angiotensina I homóloga (ECA-2 inducido por atorvastatina se asocia a menor fibrosis e hipertrofia ventricular izquierda en un modelo de cardiomiopatía diabética Atorvastatin induced increase in homologous angiotensin i converting enzyme (ACE2 mRNA is associated to decreased fibrosis and decreased left ventricular hypertrophy in a rat model of diabetic cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Cristian Aguilar

    2011-06-01

    Full Text Available Objetivos. Evaluar el efecto de atorvastatina sobre la progresión del remodelado cardiaco y la expresión de ECA-2 en el miocardio de ratas diabéticas. Materiales y métodos. La diabetes fue inducida en ratas Holtzman con una inyección intraperitoneal de estreptozotocina. Los animales fueron divididos en tres grupos: (1 ratas control, (2 ratas diabéticas y (3 ratas diabéticas tratadas con atorvastatina (50 mg/kg/día. Después de ocho semanas de tratamiento, los corazones fueron extraídos para el análisis morfométrico, la cuantificación de colágeno y la determinación de los niveles de ARNm de ECA y ECA-2. Resultados. El índice de hipertrofia ventricular y el depósito de colágeno se incrementaron significativamente en las ratas diabéticas. La administración de atorvastatina previno estos cambios sin modificar los niveles de colesterol. La hiperglicemia produjo un incremento significativo en los niveles del ARNm de ECA y una marcada disminución en la expresión de ECA-2 en el miocardio de ratas diabéticas. La administración de atorvastatina indujo la expresión del ARNm de ECA-2 e inhibió la sobreexpresión del ARNm de ECA en el miocardio de las ratas diabéticas. Conclusiones. Nuestros resultados indican que la atorvastatina, independientemente de su capacidad para disminuir el colesterol, normaliza la relación de la expresión de ECA/ECA-2 y atenúa el desarrollo del remodelado adverso en el corazón diabético.Objectives. This study has investigated the effect of atorvastatin on the progression of cardiac remodelling and ACE- 2 expression in diabetic myocardium in rats. Materials and Methods. Diabetes was induced in Holtzman rats with an intraperitoneal injection of streptozotocin. The animals were divided into 3 groups: (1 normal control rats, (2 diabetic rats and (3 diabetic rats treated orally with atorvastatin (50 mg/kg/day. After eight weeks of treatment, the hearts were removed for morphometric studies, collagen content assay and genetic expressions of ACE and ACE2 mRNA. Results. Myocardial hypertrophy index and collagen deposition were increased in diabetic rats, but not in the treated-diabetic rats, without producing changes in cholesterol levels. Myocardial ACE mRNA levels were increased while ACE2 mRNA levels were decreased in diabetic rats. Atorvastatin administration attenuated overexpression of ACE mRNA and overexpression of ACE-2 mRNA in diabetic rats. Conclusions. Our results indicate that atorvastatin, independently of its cholesterol-lowering capacity, lowers the ACE/ACE2 ratio to normal values and attenuates the development of adverse remodeling in the diabetic heart.

  10. Diagnostic imaging of cardiac hypertrophy

    International Nuclear Information System (INIS)

    As imaging techniques for cardiac hypertrophy, the ultrasonic dimension gauze technique, echocardiography, ventriculography and the RI technique including emission RI tomography were outlined. (Chiba, N.)

  11. Myocytes, myometrium, and uterine contractions.

    Science.gov (United States)

    Young, Roger C

    2007-04-01

    The pregnant uterus is unique because of the dramatic functional changes that occur in the peripartum period. To promote the concept that we have a relatively poor understanding of the physiology of parturition, we will posit 10 facts that are so obvious and so clearly accepted as facts that they probably are not even facts at all. (1) The laboring uterus undergoes peristalsis to dilate the cervix, deliver the fetus, and expel the placenta. (2) The human uterus is composed of longitudinal and circular layers of smooth muscle. (3) The functional cells of the uterus are the myocytes, which are a homogeneous cell type responsible for the generation of contraction forces, passage of action potentials, and control of contractility. (4) The phasic contractions of the uterus are typical for visceral smooth muscle. (5) The primary, and perhaps only, role of gap junctions is to allow passage of action potentials through the tissue. (6) Action potential propagation as the mechanism for global communication (over many centimeters throughout the uterus) is sufficient to recruit all regions and all myocytes of the uterus. (7) Slow waves pace the contractions of human myometrium. (8) Calcium-activated potassium channels are responsible for repolarization of the membrane potential that terminates each contraction. (9) Chloride channels are not important in uterine electrophysiology. (10) With enough computing power, it would be straightforward to build a closed model of human labor, given our current understanding of the components of myometrium. This manuscript discusses each point to stimulate questions for future investigation. PMID:17442780

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

    Czech Academy of Sciences Publication Activity Database

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

    2011-01-01

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

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

    International Nuclear Information System (INIS)

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

  14. Regulation of Cardiac Hypertrophy: the nuclear option

    OpenAIRE

    Kuster, D. W. D.

    2011-01-01

    Cardiac 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 hypertrophy tha...

  15. ?1A-Adrenergic Receptors Regulate Cardiac Hypertrophy In Vivo Through Interleukin-6 Secretion

    Science.gov (United States)

    Papay, Robert S.; Shi, Ting; Piascik, Michael T.; Naga Prasad, Sathyamangla V.

    2013-01-01

    The role of ?1-adrenergic receptors (ARs) in the regulation of cardiac hypertrophy is still unclear, because transgenic mice demonstrated hypertrophy or the lack of it despite high receptor overexpression. To further address the role of the ?1-ARs in cardiac hypertrophy, we analyzed unique transgenic mice that overexpress constitutively active mutation (CAM) ?1A-ARs or CAM ?1B-ARs under the regulation of large fragments of their native promoters. These constitutively active receptors are expressed in all tissues that endogenously express their wild-type counterparts as opposed to only myocyte-targeted transgenic mice. In this study, we discovered that CAM ?1A-AR mice in vivo have cardiac hypertrophy independent of changes in blood pressure, corroborating earlier studies, but in contrast to myocyte-targeted ?1A-AR mice. We also found cardiac hypertrophy in CAM ?1B-AR mice, in agreement with previous studies, but hypertrophy only developed in older mice. We also discovered unique ?1-AR–mediated hypertrophic signaling that was AR subtype-specific with CAM ?1A-AR mice secreting atrial naturietic factor and interleukin-6 (IL-6), whereas CAM ?1B-AR mice expressed activated nuclear factor-?B (NF-?B). These particular hypertrophic signals were blocked when the other AR subtype was coactivated. We also discovered that crossbreeding the two CAM models (double CAM ?1A/B-AR) inhibited the development of hypertrophy and was reversible with single receptor activation, suggesting that coactivation of the receptors can lead to novel antagonistic signal transduction. This was confirmed by demonstrating antagonistic signals that were even lower than normal controls in the double CAM ?1A/B-AR mice for p38, NF-?B, and the IL-6/glycoprotein 130/signal transducer and activator of transcription 3 pathway. Because ?1A/B double knockout mice fail to develop hypertrophy in response to IL-6, our results suggest that IL-6 is a major mediator of ?1A-AR cardiac hypertrophy. PMID:23404509

  16. Mitogen-activated protein kinases mediate changes in gene expression, but not cytoskeletal organization associated with cardiac muscle cell hypertrophy

    OpenAIRE

    1994-01-01

    Shortly after birth, cardiac myocytes lose the ability to divide, and, in adult animals, heart muscle grows by a process of cellular hypertrophy where each individual cell gets larger. We have previously shown that activated Ras protein can induce markers of the hypertrophic phenotype, including atrial natriuretic factor (ANF) expression and organization of contractile proteins, and that Ras is at least partially required for the hypertrophic effect of phenylephrine. In the present study, we ...

  17. 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...

  18. Left ventricular function in Friedreich's ataxia. An echocardiographic study.

    OpenAIRE

    Sutton, M. G.; Olukotun, A. Y.; Tajik, A. J.; Lovett, J. L.; Giuliani, E. R.

    1980-01-01

    Left ventricular function was assessed in seven patients with Friedreich's ataxia using computer-assisted analysis of the left ventricular echocardiograms and compared with those of 45 normal children matched for age and sex. The left ventricle in Friedreich's ataxia was symmetrically hypertrophied, cavity dimension was normal or small, and septal motion and peak velocity of circumferential shortening were normal in all patients. In diastole the duration of rapid filling was normal, peak rate...

  19. Exercise training and detraining modify the morphological and mechanical properties of single cardiac myocytes obtained from spontaneously hypertensive rats

    Scientific Electronic Library Online (English)

    M.A., Carneiro-Júnior; M.C.G., Pelúzio; C.H.O., Silva; P.R.S., Amorim; K.A., Silva; M.O., Souza; C.A., Castro; D., Roman-Campos; T.N., Prímola-Gomes; A.J., Natali.

