WorldWideScience

Sample records for ventricular myocyte hypertrophy

  1. 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.

  2. Heart rate variability in left ventricular hypertrophy.

    OpenAIRE

    Mandawat, M. K.; Wallbridge, D R; Pringle, S.D.; Riyami, A. A.; Latif, S; MacFarlane, P. W.; Lorimer, A.R.; Cobbe, S. M.

    1995-01-01

    BACKGROUND--Electrocardiographic left ventricular hypertrophy and strain are associated with increased cardiac morbidity and mortality. Impaired cardiac autonomic function, assessed non-invasively by spontaneous heart rate variability on Holter monitoring, is associated with an increased risk of sudden death after myocardial infarction. AIM--To study the effect of left ventricular hypertrophy on heart rate variability. PATIENTS--36 controls and 154 patients with left ventricular hypertrophy (...

  3. Characterization of isolated ventricular myocytes from adult zebrafish (Danio rerio)

    OpenAIRE

    Brette, Fabien; Luxan, Guillermo; Cros, Caroline; Dixey, Hayley; Wilson, Christopher; Shiels, Holly A.

    2008-01-01

    The zebrafish is widely used for human related disease studies. Surprisingly, there is no information about the electrical activity of single myocytes freshly isolated from adult zebrafish ventricle. In this study, we present an enzymatic method to isolate ventricular myocytes from zebrafish heart that yield a large number of calcium tolerant cells. Ventricular myocytes from zebrafish were imaged using light and confocal microscopy. Myocytes were mostly rod shaped and responded by vigorous co...

  4. Electrical inhomogeneity in left ventricular hypertrophy.

    Science.gov (United States)

    Gao, Changzhao; Yang, Dandan

    2014-07-01

    Recent studies designed to assess the relationship between aortic compliance and heterogeneity of heart electrical activity has shown that hypertrophy aggravates repolarization disturbances in the myocardium. Numerous mechanisms of electrical instability and inhomogeneity associated with left ventricular hypertrophy are now under investigation. Most of the studies have been found to be focused on ventricular Gradient, QT dispersion, amplitudes of isointegral maps during ventricular repolarization, abnormally low-QRST areas, dispersion of the QT interval, and spatial QRS-T(angle). These studies point to marked repolarization abnormalities in left ventricular hypertrophy and the dispersion of the QT interval as a valuable index for inhomogeneity of repolarization and the subsequent heart rate variability. The heart rate-corrected QT dispersion and QT apex dispersion seem to be significantly longer in the patients with left ventricular hypertrophy than in normal individuals. The review study has also identified QRST isointegral map as a valuable technique in assessment of the electro-cardiac events in LVH. PMID:24566960

  5. FGF23 induces left ventricular hypertrophy

    OpenAIRE

    Faul, Christian; Amaral, Ansel P.; Oskouei, Behzad; Hu, Ming-Chang; Sloan, Alexis; Isakova, Tamara; Gutiérrez, Orlando M; Aguillon-Prada, Robier; Lincoln, Joy; Hare, Joshua M; Mundel, Peter; Morales, Azorides; Scialla, Julia; Fischer, Michael; Soliman, Elsayed Z

    2011-01-01

    Chronic kidney disease (CKD) is a public health epidemic that increases risk of death due to cardiovascular disease. Left ventricular hypertrophy (LVH) is an important mechanism of cardiovascular disease in individuals with CKD. Elevated levels of FGF23 have been linked to greater risks of LVH and mortality in patients with CKD, but whether these risks represent causal effects of FGF23 is unknown. Here, we report that elevated FGF23 levels are independently associated with LVH in a large, rac...

  6. Anchored p90 Ribosomal S6 Kinase 3 is Required for Cardiac Myocyte Hypertrophy

    Science.gov (United States)

    Li, Jinliang; Kritzer, Michael D.; Carlisle Michel, Jennifer J.; Le, Andrew; Thakur, Hrishikesh; Gayanilo, Marjorie; Passariello, Catherine; Negro, Alejandra; Danial, Joshua B.; Oskouei, Behzad; Sanders, Michael; Hare, Joshua M.; Hanauer, Andre; Dodge-Kafka, Kimberly; Kapiloff, Michael S.

    2012-01-01

    Rationale Cardiac myocyte hypertrophy is the main compensatory response to chronic stress on the heart. p90 Ribosomal S6 Kinase (RSK) family members are effectors for extracellular signal-regulated kinases that induce myocyte growth. Although increased RSK activity has been observed in stressed myocytes, the functions of individual RSK family members have remained poorly defined, despite being potential therapeutic targets for cardiac disease. Objective To demonstrate that type 3 RSK (RSK3) is required for cardiac myocyte hypertrophy. Methods and Results RSK3 contains a unique N-terminal domain that is not conserved in other RSK family members. We show that this domain mediates the regulated binding of RSK3 to the muscle A-kinase anchoring protein (mAKAP) scaffold, defining a novel kinase anchoring event. Disruption of both RSK3 expression using RNA interference and RSK3 anchoring using a competing mAKAP peptide inhibited the hypertrophy of cultured myocytes. In vivo, RSK3 gene deletion in the mouse attenuated the concentric myocyte hypertrophy induced by pressure overload and catecholamine infusion. Conclusions Taken together, these data demonstrate that anchored RSK3 transduces signals that modulate pathologic myocyte growth. Targeting of signaling complexes that contain select kinase isoforms should provide an approach for the specific inhibition of cardiac myocyte hypertrophy and for the development of novel strategies for the prevention and treatment of heart failure. PMID:22997248

  7. The mAKAP? Scaffold Regulates Cardiac Myocyte Hypertrophy via Recruitment of Activated Calcineurin

    OpenAIRE

    Li, Jinliang; Negro, Alejandra; Lopez, Johanna; Bauman, Andrea L.; Henson, Edward; Dodge-Kafka, Kimberly; Kapiloff, Michael S

    2009-01-01

    mAKAP? is the scaffold for a multimolecular signaling complex in cardiac myocytes that is required for the induction of neonatal myocyte hypertrophy. We now show that the pro-hypertrophic phosphatase calcineurin binds directly to a single site on mAKAP? that does not conform to any of the previously reported consensus binding sites. Calcineurin - mAKAP? complex formation is increased in the presence of Ca2+/calmodulin and in norepinephrine-stimulated primary cardiac myocytes. This binding is ...

  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. 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, P<0.05) with similar body weights. Myocyte width was also increased in 4-week and 7-week AS mice compared with controls (19.0+/-0.8 and 25.2+/-1.8 versus 14. 1+/-0.5 microm, respectively, P<0.01). By 7 weeks, AS myocytes displayed branching with distinct differences in intercalated disk size and staining for beta(1)-integrin on both cell surface and adjacent extracellular matrix. In vivo left ventricular systolic developed pressure per gram as well as endocardial fractional shortening were similar in 4-week AS and controls but depressed in 7-week AS mice. Myocyte apoptosis estimated by in situ nick end-labeling (TUNEL) was extremely rare in 4-week AS and control mice; however, a low prevalence of TUNEL-positive myocytes and DNA laddering were detected in 7-week AS mice. The specificity of TUNEL labeling was confirmed by in situ ligation of hairpin oligonucleotides. CONCLUSIONS: Our findings indicate that myocyte apoptosis develops during the transition from hypertrophy 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.

  10. 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 ...

  11. 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

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

    Science.gov (United States)

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

    2015-03-01

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

  13. 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...

  14. Left ventricular hypertrophy in Turner syndrome

    DEFF Research Database (Denmark)

    Mortensen, Kristian Havmand; Gravholt, Claus Højbjerg; Hjerrild, Britta Eilersen; Stochholm, Kirstine; Andersen, Niels Holmark

    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.

  15. PKA, Rap1, ERK1/2, and p90RSK mediate PGE2 and EP4 signaling in neonatal ventricular myocytes

    OpenAIRE

    He, Quan; Harding, Pamela; LaPointe, Margot C.

    2009-01-01

    We have previously reported that 1) inhibition of cyclooxygenase-2 and PGE2 production reduces hypertrophy after myocardial infarction in mice and 2) PGE2 acting through its EP4 receptor causes hypertrophy of neonatal ventricular myocytes (NVMs) via ERK1/2. It is known that EP4 couples to adenylate cyclase, cAMP, and PKA. The present study was designed to determine interactions between the cAMP-PKA pathway and ERK1/2 and to further characterize events downstream of ERK1/2. We hypothesized tha...

  16. Accumulation of slowly activating delayed rectifier potassium current (IKs) in canine ventricular myocytes

    DEFF Research Database (Denmark)

    Stengl, Milan; Volders, Paul G A; Thomsen, Morten Bækgaard; Spätjens, Roel L H M G; Sipido, Karin R; Vos, Marc A

    2003-01-01

    In guinea-pig ventricular myocytes, in which the deactivation of slowly activating delayed rectifier potassium current (IKs) is slow, IKs can be increased by rapid pacing as a result of incomplete deactivation and subsequent current accumulation. Whether accumulation of IKs occurs in dogs, in which the deactivation is much faster, is still unclear. In this study the conditions under which accumulation occurs in canine ventricular myocytes were studied with regard to its physiological relevance i...

  17. Stretch-activated channel activation promotes early afterdepolarizations in rat ventricular myocytes under oxidative stress

    OpenAIRE

    Wang, Yanggan; Joyner, Ronald W.; Wagner, Mary B.; CHENG, JUN; Lai, Dongwu; Crawford, Brian H.

    2009-01-01

    Mechanical stretch and oxidative stress have been shown to prolong action potential duration (APD) and produce early afterdepolarizations (EADs). Here, we developed a simulation model to study the role of stretch-activated channel (SAC) currents in triggering EADs in ventricular myocytes under oxidative stress. We adapted our coupling clamp circuit so that a model ionic current representing the actual SAC current was injected into ventricular myocytes and added as a real-time current. This cu...

  18. 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.

  19. 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: 2.386, year: 2014

  20. 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 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

  1. 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.

  2. How to estimate left ventricular hypertrophy in hypertensive patients.

    Science.gov (United States)

    Lovic, Dragan; Erdine, Serap; Catako?lu, Alp Burak

    2014-06-01

    Left ventricular hypertrophy (LVH) is a structural remodeling of the heart developing as a response to volume and/or pressure overload. Previous studies have shown that hypertension is not an independent factor in the development of LVH and occurrence does not depend on the length and severity of hypertension, but the role played by other comorbidities such as triglycerides, age, gender, genetics, insulin resistance, obesity, physical inactivity, increased salt intake and chronic stress. LVH develops through three phases: adaptive, compensatory, and pathological phase. Contractile dysfunction is reversible in the first two phases and irreversible in the third. According to the Framingham study, LVH develops in 15-20% of patients with mild arterial hypertension, and in 50% of patients with severe hypertension. The pathophysiology of LVH includes hypertrophy of cardiomyocytes, interstitial and perivascular fibrosis, coronary microangiopathy and macroangiopathy. Individuals with LVH have 2-4 times higher risk of having adverse CV events compared to patients without LVH. PMID:24818777

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

    Directory of Open Access Journals (Sweden)

    Yang Zhen-Yu

    2010-04-01

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

  4. Cardiac arrhythmias and left ventricular hypertrophy in systemic hypertension

    International Nuclear Information System (INIS)

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

  5. Left ventricular hypertrophy, geometric patterns and clinical correlates among treated hypertensive Nigerians

    OpenAIRE

    Olayinka Akinwusi; Adeseye Akintunde; George Opadijo

    2010-01-01

    BACKGROUND: Left ventricular hypertrophy can be due to various reasons including hypertension. It constitutes an increased cardiovascular risk . Various left ventricular geometric patterns occur in hypertension and may affect the cardiovascular risk profile of hypertensive subjects. METHODS: One hundred and eighty eight hypertensive subjects participated in this study. Left ventricular hypertrophy was diagnosed by echocardiography. Relative wall thickness was derived by 2 x PWTLVIDd. Subjects...

  6. Ventricular hypertrophy and cavity dilatation in relation to body mass index in women with uncomplicated obesity.

    OpenAIRE

    Rider, OJ; Petersen, SE; Francis, JM; Ali, MK; Hudsmith, LE; Robinson MR; Clarke, K.; ~Neubauer, S.

    2011-01-01

    OBJECTIVE: The traditionally accepted mechanism for ventricular adaptation to obesity suggests that cavity dilatation in response to increased blood volume and elevated filling pressure results in ventricular hypertrophy as a compensatory mechanism. Our hypothesis was that, instead, initiation of ventricular hypertrophy in obesity may be explained by changes in hormonal milieu and not by cavity dilatation. RESEARCH DESIGN AND METHODS: 88 female subjects without identifiable cardiovascular ris...

  7. 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)

  8. 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 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.

  9. Hypertrophy, gene expression, and beating of neonatal cardiac myocytes are affected by microdomain heterogeneity in 3D.

    Science.gov (United States)

    Curtis, Matthew W; Sharma, Sadhana; Desai, Tejal A; Russell, Brenda

    2010-12-01

    Cardiac myocytes are known to be influenced by the rigidity and topography of their physical microenvironment. It was hypothesized that 3D heterogeneity introduced by purely physical microdomains regulates cardiac myocyte size and contraction. This was tested in vitro using polymeric microstructures (G'?=?1.66 GPa) suspended with random orientation in 3D by a soft Matrigel matrix (G'?=?22.9 Pa). After 10 days of culture, the presence of 100 ?m-long microstructures in 3D gels induced fold increases in neonatal rat ventricular myocyte size (1.61?±?0.06, p?activity. Together, the results demonstrate that cardiac myocyte behavior can be controlled through local 3D microdomains alone. This approach of defining physical cues as independent features may help to advance the elemental design considerations for scaffolds in cardiac tissue engineering and therapeutic microdevices. PMID:20668947

  10. Reduced L-type calcium current in ventricular myocytes from endotoxemic guinea pigs.

    Science.gov (United States)

    Zhong, J; Hwang, T C; Adams, H R; Rubin, L J

    1997-11-01

    The circulatory response to gram-negative sepsis and its experimental counterpart, endotoxemia, includes a profound dysfunction in myocardial contractility that is resident to the myocyte and associated with reduced systolic free intracellular Ca2+ concentration ([Ca2+]i). We explored the possibility that decreased systolic [Ca2+]i in endotoxemic myocytes is correlated with reduced L-type Ca2+ current (ICa,L). Ventricular myocytes were isolated from guinea pigs 4 h after an intraperitoneal injection of Escherichia coli lipopolysaccharide (LPS; 4 mg/kg). Membrane potentials and Ca2+ currents were measured using whole cell patch-clamp methods. The action potential duration of endotoxemic myocytes was significantly shorter than control values (time to 50% repolarization: LPS, 314 +/- 23 ms; control, 519 +/- 36 ms, P < 0.05). Correspondingly, endotoxemic myocytes demonstrated significantly reduced peak ICa,L density (3.5 +/- 0.2 pA/pF) and Ba2+ current (IBa) density (7.3 +/- 0.5 pA/pF) compared with respective values of control myocytes (ICa,L) density 6.1 +/- 0.3 pA/pF, IBa density 11.3 +/- 0.8 pA/pF; P < 0.05). Endotoxemia-induced reduction in peak ICa,L could not be attributed to alterations in current-voltage relationships, steady-state activation and inactivation, or recovery from inactivation. The beta-adrenoceptor agonist isoproterenol, but not the Ca2+ channel activator BAY K 8644, reversed the LPS-induced reduction in peak ICa,L, cell contraction, and systolic [Ca2+]i. These data demonstrate that part of the host response to endotoxemia involves diminished sarcolemmal ICa,L of ventricular myocytes. PMID:9374768

  11. A Ras-Dependent Pathway Regulates RNA Polymerase II Phosphorylation in Cardiac Myocytes: Implications for Cardiac Hypertrophy

    OpenAIRE

    Abdellatif, Maha; Packer, Sharon E.; Michael, Lloyd H.; Zhang, Dou; Charng, Min Ji; Schneider, Michael D.

    1998-01-01

    Despite extensive evidence implicating Ras in cardiac muscle hypertrophy, the mechanisms involved are unclear. We previously reported that Ras, through an effector-like function of Ras GTPase-activating protein (GAP) in neonatal cardiac myocytes (M. Abdellatif et al., J. Biol. Chem. 269:15423–15426, 1994; M. Abdellatif and M. D. Schneider, J. Biol. Chem. 272:527–533, 1997), can up-regulate expression from a comprehensive set of promoters, including both cardiac cell-specific and constitutive ...

  12. 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)

  13. Resolution of hypo-osmotic stress in isolated mouse ventricular myocytes causes sealing of t-tubules

    OpenAIRE

    Moench, I.; Meekhof, KE; Cheng, LF; Lopatin, AN

    2013-01-01

    It has been recently shown that various stress-inducing manipulations in isolated ventricular myocytes may lead to significant remodeling of t-tubules. Osmotic stress is one of the most common complications in various experimental and clinical settings. Therefore, this study was designed to determine the effects of a physiologically relevant type of osmotic stress, hypo-osmotic challenge, to the integrity of t-tubular system in mouse ventricular myocytes using two approaches: (1) electrophysi...

  14. 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 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.

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

    Directory of Open Access Journals (Sweden)

    Eduardo Cantoni Rosa

    2002-04-01

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

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

    Scientific Electronic Library Online (English)

    Eduardo Cantoni, Rosa; Valdir Ambrósio, Moysés; Ricardo Cintra, Sesso; Frida Liane, Plavnik; Fernando Flexa, Ribeiro; Nárcia E. B., Kohlmann; Artur Beltrame, Ribeiro; Maria Tereza, Zanella; Osvaldo, Kohlmann Jr..

    2002-04-01

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

  17. 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 de...

  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. Quantification of t-tubule area and protein distribution in rat cardiac ventricular myocytes.

    OpenAIRE

    Pásek, Michal; Brette, Fabien; Nelson, Adam; Pearce, C.; Qaiser, A.; Christé, Georges; Orchard, Clive

    2008-01-01

    The transverse (t-) tubules of cardiac ventricular myocytes are invaginations of the surface membrane that form a complex network within the cell. Many of the key proteins involved in excitation-contraction coupling appear to be located predominantly at the t-tubule membrane. Despite their importance, the fraction of cell membrane within the t-tubules remains unclear: measurement of cell capacitance following detubulation suggests approximately 32%, whereas optical measurements suggest up to ...

  20. Differential effects of the peroxynitrite donor, SIN-1, on atrial and ventricular myocyte electrophysiology

    OpenAIRE

    Ingrid M. Bonilla; Sridhar, Arun; Nishijima, Yoshinori; Györke, Sandor; Cardounel, Arturo J.; Carnes, Cynthia A.

    2013-01-01

    Oxidative stress has been implicated in the pathogenesis of heart failure and atrial fibrillation and can result in increased peroxynitrite production in the myocardium.. Atrial and ventricular canine cardiac myocytes were superfused with SIN-1 (3-morpholinosydnonimine N-ethylcarbamide), a peroxynitrite donor, to evaluate the acute electrophysiologic effects of peroxynitrite. Perforated whole cell patch clamp techniques were used to record action potentials. SIN-1 (200 ?M) increased the actio...

  1. 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 ...

  2. The cellular force-frequency response in ventricular myocytes from the varanid lizard, Varanus exanthematicus

    OpenAIRE

    Warren, Daniel E.; Galli, Gina L. J.; Patrick, Simon M.; Shiels, Holly A.

    2010-01-01

    To investigate the cellular mechanisms underlying the negative force-frequency relationship (FFR) in the ventricle of the varanid lizard, Varanus exanthematicus, we measured sarcomere and cell shortening, intracellular Ca2+ ([Ca2+]i), action potentials (APs), and K+ currents in isolated ventricular myocytes. Experiments were conducted between 0.2 and 1.0 Hz, which spans the physiological range of in vivo heart rates at 20–22°C for this species. As stimulation frequency increased, diastolic le...

  3. Left ventricular hypertrophy and obesity: only a matter of fat?

    Science.gov (United States)

    Murdolo, Giuseppe; Angeli, Fabio; Reboldi, Gianpaolo; Di Giacomo, Letizia; Aita, Adolfo; Bartolini, Claudia; Vedecchia, Paolo

    2015-03-01

    Obesity can be regarded as an energy balance disorder in which inappropriate expansion and dys-function of adipose tissue lead to unfavorable outcomes. Even in the absence of hypertension, adiposity induces structural and functional changes in the heart through hemodynamic and non hemodynamic factors. In the "obese" heart, besides the growth of cardiomyocytes, interstitial fat infiltration and triglyceride accumulation in the contractile elements importantly contribute to left-ventricular mass (LVM) accrual, hypertrophy (LVH) and geometric pattern. In harmony with this, the likelihood of LVH is greater in either obese normotensive or hypertensive individuals than in their non-obese counterparts. Interestingly, recent observations highlight the increasing prevalence of the "concentric" (ie, combined remodeling and hypertrophy), rather than "eccentric" pattern of LV geometry in obesity. Nonetheless, obesity is linked with lack of decrease, or even increase, of LVM over time, independently of blood pressure control and hypertensive treatment. Although obesity-related LV changes result in progressive systolic and diastolic heart failure, the assessment of LVM and LVH in obese individuals still remains a difficult task. In this scenario, it is tempting to speculate that therapeutic interventions for reversal of LVH in obesity should either overcome the "non-hemodynamic" factors or reduce the hemodynamic load. Indeed, weight loss, either achieved by lifestyle changes or bariatric procedures, decreases LVM and improves LV function regardless of blood pressure status. These and other mechanistic insights are discussed in this review, which focuses on "adipose dysfunction" as potential instigator of, and putative therapeutic target for, LVH regression in the setting of obesity. PMID:25117210

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

    Directory of Open Access Journals (Sweden)

    Gustavo Baptista de Almeida Faro

    2015-10-01

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

  5. 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)

  6. Dapagliflozin reduces the amplitude of shortening and Ca(2+) transient in ventricular myocytes from streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Hamouda, N N; Sydorenko, V; Qureshi, M A; Alkaabi, J M; Oz, M; Howarth, F C

    2015-02-01

    In the management of type 2 diabetes mellitus, Dapagliflozin (DAPA) is a newly introduced selective sodium-glucose co-transporter 2 inhibitor which promotes renal glucose excretion. Little is known about the effects of DAPA on the electromechanical function of the heart. This study investigated the effects of DAPA on ventricular myocyte shortening and intracellular Ca(2+) transport in streptozotocin (STZ)-induced diabetic rats. Shortening, Ca(2+) transients, myofilament sensitivity to Ca(2+) and sarcoplasmic reticulum Ca(2+), and intracellular Ca(2+) current were measured in isolated rats ventricular myocytes by video edge detection, fluorescence photometry, and whole-cell patch-clamp techniques. Diabetes was characterized in STZ-treated rats by a fourfold increase in blood glucose (440 ± 25 mg/dl, n = 21) compared to Controls (98 ± 2 mg/dl, n = 19). DAPA reduced the amplitude of shortening in Control (76.68 ± 2.28 %, n = 37) and STZ (76.58 ± 1.89 %, n = 42) ventricular myocytes, and reduced the amplitude of the Ca(2+) transients in Control and STZ ventricular myocytes with greater effects in STZ (71.45 ± 5.35 %, n = 16) myocytes compared to Controls (92.01 ± 2.72 %, n = 17). Myofilament sensitivity to Ca(2+) and sarcoplasmic reticulum Ca(2+) were not significantly altered by DAPA in either STZ or Control myocytes. L-type Ca(2+) current was reduced in STZ myocytes compared to Controls and was further reduced by DAPA. In conclusion, alterations in the mechanism(s) of Ca(2+) transport may partly underlie the negative inotropic effects of DAPA in ventricular myocytes from STZ-treated and Control rats. PMID:25351341

  7. Captopril attenuates matrix metalloproteinase-2 and -9 in monocrotaline-induced right ventricular hypertrophy in rats.

    Science.gov (United States)

    Okada, Muneyoshi; Kikuzuki, Ryuta; Harada, Toshiyuki; Hori, Yasutomo; Yamawaki, Hideyuki; Hara, Yukio

    2008-12-01

    Little is known about the influence of angiotensin converting enzyme (ACE) inhibitors on matrix metalloproteinase (MMP) in right ventricular remodeling. We investigated the effect of captopril, an ACE inhibitor, on MMP-2 and MMP-9 in monocrotaline-induced right ventricular hypertrophy. Six-week-old male Wistar rats were injected intraperitoneally with monocrotaline (60 mg/kg) or saline. The rats were administrated captopril (30 mg/kg per day) or a vehicle orally for 24 days from the day of monocrotaline injection. At day 25, echocardiography was performed and hearts were excised. Expressions and activities of MMP-2 and MMP-9 were measured by Western blotting and by gelatin zymography, respectively. In monocrotaline-injected rats, right ventricular weight/tail length ratio increased significantly. Histological analysis revealed cardiomyocyte hypertrophy and fibrosis in right ventricular sections. Echocardiography showed right ventricular dysfunction compared with saline-injected rats. The right ventricular hypertrophy, fibrosis, and dysfunction were inhibited by captopril. However, captopril did not attenuate an increase in pulmonary artery pressure. MMP-2 and MMP-9 expressions and activities in right ventricles increased significantly in monocrotaline-injected rats and captopril inhibited them. These findings indicate that captopril attenuates the development of monocrotaline-induced right ventricular hypertrophy in association with inhibition of MMP-2 and MMP-9 in rats. PMID:19057128

  8. Heart rate variability and left ventricular diastolic function in patients with borderline hypertension with and without left ventricular hypertrophy.

    OpenAIRE

    Veglio, Franco

    2001-01-01

    The relationships between heart rate variability (HRV), left ventricular mass and diastolic function in borderline hypertensive patients (BHT) were evaluated. 24 h Holter electrocardiogram (ECG) and blood pressure (BP) monitoring, M and 2 D echocardiogram and Doppler analysis in 42 BHT with and without left ventricular hypertrophy (LVH) and in 20 normotensive controls were assessed. From 24-h ECG, time domain indexes of HRV were calculated. Standard Deviation of all Cycles (SDNN) and Standard...

  9. 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.

  10. Effects of lysophosphatidylcholine on electrophysiological properties and excitation-contraction coupling in isolated guinea pig ventricular myocytes.

    OpenAIRE

    Liu, E.; Goldhaber, J I; Weiss, J N

    1991-01-01

    Lysophosphoglyceride accumulation in ischemic myocardium has been implicated as a cause of arrhythmias. We examined the effects of lysophosphatidylcholine (LPC) in isolated guinea pig ventricular myocytes. In paced myocytes loaded with the Ca2+ indicator Indo-1-AM and studied at room temperature, 20 microM LPC caused an initial positive inotropic effect followed by spontaneous automaticity, a decline in active cell shortening, and progressive diastolic shortening (contracture) leading to cell...

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

    Science.gov (United States)

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

    2015-08-25

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

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

    OpenAIRE

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

    2006-01-01

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

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

    OpenAIRE

    K Nakayama; 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. ...

  14. Fluvastatin induces apoptosis in rat neonatal cardiac myocytes: a possible mechanism of statin-attenuated cardiac hypertrophy.

    Science.gov (United States)

    Ogata, Yukiyo; Takahashi, Masafumi; Takeuchi, Koichi; Ueno, Shuichi; Mano, Hiroyuki; Ookawara, Shigeo; Kobayashi, Eiji; Ikeda, Uichi; Shimada, Kazuyuki

    2002-12-01

    Hydroxymethylglutaryl CoA (HMG-CoA) reductase inhibitors (statins) have been shown to reduce atherosclerotic cardiovascular mortality and morbidity. Recent evidence indicates that statins may also exert direct effects on vascular wall cells (including endothelial cells and smooth muscle cells) independently of their hypocholesterolemic properties. However, little is known about whether statins have direct effects on myocardium. The effect of lipophilic and hydrophilic statins (fluvastatin and pravastatin) on apoptosis and protein synthesis in rat neonatal cardiac myocytes was investigated. The presence of apoptosis was evaluated by morphologic criteria, electrophoresis of DNA fragments, 4",6"-diamidine-2"-phenylindole (DAPI) staining, and TUNEL assay. Protein synthesis was measured by H-leucine incorporation into the cells. Fluvastatin, but not pravastatin, induced apoptosis in cardiac myocytes in a time- and dose-dependent manner. The pro-apoptotic effect of fluvastatin was reversed in the presence of mevalonate or geranylgeranyl-pyrophosphate (GGPP), but not in the presence of squalene. The addition of protein prenylation inhibitor perillic acid and Rho-kinase inhibitor Y27632 significantly increased apoptosis. Fluvastatin decreased RhoA protein in the membrane fraction, whereas there were no significant changes of the RhoA protein in the cytosol fraction. Interleukin-1beta-stimulated H-leucine incorporation was completely inhibited by fluvastatin, but not by pravastatin. The findings suggest that fluvastatin induces apoptosis in cardiac myocytes via protein prenylation and the subsequent inhibition of Rho, and may play a role in the pathogenesis of cardiac hypertrophy and remodeling. PMID:12451324

  15. AAV9-mediated VEGF-B Gene Transfer Improves Systolic Function in Progressive Left Ventricular Hypertrophy

    OpenAIRE

    Huusko J; Lottonen L; Merentie M; Gurzeler E; Anisimov A; Miyanohara A; Alitalo K; Tavi P; Yl\\xe4-Herttuala S

    2012-01-01

    Mechanisms of the transition from compensatory hypertrophy to heart failure are poorly understood and the roles of vascular endothelial growth factors (VEGFs) in this process have not been fully clarified. We determined the expression profile of VEGFs and relevant receptors during the progression of left ventricular hypertrophy (LVH). C57BL mice were exposed to transversal aortic constriction (TAC) and the outcome was studied at different time points (1 day, 2, 4, and 10 weeks). A clear compe...

  16. The Role of Dyadic Organization in Regulation of Sarcoplasmic Reticulum Ca2+ Handling during Rest in Rabbit Ventricular Myocytes

    OpenAIRE

    Bovo, Elisa; de Tombe, Pieter P.; Zima, Aleksey V.

    2014-01-01

    The dyadic organization of ventricular myocytes ensures synchronized activation of sarcoplasmic reticulum (SR) Ca2+ release during systole. However, it remains obscure how the dyadic organization affects SR Ca2+ handling during diastole. By measuring intraluminal SR Ca2+ ([Ca2+]SR) decline during rest in rabbit ventricular myocytes, we found that ?76% of leaked SR Ca2+ is extruded from the cytosol and only ?24% is pumped back into the SR. Thus, the majority of Ca2+ that leaks from the SR is r...

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

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    Ana Baptista

    2015-01-01

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

  19. The relation between peripheral vascular structure, left ventricular hypertrophy, and ambulatory blood pressure in essential hypertension

    DEFF Research Database (Denmark)

    Sihm, I; Schroeder, A P; Aalkjær, Christian; Holm, M; Mørn, B; Mulvany, M; Thygesen, K; Lederballe, O

    1995-01-01

    The relations between left ventricular mass (LVM), peripheral resistance artery structure, and ambulatory BP were studied in 83 patients with previously untreated or poorly regulated essential hypertension and 20 healthy controls of similar age and sex. LVM was assessed by echocardiography. Signs of left ventricular hypertrophy (LVH) were present in 67 (81%) of the patients and in none of the controls. Peripheral resistance arteries were isolated from surgical gluteal skin biopsies and mounted i...

  20. Organic Nitrates Favor Regression of Left Ventricular Hypertrophy in Hypertensive Patients on Chronic Peritoneal Dialysis

    OpenAIRE

    Han Li; Shixiang Wang

    2013-01-01

    The aim of the study was to evaluate the effect of nitrates on left ventricular hypertrophy (LVH) in hypertensive patients on chronic peritoneal dialysis (PD). Sixty-four PD patients with hypertension were enrolled in this study. All patients accepted antihypertensive drugs at baseline. Thirty-two patients (nitrate group) took isosorbide mononitrate for 24 weeks. The remaining 32 patients (non-nitrate group) took other antihypertensive drugs. Blood pressure (BP), left ventricular mass index (...

  1. Evaluation of cardiac electrophysiological properties in an experimental model of right ventricular hypertrophy and failure

    DEFF Research Database (Denmark)

    Schultz, Jacob G; Andersen, Stine; Andersen, Asger; Erik Nielsen-Kudsk, Jens; Nielsen, Jan M

    2015-01-01

    BACKGROUND: Malignant arrhythmias are a major cause of sudden cardiac death in adults with congenital heart disease. We developed a model to serially investigate electrophysiological properties in an animal model of right ventricular hypertrophy and failure. METHOD: We created models of compensated (cHF; n=11) and decompensated (dHF; n=11) right ventricular failure in Wistar rats by pulmonary trunk banding. Healthy controls underwent sham operation (Control; n=13). Surface electrocardiography wa...

  2. 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

  3. Direct analysis of beta-adrenergic receptor subtypes on intact adult ventricular myocytes of the rat

    International Nuclear Information System (INIS)

    beta 1- and beta 2-Adrenergic receptors co-exist in the adult rat ventricle. Radioligand binding and cell purification techniques have been employed to determine the cellular origin of these receptors. The beta-adrenergic antagonist ligand (+/-)-[125I] iodocyanopindolol binds to 2 X 10(5) receptors per purified adult rat cardiomyocyte, with a dissociation constant of 70 pM. The subtype-selective antagonists betaxolol (beta 1), practolol (beta 1), and zinterol (beta 2) compete for [125I]iodocyanopindolol-binding sites on intact myocytes in monophasic manners with dissociation constants of 46, 845, and 923 nM, respectively. [125I]iodocyanopindolol binding to membranes prepared from nonmyocyte elements of rat ventricle occurs with a dissociation constant of 43 pM and a capacity of 88 fmol/mg membrane protein. Computer analysis of competition of [125I]iodocyanopindolol binding by betaxolol, practolol, and zinterol in nonmyocyte membranes demonstrates biphasic curves that comprise binding to both beta 1- and beta 2-receptors. These data demonstrate that purified adult ventricular myocytes possess only beta 1-receptors, and that the beta 2-receptors found in rat ventricle are located on nonmyocyte cell types

  4. Quantification of t-tubule area and protein distribution in rat cardiac ventricular myocytes.

    Science.gov (United States)

    Pásek, M; Brette, F; Nelson, A; Pearce, C; Qaiser, A; Christe, G; Orchard, C H

    2008-01-01

    The transverse (t-) tubules of cardiac ventricular myocytes are invaginations of the surface membrane that form a complex network within the cell. Many of the key proteins involved in excitation-contraction coupling appear to be located predominantly at the t-tubule membrane. Despite their importance, the fraction of cell membrane within the t-tubules remains unclear: measurement of cell capacitance following detubulation suggests approximately 32%, whereas optical measurements suggest up to approximately 65%. We have, therefore, investigated the factors that may account for this discrepancy. Calculation of the combinations of t-tubule radius, length and density that produce t-tubular membrane fractions of 32% or 56% suggest that the true fraction is at the upper end of this range. Assessment of detubulation using confocal and electron microscopy suggests that incomplete detubulation can account for some, but not all of the difference. High cholesterol, and a consequent decrease in specific capacitance, in the t-tubule membrane, may also cause the t-tubule fraction calculated from the loss of capacitance following detubulation to be underestimated. Correcting for both of these factors results in an estimate that is still lower than that obtained from optical measurements suggesting either that optical methods overestimate the fraction of membrane in the t-tubules, or that other, unknown, factors, reduce the apparent fraction obtained by detubulation. A biophysically realistic computer model of a rat ventricular myocyte, incorporating a t-tubule network, is used to assess the effect of the altered estimates of t-tubular membrane fraction on the calculated distribution of ion flux pathways. PMID:17881039

  5. The evaluation of left ventricular hypertrophy in hypertensive patients with subclinical hyperthyroidism.

    Science.gov (United States)

    Tamer, Ismet; Sargin, Mehmet; Sargin, Haluk; Seker, Mesut; Babalik, Erhan; Tekce, Mustafa; Yayla, Ali

    2005-08-01

    The aim of this prospective cross-sectional study was to investigate the hypertrophic effects of endogenous subclinical hyperthyroidism on myocardium and early development of left ventricular hypertrophy (LVH) in essential hypertensive patients accompanied by endogenous subclinical hyperthyroidism. A total of 31 consecutive patients with stage I hypertension were included in the study. Sixteen of them also had endogenous subclinical hyperthyroidism that they were unaware before. The patients and the controls formed out of ten healthy subjects all underwent an investigation of thyroid functions and cardiologic evaluation. The mean wall thickness of the left ventricle in the stage I hypertensive group with endogenous subclinical hyperthyroidism (group I) was significantly increased as compared with both hypertensive patients without thyroid disease (group II) and the control subjects. The mean left ventricle mass was also significantly higher in group I than group II. Both of the patients' groups had an increased prevalence of LVH as compared with the controls. In this study, hypertensive patients with subclinical hyperthyroidism presented more increase in left ventricular mass, suggesting that subclinical hyperthyroidism may contribute to left ventricular hypertrophy forming a natural progression to hypertension. The hypertensive population should always be screened for endogenous subclinical hyperthyroidism, and should be examined for the criteria of left ventricular hypertrophy by echocardiography in early stages. PMID:16127209

  6. Temporal Evaluation of Cardiac Myocyte Hypertrophy and Hyperplasia in Male Rats Secondary to Chronic Volume Overload

    OpenAIRE

    DU, YAN; Plante, Eric; Janicki, Joseph S; Brower, Gregory L

    2010-01-01

    The temporal myocardial remodeling induced by chronic ventricular volume overload in male rats was examined. Specifically, left ventricular (LV) cardiomyocyte length and width, sarcomere length, and number of nuclei were measured in male rats (n = 8 to 17) at 1, 3, 5, 7, 21, 35, and 56 days after creation of an infrarenal aortocaval fistula. In contrast to previously published reports of progressive increases in cardiomyocyte length and cross-sectional area at 5 days post-fistula and beyond i...

  7. Rapid Estrogen Receptor-Mediated Mechanisms Determine the Sexually Dimorphic Sensitivity of Ventricular Myocytes to 17?-Estradiol and the Environmental Endocrine Disruptor Bisphenol A

    OpenAIRE

    Belcher, Scott M.; Chen, Yamei; YAN, SUJUAN; Wang, Hong-Sheng

    2011-01-01

    Previously we showed that 17?-estradiol (E2) and/or the xenoestrogen bisphenol A (BPA) alter ventricular myocyte Ca2+ handing, resulting in increased cardiac arrhythmias in a female-specific manner. In the present study, the roles of estrogen receptors (ER) in mediating the rapid contractile and arrhythmogenic effects of estrogens were examined. Contractility was used as an index to assess the impact of E2 or BPA on Ca2+ handling in rodent ventricular myocytes. The concentration-response curv...

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

    International Nuclear Information System (INIS)

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

  9. 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

  10. Prevalence and Determinants of Left Ventricular Hypertrophy in Hypertensive Patients at a Primary Care Clinic

    OpenAIRE

    Ching SM; Chia YC; Wan Azman WA

    2012-01-01

    Left ventricular hypertrophy (LVH) has prognostic significance on cardiovascular mortality and morbidity. However, echocardiography screening for LVH is not routinely done for hypertensive patients in a primary care setting. thus, this quantitative study aims to determine the prevalence and factors associated with LVH in hypertensive patients at a primary care setting. this was a cross-sectional study of 359 consecutive patients with uncomplicated essential hypertension attending a hospital-b...

  11. Fibroblast Growth Factor 23 and Left Ventricular Hypertrophy in Hemodialysis Patients

    OpenAIRE

    Ayaka Saito; Takako Onuki; Yoshihisa Echida; Shigeru Otsubo; Kosaku Nitta

    2014-01-01

    Background: Left ventricular hypertrophy (LVH) is a common cardiovascular complication and an independent risk factor for cardiovascular death in hemodialysis (HD) patients. Previous studies have shown that fibroblast growth factor 23 (FGF23), which has an important role in phosphate metabolism, is elevated in HD patients. Objectives: The aim of this study was to determine the association of FGF23 and LVH and the prognostic value of serum FGF23 level in HD patients. One hundred seven HD patie...

  12. Frequency of Left Ventricular Hypertrophy in Non-Valvular Atrial Fibrillation

    DEFF Research Database (Denmark)

    Proietti, Marco; Marra, Alberto Maria; Tassone, Eliezer Joseph; De Vuono, Stefano; Corrao, Salvatore; Gobbi, Paolo; Perticone, Francesco; Corazza, Gino Roberto; Basili, Stefania; Lip, Gregory Y H; Violi, Francesco; Raparelli, Valeria

    2015-01-01

    Left ventricular hypertrophy (LVH) is significantly related to adverse clinical outcomes in patients at high risk of cardiovascular events. In patients with atrial fibrillation (AF), data on LVH, that is, prevalence and determinants, are inconsistent mainly because of different definitions and heterogeneity of study populations. We determined echocardiographic-based LVH prevalence and clinical factors independently associated with its development in a prospective cohort of patients with non-valv...

  13. Elevated oxidative stress and endothelial dysfunction in right coronary artery of right ventricular hypertrophy

    OpenAIRE

    Lu, Xiao; Dang, Charles Q.; Guo, Xiaomei; Molloi, Sabee; Wassall, Cynthia D.; Kemple, Marvin D.; Kassab, Ghassan S.

    2011-01-01

    Remodeling of right coronary artery (RCA) occurs during right ventricular hypertrophy (RVH) induced by banding of the pulmonary artery (PA). The effect of RVH on RCA endothelial function and reactive oxygen species (ROS) in vessel wall remains unclear. A swine RVH model (n = 12 pigs) induced by PA banding was used to study RCA endothelial function and ROS level. To obtain longitudinal coronary hemodynamic and geometric data, digital subtraction angiography was used during the progression of R...

  14. Tetrodotoxin attenuates isoproterenol-induced hypertrophy in H9c2 rat cardiac myocytes.

    Science.gov (United States)

    Chen, Ming-Zi; Bu, Qing-Ting; Pang, Shu-Chao; Li, Feng-Lan; Sun, Mei-Na; Chu, Er-Fu; Li, Hui

    2012-12-01

    Cardiac hypertrophy is often associated with an increased sympathetic drive, and both in vitro and in vivo studies have demonstrated the development of cardiomyocyte hypertrophy in response to either ?- or ?- adrenergic stimulation. The present study was carried out to determine whether the reversible sodium channel blocker tetrodotoxin (TTX) exerts a direct anti-hypertrophic effect on isoproterenol (ISO)-induced cell hypertrophy and find the underlying mechanism that regulate [Na(+)]( i ). The experiments were performed on cultured H9c2 cells exposed to ISO (10 ?M) alone or combined with TTX (1 ?M) for 48 h. Our results showed that ISO significantly increased cell surface area by 30 % and atrial natriuretic peptide gene expression by nearly twofold (p < 0.05 for both). These effects were associated with a significant reduction in the gene expression of Na(+)/K(+)-ATPase isoforms ?2 and ?3, whereas the ?1 isoform was unaffected. Conversely, ISO increased Na(+)-H(+) exchanger 1 (NHE-1) gene expression by approximately 40 % and significantly increased [Na(+)]( i ) level by 50 % (p < 0.05 for both). ISO was also found to significantly increase aquaporin 4 gene expression by nearly ninefold (p < 0.05). All these effects were prevented when identical experiments were carried out in the presence of TTX, but the expression of NHE-1. The expression of sodium channel protein type 5 subunit alpha was unaffected by either ISO or TTX. When taken together, these studies show that TTX attenuates the hypertrophic effect of ISO and suggest a possible approach to limiting ISO-induced hypertrophy in clinical treatment. PMID:22941212

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

    Science.gov (United States)

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

    2015-04-01

    Valvular aortic stenosis is the second most prevalent adult valve disease in the United States and causes progressive pressure overload, invariably leading to life-threatening complications. Surgical aortic valve replacement and, more recently, transcatheter aortic valve replacement effectively relieve the hemodynamic burden and improve the symptoms and survival of affected individuals. However, according to current American College of Cardiology/American Heart Association guidelines on the management of valvular heart disease, the indications for aortic valve replacement, including transcatheter aortic valve replacement, are based primarily on the development of clinical symptoms, because their presence indicates a dismal prognosis. Left ventricular hypertrophy develops in a sizeable proportion of patients before the onset of symptoms, and a growing body of literature demonstrates that regression of left ventricular hypertrophy resulting from aortic stenosis is incomplete after aortic valve replacement and associated with adverse early postoperative outcomes and worse long-term outcomes. Thus, reliance on the development of symptoms alone without consideration of structural abnormalities of the myocardium for optimal timing of aortic valve replacement potentially constitutes a missed opportunity to prevent postoperative morbidity and mortality from severe aortic stenosis, especially in the face of the quickly expanding indications of lower-risk transcatheter aortic valve replacement. The purpose of this review is to discuss the mechanisms and clinical implications of left ventricular hypertrophy in severe valvular aortic stenosis, which may eventually move to center stage as an indication for aortic valve replacement in the asymptomatic patient. PMID:25460869

  16. Evaluation of cardiac electrophysiological properties in an experimental model of right ventricular hypertrophy and failure

    DEFF Research Database (Denmark)

    Schultz, Jacob G; Andersen, Stine

    2015-01-01

    BACKGROUND: Malignant arrhythmias are a major cause of sudden cardiac death in adults with congenital heart disease. We developed a model to serially investigate electrophysiological properties in an animal model of right ventricular hypertrophy and failure. METHOD: We created models of compensated (cHF; n=11) and decompensated (dHF; n=11) right ventricular failure in Wistar rats by pulmonary trunk banding. Healthy controls underwent sham operation (Control; n=13). Surface electrocardiography was recorded from extremities, and inducibility of ventricular tachycardia was evaluated in vivo by programmed stimulation. Isolated right ventricular myocardium was analysed for mRNA expression of selected genes. RESULTS: Banding caused an increased mRNA expression of both connexin 43 and the voltage-gated sodium channel 1.5, as well as a prolongation of PQ, QRS and QTc intervals. Ventricular tachycardia was induced in the majority of banded animals compared with none in the healthy control group. No differences were found between the two degrees of failure in neither the electrophysiological parameters nor inducibility. CONCLUSIONS: The electrophysiological properties of rat hearts subjected to pulmonary trunk banding were significantly changed with increased susceptibility to ventricular tachycardia, but no differences were found between compensated and decompensated right ventricular failure. Furthermore, we demonstrate that in vivo electrophysiological evaluation is a sensitive method to characterise the cardiac electric phenotype in an experimental rat model.

  17. Effect of antipsychotic drug perphenazine on fast sodium current and transient outward potassium current in rat ventricular myocytes.

    Czech Academy of Sciences Publication Activity Database

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

    2009-01-01

    Ro?. 380, ?. 2 (2009), s. 125-133. ISSN 0028-1298 Institutional research plan: CEZ:AV0Z20760514 Keywords : perphenazine * antipsychotic drug * sodium current * transient outward current * rat ventricular myocytes Subject RIV: ED - Physiology Impact factor: 2.631, year: 2009 http://apps.isiknowledge.com/full_record.do?product=UA&search_mode=GeneralSearch&qid=1&SID=T1JpdjJ8PNNeAL7D3il&page=1&doc=3&colname=WOS

  18. Age and Ovariectomy Abolish Beneficial Effects of Female Sex on Rat Ventricular Myocytes Exposed to Simulated Ischemia and Reperfusion

    OpenAIRE

    Ross, Jenna L.; Howlett, Susan E.

    2012-01-01

    Sex differences in responses to myocardial ischemia have been described, but whether cardiomyocyte function is influenced by sex in the setting of ischemia and reperfusion has not been elucidated. This study compared contractions and intracellular Ca2+ in isolated ventricular myocytes exposed to ischemia and reperfusion. Cells were isolated from anesthetized 3-month-old male and female Fischer 344 rats, paced at 4 Hz (37°C), exposed to simulated ischemia (20 mins) and reperfused. Cell shorten...

  19. 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.

  20. 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.

  1. 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 three types of cardiac hypertrophy. (author)

  2. Apoptosis in severe, compensated pressure overload predominates in nonmyocytes and is related to the hypertrophy but not function

    OpenAIRE

    RICARDO J. GELPI; Park, Misun; Gao, Shumin; Dhar, Sunil; Vatner, Dorothy E.; Vatner, Stephen F.

    2010-01-01

    It is widely held that myocyte apoptosis in left ventricular hypertrophy (LVH) contributes to left ventricle (LV) dysfunction and heart failure. The main goal of this investigation was to determine if there is a statistical relationship among LV hypertrophy, apoptosis and LV function, and importantly whether the apoptosis occurs in myocytes or nonmyocytes in the heart. We used both rat and canine models of severe LVH induced by chronic thoracic aortic banding with resultant LV-aortic pressure...

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

    International Nuclear Information System (INIS)

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

  4. 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

  5. Dominant negative Ras attenuates pathological ventricular remodeling in pressure overload cardiac hypertrophy.

    Science.gov (United States)

    Ramos-Kuri, Manuel; Rapti, Kleopatra; Mehel, Hind; Zhang, Shihong; Dhandapany, Perundurai S; Liang, Lifan; García-Carrancá, Alejandro; Bobe, Regis; Fischmeister, Rodolphe; Adnot, Serge; Lebeche, Djamel; Hajjar, Roger J; Lipskaia, Larissa; Chemaly, Elie R

    2015-11-01

    The importance of the oncogene Ras in cardiac hypertrophy is well appreciated. The hypertrophic effects of the constitutively active mutant Ras-Val12 are revealed by clinical syndromes due to the Ras mutations and experimental studies. We examined the possible anti-hypertrophic effect of Ras inhibition in vitro using rat neonatal cardiomyocytes (NRCM) and in vivo in the setting of pressure-overload left ventricular (LV) hypertrophy (POH) in rats. Ras functions were modulated via adenovirus directed gene transfer of active mutant Ras-Val12 or dominant negative mutant N17-DN-Ras (DN-Ras). Ras-Val12 expression in vitro activates NFAT resulting in pro-hypertrophic and cardio-toxic effects on NRCM beating and Z-line organization. In contrast, the DN-Ras was antihypertrophic on NRCM, inhibited NFAT and exerted cardio-protective effects attested by preserved NRCM beating and Z line structure. Additional experiments with silencing H-Ras gene strategy corroborated the antihypertrophic effects of siRNA-H-Ras on NRCM. In vivo, with the POH model, both Ras mutants were associated with similar hypertrophy two weeks after simultaneous induction of POH and Ras-mutant gene transfer. However, LV diameters were higher and LV fractional shortening lower in the Ras-Val12 group compared to control and DN-Ras. Moreover, DN-Ras reduced the cross-sectional area of cardiomyocytes in vivo, and decreased the expression of markers of pathologic cardiac hypertrophy. In isolated adult cardiomyocytes after 2weeks of POH and Ras-mutant gene transfer, DN-Ras improved sarcomere shortening and calcium transients compared to Ras-Val12. Overall, DN-Ras promotes a more physiological form of hypertrophy, suggesting an interesting therapeutic target for pathological cardiac hypertrophy. PMID:26260012

  6. 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)

  7. 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)

  8. 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)

  9. Hemodynamics, function and perfusion of the myocardium in arterial hypertensive with varying left ventricular hypertrophy

    International Nuclear Information System (INIS)

    Seventy eight patients with arterial hypertension were examined by echo-, radiocardiography and scintigraphy of the myocardium, using 99mTc pyrophosphate and 201Tl. A relationship was found between the development of hypertrophy of the left ventricle and the impairment of it perfusion and function. At the same time there was a correlation benween the decrease in cardiac output and the deterioration of myocardial blood supply. It was demonstrated that 99mTc pyrophosphate or 201Tl myocardial scintigraphy yielded the coincident results when relative heart failure was evaluated in patients with arterial hypertension and left ventricular hypertropy

  10. Hipertrofia ventricular izquierda y factores de riesgo cardiovascular en niños y adolescentes hipertensos / Left ventricular hypertrophy and cardiovascular risk factors present in hypertensive children and adolescents

    Scientific Electronic Library Online (English)

    Juan René, Llapur Milián; Raquel, González Sánchez; Acelia, Betancourt Pérez; Doris Yisell, Rubio Olivares.

    2009-06-01

    Full Text Available INTRODUCCIÓN. La hipertrofia ventricular izquierda es la más prominente evidencia de afectación de los órganos diana, causada por la hipertensión en los niños y adolescentes. El ecocardiograma es la herramienta fundamental para su diagnóstico. El principal objetivo de esta investigación fue determin [...] ar la presencia de hipertrofia ventricular izquierda mediante ecocardiograma, en niños y adolescentes con hipertensión arterial esencial y relacionarla con algunos factores de riesgo. MÉTODOS. Se estudiaron 140 niños y adolescentes con hipertensión arterial esencial. Se evaluaron variables demográficas, antropométricas, antecedentes personales y familiares de factores de riesgo cardiovascular y la presencia o no de hipertrofia ventricular izquierda. RESULTADOS. Más de la cuarta parte del total presentó hipertrofia ventricular izquierda. De ellos, la mayor frecuencia correspondió al sexo masculino y al grupo etario de 10 a 14 años, en ambos sexos. Hubo un mayor porcentaje en los menores de 5 años y se estableció una relación estadística significativa con el antecedente personal de bajo peso y alto peso al nacer, y con el antecedente familiar de cardiopatía isquémica. CONCLUSIONES. La hipertrofia ventricular izquierda no es una complicación infrecuente de la hipertensión arterial en la infancia. Abstract in english INTRODUCTION: Left ventricular hypertrophy is the more significant evidence of target organs provoked by hypertension in children and adolescents. Echocardiogram is the main tool for its diagnosis. The main objective of present research was to determine presence of left ventricular hypertrophy be ec [...] hocardiogram in children and adolescents presenting with essential high blood pressure and to relate it with risk factors. METHODS: More of the quarter of total had left ventricular hypertrophy. From them, the great frequency was for male sex and for the age-group from 10 to 14 years in both sexes. There was a greater percentage in those under 5 years and we established a significant statistic relation with the personal low and high birth weight and with the family background of ischemic heart disease. CONCLUSIONS: Left ventricular hypertrophy is a frequent complication of hypertension in childhood.

  11. Hipertrofia ventricular izquierda y factores de riesgo cardiovascular en niños y adolescentes hipertensos Left ventricular hypertrophy and cardiovascular risk factors present in hypertensive children and adolescents

    Directory of Open Access Journals (Sweden)

    Juan René Llapur Milián

    2009-06-01

    Full Text Available INTRODUCCIÓN. La hipertrofia ventricular izquierda es la más prominente evidencia de afectación de los órganos diana, causada por la hipertensión en los niños y adolescentes. El ecocardiograma es la herramienta fundamental para su diagnóstico. El principal objetivo de esta investigación fue determinar la presencia de hipertrofia ventricular izquierda mediante ecocardiograma, en niños y adolescentes con hipertensión arterial esencial y relacionarla con algunos factores de riesgo. MÉTODOS. Se estudiaron 140 niños y adolescentes con hipertensión arterial esencial. Se evaluaron variables demográficas, antropométricas, antecedentes personales y familiares de factores de riesgo cardiovascular y la presencia o no de hipertrofia ventricular izquierda. RESULTADOS. Más de la cuarta parte del total presentó hipertrofia ventricular izquierda. De ellos, la mayor frecuencia correspondió al sexo masculino y al grupo etario de 10 a 14 años, en ambos sexos. Hubo un mayor porcentaje en los menores de 5 años y se estableció una relación estadística significativa con el antecedente personal de bajo peso y alto peso al nacer, y con el antecedente familiar de cardiopatía isquémica. CONCLUSIONES. La hipertrofia ventricular izquierda no es una complicación infrecuente de la hipertensión arterial en la infancia.INTRODUCTION: Left ventricular hypertrophy is the more significant evidence of target organs provoked by hypertension in children and adolescents. Echocardiogram is the main tool for its diagnosis. The main objective of present research was to determine presence of left ventricular hypertrophy be echocardiogram in children and adolescents presenting with essential high blood pressure and to relate it with risk factors. METHODS: More of the quarter of total had left ventricular hypertrophy. From them, the great frequency was for male sex and for the age-group from 10 to 14 years in both sexes. There was a greater percentage in those under 5 years and we established a significant statistic relation with the personal low and high birth weight and with the family background of ischemic heart disease. CONCLUSIONS: Left ventricular hypertrophy is a frequent complication of hypertension in childhood.

  12. Multiphysics model of a rat ventricular myocyte: A voltage-clamp study

    Directory of Open Access Journals (Sweden)

    Krishna Abhilash

    2012-11-01

    Full Text Available Abstract Background The objective of this study is to develop a comprehensive model of the electromechanical behavior of the rat ventricular myocyte to investigate the various factors influencing its contractile response. Methods Here, we couple a model of Ca2 + dynamics described in our previous work, with a well-known model of contractile mechanics developed by Rice, Wang, Bers and de Tombe to develop a composite multiphysics model of excitation-contraction coupling. This comprehensive cell model is studied under voltage clamp (VC conditions, since it allows to focus our study on the elaborate Ca2 + signaling system that controls the contractile mechanism. Results We examine the role of various factors influencing cellular contractile response. In particular, direct factors such as the amount of activator Ca2 + available to trigger contraction and the type of mechanical load applied (resulting in isosarcometric, isometric or unloaded contraction are investigated. We also study the impact of temperature (22 to 38°C on myofilament contractile response. The critical role of myofilament Ca2 + sensitivity in modulating developed force is likewise studied, as is the indirect coupling of intracellular contractile mechanism with the plasma membrane via the Na + /Ca2 + exchanger (NCX. Finally, we demonstrate a key linear relationship between the rate of contraction and relaxation, which is shown here to be intrinsically coupled over the full range of physiological perturbations. Conclusions Extensive testing of the composite model elucidates the importance of various direct and indirect modulatory influences on cellular twitch response with wide agreement with measured data on all accounts. Thus, the model provides mechanistic insights into whole-cell responses to a wide variety of testing approaches used in studies of cardiac myofilament contractility that have appeared in the literature over the past several decades.

  13. Improvement of diastolic function after regression of left ventricular hypertrophy / Mejora de la función diastólica tras regresión de la hipertrofia ventricular izquierda

    Scientific Electronic Library Online (English)

    Raúl, Teniente-Valente; Sergio, Solorio; Enrique, Vargas-Salado; Carlos, Aguirre-Vázquez; Martha A, Hernández-González; José Antonio, Olvera-Lopez; Leticia, Rodríguez-Mariscal; Miguel Angel, Luna-Ruiz; José Manuel, Guillén Contreras; Blanca Olivia, Murillo Ortiz.

    2008-12-01

    Full Text Available Objetivo: Evaluar la función diastólica después de revertir la hipertrofia ventricular izquierda, en hipertensión leve a moderada tratada con inhibidores de la enzima convertidora angiotensina (ECA) y, si era necesario, con un diurético. Métodos: Noventa y ocho pacientes hipertensos con hipertrofia [...] ventricular izquierda e índices de función diastólica anormal del ventrículo izquierdo recibieron captopril 50 a 200 mg/día (Capotena®) más clortalidona durante 12 meses para lograr el control de la presión arterial, definido como presión diastólica Abstract in english Objective: To evaluate the diastolic function after regression of left ventricular hypertrophy, in mild to moderate hypertension treated with angiotensin converting enzyme(ACE) inhibitor and, if necessary, with a diuretic. Methods: Ninety-eight hypertensive patients with left ventricular hypertrophy [...] (LVH) and abnormal left ventricle diastolic function indexes received captopril (Capotena® ) 50 to 200 mg/day plus chlortalidone during 12 months to reach blood pressure control, defined as a diastolic blood pressure

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

    Science.gov (United States)

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

    1998-01-01

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

  15. 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)

  16. Use-dependent block of Na+ currents by mexiletine at the single channel level in guinea-pig ventricular myocytes.

    OpenAIRE

    Sunami, A.; Fan, Z; Sawanobori, T; Hiraoka, M

    1993-01-01

    1. The mechanism of use-dependent block of Na+ current by mexiletine was studied at the single channel level in guinea-pig ventricular myocytes by the patch-clamp techniques. All experiments were performed using stimulation protocols to enable us to analyze the strict dependence of changes in channel properties on channel use. 2. In cell-attached patches, bath or pipette application of mexiletine (40 microM) produced a use-dependent reduction of the peak average current without changes in sin...

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

    OpenAIRE

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

    2010-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Yoga Yuniadi

    2006-09-01

    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

  19. 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.

  20. Sepiapterin prevents left ventricular hypertrophy and dilatory remodeling induced by pressure overload in rats.

    Science.gov (United States)

    Yoshioka, Kei; Otani, Hajime; Shimazu, Takayuki; Fujita, Masanori; Iwasaka, Toshiji; Shiojima, Ichiro

    2015-11-15

    Uncoupling of nitric oxide (NO) synthase (NOS) has been implicated in left ventricular (LV) hypertrophy (LVH) and dilatory remodeling induced by pressure overload. We investigated whether administration of sepiapterin, a substrate of the salvage pathway of tetrahydrobiopterin synthesis, prevents LVH and dilatory LV remodeling by inhibiting NOS uncoupling and increasing bioavailable NO. Pressure overload was induced in rats by transverse aortic constriction (TAC). Concentric LVH developed during 8 wk after TAC, and dilatory LV remodeling and dysfunction developed between 8 and 16 wk after TAC associated with a decrease in capillary density. Oral administration of sepiapterin or the superoxide/peroxynitrite scavenger N-(2-mercaptopropionyl)-glycine for 8 wk after TAC inhibited oxidative stress, but only sepiapterin increased bioavailable NO and inhibited cardiomyocyte hypertrophy associated with a further increase in capillary density. When sepiapterin was administered between 8 and 16 wk after TAC, cardiomyocyte hypertrophy was regressed and capillary density was restored. This was associated with the inhibition of interstitial fibrosis and dilatory LV remodeling. N-nitro-l-arginine methyl ester abrogated all the beneficial effects of sepiapterin in rats with TAC. These results suggest that sepiapterin prevents concentric LVH and dilatory remodeling after TAC primarily by increasing the bioavailability of NO. PMID:26408540

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

    OpenAIRE

    Pinya Li; Qiongtao Song; Tao Liu(Institut für Theoretische Teilchenphysik, Karlsruhe Institute of Technology (KIT), D-76128 Karlsruhe, Germany); Zhonglin Wu; Xi Chu; Xuan Zhang; Ying Zhang; Yonggang Gao; Jianping Zhang; Li Chu

    2014-01-01

    Cinobufagin (CBG), a major bioactive ingredient of the bufanolide steroid compounds of Chan Su, has been widely used to treat coronary heart disease. At present, the effect of CBG on the L-type Ca2+ current (ICa-L) of ventricular myocytes remains undefined. The aim of the present study was to characterize the effect of CBG on intracellular Ca2+ ([Ca2+]i) handling and cell contractility in rat ventricular myocytes. CBG was investigated by determining its influence on ICa-L, Ca2+ transient, and...

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

    DEFF Research Database (Denmark)

    Kjaer, Andreas; Meyer, Christian; Wachtell, Kristian; Olsen, Michael Hecht; Ibsen, Hans; Opie, Lionel; Holm, Søren; Hesse, Birger

    2005-01-01

    Myocardial perfusion (MP) may differ in physiologic and pathologic left ventricular hypertrophy (LVH). We compared MP in LVH in elite athletes and patients with hypertension with healthy, age-matched subjects. We included 12 rowers with LVH, 19 patients with hypertension with LVH, and 2 age-matched groups of healthy subjects (n = 11 and n = 12). The left ventricular mass index was determined echocardiographically. MP was measured by N-13 ammonia positron emission tomography. The maximal perfusio...

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

    OpenAIRE

    Eduardo Cantoni Rosa; Valdir Ambrósio Moysés; Ricardo Cintra Sesso; Frida Liane Plavnik; Fernando Flexa Ribeiro; Nárcia E. B. Kohlmann; Artur Beltrame Ribeiro; Maria Tereza Zanella; Osvaldo Kohlmann Jr

    2002-01-01

    PURPOSE: To evaluate left ventricular mass (LVM) index in hypertensive and normotensive obese individuals. METHODS: Using M mode echocardiography, 544 essential hypertensive and 106 normotensive patients were evaluated, and LVM was indexed for body surface area (LVM/BSA) and for height² (LVM/h²). The 2 indexes were then compared in both populations, in subgroups stratified according to body mass index (BMI): or = 30kg/m². RESULTS: The BSA index does not allow identification of significant d...

  4. 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.

  5. 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.

  6. Does reduced myocardial efficiency in systemic hypertensive-hypertrophy correlate with increased left-ventricular wall thickness?

    Science.gov (United States)

    Han, June-Chiew; Barrett, Carolyn J; Taberner, Andrew J; Loiselle, Denis S

    2015-08-01

    Elevated systemic blood pressure, and the attendant development of pathologic left ventricular (LV) hypertrophy, ultimately culminates in heart failure and death. In clinical studies, a reduction of myocardial efficiency has been implicated in systemic hypertensive-hypertrophy. However, it is uncertain whether reduced efficiency correlates with LV wall thickness. Hence, we performed experiments on isolated working hearts of spontaneously hypertensive rats (SHRs)-a widely-used experimental model of human hypertensive-hypertrophy. We contrasted their mechanoenergetic performance with that of Wistar controls at two ages: Adult (9 months) and Aged (post-18 months). The use of animal hearts allowed us to perform experiments over a wide range of afterloads. We found that mechanoenergetic performance (coronary and aortic flows, work output and oxygen consumption) declined with age. The peak efficiency of the Adult SHR was essentially similar to that of Control, but that for the Aged SHR was lower, compared with that of age-matched Wistar rats. All variables, including peak efficiency, obtained from the failing Aged SHR hearts (which also developed right ventricular hypertrophy), were greatly reduced. Our data reveal that peak efficiency of the Aged SHR, upon transitioning from compensated hypertrophy to failure, diminishes sharply, arising from compromised flows-both aortic and coronary. We further show that the reduction of myocardial efficiency in hypertensive-hypertrophy does not correlate with LV wall thickness, but instead is inversely correlated with whole-heart mass. The latter relation may serve as a prognostic and diagnostic tool in the clinical setting. PMID:25787044

  7. Reduction in left ventricular hypertrophy in hypertensive patients treated with enalapril, losartan or the combination of enalapril and losartan

    Scientific Electronic Library Online (English)

    Antônio Carlos, Avanza Jr; Lilian Mameri, El Aouar; José Geraldo, Mill.

    2000-02-01

    Full Text Available OBJECTIVE: To compare the regression of left ventricular hypertrophy in patients with moderate hypertension treated with enalapril, losartan or a combination of the two drugs at lower doses. METHODS: Patients of both sexes with moderate hypertension confirmed by ambulatory monitoring of arte-rial bl [...] ood pressure and with left ventricular hypertrophy on echocardiogram were assigned to three groups: enalapril (35 mg/day, n=15), losartan (175 mg/day, n=15) and enalapril+losartan (15 mg+100 mg/day, n=16). The patients received the drugs for 10 months. RESULTS: The three therapeutic regimens were equally effective in reducing blood pressure and left ventricular mass index (LVMI, g/m²): 141±3.9 to 123±3.6 in the enalapril group (p

  8. Rapid Estrogen Receptor-Mediated Mechanisms Determine the Sexually Dimorphic Sensitivity of Ventricular Myocytes to 17?-Estradiol and the Environmental Endocrine Disruptor Bisphenol A

    Science.gov (United States)

    Belcher, Scott M.; Chen, Yamei; Yan, Sujuan

    2012-01-01

    Previously we showed that 17?-estradiol (E2) and/or the xenoestrogen bisphenol A (BPA) alter ventricular myocyte Ca2+ handing, resulting in increased cardiac arrhythmias in a female-specific manner. In the present study, the roles of estrogen receptors (ER) in mediating the rapid contractile and arrhythmogenic effects of estrogens were examined. Contractility was used as an index to assess the impact of E2 or BPA on Ca2+ handling in rodent ventricular myocytes. The concentration-response curve for the stimulatory effects of BPA and E2 on female myocyte was inverted-U shaped. Detectable effects for each compound were observed at 10?12 m, and the most efficacious concentrations for each were at 10?9 m. Sensitivity to E2 and BPA was not observed in male myocytes and was abolished in myocytes from ovariectomized females. Analysis using protein-conjugated E2 suggests that these rapid actions are induced by membrane-associated receptors. Analysis using selective ER agonists and antagonists and a genetic ER? knockout mouse model showed that ER? and ER? have opposing actions in myocytes and that the balance between ER? and ER? signaling is the prime regulator of the sex-specific sensitivity toward estrogens. The response of female myocytes to E2 and BPA is dominated by the stimulatory ER?-mediated signaling, and the absence of BPA and E2 responsiveness in males is due to a counterbalancing-suppressive action of ER?. We conclude that the sex-specific sensitivity of myocytes to estrogens and the rapid arrhythmogenic effects of BPA and estradiol in the female heart are regulated by the balance between ER? and ER? signaling. PMID:22166976

  9. 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.

  10. 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)

  11. 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.

  12. Abrogated leptin-induced cardiac contractile response in ventricular myocytes under spontaneous hypertension: role of Jak/STAT pathway.

    Science.gov (United States)

    Wold, Loren E; Relling, David P; Duan, Jinhong; Norby, Faye L; Ren, Jun

    2002-01-01

    Leptin regulates cardiovascular function. Leptin levels are elevated in obesity and hypertension and may play a role in cardiovascular dysfunctions in these comorbidities. This study was designed to determine the influence of hypertension on the cardiac contractile response of leptin. Mechanical and intracellular Ca(2+) properties were evaluated using an IonOptix system in ventricular myocytes from spontaneously hypertensive (SHR) and age-matched Wistar Kyoto (WKY) rats. The contractile properties included peak shortening (PS), duration and maximal velocity of shortening/relengthening (TPS/TR(90), +/-dL/dt), and fura-fluorescence intensity change (DeltaFFI). NO and nitric oxide synthase (NOS) activity were assessed by the Griess and the (3)H-arginine/citrulline conversion assays, respectively. The leptin receptor (Ob-R) and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway were evaluated by Western blot analysis. SHR animals displayed significantly elevated blood pressure and plasma leptin levels. Leptin elicited a concentration-dependent inhibition of PS and DeltaFFI in WKY, but not in SHR myocytes. Leptin did not affect TPS, TR(90), or +/- dL/dt. The difference in leptin-induced contractile response between the WKY and the SHR groups was abolished by the NOS inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME), but not by elevated extracellular Ca(2+). Either the JAK2 inhibitor AG-490 or the mitogen-activated protein (MAP) kinase inhibitor SB203580 abrogated the leptin-induced response in the WKY myocytes, whereas AG-490 unmasked a negative response in PS in the SHR myocytes. SHR myocytes displayed similar Ob-R protein abundance and basal NO levels, a blunted leptin-induced increase in NOS activity as well as enhanced basal STAT3 levels compared with the WKY group. These data indicate that the leptin-induced cardiac contractile response is abolished by spontaneous hypertension, possibly because of mechanisms involving altered JAK/STAT, MAP kinase signaling, and NO response. PMID:11799081

  13. Reduction of left ventricular ejection fraction on isometric hand grip and cold pressor in hypertensive patients with left ventricular hypertrophy

    International Nuclear Information System (INIS)

    Sustained isometric handgrip (SIHG) and cold pressor (CP) tests are used to assess patients suspected of having coronary artery disease (CAD). The normal response to SIHG and CP is that the blood pressure (BP) increases and left ventricular (LV) ejection fraction (EF) either increases or remains unchanged. Both SIHG and CP tests have been shown to reduce LVEF in patients with CAD. We have assessed the effects of SIHG and CP using radionuclide angiography (RA) in hypertensive patients out of which 10 had left ventricular hypertrophy (LVH group) and 8 had no evidence of LVH (non-LVH group). All patients underwent exercice Thallium-201 (201Tl) imaging in order to rule out CAD. In the LVH group, the mean resting systolic BP (SBP) (210.5 +- 4.7 SE) and diastolic BP (DBP) (119.5 +- 2.3) < mean SBP (237 +- 7.3) and DBP (126 +- 3.1) on SIHG (P<0.0001 and <0.001, respectively). The mean resting EF in LVH group (67 +- 4.3) and the non-LVH group (70 +- 4.3) were similar (P=NS). However, on SIHG and CP the mean EF in LVH group decreased (54 +- 4.6) (P<0.0001) and (62 +- 4.3) (P<0.025) respectively. There were no significant changes in EF on SIHG and CP in the non-LVH group. This finding suggests that while screening patients for CAD using RA, reduction of EF on SIHG and CP may also be due to LVH, resulting in false positive tests for CAD, thus reducing specificity for detection of CAD by these tests

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

    Science.gov (United States)

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

    2015-01-01

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

  15. 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)

  16. Blood pressure and myocardial perfusion in hypertensive patients with and without left ventricular hypertrophy.

    Science.gov (United States)

    Boström, P A; Mansour, P; Diemer, H; Mattiasson, I; Nehoum, A; Lilja, B; Berglund, G

    1995-12-01

    To evaluate the effect of acute blood pressure (BP) changes on the myocardial perfusion in hypertensives, 10 patients with and 10 patients without left ventricular hypertrophy (LVH) were examined with 99TCm-Sestamibi scintigraphy at rest and after acute pharmacological BP reduction using nifedipine and captopril. Signs of LV ischaemia was quantified as the size of the hypoperfused area defined as isotope uptake below 70% of maximum LV uptake, and LVH was defined as ventricular mass (LVM) > 125 g/m2 BSA by use of echocardiography. Not significant relations between BP and size of the hypoperfused area was found at rest. During BP reduction patients with LVH had negative correlations (r = -0.58) between the size of the hypoperfused area and the systolic blood pressure (SBP) and the diastolic blood pressure (DBP) (r = -0.49) while patients without LVH showed positive correlations (SBP r = 0.60, DBP r = 0.48). The differences in correlation coefficients were significant (P < 0.01) for both. Thus, in hypertensives with LVH, ischaemia may develop at low BP providing a possible mechanism for the observed increased risk of cardiovascular events in some hypertensive patients with low achieved BP during follow-up. Until treatment goals are defined on scientific grounds, BP should not be decreased below 90 mm Hg in subjects with LVH. PMID:8746641

  17. Organic Nitrates Favor Regression of Left Ventricular Hypertrophy in Hypertensive Patients on Chronic Peritoneal Dialysis

    Directory of Open Access Journals (Sweden)

    Han Li

    2013-01-01

    Full Text Available The aim of the study was to evaluate the effect of nitrates on left ventricular hypertrophy (LVH in hypertensive patients on chronic peritoneal dialysis (PD. Sixty-four PD patients with hypertension were enrolled in this study. All patients accepted antihypertensive drugs at baseline. Thirty-two patients (nitrate group took isosorbide mononitrate for 24 weeks. The remaining 32 patients (non-nitrate group took other antihypertensive drugs. Blood pressure (BP, left ventricular mass index (LVMI and plasma asymmetric dimethylarginine (ADMA were monitored. Subjects with normal renal function were included as the control group (n = 30. At baseline, plasma ADMA levels in PD patients were significantly higher than the control group, but there was no significant difference in plasma ADMA levels between the two groups. At the end of the 24-week period, BP, LVMI, LVH prevalence and plasma ADMA levels in the nitrate group were significantly lower than those in the non-nitrate group. BP did not show a significant difference between 12 and 24 weeks in the nitrate group with a reduced need for other medication. Logistic regression analysis showed that nitrate supplementation and SBP reduction were independent risk factors of LVMI change in PD patients after adjusting for age, gender, diabetes history and CCB supplementation. It was concluded that organic nitrates favor regression of LVH in hypertensive patients on chronic peritoneal dialysis, and nitrates may be considered for use before employing the five other antihypertensive agents other than nitrates.

  18. ?-Adrenergic receptors on rat ventricular myocytes: characteristics and linkage to cAMP metabolism

    International Nuclear Information System (INIS)

    When incubated with purified cardiomyocytes from adult rat ventricle, the ?1-antagonist [3H]prazosin binds to a single class of sites with high affinity. Competition for [3H]prazosin binding by the ?2-selective antagonist yohimbine and the nonselective ?-antagonist phentolamine demonstrates that these receptors are of the ?1-subtype. In addition, incubation of myocyte membranes with [3H]yohimbine results in no measurable specific binding. Agonist competition for [3H]prazosin binding to membranes prepared from purified myocytes demonstrates the presence of two components of binding: 28% of ?1-receptors interact with norepinephrine with high affinity (K/sub D/ = 36 nM), whereas the majority of receptors (72%) have a low affinity for agonist (K/sub D/ = 2.2 ?M). After addition of 10 ?M GTP, norepinephrine competes for [3H]prazosin binding to a single class of sites with lower affinity (K/sub D/ = 2.2 ?M). Incubation of intact myocytes for 2 min with 1 ?M norepinephrine leads to significantly less cyclic AMP (cAMP) accumulation than stimulation with either norepinephrine plus prazosin or isoproterenol. Likewise, incubation of intact myocytes with 10-6 M norepinephrine leads to significantly less activation of cAMP-dependent protein kinase than when myocytes are stimulated by both norepinephrine and the ?1-adrenergic antagonist, prazosin or the ?-adrenergic agonist, isoproterenol. They conclude that the cardiomyocyte ?1 receptor is coupled to a guanine nucleotide-binding protein, that ?1-receptors are functionally linked to decreased intracellular cAMP content, and that this change in cellular cAMP is expressed as described activation of cAMP-dependent protein kinase

  19. -Adrenergic receptors on rat ventricular myocytes: characteristics and linkage to cAMP metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Buxton, I.L.O.; Brunton, L.L.

    1986-08-01

    When incubated with purified cardiomyocytes from adult rat ventricle, the 1-antagonist (TH)prazosin binds to a single class of sites with high affinity. Competition for (TH)prazosin binding by the 2-selective antagonist yohimbine and the nonselective -antagonist phentolamine demonstrates that these receptors are of the 1-subtype. In addition, incubation of myocyte membranes with (TH)yohimbine results in no measurable specific binding. Agonist competition for (TH)prazosin binding to membranes prepared from purified myocytes demonstrates the presence of two components of binding: 28% of 1-receptors interact with norepinephrine with high affinity (K/sub D/ = 36 nM), whereas the majority of receptors (72%) have a low affinity for agonist (K/sub D/ = 2.2 M). After addition of 10 M GTP, norepinephrine competes for (TH)prazosin binding to a single class of sites with lower affinity (K/sub D/ = 2.2 M). Incubation of intact myocytes for 2 min with 1 M norepinephrine leads to significantly less cyclic AMP (cAMP) accumulation than stimulation with either norepinephrine plus prazosin or isoproterenol. Likewise, incubation of intact myocytes with 10 W M norepinephrine leads to significantly less activation of cAMP-dependent protein kinase than when myocytes are stimulated by both norepinephrine and the 1-adrenergic antagonist, prazosin or the US -adrenergic agonist, isoproterenol. They conclude that the cardiomyocyte 1 receptor is coupled to a guanine nucleotide-binding protein, that 1-receptors are functionally linked to decreased intracellular cAMP content, and that this change in cellular cAMP is expressed as described activation of cAMP-dependent protein kinase.

  20. Hypertrophy, gene expression, and beating of neonatal cardiac myocytes are affected by microdomain heterogeneity in 3D

    OpenAIRE

    Curtis, Matthew W.; Sharma, Sadhana; DESAI, TEJAL A.; Russell, Brenda

    2010-01-01

    Cardiac myocytes are known to be influenced by the rigidity and topography of their physical microenvironment. It was hypothesized that 3D heterogeneity introduced by purely physical microdomains regulates cardiac myocyte size and contraction. This was tested in vitro using polymeric microstructures (G?=1.66 GPa) suspended with random orientation in 3D by a soft Matrigel matrix (G?=22.9 Pa). After 10 days of culture, the presence of 100 ?m-long microstructures in 3D gels induced fold increase...

  1. Simulation of the effect of rogue ryanodine receptors on a calcium wave in ventricular myocytes with heart failure

    International Nuclear Information System (INIS)

    Calcium homeostasis is considered to be one of the most important factors for the contraction and relaxation of the heart muscle. However, under some pathological conditions, such as heart failure (HF), calcium homeostasis is disordered, and spontaneous waves may occur. In this study, we developed a mathematical model of formation and propagation of a calcium wave based upon a governing system of diffusion–reaction equations presented by Izu et al (2001 Biophys. J. 80 103–20) and integrated non-clustered or 'rogue' ryanodine receptors (rogue RyRs) into a two-dimensional (2D) model of ventricular myocytes isolated from failing hearts in which sarcoplasmic reticulum (SR) Ca2+ pools are partially unloaded. The model was then used to simulate the effect of rogue RyRs on initiation and propagation of the calcium wave in ventricular myocytes with HF. Our simulation results show that rogue RyRs can amplify the diastolic SR Ca2+ leak in the form of Ca2+ quarks, increase the probability of occurrence of spontaneous Ca2+ waves even with smaller SR Ca2+ stores, accelerate Ca2+ wave propagation, and hence lead to delayed afterdepolarizations (DADs) and cardiac arrhythmia in the diseased heart. This investigation suggests that incorporating rogue RyRs in the Ca2+ wave model under HF conditions provides a new view of Ca2+ dynamics that could not be mimicked by adjusting traditional parameters involved in Ca2+ release units and other ion channels, and contributes to understanding the underlying mechanism of HF

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

    DEFF Research Database (Denmark)

    Bang, Casper N; Gerdts, Eva

    2014-01-01

    BACKGROUND: Left ventricular hypertrophy (LVH; high LV mass [LVM]) is traditionally classified as concentric or eccentric based on LV relative wall thickness. We evaluated the prediction of subsequent adverse events in a new 4-group LVH classification based on LV dilatation (high LV end-diastolic volume [EDV] index) and concentricity (mass/end-diastolic volume [M/EDV](2/3)) in hypertensive patients. METHODS AND RESULTS: In the Losartan Intervention for Endpoint Reduction (LIFE) echocardiography substudy, 939 hypertensive patients with measurable LVM at baseline were randomized to a mean of 4.8 years of losartan- or atenolol-based treatment. Patients with LVH (LVM/body surface area ?116 and ?96 g/m(2) in men and woman, respectively) were divided into 4 groups-concentric nondilated (increased M/EDV, normal EDV), eccentric dilated (increased EDV, normal M/EDV), concentric dilated (increased M/EDV and EDV), and eccentric nondilated (normal M/EDV and EDV)-and compared with patients with normal LVM. Time-varying LVH classes were tested for association with all-cause and cardiovascular mortality and a composite end point of myocardial infarction, stroke, heart failure, and cardiovascular death in multivariable Cox analyses. At baseline, the LVs were categorized as eccentric nondilated in 12%, eccentric dilated in 20%, concentric nondilated in 29%, concentric dilated in 14%, and normal LVM in 25%. Treatment changed the prevalence of 4 LVH groups to 23%, 4%, 5%, and 7%; 62% had normal LVM after 4 years. In time-varying Cox analyses, compared with normal LVM, those with eccentric dilated and both concentric nondilated and dilated LVH had increased risks of all-cause or cardiovascular mortality or the composite end point, whereas the eccentric nondilated group did not. CONCLUSIONS: Hypertensive patients with relatively mild LVH without either increased LV volume or concentricity have similar risk of all-cause mortality or cardiovascular events because hypertensive patients with normal LVM seem to be a low-risk group. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00338260.

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

    DEFF Research Database (Denmark)

    Vildbrad, Mads D; Andersen, Asger

    2014-01-01

    Pulmonary arterial hypertension (PAH) is a fatal disease, and the ultimate cause of death is right ventricular (RV) failure. In this study, we investigated the acute hemodynamic effects of levosimendan in two rat models of RV hypertrophy and failure. Wistar rats were randomized to receive sham surgery (n = 8), pulmonary trunk banding (PTB; n = 8), or monocrotaline injection (MCT; n = 7). RV function was evaluated at baseline and after injection of placebo and two concentrations of levosimendan (12 and 60 ?g/kg) using magnetic resonance imaging, echocardiography, and invasive pressure recordings. PTB and MCT injection caused hypertrophy, dilatation, and failure of the RV compared with sham surgery. Levosimendan increased RV end systolic pressure (sham surgery: 16.0% ± 3.8% [P = 0.0038]; MCT: 9.9% ± 3.1% [P = 0.018]; PTB: 24.5% ± 3.3% [P = 0.0001]; mean ± SEM) compared with placebo. Levosimendan markedly increased RV stroke volume (SV) in the MCT group (29.1% ± 8.3%; P = 0.012), did not change RV SV in the PTB group (0.4% ± 4.5%; P = 0.93), and decreased RV SV in the sham surgery group (-10.9% ± 3.7%; P = 0.020). Nitroprusside, which was used to mimic the systemic arterial vasodilator action of levosimendan, did not influence RV function. These data demonstrate that levosimendan acutely improves the failing right heart in a MCT model of PAH and that the mechanism involves a direct acute positive inotropic effect on the hypertrophic and failing RV of the rat.

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

    OpenAIRE

    Cesare Cuspidi; Francesca Negri; Alberto Zanchetti

    2008-01-01

    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...

  5. Quantitative estimation of right ventricular hypertrophy using ECG criteria in patients with pulmonary hypertension: A comparison with cardiac MRI

    OpenAIRE

    Blyth, Kevin G.; Kinsella, James; Hakacova, Nina; McLure, Lindsey E.; Siddiqui, Adeel M; Wagner, Galen S; Andrew J. Peacock

    2011-01-01

    In patients with pulmonary arterial hypertension (PAH), right ventricular mass (RVM) correlates linearly with pulmonary artery pressure, and decreases with successful treatment. Accurate measurement of RVM currently requires cardiovascular magnetic resonance (CMR) imaging. We therefore tested the relationship between RVM and a simple, 12 lead ECG-derived value, the Butler-Leggett (BL) score. This has previously been validated in patients with RV hypertrophy (RVH) due to mitral stenosis. We al...

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

    DEFF Research Database (Denmark)

    Boman, Kurt; Gerdts, Eva; Wachtell, Kristian; Dahlöf, Björn; Nieminen, Markku S; Olofsson, Mona; Papademetriou, Vasilios; Devereux, Richard B

    2009-01-01

    BACKGROUND: Exercise lowers blood pressure and improves cardiovascular function, but little is known about whether exercise impacts cardiovascular morbidity and mortality independent of left ventricular hypertrophy (LVH) and LV geometry. DESIGN: Observational analysis of prospectively obtained echocardiographic data within the context of a randomized trial of antihypertensive treatment. METHODS: A total of 937 hypertensive patients with ECG LVH were studied by echocardiography in the Losartan In...

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

    OpenAIRE

    van der Merwe, Lize; Cloete, Ruben; Revera, Miriam; Heradien, Marshall; Goosen, Althea; Corfield, Valerie A.; 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. The interdialytic weight gain: a simple marker of left ventricular hypertrophy in children on chronic haemodialysis.

    Science.gov (United States)

    Fischbach, Michael; Zaloszyc, Ariane; Shroff, Rukshana

    2015-06-01

    Despite multiple advances in haemodialysis (HD) technology over the years, the morbidity and mortality of HD patients remain unacceptably high. Cardiovascular disease is the most common cause of death, and left ventricular hypertrophy (LVH), seen in two-thirds of children on dialysis, is a significant contributor. The importance of volume control is increasingly recognized by nephrologists and now considered to be as important as urea kinetics, both in the day-to-day management and the long-term outcome of dialysis patients. The results published by Paglialonga et al. ( 10.1007/s00467-014-3005-2 ) in this issue of Pediatric Nephrology clearly demonstrate that there is a significant correlation between interdialytic weight gain (IDWG) and LVH in oligoanuric children on chronic HD and that children with an IDWG of >4 % are at high risk of LVH. One common practice to achieve euvolaemia is to prescribe very high ultrafiltration rates. However, both volume overload and aggressive fluid removal can induce circulatory stress and multi-organ injury. In adults, ultrafiltration rates of >1.24 % body weight per hour, even if well tolerated, are associated with a significant increase in mortality. Nephrologists should be aware of the risk of a high ultrafiltration rate, especially if tolerance is obtained by a positive dialysate-to-plasma sodium gradient. Haemodiafiltration, which allows for higher ultrafiltration rates with greater intradialytic haemodynamic stability, or more frequent and longer dialysis sessions allow for safe and effective fluid removal. PMID:25797887

  9. Frequency of Left Ventricular Hypertrophy in Non-Valvular Atrial Fibrillation.

    Science.gov (United States)

    Proietti, Marco; Marra, Alberto Maria; Tassone, Eliezer Joseph; De Vuono, Stefano; Corrao, Salvatore; Gobbi, Paolo; Perticone, Francesco; Corazza, Gino Roberto; Basili, Stefania; Lip, Gregory Y H; Violi, Francesco; Raparelli, Valeria

    2015-09-15

    Left ventricular hypertrophy (LVH) is significantly related to adverse clinical outcomes in patients at high risk of cardiovascular events. In patients with atrial fibrillation (AF), data on LVH, that is, prevalence and determinants, are inconsistent mainly because of different definitions and heterogeneity of study populations. We determined echocardiographic-based LVH prevalence and clinical factors independently associated with its development in a prospective cohort of patients with non-valvular (NV) AF. From the "Atrial Fibrillation Registry for Ankle-brachial Index Prevalence Assessment: Collaborative Italian Study" (ARAPACIS) population, 1,184 patients with NVAF (mean age 72 ± 11 years; 56% men) with complete data to define LVH were selected. ARAPACIS is a multicenter, observational, prospective, longitudinal on-going study designed to estimate prevalence of peripheral artery disease in patients with NVAF. We found a high prevalence of LVH (52%) in patients with NVAF. Compared to those without LVH, patients with AF with LVH were older and had a higher prevalence of hypertension, diabetes, and previous myocardial infarction (MI). A higher prevalence of ankle-brachial index ?0.90 was seen in patients with LVH (22 vs 17%, p = 0.0392). Patients with LVH were at significantly higher thromboembolic risk, with CHA2DS2-VASc ?2 seen in 93% of LVH and in 73% of patients without LVH (p gender (odds ratio [OR] 2.80, p gender, older age, hypertension, and previous MI. These patients are at high thromboembolic risk and deserve a holistic approach to cardiovascular prevention. PMID:26183791

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

    Science.gov (United States)

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

    2011-12-01

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

  11. The calcium-independent transient outward potassium current in isolated ferret right ventricular myocytes. II. Closed state reverse use- dependent block by 4-aminopyridine

    OpenAIRE

    1993-01-01

    Block of the calcium-independent transient outward K+ current, I(to), by 4-aminopyridine (4-AP) was studied in ferret right ventricular myocytes using the whole cell patch clamp technique. 4-AP reduces I(to) through a closed state blocking mechanism displaying "reverse use- dependent" behavior that was inferred from: (a) development of tonic block at hyperpolarized potentials; (b) inhibition of development of tonic block at depolarized potentials; (c) appearance of "crossover phenomena" in wh...

  12. Effect of exercise training on Ca2+ release units of left ventricular myocytes of spontaneously hypertensive rats

    Scientific Electronic Library Online (English)

    M.A., Carneiro-Júnior; J.F., Quintão-Júnior; L.R., Drummond; V.N., Lavorato; F.R., Drummond; M.A., Amadeu; E.M., Oliveira; L.B., Felix; J.S., Cruz; J.G., Mill; A.J., Natali; T.N., Prímola-Gomes.

    2014-11-01

    Full Text Available In cardiomyocytes, calcium (Ca2+) release units comprise clusters of intracellular Ca2+ release channels located on the sarcoplasmic reticulum, and hypertension is well established as a cause of defects in calcium release unit function. Our objective was to determine whether endurance exercise train [...] ing could attenuate the deleterious effects of hypertension on calcium release unit components and Ca2+ sparks in left ventricular myocytes of spontaneously hypertensive rats. Male Wistar and spontaneously hypertensive rats (4 months of age) were divided into 4 groups: normotensive (NC) and hypertensive control (HC), and normotensive (NT) and hypertensive trained (HT) animals (7 rats per group). NC and HC rats were submitted to a low-intensity treadmill running protocol (5 days/week, 1 h/day, 0% grade, and 50-60% of maximal running speed) for 8 weeks. Gene expression of the ryanodine receptor type 2 (RyR2) and FK506 binding protein (FKBP12.6) increased (270%) and decreased (88%), respectively, in HC compared to NC rats. Endurance exercise training reversed these changes by reducing RyR2 (230%) and normalizing FKBP12.6 gene expression (112%). Hypertension also increased the frequency of Ca2+ sparks (HC=7.61±0.26 vs NC=4.79±0.19 per 100 µm/s) and decreased its amplitude (HC=0.260±0.08 vs NC=0.324±0.10 ?F/F0), full width at half-maximum amplitude (HC=1.05±0.08 vs NC=1.26±0.01 µm), total duration (HC=11.51±0.12 vs NC=14.97±0.24 ms), time to peak (HC=4.84±0.06 vs NC=6.31±0.14 ms), and time constant of decay (HC=8.68±0.12 vs NC=10.21±0.22 ms). These changes were partially reversed in HT rats (frequency of Ca2+ sparks=6.26±0.19 µm/s, amplitude=0.282±0.10 ?F/F0, full width at half-maximum amplitude=1.14±0.01 µm, total duration=13.34±0.17 ms, time to peak=5.43±0.08 ms, and time constant of decay=9.43±0.15 ms). Endurance exercise training attenuated the deleterious effects of hypertension on calcium release units of left ventricular myocytes.

  13. 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

  14. Frequency of Left Ventricular Hypertrophy in Non-Valvular Atrial Fibrillation

    DEFF Research Database (Denmark)

    Proietti, Marco; Marra, Alberto Maria

    2015-01-01

    Left ventricular hypertrophy (LVH) is significantly related to adverse clinical outcomes in patients at high risk of cardiovascular events. In patients with atrial fibrillation (AF), data on LVH, that is, prevalence and determinants, are inconsistent mainly because of different definitions and heterogeneity of study populations. We determined echocardiographic-based LVH prevalence and clinical factors independently associated with its development in a prospective cohort of patients with non-valvular (NV) AF. From the "Atrial Fibrillation Registry for Ankle-brachial Index Prevalence Assessment: Collaborative Italian Study" (ARAPACIS) population, 1,184 patients with NVAF (mean age 72 ± 11 years; 56% men) with complete data to define LVH were selected. ARAPACIS is a multicenter, observational, prospective, longitudinal on-going study designed to estimate prevalence of peripheral artery disease in patients with NVAF. We found a high prevalence of LVH (52%) in patients with NVAF. Compared to those without LVH, patients with AF with LVH were older and had a higher prevalence of hypertension, diabetes, and previous myocardial infarction (MI). A higher prevalence of ankle-brachial index ?0.90 was seen in patients with LVH (22 vs 17%, p = 0.0392). Patients with LVH were at significantly higher thromboembolic risk, with CHA2DS2-VASc ?2 seen in 93% of LVH and in 73% of patients without LVH (p <0.05). Women with LVH had a higher prevalence of concentric hypertrophy than men (46% vs 29%, p = 0.0003). Logistic regression analysis demonstrated that female gender (odds ratio [OR] 2.80, p <0.0001), age (OR 1.03 per year, p <0.001), hypertension (OR 2.30, p <0.001), diabetes (OR 1.62, p = 0.004), and previous MI (OR 1.96, p = 0.001) were independently associated with LVH. In conclusion, patients with NVAF have a high prevalence of LVH, which is related to female gender, older age, hypertension, and previous MI. These patients are at high thromboembolic risk and deserve a holistic approach to cardiovascular prevention.

  15. Regresión de la hipertrofia ventricular izquierda con el uso del captopril / Regression of left ventricular hypertrophy with the use of captopril

    Scientific Electronic Library Online (English)

    Tomás Noel, Santana Téllez; Alina, Monteagudo Canto; Leandro, Segura Pujal; Angie Yohana, del Águila Grandez.

    2010-12-01

    Full Text Available Fundamento: la hipertensión arterial está asociada a cambios estructurales del aparato cardiovascular que le sirve para adaptarse al funcionamiento de un entorno de tensión alta. Objetivo: determinar la efectividad del captropil en la regresión de la hipertrofia ventricular izquierda en pacientes hi [...] pertensos, atendidos en consulta especializada en hipertensión arterial del Hospital universitario Manuel Ascunce Domenech desde Enero hasta Diciembre de 2008. Método: se realizó un estudio cuasi-experimental en ciento cuarenta y nueve pacientes. La muestra quedó constituida por cien pacientes. Resultados: se encontró un predominio de la hipertrofia ventricular izquierda en pacientes hipertensos entre treinta y seis y cuarenta y cinco años, después del uso del Captopril se produjo una disminución del 12,0% de pacientes con patrón geométrico anormal del ventrículo izquierdo con cuatro años de evolución de hipertensión arterial, y los pacientes con patrón geométrico anormal del ventrículo izquierdo con hipertensión arterial en estadio uno fueron veintiséis. Luego del uso de dicho fármaco veintiséis pacientes presentaron patrón geométrico normal del ventrículo izquierdo. Conclusiones: el captropil es efectivo en el tratamiento de la hipertrofia ventricular izquierda principalmente en pacientes con hipertensión en estadio uno, con menos de cuatros años de evolución. Abstract in english Background: arterial hypertension is associate to structural changes of the cardiovascular apparatus that are used for adapting to the function in a high tension environment. Objective: to determine the effectiveness of captopril in the regression of left ventricular hypertrophy in hypertensive pati [...] ents, attended in a specialized consultation of arterial hypertension at the Manuel Ascunce Domenech University Hospital from January to December 2008. Method: a quasi-experimental study in one hundred forty-nine patients was carried out. The sample was constituted by a hundred patients. Results: a prevalence of left ventricular hypertrophy in hypertensive patients between thirty-six and forty-five years was found, after the use of captopril brought about a decrease of 12,0% of patients with abnormal geometric pattern of left ventricle with four years of evolution of arterial hypertension, and patients with abnormal geometric pattern of left ventricle with arterial hypertension in stage one was twenty-six. After the use of this drug, twenty-six patients presented normal geometric pattern of left ventricle. Conclusions: captopril is effective in the treatment of left ventricular hypertrophy mainly in patients with hypertension in stage one, with less than four years of evolution.

  16. 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.

  17. Regression of left ventricular hypertrophy in diabetic nephropathy: loss of parasympathetic function predicts response to treatment.

    Science.gov (United States)

    Weinrauch, Larry A; Berger, Andrew J; Aronson, Doron; Gleason, Ray E; Lee, Annette T; D'Elia, John A

    2006-05-01

    Both left ventricular (LV) hypertrophy and decreased autonomic function are predictors of adverse cardiac events. Patients with diabetic nephropathy have an excess cardiovascular risk. The authors determined heart rate variability from 24-hour ambulatory electrocardiographic recordings and measures of LV mass with systolic and diastolic function from echocardiograms. Patients with diabetic nephropathy (n=16) were seen weekly for insulin and hypertension management. Glycohemoglobin decreased from 9.5+/-0.4% to 8.3+/-0.4% (p=0.01), and advanced glycated end products decreased from 12.1+/-2.2 to 7.4+/-1.2 units (p=0.03). Mean arterial pressure and body weight did not change. Serum creatinine increased (1.8+/-0.1 mg/dL to 2.0+/-0.2 mg/dL; p=0.03). The authors used a panel of markers of baseline heart rate variation to assess autonomic function. When covariance of the heart rate interval results were evaluated, the group below the median was found to have a significant decrease in LV mass, from 230 g to 184 g (p=0.013); the group above the median had an increase (182 g to 193 g; p=0.5329). Baseline covariance of the heart rate interval predicted 12-month changes in LV mass in 13 of 16 patients (predictive accuracy, 81%). Improvement in measures of heart rate variation correlated with a decrease in LV mass. Parallel improvement of LV mass and autonomic function suggests a common mechanism, allowing for prediction of LV mass improvement through analysis of baseline heart rate variation. PMID:16687941

  18. Glucose-Insulin-Potassium Solution Protects Ventricular Myocytes of Neonatal Rat in an In Vitro Coverslip Ischemia/Reperfusion Model

    Science.gov (United States)

    Chun, Woo-Jung; Bae, Jun-Ho; Chung, Jin-Wook; Lee, HyunSook; Moon, Il Soo

    2015-01-01

    Background and Objectives The benefit of high glucose-insulin-potassium (GIK) solution in clinical applications is controversial. We established a neonatal rat ventricular myocyte (NRVM) in vitro coverslip ischemia/reperfusion (I/R) model and investigated the effects of GIK solution on suppressing reactive oxygen species (ROS) and upregulating O-GlcNacylation, which protects cells from ischemic injury. Materials and Methods NRVMs were isolated from postnatal day 3-4 Sprague-Dawley rat pups and grown in Dulbecco's modified Eagle's medium containing high glucose (4.5 g/L), fetal bovine serum, and penicillin/streptomycin. The effects of the GIK solution on ROS production, apoptosis, and expression of O-GlcNAc and O-GlcNAc transferase (OGT) were investigated in the coverslip I/R model. Results Covering the 24-well culture plates for 3 hr with 12 mm diameter coverslips resulted in the appropriate ischemic shock. Glucose and insulin synergistically reduced ROS production, protected NRVM dose-dependently from apoptosis, and altered O-GlcNAc and OGT expression. Conclusion The high GIK solution protected NRVM from I/R injury in vitro by reducing ROS and altering O-GlcNacylation. PMID:26023312

  19. Gap Junction-associated Na+ Influx Is Involved in the Mediation of Ca2+ Transients in Neonatal Rat Ventricular Myocytes.