    1042-10-01

    Full Text Available We determined the effects of exercise training and detraining on the morphological and mechanical properties of left ventricular myocytes in 4-month-old spontaneously hypertensive rats (SHR) randomly divided into the following groups: sedentary for 8 weeks (SED-8), sedentary for 12 weeks (SED-12), t [...] readmill-running trained for 8 weeks (TRA, 16 m/min, 60 min/day, 5 days/week), and treadmill-running trained for 8 weeks followed by 4 weeks of detraining (DET). At sacrifice, left ventricular myocytes were isolated enzymatically, and resting cell length, width, and cell shortening after stimulation at a frequency of 1 Hz (~25°C) were measured. Cell length was greater in TRA than in SED-8 (161.30 ± 1.01 vs 156.10 ± 1.02 ?m, P

  20. Impact of arterial hypertension on the status of left ventricular myocardium: thallium-201 myocardial scintigraphic findings

    International Nuclear Information System (INIS)

    Functional relationships was examined between the parameters of myocardial perfusion, left ventricular myocardial mass, and complications developed in patients with coronary heart diseases concominant with arterial hypertension. As perfusion deficiency progressed, the patients with complicated natural history of arterial hypertension were found to increase in number with higher left ventricular myocardial mass index. In patients with arterial hypertension, the critical hypertrophy phase in which the index of left ventricular myocardial mass was 110-120 gm2 was demonstrated to be followed by myocardial perfusion deficiency. If the myocardial mass index is 90 g/m2, it means a phase of compensatory hypertrophy, which shows higher myocardial perfusion

  1. Nuclear Compartmentalization of ?1-Adrenergic Receptor Signaling in Adult Cardiac Myocytes

    Science.gov (United States)

    Wu, Steven C.

    2015-01-01

    Abstract: Although convention dictates that G protein-coupled receptors localize to and signal at the plasma membrane, accumulating evidence suggests that G protein-coupled receptors localize to and signal at intracellular membranes, most notably the nucleus. In fact, there is now significant evidence indicating that endogenous alpha-1 adrenergic receptors (?1-ARs) localize to and signal at the nuclei in adult cardiac myocytes. Cumulatively, the data suggest that ?1-ARs localize to the inner nuclear membrane, activate intranuclear signaling, and regulate physiologic function in adult cardiac myocytes. Although ?1-ARs signal through G?q, unlike other Gq-coupled receptors, ?1-ARs mediate important cardioprotective functions including adaptive/physiologic hypertrophy, protection from cell death (survival signaling), positive inotropy, and preconditioning. Also unlike other Gq-coupled receptors, most, if not all, functional ?1-ARs localize to the nuclei in adult cardiac myocytes, as opposed to the sarcolemma. Together, ?1-AR nuclear localization and cardioprotection might suggest a novel model for compartmentalization of Gq-coupled receptor signaling in which nuclear Gq-coupled receptor signaling is cardioprotective. PMID:25264754

  2. Quantitative thallium-201 myocardial imaging in assessing right ventricular pressure in patients with congenital heart defects

    International Nuclear Information System (INIS)

    Thallium-201 myocardial scintigraphy was performed in patients with congenital heart defects to determine whether, by quantification of right ventricular isotope uptake, one could assess the degree of right ventricular hypertrophy and so predict the level of right ventricular pressure. It is shown that quantitative analysis of myocardial imaging with thallium-201 is of use clinically in patients with congenital heart defects, in assessing the severity of pulmonary stenosis or the presence of pulmonary artery hypertension. (author)

  3. Influence of fatty acid oxidation rate on glycerol release from cardiac myocytes

    International Nuclear Information System (INIS)

    Quiescent cardiac myocytes are characterized by low rates of fatty acid oxidation due to the reduced energy demand compared with beating hearts. The accumulation of intracellular fatty acid metabolites may, therefore, result in feed-back inhibition of the cardiac lipase responsible for the mobilization of triacylglycerols (lipolysis). The objective of this study was to examine if interventions that increase fatty acid oxidation rates in myocytes have an effect on lipolysis. Addition of 100 ?M dinitrophenol (DNP) to calcium-tolerant rat ventricular myocytes caused an increase in the rate of 14C-oleic acid oxidation from 1.11 +/- 0.06 to 2.38 +/- 0.17 nmol 14CO2/106 cells/min (115% stimulation; mean +/- S.D., n = 3). In parallel incubations, DNP increased the rate of lipolysis from 4.4 +/- 1.7 to 13.6 +/- 3.2 nmol glycerol/106 cells/30 min (215% stimulation). The addition of 1 mM barium to a modified Ringer's incubation medium produced an increase in the contractile activity of the myocytes, and increased the rates of oleic acid oxidation from 0.62 +/- 0.16 to 0.88 +/- 0.23 nmol/106 cells/min (42% stimulation; n = 6) and lipolysis from 13.1 +/- 6.5 to 22.2 +/- 6.4 nmol/106 cells/30 min (70% stimulation). These data show that stimulation of fatty acid oxidation in myocardial myocytes is accompanied by increased lipolytic rates, the latter probably due to release of feed-back inhibition of cardiac lipases by accumulated fatty acid metabolites

  4. Attenuation of microRNA-16 derepresses the cyclins D1, D2 and E1 to provoke cardiomyocyte hypertrophy.

    Science.gov (United States)

    Huang, Shuai; Zou, Xiao; Zhu, Jie-Ning; Fu, Yong-Heng; Lin, Qiu-Xiong; Liang, Ye-You; Deng, Chun-Yu; Kuang, Su-Juan; Zhang, Meng-Zhen; Liao, Yu-Lin; Zheng, Xi-Long; Yu, Xi-Yong; Shan, Zhi-Xin

    2015-03-01

    Cyclins/retinoblastoma protein (pRb) pathway participates in cardiomyocyte hypertrophy. MicroRNAs (miRNAs), the endogenous small non-coding RNAs, 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 role of microRNA-16 (miR-16) in modulating cyclin/Rb pathway during cardiomyocyte hypertrophy. An animal model of hypertrophy was established in a rat with abdominal aortic constriction (AAC), and in a mouse with transverse aortic constriction (TAC) and in a mouse with subcutaneous injection of phenylephrine (PE) respectively. In addition, a cell model of hypertrophy was also achieved based on PE-promoted neonatal rat ventricular cardiomyocyte and based on Ang-II-induced neonatal mouse ventricular cardiomyocyte respectively. We demonstrated that miR-16 expression was markedly decreased in hypertrophic myocardium and hypertrophic cardiomyocytes in rats and mice. Overexpression of miR-16 suppressed rat cardiac hypertrophy and hypertrophic phenotype of cultured cardiomyocytes, and inhibition of miR-16 induced a hypertrophic phenotype in cardiomyocytes. Expressions of cyclins D1, D2 and E1, and the phosphorylated pRb were increased in hypertrophic myocardium and hypertrophic cardiomyocytes, but could be reversed by enforced expression of miR-16. Cyclins D1, D2 and E1, not pRb, were further validated to be modulated post-transcriptionally by miR-16. In addition, the signal transducer and activator of transcription-3 and c-Myc were activated during myocardial hypertrophy, and inhibitions of them prevented miR-16 attenuation. Therefore, attenuation of miR-16 provoke cardiomyocyte hypertrophy via derepressing the cyclins D1, D2 and E1, and activating cyclin/Rb pathway, revealing that miR-16 might be a target to manage cardiac hypertrophy. PMID:25583328

  5. 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.

  6. Optical single-channel resolution imaging of the ryanodine receptor distribution in rat cardiac myocytes

    OpenAIRE

    Baddeley, David; Jayasinghe, Isuru D.; Lam, Leo; Rossberger, Sabrina; Cannell, Mark B.; Soeller, Christian

    2009-01-01

    We have applied an optical super-resolution technique based on single-molecule localization to examine the peripheral distribution of a cardiac signaling protein, the ryanodine receptor (RyR), in rat ventricular myocytes. RyRs form clusters with a mean size of approximately 14 RyRs per cluster, which is almost an order of magnitude smaller than previously estimated. Clusters were typically not circular (as previously assumed) but elongated with an average aspect ratio of 1.9. Edge-to-edge dis...

  7. Compensative hypertrophy of the kidney

    International Nuclear Information System (INIS)

    Several measurement methods are available to practitioners to reveal a compensative hypertrophy. Mensuration of the kidney has the advantage of simplicity but is in fact an unreliable and inaccurate method. Separate clearances in their traditional form have never entered into routine use because of the disadvantages of ureteral catheterism. The use of radioactive tracers avoids this drawback, but clearances calculated in this way are only valid in the absence of obstructive urinary disorders. Solutions have been proposed, but the values obtained are no longer identical with the clearances. The Hg uptake test quantifies quite accurately the function of each kidney. From the results obtained a complete compensative hypertrophy developed on a healthy kidney and an incomplete compensative hypertrophy developed on the diseased kidney have been described. In each of these situations the degree to which compensative hypertrophy develops seems to be fixed at a given level peculiar to each patient

  8. Expanding Mouse Ventricular Cardiomyocytes through GSK-3 Inhibition

    OpenAIRE

    Buikema, Jan Willem; Zwetsloot, Peter-paul M.; Doevendans, Pieter A.; Sluijter, Joost P. G.; Domian, Ibrahim J.

    2013-01-01

    Controlled proliferation of cardiac myocytes remains a major limitation in cell biology and one of the main underlying hurdles for true modern regenerative medicine. Here we provide a technique to robustly expand early fetal-derived mouse ventricular cardiomyocytes on a platform usable for high-throughput molecular screening, tissue engineering or potentially useful for in vivo translational experiments. This method provides a small molecule-based approach to control proliferation or differen...

  9. Inhibitory Effects of Methylsulfonylmethane on Ventricular Hypertrophy Related Gene Expression

    Directory of Open Access Journals (Sweden)

    Sara Mostafalou

    2012-01-01

    Full Text Available Methylsulfonylmethane (MSM is naturally accruing organic sulphur that is known as a potent anti-inflammatory compound. The aim of this study was to investigate the effect of MSM on mRNA expressions of angiotensinogen, endothelin-1 (ET-1 and Transforming Growth Factor (TGF-?1 in rats with monocrotaline (MCT-induced pulmonary arterial hypertension. Wistar rats were randomly assigned to 38-days pretreatment or 28-days treatment. MSM was administered to either 10 days before or 14 days after a single dose of MCT. Right Ventricle (RV tissue samples were obtained to evaluate changes in the inflammatory genes expression using RT-PCR assay. The expression levels of angiotensinogen, ET-1 and TGF-?1 significantly were reduced (p<0.01 at efficient dose of MSM in MCT-induced pulmonary arterial hypertensive rats. Results suggest that harmful effects of MCT induced PAH on the RV function could be attenuated by anti-inflammatory actions through the suppression of local RAAS along with associated growth-promoting factors TGF-?1 and ET-1.

  10. Inhibitory Effects of Methylsulfonylmethane on Ventricular Hypertrophy Related Gene Expression

    OpenAIRE

    Sara Mostafalou; Masoud Darabi; Shabnam Fayezi; Yadollah Omidi; Nasrin Maleki-Dizaji; Hossein Hamzeiy; Moslem Najafi; Alireza Garjani; Sadollah Mohammadi; Kambiz Hassanzadeh; Sajjad Khani

    2012-01-01

    Methylsulfonylmethane (MSM) is naturally accruing organic sulphur that is known as a potent anti-inflammatory compound. The aim of this study was to investigate the effect of MSM on mRNA expressions of angiotensinogen, endothelin-1 (ET-1) and Transforming Growth Factor (TGF)-?1 in rats with monocrotaline (MCT)-induced pulmonary arterial hypertension. Wistar rats were randomly assigned to 38-days pretreatment or 28-days treatment. MSM was administered to either 10 days before or 14 days after...

  11. Efeitos da inibição prolongada da enzima de conversão da angiotensina sobre as características morfológicas e funcionais da hipertrofia ventricular esquerda em ratos com sobrecarga pressórica persistente / Effects of the prolonged inhibition of the angiotensin-converting enzyme on the morphological and functional characteristics of left ventricular hypertrophy in rats with persistent pressure overload

    Scientific Electronic Library Online (English)

    Edson Antonio, Bregagnollo; Katashi, Okoshi; Isamara Fernanda, Bregagnollo; Carlos Roberto, Padovani; Marina P., Okoshi; Antonio Carlos, Cicogna.

    2005-03-01

    Full Text Available SciELO Brazil | Languages: English, Portuguese Abstract in portuguese OBJETIVO: Avaliar os efeitos do lisinopril (L) sobre as taxas de mortes (M), insuficiência cardíaca (ICC), características da remodelação miocárdica, geométrica e funcional do ventrículo esquerdo (VE), em ratos com estenose aórtica supravalvar (EAS). MÉTODOS: Ratos foram submetidos a EAS ou cirurgia [...] simulada (GC:n=10). Randomizados após 6 semanas para receber L (GL:n=30) ou nenhum tratamento (GE:n=73) sendo avaliados 6s e 21s por estudos ecocardiográfico, hemodinâmico e morfológico concomitantes. RESULTADOS: As taxas de M (GE: 53,9% vs GL: 16,7% e ICC GE: 44,8% vs GL: 20% p0,05) sendo ambos maiores que os verificados no grupo GE. Comportamento semelhante foram obtidos com os valores da primeira derivada positiva e negativa da pressão do VE. CONCLUSÃO: Em ratos com EAS o L reduziu as taxas de M e ICC e exerceu efeitos benéficos sobre a remodelação e a função do VE. Abstract in english OBJECTIVE: To assess the effects of lisinopril (L) on mortality (M) rate and congestive heart failure (CHF), and the characteristics of geometrical myocardial remodeling and left ventricular function in rats with supravalvular aortic stenosis (SAS). METHODS: Some Wistar rats underwent SAS or the sim [...] ulated surgery (CG, n=10). After 6 weeks, the animals were randomized to receive lisinopril (LG, n=30) or no treatment (SG, n=73) for 15 weeks. Cardiac remodeling was assessed in the sixth and 21st weeks after the surgical procedures through concomitant echocardiographic, hemodynamic, and morphological studies. RESULTS: The M were 53.9% and 16.7% in SG and LG, respectively; the incidence of CHF was 44.8% and 20%, in SG and LG, respectively, (P0.05), and both were greater than those in SG;(P

  12. Silencing the myotrophin gene by RNA interference leads to the regression of cardiac hypertrophy

    OpenAIRE

    Gupta, Sudhiranjan; Maitra, Ratan; Young, Dave; Gupta, Anasuya; Sen, Subha

    2009-01-01

    Myotrophin-induced activation of NF-?B has been shown to be associated with cardiac hypertrophy (CH) that progresses to heart failure (HF). In the present study, we examined the cause-and-effect relationship between myotrophin and NF-?B activation using small hairpin RNA (shRNA) against myotrophin both in vitro (using neonatal rat myocytes) and in vivo [using myotrophin transgenic (Myo-Tg) mice, which overexpress myotrophin in the heart, develop CH, and gradually progress to HF]. Among seve...

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

    Scientific Electronic Library Online (English)

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

    2011-09-01

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

  14. Clinical evaluation of left ventricular wall thickness by combined technique with gated planer 201Tl image and gated cardiac pool image

    International Nuclear Information System (INIS)

    To evaluate the left ventricular (LV) wall thickness, combined technique with gated planer 201-Thallium image and gated cardiac pool image was applied to 6 patients with hypertrophic cardiomyopathy (HCM) and 4 patients with secondary hypertrophy due to hypertension (HHD) proven by electrocardiography and ultrasonic-echocardiography. Scintigraphic pattern of hypertrophy on reconstructed planer 201Tl image showed diffuse or asymmetrical apical hypertrophy in HHD, asymmetrical septal hypertrophy in HCM. It was very interesting that abnormal perfusion was shown in 201Tl image, despite symmetrical hypertrophy in echocardiography. This techniques provided useful information for evaluating the LV wall thickness and cardiac performance. (author)

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

    Scientific Electronic Library Online (English)

    Aline Cristina, Piratello; Ivana, Moraes-Silva; Janaina, Paulini; Pamella Ramona, Souza; Raquel, Sirvente; Vera, Salemi; Karin, Flues; Edson Dias, Moreira; Cristiano, Mostarda; Tatiana, Cunha; Dulce Elena, Casarini; Maria Claudia, Irigoyen.

    1345-13-01

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

  16. Therapeutic effects of vitamin D analogs on cardiac hypertrophy in spontaneously hypertensive rats.

    Science.gov (United States)

    Kong, Juan; Kim, Gene H; Wei, Minjie; Sun, Tao; Li, George; Liu, Shu Q; Li, Xinmin; Bhan, Ishir; Zhao, Qun; Thadhani, Ravi; Li, Yan Chun

    2010-08-01

    Vitamin D inhibits renin expression and blocks the compensatory induction of renin associated with the use of renin-angiotensin system inhibitors. Here we test the therapeutic effects of two commonly used vitamin D analogs and their combination with losartan on the development of left ventricular hypertrophy. One-month-old male spontaneously hypertensive rats were treated with vehicle, losartan, paricalcitol, doxercalciferol, a combination of losartan and paricalcitol, or a combination of losartan and doxercalciferol for 2 months. Blood pressure was markedly reduced by losartan, but not by paricalcitol or doxercalciferol alone. Echocardiograpy demonstrated a 65 to 80% reduction in left ventricular wall thickness with losartan, paricalcitol, or doxercalciferol monotherapy and almost complete prevention of left ventricular hypertrophy with the combination therapies. Attenuation of cardiac and cardiomyocyte hypertrophy, and suppression of atrial and brain natriuretic peptides, were most marked in the combination therapy groups. These changes were well correlated with left ventricular gene and microRNA expression profiles in the different treatment groups. Renal and cardiac renin expression was markedly increased in losartan-treated animals, but nearly normalized with combination therapy. The same vitamin D analogs suppressed plasma renin activity in patients receiving chronic hemodialysis. These data demonstrate that vitamin D analogs have potent antihypertrophic activity in part via suppression of renin in the kidney and heart, and combination of these analogs with losartan achieves much better therapeutic effects because of the blockade of the compensatory renin increase. PMID:20616348

  17. Patterns of left ventricular remodeling among patients with essential and secondary hypertension / Patrones de remodelación ventricular en pacientes con hipertensión arterial primaria y secundaria

    Scientific Electronic Library Online (English)