    Science.gov (United States)

    Yan, Xinxin; Zeng, Zheng; Chen, Min; Li, Chen; Li, Shu; Luo, Dali

    2015-07-01

    Gap junction (GJ) coupling is involved in the regulation of spontaneous Ca(2+) transients in neonatal rat ventricular myocytes (NRVMs); however, the underlying mechanism(s) remains incompletely clear. In this study, we investigated Na influx mediated by Cx43-associated GJ modulating the spontaneous NRVM excitation. Intracellular Na(+) and Ca(2+) concentrations ([Na(+)](i) and [Ca(2+)](i)) were assessed using CoroNa Green and Fluo-4 fluorescent probes, respectively, by confocal microscopy. GJ function was evaluated by measuring fluorescence recovery after photobleaching. The results showed that [Na(+)](i) and spontaneous Ca(2+) oscillating were significantly decreased by the treatment of NRVMs with GJ uncouplers or adenovirus-mediated Cx43 gene knockdown using short hairpin RNA, while both of the intracellular cation levels were increased by adenovirus-mediated Cx43 overexpression. Neither Na(+) channel blocker (tetrodotoxin) nor the GJ uncoupler (Gap27) or Cx43-short hairpin RNA adenovirus could completely suppress the Ca(2+) transients, but their combination usage could. In addition, Ca(2+) transients disappeared in NRVMs incubated in Na(+)-free, but not in Ca(2+) -free medium, in which the remained transients could be further abolished by Gap27. Collectively, our findings suggest that Cx43-associated GJ function is involved in the regulation of Na(+) influx into cardiomyocytes, which contributes, at least in part, to triggering spontaneous excitation and regulation of cardiomyocyte automaticity. PMID:25714594

  20. Cardiotrofina-1 circulante puede diferenciar la hipertrofia ventricular fisiológica del atleta de la hipertrofia patológica del paciente hipertenso Circulating cardiotrophyn-1 may help differenciate left ventricular hypertrophy seen in athletes from pathologic left ventricular hypertrophy associated to hypertension

    Directory of Open Access Journals (Sweden)

    Luigi Gabrielli

    2009-04-01

    Full Text Available Introducción: Cardiotrofina-1 (CT-1, una citoquina perteneciente a la superfamilia de la interleukina-6, se encuentra elevada en pacientes con hipertensión arterial (HTA e hipertrofia ventricular izquierda (HVI. Sus niveles se correlacionan con el tamaño auricular izquierdo y con las presiones de llenado del ventrículo izquierdo. Los niveles de CT-1 en atletas con HVI fisiológica no han sido investigados. Métodos: Estudio transversal. Se incluyeron pacientes con HTA esencial con y sin evidencia ecográfica de cardiopatía hipertensiva (CH(HVI y relación E/E'>10, recientemente diagnosticada y sin tratamiento. Un grupo de atletas normotensos con diagnóstico ecográfico de HVI y un grupo control de sujetos normotensos pareados por edad y sexo. En todos los sujetos se midieron los niveles plasmáticos de CT-1 (ELISA. Se definió HVI mediante diagnóstico ecocargiográfico, utilizando el índice de masa ventricular izquierda usando la fórmula de Devereux (hombres ³115 gramos/m², mujer ³95 gramos/m². Las presiones de llenado del VI se estimaron con la relación E/E' (doppler tisular en el anillo mitral medial. Resultados: Se incluyeron 10 pacientes por grupo. Los atletas con HVI presentaron una relación E/E' Background: Cardiotrophyn-1 (CT-1, is a cytokine which is increased in patients with hypertension (HT and left ventricular hypertrophy (LVH. This increase occurs in proportion to left atrial size and left ventricular filling pressures. CT-1 levels in athletes with LVH have not been investigated Methods: Crossectional study. We evaluated: a hypertensive patients with LVH and E/E' > 10 by echocardiography, recently diagnosed and receiving no medications; b normotensive athletes with LVH as shown by echocardiography, and c normotensive subjects, paired by age and sex. Plasma levels of CT-1 (ELISA were measured in all. LVH was defined as left ventricular mass index > 115 G/m² (males or > 95 G/m² (females. Results: E/E' was lower in athletes than hypertensive patients with LVH (6.5 ± 1 vs 12.9 ± 1.1, p<0.01. E/E' in both control subjects and patients with HTA but no LVH did not differ from E/E' in athletes. CT-1 was lower in athletes than patients with HTA and LVH (6.6 ± 0.4 vs 18.2 ± 5.6 fmol/ml, respectively, p<0.001. CT-1 levels in control subjects and hypertensive patients without LVH did not differ from that found in athletes. Conclusion: CT-1 levels are similar in athletes compared to normal subjects and patients with HTA and no LVH. Hypertensive patients with similar grades of LVH and left ventricular diastolic dysfunction had significantly greater leves of CT-1. Thus, CT-1 levels could help differentiate pathological HVI from physiologic LVH in athletes.

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

    Czech Academy of Sciences Publication Activity Database

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

    2014-01-01

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

  2. Hipertrofia cardíaca esquerda e direita em necropsias de hipertensos / Left and right ventricular hypertrophy at autopsy of hypertensive individuals

    Scientific Electronic Library Online (English)

    Mirella Pessoa, Sant' Anna; Roberto José Vieira de, Mello; Luciano Tavares, Montenegro; Mônica Modesto, Araújo.

    2012-02-01

    Full Text Available OBJETIVO: Medir a espessura ventricular direita e esquerda em falecidos com história de hipertensão arterial, submetidos a necropsias clínicas. MÉTODOS: Foram selecionados 90 casos do Serviço de Verificação de Óbitos de Recife -PE, de ambos os sexos, com história de hipertensão arterial essencial, c [...] om relação à espessura das paredes cardíacas, além da correlação com outros achados de necropsia e informes clínicos. RESULTADOS: Observouse associação significativa entre a presença de hipertrofia ventricular esquerda (HVE) e direita (HVD), e de cardiopatia hipertensiva grave e HVD. Houve predomínio da HVD e HVE em homens, na faixa etária dos 60-79 anos, com maior prevalência nas etnias parda e negra, e naqueles com estado nutricional adequado ou com sobrepeso e em obesos. CONCLUSÃO: Observou-se que a presença de HVD relaciona-se com HVE, sugerindo que há fatores patogênicos semelhantes envolvidos no desenvolvimento da hipertrofia bilateral. A HVD parece associar-se à doença cardíaca mais grave, podendo, a partir de outros estudos, ser considerada novo fator prognóstico na avaliação dos pacientes hipertensos. Abstract in english OBJECTIVE: To measure the right and left ventricular thickness in deceased individuals with a history of hypertension submitted to clinical autopsies. METHODS: We selected 90 cases from the Death Verification Service of the city of Recife, state of Pernambuco, Brazil, of both sexes, with a history o [...] f essential arterial hypertension related to heart wall thickness, in addition to correlation with autopsy findings and other clinical reports. RESULTS: There was a significant association between the presence of left ventricular hypertrophy (LVH) and right ventricular hypertrophy (RVH) and between severe hypertensive cardiomyopathy and RVH. There was a predominance of RVH and LVH in men aged 60-79 years and a higher prevalence in the Brazilian mulatto and Black ethnic groups and in those with adequate nutritional status or overweight and obese individuals. CONCLUSION: It was observed that the presence of RVH was related to LVH, suggesting that there are similar pathogenic factors involved in the development of bilateral hypertrophy. The RVH seems to be associated with more severe heart disease and may, based on other studies, be considered as a new prognostic factor in the evaluation of hypertensive patients.

  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. Endothelial Cells Contribute to Generation of Adult Ventricular Myocytes during Cardiac Homeostasis

    Directory of Open Access Journals (Sweden)

    Bryan A. Fioret

    2014-07-01

    Full Text Available Cardiac tissue undergoes renewal with low rates. Although resident stem cell populations have been identified to support cardiomyocyte turnover, the source of the cardiac stem cells and their niche remain elusive. Using Cre/Lox-based cell lineage tracing strategies, we discovered that labeling of endothelial cells in the adult heart yields progeny that have cardiac stem cell characteristics and express Gata4 and Sca1. Endothelial-derived cardiac progenitor cells were localized in the arterial coronary walls with quiescent and proliferative cells in the media and adventitia layers, respectively. Within the myocardium, we identified labeled cardiomyocytes organized in clusters of single-cell origin. Pulse-chase experiments showed that generation of individual clusters was rapid but confined to specific regions of the heart, primarily in the right anterior and left posterior ventricular walls and the junctions between the two ventricles. Our data demonstrate that endothelial cells are an intrinsic component of the cardiac renewal process.

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

    Science.gov (United States)

    Bugenhagen, Scott M.; Beard, Daniel A.

    2015-10-01

    Force?frequency relationships of isolated cardiac myocytes show complex behaviors that are thought to be specific to both the species and the conditions associated with the experimental preparation. Ca2+ signaling plays an important role in shaping the force?frequency relationship, and understanding the properties of the force?frequency relationship in vivo requires an understanding of Ca2+ dynamics under physiologically relevant conditions. Ca2+ signaling is itself a complicated process that is best understood on a quantitative level via biophysically based computational simulation. Although a large number of models are available in the literature, the models are often a conglomeration of components parameterized to data of incompatible species and/or experimental conditions. In addition, few models account for modulation of Ca2+ dynamics via ?-adrenergic and calmodulin-dependent protein kinase II (CaMKII) signaling pathways even though they are hypothesized to play an important regulatory role in vivo. Both protein-kinase-A and CaMKII are known to phosphorylate a variety of targets known to be involved in Ca2+ signaling, but the effects of these pathways on the frequency- and inotrope-dependence of Ca2+ dynamics are not currently well understood. In order to better understand Ca2+ dynamics under physiological conditions relevant to rat, a previous computational model is adapted and re-parameterized to a self-consistent dataset obtained under physiological temperature and pacing frequency and updated to include ?-adrenergic and CaMKII regulatory pathways. The necessity of specific effector mechanisms of these pathways in capturing inotrope- and frequency-dependence of the data is tested by attempting to fit the data while including and/or excluding those effector components. We find that: (1) ?-adrenergic-mediated phosphorylation of the L-type calcium channel (LCC) (and not of phospholamban (PLB)) is sufficient to explain the inotrope-dependence; and (2) that CaMKII-mediated regulation of neither the LCC nor of PLB is required to explain the frequency-dependence of the data.

  6. 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?

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

    Directory of Open Access Journals (Sweden)

    Yu-luan Xiang

    2012-03-01

    Full Text Available 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.

  9. 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 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.

  10. MicroRNA-27a Regulates Beta Cardiac Myosin Heavy Chain Gene Expression by Targeting Thyroid Hormone Receptor ?1 in Neonatal Rat Ventricular Myocytes?

    OpenAIRE

    Nishi, Hitoo; Ono, Koh; Horie, Takahiro; Nagao, Kazuya; Kinoshita, Minako; Kuwabara, Yasuhide; Watanabe, Shin; Takaya, Tomohide; Tamaki, Yodo; Takanabe-Mori, Rieko; Wada, Hiromichi; Hasegawa, Koji; Iwanaga, Yoshitaka; Kawamura, Teruhisa; Kita, Toru

    2010-01-01

    MicroRNAs (miRNAs), small noncoding RNAs, are negative regulators of gene expression and play important roles in gene regulation in the heart. To examine the role of miRNAs in the expression of the two isoforms of the cardiac myosin heavy chain (MHC) gene, ?- and ?-MHC, which regulate cardiac contractility, endogenous miRNAs were downregulated in neonatal rat ventricular myocytes (NRVMs) using lentivirus-mediated small interfering RNA (siRNA) against Dicer, an essential enzyme for miRNA biosy...

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

    OpenAIRE

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

    1993-01-01

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

  12. Galphaq-protein carboxyl terminus imitation polypeptide (GCIP)-27 inhibits right ventricular hypertrophy induced by monocrotaline in rats.

    Science.gov (United States)

    Yang, Dan-Li; Zhang, Hai-Gang; Xu, Ya-Li; Gao, Yun-Hua; Yang, Xiao-Jiao; Hao, Xue-Qin; Su, Min; Wang, Xiu-Qin; Li, Xiao-Hui

    2009-03-01

    This study was to investigate the probable inhibitory effect of Galphaq-protein carboxyl terminus imitation polypeptide-27 (GCIP-27), the optimized form of GCIP, which is a competition candidate of the activated binding sites on Galphaq, on the right ventricular (RV) hypertrophy induced by monocrotaline (MCT) in rats. We have previously shown that GCIP-27, can prevent the hypertrophyc responses in cultured rat cardiomyocytes induced by noradrenaline and angiotensin II. Male Sprague-Dawley rats were given a single dose (50 mg/kg) of MCT subcutaneouly to induce pulmonary hypertension (PH) and RV hypertrophy. GCIP-27 (30, 90 microg/kg) or vehicle was administered (twice daily, intraperitoneally) from day 1 to day 21. GCIP-27 (90 microg/kg) inhibited the elevated pulmonary arteria systolic pressure (PASP) and mean pulmonary arteria pressure induced by MCT, but its dose at 30 microg/kg only reduced the elevated PASP. And no effect could be seen on the pulmonary arteria diastolic pressure at both two doses. On the other hand, the two doses of GCIP-27 improved significantly the weight ratio of RV to left ventricle plus septum, the RV free wall thickness and pulmonary arteria acceleration time (PAAT). In morphometric observation, GCIP-27 (30, 90g/kg) could attenuate cardiomyocytes hypertrophy, interstitium fibrosis, mitochondria swelling and malformation markedly in RVs of MCT-treated rats. Furthermore, GCIP-27 (30, 90 mug/kg) significantly reduced the overexpression of the proliferating cell nuclear antigen (PCNA) induced by MCT in RV cardiocytes. The results suggest that GCIP-27 can effectively attenuate the RV hypertrophy induced by MCT in rats, which may be mediated by both the direct effect on cardiomyocyte and the secondary effect by reducing PH, and may be involved in its influence on the Gq signal pathway. PMID:19252281

  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. 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

  15. Urine albumin/creatinine ratio and echocardiographic left ventricular structure and function in hypertensive patients with electrocardiographic left ventricular hypertrophy: The LIFE Study

    DEFF Research Database (Denmark)

    Wachtell, K.; Palmieri, V.

    2002-01-01

    Background Albuminuria, reflecting systemic microvascular damage, and left ventricular (LV) geometric abnormalities have both been shown to predict increased cardiovascular morbidity and mortality. However, the relationship between these markers of cardiovascular damage has not been evaluated in a large hypertensive population. Methods The urine albumin/creatinine ratio (UACR) and echocardiographic measures of LV structure and function were obtained in 833 patients with stage I to III hypertension and LV hypertrophy determined by electrocardiogram (ECG) (Cornell voltage-duration or Sokolow-Lyon voltage criteria) after 14 days of placebo treatment. Results Patients’ mean ages were 66 years, 42% were women, 23% had microalbuminuria, and 5% had macroalbuminuria. Patients with eccentric or concentric LV hypertrophy had higher prevalences of microalbuminuria (average 26%-30% vs 9%, P < .001) and macroalbuminuria (6%-7% vs <1%, P < .001). Furthermore, patients with microalbuminuria and macroalbuminuria had a significantly higher LV mass and lower endocardial and midwall fractional shortening. Patients with abnormal diastolic LV filling parameters had a significantly increased prevalence of microalbuminuria. In univariate analyses, UACR correlated positively to LV mass, systolic blood pressure, age (all P < .001) and pulse pressure/stroke volume and negatively to relative wall thickness (both P < .01) and endocardial (P < .05) and midwall shortening (P < .001) but not to diastolic filling parameters. In multiple regression analysis higher UACR was associated with higher LV mass (? = .169, P< .001) independently of older age (? = .095, P < .01), higher systolic pressure (? = .163), black race (? = .186), and diabetes (? = .241, all P < .001). Conclusions In hypertensive patients with ECG LV hypertrophy, abnormal LV geometry and high LV mass are associated with high UACR independent of age, systolic blood pressure, diabetes, and race, suggesting parallel cardiac and microvascular damage.

  16. 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.

  17. Psoriasis is associated with subsequent atrial fibrillation in hypertensive patients with left ventricular hypertrophy : the Losartan Intervention For Endpoint study

    DEFF Research Database (Denmark)

    Bang, Casper N; Okin, Peter M

    2014-01-01

    BACKGROUND: Inflammation contributes to the pathogenesis of psoriasis as well as atrial fibrillation. The impact of psoriasis and its association with new-onset atrial fibrillation was assessed in hypertensive patients with left ventricular hypertrophy (LVH). METHODS: The predictive value of baseline or incident psoriasis for new-onset atrial fibrillation was evaluated in 7099 hypertensive patients with electrocardiographic LVH with no history of atrial fibrillation or other cardiovascular disease, in sinus rhythm on their baseline electrocardiogram. RESULTS: A total of 154 patients (2.2%) had or developed psoriasis and new-onset atrial fibrillation occurred in 506 patients (7.1%) during a mean follow-up of 4.7 ± 1.1 years. At baseline, the psoriasis patients were younger (65 ± 7 vs. 67 ± 7 years) and had less left ventricle hypertrophy by ECG Sokolow-Lyon voltage (27.6 ± 9.7 vs. 30.1 ± 10.4 mm); higher hemoglobin (6.3 ± 2.2 vs. 6.0 ± 2.7 mmol/l) and prevalence of diabetes (20.6 vs. 12.8%, P ? 0.004) than patients without psoriasis. In multivariable Cox analysis, adjusting for age, sex, hemoglobin, diabetes, time-varying SBP, heart rate, study treatment and Sokolow-Lyon hypertrophy, psoriasis, treated as a time-varying covariate, was associated with a two-fold higher risk of new-onset atrial fibrillation [hazard ratio: 1.97 (95% confidence interval (CI): 1.18-3.30), P=0.01]. Propensity-matched analysis yielded similar results (odds ratio: 3.49, 95% CI 1.24-9.81, P=0.018). CONCLUSION: Psoriasis has a similar prevalence in hypertensive patients as in the general population. Psoriasis independently predicted new-onset atrial fibrillation despite lower age and electrocardiographic LVH in psoriasis patients than in patients without psoriasis.

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

    Directory of Open Access Journals (Sweden)

    Warren Stafford G

    2010-06-01

    Full Text Available Abstract Background Resting conventional 12-lead ECG has low sensitivity for detection of coronary artery disease (CAD and left ventricular hypertrophy (LVH and low positive predictive value (PPV for prediction of left ventricular systolic dysfunction (LVSD. We hypothesized that a ~5-min resting 12-lead advanced ECG test ("A-ECG" that combined results from both the advanced and conventional ECG could more accurately screen for these conditions than strictly conventional ECG. Methods Results from nearly every conventional and advanced resting ECG parameter known from the literature to have diagnostic or predictive value were first retrospectively evaluated in 418 healthy controls and 290 patients with imaging-proven CAD, LVH and/or LVSD. Each ECG parameter was examined for potential inclusion within multi-parameter A-ECG scores derived from multivariate regression models that were designed to optimally screen for disease in general or LVSD in particular. The performance of the best retrospectively-validated A-ECG scores was then compared against that of optimized pooled criteria from the strictly conventional ECG in a test set of 315 additional individuals. Results Compared to optimized pooled criteria from the strictly conventional ECG, a 7-parameter A-ECG score validated in the training set increased the sensitivity of resting ECG for identifying disease in the test set from 78% (72-84% to 92% (88-96% (P Conclusion Resting 12-lead A-ECG scoring is more accurate than strictly conventional ECG in screening for CAD, LVH and LVSD.

  19. 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

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

    Scientific Electronic Library Online (English)

    A.M., Cabral; I.F., Silva; C.R., Gardioli; H., Mauad; E.C., Vasquez.

    1998-04-01

    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 sympathe [...] tic 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

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

    Directory of Open Access Journals (Sweden)

    T.A. Uggere

    2000-05-01

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

  2. 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 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.

  3. DA-8159, a new PDE5 inhibitor, attenuates the development of compensatory right ventricular hypertrophy in a rat model of pulmonary hypertension.

    Science.gov (United States)

    Kang, K K; Ahn, G J; Sohn, Y S; Ahn, B O; Kim, W B

    2003-01-01

    This study evaluated the effect of DA-8159, a new phosphodiesterase 5 inhibitor, on the compensatory development of right ventricular hypertrophy in monocrotaline (MCT)-induced pulmonary hypertension (PH). Rats treated with subcutaneous MCT were divided into three groups, which received DA-8159 1 mg/kg, DA-8159 5 mg/kg or saline-vehicle orally, twice daily for 21 days. The vehicle group demonstrated increased right ventricular weight, pulmonary artery medial wall thickening, myocardial fibrosis, increased plasma cyclic guanosine monophosphate (cGMP) concentration and reduced body weight gains. DA-8159, however, markedly attenuated the compensatory development of right ventricular hypertrophy and pulmonary artery medial wall thickening, amplified the increase in plasma cGMP levels and increased lung cGMP concentrations. In addition, DA-8159 prevented myocardial fibrosis induced by MCT. These results demonstrate that DA-8159 attenuates the compensatory development of right ventricular hypertrophy in a rate model of PH. DA-8159 might, therefore, be a useful treatment option for PH, but its efficacy in humans needs evaluating. PMID:14708417

  4. Caveolin-3 Overexpression Attenuates Cardiac Hypertrophy via Inhibition of T-type Ca2+ Current Modulated by Protein Kinase C? in Cardiomyocytes.

    Science.gov (United States)

    Markandeya, Yogananda S; Phelan, Laura J; Woon, Marites T; Keefe, Alexis M; Reynolds, Courtney R; August, Benjamin K; Hacker, Timothy A; Roth, David M; Patel, Hemal H; Balijepalli, Ravi C

    2015-09-01

    Pathological cardiac hypertrophy is characterized by subcellular remodeling of the ventricular myocyte with a reduction in the scaffolding protein caveolin-3 (Cav-3), altered Ca(2+) cycling, increased protein kinase C expression, and hyperactivation of calcineurin/nuclear factor of activated T cell (NFAT) signaling. However, the precise role of Cav-3 in the regulation of local Ca(2+) signaling in pathological cardiac hypertrophy is unclear. We used cardiac-specific Cav-3-overexpressing mice and in vivo and in vitro cardiac hypertrophy models to determine the essential requirement for Cav-3 expression in protection against pharmacologically and pressure overload-induced cardiac hypertrophy. Transverse aortic constriction and angiotensin-II (Ang-II) infusion in wild type (WT) mice resulted in cardiac hypertrophy characterized by significant reduction in fractional shortening, ejection fraction, and a reduced expression of Cav-3. In addition, association of PKC? and angiotensin-II receptor, type 1, with Cav-3 was disrupted in the hypertrophic ventricular myocytes. Whole cell patch clamp analysis demonstrated increased expression of T-type Ca(2+) current (ICa, T) in hypertrophic ventricular myocytes. In contrast, the Cav-3-overexpressing mice demonstrated protection from transverse aortic constriction or Ang-II-induced pathological hypertrophy with inhibition of ICa, T and intact Cav-3-associated macromolecular signaling complexes. siRNA-mediated knockdown of Cav-3 in the neonatal cardiomyocytes resulted in enhanced Ang-II stimulation of ICa, T mediated by PKC?, which caused nuclear translocation of NFAT. Overexpression of Cav-3 in neonatal myocytes prevented a PKC?-mediated increase in ICa, T and nuclear translocation of NFAT. In conclusion, we show that stable Cav-3 expression is essential for protecting the signaling mechanisms in pharmacologically and pressure overload-induced cardiac hypertrophy. PMID:26170457

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

    Science.gov (United States)

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

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

  6. 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 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

  7. Comparison of Blood Pressure Control and Left Ventricular Hypertrophy in Patients on Continuous Ambulatory Peritoneal Dialysis (CAPD) and Automated Peritoneal Dialysis (APD)

    OpenAIRE

    Jang, Jong Soon; Kwon, Soon Kil; Kim, Hye-young

    2011-01-01

    This study aimed to investigate the influence of different peritoneal dialysis regimens on blood pressure control, the diurnal pattern of blood pressure and left ventricular hypertrophy in patients on peritoneal dialysis. Forty-four patients undergoing peritoneal dialysis were enrolled into the study. Patients were treated with different regimens of peritoneal dialysis: 26 patients on continuous ambulatory peritoneal dialysis (CAPD) and 18 patients on automated peritoneal dialysis (APD). All ...

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

    Directory of Open Access Journals (Sweden)

    Assadi F ; Translated by: Akbari Asbagh P

    2007-04-01

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

  9. Prevalence, pattern, and functional impact of late gadolinium enhancement in left ventricular hypertrophy due to aortic valve stenosis

    International Nuclear Information System (INIS)

    Purpose: To assess the prevalence and pattern of myocardial late gadolinium enhancement (LGE) and its functional impact on patients with left ventricular hypertrophy caused by aortic valve stenosis. Materials and Methods: Cardiac magnetic resonance imaging of 40 patients (17 female, 23 male, mean age: 76.6 ± 22.5 years) with known aortic valve stenosis (mean aortic valve area: 89.8 ± 19.2 mm2) and without coronary artery disease was performed at 1.5 T using steady-state free precession sequences for aortic valve planimetry and for the assessment of left ventricular (LV) volumes and mass. Ten to 15 minutes after injection of 0.2 mmol Gd-DTPA per kilogram body weight, inversion-recovery prepared spoiled gradient echo images were acquired in standard long and short axis views to detect areas of LGE. Results: LGE was observed in 32.5 % (13/40) of our patients. LGE was mainly located in the basal septal and inferior LV segments, and showed a non-ischemic pattern with sparing of the subendocardial region. Patients with LGE showed lower LV ejection fractions (55.5 ± 13.8 % vs. 69.1 ± 10.7 %, p = 0.0014), higher LV end-systolic volumes (59.8 ± 33.3 ml vs. 36.6 ± 16.0 ml, p = 0.0048), and LV masses (211.0 ± 13.8 vs. 157.9 ± 37.5 g, p = 0.0002) compared to patients without LGE. (orig.)

  10. Prevalence, pattern, and functional impact of late gadolinium enhancement in left ventricular hypertrophy due to aortic valve stenosis

    Energy Technology Data Exchange (ETDEWEB)

    Nassenstein, K.; Schlosser, T. [Universitaetsklinikum Essen (Germany). Abt. fuer Diagnostische und Interventionelle Radiologie; Bruder, O. [Elisabeth-Krankenhaus Essen (Germany). Klinik fuer Kardiologie und Angiologie; Breuckmann, F.; Erbel, R. [Universitaetsklinikum Essen (Germany). Westdeutsches Herzzentrum Essen; Barkhausen, J. [Universitaetsklinikum Schleswig-Holstein, Luebeck (Germany). Klinik fuer Radiologie und Nuklearmedizin

    2009-05-15

    Purpose: To assess the prevalence and pattern of myocardial late gadolinium enhancement (LGE) and its functional impact on patients with left ventricular hypertrophy caused by aortic valve stenosis. Materials and Methods: Cardiac magnetic resonance imaging of 40 patients (17 female, 23 male, mean age: 76.6 {+-} 22.5 years) with known aortic valve stenosis (mean aortic valve area: 89.8 {+-} 19.2 mm{sup 2}) and without coronary artery disease was performed at 1.5 T using steady-state free precession sequences for aortic valve planimetry and for the assessment of left ventricular (LV) volumes and mass. Ten to 15 minutes after injection of 0.2 mmol Gd-DTPA per kilogram body weight, inversion-recovery prepared spoiled gradient echo images were acquired in standard long and short axis views to detect areas of LGE. Results: LGE was observed in 32.5 % (13/40) of our patients. LGE was mainly located in the basal septal and inferior LV segments, and showed a non-ischemic pattern with sparing of the subendocardial region. Patients with LGE showed lower LV ejection fractions (55.5 {+-} 13.8 % vs. 69.1 {+-} 10.7 %, p = 0.0014), higher LV end-systolic volumes (59.8 {+-} 33.3 ml vs. 36.6 {+-} 16.0 ml, p = 0.0048), and LV masses (211.0 {+-} 13.8 vs. 157.9 {+-} 37.5 g, p = 0.0002) compared to patients without LGE. (orig.)

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

    International Nuclear Information System (INIS)

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

  12. Papel del estrés oxidativo y nitrosativo en la hipertrofia cardiaca y remodelación ventricular Role of oxidative and nitrosative stress in cardiac hypertrophy and ventricular remodeling

    Directory of Open Access Journals (Sweden)

    Alejandro Giraldo

    2010-06-01

    Full Text Available Objetivo: hacer una revisión de los mecanismos moleculares del estrés oxidativo y nitrosativo en la fisiopatología de la falla cardiaca. Metodología: se hizo una búsqueda en Medline (Pubmed con las palabras clave: oxidative stress, ventricular remodeling, heart failure y nitrosative stress. Se consultó además bibliografía citada por autores de reconocida trayectoria en investigación en este tema. Resultados: se seleccionaron los 112 artículos más relevantes en el tema de estrés oxidativo/ nitrosativo que se relacionarán con falla cardiaca. Conclusiones: las respuestas de estrés de los cardiomiocitos y del tejido miocárdico es muy probable que constituyan un aspecto significativo del desarrollo de patologías cardiacas que desencadenan como evento final su progresión hacia falla cardiaca. El estrés oxidativo es un tema común en la fisiopatología de la cardiomiopatía isquémica y no isquémica. Patologías cardiacas como la falla cardiaca son usualmente precedidas de hipertrofia cardiaca secundaria, al menos en parte, a la generación de especies reactivas del oxígeno en los cardiomiocitos. Varios son los mecanismos implicados en la remodelación ventricular y progresión de la falla cardiaca que dependen de alteraciones homeostáticas en los sistemas que generan estrés oxidativo y/o nitrosativo. La discusión se centra en la reciente evidencia derivada de investigaciones llevadas a cabo tanto in vitro en cardiomiocitos cultivados como in vivo en modelos experimentales de patologías cardiacas. Las implicaciones clínicas de los recientes descubrimientos aunque son muy prometedoras para la terapéutica de la falla cardiaca, aun no han logrado trasladarse con total éxito a la práctica clínica en los ensayos clínicos realizados hasta el momento (Acta Med Colomb 2010; 2010; 35: 82-95.Objective: to review the molecular mechanisms of oxidative and nitrosative stress in the process of ventricular remodeling and the pathophysiology of heart failure. Metodology: a Medline (PubMed search was performed using the keywords: oxidative stress, ventricular remodeling, heart failure, nitrosative stress. Cited bibliography in key papers from renowned authors in this field of research was also examined. Results: 112 articles were selected as the most relevant regarding the several systems of oxidative stress production in the cardiovascular system in addition to their relevance to the pathophysiology of heart failure. Conclusions: the stress responses of cardiomyocytes and the myocardial tissue as a whole are likely to constitute a significant aspect of the development of cardiac pathologies. Oxidative stress is a common theme in the pathophysiology of ischemic and non-ischemic cardiomyopathy. Cardiac pathologies such as heart failure are usually preceded by cardiac hypertrophy secondary, at least in part, to the generation of reactive oxygen species in cardiomyocytes. Several mechanisms have been implicated in ventricular remodeling during heart failure progression which depends on homeostatic alterations in oxidative and nitrosative stress. The discussion is centered in the exposition of recent evidence from research carried out either in vitro in cultured cardiomyocytes as well as from in vivo models of experimental cardiac pathologies. The clinical implications of this novel understanding, although very promising for the therapeutic treatment of heart failure, up until now, have failed to translate with total success to the clinical practice in several clinical trials (Acta Med Colomb 2010; 2010; 35: 82-95.

  13. Paradigmas y paradojas de la hipertrofia ventricular izquierda: desde el laboratorio de investigación a la consulta clínica / Paradigms and paradoxes of left ventricular hypertrophy: from the research laboratory to the clinical consultation

    Scientific Electronic Library Online (English)

    Eduardo Manuel, Escudero; Oscar Andrés, Pinilla.

    2007-09-01

    Full Text Available La hipertrofia ventricular es considerada un mecanismo de adaptación del corazón ante diferentes sobrecargas; estas sobrecargas pueden generar a través de los mecanismos intracelulares utilizados distintas respuestas que se asocien o no con compromiso funcional del miocardio. Cuando la hipertrofia s [...] e acompaña de disfunción ventricular pudiendo ser el inicio de un proceso que conduce a la insuficiencia cardíaca, se pone en duda si ese mecanismo es realmente una adecuada adaptación a la sobrecarga. Analizando las modificaciones estructurales y funcionales del ventrículo izquierdo encontradas en ratas secundarias a hipertensión arterial, reducción del diámetro de la aorta ascendente, administración de isoproterenol y/o a infarto de miocardio y en pacientes hipertensos, con estenosis aórtica y con miocardio-patía hipertrófica se puede inferir la presencia de un mecanismo no adecuado de adaptación. Por el contrario las diferentes características de la respuesta ventricular ante la sobrecarga provocada por ejercicio o por el embarazo en humanos señalan una verdadera adaptación a la sobrecarga. En un verdadero desafío a lo conocido sería correcto especular con la necesidad de estimular el desarrollo de hipertrofia fisiológica en determinadas situaciones patológicas o llegar a modificar la respuesta patológica en fisiológica. Abstract in english Cardiac hypertrophy can occur as an adaptative response to increased cardiac workload. Different types of cardiac hypertrophy arise from a combination of genetic, physiologic, and environmental factors. When hypertophic growth of the heart leads to left ventricular dysfunction and heart failure, the [...] response is considered as maladaptive or pathological hypertrophy. After analyzed left ventricular functional and structural changes in rats induced by arterial hypertension, banding of aortic root, isoproterenol administration, or myocardial infarction, as well as in patients with arterial hypertension, aortic stenosis, or hypertrophic miocardiopathy, we found a maladaptive response considered as pathological hypertrophy. However, the adaptation of the left ventricle, found in response to physical activity or to pregnancy in humans, seems to help the heart adapt to the increase in workload acting as physiological hypertrophy. These considerations allow us to speculate for the use of future interventions to stimulate the development of physiological hypertrophy in several pathological situations or to change a pathological into a physiological response.

  14. 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 (

  15. Quantitative estimation of right ventricular hypertrophy using ECG criteria in patients with pulmonary hypertension: A comparison with cardiac MRI.

    Science.gov (United States)

    Blyth, Kevin G; Kinsella, James; Hakacova, Nina; McLure, Lindsey E; Siddiqui, Adeel M; Wagner, Galen S; Peacock, Andrew J

    2011-01-01

    In patients with pulmonary arterial hypertension (PAH), right ventricular mass (RVM) correlates linearly with pulmonary artery pressure, and decreases with successful treatment. Accurate measurement of RVM currently requires cardiovascular magnetic resonance (CMR) imaging. We therefore tested the relationship between RVM and a simple, 12 lead ECG-derived value, the Butler-Leggett (BL) score. This has previously been validated in patients with RV hypertrophy (RVH) due to mitral stenosis. We also tested the diagnostic accuracy of the BL score in detecting RVH. The Scottish Pulmonary Vascular Unit database was reviewed retrospectively. Twenty-eight patients with PAH were identified, in whom CMR and ECG data had been recorded no more than 28 days apart. All had completed a comprehensive clinical assessment, including right heart catheterization. CMR-derived absolute RVM and RV mass index (RVMI=RV mass/LV mass) were correlated against BL score. The ability of this score to detect RVH was tested using 2 x 2 contingency tables. RVM and RVMI correlated with BL score (r=0.77, P0.7 mV proved a highly specific but insensitive indicator of RVH, based on either absolute RVM (sensitivity 74%, specificity 100%) or a high RVMI (sensitivity 61%, specificity 100%). The BL score, which can be defined using a standard 12-lead ECG, correlates with RVM and RVMI in patients with PAH. A score >0.7 mV was a highly specific but insensitive indicator of RVH in these patients. PMID:22530102

  16. Effect of antihypertensive therapy based on new method of individual choice of drugs on left ventricular hypertrophy in elderly patients

    Directory of Open Access Journals (Sweden)

    K.I. Pshenichkin

    2007-01-01

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

  17. Myocardial perfusion in type 2 diabetes with left ventricular hypertrophy: normalisation by acute angiotensin-converting enzyme inhibition

    International Nuclear Information System (INIS)

    The purpose of this study was to assess whether acute angiotensin-converting enzyme (ACE) inhibition would improve myocardial perfusion and perfusion reserve in a subpopulation of normotensive patients with diabetes and left ventricular hypertrophy (LVH), both independent risk factors of coronary disease. Using positron emission tomography (PET), we investigated the response of regional myocardial perfusion to acute ACE inhibition with i.v. infusion of perindoprilat (vs saline infusion as control, minimum interval 3 days) in 12 diabetic patients with LVH. Myocardial perfusion was quantified with PET using nitrogen-13 ammonia infused at rest and during dipyridamole hyperaemia. Twelve healthy control subjects were included in the study, five of whom were also studied with perindoprilat. Mean blood pressure in normo-albuminuric, asymptomatic patients was 123±7/65±9 mmHg. Compared with controls, maximal perfusion was reduced in patients (1.8±0.6 vs 2.5±1.0 ml min-1 g-1; P-1 g-1, P<0.01). In the five control subjects both resting and hyperaemic perfusion remained unchanged during perindoprilat infusion. It is concluded that acute ACE inhibition with perindoprilat improves maximal achieved myocardial perfusion in non-hypertensive patients with diabetes and LVH. (orig.)

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

    Directory of Open Access Journals (Sweden)

    K. I. Pshenichkin

    2015-12-01

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

  19. 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 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.

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

    Directory of Open Access Journals (Sweden)

    Massimo Chiariello

    2010-05-01

    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.

  1. La hipertrofia ventricular izquierda no siempre revierte con el descenso de la presión arterial / Left ventricular hypertrophy not always reverts with the decrease in blood pressure / A hipertrofia ventricular esquerda nem sempre reverte com a diminuição da pressão arterial

    Scientific Electronic Library Online (English)

    Daniel, Piskorz; Alicia, Tommasi.

    2010-03-01

    Full Text Available Introdução. Em pacientes hipertensos considera-se que uma queda nos valores da pressão arterial é necessária para atingir a regressão da lesão em órgãos-alvo. O objetivo deste estudo é determinar o efeito obtido com a diminuição da pressão arterial em pacientes hipertensos arteriais na hipertrofia v [...] entricular esquerda em uma clínica especializada. Material e métodos. Os pacientes hipertensos na primeira consulta, segundo definição da IV Guias da Federação Argentina de Cardiologia, com hipertrofia ventricular esquerda diagnosticada pelo método ecocardiográfico de Devereux, considerando sua presença com um índice de massa ventricular esquerda igual ou superior a 110 g/m² em mulheres e 125 g/m², em homens, divididos em dois grupos: 1) a pressão arterial controlada: menos de 140 - 90 mm Hg ou inferior a 130 - 80 mm Hg em pacientes de alto risco, os pacientes com nefropatia diabética ou portadores de doença isquêmica do coração no final do seguimento, 2) pressão arterial não controlada: acima dos valores estabelecidos no final do seguimento. Aplicou-se na análise estadística o teste t de Student, considerando-se significância estatística p Abstract in spanish Introducción. En pacientes hipertensos se considera que el descenso de las cifras de presión arterial logra la regresión del daño en órgano blanco. El objetivo del presente estudio es determinar el efecto que se obtiene con el descenso de la presión arterial en pacientes hipertensos arteriales sobre [...] la hipertrofia ventricular izquierda en un consultorio especializado. Material y métodos. Pacientes hipertensos en primera consulta según definición de las IV Guías de la Federación Argentina de Cardiología, con hipertrofia ventricular izquierda diagnosticada en ecocardiografía por método de Devereux, considerándose su presencia con un índice de masa ventricular izquierda mayor o igual a 110 gramos/m² en las mujeres y 125 gramos/m² en los hombres; divididos en dos grupos: 1) presión arterial controlada: menor a 140-90 mm Hg o menor a 130-80 mm Hg en pacientes de alto riesgo, diabéticos, nefrópatas o portadores de cardiopatía isquémica al final del seguimiento; 2) presión arterial no controlada: por encima de las cifras enunciadas al final del seguimiento. En el análisis estadístico, se aplicó test t de students, considerándose significación estadística p Abstract in english Background. In hypertensive patients it is considered that a fall in blood pressure values is necessary to achieve the regression of target organ damage. The aim of this study is to determine the effect obtained with decreasing blood pressure in hypertensive patients on left ventricular hypertrophy [...] in a specialized clinic. Methods. Hypertensive patients at first consultation as defined by Argentina Cardiology Federation Guides IV, with left ventricular hypertrophy diagnosed by echocardiographic method of Devereux, considering its presence with a left ventricular mass index equal or greater than 110 g/m² in women and 125 g/m² in men, divided into two groups: 1) controlled blood pressure: less than 140 - 90 mm Hg or lower than 130 - 80 mm Hg in high risk patients, patients with diabetic nephropathy or ischemic heart disease carriers at end of follow up, 2) uncontrolled blood pressure: above the values set out at the end of follow up. In statistical analysis t students test was applied, considering statistical significance p

  2. Relationship of left ventricular systolic function to persistence or development of electrocardiographic left ventricular hypertrophy in hypertensive patients : implications for the development of new heart failure

    DEFF Research Database (Denmark)

    Okin, Peter M; Wachtell, Kristian

    2014-01-01

    BACKGROUND: Persistence or development of ECG left ventricular hypertrophy (LVH) by Cornell product criteria is associated with an increased risk of developing heart failure compared with regression or continued absence of LVH. We postulated that this association might be in part mediated via worse left ventricular systolic function in patients with new or persistent ECG LVH. METHODS: Baseline and year-3 ECG LVH and left ventricular midwall shortening (MWS) were examined in 725 hypertensive patients in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) echocardiographic substudy. Sex-specific criteria were used for abnormal MWS (<14% in men and <16% in women) and abnormal stress-corrected MWS (scMWS; <87% in men and <90% in women). Cornell product LVH greater than 2440?mm ms defined ECG LVH. RESULTS: Between baseline and year-3 follow-up, there was continued absence or regression of ECG LVH in 427 patients and persistence or development of new LVH in 298 patients. At baseline, although there were no significant differences in the mean values of MWS and scMWS, patients with persistence or development of ECG LVH at year 3 had significantly higher baseline prevalences of abnormal MWS (41.9 vs. 30.2%, P?=?0.001) and abnormal scMWS (27.4 vs. 20.5%, P?=?0.034). At year-3 follow-up, persistence or development of new LVH was associated with significantly lower mean MWS (16.5?±?2.3 vs. 17.2?±?1.9%, P?ventricular systolic dysfunction after 3 years' follow-up. These findings provide insight into a possible mechanism by which changes in ECG LVH are associated with the changing risk of developing heart failure. CLINICAL TRIALS REGISTRATION: http://clinicaltrials.gov/ct/show/NCT00338260?order=1.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1981-01-01

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

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

    International Nuclear Information System (INIS)

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

  5. Relationship between intracellular pH and proton mobility in rat and guinea-pig ventricular myocytes.

    OpenAIRE

    Swietach, P; Vaughan-Jones, RD

    2005-01-01

    Intracellular H+ ion mobility in eukaryotic cells is low because of intracellular buffering. We have investigated whether Hi+ mobility varies with pHi. A dual microperfusion apparatus was used to expose guinea-pig or rat myocytes to small localized doses (3-5 mm) of ammonium chloride (applied in Hepes-buffered solution). Intracellular pH (pHi) was monitored confocally using the fluorescent dye, carboxy-SNARF-1. Local ammonium exposure produced a stable, longitudinal pHi gradient. Its size was...

  6. CB1 cannabinoid receptor antagonist attenuates left ventricular hypertrophy and Akt-mediated cardiac fibrosis in experimental uremia.

    Science.gov (United States)

    Lin, Chih-Yuan; Hsu, Yu-Juei; Hsu, Shih-Che; Chen, Ying; Lee, Herng-Sheng; Lin, Shih-Hua; Huang, Shih-Ming; Tsai, Chien-Sung; Shih, Chun-Che

    2015-08-01

    Cannabinoid receptor type 1 (CB1R) plays an important role in the development of myocardial hypertrophy and fibrosis-2 pathological features of uremic cardiomyopathy. However, it remains unknown whether CB1R is involved in the pathogenesis of uremic cardiomyopathy. Here, we aimed to elucidate the role of CB1R in the development of uremic cardiomyopathy via modulation of Akt signalling. The heart size and myocardial fibrosis were evaluated by echocardiography and immunohistochemical staining, respectively, in 5/6 nephrectomy chronic kidney disease (CKD) mice treated with a CB1R antagonist. CB1R and fibrosis marker expression levels were determined by immunoblotting in H9c2 cells exposed to the uremic toxin indoxyl sulfate (IS), with an organic anion transporter 1 inhibitor or a CB1R antagonist or agonist. Akt phosphorylation was also assessed to examine the signaling pathways downstream of CB1R activation induced by IS in H9c2 cells. CKD mice exhibited marked left ventricular hypertrophy and myocardial fibrosis, which were reversed by treatment with the CB1R antagonist. CB1R, collagen I, transforming growth factor (TGF)-?, and ?-smooth muscle actin (SMA) expression showed time- and dose-dependent upregulation in H9c2 cells treated with IS. The inhibition of CB1R by either CB1R antagonist or small interfering RNA-mediated knockdown attenuated the expression of collagen I, TGF-?, and ?-SMA in IS-treated H9c2 cells, while Akt phosphorylation was enhanced by CB1R agonist and abrogated by CB1R antagonist in these cells. In summary, we conclude that CB1R blockade attenuates LVH and Akt-mediated cardiac fibrosis in a CKD mouse model. Uremic toxin IS stimulates the expression of CB1R and fibrotic markers and CB1R inhibition exerts anti-fibrotic effects via modulation of Akt signaling in H9c2 myofibroblasts. Therefore, the development of drugs targeting CB1R may have therapeutic potential in the treatment of uremic cardiomyopathy. PMID:26093151

  7. Myocardial perfusion in type 2 diabetes with left ventricular hypertrophy: normalisation by acute angiotensin-converting enzyme inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Hesse, Birger; Meyer, Christian; Hove, Jens D.; Holm, Soeren; Kofoed, Klaus F. [Department of Clinical Physiology and Nuclear Medicine, KF 4011, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100, Copenhagen (Denmark); Nielsen, Flemming S.; Sato, Asako; Parving, Hans-Henrik [Steno Diabetes Center, Gentofte (Denmark); Bang, Lia E.; Svendsen, Tage L. [Department of Internal Medicine, Naestved County Hospital (Denmark); Opie, Lionel H. [Department of Medicine, Cape Heart Center, University of Cape Town (South Africa)

    2004-03-01

    The purpose of this study was to assess whether acute angiotensin-converting enzyme (ACE) inhibition would improve myocardial perfusion and perfusion reserve in a subpopulation of normotensive patients with diabetes and left ventricular hypertrophy (LVH), both independent risk factors of coronary disease. Using positron emission tomography (PET), we investigated the response of regional myocardial perfusion to acute ACE inhibition with i.v. infusion of perindoprilat (vs saline infusion as control, minimum interval 3 days) in 12 diabetic patients with LVH. Myocardial perfusion was quantified with PET using nitrogen-13 ammonia infused at rest and during dipyridamole hyperaemia. Twelve healthy control subjects were included in the study, five of whom were also studied with perindoprilat. Mean blood pressure in normo-albuminuric, asymptomatic patients was 123{+-}7/65{+-}9 mmHg. Compared with controls, maximal perfusion was reduced in patients (1.8{+-}0.6 vs 2.5{+-}1.0 ml min{sup -1} g{sup -1}; P<0.05), and perfusion reserve was also lower, at borderline significance (2.7{+-}1.0 vs 3.6{+-}1.3; P=0.059). During perindoprilat infusion, myocardial perfusion reserve in patients increased to 3.9{+-}0.9 (P<0.001) due to normalisation of maximal perfusion (2.3{+-}0.5 ml min{sup -1} g{sup -1}, P<0.01). In the five control subjects both resting and hyperaemic perfusion remained unchanged during perindoprilat infusion. It is concluded that acute ACE inhibition with perindoprilat improves maximal achieved myocardial perfusion in non-hypertensive patients with diabetes and LVH. (orig.)

  8. 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

  9. 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.

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

    Scientific Electronic Library Online (English)

    Cléber do Lago, Mazzaro; Francisco de Assis, Costa; Maria Teresa Nogueira, Bombig; Bráulio, Luna Filho; Ângelo Amato Vincenzo de, Paola; Antonio Carlos de Camargo, Carvalho; William da, Costa; Francisco Antonio Helfenstein, Fonseca; Rui Manoel dos Santos, Póvoa.

    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 eletrocardiog [...] ráfico 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. Abstract in english 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 e [...] lectrocardiographic 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.

  11. Inhibition of the isoproterenol-induced net 45Ca uptake into the total heart of the rat in left ventricular hypertrophy due to aortic constriction

    International Nuclear Information System (INIS)

    The increase of the transmembranary Ca++ inflow is the decisive initial reaction for the cardio-action of ?-adrenergic catecholamines. For example, a single subcutaneous application of 1 mg isoproterenol/kg increases the net 45Ca uptake into the rat heart to 3 or 4 times the normal value. With experimentally induced left ventricular hypertrophy, however, the ?-adrenergic reactivity of the whole rat heart decreases substantially about three weeks after the coarctation of the aorta. This is indicated by the strong inhibition of the net 45Ca uptake by the myocardium under the influence of isoproterenol, not only in the hypertrophic left ventricle but also in the non-hypertrophic right ventricle. The reduction of the ?-adrenergic stimulation is thus not a direct effect of fibrons hypertrophy but rather a more general side-effect which may be due to a lasting increase in the sympathicotonus under stress. (orig./AK)

  12. 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.

  13. Effect of endothelin antagonism on contractility, intracellular calcium regulation and calcium regulatory protein expression in right ventricular hypertrophy of the rat.

    Science.gov (United States)

    Stessel, Heike; Brunner, Friedrich

    2004-01-01

    We have documented the effects of long-term endothelin receptor antagonism on intracellular Ca2+ regulation and Ca2+ regulatory protein expression in rat hearts with right ventricular hypertrophy without signs of heart failure. Rats were given either a single injection of monocrotaline (50 mg/kg, n=9) resulting in pulmonary hypertension-induced myocardial hypertrophy, or monocrotaline followed by daily administration of the endothelin subtype-A receptor antagonist 2-benzo(1,3)dioxol-5-yl-3-benzyl-4-(4-methoxy-phenyl-)-4-oxobut-2-enoate-Na (PD 155080, 50 mg/kg) over 9 weeks (n=8). Hearts from saline-injected rats served as controls (n=9). Monocrotaline-treated animals developed marked right-sided hypertrophy without fibrosis as evident from hydroxyproline measurements, systolic contractility was increased, fully compensating for the increased afterload, but diastolic function was impaired as evident from protracted relaxation and slowed diastolic intracellular Ca2+ handling (measured by aequorin bioluminescence). In hypertrophic hearts, quantitative immunoblotting analyses showed increased levels both of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) and phosphorylated phospholamban, along with decreased levels of total phospholamban, which is in line with strengthened right ventricular systolic function. PD 155080 reversed abnormalities in Ca2+ handling, although SERCA and phospholamban protein levels were not altered (P=not significant versus monocrotaline group). Thus, endothelin-A receptor antagonism attenuates right ventricular remodeling and improves myocardial Ca2+ handling, but has no discernable effect on elevated expression of SERCA and phospholamban observed in hypertrophic hearts. These data indicate that the hypotensive action of PD 155080 is independent of its effects, if any, on SERCA and its regulation. PMID:14725613

  14. Membrane segregation in atrioventricular nodal myocytes of the golden hamster (Mesocricetus auratus). A cytochemical study using filipin and tomatine.

    OpenAIRE

    J.N. Skepper

    1989-01-01

    The membrane systems of hamster general atrial and ventricular myocytes were studied and their reactivity with the sterol probes, filipin and tomatine, compared with that of atrioventricular nodal myocytes. The sarcolemma of atrial and atrioventricular nodal myocytes was considerably more reactive to sterol probes than the sarcolemma of general ventricular myocytes. Atrial myocyte sarcolemma was also more reactive than previously reported in rat atrial myocytes. Particle-free regions of annul...

  15. MicroRNA-27a Regulates Beta Cardiac Myosin Heavy Chain Gene Expression by Targeting Thyroid Hormone Receptor ?1 in Neonatal Rat Ventricular Myocytes?

    Science.gov (United States)

    Nishi, Hitoo; Ono, Koh; Horie, Takahiro; Nagao, Kazuya; Kinoshita, Minako; Kuwabara, Yasuhide; Watanabe, Shin; Takaya, Tomohide; Tamaki, Yodo; Takanabe-Mori, Rieko; Wada, Hiromichi; Hasegawa, Koji; Iwanaga, Yoshitaka; Kawamura, Teruhisa; Kita, Toru; Kimura, Takeshi

    2011-01-01

    MicroRNAs (miRNAs), small noncoding RNAs, are negative regulators of gene expression and play important roles in gene regulation in the heart. To examine the role of miRNAs in the expression of the two isoforms of the cardiac myosin heavy chain (MHC) gene, ?- and ?-MHC, which regulate cardiac contractility, endogenous miRNAs were downregulated in neonatal rat ventricular myocytes (NRVMs) using lentivirus-mediated small interfering RNA (siRNA) against Dicer, an essential enzyme for miRNA biosynthesis, and MHC expression levels were examined. As a result, Dicer siRNA could downregulate endogenous miRNAs simultaneously and the ?-MHC gene but not ?-MHC, which implied that specific miRNAs could upregulate the ?-MHC gene. Among 19 selected miRNAs, miR-27a was found to most strongly upregulate the ?-MHC gene but not ?-MHC. Moreover, ?-MHC protein was downregulated by silencing of endogenous miR-27a. Through a bioinformatics screening using TargetScan, we identified thyroid hormone receptor ?1 (TR?1), which negatively regulates ?-MHC transcription, as a target of miR-27a. Moreover, miR-27a was demonstrated to modulate ?-MHC gene regulation via thyroid hormone signaling and to be upregulated during the differentiation of mouse embryonic stem (ES) cells or in hypertrophic hearts in association with ?-MHC gene upregulation. These findings suggested that miR-27a regulates ?-MHC gene expression by targeting TR?1 in cardiomyocytes. PMID:21149577

  16. 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.

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

    Directory of Open Access Journals (Sweden)

    Yang Xiaomin

    2015-01-01

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

  18. [Diagnostic value of a two-dimensional echocardiographic score for left ventricular hypertrophy validated by the Imatron CT scan in familial hypertrophic cardiomyopathy].

    Science.gov (United States)

    Forissier, J F; Charron, P; du Montcel, S Tézenas; Hagège, A; Richard, P; Desnos, M; Schwartz, K; Mousseaux, E; Komajda, M; Dubourg, O

    2006-10-01

    The aim of this study was to validate a two-dimensional echocardiographic score for left ventricular hypertrophy in familial hypertrophic cardiomyopathy (HCM) by fast CT scan and to study the diagnostic value by an indexed threshold value in affected and genotyped families in comparison with the classical diagnostic method of maximal wall thickness (E max). The study was performed successively in two patient groups with HCM. The echo/CT scan population comprised 26 patients. They underwent echocardiography and Imatron CT scanning. The E max and 2D echo score (sum of the thickness of 4 segments) were measured by echocardiography and compared to the left ventricular mass obtained by the CT method. The 2D echo score was closely correlated to the CT left ventricular mass (r = 0.85) with a higher correlation coefficient than the E max (r = 0.78). The echo/generic population comprised 109 genotyped adults with an identified mutation. The E max and 2D echo score were measured. The genotype was the reference for diagnosis. A theoretical value of the 2D echo score was determined in healthy individuals by a multiple linear regression model of ages, sex and body surface area. A threshold value for abnormality was established after analysis of the ROC. The sensitivity and specificity were 63% and 100% respectively for E max and 73% and 96% respectively for the indexed 2D echo score. The improvement in sensitivity was marked in young adults (< 50 years) with 69% for the indexed 2D echo score versus 54% for E max, p < 0.04. The authors conclude that the indexed 2D score has been validated as an index of hypertrophy by the Imatron CT and has a better diagnostic value than E max, especially in young adults. This echocardiographic criterion could be proposed as an alternative diagnostic sign for screening families. PMID:17100137

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

    Directory of Open Access Journals (Sweden)

    Bassani R.A.

    2003-01-01

    Full Text Available 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 estimate 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.

  20. 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.

    2003-12-01

    Full Text Available 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-07-01

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

  2. 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.

  3. 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.

  4. Post-mortem evidence of idiopathic left ventricular hypertrophy and idiopathic interstitial myocardial fibrosis: is exercise the cause?

    OpenAIRE

    Whyte, Gregory; Sheppard, Mary; GEORGE, Keith; Shave, Robert; Prasad, Sanjay; O’Hanlon, Rory; Sharma, Sanjay

    2009-01-01

    We report the case of an experienced, highly trained marathon runner who died suddenly while running. On post-mortem examination, left ventricle hypertrophy and idiopathic interstitial myocardial fibrosis was found. We believe that life-long, repetitive bouts of arduous physical activity resulted in fibrous replacement of the myocardium, causing a pathological substrate for the propagation of fatal arrhythmias.

  5. Effect of glycemic control on the progress of left ventricular hypertrophy and diastolic dysfunction in children with type I diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Soha M. Abd El Dayem

    2012-09-01

    Full Text Available Objective: To evaluate progression of left ventricular (LV structural and functional changes in patients with type 1 diabetes and effect of glycemic control on these changes. Methods: A prospective, longitudinal study consisted of 48 patients who were originally studied. At two years follow-up, 44 patients were reevaluated, 35 patients from the original study were reevaluated after another 2 years for the 3rd time using the same protocol. The control group comprised 30 age-and sex-matched healthy volunteers. All studied patients were subjected to full history taking, clinical and cardiac examination. M-mode echocardiography was done, blood samples were taken and examined for HbA1c and urine samples were tested for the presence of albuminuria. ANOVA for repeated measurements, t-test for dependent and independent variables, and Mann-Whitney U test were used for statistical analyses. Results: Seven (14.6% of our patients had LV hypertrophy, 23 (47.9% patients had diastolic dysfunction and ten patients only achieve improvement in glycemic control. Duration of diabetes was significantly higher in patients with LV hypertrophy (LVH (p<0.05. Patients with no improvement in glycemic control had a significant increase in interventricular septum (IVS and left ventricular posterior wall (LVPW in the third examination (p<0.05 for both. Conclusion: Prevalence of LVH and diastolic dysfunction among diabetic patients is high. Glycemic control in diabetic patients could not improve LVH or diastolic dysfunction. On the other hand, failure to achieve glycemic control leads to deterioration in structural parameters.

  6. Correlation of heart rate variability with cardiac functional and metabolic variables in cyclists with training induced left ventricular hypertrophy

    OpenAIRE

    Pluim, B; Swenne, C; Zwinderman, A; Maan, A.; van der Laarse, A.; Doornbos, J; van der Wall, E.E.

    1999-01-01

    OBJECTIVE—To examine the correlation between heart rate variability and left ventricular mass in cyclists with an athlete's heart.?METHODS—Left ventricular mass and diastolic function were determined at rest and myocardial high energy phosphates were quantified at rest and during atropine-dobutamine stress in 12 male cyclists and 10 control subjects, using magnetic resonance techniques. Ambulatory 24 hour ECG recordings were obtained, and time and frequency domain heart rate variability indic...

  7. 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 Grant ostatní: GA MZd NT14301 Institutional support: RVO:61388998 Keywords : calcium efflux * calcium buffers * cardiac myocyte * computer model Subject RIV: BO - Biophysics Impact factor: 1.579, year: 2014

  8. Electrophysiological effect and the gating mechanism of astragaloside IV on L-type Ca(2+) channels of guinea-pig ventricular myocytes.

    Science.gov (United States)

    Zhao, Meimi; Shao, Dongxue; Yu, Lifeng; Sun, Xuefei; Wang, Yan; Hu, Huiyuan; Feng, Rui; Gao, Qinghua; Guo, Feng; Hao, Liying

    2015-08-01

    Astragaloside IV (AS-IV) is one of the main active ingredients of Astragalus membranaceus. This study is aimed to investigate AS-IV?s effects on Ca(2+) channel activity of single cardiomyocytes and single Ca(2+) channels. Whole-cell Ca(2+) currents in freshly dissociated cardiomyocytes were measured using the whole-cell patch-clamp technique. Single Ca(2+) channel currents were examined in cell-attached patches and inside-out patches. In the whole-cell recording, AS-IV reduced the amplitude of L-type Ca(2+) currents (ICaL) in a concentration-dependent manner. Although AS-IV did not alter the steady-state activation curves, the voltage dependence of the current inactivation curves was negatively shifted by AS-IV in a concentration dependent manner. Consistent with the results of the whole-cell recording, in the inside-out configuration the ensemble average of single Ba(2+) current via L-type Ca(2+) channel was dose-dependently reduced by AS-IV. The reduction of unitary Ba(2+) current at 0.1 or 1 µM AS-IV was accounted for a decrease in the channel activity (NPo). In addition to the decrease in NPo, there was a reduction of Po without a change in channel number or an apparent change in single channel current. Furthermore, we found that the open-closed kinetics of the channel were affected by AS-IV. AS-IV induced the shift of L-type Ca(2+) channels from either brief openings (mode 1) or long-lasting openings (mode 2) to no active opening (mode 0). Our results suggest that AS-IV blocks the currents through Ca(2+) channels in guinea-pig ventricular myocytes by affecting the open-closed kinetics of L-type Ca(2+) channels to inhibit the channel activities. This study could provide theoretical basis for the drug exploiting of the monomer of Astragalus membranaceus. PMID:25891370

  9. 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)

    Ginefra Paulo

    2003-01-01

    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.

  10. 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 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

  11. Propolis and swimming in the prevention of atherogenesis and left ventricular hypertrophy in hypercholesterolemic mice / Própolis e natação na prevenção da aterogênese e hipertrofia ventricular esquerda de camundongos hipercolesterolêmicos

    Scientific Electronic Library Online (English)

    DB., Silva; AP., Miranda; DB., Silva; LRB., D`Angelo; BB., Rosa; EA., Soares; JGDC., Ramalho; MFG., Boriollo; JAD., Garcia.

    2015-05-01

    Full Text Available Objetivos O presente estudo verificou o efeito do própolis associação ou não com a natação na dislipidemia, na hipertrofia ventricular esquerda e aterogênese de camundongos hipercolesterolêmicos. Métodos e Resultados Os experimentos foram realizados em camundongos LDLr–/–, alimentados com dieta hip [...] erlipídica por 75 dias, e divididos em quatro grupos experimentais (n = 10): HL, sedentários, foram submetidos ao estresse aquático (5 min por dia, cinco vezes por semana); NAT foram submetidos a um protocolo de natação (1 hora por dia, cinco vezes por semana) a partir do 16° dia do experimento; PRO, sedentários, submetidos a estresse aquático e que receberam extrato de própolis oral (70 uL / animal / dia) a partir do 16° dia do experimento; HL + NAC + PRO, submetidos a natação e que recebeu a própolis, como descrito acima. Após 75 dias, foi coletado sangue para análise do perfil lipídico. Calculou-se a relação entre o peso ventricular (mg) e o peso do animal (g). Os cortes histológicos do coração e aorta foram processados imunohistoquímicamente com anticorpos anti-CD40L para avaliar o processo inflamatório, corados com hematoxilina / eosina e picrossírius red, para avaliar as alterações morfológicas e morfométricas. Os camundongos HL apresentaram dislipidemia grave, aterogênese e hipertrofia do ventrículo esquerdo, associada a uma diminuição dos níveis plasmáticos de HDLc e o desenvolvimento subsequente do processo inflamatório cardiovasculares, caracterizada pelo aumento da expressão do CD40L no ventrículo esquerdo e na aorta. Natação e a própolis isolado e \\ ou associados preveniram a HVE, a aterogênese e a inflamação tanto na artéria quanto no ventrículo, diminuindo a expressão de CD40L, aumentando os níveis plasmáticos de HDLc. Conclusão A Própolis isolada ou associada a uma atividade física regular é benéfica na proteção cardiovascular através da ação anti-inflamatória. Abstract in english Aims The present study verified the effect of propolis alone and its association with swimming in dyslipidemia, left ventricular hypertrophy and atherogenesis of hypercholesterolemic mice. Methods and Results The experiments were performed in LDLr–/– mice, fed with high fat diet for 75 days, and we [...] re divided into four experimental groups (n=10): HL, sedentary, subjected to aquatic stress (5 min per day, 5 times per week); NAT submitted to a swimming protocol (1 hour per day, 5 times per week) from the 16th day of the experiment; PRO, sedentary, submitted to aquatic stress and which received oral propolis extract (70 uL/animal/day) from the 16th day of the experiment; HL+NAT+PRO, submitted to swimming and which received propolis as described above. After 75 days, blood was collected for analysis of serum lipids. The ratio between the ventricular weight (mg) and the animal weight (g) was calculated. Histological sections of the heart and aorta were processed immunohistochemically with anti-CD40L antibodies to evaluate the inflammatory process; stained with hematoxylin/eosin and picrosirius red to assess morphological and morphometric alterations. The HL animals showed severe dyslipidemia, atherogenesis and left ventricular hypertrophy, associated with a decrease in serum HDLc levels and subsequent development of cardiovascular inflammatory process, characterized by increased expression of CD40L in the left ventricle and aorta. Swimming and propolis alone and\\or associated prevented the LVH, atherogenesis and arterial and ventricular inflammation, decreasing the CD40L expression and increasing the HDLc plasmatic levels. Conclusion Propolis alone or associated with a regular physical activity is beneficial in cardiovascular protection through anti-inflammatory action.

  12. Left ventricular diastolic dysfunction in Nrf2 knock out mice is associated with cardiac hypertrophy, decreased expression of SERCA2a, and preserved endothelial function.

    Science.gov (United States)

    Erkens, Ralf; Kramer, Christian M; Lückstädt, Wiebke; Panknin, Christina; Krause, Lisann; Weidenbach, Mathias; Dirzka, Jennifer; Krenz, Thomas; Mergia, Evanthia; Suvorava, Tatsiana; Kelm, Malte; Cortese-Krott, Miriam M

    2015-12-01

    Increased production of reactive oxygen species and failure of the antioxidant defense system are considered to play a central role in the pathogenesis of cardiovascular disease. The transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a key master switch controlling the expression of antioxidant and protective enzymes, and was proposed to participate in protection of vascular and cardiac function. This study was undertaken to analyze cardiac and vascular phenotype of mice lacking Nrf2. We found that Nrf2 knock out (Nrf2 KO) mice have a left ventricular (LV) diastolic dysfunction, characterized by prolonged E wave deceleration time, relaxation time and total diastolic time, increased E/A ratio and myocardial performance index, as assessed by echocardiography. LV dysfunction in Nrf2 KO mice was associated with cardiac hypertrophy, and a downregulation of the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a) in the myocardium. Accordingly, cardiac relaxation was impaired, as demonstrated by decreased responses to ?-adrenergic stimulation by isoproterenol ex vivo, and to the cardiac glycoside ouabain in vivo. Surprisingly, we found that vascular endothelial function and endothelial nitric oxide synthase (eNOS)-mediated vascular responses were fully preserved, blood pressure was decreased, and eNOS was upregulated in the aorta and the heart of Nrf2 KO mice. Taken together, these results show that LV dysfunction in Nrf2 KO mice is mainly associated with cardiac hypertrophy and downregulation of SERCA2a, and is independent from changes in coronary vascular function or systemic hemodynamics, which are preserved by a compensatory upregulation of eNOS. These data provide new insights into how Nrf2 expression/function impacts the cardiovascular system. PMID:26475037

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

    Directory of Open Access Journals (Sweden)

    Trimarchi Francesco

    2006-02-01

    Full Text Available 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%, pituitary inflammation 5.5%, cranio-pharyngioma 3.7%, not identified pathogenesis 14.8% were enrolled. To minimize any possible interferences of BMI on the aim of this study, the control group included 20 age- and weight-matched healthy subjects. The LV geometry was identified by the relationship between LVMi (cut-off 125 g/m2 and relative wall thickness (cut-off 0.45 at echocardiography. Results There was no significant between-group difference in resting cardiac morphology and function, nor when considering age-related discrepancy. The majority of patients had normal-low LVM/LVMi, but about one fourth of them showed higher values. These findings correlated to relatively high circulating IGF-1 and systolic blood pressure at rest. The main LV geometric pattern was eccentric hypertrophy in 22% of GHD population (26% of with severe GHD and in 15% of controls (p = NS. Conclusion Though the lack of significant differences in resting LV morphology and function, about 25% of GHD patients showed high LVMi (consisting of eccentric hypertrophy, not dissimilarly to overweight controls. This finding, which prognostic role is well known in obese and hypertensive patients, is worthy to be investigated in GHD patients through wider controlled trials.

  14. 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

  15. Developmental changes in gene expression of Epac and its upregulation in myocardial hypertrophy.

    Science.gov (United States)

    Ulucan, Coskun; Wang, Xu; Baljinnyam, Erdene; Bai, Yunzhe; Okumura, Satoshi; Sato, Motohiko; Minamisawa, Susumu; Hirotani, Shinichi; Ishikawa, Yoshihiro

    2007-09-01

    Although it has been shown that Epac1 mRNA is expressed ubiquitously and Epac2 mRNA predominantly in the brain and endocrine tissues, developmental and pathophysiological changes of these molecules have not been characterized. Developmental changes were analyzed in murine heart, brain, kidneys, and lungs by RT-PCR analysis, which revealed more drastic developmental changes of Epac2 mRNA than Epac1. Only the Epac2 mRNA in kidney showed a transient expression pattern with dramatic decline into adulthood. In addition to developmental changes, we found that Epac gene expression was upregulated in myocardial hypertrophy induced by chronic isoproterenol infusion or pressure overload by transverse aortic banding. Both Epac1 and Epac2 mRNA were upregulated in isoproterenol-induced left ventricular hypertrophy, whereas only Epac1 was increased in pressure overload-induced hypertrophy. Stimulation of H9c2, cardiac myoblast cells, with fetal calf serum, which can induce myocyte hypertrophy, upregulated Epac1 protein expression. We also demonstrated that Epac was the limiting moiety, relative to Rap, in the Epac-Rap signaling pathway in terms of stoichiometry and that Epac stimulation led to the activation of ERK1/2. Our data suggest the functional involvement of Epac in organogenesis and also in physiological as well as pathophysiological processes, such as cardiac hypertrophy. Furthermore, our results suggest the importance of the stoichiometry of Epac over that of Rap in cellular biological effects. PMID:17557924

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

    Scientific Electronic Library Online (English)

    Antonio Carlos, Cicogna; Kathleen G., Robinson; Chester H., Conrad; Robin, Squire; Marina P., Okoshi; Oscar H. L., Bing.

    1997-12-01

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

  17. 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.

  18. 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.

  19. Fatores e mecanismos envolvidos na hipertrofia ventricular esquerda e o papel anti-hipertrófico do óxido nítrico / Factors and mechanisms involved in left ventricular hypertrophy and the anti-hypertrophic role of nitric oxide

    Scientific Electronic Library Online (English)

    José Antonio Dias, Garcia; Erika Kristina, Incerpi.

    2008-06-01

    Full Text Available A hipertrofia ventricular esquerda (HVE) ocorre em reposta à sobrecarga hemodinâmica relatada em várias condições fisiológicas e patológicas. Entretanto, ainda não está completamente elucidado se o estímulo primário para a hipertrofia é o estiramento mecânico do coração, fatores neuro-humorais, ou m [...] esmo a interação de ambos. Esses fatores são traduzidos no interior da célula como alterações bioquímicas que levam à ativação de segundos (citosólicos) e terceiros (nucleares) mensageiros que irão agir no núcleo da célula, regulando a transcrição, e finalmente determinarão a expressão gênica que induza HVE. A HVE é caracterizada por alterações estruturais decorrentes do aumento das dimensões dos cardiomiócitos, da proliferação do tecido conjuntivo intersticial e da rarefação da microcirculação coronariana. Nos últimos anos, o óxido nítrico (•NO) surgiu como um importante regulador do remodelamento cardíaco, especificamente reconhecido como um mediador anti-hipertrófico. Vários estudos têm demonstrado os alvos celulares, as vias de sinalização anti-hipertrófica e o papel funcional do •NO. Portanto, a HVE parece desenvolver-se em decorrência da perda do balanço entre as vias de sinalização pró e anti-hipertróficas. Esses novos conhecimentos sobre as vias de sinalização pró e anti-hipertróficas permitirão desenvolver novas estratégicas no tratamento das HVE patológicas. Abstract in english The left ventricular hypertrophy (LVH) occurs in response to the hemodynamic overload in some physiological and pathological conditions. However, it has not been completely elucidated whether the primary stimulation for the hypertrophy is the mechanical stretching of the heart, neurohumoral factors, [...] or even the interaction of both. These factors are translated inside the cell as biochemical alterations that lead to the activation of second (cytosolic) and third (nuclear) messengers that will act in the cell nucleus, regulating transcription, and will finally determine the genic expression that induces LVH. The LVH is characterized by structural alterations due to the increase in the cardiomyocyte dimensions, the proliferation of the interstitial connective tissue and the rarefaction of the coronary microcirculation. Recently, nitric oxide (•NO) has appeared as an important regulator of cardiac remodeling, specifically recognized as an anti-hypertrophic mediator. Some studies have demonstrated the cellular targets, the anti-hypertrophic signaling pathways and the functional role of •NO. Thus, the LVH seems to develop as a result of the loss of the balance between the pro and the anti-hypertrophic signaling pathways. This new knowledge about the pro and anti-hypertrophic signaling pathways will allow the development of new strategies in the treatment of pathological LVH.

  20. 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.

  1. 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

  2. Polydatin attenuates cardiac hypertrophy through modulation of cardiac Ca2+ handling and calcineurin-NFAT signaling pathway.

    Science.gov (United States)

    Ding, Wenwen; Dong, Ming; Deng, Jianxin; Yan, Dewen; Liu, Yun; Xu, Teng; Liu, Jie

    2014-09-01

    Polydatin (PD), a resveratrol glucoside extracted from the perennial herbage Polygonum cuspidatum, has been suggested to have wide cardioprotective effects. This study aimed to explore the direct antihypertrophic role of PD in cultured neonatal rat ventricular myocytes (NRVMs) and its therapeutic effects against pressure overload (PO)-induced hypertrophic remodeling and heart failure. Furthermore, we investigated the mechanisms underlying the actions of PD. Treatment of NRVMs with phenylephrine for 72 h induced myocyte hypertrophy, where the cell surface area and protein levels of atrial natriuretic peptide and ?-myosin heavy chain (?-MHC) were significantly increased. The amplitude of systolic Ca(2+) transient was increased, and sarcoplasmic reticulum Ca(2+) recycling was prolonged. Concomitantly, calcineurin activity was increased and NFAT protein was imported into the nucleus. PD treatment restored Ca(2+) handling and inhibited calcineurin-NFAT signaling, thus attenuating the hypertrophic remodeling in NRVMs. PO-induced cardiac hypertrophy was produced by transverse aortic constriction (TAC) in C57BL/6 mice, where the left ventricular posterior wall thickness and heart-to-body weight ratio were significantly increased. The cardiac function was increased at 5 wk of TAC, but significantly decreased at 13 wk of TAC. The amplitude of Ca(2+) transient and calcineurin activity were increased at 5 wk of TAC. PD treatment largely abolished TAC-induced hypertrophic remodeling by inhibiting the Ca(2+)-calcineurin pathway. Surprisingly, PD did not inhibit myocyte contractility despite that the amplitude of Ca(2+) transient was decreased. The cardiac function remained intact at 13 wk of TAC. In conclusion, PD is beneficial against PO-induced cardiac hypertrophy and heart failure largely through inhibiting the Ca(2+)-calcineurin pathway without compromising cardiac contractility. PMID:25015961

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

    International Nuclear Information System (INIS)

    Exercise ECG and myocardial single-photon emission tomography (SPET) are fundamental in the non-invasive evaluation of patients suspected of having coronary artery disease (CAD). The purpose of the present study was to investigate the influence of physiological left ventricular hypertrophy (LVH) on myocardial sestamibi SPET in healthy young and old athletes. Eighteen young male elite athletes (ten rowers, five power/weight lifters and three triathletes) and 14 well-trained elderly rowers were studied. All underwent a bicycle test as part of a 2-day sestamibi SPET protocol. Attenuation correction was not performed. The studies were evaluated visually and quantitatively analysed by the CEqual program with its reference files and with a file from a local non-athletic age-matched population. Echocardiographic LVH was an inclusion criterion in the young athletes. Exercise ECG was normal in all subjects. In at least three of the young athletes a reversible defect was observed by visual analysis. On quantitative analysis one-third of the young athletes had ''significant'' (>10 pixels) defects compared with both the local reference base and the CEqual reference population. Nearly all defects were found in the anterior or inferior wall. The remaining subjects, including all old rowers, had normal SPET findings. Anterior and inferior wall defects are so common in healthy athletes with physiological LVH that the specificity of myocardial SPET, in contrast to exercise ECG, seems to be too low for evaluation of chest pain in this group. The mechanism of anterior and inferior defects may be related to hot spots (papillary muscles?) in the lateral wall. The specificity of SPET is maintained in athletes without LVH. (orig.)

  4. Attenuation of compensatory right ventricular hypertrophy and heart failure following monocrotaline-induced pulmonary vascular injury by the Na+-H+ exchange inhibitor cariporide.

    Science.gov (United States)

    Chen, L; Gan, X T; Haist, J V; Feng, Q; Lu, X; Chakrabarti, S; Karmazyn, M

    2001-08-01

    Pulmonary hypertension results in compensatory right ventricular (RV) hypertrophy. We studied the role of the Na+-H+ exchange (NHE) in the latter process by determining the effect of the NHE-1 inhibitor cariporide after monocrotaline-induced pulmonary artery injury. Sprague-Dawley rats received a control or cariporide diet for 7 days, at which time they were administered either monocrotaline (60 mg/kg) or its vehicle. Twenty-one days later, monocrotaline control, but not cariporide-fed animals, demonstrated increased RV weights and cell size of 65 and 52%, respectively. Monocrotaline alone significantly increased RV systolic pressure and end diastolic pressure by 70 and 94%, respectively, whereas corresponding values with cariporide were significantly reduced to 33 and 42%. Central venous pressure increased by 414% in control animals, which was significantly reduced by cariporide. Monocrotaline treatment produced a decrease in cardiac output of 28 and 8% in the absence or presence of cariporide (P monocrotaline-treated groups compared with vehicle treatment, with cariporide the net gain in body weight was twice that seen in the monocrotaline-treated animals without cariporide. Monocrotaline also increased RV NHE-1 and atrial natriuretic peptide mRNA expression, which was abrogated by cariporide. Monocrotaline-induced myocardial necrosis, fibrosis, and mononuclear infiltration was completely prevented by cariporide. Cariporide had no effect on monocrotaline-induced pulmonary intimal wall thickening. Our results demonstrate that cariporide directly attenuates myocardial dysfunction after monocrotaline administration independent of pulmonary vascular effects. NHE-1 inhibition may represent an effective adjunctive therapy that selectively targets myocardial hypertrophic responses in pulmonary vascular injury. PMID:11454907

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

    DEFF Research Database (Denmark)

    Molina, C.E.; Gesser, Hans; Llach, A.; Tort, L.; Hove-Madsen, L.

    2007-01-01

    Application of the current-clamp technique in rainbow trout atrial myocytes has yielded resting membrane potentials that are incompatible with normal atrial function. To investigate this paradox, we recorded the whole membrane current (Im) and compared membrane potentials recorded in isolated cardiac myocytes and multicellular preparations. Atrial tissue and ventricular myocytes had stable resting potentials of -87 ± 2 mV and -83.9 ± 0.4 mV, respectively. In contrast, 50 out of 59 atrial myocyte...

  6. Isoproterenol-induced myocardial fibrosis in relation to myocyte necrosis

    International Nuclear Information System (INIS)

    Treatment of rats with the beta-adrenergic agonist isoproterenol results in cardiac hypertrophy, myocyte necrosis, and interstitial cell fibrosis. Our objectives in this study have been to examine whether hypertrophy and fibrosis occur in a compensatory and reparative response to myocyte loss or whether either process may be occurring independently of myocyte loss and thus be a reactive response to adrenergic hormone stimulation. We have examined this question by evaluating each of these responses in rats treated with different doses and forms of isoproterenol administration. Myocyte necrosis was evaluated using in vivo labeling with monoclonal antimyosin for identification of myocytes with permeable sarcolemma, which was indicative of irreversible injury. Myocardial fibrosis was evaluated by morphometric point counting of Gomori-stained tissue sections and by assessment of the stimulation of fibroblast proliferation by determination of increased levels of DNA synthesis. Stimulation of fibroblast DNA synthesis was determined from DNA specific radioactivities and radioautography after pulse labeling with [3H]thymidine. The evidence provided by this study suggests that the degree and timing of myocardial hypertrophy does not follow the course of myocyte loss and, thus, appears to be either a response to altered cardiac loading or a reactive response to beta-adrenergic hormone stimulation rather than a compensation for myocyte loss. Myocardial fibrosis, on the other hand, appears to be more closely related to myocyte necrosis with respect to collagen accumulation in the same areas of the heart, its dose-response relation to the amount of isoproterenol administered, and the timing of increased DNA synthesis, or fibroblast proliferation, after myocyte loss

  7. 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.

  8. 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.

  9. 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 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

  10. 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

  11. 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 ...

  12. Beat?to?Beat Spatiotemporal Variability in the T Vector Is Associated With Sudden Cardiac Death in Participants Without Left Ventricular Hypertrophy: The Atherosclerosis Risk in Communities (ARIC) Study

    Science.gov (United States)

    Waks, Jonathan W.; Soliman, Elsayed Z.; Henrikson, Charles A.; Sotoodehnia, Nona; Han, Lichy; Agarwal, Sunil K.; Arking, Dan E.; Siscovick, David S.; Solomon, Scott D.; Post, Wendy S.; Josephson, Mark E.; Coresh, Josef; Tereshchenko, Larisa G.

    2015-01-01

    Background Despite advances in prevention and treatment of cardiovascular disease, sudden cardiac death (SCD) remains a clinical challenge. Risk stratification in the general population is needed. Methods and Results Beat?to?beat spatiotemporal variability in the T vector was measured as the mean angle between consecutive T?wave vectors (mean TT? angle) on standard 12?lead ECGs in 14 024 participants in the Atherosclerosis Risk in Communities (ARIC) study. Subjects with left ventricular hypertrophy, atrial arrhythmias, frequent ectopy, ventricular pacing, or QRS duration ?120 ms were excluded. The mean spatial TT? angle was 5.21±3.55°. During a median of 14 years of follow?up, 235 SCDs occurred (1.24 per 1000 person?years). After adjustment for demographics, coronary heart disease risk factors, and known ECG markers for SCD, mean TT? angle was independently associated with SCD (hazard ratio 1.089; 95% CI 1.044 to 1.137; P90th percentile (>9.57°) was associated with a 2?fold increase in the hazard for SCD (hazard ratio 2.01; 95% CI 1.28 to 3.16; P=0.002). In a subgroup of patients with T?vector amplitude ?0.2 mV, the association with SCD was almost twice as strong (hazard ratio 3.92; 95% CI 1.91 to 8.05; P<0.0001). A significant interaction between mean TT? angle and age was found: TT? angle was associated with SCD in participants aged <55 years (hazard ratio 1.096; 95% CI 0.043 to 1.152; P<0.0001) but not in participants aged ?55 years (Pinteraction=0.009). Conclusions In a large, prospective, community?based cohort of left ventricular hypertrophy–free participants, increased beat?to?beat spatiotemporal variability in the T vector, as assessed by increasing TT? angle, was associated with SCD. PMID:25600143

  13. Thyroid hormone improves function and Ca2+ handling in pressure overload hypertrophy. Association with increased sarcoplasmic reticulum Ca2+-ATPase and alpha-myosin heavy chain in rat hearts.

    OpenAIRE

    Chang, K C; Figueredo, V M; Schreur, J H; Kariya, K; Weiner, M.W.; Simpson, P C; Camacho, S A

    1997-01-01

    We asked whether thyroid hormone (T4) would improve heart function in left ventricular hypertrophy (LVH) induced by pressure overload (aortic banding). After banding for 10-22 wk, rats were treated with T4 or saline for 10-14 d. Isovolumic LV pressure and cytosolic [Ca2+] (indo-1) were assessed in perfused hearts. Sarcoplasmic reticulum Ca2+-ATPase (SERCA), phospholamban, and alpha- and beta-myosin heavy chain (MHC) proteins were assayed in homogenates of myocytes isolated from the same heart...

  14. Quality Metrics for Stem Cell-Derived Cardiac Myocytes

    Directory of Open Access Journals (Sweden)

    Sean P. Sheehy

    2014-03-01

    Full Text Available Advances in stem cell manufacturing methods have made it possible to produce stem cell-derived cardiac myocytes at industrial scales for in vitro muscle physiology research purposes. Although FDA-mandated quality assurance metrics address safety issues in the manufacture of stem cell-based products, no standardized guidelines currently exist for the evaluation of stem cell-derived myocyte functionality. As a result, it is unclear whether the various stem cell-derived myocyte cell lines on the market perform similarly, or whether any of them accurately recapitulate the characteristics of native cardiac myocytes. We propose a multiparametric quality assessment rubric in which genetic, structural, electrophysiological, and contractile measurements are coupled with comparison against values for these measurements that are representative of the ventricular myocyte phenotype. We demonstrated this procedure using commercially available, mass-produced murine embryonic stem cell- and induced pluripotent stem cell-derived myocytes compared with a neonatal mouse ventricular myocyte target phenotype in coupled in vitro assays.

  15. Enhanced G?q signaling: A common pathway mediates cardiac hypertrophy and apoptotic heart failure

    OpenAIRE

    Adams, John W.; Sakata, Yoshihito; Davis, Michael G.; Sah, Valerie P.; Wang, Yibin; Liggett, Stephen B; Chien, Kenneth R; Brown, Joan Heller; Dorn, Gerald W., II

    1998-01-01

    Receptor-mediated Gq signaling promotes hypertrophic growth of cultured neonatal rat cardiac myocytes and is postulated to transduce in vivo cardiac pressure overload hypertrophy. Although initially compensatory, hypertrophy can proceed by unknown mechanisms to cardiac failure. We used adenoviral infection and transgenic overexpression of the alpha subunit of Gq to autonomously activate Gq signaling in cardiomyocytes. In cultured cardiac myocytes, overexpression of wild-type G?q resulted in h...

  16. 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 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.

  17. A state of reversible compensated ventricular dysfunction precedes pathological remodelling in response to cardiomyocyte-specific activity of angiotensin II type-1 receptor in mice.

    Science.gov (United States)

    Frentzou, Georgia A; Drinkhill, Mark J; Turner, Neil A; Ball, Stephen G; Ainscough, Justin F X

    2015-08-01

    Cardiac dysfunction is commonly associated with high-blood-pressure-induced cardiomyocyte hypertrophy, in response to aberrant renin-angiotensin system (RAS) activity. Ensuing pathological remodelling promotes cardiomyocyte death and cardiac fibroblast activation, leading to cardiac fibrosis. The initiating cellular mechanisms that underlie this progressive disease are poorly understood. We previously reported a conditional mouse model in which a human angiotensin II type-I receptor transgene (HART) was expressed in differentiated cardiomyocytes after they had fully matured, but not during development. Twelve-month-old HART mice exhibited ventricular dysfunction and cardiomyocyte hypertrophy with interstitial fibrosis following full receptor stimulation, without affecting blood pressure. Here, we show that chronic HART activity in young adult mice causes ventricular dysfunction without hypertrophy, fibrosis or cardiomyocyte death. Dysfunction correlated with reduced expression of pro-hypertrophy markers and increased expression of pro-angiogenic markers in the cardiomyocytes experiencing increased receptor load. This stimulates responsive changes in closely associated non-myocyte cells, including the downregulation of pro-angiogenic genes, a dampened inflammatory response and upregulation of Tgf?. Importantly, this state of compensated dysfunction was reversible. Furthermore, increased stimulation of the receptors on the cardiomyocytes caused a switch in the secondary response from the non-myocyte cells. Progressive cardiac remodelling was stimulated through hypertrophy and death of individual cardiomyocytes, with infiltration, proliferation and activation of fibroblast and inflammatory cells, leading to increased angiogenic and inflammatory signalling. Together, these data demonstrate that a state of pre-hypertrophic compensated dysfunction can exist in affected individuals before common markers of heart disease are detectable. The data also suggest that there is an initial response from the housekeeping cells of the heart to signals emanating from distressed neighbouring cardiomyocytes to suppress those changes most commonly associated with progressive heart disease. We suggest that the reversible nature of this state of compensated dysfunction presents an ideal window of opportunity for personalised therapeutic intervention. PMID:26092119

  18. 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

  19. 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

  20. Systolic left ventricular function according to left ventricular concentricity and dilatation in hypertensive patients : the Losartan Intervention For Endpoint reduction in hypertension study

    DEFF Research Database (Denmark)

    Bang, Casper; Gerdts, Eva

    2013-01-01

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

  1. Characterization of myocardial deformation in patients with different etiologies of left ventricular hypertrophy by using strain distribution from Magnetic Resonance Imaging

    OpenAIRE

    Piella Fenoy, Gemma; De Craene, Mathieu; Bijnens B.H.; Tobón Gómez, Catalina, 1981-; Huguet, Marina; Avegliano, G.; Frangi Caregnato, Alejandro

    2010-01-01

    Introducción y objetivos. Se ha señalado que, en la miocardiopatía hipertrófica (MCH), la desorganización de las fibras regionales da lugar a segmentos en los que la deformación es nula o está gravemente reducida, y que estos segmentos tienen una distribución no uniforme en el ventrículo izquierdo (VI). Esto contrasta con lo observado en otros tipos de hipertrofia como en el corazón de atleta o la hipertrofia ventricular izquierda hipertensiva (HVI-HT), en los que puede haber una deformación ...

  2. 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 concentr...

  3. [Myocardial hypertrophy and arterial hypertension].

    Science.gov (United States)

    Trevi, G; Sheiban, I; Gorni, R

    1995-10-01

    Myocardial hypertrophy in different cardiac diseases is considered to be an adaptive mechanism to the increase of hemodynamic load which might restore to normal radius/wall thickness ratio and consequently to normalize wall stress. However, it has been widely demonstrated that beside the hemodynamic load, other factors contribute to the development of myocardial hypertrophy. It has been shown that in hypertensive patients, functional abnormalities (increased contribution of atrial systole to total diastolic filling, increased isovolumic relaxation period, prolonged diastolic duration, slowed ventricular filling and altered diastolic distensibility) precede the development of myocardial hypertrophy. Thus, in hypertensive patients, sign and symptoms of heart failure could be manifested in absence of myocardial hypertrophy, and might be exclusively due to diastolic dysfunction (with normal systolic function). Systolic function might be involved and compromised late when focal myocardial cell death and fibrosis occur and consequently ¿adequate¿ hypertrophy is shifted to ¿inadequate¿. This evolution is accompanied by morphological and functional changes of the myocardium similar to those encountered in dilated cardiomyopathy. Impairment of systolic function in ¿inadequate¿ hypertrophy is also due to structural changes; altered ratio between sarcomers and mitochondria, increased intercapillary distance, sarcoplasmatic reticulum dysfunction, increase of collagene component with a consequent increment of wall rigidity, hypertrophy of arterial tunica media, which alters coronary flow and coronary reserve. The progression of these morpho-functional abnormalities is a very slow process, in which adaptive mechanism mediated by several enzymes and contractile protein, contribute to maintain myocardial viability. However, over the long course, disseminated focal myocardial cell necrosis and fibrosis, which is an evolving process, is considered to be the main responsible factor for the irreversible myocardial damage and systolic dysfunction in advanced myocardial inadequate hypertrophy. PMID:8682229

  4. Small-conductance Ca2+-activated K+ current is upregulated via the phosphorylation of CaMKII in cardiac hypertrophy from spontaneously hypertensive rats.

    Science.gov (United States)

    Mizukami, Kazuya; Yokoshiki, Hisashi; Mitsuyama, Hirofumi; Watanabe, Masaya; Tenma, Taro; Takada, Shingo; Tsutsui, Hiroyuki

    2015-09-15

    Left ventricular hypertrophy is associated with an increased risk of ventricular arrhythmias. However, the underlying molecular basis is poorly understood. It has been reported that small-conductance Ca(2+)-activated K(+) (SK) channels are involved in the pathogenesis of ventricular arrhythmias in heart failure. The present study aimed to test the hypothesis that SK channel activity is increased via the Ca(2+)/calmodulin-dependent protein kinase II (CaMKII)-dependent pathway in hypertensive cardiac hypertrophy. Normotensive Wistar-Kyoto (WKY) rats and spontaneous hypertensive rats (SHRs) were used. Whole cell membrane currents were recorded in isolated ventricular myocytes by the patch-clamp method, and apamin-sensitive K(+) current (IKAS), which is inhibited by apamin (100 nM), an SK channel blocker, was evaluated. IKAS at 40 mV was present in SHRs, whereas it was hardly detectable in WKY rats (0.579 ± 0.046 vs. 0.022 ± 0.062 pA/pF, both n = 6, P apamin prolonged the late phase of repolarization only in SHRs. Western blot analysis of SK channel protein isoforms demonstrated that SK2 was significantly increased in SHRs compared with WKY rats (SK2/GAPDH: 0.66 ± 0.07 vs. 0.40 ± 0.02, both n = 6, P < 0.05), whereas SK1 and SK3 did not differ between groups. In addition, autophosphorylated CaMKII was significantly increased in SHRs (phosphorylated CaMKII/GAPDH: 0.80 ± 0.06 vs. 0.58 ± 0.06, both n = 6, P < 0.05) despite a comparable total amount of CaMKII between groups. In conclusion, SK channels are upregulated via the enhanced activation of CaMKII in cardiac hypertrophy in SHRs. PMID:26297230

  5. 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.

  6. 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 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

  7. Frecuencia y factores de riesgo de la hipertrofia ventricular izquierda como marcador de daño cardiovascular en el trasplante renal Frequency and risk factors of the left ventricular hypertrophy like scoreboard of cardiovascular damage in renal transplant

    Directory of Open Access Journals (Sweden)

    Gerardo Borroto Díaz

    2012-06-01

    Full Text Available Introducción: las complicaciones cardiovasculares son frecuentes y constituyen la principal causa de muerte en los pacientes con trasplantes renales, su alta incidencia está dada por múltiples factores de riesgo. Objetivos: determinar la frecuencia de la hipertrofia del ventrículo izquierdo como marcador de daño cardiovascular, y los factores de riesgo que facilitarían su aparición. Métodos: se hizo un estudio prospectivo, de corte transversal y de tipo casos y controles, a 70 enfermos con trasplantes renales a los cuales se les realizó un ecocardiograma convencional para determinar la presencia o no de hipertrofia del ventrículo izquierdo y se relacionó, mediante un estudio univariado y multivariado (regresión logística, con factores de riesgo cardiovascular. Resultados: las afecciones cardiovasculares constituyeron la segunda causa de pérdida de los pacientes en este estudio (33,1 %, La hipertrofia del ventrículo izquierdo se encontró en 45 (64 % de los enfermos pesquisados. La dislipemia, el uso de la ciclosporina A y la disfunción del injerto, fueron las complicaciones que constituyeron, tanto en el estudio univariado como multivariado (factor independiente, p Introduction: the cardiovascular complications are frequent and are the leading cause of death in patients underwent renal transplantation and its high incidence is due to multiple risk factors. Objectives: to determine the frequency of the left ventricle hypertrophy as a marker of cardiovascular damage and the risk factors leading to its appearance. Methods: a case-control, cross-sectional and prospective study was conducted in 70 patients with renal transplantations and underwent a conventional echocardiogram to determine the presence or not of left ventricle hypertrophy and it was related to cardiovascular risk factors by means of a univariate and multivariate study (logistic regression with cardiovascular risk factors. Results: the cardiovascular affections were the second cause of loss of patients in present study (33,1%. The left ventricle hypertrophy was found in the 45 (64 % of screened patients. The dyslipidemia, the use of A cyclosporine and the graft dysfunction, were the complications in the univariate and the multivariate study (independent factor , p < 0,05, the conditional favoring the existence of left ventricle hypertrophy, assertions that are the research conclusions.

  8. Cardiac pressure overload hypertrophy is differentially regulated by ?-adrenergic receptor subtypes

    OpenAIRE

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

    2011-01-01

    In isolated myocytes, hypertrophy induced by norepinephrine is mediated via ?1-adrenergic receptors (ARs) and not ?-ARs. However, mice with deletions of both major cardiac ?1-ARs still develop hypertrophy in response to pressure overload. Our purpose was to better define the role of ?-AR subtypes in regulating cardiac hypertrophy in vivo, important given the widespread clinical use of ?-AR antagonists and the likelihood that patients treated with these agents could develop conditions of furth...

  9. 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; Marc B. Hershenson; 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...

  10. Collagen network remodelling and diastolic stiffness of the rat left ventricle with pressure overload hypertrophy.

    Science.gov (United States)

    Doering, C W; Jalil, J E; Janicki, J S; Pick, R; Aghili, S; Abrahams, C; Weber, K T

    1988-10-01

    This study had two objectives: (a) to determine the accumulation of collagen and its structural remodelling in the hypertrophied rat left ventricle after 4 and 8 weeks of abdominal aorta banding; and (b) to correlate these findings with the diastolic stress-strain relation of the intact myocardium. In comparison to age and sex matched controls, the collagen volume fraction of the hypertrophied myocardium after 4 and 8 weeks of aortic banding increased significantly from 3.5(SD1.0)% to 7.8(4.2)% and 6.2(2.0)% respectively. This accumulation of collagen, or fibrosis, occurred in the absence of myocyte necrosis. Scanning electron microscopy showed increased density and thickness of the collagen weave and tendons. At 4 weeks, light microscopy showed interstitial oedema and disrupted collagen fibrils. Left ventricular diastolic stress-strain relations of both pressure overload groups were significantly steeper than that of the control group. Thus the response of the interstitium to the hypertrophic process that accompanies abdominal aorta banding is a complex process that includes a structural remodelling of the fibrillar collagen matrix and the early appearance of interstitial oedema, each of which may contribute to a rise in the passive stiffness of the intact myocardium. PMID:2978464

  11. Frecuencia y factores de riesgo de la hipertrofia ventricular izquierda como marcador de daño cardiovascular en el trasplante renal / Frequency and risk factors of the left ventricular hypertrophy like scoreboard of cardiovascular damage in renal transplant

    Scientific Electronic Library Online (English)

    Gerardo, Borroto Díaz; Haruka, Tsuno López; Oyantay, Mérida Álvarez; Carlos, Guerrero Díaz; Malicela, Barceló Acosta.

    2012-06-01

    Full Text Available Introducción: las complicaciones cardiovasculares son frecuentes y constituyen la principal causa de muerte en los pacientes con trasplantes renales, su alta incidencia está dada por múltiples factores de riesgo. Objetivos: determinar la frecuencia de la hipertrofia del ventrículo izquierdo como mar [...] cador de daño cardiovascular, y los factores de riesgo que facilitarían su aparición. Métodos: se hizo un estudio prospectivo, de corte transversal y de tipo casos y controles, a 70 enfermos con trasplantes renales a los cuales se les realizó un ecocardiograma convencional para determinar la presencia o no de hipertrofia del ventrículo izquierdo y se relacionó, mediante un estudio univariado y multivariado (regresión logística), con factores de riesgo cardiovascular. Resultados: las afecciones cardiovasculares constituyeron la segunda causa de pérdida de los pacientes en este estudio (33,1 %), La hipertrofia del ventrículo izquierdo se encontró en 45 (64 %) de los enfermos pesquisados. La dislipemia, el uso de la ciclosporina A y la disfunción del injerto, fueron las complicaciones que constituyeron, tanto en el estudio univariado como multivariado (factor independiente), p Abstract in english Introduction: the cardiovascular complications are frequent and are the leading cause of death in patients underwent renal transplantation and its high incidence is due to multiple risk factors. Objectives: to determine the frequency of the left ventricle hypertrophy as a marker of cardiovascular da [...] mage and the risk factors leading to its appearance. Methods: a case-control, cross-sectional and prospective study was conducted in 70 patients with renal transplantations and underwent a conventional echocardiogram to determine the presence or not of left ventricle hypertrophy and it was related to cardiovascular risk factors by means of a univariate and multivariate study (logistic regression) with cardiovascular risk factors. Results: the cardiovascular affections were the second cause of loss of patients in present study (33,1%). The left ventricle hypertrophy was found in the 45 (64 %) of screened patients. The dyslipidemia, the use of A cyclosporine and the graft dysfunction, were the complications in the univariate and the multivariate study (independent factor) , p

  12. 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

  13. Apoptosis and the systolic dysfunction in congestive heart failure. Story of apoptosis interruptus and zombie myocytes.

    Science.gov (United States)

    Narula, J; Arbustini, E; Chandrashekhar, Y; Schwaiger, M

    2001-02-01

    Although previously it was believed that apoptosis could not occur in the terminally differentiated tissue, such as adult heart muscle cells, recent studies in endomyocardial biopsies from patients with dilated cardiomyopathy and in explanted hearts from patients with end-stage heart failure undergoing cardiac transplantation have demonstrated histologic evidence of apoptosis. Whereas neurohormonal activation during heart failure leads to compensatory hemodynamic alterations, coupled with ventricular dilatation, it induces transcription factors and myocyte hypertrophy. Persistent growth stimulation in terminally differentiated cells may lead paradoxically to apoptotic cell death. The apoptosis in cardiomyopathic hearts is associated with cytochrome c release from mitochondria to cytoplasm and activation of proteolytic caspase-8 and -3. Although the caspases are duly processed, the fragmentation of the nuclear proteins (including DNA) is completed less frequently, and only a variable degree of fragmentation of cytoplasmic proteins (including contractile proteins) is observed. It is hypothesized that release of cytochrome c from mitochondria should interfere with energy production and lead to functional impairment and variable loss of contractile proteins in a living heart muscle cell should contribute to systolic dysfunction. Because a nuclear blueprint is retained, however, the dysfunctional cell may continue to exist and in favorable conditions, such as with LVAD support, the apoptotic process may subside. Potential feasibility of reversal of heart failure should renew efforts to develop more targeted pharmaceutical intervention within the apoptotic cascade and allow newer paradigm for the management of heart failure. PMID:11787805

  14. ?-Adrenergic Receptor Stimulation Induces Endoplasmic Reticulum Stress in Adult Cardiac Myocytes: Role in Apoptosis

    OpenAIRE

    Dalal, Suman; Foster, Cerrone R.; Das, Bhudev C.; Singh, Mahipal; Singh, Krishna

    2012-01-01

    Accumulation of misfolded proteins and alterations in calcium homeostasis induces endoplasmic reticulum (ER) stress, leading to apoptosis. Here we tested the hypothesis that ?-AR stimulation induces ER stress, and induction of ER stress plays a pro-apoptotic role in cardiac myocytes. Using thapsigargin and brefeldin A, we demonstrate that ER stress induces apoptosis in adult rat ventricular myocytes (ARVMs). ?-AR-stimulation (isoproterenol; 3h) significantly increased expression of ER stress ...

  15. Chronic Akt blockade aggravates pathological hypertrophy and inhibits physiological hypertrophy.

    Science.gov (United States)

    Buss, Sebastian J; Riffel, Johannes H; Malekar, Pratima; Hagenmueller, Marco; Asel, Christina; Zhang, Min; Weiss, Celine; Katus, Hugo A; Hardt, Stefan E

    2012-01-01

    The attenuation of adverse myocardial remodeling and pathological left ventricular (LV) hypertrophy is one of the hallmarks for improving the prognosis after myocardial infarction (MI). The protein kinase Akt plays a central role in regulating cardiac hypertrophy, but the in vivo effects of chronic pharmacological inhibition of Akt are unknown. We investigated the effect of chronic Akt blockade with deguelin on the development of pathological [MI and aortic banding (AB)] and physiological (controlled treadmill running) hypertrophy. Primary cardiomyocyte cultures were incubated with 10 ?mol deguelin for 48 h, and Wistar rats were treated orally with deguelin (4.0 mg·kg(-1)·day(-1)) for 4 wk starting 1 day after the induction of MI or AB. Exercise-trained animals received deguelin for 4 wk during the training period. In vitro, we observed reduced phosphorylation of Akt and glycogen synthase kinase (GSK)-3? after an incubation with deguelin, whereas MAPK signaling was not significantly affected. In vivo, treatment with deguelin led to attenuated phosphorylation of Akt and GSK-3? 4 wk after MI. These animals showed significantly increased heart weights and impaired LV function with increased end-diastolic diameters (12.0 ± 0.3 vs. 11.1 ± 0.3 mm, P deguelin-treated MI animals was increased compared with the vehicle-treated group. Four wk after AB, we observed an augmentation of pathological hypertrophy in the deguelin-treated group with a significant increase in heart weights and cardiomyocyte sizes (>20%, P deguelin treatment in exercise-trained animals. In conclusion, chronic Akt blockade with deguelin aggravates adverse myocardial remodeling and antagonizes physiological hypertrophy. PMID:22058151

  16. 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 rate...