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

    1520-15-01

    Full Text Available Antecedentes: La hipertensión arterial causa hipertrofia ventricular izquierda, un factor de mal pronóstico en pacientes hipertensos. Objetivo: Evaluar patrones de remodelación ventricular en pacientes con hipertensión arterial esencial y secundaria a daño renal. Material y Métodos: Análisis de ecoc [...] ardiogramas efectuados a 250 pacientes con hipertensión arterial primaria (150 mujeres) y 100 pacientes con hipertensión secundaria (60 mujeres). Se midió el grosor del septum interventricular y de la pared ventricular posterior. La masa ventricular izquierda se calculó usando la fórmula de Devereaux. Resultados: Los tipos más frecuentes de remodelación ventricular en mujeres y hombres con hipertensión esencial fueron la hipertrofia ventricular excéntrica y concéntrica, respectivamente. En pacientes con hipertensión arterial secundaria, la hipertrofia concéntrica fue más frecuente. La prevalencia de hipertrofia ventricular izquierda fue más alta en pacientes con hipertensión secundaria. El índice de masa ventricular izquierda y el grosor relativo de la pared ventricular izquierda fueron mayores en pacientes con hipertensión secundaria. La edad, los valores de presión arterial y la duración de la hipertensión influyeron en los patrones de remodelación. Conclusiones: Documentamos una mayor prevalencia de hipertrofia ventricular izquierda en pacientes con hipertensión secundaria. El tipo de remodelación depende de la edad, género, tipo de hipertensión, valores de presión arterial y duración de la hipertensión Abstract in english Background: High blood pressure causes left ventricular hypertrophy, which is a negative prognostic factor among hypertensive patients. Aim: To assess left ventricular geometric remodeling patterns in patients with essential hypertension or with hypertension secondary to parenchymal renal disease. M [...] aterial and Methods: We analyzed data from echocardiograms performed in 250patients with essential hypertension (150 females) and 100 patients with secondary hypertension (60 females). The interventricular septum and the left ventricular posterior wall thickness were measured in the parasternal long-axis. Left ventricular mass was calculated using the Devereaux formula. Results: The most common remodeling type in females and males with essential hypertension were eccentric and concentric left ventricular hypertrophy (cLVH), respectively. Among patients with secondary arterial hypertension, cLVH was most commonly observed in both genders. The prevalence of left ventricular hypertrophy was higher among patients with secondary hypertension. The left ventricular mass index and the relative left ventricular wall thickness were higher in males and also in the secondary hypertension group. Age, blood pressure values and the duration of hypertension, influenced remodeling patterns. Conclusions: We documented a higher prevalence of LVH among patients with secondary hypertension. The type of ventricular remodeling depends on gender, age, type of hypertension, blood pressure values and the duration of hypertension.

  18. 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.

    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. Left ventricular hypertrophy was diagnosed as left ventricular mass divided by height(2.7) >or=46.7 g/m(2.7) and 49.2 g/m(2.7) in women and men, respectively, and systolic function as ejection fraction and stress-corrected midwall fractional shortening. Women included more patients with obesity, isolated systolic hypertension, and mitral regurgitation (all P<0.01). Ejection fraction, stress-corrected midwall shortening, and prevalence of left ventricular hypertrophy were higher in women at baseline and at the end of study (all P<0.01). In particular, more women had residual eccentric hypertrophy (47% versus 32%; P<0.01) in spite of similar in-treatment 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<0.01) independent of other significant covariates. In linear regression analyses, female gender also predicted 2% higher mean in-treatment ejection fraction and 2% higher mean stress-corrected midwall shortening (both beta=0.07; P<0.01). Hypertensive women in this study retained higher left ventricular ejection fraction and stress-corrected midwall shortening in spite of less hypertrophy regression during long-term antihypertensive treatment Udgivelsesdato: 2008/4

  19. Experimental myocardial hypertrophy induced by a minimally invasive ascending aorta coarctation

    Directory of Open Access Journals (Sweden)

    Martins A.S.

    2001-01-01

    Full Text Available Ascending aorta coarctation was produced by a minimally invasive technique in rabbits. Animal mortality was 5%. Morphometric and hemodynamic parameters were evaluated. A parabiotically isolated heart model was used to assess the hemodynamic parameters. Left ventricular weight/body weight ratio and muscle area showed clear evidence of hypertrophy when compared to control. The hemodynamic changes in the isolated heart model suggested decreased diastolic and systolic function in the coarcted group. The present model produced hypertrophy with low mortality rates as a result of its less invasive nature.

  20. Telmisartan, a unique ARB, improves left ventricular remodeling of infarcted heart by activating PPAR gamma.

    Science.gov (United States)

    Maejima, Yasuhiro; Okada, Hiroyuki; Haraguchi, Go; Onai, Yasuyuki; Kosuge, Hisanori; Suzuki, Jun-Ichi; Isobe, Mitsuaki

    2011-06-01

    Unfavorable left ventricular (LV) remodeling after myocardial infarction (MI) leads to cardiac dysfunction. We examined whether Telmisartan, an angiotensin (Ang) II type I receptor blocker (ARB), could improve the recovery of LV function in a rat model of MI. The effect of Telmisartan as a peroxisome proliferator-activated receptor-? (PPAR-?) agonist was also investigated. After 28 days of MI, a significant improvement of survival was observed in the Telmisartan-treated rat group compared with the vehicle control rat group, non-PPAR-? agonistic ARB (Losartan)-treated rat group, and Telmisartan plus specific PPAR-? antagonist (GW9662)-treated rat group. Although no significant differences of blood pressure or infarct size were observed among these four groups, the Telmisartan group had better systolic and diastolic LV function. There was a significant reduction of the plasma brain natriuretic peptide level, cardiac fibrosis area, infiltration of macrophages, size of cardiomyocytes, terminal deoxynucleotidyl transferase dUTP nick end labeling-positive myocytes, activation of matrix metalloproteinases-2 and -9 (MMPs-2/9), and expression of transforming growth factor ?-1 (TGF-?1), connective tissue growth factor (CTGF), and osteopontin (OPN), while expression of PPAR-? and activation of tissue inhibitor of metalloproteinase-1 (TIMP-1) was enhanced, in the noninfarcted myocardium of rats from the Telmisartan group compared with the other three groups. To mimic ischemic conditions in vitro, neonatal rat cardiomyocytes and cardiac fibroblasts were incubated in hypoxic condition for 24?h. Increased transcriptional activation of PPAR-? and TIMP-1, and inhibition of TGF-?1 expression were observed in cardiomyocytes, while decreased activation of MMPs-2/9 and decrease in CTGF and OPN expression was seen in cardiac fibroblasts cultured with Telmisartan. In conclusion, Telmisartan prevented unfavorable cardiac remodeling through a reduction of cardiac hypertrophy and fibrosis. An anti-inflammatory effect and PPAR-? activation were suggested to be important in addition to suppression of Ang II activity. PMID:21403641

  1. Prolactin induces adrenal hypertrophy

    Directory of Open Access Journals (Sweden)

    Silva E.J.

    2004-01-01

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

  2. Reduction of isoproterenol-induced cardiac hypertrophy and modulation of myocardial connexin43 by a KATP channel agonist.

    Science.gov (United States)

    Sun, Ji-Min; Wang, Chun-Miao; Guo, Zeng; Hao, Yu-Yu; Xie, Yang-Jing; Gu, Jian; Wang, Ai-Ling

    2015-03-01

    Cardiac hypertrophy is a compensatory mechanism that occurs in conjunction with cardiovascular diseases. Although hypertrophy of the myocardium provides certain benefits during the early stages of cardiovascular disease, prolonged hypertrophy is potentially harmful to the heart and can result in arrhythmia and heart failure. The aim of this study was to investigate whether an ATP?sensitive K+ (KATP) channel agonist was capable of reducing isoproterenol (Iso)?induced cardiac hypertrophy and modulating myocardial connexin43 (Cx43) expression. Fifty male Sprague Dawley rats were randomly assigned to five groups: Normal, vehicle, nicorandil, glibenclamide and nicorandil plus glibenclamide. Rats in the four treatment groups received Iso injection for seven days, followed by administration with saline, nicorandil, glibenclamide or a combination of nicorandil and glibenclamide, respectively, for four weeks. Cardiac hypertrophy was then evaluated by measuring body weight, heart weight and left?ventricular weight, and plasma B?type natriuretic peptide levels were evaluated by ELISA. Immunocytochemistry and a reverse transcription?polymerase chain reaction were performed to detect the spatial distribution and gene expression of myocardial Cx43, respectively. The KATP channel agonist nicorandil markedly attenuated the degree of myocardial hypertrophy induced by Iso as compared with the vehicle group. Myocardial Cx43 expression was significantly decreased and redistributed following cardiac hypertrophy. The decrease and redistribution of Cx43 was reduced following treatment with the KATP channel agonist nicorandil. Addition of the KATP channel blocker glibenclamide eliminated the beneficial effects of nicorandil against hypertrophy and on connexin43. In conclusion, the present study indicated that chronic use of KATP channel agonists following cardiac hypertrophy can attenuate ventricular remodeling and upregulate the expression level and spatial distribution of Cx43. PMID:25411819

  3. Ca2+ Release Events in Cardiac Myocytes Up Close: Insights from Fast Confocal Imaging

    Science.gov (United States)

    Shkryl, Vyacheslav M.; Blatter, Lothar A.