  17. Differential Myocyte Responses in Patients with Cardiac Transthyretin Amyloidosis and Light-Chain Amyloidosis: A Cardiac MR Imaging Study.

    Science.gov (United States)

    Fontana, Marianna; Banypersad, Sanjay M; Treibel, Thomas A; Abdel-Gadir, Amna; Maestrini, Viviana; Lane, Thirusha; Gilbertson, Janet A; Hutt, David F; Lachmann, Helen J; Whelan, Carol J; Wechalekar, Ashutosh D; Herrey, Anna S; Gillmore, Julian D; Hawkins, Philip N; Moon, James C

    2015-11-01

    Purpose To investigate cardiac magnetic resonance (MR) imaging measurements of extracellular volume (ECV) and total cell volume in immunoglobulin light-chain amyloidosis (AL) and transthyretin amyloidosis (ATTR) in order to evaluate the amyloid and myocyte volumes. Materials and Methods All ethics were approved, and participants provided written informed consent. Of the 257 subjects who were recruited, 92 had AL (mean age, 62 years ± 10), 44 had mutant ATTR (mean age, 68 years ± 10), and 66 had wild-type ATTR (mean age, 75 years ± 7). In addition, eight healthy subjects with ATTR mutations (mean age, 47 years ± 6) and 47 healthy volunteers (mean age, 45 years ± 15) participated. All participants underwent equilibrium contrast material-enhanced cardiac MR imaging. ECV and total cell volume were measured in the heart. T test, ?(2), and one-way analysis of variance with posthoc Bonferroni correction were used. Results Both the left ventricular indexed mass and ECV were elevated in patients with amyloidosis. For left ventricular indexed mass, mean AL was 107 g/m(2) ± 30; mean mutant ATTR was 137 g/m(2) ± 29; and mean wild-type ATTR was 133 g/m(2) ± 27 versus 65 g/m(2) ± 15 in healthy subjects (P .99). The result is that, in patients with AL, all of the increase in left ventricular indexed mass is extracellular volume, whereas in patients with ATTR, the increase is extracellular, with an additional 18% increase in the intracellular space. Conclusion Quantification of ECV measures cardiac amyloid deposition in both types of amyloidosis and shows that amyloid deposition is more extensive in patients with ATTR than in those with AL; however, ATTR is associated with higher cell volume, which suggests concomitant cell hypertrophy. (©) RSNA, 2015. PMID:25997029

  18. 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 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

  19. 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 [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

  20. Integrin binding angiopoietin-1 monomers reduce cardiac hypertrophy

    OpenAIRE

    Dallabrida, Susan M.; Ismail, Nesreen S.; Pravda, Elke A; Parodi, Emily M.; Dickie, Renee; Durand, Ellen M.; Lai, Jean; Cassiola, Flavia; Rogers, Rick A.; Rupnick, Maria A.

    2008-01-01

    Angiopoietins were thought to be endothelial cell-specific via the tie2 receptor. We showed that angiopoietin-1 (ang1) also interacts with integrins on cardiac myocytes (CMs) to increase survival. Because ang1 monomers bind and activate integrins (not tie2), we determined their function in vivo. We examined monomer and multimer expressions during physiological and pathological cardiac remodeling and overexpressed ang1 monomers in phenylephrine-induced cardiac hypertrophy. Cardiac ang1 levels ...

  1. 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

  2. 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 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.

  3. Decreased Gs alpha mRNA levels accompany the fall in Gs and adenylyl cyclase activities in compensated left ventricular hypertrophy. In heart failure, only the impairment in adenylyl cyclase activation progresses.

    OpenAIRE

    CHEN L.A.; Vatner, D E; Vatner, S.F.; Hittinger, L; Homcy, C J

    1991-01-01

    We have previously reported that there is a global reduction in adenylyl cyclase associated with a decrement in Gs functional activity in cardiac sarcolemma from animals with pressure overload-induced hypertrophy and heart failure. This study was performed to determine whether hypertrophy alone in the absence of heart failure is sufficient to promote these changes and whether the superimposition of heart failure intensified these changes. Basal and stimulated adenylyl cyclase and Gs activity,...

  4. 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.

  5. Mechanisms of Disease: molecular genetics of arrhythmogenic right ventricular dysplasia/cardiomyopathy

    OpenAIRE

    Awad, Mark M; Calkins, Hugh; Judge, Daniel P.

    2008-01-01

    Arrhythmogenic right ventricular dysplasia/cardiomyopathy is an inherited cardiomyopathy estimated to affect approximately 1 in 5,000 individuals. Cardinal manifestations include right ventricular enlargement and dysfunction, fibrofatty replacement of myocytes in the right ventricle, characteristic electrocardiographic abnormalities, and ventricular arrhythmia most commonly arising from the right ventricle. The disease is frequently familial and typically involves autosomal dominant transmiss...

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

    DEFF Research Database (Denmark)

    Olsen, M H; Christensen, M K; Wachtell, K; Tuxen, Christian; Fossum, E; Bang, L E; Wiinberg, N; Devereux, R B; Kjeldsen, S E; Hildebrandt, Per; Dige-Petersen, H; Rokkedal, J; Ibsen, H

    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 ech...

  7. Parasistolia ventricular / Ventricular parasistolia

    Scientific Electronic Library Online (English)

    Antonio, Cortés-Ortiz.

    2014-03-01

    Full Text Available Se presenta el caso de un hombre de 54 años de edad con historia de un infarto del miocardio inferior antiguo y función ventricular izquierda normal, cuya atención en la consulta externa de nuestra institución se inició por palpitaciones frecuentes. El electrocardiograma mostró extrasístoles ventric [...] ulares de una morfología y en el monitoreo Holter se documentó extrasístoles ventriculares frecuentes de una morfología con periodos de acoplamiento variable y con latidos de fusión. Se concluyó la presencia de un foco parasistólico ventricular. Abstract in english We present a case of a 54 years old male who had had an inferior myocardial infarction previously, with normal ejection fraction of the left ventricle whose care in the autopatient clinic of our institution started by frequent palpitations. The electrocardiogram showed premature ventricular contract [...] ions and Holter monitoring documented frequent premature ventricular contractions with periods of variable coupling and fusion beats. It was concluded the presence of ventricular parasystole.

  8. 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

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

    OpenAIRE

    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 Lima

    2009-01-01

    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 critérios 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 4...

  10. EGCG Blocked Phenylephrin-Induced Hypertrophy in H9C2 Cardiomyocytes, by Activating AMPK-Dependent Pathway

    OpenAIRE

    Cai, Yi; Zhao, Li; Qin, Yuan; Wu, Xiao-Qian

    2015-01-01

    AMP-activated protein kinase (AMPK) is a key regulator of energy metabolism. Previous studies have shown that activation of AMPK results in suppression of cardiac myocyte hypertrophy via inhibition of the p70S6 kinase (p70S6K) and eukaryotic elongation factor-2 (eEF2) signaling pathways. Epigallocatechin-3-gallate (EGCG), the major polyphenol found in green tea, possesses multiple protective effects on the cardiovascular system including cardiac hypertrophy. However, the molecular mechanisms ...

  11. Low carbohydrate/high-fat diet attenuates cardiac hypertrophy, remodeling, and altered gene expression in hypertension

    Science.gov (United States)

    The effects of dietary fat intake on the development of left ventricular hypertrophy and accompanying structural and molecular remodeling in response to hypertension are not understood. The present study compared the effects of a high-fat versus a low-fat diet on development of left ventricular hype...

  12. Cellular Mechanism of the Nonmonotonic Dose Response of Bisphenol A in Rat Cardiac Myocytes

    Science.gov (United States)

    Liang, Qian; Gao, Xiaoqian; Chen, Yamei; Hong, Kui

    2014-01-01

    Background: The need for mechanistic understanding of nonmonotonic dose responses has been identified as one of the major data gaps in the study of bisphenol A (BPA). Previously we reported that acute exposure to BPA promotes arrhythmogenesis in female hearts through alteration of myocyte Ca2+ handling, and that the dose response of BPA was inverted U-shaped. Objective: We sought to define the cellular mechanism underlying the nonmonotonic dose response of BPA in the heart. Methods: We examined rapid effects of BPA in female rat ventricular myocytes using video-edge detection, confocal and conventional fluorescence imaging, and patch clamp. Results: The rapid effects of BPA in cardiac myocytes, as measured by multiple end points, including development of arrhythmic activities, myocyte mechanics, and Ca2+ transient, were characterized by nonmonotonic dose responses. Interestingly, the effects of BPA on individual processes of myocyte Ca2+ handling were monotonic. Over the concentration range of 10–12 to 10–6 M, BPA progressively increased sarcoplasmic reticulum (SR) Ca2+ release and Ca2+ reuptake and inhibited the L-type Ca2+ current (ICaL). These effects on myocyte Ca2+ handling were mediated by estrogen receptor (ER) ? signaling. The nonmonotonic dose responses of BPA can be accounted for by the combined effects of progressively increased SR Ca2+ reuptake/release and decreased Ca2+ influx through ICaL. Conclusion: The rapid effects of BPA on female rat cardiac myocytes are characterized by nonmonotonic dose responses as measured by multiple end points. The nonmonotonic dose response was produced by ER?-mediated monotonic effects on multiple cellular Ca2+ handling processes. This represents a distinct mechanism underlying the nonmonotonicity of BPA’s actions. Citation: Liang Q, Gao X, Chen Y, Hong K, Wang HS. 2014. Cellular mechanism of the nonmonotonic dose response of bisphenol A in rat cardiac myocytes. Environ Health Perspect 122:601–608;?http://dx.doi.org/10.1289/ehp.1307491 PMID:24569941

  13. 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.

  14. Increased Clearance of Reactive Aldehydes and Damaged Proteins in Hypertension-Induced Compensated Cardiac Hypertrophy: Impact of Exercise Training

    OpenAIRE

    Campos, Juliane Cruz; Fernandes, Tiago; Bechara, Luiz Roberto Grassmann; da Paixão, Nathalie Alves; Brum, Patricia Chakur; Oliveira, Edilamar Menezes; Ferreira, Julio Cesar Batista

    2015-01-01

    Background. We previously reported that exercise training (ET) facilitates the clearance of damaged proteins in heart failure. Here, we characterized the impact of ET on cardiac protein quality control during compensated ventricular hypertrophy in spontaneously hypertensive rats (SHR). Methods and Results. SHR were randomly assigned into sedentary and swimming-trained groups. Sedentary SHR displayed cardiac hypertrophy with preserved ventricular function compared to normotensive rats, charact...

  15. Heart-Healthy Hypertrophy

    OpenAIRE

    Trivedi, Chinmay M.; Epstein, Jonathan A

    2011-01-01

    Exercise induces growth of heart muscle cells and heart size. A new report in Cell (Boström et al., 2010) suggests that mice also respond to exercise with increased cardiac myocyte proliferation, and the molecular regulators of this pathway are linked to maladaptive and pathologic responses to cardiac stresses such as pressure overload.

  16. 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.

  17. 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 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

  18. 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

  19. A study on premature ventricular contractions caused by ultrasound exposure with microbubbles using cultured ventricular muscle cells

    International Nuclear Information System (INIS)

    It has been shown that diagnostic ultrasound examination using a contrast agent can cause premature ventricular contractions (PVCs). In this study, we investigated a usefulness of a new technique using cultured cardiac myocytes to study mechanisms of PVC production. Cardiac myocytes were isolated from neonatal rats and cultured on a cover glass. The cover glass was attached to an observation chamber in which it was possible to observe changes in myocytes during ultrasound exposure. In the experiments, cardiac myocytes were exposed to pulsed ultrasound in the presence and absence of microbubbles. The pressure amplitudes (peak-negative pressures) were set at 5 steps, -0.28, -0.55, -0.73, -0.92 and -1.1 MPa, and threshold pressure to produce a PVC was recorded. The results showed that the presence of microbubbles attached to a cell reduces threshold pressure for producing PVCs, and it was concluded that our method is useful for studying the mechanisms of PVC production

  20. A study on premature ventricular contractions caused by ultrasound exposure with microbubbles using cultured ventricular muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Kudo, N; Yokoyama, G; Ikebuchi, M; Okada, K; Kawahara, K; Yamamoto, K [Graduate School of Information Science and Technology, Hokkaido University, N14W8, Kita-ku, Sapporo, 060-8628 (Japan)

    2004-01-01

    It has been shown that diagnostic ultrasound examination using a contrast agent can cause premature ventricular contractions (PVCs). In this study, we investigated a usefulness of a new technique using cultured cardiac myocytes to study mechanisms of PVC production. Cardiac myocytes were isolated from neonatal rats and cultured on a cover glass. The cover glass was attached to an observation chamber in which it was possible to observe changes in myocytes during ultrasound exposure. In the experiments, cardiac myocytes were exposed to pulsed ultrasound in the presence and absence of microbubbles. The pressure amplitudes (peak-negative pressures) were set at 5 steps, -0.28, -0.55, -0.73, -0.92 and -1.1 MPa, and threshold pressure to produce a PVC was recorded. The results showed that the presence of microbubbles attached to a cell reduces threshold pressure for producing PVCs, and it was concluded that our method is useful for studying the mechanisms of PVC production.

  1. 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 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

  2. 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.].

  3. Uremic cardiac hypertrophy is reversed by rapamycin but not by lowering of blood pressure

    OpenAIRE

    Siedlecki, Andrew M.; JIN, XIAOHUA; Muslin, Anthony J.

    2009-01-01

    Chronic kidney disease is often complicated by uremic cardiomyopathy that consists of left ventricular hypertrophy and interstitial fibrosis. It is thought that hypertension and volume overload are major causes of this disease, but here we sought to identify additional mechanisms using a mouse model of chronic renal insufficiency. Mice with a remnant kidney developed an elevated blood urea nitrogen by 1 week, as expected, and showed progressive cardiac hypertrophy and fibrosis at 4 and 8 week...

  4. The Upper Limit of Physiological Cardiac Hypertrophy in Elite Male Athletes

    OpenAIRE

    Mohammad A. Hnidawei; Majed MjallI; Ziad Zayed

    2010-01-01

    Problem statement: Establishment of upper normal limits of physiological hypertrophy in response to physical training is important in the differentiation of physiological and pathological left ventricular hypertrophy. The goal of our study was to investigate the normal upper limits of cardiac dimensions in elite athletes in Jordan in different types of sports (8 soccer players, 8 sprinters, 8 long distance runners, 6 weight lifters, 6 body builders). Approach: A total of 3...

  5. Investigating the Mechanism of Hyperglycemia-Induced Fetal Cardiac Hypertrophy

    Science.gov (United States)

    Ma, Zheng-lai; Jia, Wei-jing; Wu, Xia; Wang, Xiao-yu; He, Mei-yao; Cheng, Xin; Li, Wei-jing; Yang, Xuesong; Liu, Guo-sheng

    2015-01-01

    Hyperglycemia in diabetic mothers enhances the risk of fetal cardiac hypertrophy during gestation. However, the mechanism of high-glucose-induced cardiac hypertrophy is not largely understood. In this study, we first demonstrated that the incidence rate of cardiac hypertrophy dramatically increased in fetuses of diabetic mothers using color ultrasound examination. In addition, human fetal cardiac hypertrophy was successfully mimicked in a streptozotocin (STZ)-induced diabetes mouse model, in which mouse cardiac hypertrophy was diagnosed using type-M ultrasound and a histological assay. PH3 immunofluorescent staining of mouse fetal hearts and in vitro-cultured H9c2 cells indicated that cell proliferation decreased in E18.5, E15.5 and E13.5 mice, and cell apoptosis in H9c2 cells increased in the presence of high glucose in a dose-dependent manner. Next, we found that the individual cardiomyocyte size increased in pre-gestational diabetes mellitus mice and in response to high glucose exposure. Meanwhile, the expression of ?-MHC and BMP-10 was up-regulated. Nkx2.5 immunofluorescent staining showed that the expression of Nkx2.5, a crucial cardiac transcription factor, was suppressed in the ventricular septum, left ventricular wall and right ventricular wall of E18.5, E15.5 and E13.5 mouse hearts. However, cardiac hypertrophy did not morphologically occur in E13.5 mouse hearts. In cultured H9c2 cells exposed to high glucose, Nkx2.5 expression decreased, as detected by both immunostaining and western blotting, and the expression of KCNE1 and Cx43 was also restricted. Taken together, alterations in cell size rather than cell proliferation or apoptosis are responsible for hyperglycemia-induced fetal cardiac hypertrophy. The aberrant expression of Nkx2.5 and its regulatory target genes in the presence of high glucose could be a principal component of pathogenesis in the development of fetal cardiac hypertrophy. PMID:26418041

  6. Cathepsin K Knockout Alleviates Pressure Overload–Induced Cardiac Hypertrophy

    OpenAIRE

    Hua, Yinan; Xu, Xihui; Shi, Guo-Ping; Chicco, Adam J; Ren, Jun; Nair, Sreejayan

    2013-01-01

    Evidence from human and animal studies has documented elevated levels of lysosomal cysteine protease cathepsin K in failing hearts. Here, we hypothesized that ablation of cathepsin K mitigates pressure overload–induced cardiac hypertrophy. Cathepsin K knockout mice and their wild-type littermates were subjected to abdominal aortic constriction, resulting in cardiac remodeling (heart weight, cardiomyocyte size, left ventricular wall thickness, and end diastolic and end systol...

  7. 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 as in diagnosing myocardial ischemia. (J.P.N.)

  8. 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 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

  9. Growth of left ventricular mass with military basic training in army recruits

    OpenAIRE

    Batterham, AM; George, KP; Birch, KM; Pennell, DJ; Myerson, SG

    2011-01-01

    Exercise-induced left ventricular hypertrophy is well documented, but whether this occurs merely in line with concomitant increases in lean body mass is unclear. PURPOSE: Our aim was to model the extent of left ventricular hypertrophy associated with increased lean body mass attributable to an exercise training program. METHODS: Cardiac and whole-body magnetic resonance imaging was performed before and after a 10-wk intensive British Army basic training program in a sample of 116 healthy Cauc...

  10. Cytoskeletal mechanics in pressure-overload cardiac hypertrophy

    Science.gov (United States)

    Tagawa, H.; Wang, N.; Narishige, T.; Ingber, D. E.; Zile, M. R.; Cooper, G. 4th

    1997-01-01

    We have shown that the cellular contractile dysfunction characteristic of pressure-overload cardiac hypertrophy results not from an abnormality intrinsic to the myofilament portion of the cardiocyte cytoskeleton but rather from an increased density of the microtubule component of the extramyofilament portion of the cardiocyte cytoskeleton. To determine how, in physical terms, this increased microtubule density mechanically overloads the contractile apparatus at the cellular level, we measured cytoskeletal stiffness and apparent viscosity in isolated cardiocytes via magnetic twisting cytometry, a technique by which magnetically induced force is applied directly to the cytoskeleton through integrin-coupled ferromagnetic beads coated with Arg-Gly-Asp (RGD) peptide. Measurements were made in two groups of cardiocytes from cats with right ventricular (RV) hypertrophy induced by pulmonary artery banding: (1) those from the pressure-overloaded RV and (2) those from the normally loaded same-animal control left ventricle (LV). Cytoskeletal stiffness increased almost twofold, from 8.53 +/- 0.77 dyne/cm2 in the normally loaded LV cardiocytes to 16.46 +/- 1.32 dyne/cm2 in the hypertrophied RV cardiocytes. Cytoskeletal apparent viscosity increased almost fourfold, from 20.97 +/- 1.92 poise in the normally loaded LV cardiocytes to 87.85 +/- 6.95 poise in the hypertrophied RV cardiocytes. In addition to these baseline data showing differing stiffness and, especially, apparent viscosity in the two groups of cardiocytes, microtubule depolymerization by colchicine was found to return both the stiffness and the apparent viscosity of the pressure overload-hypertrophied RV cells fully to normal. Conversely, microtubule hyperpolymerization by taxol increased the stiffness and apparent viscosity values of normally loaded LV cardiocytes to the abnormal values given above for pressure-hypertrophied RV cardiocytes. Thus, increased microtubule density constitutes primarily a viscous load on the cardiocyte contractile apparatus in pressure-overload cardiac hypertrophy.

  11. 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 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.

  12. 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.)

  13. Calcium handling by vascular myocytes in hypertension

    OpenAIRE

    R.C.A. Tostes; D.W. Wilde; L.M. Bendhack; Webb, R C

    1997-01-01

    Calcium ions (Ca2+) trigger the contraction of vascular myocytes and the level of free intracellular Ca2+ within the myocyte is precisely regulated by sequestration and extrusion mechanisms. Extensive evidence indicates that a defect in the regulation of intracellular Ca2+ plays a role in the augmented vascular reactivity characteristic of clinical and experimental hypertension. For example, arteries from spontaneously hypertensive rats (SHR) have an increased contractile sensitivity to extra...

  14. Smooth Muscle Hypertrophy Following Partial Bladder Outlet Obstruction Is Associated with Overexpression of Non-Muscle Caldesmon

    OpenAIRE

    Zhang, Erik Y.; Stein, Raimund; Chang, Shaohua; Zheng, Yongmu; Zderic, Stephen A.; Wein, Alan J.; Chacko, Samuel

    2004-01-01

    Partial bladder outlet obstruction (PBOO) induces remodeling of urinary bladder smooth muscle (detrusor). We demonstrate an increase in bladder wall mass, muscle bundle size, and a threefold increase in the cross-sectional area of detrusor myocytes following PBOO in male New Zealand White rabbits compared to that of controls. Some bladders with detrusor hypertrophy function close to normal (compensated), whereas others were dysfunctional (decompensated), showing high intravesical pressure, la...

  15. Rate-dependency of action potential duration and refractoriness in isolated myocytes from the rabbit AV node and atrium

    OpenAIRE

    Workman, A.J.; Kane, K. A.; Rankin, A. C.

    2000-01-01

    During atrial fibrillation, ventricular rate is determined by atrioventricular nodal (AVN) conduction, which in part is dependent upon the refractoriness of single AVN cells. The aims of this study were to investigate the rate-dependency of the action potential duration (APD) and effective refractory period (ERP) in single myocytes isolated from the AV node and atrium of rabbit hearts, using whole cell patch clamping, and to determine the contribution of the 4-aminopyridine (4-AP)-sensitive c...

  16. 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

  17. 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

  18. Current concepts on ventricular fibrillation: A Vicious Circle of Cardiomyocyte Calcium Overload in the Initiation, Maintenance, and Termination of Ventricular Fibrillation

    OpenAIRE

    Zaugg, Christian E.

    2004-01-01

    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, myocar...

  19. 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...

  20. Mouse models for the study of postnatal cardiac hypertrophy

    Directory of Open Access Journals (Sweden)

    A. Del Olmo-Turrubiarte

    2015-06-01

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

  1. Differential extracellular signal-regulated kinases 1 and 2 activation by the angiotensin type 1 receptor supports distinct phenotypes of cardiac myocytes

    DEFF Research Database (Denmark)

    Frederiksen, Mark Aplin; Christensen, Gitte Lund

    2007-01-01

    The angiotensin II (AngII) type 1 receptor (AT(1)R) is a seven-transmembrane receptor well established to activate extracellular signal-regulated kinases 1 and 2 (ERK1/2) by discrete G protein-dependent and beta-arrestin2-dependent pathways. The biological importance of this, however, remains obscure. Application of the modified analogue [Sar(1), Ile(4), Ile(8)]-AngII ([SII] AngII) allowed us to dissect the two pathways of ERK1/2 activation in native cardiac myocytes. Although cytosol-retained, the beta-arrestin2-bound pool of ERK1/2 represents an active signalling component that phosphorylates p90 Ribosomal S6 Kinase, a ubiquitous and versatile mediator of ERK1/2 signal transduction. Moreover, the beta-arrestin2-dependent ERK1/2 signal supports intact proliferation of cardiac myocytes. In contrast to G(q)-activated ERK1/2, and in keeping with its failure to translocate to the nucleus, the beta-arrestin2-scaffolded pool of ERK1/2 does not phosphorylate the transcription factor Elk-1, induces no increased transcription of the immediate-early gene c-Fos, and does not entail myocyte hypertrophy. These results clearly demonstrate the biological significance of differential signalling by the AT(1)R. The opportunity to separate desirable cardiac myocyte division from detrimental hypertrophy holds promise that novel pharmacological approaches will allow targeting of pathway-specific actions.

  2. [Ventricular tachycardia].

    Science.gov (United States)

    Brunckhorst, C; Duru, F; Scharf, C; Schalcher, C; Candinas, R

    2001-06-14

    In patients with ventricular tachycardias, various structural and functional conditions can be influenced by certain triggers, initiating the mechanism of the arrhythmia. Thorough understanding of these different factors is paramount for the appropriate choice of treatment. Several options are available for the management of ventricular tachycardias: antiarrhythmic drugs, ICD implantation and catheter ablation or a combination of the above. The prognosis of an individual patient is determined by the underlying disease, the mechanism of tachycardia and the selected therapy. The complexity of several conditions requires a specialized diagnostic approach and tailored medical management. Therefore the patients with the following diagnoses should be referred to a specialized electrophysiology center: survivors of sudden cardiac death old infarct scar, reduced ejection fraction and complex ectopy Cardiomyopathy with syncope or ventricular tachycardias Long QT-Syndrome Brugada Syndrome Right Ventricular Dysplasia recurrent syncopes of unclear etiology. PMID:11458774

  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

    Directory of Open Access Journals (Sweden)

    Edson Antonio Bregagnollo

    2007-02-01

    Full Text Available 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. MÉTODOS: 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, pOBJECTIVE: 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: Twenty 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<0.05. In the SG-HF group, LV geometric remodeling was characterized by a significant increase in dimensions and relative thickness of the normal wall (excentric remodeling, whereas the SG group presented a concentric remodeling. Indexes of LV performance in the SG-HF group were significantly lower than those of the SG group. CONCLUSION: The SG-HF and SG groups differed primarily in the LV geometric remodeling and structural myocardial remodeling process, which established a chronically compensated state in the SG group and triggered CHF in the SG-HF group in the presence of equivalent degrees of impaired contractility.

  4. Left ventricular geometric patterns in newly presenting nigerian hypertensives: An echocardiographic study

    OpenAIRE

    Ogah Okechukwu S; Dada Adekola; Oladapo Olulola O; Adebiyi Adewole A; Aje Akinyemi; Ojji Dike B; Falase Ayodele O

    2006-01-01

    Abstract Background Hypertension is a global problem and it is prevalent in Nigeria. Left ventricular hypertrophy is a major complication of hypertension with risk of sudden death and arrhythmias among others. Abnormal left ventricular geometric patterns also increase the burden of morbidity and mortality. It is therefore important to know the different left ventricular geometric patterns in Nigerian hypertensives because of their prognostic significance. Methods One hundred (100) newly prese...

  5. 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)

  6. Pitfalls in the Diagnosis of Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia

    OpenAIRE

    Marcus, Frank; Basso, Cristina; Gear, Kathleen; Sorrell, Vincent L

    2010-01-01

    The diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is based on Task Force Criteria published in 1994 that included imaging abnormalities of the right ventricle as well as diagnostic pathological evaluation of the right ventricular myocardium by endomyocardial biopsy. These have recently been modified to include evaluation by cardiac magnetic resonance (CMR). In addition quantitative criteria for the percent of fibrosis and decrease in myocyte are included in t...

  7. 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.

  8. Calcium handling by vascular myocytes in hypertension

    Scientific Electronic Library Online (English)

    R.C.A., Tostes; D.W., Wilde; L.M., Bendhack; R.C., Webb.

    1997-03-01

    Full Text Available Calcium ions (Ca2+) trigger the contraction of vascular myocytes and the level of free intracellular Ca2+ within the myocyte is precisely regulated by sequestration and extrusion mechanisms. Extensive evidence indicates that a defect in the regulation of intracellular Ca2+ plays a role in the augmen [...] ted vascular reactivity characteristic of clinical and experimental hypertension. For example, arteries from spontaneously hypertensive rats (SHR) have an increased contractile sensitivity to extracellular Ca2+ and intracellular Ca2+ levels are elevated in aortic smooth muscle cells of SHR. We hypothesize that these changes are due to an increase in membrane Ca2+ channel density and possibly function in vascular myocytes from hypertensive animals. Several observations using various experimental approaches support this hypothesis: 1) the contractile activity in response to depolarizing stimuli is increased in arteries from hypertensive animals demonstrating increased voltage-dependent Ca2+ channel activity in hypertension; 2) Ca2+ channel agonists such as Bay K 8644 produce contractions in isolated arterial segments from hypertensive rats and minimal contraction in those from normotensive rats; 3) intracellular Ca2+ concentration is abnormally increased in vascular myocytes from hypertensive animals following treatment with Ca2+ channel agonists and depolarizing interventions, and 4) using the voltage-clamp technique, the inward Ca2+ current in arterial myocytes from hypertensive rats is nearly twice as large as that from myocytes of normotensive rats. We suggest that an alteration in Ca2+ channel function and/or an increase in Ca2+ channel density, resulting from increased channel synthesis or reduced turnover, underlies the increased vascular reactivity characteristic of hypertension

  9. Calcium handling by vascular myocytes in hypertension

    Directory of Open Access Journals (Sweden)

    R.C.A. Tostes

    1997-03-01

    Full Text Available Calcium ions (Ca2+ trigger the contraction of vascular myocytes and the level of free intracellular Ca2+ within the myocyte is precisely regulated by sequestration and extrusion mechanisms. Extensive evidence indicates that a defect in the regulation of intracellular Ca2+ plays a role in the augmented vascular reactivity characteristic of clinical and experimental hypertension. For example, arteries from spontaneously hypertensive rats (SHR have an increased contractile sensitivity to extracellular Ca2+ and intracellular Ca2+ levels are elevated in aortic smooth muscle cells of SHR. We hypothesize that these changes are due to an increase in membrane Ca2+ channel density and possibly function in vascular myocytes from hypertensive animals. Several observations using various experimental approaches support this hypothesis: 1 the contractile activity in response to depolarizing stimuli is increased in arteries from hypertensive animals demonstrating increased voltage-dependent Ca2+ channel activity in hypertension; 2 Ca2+ channel agonists such as Bay K 8644 produce contractions in isolated arterial segments from hypertensive rats and minimal contraction in those from normotensive rats; 3 intracellular Ca2+ concentration is abnormally increased in vascular myocytes from hypertensive animals following treatment with Ca2+ channel agonists and depolarizing interventions, and 4 using the voltage-clamp technique, the inward Ca2+ current in arterial myocytes from hypertensive rats is nearly twice as large as that from myocytes of normotensive rats. We suggest that an alteration in Ca2+ channel function and/or an increase in Ca2+ channel density, resulting from increased channel synthesis or reduced turnover, underlies the increased vascular reactivity characteristic of hypertension

  10. Bnip3 Binds and Activates p300: Possible Role in Cardiac Transcription and Myocyte Morphology.

    Science.gov (United States)

    Thompson, John W; Wei, Jianqin; Appau, Kweku; Wang, Huilan; Yu, Hong; Spiga, Maria G; Graham, Regina M; Webster, Keith A

    2015-01-01

    Bnip3 is a hypoxia-regulated member of the Bcl-2 family of proteins that is implicated in apoptosis, programmed necrosis, autophagy and mitophagy. Mitochondria are thought to be the primary targets of Bnip3 although its activities may extend to the ER, cytoplasm, and nucleus. Bnip3 is induced in the heart by ischemia and pressure-overload, and may contribute to cardiomyopathy and heart failure. Only mitochondrial-dependent programmed death actions have been described for Bnip3 in the heart. Here we describe a novel activity of Bnip3 in cultured cardiac myocytes and transgenic mice overexpressing Bnip3 in the heart (Bnip3-TG). In cultured myocytes Bnip3 bound and activated the acetyltransferase p300, increased acetylation of histones and the transcription factor GATA4, and conferred p300 and GATA4-sensitive cellular morphological changes. In intact Bnip3-TG hearts Bnip3 also bound p300 and GATA4 and conferred enhanced GATA4 acetylation. Bnip3-TG mice underwent age-dependent ventricular dilation and heart failure that was partially prevented by p300 inhibition with curcumin. The results suggest that Bnip3 regulates cardiac gene expression and perhaps myocyte morphology by activating nuclear p300 acetyltransferase activity and hyperacetylating histones and p300-selective transcription factors. PMID:26317696

  11. 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 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.

  12. 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

  13. 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.

    2013-12-01

    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.

  14. Integrin binding angiopoietin-1 monomers reduce cardiac hypertrophy.

    Science.gov (United States)

    Dallabrida, Susan M; Ismail, Nesreen S; Pravda, Elke A; Parodi, Emily M; Dickie, Renee; Durand, Ellen M; Lai, Jean; Cassiola, Flavia; Rogers, Rick A; Rupnick, Maria A

    2008-08-01

    Angiopoietins were thought to be endothelial cell-specific via the tie2 receptor. We showed that angiopoietin-1 (ang1) also interacts with integrins on cardiac myocytes (CMs) to increase survival. Because ang1 monomers bind and activate integrins (not tie2), we determined their function in vivo. We examined monomer and multimer expressions during physiological and pathological cardiac remodeling and overexpressed ang1 monomers in phenylephrine-induced cardiac hypertrophy. Cardiac ang1 levels (mRNA, protein) increased during postnatal development and decreased with phenylephrine-induced cardiac hypertrophy, whereas tie2 phosphorylations were unchanged. We found that most or all of the changes during cardiac remodeling were in monomers, offering an explanation for unchanged tie2 activity. Heart tissue contains abundant ang1 monomers and few multimers (Western blotting). We generated plasmids that produce ang1 monomers (ang1-256), injected them into mice, and confirmed cardiac expression (immunohistochemistry, RT-PCR). Ang1 monomers localize to CMs, smooth muscle cells, and endothelial cells. In phenylephrine-induced cardiac hypertrophy, ang1-256 reduced left ventricle (LV)/tibia ratios, fetal gene expressions (atrial and brain natriuretic peptides, skeletal actin, beta-myosin heavy chain), and fibrosis (collagen III), and increased LV prosurvival signaling (akt, MAPK(p42/44)), and AMPK(T172). However, tie2 phosphorylations were unchanged. Ang1-256 increased integrin-linked kinase, a key regulator of integrin signaling and cardiac health. Collectively, these results suggest a role for ang1 monomers in cardiac remodeling. PMID:18502941

  15. 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.

  16. Genetically engineered cardiac pacemaker: Stem cells transfected with HCN2 gene and myocytes—A model

    Science.gov (United States)

    Kanani, S.; Pumir, A.; Krinsky, V.

    2008-01-01

    One of the successfully tested methods to design genetically engineered cardiac pacemaker cells consists in transfecting a human mesenchymal stem cell (hMSC) with a HCN2 gene and connecting it to a myocyte. We develop and study a mathematical model, describing a myocyte connected to a hMSC transfected with a HCN2 gene. The cardiac action potential is described both with the simple Beeler Reuter model, as well as with the elaborate dynamic Luo Rudy model. The HCN2 channel is described by fitting electrophysiological records, in the spirit of Hodgkin Huxley. The model shows that oscillations can occur in a pair myocyte-stem cell, that was not observed in the experiments yet. The model predicted that: (1) HCN pacemaker channels can induce oscillations only if the number of expressed I channels is low enough. At too high an expression level of I channels, oscillations cannot be induced, no matter how many pacemaker channels are expressed. (2) At low expression levels of I channels, a large domain of values in the parameter space (n, N) exists, where oscillations should be observed. We denote N the number of expressed pacemaker channels in the stem cell, and n the number of gap junction channels coupling the stem cell and the myocyte. (3) The expression levels of I channels observed in ventricular myocytes, both in the Beeler Reuter and in the dynamic Luo Rudy models are too high to allow to observe oscillations. With expression levels below ˜1/4 of the original value, oscillations can be observed. The main consequence of this work is that in order to obtain oscillations in an experiment with a myocyte-stem cell pair, increasing the values of n, N is unlikely to be helpful, unless the expression level of I has been reduced enough. The model also allows us to explore levels of gene expression not yet achieved in experiments, and could be useful to plan new experiments, aimed at improving the robustness of the oscillations.

  17. Targeting the CaMKII/ERK Interaction in the Heart Prevents Cardiac Hypertrophy

    Science.gov (United States)

    Cipolletta, Ersilia; Rusciano, Maria Rosaria; Maione, Angela Serena; Santulli, Gaetano; Sorriento, Daniela; Del Giudice, Carmine; Ciccarelli, Michele; Franco, Antonietta; Crola, Catherine; Campiglia, Pietro; Sala, Marina; Gomez-Monterrey, Isabel; De Luca, Nicola; Trimarco, Bruno; Iaccarino, Guido; Illario, Maddalena

    2015-01-01

    Aims Activation of Ca2+/Calmodulin protein kinase II (CaMKII) is an important step in signaling of cardiac hypertrophy. The molecular mechanisms by which CaMKII integrates with other pathways in the heart are incompletely understood. We hypothesize that CaMKII association with extracellular regulated kinase (ERK), promotes cardiac hypertrophy through ERK nuclear localization. Methods and Results In H9C2 cardiomyoblasts, the selective CaMKII peptide inhibitor AntCaNtide, its penetratin conjugated minimal inhibitory sequence analog tat-CN17?, and the MEK/ERK inhibitor UO126 all reduce phenylephrine (PE)-mediated ERK and CaMKII activation and their interaction. Moreover, AntCaNtide or tat-CN17? pretreatment prevented PE induced CaMKII and ERK nuclear accumulation in H9C2s and reduced the hypertrophy responses. To determine the role of CaMKII in cardiac hypertrophy in vivo, spontaneously hypertensive rats were subjected to intramyocardial injections of AntCaNtide or tat-CN17?. Left ventricular hypertrophy was evaluated weekly for 3 weeks by cardiac ultrasounds. We observed that the treatment with CaMKII inhibitors induced similar but significant reduction of cardiac size, left ventricular mass, and thickness of cardiac wall. The treatment with CaMKII inhibitors caused a significant reduction of CaMKII and ERK phosphorylation levels and their nuclear localization in the heart. Conclusion These results indicate that CaMKII and ERK interact to promote activation in hypertrophy; the inhibition of CaMKII-ERK interaction offers a novel therapeutic approach to limit cardiac hypertrophy. PMID:26110816

  18. Analysis of Cripto expression during mouse cardiac myocyte differentiation.

    Science.gov (United States)

    Jin, Jiu-Zhen; Tan, Min; Ding, Jixiang

    2013-01-01

    Vertebrate cardiac progenitor cells are initially allocated in two distinct domains, the first and second heart fields. It has been demonstrated that first heart field cells give rise to the myocardial cells in the left ventricle and part of the atria, whereas second heart field cells move into the developing heart tube and contribute to the myocardium of the outflow tract and right ventricle and the majority of atria. In this study, we have examined the expression of the mouse Cripto gene and the lineage of Cripto-expressing cells, focusing on its relationship with cardiac myocyte differentiation. The mouse Cripto gene is initially expressed at late head fold (LHF) stages in the cardiac crescent region, known as the first heart field; later in the medial region of the early heart tube, and by embryonic day 8.5, it is localized to the outflow tract. Using a Cripto-LacZ allele, we found that Cripto- expressing progeny cells contribute to the myocardium of the entire outflow tract and right ventricle, as well as to a majority of cells within the left ventricle. In contrast, no Cripto- expressing progeny cells were found in the atria or atrio-ventricular canal. Therefore, Cripto is transiently expressed in early differentiating myocardial cells of the left ventricle, right ventricle and outflow tract between LHF stages and E8.5. Cripto expression is subsequently downregulated as cells undergo further differentiation. PMID:24307303

  19. Increased clearance of reactive aldehydes and damaged proteins in hypertension-induced compensated cardiac hypertrophy : impact of exercise training

    DEFF Research Database (Denmark)

    Campos, Juliane Cruz; Fernandes, Tiago

    2015-01-01

    Background. We previously reported that exercise training (ET) facilitates the clearance of damaged proteins in heart failure. Here, we characterized the impact of ET on cardiac protein quality control during compensated ventricular hypertrophy in spontaneously hypertensive rats (SHR). Methods and Results. SHR were randomly assigned into sedentary and swimming-trained groups. Sedentary SHR displayed cardiac hypertrophy with preserved ventricular function compared to normotensive rats, characterizing a compensated cardiac hypertrophy. Hypertensive rats presented signs of cardiac oxidative stress, depicted by increased lipid peroxidation. However, these changes were not followed by accumulation of lipid peroxidation-generated reactive aldehydes and damaged proteins. This scenario was explained, at least in part, by the increased catalytic activity of both aldehyde dehydrogenase 2 (ALDH2) and proteasome. Of interest, ET exacerbated cardiac hypertrophy, improved ventricular function, induced resting bradycardia, and decreased blood pressure in SHR. These changes were accompanied by reduced cardiac oxidative stress and a consequent decrease in ALDH2 and proteasome activities, without affecting small chaperones levels and apoptosis in SHR. Conclusion. Increased cardiac ALDH2 and proteasomal activities counteract the deleterious effect of excessive oxidative stress in hypertension-induced compensated cardiac hypertrophy in rats. ET has a positive effect in reducing cardiac oxidative stress without affecting protein quality control.

  20. Comparative study of Scrophulariae and Aconite in inhibiting myocardial hypertrophy in rats and mice

    Directory of Open Access Journals (Sweden)

    Wei-liang GU

    2008-04-01

    Full Text Available Objective: To explore the effects of Scrophulariae of cold nature and Aconite of hot nature on myocardial hypertrophy and neuroendocrine factors in rats and mice.Methods: A mouse model of myocardial hypertrophy was established by hypodermic injection of isoproterenol. Sixty myocardial hypertrophy mice were randomly divided into five groups: normal control group, untreated group, metoprolol-treated group, Scrophulariae-treated group and Aconite-treated group. A rat model of myocardial hypertrophy was established by peritoneal injection of L-thyroxin. Fifty rats were randomly divided into five groups: normal control group, untreated group, captopril-treated group, Scrophulariae-treated group and Aconite-treated group. After 7-9 days of treatment with intragastric administration of the corresponding drugs, the effects of Scrophulariae and Aconite on left ventricular weight index (LVWI and heart weight index (HWI were determined. The concentrations of cyclic adenosine monophosphate (cAMP in plasma and angiotensin? (Ang? in myocardium were detected through radio-immunity method. Cardiocyte cross-section area was determined by using HE staining. Results: Scrophulariae of cold nature could significantly reduce the LVWI, HWI and cardiocyte cross-section area, and could decrease the content of cAMP and Ang?. However, Aconite had no such effects. Conclusion: Scrophulariae of cold nature can inhibit myocardial hypertrophy through restraining the activity of sympathetic nervous system and decreasing the level of Ang?. The inhibition of Aconite of hot nature on cardiac hypertrophy is not significant.

  1. Effects of rosiglitazone on fibroblast conditioned growth medium-induced myocardial hypertrophy and its mechanism in rats

    Directory of Open Access Journals (Sweden)

    Xiao-xing ZHU

    2011-07-01

    Full Text Available Objective To investigate the inhibitory effect of rosiglitazone(RSG on fibroblast conditioned growth medium(FCGM-induced myocardial hypertrophy and its mechanism in rats.Methods FCGM-stimulated protein synthesis and protein kinase C(PKC activity were measured in neonatal rat ventricular cardiomyocytes in the absence or presence of RSG or the PKC inhibitor chelerythrine(che.Results Cultured neonatal rat ventricular fibroblast conditioned growth medium significantly enhanced protein synthesis of cardiomyocytes.Meanwhile ET-1 was detected in FCGM using the enzyme-linked immunosorbent assay(ELISA.RSG and che counteracted the growth promoting effect of FCGM possibly via suppressing PKC activity.Conclusion FCGM-induced myocardial hypertrophy may be associated with ET-1.The inhibitory effects of RSG on myocardial hypertrophy may be mediated through ET-1 and PKC.

  2. Left ventricular non-compaction cardiomyopathy.

    Science.gov (United States)

    Towbin, Jeffrey A; Lorts, Angela; Jefferies, John Lynn

    2015-08-22

    Left ventricular non-compaction, the most recently classified form of cardiomyopathy, is characterised by abnormal trabeculations in the left ventricle, most frequently at the apex. It can be associated with left ventricular dilation or hypertrophy, systolic or diastolic dysfunction, or both, or various forms of congenital heart disease. Affected individuals are at risk of left or right ventricular failure, or both. Heart failure symptoms can be induced by exercise or be persistent at rest, but many patients are asymptomatic. Patients on chronic treatment for compensated heart failure sometimes present acutely with decompensated heart failure. Other life-threatening risks of left ventricular non-compaction are ventricular arrhythmias or complete atrioventricular block, presenting clinically as syncope, and sudden death. Genetic inheritance arises in at least 30-50% of patients, and several genes that cause left ventricular non-compaction have been identified. These genes seem generally to encode sarcomeric (contractile apparatus) or cytoskeletal proteins, although, in the case of left ventricular non-compaction with congenital heart disease, disturbance of the NOTCH signalling pathway seems part of a final common pathway for this form of the disease. Disrupted mitochondrial function and metabolic abnormalities have a causal role too. Treatments focus on improvement of cardiac efficiency and reduction of mechanical stress in patients with systolic dysfunction. Further, treatment of arrhythmia and implantation of an automatic implantable cardioverter-defibrillator for prevention of sudden death are mainstays of therapy when deemed necessary and appropriate. Patients with left ventricular non-compaction and congenital heart disease often need surgical or catheter-based interventions. Despite progress in diagnosis and treatment in the past 10 years, understanding of the disorder and outcomes need to be improved. PMID:25865865

  3. Acetyl salicylic acid attenuates cardiac hypertrophy through Wnt signaling.

    Science.gov (United States)

    Gitau, Samuel Chege; Li, Xuelian; Zhao, Dandan; Guo, Zhenfeng; Liang, Haihai; Qian, Ming; Lv, Lifang; Li, Tianshi; Xu, Bozhi; Wang, Zhiguo; Zhang, Yong; Xu, Chaoqian; Lu, Yanjie; Du, Zhiming; Shan, Hongli; Yang, Baofeng

    2015-12-01

    Ventricular hypertrophy is a powerful and independent predictor of cardiovascular morbid events. The vascular properties of low-dose acetyl salicylic acid (aspirin) provide cardiovascular benefits through the irreversible inhibition of platelet cyclooxygenase 1; however, the possible anti-hypertrophic properties and potential mechanism of aspirin have not been investigated in detail. In this study, healthy wild-type male mice were randomly divided into three groups and subjected to transverse aortic constriction (TAC) or sham operation. The TAC-operated mice were treated with the human equivalent of low-dose aspirin (10 mg·kg(-1)·d(-1)); the remaining mice received an equal amount of phosphate buffered saline with 0.65% ethanol, which was used as a vehicle. A cardiomyocyte hypertrophy model induced by angiotensin II (10 nmol·L(-1)) was treated with the human equivalent of low (10 or 100 ?mol·L(-1)) and high (1000 ?mol·L(-1)) aspirin concentrations in plasma. Changes in the cardiac structure and function were assessed through echocardiography and transmission electron microscopy. Gene expression was determined through RT-PCR and western blot analysis. Results indicated that aspirin treatment abrogated the increased thickness of the left ventricular anterior and posterior walls, the swelling of mitochondria, and the increased surface area in in vivo and in vitro hypertrophy models. Aspirin also normalized the upregulated hypertrophic biomarkers, ?-myosin heavy chain (?-MHC), atrial natriuretic peptide (ANP), and b-type natriuretic peptide (BNP). Aspirin efficiently reversed the upregulation of ?-catenin and P-Akt expression and the TAC- or ANG II-induced downregulation of GSK-3?. Therefore, low-dose aspirin possesses significant anti-hypertrophic properties at clinically relevant concentrations for anti-thrombotic therapy. The downregulation of ?-catenin and Akt may be the underlying signaling mechanism of the effects of aspirin. PMID:26626190

  4. TRPC3 and TRPC6 are essential for angiotensin II-induced cardiac hypertrophy

    Science.gov (United States)

    Onohara, Naoya; Nishida, Motohiro; Inoue, Ryuji; Kobayashi, Hiroyuki; Sumimoto, Hideki; Sato, Yoji; Mori, Yasuo; Nagao, Taku; Kurose, Hitoshi

    2006-01-01

    Angiotensin (Ang) II participates in the pathogenesis of heart failure through induction of cardiac hypertrophy. Ang II-induced hypertrophic growth of cardiomyocytes is mediated by nuclear factor of activated T cells (NFAT), a Ca2+-responsive transcriptional factor. It is believed that phospholipase C (PLC)-mediated production of inositol-1,4,5-trisphosphate (IP3) is responsible for Ca2+ increase that is necessary for NFAT activation. However, we demonstrate that PLC-mediated production of diacylglycerol (DAG) but not IP3 is essential for Ang II-induced NFAT activation in rat cardiac myocytes. NFAT activation and hypertrophic responses by Ang II stimulation required the enhanced frequency of Ca2+ oscillation triggered by membrane depolarization through activation of DAG-sensitive TRPC channels, which leads to activation of L-type Ca2+ channel. Patch clamp recordings from single myocytes revealed that Ang II activated DAG-sensitive TRPC-like currents. Among DAG-activating TRPC channels (TRPC3, TRPC6, and TRPC7), the activities of TRPC3 and TRPC6 channels correlated with Ang II-induced NFAT activation and hypertrophic responses. These data suggest that DAG-induced Ca2+ signaling pathway through TRPC3 and TRPC6 is essential for Ang II-induced NFAT activation and cardiac hypertrophy. PMID:17082763

  5. Reduced effects of BAY K 8644 on L-type Ca2+ current in failing human cardiac myocytes are related to abnormal adrenergic regulation

    OpenAIRE

    Chen, Xiongwen; Zhang, Xiaoying; Harris, David M.; Piacentino, Valentino; Berretta, Remus M; Margulies, Kenneth B; Houser, Steven R

    2008-01-01

    Abnormal L-type Ca2+ channel (LTCC, also named Cav1.2) density and regulation are important contributors to depressed contractility in failing hearts. The LTCC agonist BAY K 8644 (BAY K) has reduced inotropic effects on failing myocardium. We hypothesized that BAY K effects on the LTCC current (ICaL) in failing myocytes would be reduced because of increased basal activity. Since support of the failing heart with a left ventricular assist device (LVAD) improves contractility and adrenergic res...

  6. 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.)

  7. Myocardial oxygen consumption in aortic valve disease with and without left ventricular dysfunction.

    OpenAIRE

    Schwitter, J; Eberli, F R; Ritter, M.; Turina, M.; Krayenbuehl, H P

    1992-01-01

    OBJECTIVE--To assess whether and to what extent myocardial oxygen consumption is modified by hypertrophy and alterations in contractility in patients with aortic valve disease and to evaluate the influence of regression of left ventricular hypertrophy and improvement of contractility on myocardial oxygen consumption after successful aortic valve replacement. DESIGN--A cohort analytical study to investigate the influence of the "explanatory" variables of myocardial oxygen consumption by multip...

  8. Effect of increased wall thickness on indices of left ventricular pump function in children.

    OpenAIRE

    Wessel, A.; Schüller, W C; Yelbuz, T. M.; Bürsch, J H

    1994-01-01

    OBJECTIVE--To investigate whether augmented chamber performance in children with a concentric hypertrophied left ventricle is due to increased myocardial shortening or a geometric effect of the thickened ventricular wall. DESIGN--Chamber performance in terms of fractional area change and myocardial shortening--that is, circumferential midwall shortening--were measured by cross sectional echocardiography in young people with normal left ventricles and those with concentric hypertrophy of the l...

  9. Functional consequences of caspase activation in cardiac myocytes

    Science.gov (United States)

    Communal, Catherine; Sumandea, Marius; de Tombe, Pieter; Narula, Jagat; Solaro, R. John; Hajjar, Roger J.

    2002-04-01

    Cardiomyocyte apoptosis is present in many cardiac disease states, including heart failure and ischemic heart disease. Apoptosis is associated with the activation of caspases that mediate the cleavage of vital and structural proteins. However, the functional contribution of apoptosis to these conditions is not known. Furthermore, in cardiac myocytes, apoptosis may not be complete, allowing the cells to persist for a prolonged period within the myocardium. Therefore, we examined whether caspase-3 cleaved cardiac myofibrillar proteins and, if so, whether it affects contractile function. The effects of caspase-3 were studied in vitro on individual components of the cardiac myofilament including -actin, -actinin, myosin heavy chain, myosin light chain 1/2, tropomyosin, cardiac troponins (T, I, C), and the trimeric troponin complex. Exposure of the myofibrillar protein (listed above) to caspase-3 for 4 h resulted in the cleavage of -actin and -actinin, but not myosin heavy chain, myosin light chain 1/2, and tropomyosin, into three fragments (30, 20, and 15 kDa) and one major fragment (45 kDa), respectively. When cTnT, cTnI, and cTnC were incubated individually with caspase-3, there was no detectable cleavage. However, when the recombinant troponin complex was exposed to caspase-3, cTnT was cleaved, resulting in fragments of 25 kDa. Furthermore, rat cardiac myofilaments exposed to caspase-3 exhibited similar patterns of myofibrillar protein cleavage. Treatment with the caspase inhibitor DEVD-CHO or z-VAD-fmk abolished the cleavage. Myofilaments, isolated from adult rat ventricular myocytes after induction of apoptotic pathway by using -adrenergic stimulation, displayed a similar pattern of actin and TnT cleavage. Exposure of skinned fiber to caspase-3 decreased maximal Ca2+-activated force and myofibrillar ATPase activity. Our results indicate that caspase-3 cleaved myofibrillar proteins, resulting in an impaired force/Ca2+ relationship and myofibrillar ATPase activity. Induction of apoptosis in cardiac cells was associated with similar cleavage of myofilaments. Therefore, activation of apoptotic pathways may lead to contractile dysfunction before cell death.

  10. 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…

  11. Fibroblast Growth Factor 2 Mediates Isoproterenol-induced Cardiac Hypertrophy through Activation of the Extracellular Regulated Kinase

    Directory of Open Access Journals (Sweden)

    Stacey L. House

    2010-01-01

    Full Text Available Fibroblast growth factor 2 (basic FGF or FGF2 has been shown to affect growth and differentiation in some tissues and to be required for cardiac hypertrophy in vivo. FGF2 has been shown in vitro to signal through the mitogen-activated protein kinase (MAPK to affect cell survival and growth. To ascertain the role of FGF2 in cardiac hypertrophy, wildtype, Fgf2 knockout, non-transgenic, and FGF2 transgenic mice were treated with isoproterenol or saline via subcutaneous mini-osmotic pump implants to induce a hypertrophic response to b-adrenergic stimulation. Fgf2 knockout hearts are protected from isoproterenol-induced cardiac hypertrophy; whereas, FGF2 transgenic hearts show exacerbated cardiac hypertrophy as assessed by heart weight-to-body weight ratios and myocyte cross-sectional area. Echocardiography reveals significantly decreased fractional shortening in isoproterenol-treated FGF2 transgenic mice but not in Fgf2 knockout mice suggesting that FGF2 mediates the maladaptive cardiac dysfunction seen in cardiac hypertrophy induced by isoproterenol. Western blot analysis also reveals alterations in MAPK signaling in Fgf2 knockout and FGF2 transgenic hearts subjected to isoproterenol treatment, suggesting that this cascade mediates FGF2's pro-hypertrophic effect.

  12. Disruption of ROCK1 gene attenuates cardiac dilation and improves contractile function in pathological cardiac hypertrophy

    OpenAIRE

    Shi, Jianjian; Zhang, Yi-Wei; Summers, Lelia J.; Dorn, Gerald W., II; Wei, Lei

    2007-01-01

    The development of left ventricular cardiomyocyte hypertrophy in response to increased hemodynamic load and neurohormonal stress is initially a compensatory response. However, persistent stress eventually leads to dilated heart failure, which is a common cause of heart failure in human hypertensive and valvular heart disease. We have recently reported that Rho-associated coiled-coil containing protein kinase 1 (ROCK1) homozygous knockout mice exhibited reduced cardiac fibrosis and cardiomyocy...

  13. 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.

  14. Regulatory Volume Decrease of Cardiac Myocytes Induced by ?-Adrenergic Activation of the Cl? Channel in Guinea Pig

    OpenAIRE

    Wang, Zhuren; Mitsuiye, Tamotsu; Rees, Siân 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 = ...

  15. Improved bioavailability of targeted Curcumin delivery efficiently regressed cardiac hypertrophy by modulating apoptotic load within cardiac microenvironment.

    Science.gov (United States)

    Ray, Aramita; Rana, Santanu; Banerjee, Durba; Mitra, Arkadeep; Datta, Ritwik; Naskar, Shaon; Sarkar, Sagartirtha

    2016-01-01

    Cardiomyocyte apoptosis acts as a prime modulator of cardiac hypertrophy leading to heart failure, a major cause of human mortality worldwide. Recent therapeutic interventions have focussed on translational applications of diverse pharmaceutical regimes among which, Curcumin (from Curcuma longa) is known to have an anti-hypertrophic potential but with limited pharmacological efficacies due to low aqueous solubility and poor bioavailability. In this study, Curcumin encapsulated by carboxymethyl chitosan (CMC) nanoparticle conjugated to a myocyte specific homing peptide was successfully delivered in bioactive form to pathological myocardium for effective regression of cardiac hypertrophy in a rat (Rattus norvegicus) model. Targeted nanotization showed higher cardiac bioavailability of Curcumin at a low dose of 5mg/kg body weight compared to free Curcumin at 35mg/kg body weight. Moreover, Curcumin/CMC-peptide treatment during hypertrophy significantly improved cardiac function by downregulating expression of hypertrophy marker genes (ANF, ?-MHC), apoptotic mediators (Bax, Cytochrome-c) and activity of apoptotic markers (Caspase 3 and PARP); whereas free Curcumin in much higher dose showed minimal improvement during compromised cardiac function. Targeted Curcumin treatment significantly lowered p53 expression and activation in diseased myocardium via inhibited interaction of p53 with p300-HAT. Thus attenuated acetylation of p53 facilitated p53 ubiquitination and reduced the apoptotic load in hypertrophied cardiomyocytes; thereby limiting cardiomyocytes' need to enter the regeneration cycle during hypertrophy. This study elucidates for the first time an efficient targeted delivery regimen for Curcumin and also attributes towards probable mechanistic insight into its therapeutic potential as a cardio-protective agent for regression of cardiac hypertrophy. PMID:26612707

  16. NF-?B (p65) negatively regulates myocardin-induced cardiomyocyte hypertrophy through multiple mechanisms.

    Science.gov (United States)

    Liao, Xing-Hua; Wang, Nan; Zhao, Dong-Wei; Zheng, De-Liang; Zheng, Li; Xing, Wen-Jing; Zhou, Hao; Cao, Dong-Sun; Zhang, Tong-Cun

    2014-12-01

    Myocardin is well known to play a key role in the development of cardiomyocyte hypertrophy. But the exact molecular mechanism regulating myocardin stability and transactivity to affect cardiomyocyte hypertrophy has not been studied clearly. We now report that NF-?B (p65) can inhibit myocardin-induced cardiomyocyte hypertrophy. Then we explore the molecular mechanism of this response. First, we show that p65 can functionally repress myocardin transcriptional activity and also reduce the protein expression of myocardin. Second, the function of myocardin can be regulated by epigenetic modifications. Myocardin sumoylation is known to transactivate cardiac genes, but whether p65 can inhibit SUMO modification of myocardin is still not clear. Our data show that p65 weakens myocardin transcriptional activity through attenuating SUMO modification of myocardin by SUMO1/PIAS1, thereby impairing myocardin-mediated cardiomyocyte hypertrophy. Furthermore, the expression of myocardin can be regulated by several microRNAs, which play important roles in the development and function of the heart and muscle. We next investigated potential role of miR-1 in cardiac hypotrophy. Our results show that p65 can upregulate the level of miR-1 and miR-1 can decrease protein expression of myocardin in cardiac myocytes. Notably, miR-1 expression is also controlled by myocardin, leading to a feedback loop. These data thus provide important and novel insights into the function that p65 inhibits myocardin-mediated cardiomyocyte hypertrophy by downregulating the expression and SUMO modification of myocardin and enhancing the expression of miR-1. PMID:25152367

  17. 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.

  18. [Aortico-left ventricular tunnel].

    Science.gov (United States)

    Sutli?, Z; Kokos, Z; Fabeci?-Sabadi, V; Biocina, B; Protrka, N; Sokoli?, J

    1993-01-01

    The boy was first admitted to the Department of Pediatric Cardiology at the age of 4 1/2 because of cardiac murmur diagnosed on the third day of life. A diastolic murmur of a grade 4/6, left ventricular hypertrophy as well as left aortal and ventricular dilatation were discovered. The findings showed a tendency of increase with time, but the patient had no symptoms. X-ray in the long axis view revealed a defect within the upper part of the interventricular septum immediately below the aorta, and dilated right coronary sinus. An invasive diagnostic method was undertaken, as well. The operative procedure was done with a total cardio-pulmonary bypass and hypothermia (29 degrees C). A tunnel from the anterior aortal wall through the outflow tract of the right ventricle to the left side of the heart was established intraoperatively. The defect was solved by a "sandwich" technique (two patch technique). Postoperative period was uneventful. A Doppler echocardiogram demonstrated the normal hemodynamic status of the patient without the left-to-right or right-to-left shunt and aortal insufficiency. PMID:8139366

  19. The Scaffold Protein Muscle A-Kinase Anchoring Protein ? Orchestrates Cardiac Myocyte Hypertrophic Signaling Required for the Development of Heart Failure

    Science.gov (United States)

    Kritzer, Michael D.; Li, Jinliang; Passariello, Catherine L.; Gayanilo, Marjorie; Thakur, Hrishikesh; Dayan, Joseph; Dodge-Kafka, Kimberly; Kapiloff, Michael S.

    2014-01-01

    Background Cardiac myocyte hypertrophy is regulated by an extensive intracellular signal transduction network. In vitro evidence suggests that the scaffold protein muscle A-kinase anchoring protein ? (mAKAP?) serves as a nodal organizer of hypertrophic signaling. However, the relevance of mAKAP? signalosomes to pathological remodeling and heart failure in vivo remains unknown. Methods and Results Using conditional, cardiac myocyte–specific gene deletion, we now demonstrate that mAKAP? expression in mice is important for the cardiac hypertrophy induced by pressure overload and catecholamine toxicity. mAKAP? targeting prevented the development of heart failure associated with long-term transverse aortic constriction, conferring a survival benefit. In contrast to 29% of control mice (n=24), only 6% of mAKAP? knockout mice (n=31) died in the 16 weeks of pressure overload (P=0.02). Accordingly, mAKAP? knockout inhibited myocardial apoptosis and the development of interstitial fibrosis, left atrial hypertrophy, and pulmonary edema. This improvement in cardiac status correlated with the attenuated activation of signaling pathways coordinated by the mAKAP? scaffold, including the decreased phosphorylation of protein kinase D1 and histone deacetylase 4 that we reveal to participate in a new mAKAP signaling module. Furthermore, mAKAP? knockout inhibited pathological gene expression directed by myocyte-enhancer factor-2 and nuclear factor of activated T-cell transcription factors that associate with the scaffold. Conclusions mAKAP? orchestrates signaling that regulates pathological cardiac remodeling in mice. Targeting of the underlying physical architecture of signaling networks, including mAKAP? signalosome formation, may constitute an effective therapeutic strategy for the prevention and treatment of pathological remodeling and heart failure. PMID:24812305

  20. 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 myofilament sensitivity to Ca2+ increased. Interestingly, the decay kinetics of global Ca2+ transients and Ca2+ waves accelerated in PGC-1?-expressing cells, but the decay rate of caffeine-elicited Ca2+ transients showed no significant change. This suggests that sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a), but not Na+/Ca2+ exchange (NCX) contribute to PGC-1?-induced cytosolic Ca2+ clearance. Furthermore, PGC-1? induced the expression of SERCA2a in cultured cardiac myocytes. Importantly, overexpressing PGC-1? did not disturb cardiac Ca2+ homeostasis, because SR Ca2+ load and the propensity for Ca2+ waves remained unchanged. These data suggest that PGC-1? can ameliorate cardiac Ca2+ cycling and improve cardiac work output in response to physiological stress. Unraveling the PGC-1?-calcium handing pathway sheds new light on the role of PGC-1? in the therapy of cardiac diseases.

  1. Myomaker mediates fusion of fast myocytes in zebrafish embryos

    International Nuclear Information System (INIS)

    Highlights: • Myomaker is transiently expressed in fast myocytes during embryonic myogenesis. • Myomaker is essential for fast myocyte fusion in zebrafish. • The function of myomaker is conserved among Teleostomi. - Abstract: Myomaker (also called Tmem8c), a new membrane activator of myocyte fusion was recently discovered in mice. Using whole mount in situ hybridization on zebrafish embryos at different stages of embryonic development, we show that myomaker is transiently expressed in fast myocytes forming the bulk of zebrafish myotome. Zebrafish embryos injected with morpholino targeted against myomaker were alive after yolk resorption and appeared morphologically normal, but they were unable to swim, even under effect of a tactile stimulation. Confocal observations showed a marked phenotype characterized by the persistence of mononucleated muscle cells in the fast myotome at developmental stages where these cells normally fuse to form multinucleated myotubes. This indicates that myomaker is essential for myocyte fusion in zebrafish. Thus, there is an evolutionary conservation of myomaker expression and function among Teleostomi

  2. Localised Ca channel phosphorylation modulates the distribution of L-type Ca current in cardiac myocytes.

    Science.gov (United States)

    Chase, Anabelle; Colyer, John; Orchard, Clive H

    2010-07-01

    The t-tubule network is central to excitation-contraction coupling in mammalian cardiac ventricular myocytes, with recent studies showing that the majority of Ca influx via the L-type Ca current (I(Ca)) occurs across the t-tubule membrane. The present study investigated whether tonic phosphorylation of the L-type Ca channel is different at the t-tubule and surface membranes, and if this could account for the high density of I(Ca) at the t-tubules. Ventricular myocytes were isolated from male Wistar rats and detubulated using formamide. I(Ca) was recorded using the whole cell patch clamp technique, and Ca transients were recorded using fluo-3 in conjunction with confocal microscopy. The protein kinase A (PKA) inhibitor H-89 (10micromol/L) and the CaMKII inhibitor KN-93 (5micromol/L) decreased the amplitude of I(Ca) in intact cells but had no effect on I(Ca) amplitude in detubulated cells. These inhibitors also decreased the amplitude of the Ca transient in intact cells but not in detubulated cells. Antibody staining for phosphorylated L-type Ca channel showed significantly higher phosphorylation at the t-tubules than at the surface membrane in intact cells. Thus it appears that tonic phosphorylation of the L-type Ca channel maintains the amplitude of I(Ca) and occurs predominantly at the t-tubules. This may have important implications in heart disease, in which changes of phosphorylation and t-tubule density have been reported. PMID:20188735

  3. 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...

  4. The role of frataxin in doxorubicin-mediated cardiac hypertrophy.

    Science.gov (United States)

    Mouli, Shravanthi; Nanayakkara, Gayani; AlAlasmari, Abdullah; Eldoumani, Haitham; Fu, Xiaoyu; Berlin, Avery; Lohani, Madhukar; Nie, Ben; Arnold, Robert D; Kavazis, Andreas; Smith, Forrest; Beyers, Ronald; Denney, Thomas; Dhanasekaran, Muralikrishnan; Zhong, Juming; Quindry, John; Amin, Rajesh

    2015-09-01

    Doxorubicin (DOX) is a highly effective anti-neoplastic agent; however, its cumulative dosing schedules are clinically limited by the development of cardiotoxicity. Previous studies have attributed the cause of DOX-mediated cardiotoxicity to mitochondrial iron accumulation and the ensuing reactive oxygen species (ROS) formation. The present study investigates the role of frataxin (FXN), a mitochondrial iron-sulfur biogenesis protein, and its role in development of DOX-mediated mitochondrial dysfunction. Athymic mice treated with DOX (5 mg/kg, 1 dose/wk with treatments, followed by 2-wk recovery) displayed left ventricular hypertrophy, as observed by impaired cardiac hemodynamic performance parameters. Furthermore, we also observed significant reduction in FXN expression in DOX-treated animals and H9C2 cardiomyoblast cell lines, resulting in increased mitochondrial iron accumulation and the ensuing ROS formation. This observation was paralleled in DOX-treated H9C2 cells by a significant reduction in the mitochondrial bioenergetics, as observed by the reduction of myocardial energy regulation. Surprisingly, similar results were observed in our FXN knockdown stable cell lines constructed by lentiviral technology using short hairpin RNA. To better understand the cardioprotective role of FXN against DOX, we constructed FXN overexpressing cardiomyoblasts, which displayed cardioprotection against mitochondrial iron accumulation, ROS formation, and reduction of mitochondrial bioenergetics. Lastly, our FXN overexpressing cardiomyoblasts were protected from DOX-mediated cardiac hypertrophy. Together, our findings reveal novel insights into the development of DOX-mediated cardiomyopathy. PMID:26209053

  5. Physiological changes induced in cardiac myocytes by cytotoxic T lymphocytes

    International Nuclear Information System (INIS)

    The lethal hit induced by viral specific, sensitized, cytotoxic T lymphocytes (CTL) attacking virus-infected heart cells is important in the pathogenesis of viral myocarditis and reflects the key role of CTL in this immune response. The mechanisms involved are incompletely understood. Studies of the physiological changes induced in mengovirus-infected, cultured, neonatal, rat heart cells by CTL that had been previously sensitized by the same virus are presented. The CTL were obtained from spleens of mengovirus-infected, major histocompatibility complex (MHC) matched adult rats. Cell wall motion was measured by an optical method, action potentials with intracellular microelectrodes, and total exchangeable calcium content by 45Ca tracer measurements after loading the myocytes with 45Ca and then exposing them to CTL. After 50 min (mean time) of exposing mengovirus-infected myocytes to the CTL, the mechanical relaxation of the myocyte was slowed, with a subsequent slowing of beating rate and a reduced amplitude of contraction. Impaired relaxation progressed, and prolonged oscillatory contractions lasting up to several seconds appeared, with accompanying oscillations in the prolonged plateau phase of the action potentials. Arrest of the myocyte contractions appeared 98 min (mean time) after exposure to CTL. It is concluded that infection of cultured myocytes with mengovirus predisposes them to attack by mengovirus specific CTL, and that persistent dysfunction of the myocyte is preceded by reversible changes in membrane potential and contraction. This is suggestive of an altered calcium handling by the myocytes possibly resulting in the cytotoxic effect

  6. Ventricular torsional relation to ventricular fiber arrangement

    CERN Document Server

    Ranjbar, Saeed; Meybodi, Mahmood Emami

    2014-01-01

    Left ventricular torsion from helically oriented myofibers is a key parameter of cardiac performance. Physicians observing heart motion on echocardiograms, during cardiac catheterization, or in the operating room, are impressed by the twisting or rotary motion of the left ventricle during systole. Conceptually, the heart has been treated as a pressure chamber. The rotary or torsional deformation has been poorly understood by basic scientists and has lacked clinical relevance. The aim of this paper attempts to discuss about this question: Is ventricular twisting related to ventricular fiber arrangement? That is dependent to an assumed model of the left ventricular structure.

  7. Highly efficient derivation of ventricular cardiomyocytes from induced pluripotent stem cells with a distinct epigenetic signature

    OpenAIRE

    Xu, Huansheng; Yi, B. Alexander; Wu, Hao; Bock, Christoph; Gu, Hongcang; Lui, Kathy O.; Park, Joo-Hye C; Shao, Ying; Riley, Alyssa K; Ibrahim J. Domian; Hu, Erding; Willette, Robert; Lepore, John; Meissner, Alexander; Wang, Zhong

    2011-01-01

    Cardiomyocytes derived from pluripotent stem cells can be applied in drug testing, disease modeling and cell-based therapy. However, without procardiogenic growth factors, the efficiency of cardiomyogenesis from pluripotent stem cells is usually low and the resulting cardiomyocyte population is heterogeneous. Here, we demonstrate that induced pluripotent stem cells (iPSCs) can be derived from murine ventricular myocytes (VMs), and consistent with other reports of iPSCs derived from various so...

  8. Inward rectification of a potassium channel in cardiac ventricular cells depends on internal magnesium ions.

    OpenAIRE

    Vandenberg, C A

    1987-01-01

    The mechanism of rectification of the inwardly rectifying potassium channel was examined with single-channel recording techniques in isolated ventricular myocytes from adult guinea pig heart. Inward, or anomalous, rectification describes the property that potassium (K) current can enter the cell at potentials negative to the potassium equilibrium potential, EK, more readily than it can leave the cell at positive potentials. Voltage ramps applied to single inward rectifier channels in cell-att...

  9. Endothelial and non-endothelial coronary blood flow reserve and left ventricular dysfunction in systemic hypertension

    Scientific Electronic Library Online (English)

    Aloísio Marchi, Rocha; Vera Maria Cury, Salemi; Pedro Alves, Lemos Neto; Afonso Yoshikiro, Matsumoto; Valéria Fontenelle Angelim, Pereira; Fábio, Fernandes; Luciano, Nastari; Charles, Mady.

    2009-04-01

    Full Text Available OBJECTIVES: We evaluated the impairment of endothelium-dependent and endothelium-independent coronary blood flow reserve after administration of intracoronary acetylcholine and adenosine, and its association with hypertensive cardiac disease. INTRODUCTION: Coronary blood flow reserve reduction has b [...] een proposed as a mechanism for the progression of compensated left ventricular hypertrophy to ventricular dysfunction. METHODS: Eighteen hypertensive patients with normal epicardial coronary arteries on angiography were divided into two groups according to left ventricular fractional shortening (FS). Group 1 (FS >0.25): n=8, FS=0.29 ± 0.03; Group 2 (FS

  10. Whole transcriptome microarrays identify long non-coding RNAs associated with cardiac hypertrophy

    Directory of Open Access Journals (Sweden)

    Lu Zhang

    2015-09-01

    Full Text Available Long non-coding RNAs (lncRNAs have recently emerged as a novel group of non-coding RNAs able to regulate gene expression. While their role in cardiac disease is only starting to be understood, their involvement in cardiac hypertrophy is poorly known. We studied the association between lncRNAs and left ventricular hypertrophy using whole transcriptome microarrays. Wild-type mice and mice overexpressing the adenosine A2A receptor were subjected to transverse aortic constriction (TAC to induce left ventricular hypertrophy. Expression profiles of lncRNAs in the heart were characterized using genome-wide microarrays. An analytical pipeline was specifically developed to extract lncRNA data from microarrays. We identified 2 lncRNAs up-regulated and 3 lncRNAs down-regulated in the hearts of A2A-receptor overexpressing-mice subjected to TAC compared to wild-type mice. Differential expression of these 2 lncRNAs was validated by quantitative PCR. Complete microarray dataset is available at Gene Expression Omnibus (GEO database (http://www.ncbi.nlm.nih.gov/geo/ under the accession number GSE45423. Here, we describe in details the experimental design, microarray performance and analysis.

  11. Estrogen inhibits cardiac hypertrophy: role of estrogen receptor-beta to inhibit calcineurin.

    Science.gov (United States)

    Pedram, Ali; Razandi, Mahnaz; Lubahn, Dennis; Liu, Jinghua; Vannan, Mani; Levin, Ellis R

    2008-07-01

    Estrogen has been reported to prevent development of cardiac hypertrophy in female rodent models and in humans. However, the mechanisms of sex steroid action are incompletely understood. We determined the cellular effects by which 17beta-estradiol (E2) inhibits angiotensin II (AngII)-induced cardiac hypertrophy in vivo. Two weeks of angiotensin infusion in female mice resulted in marked hypertrophy of the left ventricle, exacerbated by the loss of ovarian steroid hormones from oophorectomy. Hypertrophy was 51% reversed by the administration of E2 (insertion of 0.1 mg/21-d-release tablets). The effects of E2 were mainly mediated by the estrogen receptor (ER) beta-isoform, because E2 had little effect in ERbeta-null mice but comparably inhibited AngII-induced hypertrophy in wild-type or ERalpha-null mice. AngII induced a switch of myosin heavy chain production from alpha to beta, but this was inhibited by E2 via ERbeta. AngII-induced ERK activation was also inhibited by E2 through the beta-receptor. E2 stimulated brain natriuretic peptide protein expression and substantially prevented ventricular interstitial cardiac fibrosis (collagen deposition) as induced by AngII. Importantly, E2 inhibited calcineurin activity that was stimulated by AngII, related to E2 stimulating the modulatory calcineurin-interacting protein (MCIP) 1 gene and protein expression. E2 acting mainly through ERbeta mitigates the important signaling by AngII that produces cardiac hypertrophy and fibrosis in female mice. PMID:18372323

  12. Leptin decreases heart rate associated with increased ventricular repolarization via its receptor.

    Science.gov (United States)

    Lin, Yen-Chang; Huang, Jianying; Hileman, Stan; Martin, Karen H; Hull, Robert; Davis, Mary; Yu, Han-Gang

    2015-11-15

    Leptin has been proposed to modulate cardiac electrical properties via ?-adrenergic receptor activation. The presence of leptin receptors and adipocytes in myocardium raised a question as to whether leptin can directly modulate cardiac electrical properties such as heart rate and QT interval via its receptor. In this work, the role of local direct actions of leptin on heart rate and ventricular repolarization was investigated. We identified the protein expression of leptin receptors at cell surface of sinus node, atrial, and ventricular myocytes isolated from rat heart. Leptin at low doses (0.1-30 ?g/kg) decreased resting heart rate; at high doses (150-300 ?g/kg), leptin induced a biphasic effect (decrease and then increase) on heart rate. In the presence of high-dose propranolol (30 mg/kg), high-dose leptin only reduced heart rate and sometimes caused sinus pauses and ventricular tachycardia. The leptin-induced inhibition of resting heart rate was fully reversed by leptin antagonist. Leptin also increased heart rate-corrected QT interval (QTc), and leptin antagonist did not. In isolated ventricular myocytes, leptin (0.03-0.3 ?g/ml) reversibly increased the action potential duration. These results supported our hypothesis that in addition to indirect pathway via sympathetic tone, leptin can directly decrease heart rate and increase QT interval via its receptor independent of ?-adrenergic receptor stimulation. During inhibition of ?-adrenergic receptor activity, high concentration of leptin in myocardium can cause deep bradycardia, prolonged QT interval, and ventricular arrhythmias. PMID:26408544

  13. Diabetic cardiomyopathy. Resistin: a control of a myocardial hypertrophy

    Directory of Open Access Journals (Sweden)

    An.A. Aleksandrov

    2014-11-01

    Full Text Available Aim. To evaluate the association of serum resistin with morphological and functional indices of hypertrophic myocardium in patients with type 2 diabetes and chronic heart failure (CHF with preserved left ventricular ejection fraction. Material and methods. Patients (n=60; 12 men and 48 women with type 2 diabetes and ischemic heart disease and CHF class II-III (NYHA were included into the study. Clinical, laboratory and instrumental examinations, as well as determination of serum resistin were performed in all patients. Results. Positive correlation was found between serum resistin level and left ventricle end-diastolic pressure (LV EDP; r=0.43; p=0.02 in patients with concentric left ventricular hypertrophy (LVH. Negative correlation was found between serum resistin level and LV EDP (r=-0.61; p=0.000 in patients with eccentric LVH. A number of supraventricular extrasystoles positively correlated with the serum resistin level (r=0.34; p=0.033 in patients with concentric LVH. Conclusion. The role of "physiological" levels of resistin in the formation of cardiovascular indicators of the hypertrophic myocardium as well as possible prognostic significance of different levels of resistin for optimization of therapy are shown in patients with type 2 diabetes with CHF.

  14. Quantitative FDG-uptake by positron emission tomography in progressive hypertrophy of rat hearts in vivo

    International Nuclear Information System (INIS)

    Quantitative myocardial fluorodeoxyglucose positron emission tomography (FDG-PET) for assessing glucose uptake in vivo is reliable in normal rat heart. The objective of this study was to assess the applicability of myocardial FDG-PET on multiple occasions in the longitudinal disease process of progressive hypertrophy of rat heart. Six salt-sensitive Dahl rats (Dahl-S) developing progressive hypertrophy with subsequent dilated cardiomyopathy were compared with salt-resistant Dahl rats (controls). FDG-PET was applied twice at early stage (ES: 14-18 weeks) and at late stage (LS: 22-26 weeks) of hypertrophy. Standardized uptake value (SUV) was calculated for comparing between different animal weights and different injection dosages of FDG. For validating the quantitative study, radioactivity of a total of 36 tissue samples was compared with the corresponding PET values. The left ventricular mass in Dahl-S increased by 17% at ES and by 25% at LS. The SUV in Dahl-S was 95% of controls at ES and reduced to 62% at LS (P=0.023). The heart function started to deteriorate after LS. Linear regression analysis showed a good correlation between the radioactivity of tissue samples and PET values (Y=1.20 X, P2=0.979). Small animal PET studies on longitudinal multiple occasions in vivo were feasible and useful for the repeating assessment of glucose uptake. The reduction of glucose uptake in progressive hypertrophy of heart over time may precede its progression to heart failure. (author)

  15. Pathophysiology of cardiac hypertrophy and heart failure: signaling pathways and novel therapeutic targets.

    Science.gov (United States)

    Tham, Yow Keat; Bernardo, Bianca C; Ooi, Jenny Y Y; Weeks, Kate L; McMullen, Julie R

    2015-09-01

    The onset of heart failure is typically preceded by cardiac hypertrophy, a response of the heart to increased workload, a cardiac insult such as a heart attack or genetic mutation. Cardiac hypertrophy is usually characterized by an increase in cardiomyocyte size and thickening of ventricular walls. Initially, such growth is an adaptive response to maintain cardiac function; however, in settings of sustained stress and as time progresses, these changes become maladaptive and the heart ultimately fails. In this review, we discuss the key features of pathological cardiac hypertrophy and the numerous mediators that have been found to be involved in the pathogenesis of cardiac hypertrophy affecting gene transcription, calcium handling, protein synthesis, metabolism, autophagy, oxidative stress and inflammation. We also discuss new mediators including signaling proteins, microRNAs, long noncoding RNAs and new findings related to the role of calcineurin and calcium-/calmodulin-dependent protein kinases. We also highlight mediators and processes which contribute to the transition from adaptive cardiac remodeling to maladaptive remodeling and heart failure. Treatment strategies for heart failure commonly include diuretics, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers and ?-blockers; however, mortality rates remain high. Here, we discuss new therapeutic approaches (e.g., RNA-based therapies, dietary supplementation, small molecules) either entering clinical trials or in preclinical development. Finally, we address the challenges that remain in translating these discoveries to new and approved therapies for heart failure. PMID:25708889

  16. Vagus nerve stimulation mitigates intrinsic cardiac neuronal and adverse myocyte remodeling postmyocardial infarction.

    Science.gov (United States)

    Beaumont, Eric; Southerland, Elizabeth M; Hardwick, Jean C; Wright, Gary L; Ryan, Shannon; Li, Ying; KenKnight, Bruce H; Armour, J Andrew; Ardell, Jeffrey L

    2015-10-01

    This paper aims to determine whether chronic vagus nerve stimulation (VNS) mitigates myocardial infarction (MI)-induced remodeling of the intrinsic cardiac nervous system (ICNS), along with the cardiac tissue it regulates. Guinea pigs underwent VNS implantation on the right cervical vagus. Two weeks later, MI was produced by ligating the ventral descending coronary artery. VNS stimulation started 7 days post-MI (20 Hz, 0.9 ± 0.2 mA, 14 s on, 48 s off; VNS-MI, n = 7) and was compared with time-matched MI animals with sham VNS (MI n = 7) vs. untreated controls (n = 8). Echocardiograms were performed before and at 90 days post-MI. At termination, IC neuronal intracellular voltage recordings were obtained from whole-mount neuronal plexuses. MI increased left ventricular end systolic volume (LVESV) 30% (P = 0.027) and reduced LV ejection fraction (LVEF) 6.5% (P VNS-MI group, LVESV and LVEF did not differ from baseline. IC neurons showed depolarization of resting membrane potentials and increased input resistance in MI compared with VNS-MI and sham controls (P VNS-MI groups compared with controls (P VNS-MI compared with MI or controls (P VNS induced changes in myocytes, consistent with enhanced glycogenolysis, and blunted the MI-induced increase in the proapoptotic Bcl-2-associated X protein (P VNS mitigates MI-induced remodeling of the ICNS, correspondingly preserving ventricular function via both neural and cardiomyocyte-dependent actions. PMID:26276818

  17. Swimming training increases cardiac vagal activity and induces cardiac hypertrophy in rats

    Directory of Open Access Journals (Sweden)

    Medeiros A.

    2004-01-01

    Full Text Available The effect of swimming training (ST on vagal and sympathetic cardiac effects was investigated in sedentary (S, N = 12 and trained (T, N = 12 male Wistar rats (200-220 g. ST consisted of 60-min swimming sessions 5 days/week for 8 weeks, with a 5% body weight load attached to the tail. The effect of the autonomic nervous system in generating training-induced resting bradycardia (RB was examined indirectly after cardiac muscarinic and adrenergic receptor blockade. Cardiac hypertrophy was evaluated by cardiac weight and myocyte morphometry. Plasma catecholamine concentrations and citrate synthase activity in soleus muscle were also determined in both groups. Resting heart rate was significantly reduced in T rats (355 ± 16 vs 330 ± 20 bpm. RB was associated with a significantly increased cardiac vagal effect in T rats (103 ± 25 vs 158 ± 40 bpm, since the sympathetic cardiac effect and intrinsic heart rate were similar for the two groups. Likewise, no significant difference was observed for plasma catecholamine concentrations between S and T rats. In T rats, left ventricle weight (13% and myocyte dimension (21% were significantly increased, suggesting cardiac hypertrophy. Skeletal muscle citrate synthase activity was significantly increased by 52% in T rats, indicating endurance conditioning. These data suggest that RB induced by ST is mainly mediated parasympathetically and differs from other training modes, like running, that seems to mainly decrease intrinsic heart rate in rats. The increased cardiac vagal activity associated with ST is of clinical relevance, since both are related to increased life expectancy and prevention of cardiac events.

  18. Swimming training increases cardiac vagal activity and induces cardiac hypertrophy in rats

    Scientific Electronic Library Online (English)

    A., Medeiros; E.M., Oliveira; R., Gianolla; D.E., Casarini; C.E., Negrão; P.C., Brum.

    2004-12-01

    Full Text Available The effect of swimming training (ST) on vagal and sympathetic cardiac effects was investigated in sedentary (S, N = 12) and trained (T, N = 12) male Wistar rats (200-220 g). ST consisted of 60-min swimming sessions 5 days/week for 8 weeks, with a 5% body weight load attached to the tail. The effect [...] of the autonomic nervous system in generating training-induced resting bradycardia (RB) was examined indirectly after cardiac muscarinic and adrenergic receptor blockade. Cardiac hypertrophy was evaluated by cardiac weight and myocyte morphometry. Plasma catecholamine concentrations and citrate synthase activity in soleus muscle were also determined in both groups. Resting heart rate was significantly reduced in T rats (355 ± 16 vs 330 ± 20 bpm). RB was associated with a significantly increased cardiac vagal effect in T rats (103 ± 25 vs 158 ± 40 bpm), since the sympathetic cardiac effect and intrinsic heart rate were similar for the two groups. Likewise, no significant difference was observed for plasma catecholamine concentrations between S and T rats. In T rats, left ventricle weight (13%) and myocyte dimension (21%) were significantly increased, suggesting cardiac hypertrophy. Skeletal muscle citrate synthase activity was significantly increased by 52% in T rats, indicating endurance conditioning. These data suggest that RB induced by ST is mainly mediated parasympathetically and differs from other training modes, like running, that seems to mainly decrease intrinsic heart rate in rats. The increased cardiac vagal activity associated with ST is of clinical relevance, since both are related to increased life expectancy and prevention of cardiac events.

  19. Cardiac myocyte exosomes: stability, HSP60, and proteomics

    OpenAIRE

    Malik, Z. A.; Kott, K. S.; Poe, A. J.; Kuo, T.; Chen, L; Ferrara, K W; Knowlton, A A

    2013-01-01

    Exosomes, which are 50- to 100-nm-diameter lipid vesicles, have been implicated in intercellular communication, including transmitting malignancy, and as a way for viral particles to evade detection while spreading to new cells. Previously, we demonstrated that adult cardiac myocytes release heat shock protein (HSP)60 in exosomes. Extracellular HSP60, when not in exosomes, causes cardiac myocyte apoptosis via the activation of Toll-like receptor 4. Thus, release of HSP60 from exosomes would b...

  20. Endogenous antioxidant defense induction by melon superoxide dismutase reduces cardiac hypertrophy in spontaneously hypertensive rats.

    Science.gov (United States)

    Carillon, Julie; Rugale, Caroline; Rouanet, Jean-Max; Cristol, Jean-Paul; Lacan, Dominique; Jover, Bernard

    2014-08-01

    We assessed the influence of SODB, a melon superoxide dismutase (SOD), on left ventricular (LV) hypertrophy in SHR. SODB (4 or 40U SOD) was given orally for 4 or 28 days to SHR. For each treatment period, LV weight index (LVWI) and cardiomyocytes size were measured. SOD, glutathione peroxidase (GPx) and catalase expressions, and LV production and presence of superoxide anion were determined. Pro-inflammatory markers were also measured. SODB reduced LVWI and cardiomyocytes size after 4 or 28 days. Cardiac SOD and GPx increased by 30-40% with SODB. The presence but not production of superoxide anion was significantly reduced by SODB. No effect of SODB was detected on inflammatory status in any group. The beneficial effect of SODB on cardiac hypertrophy seems to be related to the stimulation of endogenous antioxidant defense, suggesting that SODB may be of interest as a dietary supplementation during conventional antihypertensive therapy. PMID:24601674

  1. Rapid Responses and Mechanism of Action for Low-Dose Bisphenol S on ex Vivo Rat Hearts and Isolated Myocytes: Evidence of Female-Specific Proarrhythmic Effects

    Science.gov (United States)

    Gao, Xiaoqian; Ma, Jianyong; Chen, Yamei

    2015-01-01

    Background Bisphenol S (BPS) has increasingly been used as a substitute for bisphenol A (BPA) in some “BPA-free” consumer goods and in thermal papers. Wide human exposure to BPS has been reported; however, the biological and potential toxic effects of BPS are poorly understood. Objective In this study, we sought to elucidate the sex-specific rapid effect of BPS in rat hearts and its underlying mechanism. Methods We examined the rapid effects of BPS in rat hearts using electrophysiology, confocal and conventional fluorescence imaging, and immunoblotting. Treatment was administered via acute perfusion of excised hearts or isolated cardiac myocytes. Results In female rat hearts acutely exposed to 10–9 M BPS, the heart rate was increased; in the presence of catecholamine-induced stress, the frequency of ventricular arrhythmia events was markedly increased. BPS-exposed hearts showed increased incidence of arrhythmogenic-triggered activities in female ventricular myocytes and altered myocyte Ca2+ handling, particularly spontaneous Ca2+ release from the sarcoplasmic reticulum. The dose responses of BPS actions were inverted U-shaped. The impact of BPS on myocyte Ca2+ handling was mediated by estrogen receptor ? signaling and by rapid increases in the phosphorylation of key Ca2+ handling proteins, including ryanodine receptor and phospholamban. The proarrhythmic effects of BPS were female specific; male rat hearts were not affected by BPS at the organ, myocyte, or protein levels. Conclusion Rapid exposure to low-dose BPS showed proarrhythmic impact on female rat hearts; these effects at the organ, cellular, and molecular levels are remarkably similar to those reported for BPA. Evaluation of the bioactivity and safety of BPS and other BPA analogs is necessary before they are used as BPA alternatives in consumer products. Citation Gao X, Ma J, Chen Y, Wang HS. 2015. Rapid responses and mechanism of action for low-dose bisphenol S on ex vivo rat hearts and isolated myocytes: evidence of female-specific proarrhythmic effects. Environ Health Perspect 123:571–578;?http://dx.doi.org/10.1289/ehp.1408679 PMID:25723814

  2. Reduction by beta-adrenoceptor blockade of hypoxia-induced right heart hypertrophy in the rat.

    OpenAIRE

    Ostman-Smith, I

    1995-01-01

    1. The study was undertaken to assess the role of beta-adrenoceptors in the induction of compensatory cardiac hypertrophy in an in vivo model. 2. In the rat, exposure to severe hypoxia (6% inspired oxygen for 8 h day) caused a 51% increase in right heart weight and a 75% increase in haematocrit. 3. The hypoxia-induced right ventricular hypertrophic response was reduced by 65% by oral treatment with a high dose of the non-selective beta-adrenoceptor antagonist, propranolol (80 mg kg-1 body wei...

  3. Genetic background influences adaptation to cardiac hypertrophy and Ca2+ handling gene expression

    OpenAIRE

    Waters, Steve B.; Diak, Douglass M.; Zuckermann, Matthew; Goldspink, Paul H.; Leoni, Lara; Roman, Brian B.

    2013-01-01

    Genetic variability has a profound effect on the development of cardiac hypertrophy in response to stress. Consequently, using a variety of inbred mouse strains with known genetic profiles may be powerful models for studying the response to cardiovascular stress. To explore this approach we looked at male C57BL/6J and 129/SvJ mice. Hemodynamic analyses of left ventricular pressures (LVPs) indicated significant differences in 129/SvJ and C57BL/6J mice that implied altered Ca2+ handling. Specif...

  4. Genetic Background Influences Adaptation To Cardiac Hypertrophy and Ca2+ Handling Gene Expression

    OpenAIRE

    BrianBRoman; PaulHarveyGoldspink

    2013-01-01

    Genetic variability has a profound effect on the development of cardiac hypertrophy in response to stress. Consequently, using a variety of inbred mouse strains with known genetic profiles may be powerful models for studying the response to cardiovascular stress. To explore this approach we looked at male C57BL/6J and 129/SvJ mice. Hemodynamic analyses of left ventricular pressures indicated significant differences in 129/SvJ and C57BL/6J mice that implied altered Ca2+ handling. Specifically...

  5. Angiopoietin-1 promotes cardiac and skeletal myocyte survival through integrins.

    Science.gov (United States)

    Dallabrida, Susan M; Ismail, Nesreen; Oberle, Julianne R; Himes, Blanca E; Rupnick, Maria A

    2005-03-01

    Cardiac myocyte loss, regardless of insult, can trigger compensatory myocardial remodeling leading to heart failure. Identifying mediators of cardiac myocyte survival may advance clinical efforts toward myocardial preservation. Angiopoietin-1 limits ischemia-induced cardiac injury. This benefit is ascribed to angiogenesis because the receptor, tie2, is largely endothelial-specific. We propose that direct, non-tie2 interactions of angiopoietin-1 on cardiac myocytes contribute to this cardioprotection. We found that mouse C2C12 skeletal myocytes lack tie2, yet dose-dependently adhered to angiopoietin-1 and angiopoietin-2 similarly to laminin, fibronectin, vitronectin, and more than to collagen-I, -III, and -IV. Adhesion was divalent cation-mediated (Mn2+, Ca2+, not Mg2+), blocked with EDTA/EGTA, RGD-based peptides, and select integrin subunit antibodies. Similar findings were obtained with human skeletal myocytes (HSMs) and freshly isolated rat neonatal cardiac myocytes (NCMs). Furthermore, angiopoietin-1 conferred significant survival advantage exceeding that of most cell matrices, which was not fully explained by differences in cell adhesion. Angiopoietin-1 promoted survival of serum-starved C2C12, HSM, and NCM (MTT, trypan blue) and prevented taxol-induced apoptosis (caspase-3). Immobilized and soluble angiopoietin-1 phosphorylated Akt(S473) and MAPK(p42/44), (not FAK(Y397)) in C2C12 more than in endothelial cells and more than did angiopoietin-2 or cell matrices. EDTA, RGD-based peptides, and some integrin antibodies blocked these responses. Angiopoietin-1 activated HSM and NCM Akt(S473) and MAPK(p42/44) survival pathways. We propose that this novel function contributes to developmental and cardioprotective actions of angiopoietin-1 presently attributed to vascular effects alone. Angiopoietin-1 may prove therapeutically valuable in cardiac remodeling by supporting myocyte viability and preserving pump function. The full text of this article is available online at http://circres.ahajournals.org. PMID:15692086

  6. Duration-controlled swimming exercise training induces cardiac hypertrophy in mice

    Scientific Electronic Library Online (English)

    F.S., Evangelista; P.C., Brum; J.E., Krieger.

    2003-12-01

    Full Text Available Exercise training associated with robust conditioning can be useful for the study of molecular mechanisms underlying exercise-induced cardiac hypertrophy. A swimming apparatus is described to control training regimens in terms of duration, load, and frequency of exercise. Mice were submitted to 60- [...] vs 90-min session/day, once vs twice a day, with 2 or 4% of the weight of the mouse or no workload attached to the tail, for 4 vs 6 weeks of exercise training. Blood pressure was unchanged in all groups while resting heart rate decreased in the trained groups (8-18%). Skeletal muscle citrate synthase activity, measured spectrophotometrically, increased (45-58%) only as a result of duration and frequency-controlled exercise training, indicating that endurance conditioning was obtained. In groups which received duration and endurance conditioning, cardiac weight (14-25%) and myocyte dimension (13-20%) increased. The best conditioning protocol to promote physiological hypertrophy, our primary goal in the present study, was 90 min, twice a day, 5 days a week for 4 weeks with no overload attached to the body. Thus, duration- and frequency-controlled exercise training in mice induces a significant conditioning response qualitatively similar to that observed in humans.

  7. Duration-controlled swimming exercise training induces cardiac hypertrophy in mice

    Directory of Open Access Journals (Sweden)

    F.S. Evangelista

    2003-12-01

    Full Text Available Exercise training associated with robust conditioning can be useful for the study of molecular mechanisms underlying exercise-induced cardiac hypertrophy. A swimming apparatus is described to control training regimens in terms of duration, load, and frequency of exercise. Mice were submitted to 60- vs 90-min session/day, once vs twice a day, with 2 or 4% of the weight of the mouse or no workload attached to the tail, for 4 vs 6 weeks of exercise training. Blood pressure was unchanged in all groups while resting heart rate decreased in the trained groups (8-18%. Skeletal muscle citrate synthase activity, measured spectrophotometrically, increased (45-58% only as a result of duration and frequency-controlled exercise training, indicating that endurance conditioning was obtained. In groups which received duration and endurance conditioning, cardiac weight (14-25% and myocyte dimension (13-20% increased. The best conditioning protocol to promote physiological hypertrophy, our primary goal in the present study, was 90 min, twice a day, 5 days a week for 4 weeks with no overload attached to the body. Thus, duration- and frequency-controlled exercise training in mice induces a significant conditioning response qualitatively similar to that observed in humans.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-10-09

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

  9. Local calcium release activation by DHPR calcium channel openings in rat cardiac myocytes.

    Science.gov (United States)

    Poláková, Eva; Zahradníková, Alexandra; Pavelková, Jana; Zahradník, Ivan; Zahradníková, Alexandra

    2008-08-15

    The principal role of calcium current in the triggering of calcium release in cardiac myocytes is well recognized. The mechanism of how calcium current (I(Ca)) controls the intensity of calcium release is not clear because of the stochastic nature of voltage-dependent gating of calcium channels (DHPRs) and of calcium-dependent gating of ryanodine receptors (RyRs). To disclose the relation between DHPR openings and the probability of calcium release, local calcium release activation by I(Ca) was investigated in rat ventricular myocytes using patch-clamp and confocal microscopy. Calcium spikes were activated by temporally synchronized DHPR calcium current triggers, generated by instantaneous 'tail' I(Ca) and modulated by prepulse duration, by tail potential, and by the DHPR agonist BayK 8644. The DHPR-RyR coupling fidelity was determined from the temporal distribution of calcium spike latencies using a model based on exponentially distributed DHPR open times. The analysis provided a DHPR mean open time of approximately 0.5 ms, RyR activation time constant of approximately 0.6 ms, and RyR activation kinetics of the 4th order. The coupling fidelity was low due to the inherent prevalence of very short DHPR openings but was increased when DHPR openings were prolonged by BayK 8644. The probability of calcium release activation was high, despite low coupling fidelity, due to the activation of many DHPRs at individual release sites. We conclude that the control of calcium release intensity by physiological stimuli can be achieved by modulating the number and duration of DHPR openings at low coupling fidelity, thus avoiding the danger of inadvertently triggering calcium release events. PMID:18591191

  10. Curcumin prevents and reverses murine cardiac hypertrophy

    OpenAIRE

    Li, Hong-Liang; Liu, Chen; de Couto, Geoffrey; Ouzounian, Maral; SUN, MEI; Wang, Ai-Bing; Huang, Yue; He, Cheng-Wei; SHI, YU; Chen, Xin; Nghiem, Mai P.; Liu, Youan; Chen, Manyin; Dawood, Fayez; Fukuoka, Masahiro

    2009-01-01

    Chromatin remodeling, particularly histone acetylation, plays a critical role in the progression of pathological cardiac hypertrophy and heart failure. We hypothesized that curcumin, a natural polyphenolic compound abundant in the spice turmeric and a known suppressor of histone acetylation, would suppress cardiac hypertrophy through the disruption of p300 histone acetyltransferase–dependent (p300-HAT–dependent) transcriptional activation. We tested this hypothesis using primary cultured rat ...

  11. Functions of Autophagy in Pathological Cardiac Hypertrophy

    OpenAIRE

    Zhenhua LI; WANG, JIAN; YANG Xiao

    2015-01-01

    Pathological cardiac hypertrophy is the response of heart to various biomechanical and physiopathological stimuli, such as aging, myocardial ischemia and hypertension. However, a long-term exposure to the stress makes heart progress to heart failure. Autophagy is a dynamic self-degradative process necessary for the maintenance of cellular homeostasis. Accumulating evidence has revealed a tight link between cardiomyocyte autophagy and cardiac hypertrophy. Sophisticatedly regulated autophagy pr...

  12. Septal myocardial protection during cardiac surgery for prevention of right ventricular dysfunction

    Directory of Open Access Journals (Sweden)

    Gerald Buckberg

    2008-11-01

    Full Text Available Postoperative right ventricular (RV failure is difficult to treat and develops from functional impairment of the underlying free wall and septum. This report describes the vital importance of the ventricular septum in RV structure /function relationships, demonstrates how the helical ventricular myocardial band model defines spatial geometry of the free wall and septum to provide architectural reasons for RV dynamic action, and focuses upon pathophysiologic reasons for adverse perioperative events resulting in right ventricular failure. Myocyte fiber orientation is the key to ventricular performance in health and disease. The transverse geometry of the free wall allows constriction (bellows type motion, whereas oblique septal fiber orientation and midline septal position is essential for ventricular twisting, the vital mechanism for RV ejection against increased pulmonary vascular resistance. The septum is considered “the lion or motor of RV performance”. This central muscle mass occupies ~40% of myocardial ventricular weight, and injury from impaired myocardial protection is a preventable event. Septal function should be the index of adequacy of myocardial protection and we will show echocardiographic evidence that the integrated cardioplegic method prevents its injury. Dysfunction of a normally functioning septum following surgical cardiac procedures calls for reevaluation of myocardial protection methods.