    2013-01-01

    The spatio-temporal properties of Ca2+ transients during excitation-contraction coupling and elementary Ca2+ release events (Ca2+ 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. Ca2+ 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. Ca2+ sparks in atrial cells originating from non-junctional SR and in ventricular myocytes were symmetrical. Ca2+ spark recording in line scan mode at 40,000 lines/s uncovered step-like increases of [Ca2+]i. 2-D imaging of Ca2+ transients revealed an asynchronous activation of release sites and allowed the sequential recording of Ca2+ entry through surface membrane Ca2+ channels and subsequent activation of Ca2+-induced Ca2+ release. With a latency of 2.5 ms after application of an electrical stimulus, Ca2+ entry could be detected that was followed by SR Ca2+ release after an additional 3 ms delay. Maximum Ca2+ release was observed 4 ms after the beginning of release. The timing of Ca2+ entry and release was confirmed by simultaneous [Ca2+]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 Ca2+ release events that fused into a peripheral ring of elevated [Ca2+]i that subsequently propagated in a wave-like fashion towards the center of the cell. In ventricular myocytes asynchronous Ca2+ release signals from discrete sites with no preferential subcellular location preceded the whole-cell Ca2+ transient. In summary, ultra-fast confocal imaging allows investigation of Ca2+ signals with a time resolution similar to patch clamp technique, however in a less invasive fashion. PMID:23637847

  4. Ca(2+) release events in cardiac myocytes up close: insights from fast confocal imaging.

    Science.gov (United States)

    Shkryl, Vyacheslav M; Blatter, Lothar A

    2013-01-01

    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. PMID:23637847

  5. Analysis of moricizine block of sodium current in isolated guinea-pig atrial myocytes. Atrioventricular difference of moricizine block.

    Science.gov (United States)

    Ahmmed, Gias U; Hisatome, Ichiro; Kurata, Yasutaka; Makita, Naomasa; Tanaka, Yasunori; Tanaka, Hiroaki; Okamura, Tomohisa; Sonoyama, Kazuhiko; Furuse, Yoshiyuki; Kato, Masaru; Yamamoto, Yasutaka; Ogura, Kazuhiko; Shimoyama, Masaki; Miake, Junichiro; Sasaki, Norihito; Ogino, Kazuhide; Igawa, Osamu; Yoshida, Akio; Shigemasa, Chiak

    2002-03-01

    The effects of moricizine on Na+ channel currents (INa) were investigated in guinea-pig atrial myocytes and its effects on INa in ventricular myocytes and on cloned hH1 current were compared using the whole-cell, patch-clamp technique. Moricizine induced the tonic block of INa with the apparent dissociation constant (Kd,app) of 6.3 microM at -100 mV and 99.3 microM at -140 mV. Moricizine at 30 microM shifted the h infinity curve to the hyperpolarizing direction by 8.6 +/- 2.4 mV. Moricizine also produced the phasic block of INa, which was enhanced with the increase in the duration of train pulses, and was more prominent with a holding potential (HP) of -100 mV than with an HP of -140 mV. The onset block of INa induced by moricizine during depolarization to -20 mV was continuously increased with increasing the pulse duration, and was enhanced at the less negative HP. The slower component of recovery of the moricizine-induced INa block was relatively slow, with a time constant of 4.2 +/- 2.0 s at -100 mV and 3.0 +/- 1.2 s at -140 mV. Since moricizine induced the tonic block of ventricular INa with Kd,app of 3.1 +/- 0.8 microM at HP = -100 mV and 30.2 +/- 6.8 microM at HP = -140 mV, and cloned hH1 with Kd,app of 3.0 +/- 0.5 microM at HP = -100 mV and 22.0 +/- 3.2 microM at HP = -140 mV, respectively, either ventricular INa or cloned hH1 had significantly higher sensitivity to moricizine than atrial INa. The h infinity curve of ventricular INa was shifted by 10.5 +/- 3.5 mV by 3 microM moricizine and that of hH1 was shifted by 5.0 +/- 2.3 mV by 30 microM moricizine. From the modulated receptor theory, we have estimated the dissociation constants for the resting and inactivated state to be 99.3 and 1.2 microM in atrial myocytes, 30 and 0.17 microM in ventricular myocytes, and 22 and 0.2 microM in cloned hH1, respectively. We conclude that moricizine has a higher affinity for the inactivated Na+ channel than for the resting state channel in atrial myocytes, and moricizine showed the significant atrioventricular difference of moricizine block on INa. Moricizine would exert an antiarrhythmic action on atrial myocytes, as well as on ventricular myocytes, by blocking Na+ channels with a high affinity to the inactivated state and a slow dissociation kinetics. PMID:12402511

  6. Effects of cholesterol depletion on compartmentalized cAMP responses in adult cardiac myocytes.

    Science.gov (United States)

    Agarwal, Shailesh R; MacDougall, David A; Tyser, Richard; Pugh, Sara D; Calaghan, Sarah C; Harvey, Robert D

    2011-03-01

    ?(1)-Adrenergic receptors (?(1)ARs) and E-type prostaglandin receptors (EPRs) both produce compartmentalized cAMP responses in cardiac myocytes. The role of cholesterol-dependent lipid rafts in producing these compartmentalized responses was investigated in adult rat ventricular myocytes. ?(1)ARs were found in lipid raft and non-lipid raft containing membrane fractions, while EPRs were only found in non-lipid raft fractions. Furthermore, ?(1)AR activation enhanced the L-type Ca(2+) current, intracellular Ca(2+) transient, and myocyte shortening, while EPR activation had no effect, consistent with the idea that these functional responses are regulated by cAMP produced by receptors found in lipid raft domains. Using methyl-?-cyclodextrin to disrupt lipid rafts by depleting membrane cholesterol did not eliminate compartmentalized behavior, but it did selectively alter specific receptor-mediated responses. Cholesterol depletion enhanced the sensitivity of functional responses produced by ?(1)ARs without having any effect on EPR activation. Changes in cAMP activity were also measured in intact cells using two different FRET-based biosensors: a type II PKA-based probe to monitor cAMP in subcellular compartments that include microdomains associated with caveolar lipid rafts and a freely diffusible Epac2-based probe to monitor total cytosolic cAMP. ?(1)AR and EPR activation elicited responses detected by both FRET probes. However, cholesterol depletion only affected ?(1)AR responses detected by the PKA probe. These results indicate that lipid rafts alone are not sufficient to explain the difference between ?(1)AR and EPR responses. They also suggest that ?(1)AR regulation of myocyte contraction involves the local production of cAMP by a subpopulation of receptors associated with caveolar lipid rafts. PMID:21115018

  7. Hypertrophy, Tonsillar (Enlarged Tonsils) (For Parents)

    Science.gov (United States)

    ... Precautions Checkups: What to Expect A to Z: Hypertrophy, Tonsillar (Enlarged Tonsils) KidsHealth > Parents > A to Z > ... to Know Keep in Mind A to Z: Hypertrophy, Tonsillar (Enlarged Tonsils) May also be called: Enlarged ...

  8. 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.)

  9. Myosin Regulatory Light Chain Phosphorylation Attenuates Cardiac Hypertrophy*S?

    OpenAIRE

    Huang, Jian; Shelton, John M.; Richardson, James A.; Kamm, Kristine E.; Stull, James T.

    2008-01-01

    Hyperphosphorylation of myosin regulatory light chain (RLC) in cardiac muscle is proposed to cause compensatory hypertrophy. We therefore investigated potential mechanisms in genetically modified mice. Transgenic (TG) mice were generated to overexpress Ca2+/calmodulin-dependent myosin light chain kinase specifically in cardiomyocytes. Phosphorylation of sarcomeric cardiac RLC and cytoplasmic nonmuscle RLC increased markedly in hearts from TG mice compared with hearts f...

  10. 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

    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, we measured sitting BP, serum collagen type I carboxy-terminal telopeptide (ICTP) reflecting degradation, procollagen type I carboxy-terminal propeptide (PICP) reflecting synthesis and LV mass by echocardiography after 2 weeks of placebo treatment and after 1 year of antihypertensive treatment with a losartan- or an atenolol-based regimen. Furthermore, we measured intima-media thickness of the common carotid arteries (IMT), minimal forearm vascular resistance (MFVR) by plethysmography and ambulatory 24-h BP in around half of the patients. At baseline, PICP/ICTP was positively related to IMT (r=0.24, P

  11. Role of microtubules in the contractile dysfunction of hypertrophied myocardium

    Science.gov (United States)

    Zile, M. R.; Koide, M.; Sato, H.; Ishiguro, Y.; Conrad, C. H.; Buckley, J. M.; Morgan, J. P.; Cooper, G. 4th

    1999-01-01

    OBJECTIVES: We sought to determine whether the ameliorative effects of microtubule depolymerization on cellular contractile dysfunction in pressure overload cardiac hypertrophy apply at the tissue level. BACKGROUND: A selective and persistent increase in microtubule density causes decreased contractile function of cardiocytes from cats with hypertrophy produced by chronic right ventricular (RV) pressure overloading. Microtubule depolymerization by colchicine normalizes contractility in these isolated cardiocytes. However, whether these changes in cellular function might contribute to changes in function at the more highly integrated and complex cardiac tissue level was unknown. METHODS: Accordingly, RV papillary muscles were isolated from 25 cats with RV pressure overload hypertrophy induced by pulmonary artery banding (PAB) for 4 weeks and 25 control cats. Contractile state was measured using physiologically sequenced contractions before and 90 min after treatment with 10(-5) mol/liter colchicine. RESULTS: The PAB significantly increased RV systolic pressure and the RV weight/body weight ratio in PAB; it significantly decreased developed tension from 59+/-3 mN/mm2 in control to 25+/-4 mN/mm2 in PAB, shortening extent from 0.21+/-0.01 muscle lengths (ML) in control to 0.12+/-0.01 ML in PAB, and shortening rate from 1.12+/-0.07 ML/s in control to 0.55+/-0.03 ML/s in PAB. Indirect immunofluorescence confocal microscopy showed that PAB muscles had a selective increase in microtubule density and that colchicine caused complete microtubule depolymerization in both control and PAB papillary muscles. Microtubule depolymerization normalized myocardial contractility in papillary muscles of PAB cats but did not alter contractility in control muscles. CONCLUSIONS: Excess microtubule density, therefore, is equally important to both cellular and to myocardial contractile dysfunction caused by chronic, severe pressure-overload cardiac hypertrophy.

  12. 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…

  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. Experimental myocardial hypertrophy induced by a minimally invasive ascending aorta coarctation

    OpenAIRE

    Martins, A. S.; Aguilera, N. W.; Matsubara, B. B.; Bregagnollo, E. A.

    2001-01-01

    Ascending aorta coarctation was produced by a minimally invasive technique in rabbits. Animal mortality was 5%. Morphometric and hemodynamic parameters were evaluated. A parabiotically isolated heart model was used to assess the hemodynamic parameters. Left ventricular weight/body weight ratio and muscle area showed clear evidence of hypertrophy when compared to control. The hemodynamic changes in the isolated heart model suggested decreased diastolic and systolic function in the coarcted gro...

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

    International Nuclear Information System (INIS)

    Asymmetric septal hypertrophy with abnormal thallium scintigram and elevated cardiac enzymes were observed in five patients and were studied with special reference to the clinical significance of their clinicopathological features. They were not familial cardiomyopathy patients. Two of the five patients (Cases 1 and 2) exhibited the clinical features characteristic of hypertrophic cardiomyopathy without abnormal thallium perfusion and serum cardiac enzyme levels. A right endomyocardial biopsy for Case 1 disclosed myocardial fibrosis in addition to hypertrophy and disarray of myocardial fibers. The left ventricular cavities of two other patients (Cases 4 and 5) tended to be dilated with signs of impaired systolic function and asymmetric septal hypertrophy. A regional area of reduced thickness was observed in the medial portion of the left ventricular posterior wall of Case 4. The remaining case (Case 3) exhibited left ventricular dilatation and reduced left ventricular systolic function, disproportionate hypertrophy, and had clinical signs of congestive heart failure. Necropsy disclosed massive fibrosis and diffuse disarray of myocardial fibers. Some patients with familial hypertrophic cardiomyopathy progress to exhibit clinical features of dilated cardiomyopathy in the termimal stages, and have massive fibrosis of the myocardium histologically. Thallium scintigraphic abnormalities and elevated serum levels of cardiac enzymes, especially the LDH1 isoenzyme, especially the LDH1 isoenzyme, in patients with hypertrophic cardiomyopathy may be a meaningful indicator of such progression in its early stages. The five patients in the present study exhibited a variety of clinical and histological features which may comprise a spectrum of clinical conditions during the progression from hypertrophic cardiomyopathy to a condition like dilated cardiomyopathy, similar to that in familial patients. This progression and the factors promoting it should be studied further in the near future. (author)

  16. Therapeutic Effects of Vitamin D Analogs on Cardiac Hypertrophy in Spontaneously Hypertensive Rats

    OpenAIRE

    Kong, Juan; Kim, Gene H.; Wei, Minjie; Sun, Tao; Li, George; Liu, Shu Q.; Li, Xinmin; Bhan, Ishir; Zhao, Qun; Thadhani, Ravi; Li, Yan Chun

    2010-01-01

    Vitamin D inhibits renin expression and blocks the compensatory induction of renin associated with the use of renin-angiotensin system inhibitors. Here we test the therapeutic effects of two commonly used vitamin D analogs and their combination with losartan on the development of left ventricular hypertrophy. One-month-old male spontaneously hypertensive rats were treated with vehicle, losartan, paricalcitol, doxercalciferol, a combination of losartan and paricalcitol, or a combination of los...

  17. Early sequence of cardiac adaptations and growth factor formation in pressure- and volume-overload hypertrophy.

    Science.gov (United States)

    Modesti, P A; Vanni, S; Bertolozzi, I; Cecioni, I; Polidori, G; Paniccia, R; Bandinelli, B; Perna, A; Liguori, P; Boddi, M; Galanti, G; Serneri, G G

    2000-09-01

    To investigate the time sequence of cardiac growth factor formation, echocardiographic and hemodynamic measurements were performed at scheduled times, and mRNAs for angiotensinogen, prepro-endothelin-1 (ppET-1), and insulin-like growth factor I (IGF-I) were quantified with RT-PCR and localized with in situ hybridization in pigs (fluothane anesthesia) by use of pressure or volume overload (aortic banding and aorta-cava fistula, respectively). Relative peptide formation was also measured by radioimmunoassay. In pressure overload, angiotensinogen and ppET-1 mRNA overexpression on myocytes (13 times vs. sham at 3 h and 112 times at 6 h, respectively) was followed by recovery (12 h) of initially decreased (0.5-6 h) myocardial contractility. In volume overload, contractility was not decreased, the angiotensinogen gene was slightly upregulated at 6 h (6.7 times), and ppET-1 was not overexpressed. IGF-I mRNA was overexpressed on myocytes (at 24 h) in both volume and pressure overload (14 times and 37 times, respectively). In the latter setting, a second ppET-1 overexpression was detectable on myocytes at 7 days. In conclusion, acute cardiac adaptation responses involve different growth factor activation over time in pressure versus volume overload; growth factors initially support myocardial contractility and thereafter induce myocardial hypertrophy. PMID:10993758

  18. Effect of 3-Aminobenzamide, an Inhibitor of Poly (ADP-RibosePolymerase in Experimental Cardiac Hypertrophy

    Directory of Open Access Journals (Sweden)

    P. Balakumar

    2006-01-01

    Full Text Available The male Wistar rats were anaesthetized with thiopentone sodium (35 mg kg-1, i.p., and were subjected to Partial Abdominal Aortic Constriction (PAAC for 4 wk. 3-aminobenzamide (10, 20 mg kg-1 i.p., b.i.d treatment was started three days before surgery and it was continued for 4 weeks after surgery. The Left Ventricular (LV hypertrophy and LV dysfunction were assessed by measuring ratio of LV weight to body weight (LVW/BW, LV wall thickness (LVWT, LV collagen content, protein content, RNA concentration, Left Ventricular Developed Pressure (LVDP, rate of pressure development (dp/dtmax and rate of pressure decay (dp/dtmin. Further, Venous Pressure (VP and Mean Arterial Blood Pressure (MABP were recorded. The PAAC produced LV hypertrophy by increasing LVW/BW, LVWT, LV protein content and LV RNA concentration. Further, PAAC was noted to produce LV dysfunction by decreasing LVDP, dp/dtmax, dp/dtmin and increasing LV collagen content. Moreover, PAAC has significantly increased VP and MABP. 3-Aminobenzamide, a PARP inhibitor markedly attenuated PAAC-induced LV hypertrophy, LV dysfunction, increase in VP and MABP. These results suggest that 3-aminobenzamide prevented PAAC-induced cardiac hypertrophy and LV dysfunction which may be due to inhibition of PARP.

  19. Mitofusin-2 Maintains Mitochondrial Structure and Contributes to Stress-Induced Permeability Transition in Cardiac Myocytes ? †

    Science.gov (United States)

    Papanicolaou, Kyriakos N.; Khairallah, Ramzi J.; Ngoh, Gladys A.; Chikando, Aristide; Luptak, Ivan; O'Shea, Karen M.; Riley, Dushon D.; Lugus, Jesse J.; Colucci, Wilson S.; Lederer, W. Jonathan; Stanley, William C.; Walsh, Kenneth

    2011-01-01

    Mitofusin-2 (Mfn-2) is a dynamin-like protein that is involved in the rearrangement of the outer mitochondrial membrane. Research using various experimental systems has shown that Mfn-2 is a mediator of mitochondrial fusion, an evolutionarily conserved process responsible for the surveillance of mitochondrial homeostasis. Here, we find that cardiac myocyte mitochondria lacking Mfn-2 are pleiomorphic and have the propensity to become enlarged. Consistent with an underlying mild mitochondrial dysfunction, Mfn-2-deficient mice display modest cardiac hypertrophy accompanied by slight functional deterioration. The absence of Mfn-2 is associated with a marked delay in mitochondrial permeability transition downstream of Ca2+ stimulation or due to local generation of reactive oxygen species (ROS). Consequently, Mfn-2-deficient adult cardiomyocytes are protected from a number of cell death-inducing stimuli and Mfn-2 knockout hearts display better recovery following reperfusion injury. We conclude that in cardiac myocytes, Mfn-2 controls mitochondrial morphogenesis and serves to predispose cells to mitochondrial permeability transition and to trigger cell death. PMID:21245373

  20. 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.