  13. Combined TRPC3 and TRPC6 blockade by selective small-molecule or genetic deletion inhibits pathological cardiac hypertrophy

    DEFF Research Database (Denmark)

    Seo, Kinya; Rainer, Peter P

    2014-01-01

    Chronic neurohormonal and mechanical stresses are central features of heart disease. Increasing evidence supports a role for the transient receptor potential canonical channels TRPC3 and TRPC6 in this pathophysiology. Channel expression for both is normally very low but is increased by cardiac disease, and genetic gain- or loss-of-function studies support contributions to hypertrophy and dysfunction. Selective small-molecule inhibitors remain scarce, and none target both channels, which may be useful given the high homology among them and evidence of redundant signaling. Here we tested selective TRPC3/6 antagonists (GSK2332255B and GSK2833503A; IC50, 3-21 nM against TRPC3 and TRPC6) and found dose-dependent blockade of cell hypertrophy signaling triggered by angiotensin II or endothelin-1 in HEK293T cells as well as in neonatal and adult cardiac myocytes. In vivo efficacy in mice and rats was greatly limited by rapid metabolism and high protein binding, although antifibrotic effects with pressure overload were observed. Intriguingly, although gene deletion of TRPC3 or TRPC6 alone did not protect against hypertrophy or dysfunction from pressure overload, combined deletion was protective, supporting the value of dual inhibition. Further development of this pharmaceutical class may yield a useful therapeutic agent for heart disease management.

  14. Effect of melatonin, captopril, spironolactone and simvastatin on blood pressure and left ventricular remodelling in spontaneously hypertensive rats.

    Czech Academy of Sciences Publication Activity Database

    Šimko, F.; Pechá?ová, Olga; Pelouch, Václav; Kraj?írovi?ová, K.; Müllerová, M.; Bednárová, K.; Adamcová, M.; Paulis, L.

    2009-01-01

    Ro?. 27, Suppl.6 (2009), S5-S10. ISSN 0263-6352 R&D Projects: GA ?R GA305/09/0336 Institutional research plan: CEZ:AV0Z50110509 Keywords : cardiac hypertrophy * fibrosis * ventricular remodeling Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 4.988, year: 2009

  15. [Left ventricular function in patients with arterial hypertension during the performance of acute drug tests with captopril and nifedipine].

    Science.gov (United States)

    Savchenko, A P; Smirnov, A A; Bekzhigitov, S B; Abugov, S A; Shapkina, L S; Arabidze, G G

    1993-01-01

    An examination was made of 22 hypertensive patients with clinical and echoCG symptoms of left ventricular hypertrophy. All the patients underwent coronary angiography, transvenous multiphase left ventriculography and acute captopril (11 patients), nifedipine (11 patients) tests. A single oral 25 mg dose of captopril increased energetic efficacy of cardiocycle, restored diastolic function of the left ventricle, aroused myocardial contractility. PMID:8211794

  16. Hypertrophy of Ligament of Treitz

    Directory of Open Access Journals (Sweden)

    Siddharth P. Dubhashi

    2015-04-01

    Full Text Available Congenital duodenal obstruction commonly occurs due to malrotation, atresia, stenosis and annular pancreas in decreasing order of frequency. This is a case report of a 12 year old male child who presented with complaints of non-projectile vomiting and abdominal distension and pain after meals since 7 years. Barium study showed narrowing of the Duodeno-jejunal(DJ junction due to hypertrophied ligament of Treitz. Exploratory laparotomy revealed a dilated stomach and collapsed bowel loops. There were adhesions at DJ junction and other parts of the small intestine. Adhesiolysis was done. The followup revealed a weight gain of 2 kg. The barium study was repeated which also revealed a normal study. Congenital obstruction of duodeno-jejunal junction due to extrinsic band or due to narrower attachment of ligament of Treitz at duodeno-jejunal flexure is a rare cause of bilious vomiting in the newborn period. A broad attachment of the ligament of Treitz makes a smooth obtuse angle at the duodeno-jejunum junction whereas a narrower insertion creates an acute angle that predisposes to obstruction.Duodenal obstruction may rarely occur in the presence of a normally rotated gut.

  17. Morphologic features and nuclide composition of infarction-associated cardiac myocyte mineralization in humans.

    OpenAIRE

    Lockard, V. G.; Bloom, S.

    1991-01-01

    Low dietary Mg results in Ca loading of cardiac myocytes, which increases the likelihood of myocyte calcification in the event of acute myocardial infarction (AMI), and possibly increases myocyte vulnerability to necrosis. Bloom and Peric-Golia1 previously reported an autopsy study of cases from the Washington, D.C. area (a region with low levels of Mg in the drinking water), demonstrating AMI-associated mineralization in myocytes with histologically normal nuclei and cross striations, as wel...

  18. Low-Dose Bisphenol A and Estrogen Increase Ventricular Arrhythmias Following Ischemia-Reperfusion in Female Rat Hearts

    OpenAIRE

    YAN, SUJUAN; Song, Weizhong; Chen, Yamei; HONG, KUI; Rubinstein, Jack; Wang, Hong-Sheng

    2013-01-01

    Bisphenol A (BPA) is an environmental estrogenic endocrine disruptor that may have adverse health impacts on a range of tissue/systems. In previous studies, we reported that BPA rapidly promoted arrhythmias in female rodent hearts through alteration of myocyte calcium handling. In the present study we investigated the acute effects of BPA on ventricular arrhythmias and infarction following ischemia-reperfusion in rat hearts. Rat hearts were subjected to 20 minutes of global ischemia followed ...

  19. Ventricular dysfunction in children with obstructive sleep apnea: radionuclide assessment

    Energy Technology Data Exchange (ETDEWEB)

    Tal, A.; Leiberman, A.; Margulis, G.; Sofer, S.

    1988-01-01

    Ventricular function was evaluated using radionuclide ventriculography in 27 children with oropharyngeal obstruction and clinical features of obstructive sleep apnea. Their mean age was 3.5 years (9 months to 7.5 years). Conventional clinical assessment did not detect cardiac involvement in 25 of 27 children; however, reduced right ventricular ejection fraction (less than 35%) was found in 10 (37%) patients (mean: 19.5 +/- 2.3% SE, range: 8-28%). In 18 patients wall motion abnormality was detected. In 11 children in whom radionuclide ventriculography was performed before and after adenotonsillectomy, right ventricular ejection fraction rose from 24.4 +/- 3.6% to 46.7 +/- 3.4% (P less than 0.005), and in all cases wall motion showed a definite improvement. In five children, left ventricular ejection fraction rose greater than 10% after removal of oropharyngeal obstruction. It is concluded that right ventricular function may be compromised in children with obstructive sleep apnea secondary to adenotonsillar hypertrophy, even before clinical signs of cardiac involvement are present.

  20. Ventricular dysfunction in children with obstructive sleep apnea: radionuclide assessment

    International Nuclear Information System (INIS)

    Ventricular function was evaluated using radionuclide ventriculography in 27 children with oropharyngeal obstruction and clinical features of obstructive sleep apnea. Their mean age was 3.5 years (9 months to 7.5 years). Conventional clinical assessment did not detect cardiac involvement in 25 of 27 children; however, reduced right ventricular ejection fraction (less than 35%) was found in 10 (37%) patients (mean: 19.5 +/- 2.3% SE, range: 8-28%). In 18 patients wall motion abnormality was detected. In 11 children in whom radionuclide ventriculography was performed before and after adenotonsillectomy, right ventricular ejection fraction rose from 24.4 +/- 3.6% to 46.7 +/- 3.4% (P less than 0.005), and in all cases wall motion showed a definite improvement. In five children, left ventricular ejection fraction rose greater than 10% after removal of oropharyngeal obstruction. It is concluded that right ventricular function may be compromised in children with obstructive sleep apnea secondary to adenotonsillar hypertrophy, even before clinical signs of cardiac involvement are present

  1. PGC-1{alpha} accelerates cytosolic Ca{sup 2+} clearance without disturbing Ca{sup 2+} homeostasis in cardiac myocytes

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Min, E-mail: chenminyx@gmail.com [Institute of Molecular Medicine, State Key Laboratory of Biomembrane and Membrane Biotechnology, Peking University, Beijing 100871 (China); Yunnan Centers for Diseases Prevention and Control, Kunming 650022 (China); Wang, Yanru [Institute of Molecular Medicine, State Key Laboratory of Biomembrane and Membrane Biotechnology, Peking University, Beijing 100871 (China); Qu, Aijuan [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)

    2010-06-11

    Energy metabolism and Ca{sup 2+} handling serve critical roles in cardiac physiology and pathophysiology. Peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1{alpha}) 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{alpha} in cardiac Ca{sup 2+} 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{alpha} via adenoviral transduction. Our data shows that overexpressing PGC-1{alpha} improved myocyte contractility without increasing the amplitude of Ca{sup 2+} transients, suggesting that myofilament sensitivity to Ca{sup 2+} increased. Interestingly, the decay kinetics of global Ca{sup 2+} transients and Ca{sup 2+} waves accelerated in PGC-1{alpha}-expressing cells, but the decay rate of caffeine-elicited Ca{sup 2+} transients showed no significant change. This suggests that sarcoplasmic reticulum (SR) Ca{sup 2+}-ATPase (SERCA2a), but not Na{sup +}/Ca{sup 2+} exchange (NCX) contribute to PGC-1{alpha}-induced cytosolic Ca{sup 2+} clearance. Furthermore, PGC-1{alpha} induced the expression of SERCA2a in cultured cardiac myocytes. Importantly, overexpressing PGC-1{alpha} did not disturb cardiac Ca{sup 2+} homeostasis, because SR Ca{sup 2+} load and the propensity for Ca{sup 2+} waves remained unchanged. These data suggest that PGC-1{alpha} can ameliorate cardiac Ca{sup 2+} cycling and improve cardiac work output in response to physiological stress. Unraveling the PGC-1{alpha}-calcium handing pathway sheds new light on the role of PGC-1{alpha} in the therapy of cardiac diseases.

  2. Mechanisms of nascent fiber formation during avian skeletal muscle hypertrophy

    Science.gov (United States)

    McCormick, K. M.; Schultz, E.

    1992-01-01

    This study examined two putative mechanisms of new fiber formation in postnatal skeletal muscle, namely longitudinal fragmentation of existing fibers and de novo formation. The relative contributions of these two mechanisms to fiber formation in hypertrophying anterior latissimus dorsi (ALD) muscle were assessed by quantitative analysis of their nuclear populations. Muscle hypertrophy was induced by wing-weighting for 1 week. All nuclei formed during the weighting period were labeled by continuous infusion of 5-bromo-2'-deoxyuridine (BrdU), a thymidine analog, and embryonic-like fibers were identified using an antibody to ventricular-like embryonic (V-EMB) myosin. The number of BrdU-labeled and unlabeled nuclei in V-EMB-positive fibers were counted. Wing-weighting resulted in significant muscle enlargement and the appearance of many V-EMB+ fibers. The majority of V-EMB+ fibers were completely independent of mature fibers and had a nuclear density characteristics of developing fibers. Furthermore, nearly 100% of the nuclei in independent V-EMB+ fibers were labeled. These findings strongly suggest that most V-EMB+ fibers were nascent fibers formed de novo during the weighting period by satellite cell activation and fusion. Nascent fibers were found primarily in the space between fascicles where they formed a complex anastomosing network of fibers running at angles to one another. Although wing-weighting induced an increase in the number of branched fibers, there was no evidence that V-EMB+ fibers were formed by longitudinal fragmentation. The location of newly formed fibers in wing-weighted and regenerating ALD muscle was compared to determine whether satellite cells in the ALD muscle were unusual in that, if stimulated to divide, they would form fibers in the inter- and intrafascicular space. In contrast to wing-weighted muscle, nascent fibers were always found closely associated with necrotic fibers. These results suggest that wing-weighting is not simply another model of regeneration, but rather produces a unique environment which induces satellite cell migration and subsequent fiber formation in the interfascicular space. De novo fiber formation is apparently the principal mechanism for the hyperplasia reported to occur in the ALD muscle undergoing hypertrophy induced by wing-weighting.

  3. Chronic cardiac resynchronization therapy and reverse ventricular remodeling in a model of nonischemic cardiomyopathy.

    Science.gov (United States)

    Nishijima, Yoshinori; Sridhar, Arun; Viatchenko-Karpinski, Serge; Shaw, Courtney; Bonagura, John D; Abraham, William T; Joshi, Mandar S; Bauer, John Anthony; Hamlin, Robert L; Györke, Sandor; Feldman, David S; Carnes, Cynthia A

    2007-09-15

    While cardiac resynchronization therapy (CRT) has been shown to reduce morbidity and mortality in heart failure (HF) patients, the fundamental mechanisms for the efficacy of CRT are poorly understood. The lack of understanding of these basic mechanisms represents a significant barrier to our understanding of the pathogenesis of HF and potential recovery mechanisms. Our purpose was to determine cellular mechanisms for the observed improvement in chronic HF after CRT. We used a canine model of chronic nonischemic cardiomyopathy. After 15 months, dogs were randomized to continued RV tachypacing (untreated HF) or CRT for an additional 9 months. Six minute walk tests, echocardiograms, and electrocardiograms were done to assess the functional response to therapy. Left ventricular (LV) midmyocardial myocytes were isolated to study electrophysiology and intracellular calcium regulation. Compared to untreated HF, CRT improved HF-induced increases in LV volumes, diameters and mass (pHF-induced prolongations in LV myocyte repolarization (pHF-induced depolarization (pHF-induced reductions in calcium (pHF-induced increases in LV interstitial fibrosis. Using a translational approach in a chronic HF model, CRT significantly improved LV structure; this was accompanied by improved LV myocyte electrophysiology and calcium regulation. The beneficial effects of CRT may be attributable, in part, to improved LV myocyte function. PMID:17884106

  4. Automaticity in acute ischemia: Bifurcation analysis of a human ventricular model

    Science.gov (United States)

    Bouchard, Sylvain; Jacquemet, Vincent; Vinet, Alain

    2011-01-01

    Acute ischemia (restriction in blood supply to part of the heart as a result of myocardial infarction) induces major changes in the electrophysiological properties of the ventricular tissue. Extracellular potassium concentration ([Ko+]) increases in the ischemic zone, leading to an elevation of the resting membrane potential that creates an “injury current” (IS) between the infarcted and the healthy zone. In addition, the lack of oxygen impairs the metabolic activity of the myocytes and decreases ATP production, thereby affecting ATP-sensitive potassium channels (IKatp). Frequent complications of myocardial infarction are tachycardia, fibrillation, and sudden cardiac death, but the mechanisms underlying their initiation are still debated. One hypothesis is that these arrhythmias may be triggered by abnormal automaticity. We investigated the effect of ischemia on myocyte automaticity by performing a comprehensive bifurcation analysis (fixed points, cycles, and their stability) of a human ventricular myocyte model [K. H. W. J. ten Tusscher and A. V. Panfilov, Am. J. Physiol. Heart Circ. Physiol.AJPHAP0363-613510.1152/ajpheart.00109.2006 291, H1088 (2006)] as a function of three ischemia-relevant parameters [Ko+], IS, and IKatp. In this single-cell model, we found that automatic activity was possible only in the presence of an injury current. Changes in [Ko+] and IKatp significantly altered the bifurcation structure of IS, including the occurrence of early-after depolarization. The results provide a sound basis for studying higher-dimensional tissue structures representing an ischemic heart.

  5. Pitfalls in the diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia.

    Science.gov (United States)

    Marcus, Frank; Basso, Cristina; Gear, Kathleen; Sorrell, Vincent L

    2010-04-01

    The diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia is determined according to Task Force Criteria published in 1994 that included imaging abnormalities of the right ventricle and diagnostic pathologic evaluation findings of the right ventricular myocardium by endomyocardial biopsy. These have recently been modified to include evaluation using cardiac magnetic resonance imaging. In addition, quantitative criteria for the percentage of fibrosis and the decrease in myocytes have been included in the new criteria. The pitfalls of determining the presence of arrhythmogenic right ventricular cardiomyopathy/dysplasia at autopsy and the difficulty in assessing the presence of this disease in family members are well illustrated in the present report. In conclusion, we have illustrated the need to subscribe to the modified criteria to avoid misdiagnosis. PMID:20346327

  6. Rol del óxido nítrico en la hipertrofia arteriolar pulmonar y ventricular cardiaca derecha en pollos a nivel del mar y expuestos a Hipoxia de la altura: The role of nitric oxide in pulmonary arteriolar and right heart ventricle hypertrophy in chickens at sea level and exposed to high altitude Hypoxia

    Scientific Electronic Library Online (English)

    María, Vásquez C.; Sergio, Cueva M.; Boris, Lira M.; Milder, Ayón S.; José, Rodríguez G.; Pedro, Angulo H.; Néstor, Falcón P..

    Full Text Available El objetivo del presente estudio fue determinar los valores de nitritos y nitratos, metabolitos estables del óxido nítrico (ON), y su correlación con el grado de hipertrofia arteriolar pulmonar en aves sometidas a hipoxia ambiental. Se emplearon 135 aves machos de la línea Cobb-Vantres, nacidos a ni [...] vel del mar. De estas, 120 fueron divididos en dos grupos: 60 aves criadas a nivel del mar (NM) y 60 aves criadas en altura a 3320 msnm (A), en tanto que las 15 aves restantes fueron sacrificadas al primer día de edad. Quince aves seleccionadas al azar de cada grupo fueron sacrificadas a los 10, 20, 30 y 40 días de edad. Se determinó el peso corporal (PC), hematocrito (Ht), nitritos y nitratos, relación capa muscular/diámetro arteriolar pulmonar (CM/DA), relación peso del ventrículo derecho/ peso total del ventrículo (VD/VT), y relación peso ventrículo derecho/peso corporal (VD/PC). El PC fue mayor a NM que en A (p Abstract in english The aim of this study was to determine the nitrites and nitrates concentration, stable metabolites of NO, and its correlation with the degree of pulmonary arteriole hypertrophy in chickens raised at environmental hypoxia. A total of 135 Cobb-Vantres male chickens, born at sea level were used. Of thi [...] s, 60 chicks raised at sea level (SL), and 60 at high altitude (A), 3230 m above sea level; while the remaining 15 birds were slaughtered at 1 day of age. Fifteen 15 chicks per group were randomly selected and slaughtered at 10, 20, 30 and 40 days of age. It was determined body weight (BW), hematocrite (Ht), nitrites and nitrates, muscular wall/arteriolar diameter (CM/DA) ratio, right ventricle weight/total ventricle weight ratio (RV/TV), and right ventricle weight/body weight ratio (RV/BW) ratio. BW was greater at SL than at A (p

  7. Measurement of isolated myocyte volume using the Coulter models Z2 and ZM/C256: a comparison of instrument function.

    Science.gov (United States)

    Said, S; Tamura, T; Gerdes, A M

    1998-09-01

    Changes in cardiac structure that depart from normal have generally been termed "remodeling". Assessment of ventricular remodeling at the cellular level should include measurement of myocyte dimensions. A well-established and reliable method to assess myocyte remodeling uses isolated cells and the Coulter Counter/Channelyzer system. The new Coulter Model Z2 has numerous modifications and improvements from the Model Z predecessor(s) interfaced to a pulse-height analyzer (e.g., channelyzer). Improvements of the Model Z2 over older instruments include: (i) elimination of the mercury manometer with accompanying oil-displacement pump; (ii) reduced size and weight; (iii) a higher degree of mechanization and automation; (iv) inclusion of an advanced comprehensive statistical package and (v) a substantial reduction in cost. The purpose of this study was to determine if the newly modified instrument produces the same results as the previous instrument combinations, which were shown to produce reliable cell volume data from irregularly shaped cells such as cardiac myocytes. PMID:9762450

  8. P2X4 receptor–eNOS signaling pathway in cardiac myocytes as a novel protective mechanism in heart failure

    Science.gov (United States)

    Yang, Ronghua; Beqiri, Dardan; Shen, Jian-Bing; Redden, John M.; Dodge-Kafka, Kimberly; Jacobson, Kenneth A.; Liang, Bruce T.

    2014-01-01

    We have demonstrated using immunoprecipitation and immunostaining a novel physical association of the P2X4 receptor (P2X4R), a ligand-gated ion channel, with the cardioprotective, calcium-dependent enzyme endothelial nitric oxide synthase (eNOS). Treatment of murine ventricular myocytes with the P2XR agonist 2-methylthioATP (2-meSATP) to induce a current (mainly Na+) increased the formation of nitric oxide (NO), as measured using a fluorescent probe. Possible candidates for downstream effectors mediating eNOS activity include cyclic GMP and PKG or cellular protein nitrosylation. A cardiac-specific P2X4R overexpressing mouse line was protected from heart failure (HF) with improved cardiac function and survival in post-infarct, pressure overload, and calsequestrin (CSQ) overexpression models of HF. Although the role of the P2X4R in other tissues such as the endothelium and monocytes awaits characterization in tissue-specific KO, cardiac-specific activation of eNOS may be more cardioprotective than an increased activity of global systemic eNOS. The intra-myocyte formation of NO may be more advantageous over NO derived externally from a donor. A small molecule drug stimulating this sarcolemmal pathway or gene therapy-mediated overexpression of the P2X4R in cardiac myocytes may represent a new therapy for both ischemic and pressure overloaded HF. PMID:25750695

  9. Left ventricular mass is associated with ventricular repolarization heterogeneity one year after renal transplantation.

    Science.gov (United States)

    Arnol, M; Starc, V; Knap, B; Potocnik, N; Bren, A F; Kandus, A

    2008-02-01

    Ventricular repolarization heterogeneity (VRH) is associated with the risk of arrhythmia and cardiac death. This study investigated the association between VRH and left ventricular mass (LVM) in renal transplant recipients 1 year after transplantation. Echocardiography and 5-min 12-lead electrocardiogram were recorded and GFR was estimated (eGFR) in 68 nondiabetic patients. Beat-to-beat QT interval variability algorithm was used to calculate SDNN-QT and rMSSD-QT indices of VRH. To quantify QT interval variability relative to heart rate fluctuations, QTRR index was calculated. Left ventricular hypertrophy (LVH) was present in 44 patients (65%). LVM and incidence of LVH were increased in 28 patients with eGFR or =60 mL/min/1.73 m(2) (248 +/- 61 g and 86% vs. 210 +/- 46 g and 50%, respectively; p < 0.01). A direct correlation was found between LVM and SDNN-QT (R = 0.47, R(2)= 0.23; p < 0.001), rMSSD-QT (R = 0.27; R(2)= 0.10; p = 0.034), and QTRR (R = 0.55; R(2)= 0.31; p < 0.001) indices. In conclusion, greater LVM is associated with increased VRH in renal transplant recipients, providing a link with the high risk of arrhythmia and cardiac death, specifically in patients with decreased graft function. PMID:18190661

  10. A new quantitative description of intracellular Ca2+ dynamics in the model of rat ventricular myocyte.

    Czech Academy of Sciences Publication Activity Database

    Pásek, Michal; Šimurda, J.

    Prague : Institute of Thermomechanics AS CR, v. v. i., 2011 - (Fuis, V.), s. 451-454 ISBN 978-80-87012-33-8. [Engineering Mechanics 2011 /17./. Svratka (CZ), 09.05.2011-12.05.2011] Institutional research plan: CEZ:AV0Z20760514 Keywords : cardiac cell * intracellular Ca dynamics * quantitative modelling Subject RIV: BO - Biophysics

  11. Increased ventricular preload is compensated by myocyte proliferation in normal and hypoplastic fetal chick left ventricle.

    Czech Academy of Sciences Publication Activity Database

    Dealmeida, A.; McQuinn, T. C.; Sedmera, David

    2007-01-01

    Ro?. 100, - (2007), s. 1363-1370. ISSN 0009-7330 Institutional research plan: CEZ:AV0Z50450515 Keywords : chick embryo * hemodynamics * fetal surgery * hypoplastic left heart syndrome Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 9.721, year: 2007

  12. Quantification of t-tubule area and protein distribution in rat cardiac ventricular myocytes.

    Czech Academy of Sciences Publication Activity Database

    Pásek, Michal; Brette, F.; Nelson, A.; Pearce, C.; Qaiser, A.; Christé, G.; Orchard, C.

    2008-01-01

    Ro?. 96, - (2008), s. 244-257. ISSN 0079-6107 Institutional research plan: CEZ:AV0Z20760514 Keywords : cardiac cell * transverse-axial tubular system * tubular membrane area * tubular membrane capacitance Subject RIV: BO - Biophysics Impact factor: 6.388, year: 2008

  13. VENTRICULAR ARRHYTHMIAS IN CHILDHOOD

    Directory of Open Access Journals (Sweden)

    AL Sami

    2005-01-01

    Full Text Available Isolated premature ventricular beats may be seen in 15% of normal newborns, 30% of normal adolescents and 66% of adolescents with repaired heart disease. Sustained ventricular arrhythmias are relatively rare în young normal hearts. Sudden cardiac death is also rare în young with normal hearts, although there is an increased incidence in dilated and hypertrophic cardiomyopathies and following repair of particular congenital heart lesions.Patients with cardiomyopathy (CM often have ventricular arrhythmias, although the risk of mortality is more closely linked to ventricular function. There are many infants and pediatric patients with apparently normal hearts who have asymptomatic nonsustained ventricular tachycardia.The main concern is to identify diagnoses such as long QT syndrome associated with recurrent cardiac syncope so that appropriate choices can be made regarding drug and/or device therapy.

  14. The Upper Limit of Physiological Cardiac Hypertrophy in Elite Male Athletes

    Directory of Open Access Journals (Sweden)

    Mohammad A. Hnidawei

    2010-01-01

    Full Text Available Problem statement: Establishment of upper normal limits of physiological hypertrophy in response to physical training is important in the differentiation of physiological and pathological left ventricular hypertrophy. The goal of our study was to investigate the normal upper limits of cardiac dimensions in elite athletes in Jordan in different types of sports (8 soccer players, 8 sprinters, 8 long distance runners, 6 weight lifters, 6 body builders. Approach: A total of 36 male athletes age 25±5 years of age, representing various sports were examined using standard two-dimensional guided M-mode and Doppler echocardiography to evaluate cardiac dimensions. Results: Results showed that 36 male athletes, 24 (66.6% presented with LVEDD �50 mm with an upper limits of 53.4 mm sd 3.15, only 12 subjects (33.3% presented with wall thickness values �11 mm, sd 0.53. None were found to have maximum wall thickness greater than 13 mm. There was a significant difference (pConclusion: There is a sport-specific left ventricular adaptation, the endurance heart differ significantly from the rest of the athletes investigated heart.

  15. Bases moleculares de la hipertrofia ventricular izquierda: papel del estrés oxidativo

    Directory of Open Access Journals (Sweden)

    Félix Broche Valle

    1997-12-01

    Full Text Available La hipertensión arterial (HTA como enfermedad primaria es una de las primeras causas de morbilidad y mortalidad general en muchos países. La cardiopatía isquémica y otras formas clínicas de la enfermedad cardiovascular aterosclerótica se presentan con mayor frecuencia en los pacientes hipertensos. La aparición y severidad de las manifestaciones de isquemia miocárdica se incrementan si coexiste hipertrofia ventricular izquierda. En el miocardio hipertrófico se producen eventos de isquemia/reperfusión durante cada ciclo cardíaco. En estas condiciones, diversos factores conducen al estrés oxidativo cuyas consecuencias se expresan por alteraciones morfofuncionales en el corazón y otros sistemas. En este trabajo se presentan los principales mecanismos conocidos que aportan las bases moleculares de la hipertrofia ventricular y de la pared arterial en los pacientes hipertensos, así como el origen y significado fisiopatológico del estrés oxidativo en esta entidad con el propósito de contribuir a la sustentación teórica de los criterios para diagnóstico, pronóstico, evolución y tratamiento del paciente hipertenso con hipertrofia ventricular izquierda.Arterial hypertension (AHT as a primary disease is one of the first causes of morbidity and general mortality in many countries. Ischemic cardiopathy and other clinical forms of the atherosclerotic cardiovascular disease are more common among hypertensives. The appearance and severity of the manifestations of myocardial infarction increase if left ventricular hypertrophy coexists. In the hypertrophic myocardium, events of ischemia/reperfusion take place during each cardiac cycle. Under these conditions, different factors lead to the oxidative stress, whose consequences are expressed by morph ofunctional alterations of the heart and other systems. In this paper, the main mechanisms giving molecular bases of ventricular hypertrophy ahod of the arterial wall in hypertensives, as well as the origin and physiopathologic significance of the oxidative stress in this disease, are presented aimed at contributing to the theoretical support of the criteria for diagnosis, prognosis, evolution and treatment of the hypertensive patient suffering from left ventricular hypertrophy.

  16. Decreased cardiac L-type Ca²? channel activity induces hypertrophy and heart failure in mice.

    Science.gov (United States)

    Goonasekera, Sanjeewa A; Hammer, Karin; Auger-Messier, Mannix; Bodi, Ilona; Chen, Xiongwen; Zhang, Hongyu; Reiken, Steven; Elrod, John W; Correll, Robert N; York, Allen J; Sargent, Michelle A; Hofmann, Franz; Moosmang, Sven; Marks, Andrew R; Houser, Steven R; Bers, Donald M; Molkentin, Jeffery D

    2012-01-01

    Antagonists of L-type Ca²? channels (LTCCs) have been used to treat human cardiovascular diseases for decades. However, these inhibitors can have untoward effects in patients with heart failure, and their overall therapeutic profile remains nebulous given differential effects in the vasculature when compared with those in cardiomyocytes. To investigate this issue, we examined mice heterozygous for the gene encoding the pore-forming subunit of LTCC (calcium channel, voltage-dependent, L type, ?1C subunit [Cacna1c mice; referred to herein as ?1C?/? mice]) and mice in which this gene was loxP targeted to achieve graded heart-specific gene deletion (termed herein ?1C-loxP mice). Adult cardiomyocytes from the hearts of ?1C?/? mice at 10 weeks of age showed a decrease in LTCC current and a modest decrease in cardiac function, which we initially hypothesized would be cardioprotective. However, ?1C?/? mice subjected to pressure overload stimulation, isoproterenol infusion, and swimming showed greater cardiac hypertrophy, greater reductions in ventricular performance, and greater ventricular dilation than ?1C?/? controls. The same detrimental effects were observed in ?1C-loxP animals with a cardiomyocyte-specific deletion of one allele. More severe reductions in ?1C protein levels with combinatorial deleted alleles produced spontaneous cardiac hypertrophy before 3 months of age, with early adulthood lethality. Mechanistically, our data suggest that a reduction in LTCC current leads to neuroendocrine stress, with sensitized and leaky sarcoplasmic reticulum Ca²? release as a compensatory mechanism to preserve contractility. This state results in calcineurin/nuclear factor of activated T cells signaling that promotes hypertrophy and disease. PMID:22133878

  17. Deficiency of cardiac Acyl-CoA synthetase-1 induces diastolic dysfunction, but pathologic hypertrophy is reversed by rapamycin.

    Science.gov (United States)

    Paul, David S; Grevengoed, Trisha J; Pascual, Florencia; Ellis, Jessica M; Willis, Monte S; Coleman, Rosalind A

    2014-06-01

    In mice with temporally-induced cardiac-specific deficiency of acyl-CoA synthetase-1 (Acsl1(H-/-)), the heart is unable to oxidize long-chain fatty acids and relies primarily on glucose for energy. These metabolic changes result in the development of both a spontaneous cardiac hypertrophy and increased phosphorylated S6 kinase (S6K), a substrate of the mechanistic target of rapamycin, mTOR. Doppler echocardiography revealed evidence of significant diastolic dysfunction, indicated by a reduced E/A ratio and increased mean performance index, although the deceleration time and the expression of sarco/endoplasmic reticulum calcium ATPase and phospholamban showed no difference between genotypes. To determine the role of mTOR in the development of cardiac hypertrophy, we treated Acsl1(H-/-) mice with rapamycin. Six to eight week old Acsl1(H-/-) mice and their littermate controls were given i.p. tamoxifen to eliminate cardiac Acsl1, then concomitantly treated for 10weeks with i.p. rapamycin or vehicle alone. Rapamycin completely blocked the enhanced ventricular S6K phosphorylation and cardiac hypertrophy and attenuated the expression of hypertrophy-associated fetal genes, including ?-skeletal actin and B-type natriuretic peptide. mTOR activation of the related Acsl3 gene, usually associated with pathologic hypertrophy, was also attenuated in the Acsl1(H-/-) hearts, indicating that alternative pathways of fatty acid activation did not compensate for the loss of Acsl1. Compared to controls, Acsl1(H-/-) hearts exhibited an 8-fold higher uptake of 2-deoxy[1-(14)C]glucose and a 35% lower uptake of the fatty acid analog 2-bromo[1-(14)C]palmitate. These data indicate that Acsl1-deficiency causes diastolic dysfunction and that mTOR activation is linked to the development of cardiac hypertrophy in Acsl1(H-/-) mice. PMID:24631848

  18. Deficiency of cardiac Acyl-CoA synthetase-1 induces diastolic dysfunction, but pathologic hypertrophy is reversed by rapamycin

    DEFF Research Database (Denmark)

    Paul, David S; Grevengoed, Trisha J

    2014-01-01

    In mice with temporally-induced cardiac-specific deficiency of acyl-CoA synthetase-1 (Acsl1(H-/-)), the heart is unable to oxidize long-chain fatty acids and relies primarily on glucose for energy. These metabolic changes result in the development of both a spontaneous cardiac hypertrophy and increased phosphorylated S6 kinase (S6K), a substrate of the mechanistic target of rapamycin, mTOR. Doppler echocardiography revealed evidence of significant diastolic dysfunction, indicated by a reduced E/A ratio and increased mean performance index, although the deceleration time and the expression of sarco/endoplasmic reticulum calcium ATPase and phospholamban showed no difference between genotypes. To determine the role of mTOR in the development of cardiac hypertrophy, we treated Acsl1(H-/-) mice with rapamycin. Six to eight week old Acsl1(H-/-) mice and their littermate controls were given i.p. tamoxifen to eliminate cardiac Acsl1, then concomitantly treated for 10weeks with i.p. rapamycin or vehicle alone. Rapamycin completely blocked the enhanced ventricular S6K phosphorylation and cardiac hypertrophy and attenuated the expression of hypertrophy-associated fetal genes, including ?-skeletal actin and B-type natriuretic peptide. mTOR activation of the related Acsl3 gene, usually associated with pathologic hypertrophy, was also attenuated in the Acsl1(H-/-) hearts, indicating that alternative pathways of fatty acid activation did not compensate for the loss of Acsl1. Compared to controls, Acsl1(H-/-) hearts exhibited an 8-fold higher uptake of 2-deoxy[1-(14)C]glucose and a 35% lower uptake of the fatty acid analog 2-bromo[1-(14)C]palmitate. These data indicate that Acsl1-deficiency causes diastolic dysfunction and that mTOR activation is linked to the development of cardiac hypertrophy in Acsl1(H-/-) mice.

  19. The Relationship between the Transforming Growth Factor ?1 T29C Gene Polymorphism and Left Ventricular Geometry and Function in Hypertensive Subjects

    OpenAIRE

    Salvatore Corrao; Maria Cristina Fiore; Daniela Colomba; Domenico Nuzzo; Tiziana Di Chiara; Giovanni Duro; Christiano Argano; Rosario Scaglione; Giuseppe Licata

    2010-01-01

    The distribution of the T29C TGF?1 gene polymorphism was analyzed in 198 hypertensives with left ventricular hypertrophy (LVH) and in 235 hypertensives without LVH. Circulating TGF?1 levels, procollagen type III levels, microalbuminuria, and left ventricular geometry and function were evaluated in all the hypertensives with LVH subgrouped according to T29C TGF?1 gene polymorphism. Circulating TGF?1 was evaluated by ELISA technique, procollagen type III by a specifi...

  20. Infarto del ventrículo derecho Right ventricular infarction

    Directory of Open Access Journals (Sweden)

    Alberto Barón C

    Full Text Available Por lo general, el infarto del ventrículo derecho se asocia con infarto de la pared inferior del ventrículo izquierdo. La enfermedad pulmonar obstructiva crónica y la hipertrofia del ventrículo derecho, son factores que lo predisponen. Casi siempre ocurre como consecuencia de obstrucción proximal de la arteria coronaria derecha que conduce a disfunción sistólica y diastólica del ventrículo derecho. El volumen latido disminuye y el volumen diastólico y la presión de llenado del ventrículo derecho aumentan, con lo que se ocasiona hipotensión y congestión periférica. Se disminuyen el flujo sanguíneo pulmonar y el retorno venoso para el ventrículo izquierdo que puede llevar a estado de choque. Además, se pueden presentar complicaciones como bloqueo aurículo-ventricular, disfunción sinusal y aneurisma ventricular. El electrocardiograma muestra supradesnivel del ST en las derivaciones III, V1 a V3 y en V4R. El ecocardiograma muestra hipoquinesia o aquinesia de la pared libre del ventrículo derecho y hay dilatación de las cavidades derechas e insuficiencia tricúspide. El Doppler demuestra aumento en la duración de los intervalos de contracción y relajación isovolumétrica; el período eyectivo se acorta y el índice de desempeño miocárdico aumenta a valores anormales. El Doppler tisular es anormal por la disminución de la velocidad sistólica del anillo tricúspide. Una parte importante del tratamiento es optimizar el ritmo y la frecuencia cardiaca por lo que se debe evitar el uso de beta-bloqueadores; dependiendo de la severidad de la bradicardia se puede usar atropina, aminofilina o marcapasos transitorio, con la finalidad de asegurar una frecuencia adecuada. En caso de fibrilación auricular se pueden usar antiarrítmicos o cardioversión eléctrica. Se debe asegurar un adecuado volumen de llenado, para mantener la presión venosa central mayor de 15 mm Hg. El uso de vasodilatadores o diuréticos está contraindicado. Es importante recanalizar rápidamente la arteria obstruida mediante trombólisis o angioplastia. Si persisten signos de bajo gasto se debe usar inotrópico parenteral. Se puede usar un balón de contrapulsación aórtica o dispositivo de asistencia mecánica. Recientemente, se ha descrito el uso de óxido nítrico para reducir la resistencia vascular pulmonar y mejorar el gasto cardiaco.In general, right ventricular infarction is associated with left ventricular inferior wall infarction. Obstructive chronic pulmonary disease and right ventricular hypertrophy are predisposing factors. It usually occurs as a consequence of proximal obstruction of the right coronary artery, which leads to right systolic and diastolic ventricle dysfunction. Stroke volume is diminished and diastolic volume and right ventricular filling pressure increase, causing hypotension and peripheral congestion. Pulmonary blood flow and left ventricular venous return are diminished, which may lead to shock. Besides, complications such as atrioventricular block, sinus dysfunction and ventricular aneurysm may occur. The electrocardiogram shows ST elevation in leads III, V1 to V3 and in V4R. The echocardiogram shows right ventricular free wall hypokinesis or akinesis and there is right cavities dilation and tricuspid regurgitation. The Doppler shows an increment in the duration of isovolumetric contraction and relaxation intervals; the ejection period is shortened and the myocardial performance index increase to abnormal values. The tissue Doppler is abnormal because of the decrease of systolic velocity in the tricuspid annulus. The optimization of rhythm and heart rate is an important part of treatment, and by this reason, beta-blockers may be avoided; depending on the severity of bradycardia, atropine, aminophylline or transient pace-maker can be used in order to ensure an adequate heart rate. In case of atrial fibrillation, anti-arrhythmic drugs or electric cardioversion may be used. An adequate filling volume may be guaranteed for maintaining the central venous pressure over 15 mm Hg. The use o

  1. Infarto del ventrículo derecho / Right ventricular infarction

    Scientific Electronic Library Online (English)

    Alberto, Barón C.

    2007-05-13

    Full Text Available Por lo general, el infarto del ventrículo derecho se asocia con infarto de la pared inferior del ventrículo izquierdo. La enfermedad pulmonar obstructiva crónica y la hipertrofia del ventrículo derecho, son factores que lo predisponen. Casi siempre ocurre como consecuencia de obstrucción proximal de [...] la arteria coronaria derecha que conduce a disfunción sistólica y diastólica del ventrículo derecho. El volumen latido disminuye y el volumen diastólico y la presión de llenado del ventrículo derecho aumentan, con lo que se ocasiona hipotensión y congestión periférica. Se disminuyen el flujo sanguíneo pulmonar y el retorno venoso para el ventrículo izquierdo que puede llevar a estado de choque. Además, se pueden presentar complicaciones como bloqueo aurículo-ventricular, disfunción sinusal y aneurisma ventricular. El electrocardiograma muestra supradesnivel del ST en las derivaciones III, V1 a V3 y en V4R. El ecocardiograma muestra hipoquinesia o aquinesia de la pared libre del ventrículo derecho y hay dilatación de las cavidades derechas e insuficiencia tricúspide. El Doppler demuestra aumento en la duración de los intervalos de contracción y relajación isovolumétrica; el período eyectivo se acorta y el índice de desempeño miocárdico aumenta a valores anormales. El Doppler tisular es anormal por la disminución de la velocidad sistólica del anillo tricúspide. Una parte importante del tratamiento es optimizar el ritmo y la frecuencia cardiaca por lo que se debe evitar el uso de beta-bloqueadores; dependiendo de la severidad de la bradicardia se puede usar atropina, aminofilina o marcapasos transitorio, con la finalidad de asegurar una frecuencia adecuada. En caso de fibrilación auricular se pueden usar antiarrítmicos o cardioversión eléctrica. Se debe asegurar un adecuado volumen de llenado, para mantener la presión venosa central mayor de 15 mm Hg. El uso de vasodilatadores o diuréticos está contraindicado. Es importante recanalizar rápidamente la arteria obstruida mediante trombólisis o angioplastia. Si persisten signos de bajo gasto se debe usar inotrópico parenteral. Se puede usar un balón de contrapulsación aórtica o dispositivo de asistencia mecánica. Recientemente, se ha descrito el uso de óxido nítrico para reducir la resistencia vascular pulmonar y mejorar el gasto cardiaco. Abstract in english In general, right ventricular infarction is associated with left ventricular inferior wall infarction. Obstructive chronic pulmonary disease and right ventricular hypertrophy are predisposing factors. It usually occurs as a consequence of proximal obstruction of the right coronary artery, which lead [...] s to right systolic and diastolic ventricle dysfunction. Stroke volume is diminished and diastolic volume and right ventricular filling pressure increase, causing hypotension and peripheral congestion. Pulmonary blood flow and left ventricular venous return are diminished, which may lead to shock. Besides, complications such as atrioventricular block, sinus dysfunction and ventricular aneurysm may occur. The electrocardiogram shows ST elevation in leads III, V1 to V3 and in V4R. The echocardiogram shows right ventricular free wall hypokinesis or akinesis and there is right cavities dilation and tricuspid regurgitation. The Doppler shows an increment in the duration of isovolumetric contraction and relaxation intervals; the ejection period is shortened and the myocardial performance index increase to abnormal values. The tissue Doppler is abnormal because of the decrease of systolic velocity in the tricuspid annulus. The optimization of rhythm and heart rate is an important part of treatment, and by this reason, beta-blockers may be avoided; depending on the severity of bradycardia, atropine, aminophylline or transient pace-maker can be used in order to ensure an adequate heart rate. In case of atrial fibrillation, anti-arrhythmic drugs or electric cardioversion may be used. An adequate filling volume may be guaranteed for maintaining the central venous

  2. Modulation of sarcoplasmic reticulum calcium release by calsequestrin in cardiac myocytes

    Directory of Open Access Journals (Sweden)

    SANDOR GYÖRKE

    2004-01-01

    Full Text Available Calsequestrin (CASQ2 is a high capacity Ca-binding protein expressed inside the sarcoplasmic reticulum (SR. Mutations in the cardiac calsequestrin gene (CASQ2 have been linked to arrhythmias and sudden death induced by exercise and emotional stress. We have studied the function of CASQ2 and the consequences of arrhythmogenic CASQ2 mutations on intracellular Ca signalling using a combination of approaches of reverse genetics and cellular physiology in adult cardiac myocytes. We have found that CASQ2 is an essential determinant of the ability of the SR to store and release Ca2+ in cardiac muscle. CASQ2 serves as a reservoir for Ca2+ that is readily accessible for Ca2+-induced Ca2+ release (CICR and also as an active Ca2+ buffer that modulates the local luminal Ca-dependent closure of the SR Ca2+ release channels. At the same time, CASQ2 stabilizes the CICR process by slowing the functional recharging of SR Ca2+ stores. Abnormal restitution of the Ca2+ release channels from a luminal Ca-dependent refractory state could account for ventricular arrhythmias associated with mutations in the CASQ2 gene.

  3. Modulation of sarcoplasmic reticulum calcium release by calsequestrin in cardiac myocytes

    Scientific Electronic Library Online (English)

    SANDOR, GYÖRKE; INNA, GYÖRKE; DMITRY, TERENTYEV; SERGE, VIATCHENKO-KARPINSKI; SIMON C, WILLIAMS.

    Full Text Available Calsequestrin (CASQ2) is a high capacity Ca-binding protein expressed inside the sarcoplasmic reticulum (SR). Mutations in the cardiac calsequestrin gene (CASQ2) have been linked to arrhythmias and sudden death induced by exercise and emotional stress. We have studied the function of CASQ2 and the c [...] onsequences of arrhythmogenic CASQ2 mutations on intracellular Ca signalling using a combination of approaches of reverse genetics and cellular physiology in adult cardiac myocytes. We have found that CASQ2 is an essential determinant of the ability of the SR to store and release Ca2+ in cardiac muscle. CASQ2 serves as a reservoir for Ca2+ that is readily accessible for Ca2+-induced Ca2+ release (CICR) and also as an active Ca2+ buffer that modulates the local luminal Ca-dependent closure of the SR Ca2+ release channels. At the same time, CASQ2 stabilizes the CICR process by slowing the functional recharging of SR Ca2+ stores. Abnormal restitution of the Ca2+ release channels from a luminal Ca-dependent refractory state could account for ventricular arrhythmias associated with mutations in the CASQ2 gene.

  4. Displasia arritmogênica do ventrículo direito / Arrythmogenic right ventricular dysplasia

    Scientific Electronic Library Online (English)

    Rogério Ferreira da, Silva; Karina, Morgarbel; Christian Moreno, Luize; Carla Gonçalves, Rosa; Marcelo, Romano; Ieda Maria, Liguori.

    2008-10-01

    Full Text Available A displasia arritmogênica do ventrículo direito (DAVD) é caracterizada pela substituição dos miócitos por tecido fibrogorduroso. Descrita em 1977, é considerada uma doença cardíaca potencialmente letal ainda pouco entendida. Afeta primariamente o ventrículo direito e tem sido associada a arritmias, [...] insuficiência cardíaca e morte súbita. O objetivo deste artigo é descrever o caso clínico de um paciente de 25 anos com síncope associada a extra-sístoles ventriculares e achados de ressonância magnética do coração compatíveis com DAVD. Abstract in english Arritmogenic right ventricular dysplasia (ARVD) is characterized by the gradual replacement of myocytes by adipose and fibrous tissue. Described in 1977, is considered a potentially lethal cause of cardiac disease poorly understood. This disorder usually involves the right ventricle and has been ass [...] ociated with arrthymia, heart failure, and sudden death. In this paper, we report a case of a 25-years-old patient with syncope associated with ventricular extrasystoles. A magnetic resonance imaging was performed and showed findings that support ARVD diagnose.

  5. RELATION BETWEEN PLASMA LEPTIN LEVEL AND LEFT VENTRICULAR FUNCTION IN OBESE FEMALES WITH INSULIN RESISTANCE

    OpenAIRE

    Dina Mohamed Abaza1, Hoda Abd El Basset2, Nagwa Moustafa Mohamed Hassanein3

    2011-01-01

    An association between obesity and cardiac mass has been recognized for almost two decades, whereas the precise nature of the association remains elusive Theoretical consideration have long suggested that it may be mediated at least in part by insulin resistance (Mc, Nutly ,2003).Several studies have found an association between insulin resistance and left ventricular hypertrophy.(Lacobellis et al,2003) In human, production of leptin( an adipocyte ­ derived peptide), has been linked to obesit...

  6. Echocardiographic Assessment of Left Ventricular Geometric Patterns in Hypertensive Patients in Nigeria

    OpenAIRE

    Rasaaq A. Adebayo; Bamikole, Olaniyi J.; Balogun, Michael O.; Akintomide, Anthony O.; Victor O. Adeyeye; Bisiriyu, Luqman A.; Tuoyo O. Mene-Afejuku; Ebenezer A. Ajayi; Abiodun, Olugbenga O

    2013-01-01

    Left ventricular (LV) hypertrophy is an important predictor of morbidity and mortality in hypertensive patients, and its geometric pattern is a useful determinant of severity and prognosis of heart disease. Studies on LV geometric pattern involving large number of Nigerian hypertensive patients are limited. We examined the LV geometric pattern in hypertensive patients seen in our echocardiographic laboratory. A two-dimensional, pulsed, continuous and color flow Doppler echocardiographic evalu...

  7. INTRALIPID PREVENTS AND RESCUES FATAL PULMONARY ARTERIAL HYPERTENSION AND RIGHT VENTRICULAR FAILURE IN RATS

    OpenAIRE

    Umar, Soban; Nadadur, Rangarajan; Li, Jingyuan; Maltese, Federica; Partownavid, Parisa; Laarse, Arnoud van der; Eghbali, Mansoureh

    2011-01-01

    Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling leading to right ventricular (RV) hypertrophy and failure. Intralipid®, a source of parenteral nutrition for patients, contains ?-linolenic acid and soy-derived phytoestrogens that are protective for lungs and heart. We therefore investigated the therapeutic potential of Intralipid® in preventing and rescuing monocrotaline-induced PAH and RV dysfunction. PAH was induced in male rats with monocrotaline (60m...

  8. Dyad content is reduced in cardiac myocytes of mice with impaired calmodulin regulation of RyR2.

    Science.gov (United States)

    Lavorato, Manuela; Huang, Tai-Qin; Iyer, Venkat Ramesh; Perni, Stefano; Meissner, Gerhard; Franzini-Armstrong, Clara

    2015-04-01

    In cardiac muscle, calmodulin (CaM) regulates the activity of several membrane proteins involved in Ca(2+) homeostasis (CaV1.2; RyR2, SERCA2, PMCA). Three engineered amino acid substitutions in the CaM binding site of the cardiac ryanodine receptor (RyR2) in mice (Ryr2 (ADA/ADA) ) strongly affect cardiac function, with impaired CaM inhibition of RyR2, reduced SR Ca(2+) sequestration, and early cardiac hypertrophy and death (Yamaguchi et al., J Clin Invest 117:1344-1353, 2007). We have examined the ultrastructure and RyR2 immunolocalization in WT and Ryr2 (ADA/ADA) hearts at ~10 days after birth. The myocytes show only minor evidence of structural damage: some increase in intermyofibrillar space, with occasional areas of irregular SR disposition and an increase in frequency of smaller myofibrils, despite an increase of about 15 % in average myocyte cross sectional area. Z line streaming, a sign of myofibrillar stress, is limited and fairly rare. Immunolabeling with an anti-RyR2 antibody shows that RyR-positive foci located at the level of the Z lines are less frequent in mutant hearts. A dramatic decrease in the frequency and size of dyads, accompanied by a decrease in occupancy of the gap by RyR2, but without obvious alterations in location and general structure is a notable ultrastructural feature. The data suggest that the uneven distribution of dyads or calcium release sites within the cells resulting from an overall reduction in RyR2 content may contribute to the poor cardiac performance and early death of Ryr2 (ADA/ADA) mice. An unusual fragmentation of mitochondria, perhaps related to imbalances in free cytoplasmic calcium levels, accompanies these changes. PMID:25694159

  9. Surgical Ventricular Reconstruction

    Medline Plus

    Full Text Available SURGICAL VENTRICULAR RECONSTRUCTION MONTEFIORE-EINSTEIN HEART CENTER NEW YORK CITY, NEW YORK February 13, 2008 00:00:09 NARRATOR: Welcome to the Montefiore-Einstein Heart Center in New York City. In ...