  1. Cytokine-mediated apoptosis in cardiac myocytes: the role of inducible nitric oxide synthase induction and peroxynitrite generation.

    Science.gov (United States)

    Arstall, M A; Sawyer, D B; Fukazawa, R; Kelly, R A

    1999-10-29

    Increased production of nitric oxide (NO) after induction of the cytokine-inducible isoform of nitric oxide synthase (iNOS or NOS2) in cardiac myocytes and other parenchymal cells within the heart may in addition to contributing to myocyte contractile dysfunction also contribute to the induction of programmed cell death (apoptosis). To investigate the mechanism(s) by which increased NO production leads to apoptosis, we examined the role of NO in primary cultures of neonatal rat ventricular myocytes (NRVMs) after induction by the cytokines interleukin-1beta (IL-1beta) and interferon gamma (IFNgamma) or exposure to the exogenous NO donor S-nitroso-N-acetylcysteine (SNAC) or peroxynitrite (ONOO(-)). Both SNAC (1 mmol/L) and ONOO(-) (100 micromol/L), but not their respective controls (ie, N-acetylcysteine and pH-inactivated ONOO(-)), induced apoptosis in confluent, serum-starved NRVMs at 48 hours. Similarly, incubation of NRVMs with IL-1beta and IFNgamma for 48 hours resulted in an increase in iNOS expression, nitrite production, and programmed cell death. Both the cytokine-induced nitrite accumulation and myocyte apoptosis could be completely prevented by the nonselective NOS inhibitor L-nitroarginine (3 mmol/L) or the specific iNOS inhibitor 2-amino-5, 6-dihydro-6-methyl-4H-1,3-thiazine (AMT, 100 micromol/L). NO-mediated myocyte apoptosis was not attenuated by the inhibition of soluble guanylyl cyclase with ODQ, nor could apoptosis be induced by the incubation of NRVMs with 1 mmol/L 8-bromo-cGMP, a cell-permeant cGMP analogue. However, NO-mediated apoptosis was significantly attenuated by the superoxide dismutase mimetic and ONOO(-) scavenger Mn(III)tetrakis (4-benzoic acid) porphyrin (MnTBAP, 100 micromol/L). NO/ONOO(-)-mediated apoptosis was associated with increased expression of Bax with no change in Bcl-2 mRNA abundance. Furthermore, apoptotic cell death was also confirmed in adult rat ventricular myocytes (ARVMs) when grown in heteroculture with IL-1beta- and IFNgamma-treated rat cardiac microvascular endothelial cells. Therefore, cytokine-induced apoptosis in NRVMs and ARVMs is mediated by iNOS induction, ONOO(-), and associated with an increase in Bax levels. PMID:10532951

  2. 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. PMID:24311803

  3. Manganese-enhanced MRI detection of impaired calcium regulation in a mouse model of cardiac hypertrophy.

    Science.gov (United States)

    Andrews, Martin; Giger, Maryellen L; Roman, Brian B

    2015-02-01

    The aim of this study was to use manganese (Mn)-enhanced MRI (MEMRI) to detect changes in calcium handling associated with cardiac hypertrophy in a mouse model, and to determine whether the impact of creatine kinase ablation is detectable using this method. Male C57BL/6 (C57, n?=?11) and male creatine kinase double-knockout (CK-M/Mito(-/-) , DBKO, n?=?12) mice were imaged using the saturation recovery Look-Locker T1 mapping sequence before and after the development of cardiac hypertrophy. Hypertrophy was induced via subcutaneous continuous 3-day infusion of isoproterenol, and sham mice not subjected to cardiac hypertrophy were also imaged. During each scan, the contrast agent Mn was administered and the resulting change in R1 (=1/T1) was calculated. Two anatomical regions of interest (ROIs) were considered, the left-ventricular free wall (LVFW) and the septum, and one ROI in an Mn-containing standard placed next to the mouse. We found statistically significant (p?hypertrophy. No statistically significant decreases were detected in the standard, and no statistically significant differences were found among the sham mice. Using a murine model, we successfully demonstrated that changes in Mn uptake as a result of cardiac hypertrophy are detectable using the functional contrast agent and calcium mimetic Mn. Our measurements showed a decrease in the relaxivity (R1) of the myocardium following cardiac hypertrophy compared with normal control mice. PMID:25523065

  4. Use of scintigraphic studies in mid-ventricular obstructive cardiomyopathy to rule out pseudoaneurysm

    International Nuclear Information System (INIS)

    A pseudo-pseudo aneurysm of the left ventricle due to mid-ventricular obstruction from asymmetric septal hypertrophy is presented. A case of mid-ventricular hypertrophic obstructive cardiomyopathy (MVHOCM) was evaluated by means of echocardiography, angiocardiography, gated cardiac blood pool scanning, and a TI-201 myocardial scan. The gated cardiac blood pool scan appearance of MVHOCM is similar to pseudoaneurysm of the left ventricle. TI-201 myocardial imaging, however, was able to distinguish between MVHOCM and pseudoaneurysm of the left ventricle

  5. Current concepts on ventricular fibrillation: A Vicious Circle of Cardiomyocyte Calcium Overload in the Initiation, Maintenance, and Termination of Ventricular Fibrillation

    Directory of Open Access Journals (Sweden)

    Christian E. Zaugg

    2004-04-01

    Full Text Available Based on recent experimental studies, this review article introduces the novel concept that cardiomyocyte Ca2+ and ventricular fibrillation (VF are mutually related, forming a self-maintaining vicious circle in the initiation, maintenance, and termination of VF. On the one hand, elevated myocyte Ca2+ can cause delayed afterdepolarizations, triggered activity, and consequently life-threatening ventricular tachyarrhythmias in various pathological conditions such as digitalis toxicity, myocardial ischemia, or heart failure. On the other hand, VF itself directly and rapidly causes progressive myocyte Ca2+ overload that maintains VF and renders termination of VF increasingly difficult. Accordingly, energy levels for successful electrical defibrillation (defibrillation thresholds increase as both VF and Ca2+ overload progress. Furthermore, VF-induced myocyte Ca2+ overload can promote re-induction of VF after defibrillation and/or postfibrillatory myocardial dysfunction (postresuscitation stunning due to reduced myofilament Ca2+ responsiveness. The probability of these adverse events is best reduced by early detection and rapid termination of VF to prevent or limit Ca2+ overload. Early additional therapy targeting transsarcolemmal Ca2+ entry, particularly during the first 2 min of VF, may partially prevent myocyte Ca2+ overload and thus, increase the likelihood of successful defibrillation as well as prevent postfibrillatory myocardial dysfunction.

  6. Cardiac myocyte–secreted cAMP exerts paracrine action via adenosine receptor activation

    Science.gov (United States)

    Sassi, Yassine; Ahles, Andrea; Truong, Dong-Jiunn Jeffery; Baqi, Younis; Lee, Sang-Yong; Husse, Britta; Hulot, Jean-Sébastien; Foinquinos, Ariana; Thum, Thomas; Müller, Christa E.; Dendorfer, Andreas; Laggerbauer, Bernhard; Engelhardt, Stefan

    2014-01-01

    Acute stimulation of cardiac ?-adrenoceptors is crucial to increasing cardiac function under stress; however, sustained ?-adrenergic stimulation has been implicated in pathological myocardial remodeling and heart failure. Here, we have demonstrated that export of cAMP from cardiac myocytes is an intrinsic cardioprotective mechanism in response to cardiac stress. We report that infusion of cAMP into mice averted myocardial hypertrophy and fibrosis in a disease model of cardiac pressure overload. The protective effect of exogenous cAMP required adenosine receptor signaling. This observation led to the identification of a potent paracrine mechanism that is dependent on secreted cAMP. Specifically, FRET-based imaging of cAMP formation in primary cells and in myocardial tissue from murine hearts revealed that cardiomyocytes depend on the transporter ABCC4 to export cAMP as an extracellular signal. Extracellular cAMP, through its metabolite adenosine, reduced cardiomyocyte cAMP formation and hypertrophy by activating A1 adenosine receptors while delivering an antifibrotic signal to cardiac fibroblasts by A2 adenosine receptor activation. Together, our data reveal a paracrine role for secreted cAMP in intercellular signaling in the myocardium, and we postulate that secreted cAMP may also constitute an important signal in other tissues. PMID:25401477

  7. Cardiac myocyte-secreted cAMP exerts paracrine action via adenosine receptor activation.

    Science.gov (United States)

    Sassi, Yassine; Ahles, Andrea; Truong, Dong-Jiunn Jeffery; Baqi, Younis; Lee, Sang-Yong; Husse, Britta; Hulot, Jean-Sébastien; Foinquinos, Ariana; Thum, Thomas; Müller, Christa E; Dendorfer, Andreas; Laggerbauer, Bernhard; Engelhardt, Stefan

    2014-12-01

    Acute stimulation of cardiac ?-adrenoceptors is crucial to increasing cardiac function under stress; however, sustained ?-adrenergic stimulation has been implicated in pathological myocardial remodeling and heart failure. Here, we have demonstrated that export of cAMP from cardiac myocytes is an intrinsic cardioprotective mechanism in response to cardiac stress. We report that infusion of cAMP into mice averted myocardial hypertrophy and fibrosis in a disease model of cardiac pressure overload. The protective effect of exogenous cAMP required adenosine receptor signaling. This observation led to the identification of a potent paracrine mechanism that is dependent on secreted cAMP. Specifically, FRET-based imaging of cAMP formation in primary cells and in myocardial tissue from murine hearts revealed that cardiomyocytes depend on the transporter ABCC4 to export cAMP as an extracellular signal. Extracellular cAMP, through its metabolite adenosine, reduced cardiomyocyte cAMP formation and hypertrophy by activating A1 adenosine receptors while delivering an antifibrotic signal to cardiac fibroblasts by A2 adenosine receptor activation. Together, our data reveal a paracrine role for secreted cAMP in intercellular signaling in the myocardium, and we postulate that secreted cAMP may also constitute an important signal in other tissues. PMID:25401477

  8. Masseter muscle hypertrophy: case report

    Scientific Electronic Library Online (English)

    Eduardo Kazuo, Sannomya; Marcelo, Gonçalves; Marcelo Paraíso, Cavalcanti.

    Full Text Available SciELO Brazil | Language: English Abstract in portuguese A hipertrofia dos músculos masseteres caracteriza-se aumento uni ou bilateral dos músculos masseteres, atingindo igualmente homens e mulheres depois da puberdade. Sua etiologia é desconhecida. Os sintomas incluem limitação da abertura bucal e tensão na região dos músculos hipertrofiados. Este artigo [...] apresenta um caso de hipertrofia de músculo masseter, com várias modalidades imagens, tais como radiografia convencional, tomografia computadorizada e ressonância magnética. É muito importante um conhecimento profundo desta condição para estabelecer o diagnostico diferencial de outras patologias, como tumores da glândula parótida e infecção dental. Abstract in english Masseter muscle hypertrophy is characterized by unilateral or bilateral enlargement of the masseter muscles affecting both males and females after puberty. Its etiology remains unknown. Limitations on mouth opening and also tension in the region of the hypertrophied muscle are symptoms reported. Thi [...] s paper reports a case of masseter muscle hypertrophy diagnosed using imaging modalities such as conventional radiography, computed tomography and magnetic resonance imaging scans. The familiarity with this condition is important to settle the differential diagnosis with other pathologies such as parotid gland tumors and dental infection.

  9. Regulatory Volume Decrease of Cardiac Myocytes Induced by ?-Adrenergic Activation of the Cl? Channel in Guinea Pig

    OpenAIRE

    Wang, Zhuren; Mitsuiye, Tamotsu; Rees, Sia?n A.; Noma, Akinori

    1997-01-01

    A new method was developed to automatically measure the thickness of a single ventricular myocyte of guinea-pig heart. A fine marker was attached on the cell's upper surface and changes in its vertical position were measured by focusing it under the microscope. When the osmolarity of the bath solution was varied, the cell thickness reached a new steady level without any obvious regulatory volume change within the period of observation up to 15 min. The cell thickness was 7.8 ± 0.2 ?m (n ...

  10. ROS and endothelial nitric oxide synthase (eNOS)-dependent trafficking of angiotensin II type 2 receptor begets neuronal NOS in cardiac myocytes.

    Science.gov (United States)

    Jang, Ji Hyun; Chun, Jung Nyeo; Godo, Shigeo; Wu, Guangyu; Shimokawa, Hiroaki; Jin, Chun Zi; Jeon, Ju Hong; Kim, Sung Joon; Jin, Zhe Hu; Zhang, Yin Hua

    2015-05-01

    Angiotensin II (Ang II), a potent precursor of hypertrophy and heart failure, upregulates neuronal nitric oxide synthase (nNOS or NOS1) in the myocardium. Here, we investigate the involvement of type 1 and 2 angiotensin receptors (AT1R and AT2R) and molecular mechanisms mediating Ang II-upregulation of nNOS. Our results showed that pre-treatment of left ventricular (LV) myocytes with antagonists of AT1R or AT2R (losartan, PD123319) and ROS scavengers (apocynin, tiron or PEG-catalase) blocked Ang II-upregulation of nNOS. Surface biotinylation or immunocytochemistry experiments demonstrated that AT1R expression in plasma membrane was progressively decreased (internalization), whereas AT2R was increased (membrane trafficking) by Ang II. Inhibition of AT1R or ROS scavengers prevented Ang II-induced translocation of AT2R to plasma membrane, suggesting an alignment of AT1R-ROS-AT2R. Furthermore, Ang II increased eNOS-Ser(1177) but decreased eNOS-Thr(495), indicating concomitant activation of eNOS. Intriguingly, ROS scavengers but not AT2R antagonist prevented Ang II-activation of eNOS. NOS inhibitor (L-NG-Nitroarginine Methyl Ester, L-NAME) or eNOS gene deletion (eNOS(-/-)) abolished Ang II-induced membrane trafficking of AT2R, nNOS protein expression and activity. Mechanistically, S-nitrosation of AT2R was increased by sodium nitroprusside (SNP), a NO donor. Site-specific mutagenesis analysis reveals that C-terminal cysteine 349 in AT2R is essential in AT2R translocation to plasma membrane. Taken together, we demonstrate, for the first time, that Ang II upregulates nNOS protein expression and activity via AT1R/ROS/eNOS-dependent S-nitrosation and membrane translocation of AT2R. Our results suggest a novel crosstalk between AT1R and AT2R in regulating nNOS via eNOS in the myocardium under pathogenic stimuli. PMID:25804308

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

    Science.gov (United States)

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

    2015-04-01

    Fibrates are peroxisome proliferator-activated receptor-? agonists and are clinically used for treatment of dyslipidemia and hypertriglyceridemia. Fenofibrate is reported as a cardioprotective agent in various models of cardiac dysfunction; however, limited literature is available regarding the role of gemfibrozil as a possible cardioprotective agent, especially in a non-obese model of cardiac remodelling. The present study investigated the role of gemfibrozil against partial abdominal aortic constriction-induced cardiac hypertrophy in rats. Cardiac hypertrophy was induced by partial abdominal aortic constriction in rats and they survived for 4 weeks. The cardiac hypertrophy was assessed by measuring left ventricular weight to body weight ratio, left ventricular wall thickness, and protein and collagen content. The oxidative stress in the cardiac tissues was assessed by measuring thiobarbituric acid-reactive substances, superoxide anion generation, and reduced glutathione level. The haematoxylin-eosin and picrosirius red staining was used to observe cardiomyocyte diameter and collagen deposition, respectively. Moreover, serum levels of cholesterol, high-density lipoproteins, triglycerides, and glucose were also measured. Gemfibrozil (30 mg/kg, p.o.) was administered since the first day of partial abdominal aortic constriction and continued for 4 weeks. The partial abdominal aortic constriction-induced cardiac oxidative stress and hypertrophy are indicated by significant change in various parameters used in the present study that were ameliorated with gemfibrozil treatment in rats. No significant change in serum parameters was observed between various groups used in the present study. It is concluded that gemfibrozil ameliorates partial abdominal aortic constriction-induced cardiac oxidative stress and hypertrophy and in rats. PMID:24905340

  12. Masseter and medial pterygoid muscle hypertrophy

    OpenAIRE

    R, Guruprasad; Rishi, Sudhirkumar; Nair, Preeti P.; Thomas, Shaji

    2011-01-01

    Hypertrophy refers to an enlargement caused by an increase in the size but not in the number of cells. Generalised masticatory muscle hypertrophy may affect the temporalis muscle, masseters and medial pterygoids in a variety of combinations. Masseteric hypertrophy may present as either unilateral or bilateral painless swelling of unknown origin in the region of angle of mandible. It is a relatively rare condition and presents a diagnostic dilemma. While the history and clinical examination ar...

  13. PGC-1? accelerates cytosolic Ca2+ clearance without disturbing Ca2+ homeostasis in cardiac myocytes

    International Nuclear Information System (INIS)

    Energy metabolism and Ca2+ handling serve critical roles in cardiac physiology and pathophysiology. Peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1?) is a multi-functional coactivator that is involved in the regulation of cardiac mitochondrial functional capacity and cellular energy metabolism. However, the regulation of PGC-1? in cardiac Ca2+ signaling has not been fully elucidated. To address this issue, we combined confocal line-scan imaging with off-line imaging processing to characterize calcium signaling in cultured adult rat ventricular myocytes expressing PGC-1? via adenoviral transduction. Our data shows that overexpressing PGC-1? improved myocyte contractility without increasing the amplitude of Ca2+ transients, suggesting that m