  10. Surgical Ventricular Reconstruction

    Medline Plus

    Full Text Available ... of the procedures that we perform are high risk mitral valve surgery. Previously, rather than the Dor ... MD: Excellent. Another question is whether there's a risk of the development of a ventricular aneurysm after ...

  11. Surgical Ventricular Reconstruction

    Medline Plus

    Full Text Available SURGICAL VENTRICULAR RECONSTRUCTION MONTEFIORE-EINSTEIN HEART CENTER NEW YORK CITY, NEW YORK February 13, 2008 00:00:09 NARRATOR: Welcome to the Montefiore-Einstein Heart Center in ...

  12. Surgical Ventricular Reconstruction

    Medline Plus

    Full Text Available ... this procedure. And what are the EC change…ECG changes, the electrocardiographic changes that can be seen ... performing the surgical ventricular reconstruction. We may see ECG changes related to coronary artery disease, and those ...

  13. Surgical Ventricular Reconstruction

    Medline Plus

    Full Text Available ... a matter of fact, in one of the observational studies that was performed on this procedure, approximately twenty ... the Restore Group which was really just an observational study of how well patients did after surgical ventricular ...

  14. Surgical Ventricular Reconstruction

    Medline Plus

    Full Text Available ... moments, you'll see an expert discussion concerning a surgical ventricular reconstruction. The surgery was performed by ... from Dr. Richard Bello. The presentation will include a range of discussion topics, including a clinical discussion ...

  15. Surgical Ventricular Reconstruction

    Medline Plus

    Full Text Available ... is a better procedure, the ventricular reconstruction or heart transplantation. This particular viewer actually saw our previous video on heart transplantation. And to answer that question, they are both ...

  16. Surgical Ventricular Reconstruction

    Medline Plus

    Full Text Available ... you require an intraaortic balloon pump in the management of these patients. Do you want to answer ... MD: Excellent. Another question is whether there's a risk of the development of a ventricular aneurysm after ...

  17. Surgical Ventricular Reconstruction

    Medline Plus

    Full Text Available ... that question, they are both good procedures. The gold standard therapy for heart failure is, in fact, ... to surgical ventricular reconstruction would add to the recovery period. And what we've found is that ...

  18. Surgical Ventricular Reconstruction

    Medline Plus

    Full Text Available ... It kills more people than the most seven leading causes of death added together. And this is, ... have coronary artery disease and poor left ventricular function. If a patient has poor left and right ...

  19. Surgical Ventricular Reconstruction

    Medline Plus

    Full Text Available ... you require an intraaortic balloon pump in the management of these patients. Do you want to answer ... have coronary artery disease and poor left ventricular function. If a patient has poor left and right ...

  20. Surgical Ventricular Reconstruction

    Medline Plus

    Full Text Available ... don't you tell us how this patient did after the operation and then we'll field ... just an observational study of how well patients did after surgical ventricular reconstruction and bypass surgery. I ...

  1. Surgical Ventricular Reconstruction

    Medline Plus

    Full Text Available ... undergone a repeat echocardiogram which indicated slightly more improvement approximately two months after the procedure. He has ... the patient's quality of life, due to the improvement in ventricular performance. 00:53:18 ROBERT E. ...

  2. Surgical Ventricular Reconstruction

    Medline Plus

    Full Text Available ... scar. We repaired the mitral valve with a single valve stitch and then we performed a remodeling ... can, in fact, improve the patient's quality of life, due to the improvement in ventricular performance. 00: ...

  3. Surgical Ventricular Reconstruction

    Medline Plus

    Full Text Available ... you require an intraaortic balloon pump in the management of these patients. Do you want to answer ... because it can, in fact, improve the patient's quality of life, due to the improvement in ventricular ...

  4. Surgical Ventricular Reconstruction

    Medline Plus

    Full Text Available Page 1 of 15 SURGICAL VENTRICULAR RECONSTRUCTION MONTEFIORE-EINSTEIN HEART CENTER NEW YORK CITY, NEW YORK February ... 00:00:09 NARRATOR: Welcome to the Montefiore-Einstein Heart Center in New York City. In just ...

  5. Surgical Ventricular Reconstruction

    Medline Plus

    Full Text Available ... 1 of 15 SURGICAL VENTRICULAR RECONSTRUCTION MONTEFIORE-EINSTEIN HEART CENTER NEW YORK CITY, NEW YORK February 13, ... 00:09 NARRATOR: Welcome to the Montefiore-Einstein Heart Center in New York City. In just moments, ...

  6. Surgical Ventricular Reconstruction

    Medline Plus

    Full Text Available ... In just moments, you'll see an expert discussion concerning a surgical ventricular reconstruction. The surgery was ... Bello. The presentation will include a range of discussion topics, including a clinical discussion of the procedure ...

  7. The influence of renal alograft function on cardiovscular status and left ventricular remodelling.

    Science.gov (United States)

    Dzemidzi?, Jasminka; Rasi?, Senija; Saracevi?, Adnan

    2009-05-01

    The synergy and shared co-morbidity, certainly interplay between kidney and cardiovascular disease, where advanced renal failure influences on progression of cardiac disease in bi-direction relationship. Cardiovascular diseases are cause of death in almost 50% of uremic patients. Correction of uremia after successful renal transplantation leads to improved cardiovascular status in the majority of kidney transplanted patients. The aim of this study was an evaluation of the influence of renal allograft function on left ventricular remodelling in the first year after transplantation comparing echocardiographic findings before and twelve months after transplantation had been done. In retrospective-prospective study we followed up 30 patients with renal allograft in the first post transplant year. During the study values of serum creatinine and creatinine clearance were monthly monitored. Echocardiographic examination was done before transplantation and one year after the kidney transplantation. Results of our study showed that before transplantation 67% of patients had echocardiographic signs of left ventricular (LV) hypertrophy, while 33% of patients had normal echocardiographic findings. After first post transplant year, 63% of patients showed normal view of LV, and 37% remained with LV hypertrophy. Diastolic dysfunction of LV till the end of study had been reduced from 70% to 40% of patients. The positive echocardiographic remodelling of LV significantly correlated with the rise in creatinine clearance and with the reduction of the serum creatinine. These results confirm positive correlation between renal allograft functional status and remodelling of left ventricular hypertrophy after successful renal transplantation. PMID:19485940

  8. Left ventricular function in right ventricular overload

    International Nuclear Information System (INIS)

    This study clarified regional and global functions of the distorted left ventricle due to right ventricular overload by gated radionuclide ventriculography (RNV). Cardiac catheterization and RNV were performed in 13 cases of atrial septal defect (ASD), 13 of pure mitral stenosis (MS), 10 of primary pulmonary hypertension (PPH), and 10 of normal subjects (NL). Right ventricular systolic pressure (RVSP) was 32.9±13.9, 45.0±12.2, 88.3±17.1, and 21.2±4.5 mmHg, respectively. The end-systolic LAO view of the left ventricle was halved into septal and free-wall sides. The end-diastolic halves were determined in the same plane. Ejection fractions of the global left ventricle (LVEF), global right ventricle (RVEF), the septal half of the left ventricle (SEPEF), and the free-wall half of the left ventricle (FWEF) were obtained. LVEF was 56.8±9.8% in NL, 52.8±10.5% in ASD, and 49.5±12.9% in PPH. In MS, LVEF (47.0±13.0%) was smaller than those in the other groups. RVEF was 37.0±5.2% in NL, 43.7±15.5% in ASD, and 32.8±11.5% in MS. In PPH, RVEF (25.0±10.6%) was smaller than those in the other groups. SEPEF was smaller in ASD (42.5±13.2%), MS (40.4±13.1%), PPH (40.5±12.5%) than in NL (53.5±8.5%). Systolic function of the septal half of the left ventricle was disturbed by right ventricular overload. RVEF (r=-0.35, p<0.05) and SEPEF (r=-0.51, p<0.01) had negative correlations with RVSP. As RVSP rose, systolic function of the septal half of the left ventricle was more severely disturbed. FWEF was the same among the four groups; NL (57.0±12.6%), ASD (48.6±15.2%), MS (50.5±12.0%), and PPH (51.1±12.3%). There was a good correlation between SEPEF and LVEF in NL (r=0.81), although in PPH this correlation was poor (r=0.64). These data showed that the distorted left ventricular due to right ventricular overload maintains its global function with preserved function of the free-wall side. (J.P.N.)

  9. Postconditioning (PostC) cardioprotection in experimental modelsof cardiac hypertrophy: spontaneously hypertensive (SHR) and nandrolone (ND)-abuse rats

    OpenAIRE

    PAGLIARO, Pasquale; Perrelli, Maria-Giulia; TULLIO, FRANCESCA; ANGOTTI, CARMELINA; CARRIERO, VITINA MARIA ANNA; PENNA, Claudia

    2012-01-01

    Background: Cardiac PostC reduces ischemia/reperfusion (I/R) injury via a redox-sensitive mechanism. However in the presence of comorbidities the effectiveness of PostC is reduced. We studied whether PostC can reduce I/R injury in the presence of ventricular hypertrophy induced by hypertension or ND, an anabolic-androgenic steroid. Methods: A) Hypertension model: hearts isolated from SHR and Wistar-Kyoto (WKY) rats were subjected to: 30-min ischemia and 120-min reperfusio...

  10. Padrão de remodelação e função ventricular em ratos expostos à fumaça do cigarro / Remodeling pattern and ventricular function in rats exposed to cigarette smoke / Estándar de remodelación y función ventricular en ratones expuestos al humo del cigarrillo

    Scientific Electronic Library Online (English)

    Paula S., Azevedo; Marcos F., Minicucci; Beatriz B., Matsubara; Luiz S., Matsubara; Daniella R., Duarte; Sergio A. R., Paiva; Leonardo A. M., Zornoff.

    2010-02-01

    Full Text Available FUNDAMENTO: A relevância do padrão de remodelação no modelo de ratos expostos à fumaça do cigarro não é conhecida. OBJETIVO: Analisar a presença de diferentes padrões de remodelação nesse modelo e sua relação com a função ventricular. MÉTODOS: Ratos fumantes (n=47) foram divididos de acordo com o pa [...] drão de geometria, analisado pelo ecocardiograma: normal (índice de massa normal e espessura relativa normal), remodelação concêntrica (índice de massa normal e espessura relativa aumentada), hipertrofia concêntrica (índice de massa aumentado e espessura relativa aumentada) e hipertrofia excêntrica (índice de massa aumentado e espessura relativa normal). RESULTADOS: Os ratos fumantes apresentaram um dos quatro padrões de geometria: padrão normal, 51%; hipertrofia excêntrica:,32%; hipertrofia concêntrica, 13% e remodelação concêntrica, 4%. Os grupos normal e hipertrofia excêntrica apresentaram menores valores de fração de ejeção e porcentagem de encurtamento que o grupo hipertrofia concêntrica. Treze animais (28%) apresentaram disfunção sistólica, detectada pela fração de ejeção e pela porcentagem de encurtamento. Na análise de regressão univariada, os padrões de geometria e o índice de massa não foram fator de predição de disfunção ventricular (p>0,05). Por outro lado, o aumento da espessura relativa da parede foi fator de predição de disfunção ventricular na análise univariada (p Abstract in spanish FUNDAMENTO: No se conoce la relevancia del estándar de remodelación en el modelo de ratones expuestos al humo del cigarrillo. OBJETIVO: Analizar la presencia de diferentes estándares de remodelación en este modelo y su relación con la función ventricular. MÉTODOS: Ratones fumadores (n=47) se dividie [...] ron según el estándar de geometría, analizado por el ecocardiograma: normal (índice de masa normal y espesor relativo normal), remodelación concéntrico (índice de masa normal y espesor relativo aumentado), hipertrofia concéntrica (índice de masa aumentado y espesor relativo aumentado) y hipertrofia excéntrica (índice de masa aumentado y espesor relativo normal). RESULTADOS: Los ratos fumadores presentaron uno de los cuatro estándares de geometría: estándar normal, el 51%; hipertrofia excéntrica: el 32%; hipertrofia concéntrica, el 13% y remodelación concéntrica, el 4%. Los grupos normal e hipertrofia excéntrica presentaron menores valores de fracción de eyección y porcentaje de acortamiento que el grupo hipertrofia concéntrica. Trece animales (28%) presentaron disfunción sistólica, detectada por la fracción de eyección y por el porcentaje de acortamiento. En el análisis de regresión univariado, los estándares de geometría y el índice de masa no fueron factor de predicción de disfunción ventricular (p > 0,05). Por otro lado, el aumento del espesor relativo de la pared fue factor de predicción de disfunción ventricular en el análisis univariado (p Abstract in english BACKGROUND: The relevance of the remodeling pattern in the model of rats exposed to cigarette smoke is not known. OBJECTIVE: Analyzing the presence of different remodeling patterns in this model and its relation with the ventricular function. METHODS: Smoking rats (n=47) have been divided according [...] to the geometry pattern, analyzed by echocardiogram: normal (normal mass index and normal relative wall thickness), concentric remodeling (normal mass index and increased relative wall thickness), concentric hypertrophy (increased mass index and increased relative wall thickness) and eccentric hypertrophy (increased mass index and normal relative wall thickness). RESULTS: Smoking rats presented one of the following geometry patterns: normal pattern, 51%; eccentric hypertrophy; 32%; concentric hypertrophy, 13% and concentric remodeling, 4%. The normal and eccentric hypertrophy groups presented smaller ejection fraction values and fractional shortening than the concentric hypertrophy group. Thirteen animals (28%) presented systolic dysfunctio

  11. Arrhythmogenic right ventricular dysplasia

    International Nuclear Information System (INIS)

    The arrhythmogenic right ventricular dysplasia is a condition predominantly well defined with arrhythmic events. We analyze three cases diagnosed by the group. These cases were presented as ventricular tachycardia with a morphology of left bundle branch block, presenting one of them aborted sudden death in evolution. The baseline electrocardiogram and signal averaging were abnormal in two of the three cases, like the echocardiogram. The electrophysiological study was able to induce in the three patients with sustained monomorphic ventricular tachycardia morphology of left bundle branch block. The definitive diagnosis was made by right ventriculography in two cases and magnetic resonance imaging in the other. Treatment included antiarrhythmic drugs in the three cases and the placement of an automatic defibrillator which survived a sudden death (Author)

  12. Effects of Guanxinkang on expressions of ATP-sensitive potassium channel subunits Kir6.1, Kir6.2, SUR2A and SUR2B in ischemic myocytes of rats

    Directory of Open Access Journals (Sweden)

    Fu-rong CHEN

    2010-05-01

    Full Text Available Objective: To observe the effects of Guanxinkang injection, a compound traditional Chinese herbal medicine, on ATP-sensitive potassium (KATP channel subunits in ischemic myocardial cells of rats, and to explore the mechanism of Guanxinkang in protecting myocardial ischemic reperfusion injuries.Methods: Forty-eight Wistar rats were randomly divided into normal group, untreated group, glibenclamide group, pinacidil group, Guanxinkang group and Guanxinkang plus glibenclamide group. The ventricular myocytes were prepared from hearts of normal rats by enzymatic dissociation method. The ischemic ventricular myocytes underwent perfusion with normal Tyrode' solution for 10 min, then stopping perfusion 30 min, and followed by 45 min of reperfusion. The glibenclamide, pinacidil and Guanxinkang were added into ventricular myocytes solution directly. Then the solutions were placed at 4 ?. After 24-hour freezing at ?80 ?, mRNA and protein expressions of KATP subunits Kir6.1, Kir6.2, SUR2A and SUR2B were measured by real-time quantitative polymerase chain reaction and Western blotting respectively. Results: In normal rat myocardial cells, there were SUR2A, Kir6.1, and Kir6.2 protein and gene expressions but no expression of SUR2B protein. In the untreated group, all subunit mRNA and protein expressions of KATP increased to some extent as compared with the normal group. Pinacidil, a potassium channel opener, significantly increased mRNA and protein expressions of KATP subunits, while the blocker glibenclamide had a reverse effect. Meanwhile, Guanxinkang injection significantly increased mRNA and protein expressions of KATP subunits but with no significant difference as compared with pinacidil. Conclusion: Guanxinkang injection can obviously enhance the open of KATP channel and thus play a role in cardiovascular protection.

  13. Heat stress inhibits skeletal muscle hypertrophy

    OpenAIRE

    Frier, Bruce C.; Locke, Marius

    2007-01-01

    Heat shock proteins (Hsps) are molecular chaperones that aid in protein synthesis and trafficking and have been shown to protect cells/tissues from various protein damaging stressors. To determine the extent to which a single heat stress and the concurrent accumulation of Hsps influences the early events of skeletal muscle hypertrophy, Sprague-Dawley rats were heat stressed (42°C, 15 minutes) 24 hours prior to overloading 1 plantaris muscle by surgical removal of the gastrocnemius muscle. The...

  14. Ribosome biogenesis during skeletal muscle hypertrophy

    OpenAIRE

    von Walden, Ferdinand

    2014-01-01

    Muscle adaptation to chronic resistance exercise (RE) is the result of a cumulative effect on gene expression and protein content. Following a bout of RE, muscle protein synthesis increases and, if followed by consecutive bouts (training), protein accretion and muscle hypertrophy develops. The protein synthetic capacity of the muscle is dictated by ribosome content. Therefore, the general aim of this thesis is to investigate the regulation of ribosome biogenesis during skeletal muscle hypertr...

  15. DISSEMINATED CYSTICERCOSIS WITH HUGE MUSCLE HYPERTROPHY

    OpenAIRE

    Bandyopadhyay Debabrata; Sen Sumit

    2009-01-01

    Cysticercosis is caused by cysticercus cellulose, which is the larva of Taenia solium , the pork tapeworm. The larvae are carried in the blood stream after penetrating the walls of the alimentary tract and they lodge in different tissues like the skin, skeletal muscles, brain, fundus and heart, to cause disseminated cysticercosis. Cases of disseminated cysticercosis have rarely been reported in the literature. They may inhabit the muscles and cause muscular hypertrophy, which, at times, may ...

  16. Tropomyosin Dephosphorylation Results in Compensated Cardiac Hypertrophy*

    Science.gov (United States)

    Schulz, Emily M.; Correll, Richard N.; Sheikh, Hajer N.; Lofrano-Alves, Marco S.; Engel, Patti L.; Newman, Gilbert; Schultz, Jo El J.; Molkentin, Jeffery D.; Wolska, Beata M.; Solaro, R. John; Wieczorek, David F.

    2012-01-01

    Phosphorylation of tropomyosin (Tm) has been shown to vary in mouse models of cardiac hypertrophy. Little is known about the in vivo role of Tm phosphorylation. This study examines the consequences of Tm dephosphorylation in the murine heart. Transgenic (TG) mice were generated with cardiac specific expression of ?-Tm with serine 283, the phosphorylation site of Tm, mutated to alanine. Echocardiographic analysis and cardiomyocyte cross-sectional area measurements show that ?-Tm S283A TG mice exhibit a hypertrophic phenotype at basal levels. Interestingly, there are no alterations in cardiac function, myofilament calcium (Ca2+) sensitivity, cooperativity, or response to ?-adrenergic stimulus. Studies of Ca2+ handling proteins show significant increases in sarcoplasmic reticulum ATPase (SERCA2a) protein expression and an increase in phospholamban phosphorylation at serine 16, similar to hearts under exercise training. Compared with controls, the decrease in phosphorylation of ?-Tm results in greater functional defects in TG animals stressed by transaortic constriction to induce pressure overload-hypertrophy. This is the first study to investigate the in vivo role of Tm dephosphorylation under both normal and cardiac stress conditions, documenting a role for Tm dephosphorylation in the maintenance of a compensated or physiological phenotype. Collectively, these results suggest that modification of the Tm phosphorylation status in the heart, depending upon the cardiac state/condition, may modulate the development of cardiac hypertrophy. PMID:23148217

  17. Double-chambered right ventricle, ventricular septal defect, patent ductus arteriosus in a dog

    International Nuclear Information System (INIS)

    A 4-month-old female mongrel puppy was presented with an anophthalmos. On physical examination, systolic murmur was heard at the 4th left intercostal space near the sternum. However the dog appeared healthy without cyanosis and had no history of exercise intolerance. The phonocardiogram revealed a pansystolic murmur and a continuous murmur on the mitral area. A systolic ejection murmur was also recorded on the pulmonic area. The electrocardiogram indicated bi-ventricular hypertrophy. Left ventricular enlargement was seen on chest radiographs. Ventricular septal defect (VSD) and patent ductus arteriosus (PDA) were diagnosed from these findings. PDA closure was performed at 2 years of age. After 2 months from the operation, the dog died during an attempted repair of the VSD. At necropsy, it was found that the double-chambered right ventricle (DCRV) was formed by an anomalous septal band. The VSD was localized on the proximal conus and was 8 mm in diameter. (author)

  18. Right ventricular visualization by thallium 201 myocardial scintigraphy in chronic obstructive pulmonary disease

    International Nuclear Information System (INIS)

    The right ventricle is not normally displayed by studies with thallium 201 in patients at rest, but it can be shown by thallium 201 myocardial scintigraphy with pressure or volume overload of the right ventricle and with right ventricular hypertrophy. We sought to determine the frequency of right ventricular demonstration by thallium 201 in 20 patients at rest, who had chronic obstructive pulmonary disease of varying severity studied at baseline. The ventricle was viewed in 11 of 20 patients (55%); these patients had significantly lower values for forced expiratory volume in one second (FEV1) and PO2. Eight patients had catheterization of the right side of the heart; mean pulmonary artery pressure and pulmonary vascular resistance were significantly higher in patients with right ventricular visualization. We conclude that thallium 201 scintigraphy frequently shows the right ventricle in patients with chronic obstructive pulmonary disease and that such visualization correlates with the severity of the ventilatory defect and with pulmonary hypertension

  19. Gender and post-ischemic recovery of hypertrophied rat hearts

    Directory of Open Access Journals (Sweden)

    Popov Kirill M

    2006-03-01

    Full Text Available Abstract Background Gender influences the cardiac response to prolonged increases in workload, with differences at structural, functional, and molecular levels. However, it is unknown if post-ischemic function or metabolism of female hypertrophied hearts differ from male hypertrophied hearts. Thus, we tested the hypothesis that gender influences post-ischemic function of pressure-overload hypertrophied hearts and determined if the effect of gender on post-ischemic outcome could be explained by differences in metabolism, especially the catabolic fate of glucose. Methods Function and metabolism of isolated working hearts from sham-operated and aortic-constricted male and female Sprague-Dawley rats before and after 20 min of no-flow ischemia (N = 17 to 27 per group were compared. Parallel series of hearts were perfused with Krebs-Henseleit solution containing 5.5 mM [5-3H/U-14C]-glucose, 1.2 mM [1-14C]-palmitate, 0.5 mM [U-14C]-lactate, and 100 mU/L insulin to measure glycolysis and glucose oxidation in one series and oxidation of palmitate and lactate in the second. Statistical analysis was performed using two-way analysis of variance. The sequential rejective Bonferroni procedure was used to correct for multiple comparisons and tests. Results Female gender negatively influenced post-ischemic function of non-hypertrophied hearts, but did not significantly influence function of hypertrophied hearts after ischemia such that mass-corrected hypertrophied heart function did not differ between genders. Before ischemia, glycolysis was accelerated in hypertrophied hearts, but to a greater extent in males, and did not differ between male and female non-hypertrophied hearts. Glycolysis fell in all groups after ischemia, except in non-hypertrophied female hearts, with the reduction in glycolysis after ischemia being greatest in males. Post-ischemic glycolytic rates were, therefore, similarly accelerated in hypertrophied male and female hearts and higher in female than male non-hypertrophied hearts. Glucose oxidation was lower in female than male hearts and was unaffected by hypertrophy or ischemia. Consequently, non-oxidative catabolism of glucose after ischemia was lowest in male non-hypertrophied hearts and comparably elevated in hypertrophied hearts of both sexes. These differences in non-oxidative glucose catabolism were inversely related to post-ischemic functional recovery. Conclusion Gender does not significantly influence post-ischemic function of hypertrophied hearts, even though female sex is detrimental to post-ischemic function in non-hypertrophied hearts. Differences in glucose catabolism may contribute to hypertrophy-induced and gender-related differences in post-ischemic function.

  20. Surgical Ventricular Reconstruction

    Medline Plus

    Full Text Available ... surgical ventricular reconstruction. We may see ECG changes related to coronary artery disease, and those are…and those we don't anticipate seeing because we're performing bypass surgery. So effectively this ... have another question related to how often you monitor the patient after ...

  1. Surgical Ventricular Reconstruction

    Medline Plus

    Full Text Available ... 15 SURGICAL VENTRICULAR RECONSTRUCTION MONTEFIORE-EINSTEIN HEART CENTER NEW YORK CITY, NEW YORK February 13, 2008 00:00:09 NARRATOR: Welcome to the Montefiore-Einstein Heart Center in New York City. In just moments, you'll see an ...

  2. Surgical Ventricular Reconstruction

    Medline Plus

    Full Text Available ... you require an intraaortic balloon pump in the management of these patients. Do you want to answer ... observational study of approximately 662 patients. In their data they found that ... the patient's quality of life, due to the improvement in ventricular ...

  3. Surgical Ventricular Reconstruction

    Medline Plus

    Full Text Available ... VENTRICULAR RECONSTRUCTION MONTEFIORE-EINSTEIN HEART CENTER NEW YORK CITY, NEW YORK February 13, 2008 00:00:09 ... the Montefiore-Einstein Heart Center in New York City. In just moments, you'll see an expert ...

  4. Surgical Ventricular Reconstruction

    Medline Plus

    Full Text Available ... SURGICAL VENTRICULAR RECONSTRUCTION MONTEFIORE-EINSTEIN HEART CENTER NEW YORK CITY, NEW YORK February 13, 2008 00:00:09 NARRATOR: Welcome to the Montefiore-Einstein Heart Center in New York City. In just moments, you'll see an ...

  5. Raf-mediated cardiac hypertrophy in adult Drosophila

    OpenAIRE

    Yu, Lin; Daniels, Joseph; Glaser, Alex E.; Wolf, Matthew J.

    2013-01-01

    In response to stress and extracellular signals, the heart undergoes a process called cardiac hypertrophy during which cardiomyocytes increase in size. If untreated, cardiac hypertrophy can progress to overt heart failure that causes significant morbidity and mortality. The identification of molecular signals that cause or modify cardiomyopathies is necessary to understand how the normal heart progresses to cardiac hypertrophy and heart failure. Receptor tyrosine kinase (RTK) signaling is ess...

  6. Cardiac hypertrophy : transcription patterns, hypertrophicprogression and extracellular signalling

    OpenAIRE

    Gennebäck, Nina

    2012-01-01

    Background: The aim of this thesis was to study transcription patterns and extracellular signalling of the hypertrophic heart to better understand the mechanisms initiating, controlling and maintaining cardiac hypertrophy. Cardiac hypertrophy is a risk factor for cardiovascular morbidity and mortality. Hypertrophy of the myocardium is a state, independent of underlying disease, where the myocardium strives to compensate for an increased workload. This remodelling of the heart includes physiol...

  7. Transforming Growth Factor-? Induces Airway Smooth Muscle Hypertrophy

    OpenAIRE

    Goldsmith, Adam M; Bentley, J Kelley; Zhou, Limei; Jia, Yue; Bitar, Khalil N; Fingar, Diane C; Marc B. Hershenson

    2005-01-01

    Although smooth muscle hypertrophy is present in asthmatic airways, little is known about the biochemical pathways regulating airway smooth muscle protein synthesis, cell size, or accumulation of contractile apparatus proteins. We sought to develop a model of airway smooth muscle hypertrophy in primary cells using a physiologically relevant stimulus. We hypothesized that transforming growth factor (TGF)-? induces hypertrophy in primary bronchial smooth muscle cells. Primary human bronchial sm...

  8. Intrinsic-mediated caspase activation is essential for cardiomyocyte hypertrophy

    OpenAIRE

    Putinski, Charis; ABDUL-GHANI, MOHAMMAD; Stiles, Rebecca; Brunette, Steve; Dick, Sarah A.; Fernando, Pasan; Megeney, Lynn A.

    2013-01-01

    Cardiac hypertrophy is a pathologic enlargement of the heart, an alteration that leads to contractile dysfunction and eventual organ failure. The hypertrophy phenotype originates from concentric growth of heart muscle cells and shares many biochemical features with programmed cell death, implying a common molecular origin. Here, we show cell-autonomous activation of a mitochondrial cell death pathway during initial stages of muscle cell hypertrophy, a signal that is essential and sufficient t...

  9. Prevalence of myocardial hypertrophy in a population of asymptomatic Swedish Maine coon cats

    Directory of Open Access Journals (Sweden)

    Häggström Jens

    2008-06-01

    Full Text Available Abstract Background Maine coon cats have a familial disposition for developing hypertrophic cardiomyopathy (HCM with evidence of an autosomal dominant mode of inheritance 1. The current mode to diagnose HCM is by use of echocardiography. However, definite reference criteria have not been established. The objective of the study was to determine the prevalence of echocardigraphic changes consistent with hypertrophic cardiomyopathy in Swedish Maine coon cats, and to compare echocardiographic measurements with previously published reference values. Methods All cats over the age of 8 months owned by breeders living in Stockholm, listed on the website of the Maine Coon breeders in Sweden by February 2001, were invited to participate in the study. Physical examination and M-mode and 2D echocardiographic examinations were performed in all cats. Results Examinations of 42 asymptomatic Maine coon cats (10 males and 32 females were performed. The age of the cats ranged from 0,7 to 9,3 years with a mean of 4,8 ± 2,3 years. Four cats (9,5% had a diastolic interventricular septal (IVSd or left ventricular free wall (LVPWd thickness exceeding 6,0 mm. In 3 of these cats the hypertrophy was segmental. Two cats (4,8% had systolic anterior motion (SAM of the mitral valve without concomitant hypertrophy. Five cats (11,9% had IVSd or LVPWd exceeding 5,0 mm but less than 6,0 mm. Conclusion Depending on the reference values used, the prevalence of HCM in this study varied from 9,5% to 26,2%. Our study suggests that the left ventricular wall thickness of a normal cat is 5,0 mm or less, rather than 6,0 mm, previously used by most cardiologists. Appropriate echocardiographic reference values for Maine coon cats, and diagnostic criteria for HCM need to be further investigated.

  10. Cardiac Hypertrophy: A Review on Pathogenesis and Treatment

    Directory of Open Access Journals (Sweden)

    Ankur Rohilla

    2012-07-01

    Full Text Available Cardiac hypertrophy has been considered as an important risk factor for cardiac morbidity and mortality whose prevalence has increased during the last few decades. Cardiac hypertrophy, a disease associated with the myocardium, is characterized by thickening of ventricle wall of heart and consequent reduction in the contracting ability of heart to pump the blood. Cardiac hypertrophy has been divided into two types, i.e. physiological and pathological hypertrophy. The exercise-induced increase in the ability of pumping blood leads to thickening of ventricle wall, referred to as physiological hypertrophy. On the other hand, reduced ability of pumping blood as a result of hypertension and volume overload on heart denotes pathological hypertrophy. Numerous mediators have been found to be involved in the pathogenesis of cardiac hypertrophy that include mitogen-activated protein kinase (MAPK, protein kinase C (PKC insulin-like growth factor-I (IGF-I, phosphatidylinositol 3-kinase (PI3K-AKT/PKB, calcinurin-nuclear factor of activated T cells (NFAT and mammalian target of rapamycin (mTOR. The prevention strategy for cardiac hypertrophy involve thiazide diuretics, angiotensin-converting enzyme (ACE inhibitors, angiotensin (Ang II receptor blockers, beta blockers and calcium channel blockers. The present review article highlights the signaling mechanisms involved and the approaches required in the treatment of cardiac hypertrophy.

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

    International Nuclear Information System (INIS)

    Tl-201 myocardial scintigraphy was performed in 130 patients with chronic obstructive pulmonary disease (COPD) to evaluate right ventricular hypertrophy, and the clinical significance of this method was studied. Tl-201 uptake ratios of the right ventricle, which represents the ratio of total counts of the right ventricle to counts of the administered dose of Tl-201, was higher in COPD, especially in pulmonary emphysema and B type COPD by Burrows classification than in controls. The grade of visualization of the right ventricle by visual assessment (RVV) was marked (+++) in only a few cases and moderate (++) in many cases (more than 80%) in all diseases except bronchial asthma. The incidence of right ventricular hypertrophy by electrocardiogram, right-sided heart failure and marked dyspnea (Hugh-Jones 4·5) were very low in cases with RVV grade ++ and very high in cases with +++. The grade of RVV was related to the severity of pulmonary perfusion impairment, although in diffuse panbronchiolitis the RVV was relatively slight compared with the impairment of perfusion. May parameters of pulmonary function such as %VC, FEV1.0%, RV/TLC, V25, %DLCO, Raw, ?N2 and PaO2 showed abnormal values in patients with RVV grade of (++) or (+++) in all diseases except bronchial asthma. In COPD, Tl-201 myocardial scintigraphy seems to be useful for assessment of right ventricular overloading, and for follow-up observation and differentiation between cor pulmonale and right ventricular hypertrophy secondary to cardiac diseases by observing Tl-201 uptake of the lung and left ventricle. (author)

  12. Does Resistance Training Stimulate Cardiac Muscle Hypertrophy?

    Science.gov (United States)

    Bloomer, Richard J.

    2003-01-01

    Reviews the literature on the left ventricular structural adaptations induced by resistance/strength exercise, focusing on human work, particularly well-trained strength athletes engaged in regular, moderate- to high-intensity resistance training (RT). The article discusses both genders and examines the use of anabolic-androgenic steroids in…

  13. Acute DNase1 treatment improves left ventricular remodeling after myocardial infarction by disruption of free chromatin.

    Science.gov (United States)

    Vogel, Benjamin; Shinagawa, Hisahito; Hofmann, Ulrich; Ertl, Georg; Frantz, Stefan

    2015-03-01

    Myocardial infarction (MI) leads to necrosis and uncontrolled release of cellular content. Binucleated and polyploid cardiomyocytes contain high amounts of chromatin, a DNA polymer of histones which are cytotoxic. We hypothesized that chromatin from necrotic cells accumulates in the non-perfused, ischemic infarct region, causing local high concentrations of cytotoxic histones, thereby potentiating damage to the heart after MI. The endonuclease DNase1 is capable of dispersing extracellular chromatin through linker DNA digestion which could lead to a decrease in local histone concentrations and cytotoxicity. It was confirmed that after permanent coronary artery ligation in mice, extracellular histones accumulated within the infarcted myocardium. In vitro, histones caused myocyte cytotoxicity. For protection against histone-mediated cytotoxicity after MI in vivo, DNase1 was administered within the first 6 h after induction. Indeed, DNase1 accumulation in the infarcted region of the heart was observed, as well as effective disruption of extracellular cytotoxic chromatin and subsequent reduction of high local histone concentrations. Functionally, acute DNase1 treatment resulted in significantly improved left ventricular remodeling in mice as measured by serial echocardiography, while mortality, infarct size and inflammatory parameters were unaffected. Notably, improved cardiomyocyte survival within the infarct region was observed and might account for the protective effects in acutely DNase1-treated animals. Disruption of extracellular cytotoxic chromatin within the infarcted heart by acute DNase1 treatment is a promising approach to protect myocytes from histone-induced cell death and subsequent left ventricular dysfunction after MI. PMID:25702039

  14. Right Ventricular Adaptation in Congenital Heart Diseases

    Directory of Open Access Journals (Sweden)

    Beatrijs Bartelds

    2014-05-01

    Full Text Available In the last four decades, enormous progress has been made in the treatment of congenital heart diseases (CHD; most patients now survive into adulthood, albeit with residual lesions. As a consequence, the focus has shifted from initial treatment to long-term morbidity and mortality. An important predictor for long-term outcome is right ventricular (RV dysfunction, but knowledge on the mechanisms of RV adaptation and dysfunction is still scarce. This review will summarize the main features of RV adaptation to CHD, focusing on recent knowledge obtained in experimental models of the most prevalent abnormal loading conditions, i.e., pressure load and volume load. Models of increased pressure load for the RV have shown a similar pattern of responses, i.e., increased contractility, RV dilatation and hypertrophy. Evidence is accumulating that RV failure in response to increased pressure load is marked by progressive diastolic dysfunction. The mechanisms of this progressive dysfunction are insufficiently known. The RV response to pressure load shares similarities with that of the LV, but also has specific features, e.g., capillary rarefaction, oxidative stress and inflammation. The contribution of these pathways to the development of failure needs further exploration. The RV adaptation to increased volume load is an understudied area, but becomes increasingly important in the growing groups of survivors of CHD, especially with tetralogy of Fallot. Recently developed animal models may add to the investigation of the mechanisms of RV adaptation and failure, leading to the development of new RV-specific therapies.

  15. Atrial – Ventricular Septal Defect

    Directory of Open Access Journals (Sweden)

    T Panagiotopoulos

    2009-05-01

    Full Text Available Atrial and ventricular septal defect constitute the most common congenital heart disease.Aim: ?he aim of the present retrospective study was to record data and factors that affect atrial and ventricular septal defect.Method and material: The sample study included patients of both sexes who were hospitalized with diagnosis atrial and ventricular septal defect in a Cardiac Surgery hospital of Athens. A specially constructed printed form was used for data collection, where were recorded the demographic and personal variables, the pathological, surgical, cardiology and obstetric history, the habits of adults, as well as the personal characteristics of mothers. Analysis of data was performed by descriptive statistical analysis.Results: The sample study consisted of 101 individuals with diagnosis atrial or ventricular Septal Defect, of which 40% were boys and 60% girls. The 70% of the sample study suffered from atrial Septal Defect and the 30% suffered from ventricular Septal Defect. Regarding age, 12% of the sample study was 0-1 years old, 35% was >1 years old, 8% was >12-18 years old and 45% over than 18 years old. Regarding educational status of the adult participants, 9% was of 0-6 years education, 22%>6 -12 years, 13%>12 years. 14% of the adult paticipants smoked, 4% consumed alcohol and 5% smoked in conjunction with alcohol. In terms of the obstetric history of the sample studied, 32% of the cases had normal birth, 4% had a twin birth and 1% had a triplet one. According to the variables related to mothers, the mean age of the mother was 30 years and 3 months, 10% were smokers at pregnancy and 3% used chemical substance and mainly hair color. Also, the results of the present study showed that individuals of 12-18 and >18 years old did not suffer from ventricular Septal Defect, whereas the infants 0-1 years old did not suffer from Atrial Septal Defect. The mean value of age at the admission in intensive care unit was 7 months (12% for the infants, 4 years and 8 months for children (35%, 15 years and 2 months (8% for adolescents and 41 years and 4 months for the adult. 58% of the sample study manifested clinical symptoms at the admission in intensive care unit, whereas complications during their care manifested the 79% of cases.Conclusions: It is a matter of great importance, if society in collaboration with health care professionals could early organize systematic diagnostic and educational programs for improving the knowledge of the disease.

  16. Disseminated cysticercosis with huge muscle hypertrophy

    Directory of Open Access Journals (Sweden)

    Bandyopadhyay Debabrata

    2009-01-01

    Full Text Available Cysticercosis is caused by cysticercus cellulose, which is the larva of Taenia solium , the pork tapeworm. The larvae are carried in the blood stream after penetrating the walls of the alimentary tract and they lodge in different tissues like the skin, skeletal muscles, brain, fundus and heart, to cause disseminated cysticercosis. Cases of disseminated cysticercosis have rarely been reported in the literature. They may inhabit the muscles and cause muscular hypertrophy, which, at times, may assume gross proportions. Morbidity is usually caused by the involvement of the central nervous system or the eyes.

  17. The total length of myocytes and capillaries, and total number of myocyte nuclei in the rat heart are time-dependently increased by growth hormone

    DEFF Research Database (Denmark)

    Brüel, Annemarie; Oxlund, Hans

    2005-01-01

    Growth hormone (GH) can increase size and dimensions of rat hearts. The aim was to study how GH administration influences the growth of cardiac myocytes and capillaries in relation to time. Three-month-old female rats were divided into 10 groups (n=3), and injected with either GH (5mg/kg/day) or vehicle for 5, 10, 20, 40, or 80 days. From the left ventricle (LV) histological sections were made and stereological methods applied. Linear regression showed that GH time-dependently increased: LV volume (r=0.96, P<0.001), total volume of myocytes (r=0.96, P<0.001) and capillaries (r=0.64, P<0.05), total length of myocytes (r=0.90, P<0.001) and capillaries (r=0.78, P<0.001), and total number of myocyte nuclei (r=0.85, P<0.001). In conclusion, during 80 days of GH treatment the total volume and length of myocytes and capillaries, and total number of myocyte nuclei increased in a linear way. The results indicate that GH is a potent mediator of myocardial growth.

  18. High-dose chloroquine is metabolically cardiotoxic by inducing lysosomes and mitochondria dysfunction in a rat model of pressure overload hypertrophy.

    Science.gov (United States)

    Chaanine, Antoine H; Gordon, Ronald E; Nonnenmacher, Mathieu; Kohlbrenner, Erik; Benard, Ludovic; Hajjar, Roger J

    2015-07-01

    Autophagy, macroautophagy and chaperone-mediated autophagy (CMA), are upregulated in pressure overload (PO) hypertrophy. In this study, we targeted this process at its induction using 3 methyladenine and at the lysosomal level using chloroquine and evaluated the effects of these modulations on cardiac function and myocyte ultrastructure. Sprague-Dawley rats weighing 200 g were subjected to ascending aortic banding. After 1 week of PO, animals were randomized to receive 3 methyladenine versus chloroquine, intraperitoneally, for 2 weeks at a dose of 40 and 50 mg/kg/day, respectively. Saline injection was used as control. Chloroquine treatment, in PO, resulted in regression in cardiac hypertrophy but with significant impairments in cardiac relaxation and contractility. Ultrastructurally, chloroquine accentuated mitochondrial fragmentation and cristae destruction with a plethora of autophagosomes containing collapsed mitochondria and lysosomal lamellar bodies. In contrast, 3 methyladenine improved cardiac function and attenuated mitochondrial fragmentation and autophagososme formation. Markers of macroautophagy and CMA were significantly decreased in the chloroquine group; whereas 3 methyladenine treatment significantly attenuated macroautophagy with a compensatory increase in CMA. Furthermore, chloroquine accentuated PO induced oxidative stress through the further decrease in the expression of manganese superoxide dismutase; whereas, 3 MA had a completely opposite effect. Taken together, these data suggest that high-dose chloroquine, in addition to its effect on the autophagy-lysosome pathway, significantly impairs mitochondrial antioxidant buffering capacity and accentuates oxidative stress and mitochondrial dysfunction in PO hypertrophy; highlighting, the cautious administration of this drug in high oxidative stress conditions, such as pathological hypertrophy or heart failure. PMID:26152691

  19. Right coronary artery becomes stiffer with increase in elastin and collagen in right ventricular hypertrophy

    OpenAIRE

    Garcia, Marisa; Kassab, Ghassan S.

    2009-01-01

    Changes in blood flow influence the structure, function, mechanical properties, and remodeling of arteries. The objective of the present study was to investigate the role of increased blood flow on the biaxial incremental elastic moduli of the porcine right coronary artery (RCA) and to determine the microstructural basis for the changes in moduli. We hypothesized that an increase in RCA flow will lead to increased stiffness in conjunction with remodeling of elastin and collagen in the vessel ...

  20. Diagnostic value of perfusion 201Tl scintigraphy of the myocardium in assessing right ventricular hypertrophy

    International Nuclear Information System (INIS)

    Perfusion scintigraphy of the heart muscle with Tl201 was tested in the diagnosis of overloading of the right ventricle in a group of 24 patients with chronic pulmonary disease and in a group of 26 patients with mitral stenosis only. The results of scintigraphy of the heart muscle and ECG examination were compared with results of the examination of haemodynamics of the lesser circulation, blood gases and spirometric examination. The study shows that thallium scintigraphy is a fairly sensitive method for noninvasive diagnosis of pulmonary arterial hypertension. It is an auxiliary method and its validity increases when combined with other noninvasive methods. (author)

  1. The role of cardiac magnetic resonance imaging in differentiating the underlying causes of left ventricular hypertrophy

    OpenAIRE

    Germans, T.; Nijveldt, R.; Brouwer, W.P; Groothuis, J.G.J.; Beek, A M; Götte, M.J.W.; Rossum, A.C. van

    2010-01-01

    The onset of sudden cardiac death and large inter- and intra-familial clinical variability of hypertrophic cardiomyopathy pose an important clinical challenge. Cardiac magnetic resonance imaging is a high-resolution imaging modality that has become increasingly available in the past decade and has the unique possibility to demonstrate the presence of fibrosis or scar using late gadolinium enhancement imaging. As a result, the diagnostic and prognostic potential of cardiac magnetic resonance i...

  2. Monitoring of ANP secretion from single atrial myocytes using densitometry.

    Science.gov (United States)

    Ryu, Shin Young; Lee, Suk-Ho; Isenberg, Gerrit; Ho, Won-Kyung; Earm, Yung E

    2002-07-01

    Atrial myocytes secrete atrial natriuretic peptide (ANP) in response to mechanical stretch and can serve as a challenging model for studying stretch-secretion coupling. We have developed a technique for monitoring ANP secretion from single atrial myocytes, using neutral red and a CCD video camera. Atrial-specific granules (ASGs) containing ANP were stained with neutral red. The cells were illuminated with monochromatic light (550 mm) and the grey value monitored within the region of interest (ROI) surrounding the region in which ASGs were densely located. Assuming that neutral red is evenly distributed in ASGs, the change in optical density (OD) was considered to represent the total amount of secretion. Under control, non-stimulated conditions, the OD decreased spontaneously (19.7+/-1.4%/10 min, n=14). Direct mechanical stretch (cell length increased by 20%) with two micropipettes or hypotonic swelling (200 mOsm) accelerated the decrease in OD significantly (48.7+/-7.4%/10 min; n=3, 47.2+/-2.4%/10 min; n=7, respectively). In conclusion, this method allows monitoring of ANP secretion with a relatively high time resolution while mechanical stress is applied. Furthermore, patch-clamp or intracellular perfusion techniques can be combined with the present technique for studying cellular mechanisms of stretch-secretion coupling. PMID:12136277

  3. Identification of cardiac stem cells within mature cardiac myocytes.

    Science.gov (United States)

    Belostotskaya, Galina; Nevorotin, Alexey; Galagudza, Michael

    2015-10-01

    Cardiac stem cells are described in a number of mammalian species including humans. Cardiac stem cell clusters consisting of both lineage-negative and partially committed cells are generally identified between contracting cardiac myocytes. In the present study, c-kit(+), Sca(+), and Isl1(+) stem cells were revealed to be located inside the sarcoplasm of cardiac myocytes in myocardial cell cultures derived from newborn, 20-, and 40-day-old rats. Intracellularly localized cardiac stem cells had a coating or capsule with a few pores that opened into the host cell sarcoplasm. The similar structures were also identified in the suspension of freshly isolated myocardial cells (ex vivo) of 20- and 40-day-old rats. The results from this study provide direct evidence for the replicative division of encapsulated stem cells, followed by their partial cardiomyogenic differentiation. The latter is substantiated by the release of multiple transient amplifying cells following the capsule rupture. In conclusion, functional cardiac stem cells can reside not only exterior to but also within cardiomyocytes. PMID:26280107

  4. Classification of ventricular septal defects.

    OpenAIRE

    Soto, B; Becker, A.E.; Moulaert, A J; Lie, J. T.; Anderson, R H

    1980-01-01

    A classification with clinical significance is proposed for ventricular septal defect based on the study of 220 hearts with defects of the ventricular septum. All had atrioventricular and ventriculoarterial concordance with normal relations of cardiac structure. For the purpose of classification, the ventricular septum was considered as possessing muscular and membranous portions, the muscular septum itself being divided into inlet, trabecular, and outlet (or infundibular) components. Defects...

  5. Evaluation on the clinical effect of transcatheter closure for perimembranous ventricular septal defects

    International Nuclear Information System (INIS)

    Objective: To evaluate the clinical effect of transcatheter occlusion for perimembranous ventricular septal defects (PVSD). Methods: 89 cases of PVSD were retrospectively studied. All cases presented dyspnea during exercise for several years. Physical examination had III-IV/VI systolic murmurs along the lower left sternal border, the intensity of the pulmonary second sound was increased or splitting; ECG showed left ventricular hypertrophy in 17 cases, left atrial hypertrophy in 8 cases; the size of the PVSD was 4 - 8 mm in UCG. The diameter of PVSD ranged from 3 to 10 (4.9 ± 1.8) mm in left ventricular angiographies, the superior margin of PVSD was 1 - 5(2.3 ± 0.9) mm away from the aortic valve. Aneurysm of the membranous septum was present in 36 cases, with patent arterial duct in 2 and with mild aortic insufficiency in 1 case. The procedure was performed successfully in 88 cases, including 82 with a perimembarranous ventricular septal occluder (PVSO) and 7 with Amplatzer duct occluder. Crossing the PVSD from the left ventricular side with a Terumo wire using a Judkins right coronary catheter; the wire was snared and pulled out to the femoral vein. The device size ranged from 6 - 14 (7.5 ± 1.8) mm. Results: There were 67 cases with immediately complete closure of the defect, 21 had trivial residual shunt. One patient had a detached device embolism in to left pulmonary vessel, but successfully tracked out with snare catheter. The patient was operated because his VSD belonged to intra-crista type. All patents showed complete abolition of the shunt on a follow-up of 1 - 15 months. There were no other complications. Conclusion: Although the procedure is complex and requires high technical expertise, the transcatheter closure of PVSD is safe and effective for selected cases of PVSD. Further clinical trials are underway to probe the long-term efficacy. (author)

  6. Genetic and clinical profile of Indian patients of idiopathic restrictive cardiomyopathy with and without hypertrophy

    DEFF Research Database (Denmark)

    Rai, Taranjit Singh; Ahmad, Shamim

    2009-01-01

    Both idiopathic restrictive cardiomyopathy (IRCM) and hypertrophic cardiomyopathy (HCM) are part of the same disease spectrum and are due to sarcomeric gene mutations. A patient with restrictive physiology without left ventricular hypertrophy (LVH) would be diagnosed as IRCM, while one with LVH would be diagnosed as HCM with restrictive physiology. We studied a group of patients with restrictive physiology for mutations in beta-myosin heavy chain (MYH7) and troponin I (TNNI3) gene. Consecutive probands in the HCM and IRCM cohort over a 4-year period were considered for this study. These included 10 IRCM and 102 HCM patients. All were Asian Indians. Among the 17 patients who had restrictive physiology 10 were IRCM patients and seven were HCM patients. Of the HCM patients, seven (6.9%) had restrictive physiology. Mean age of these 17 patients was 40.1 +/- 19.2 years (range: 15-67 ), six (35.3%) were males. Maximal left ventricular wall thickness of the seven HCM probands was 20.7