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Signaling responses after exposure to 5?-dihydrotestosterone or 17?-estradiol in norepinephrine-induced hypertrophy of neonatal rat ventricular myocytes  

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Androgens appear to enhance, whereas estrogens mitigate, cardiac hypertrophy. However, signaling pathways in cells for short (3 min) and longer term (48 h) treatment with 17?-estradiol (E2) or 5?-dihydrotestosterone (DHT) are understudied. We compared the effect of adrenergic stimulation by norepinephrine (NE; 1 ?M) alone or in combination with DHT (10 nM) or E2 (10 nM) treatment in neonatal rat ventricular myocytes (NRVMs) by cell area, protein synthesis, sarcomeric structure, gene expres...

Koshman, Yevgeniya E.; Piano, Mariann R.; Russell, Brenda; Schwertz, Dorie W.

2010-01-01

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

Scientific Electronic Library Online (English)

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

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

2003-05-01

3

Ventricular hypertrophy in cardiomyopathy.  

Science.gov (United States)

Semantic difficulties arise when hypertrophic obstructive cardiomyopathy is seen without obstruction and with congestive failure, and also when congestive cardiomyopathy is seen with gross hypertrophy but without heart failure. Retention of a small left ventricular cavity and a normal ejection fraction characterizes hypertrophic cardiomyopathy at all stages of the disorder. Congestive cardiomyopathy is recognized by the presence of a dilated left ventricular cavity and reduced ejection fraction regardless of the amount of hypertrophy and the presence or not of heart failure. Longevity in congestive cardiomyopathy seems to be promoted when hypertrophy is great relative to the amount of pump failure as measured by increase in cavity size. Conversely, death in hypertrophic cardiomyopathy is most likely when hypertrophy is greatest at a time when outflow tract obstruction has been replaced by inflow restriction caused by diminishing ventricular distensibility. Hypertrophy is thus beneficial and compensatory in congestive cardiomyopathy, whereas it may be the primary disorder and eventual cause of death in hypertrophic cardiomyopathy. Reasons are given for believing that hypertension may have been the original cause of left ventricular dilatation in some case of congestive cardiomyopathy in which loss of stroke output thenceforward is followed by normotension. Development of severe hypertension in these patients after recovery from a prolonged period of left ventricular failure with normotension lends weight to this hypothesis. No fault has been found in the large or small coronary arteries in either hypertrophic cardiomyopathy or congestive cardiomyopathy when they have been examined in life by selective coronary angiography, or by histological methods in biopsy or post-mortem material. Coronary blood supply may be a limiting factor in the compensatory hypertrophy of congestive cardiomyopathy, and the ability to hypertrophy may explain the better prognosis of some patients. In hypertrophic cardiomyopathy excessive metabolic demand may not be met, and inadequacy of blood flow may contribute both to sudden death and to progressive replacement fibrosis in this disease. Histochemical and ultrastructural methods have failed to show any fundamental differences between hypertrophic cardiomyopathy and congestive cardiomyopathy, whereas conventional histology permits recognition of hypertrophic cardiomyopathy and distinction both from congestive cardiomyopathy and from ;normal' secondary hypertrophy in organic aortic stenosis. PMID:4252244

Oakley, C

1971-01-01

4

High-Mobility Group Box 1 Induces Calcineurin-Mediated Cell Hypertrophy in Neonatal Rat Ventricular Myocytes  

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Cardiac hypertrophy is an independent predictor of cardiovascular morbidity and mortality. In recent years, evidences suggest that high-mobility group box 1 (HMGB1) protein, an inflammatory cytokine, participates in cardiac remodeling; however, the involvement of HMGB1 in the pathogenesis of cardiac hypertrophy remains unknown. The aim of this study was to investigate whether HMGB1 is sufficient to induce cardiomyocyte hypertrophy and to identify the possible mechanisms underlying the hypertr...

Su, Fei-fei; Shi, Miao-qian; Guo, Wan-gang; Liu, Xiong-tao; Wang, Hong-tao; Lu, Zi-fan; Zheng, Qiang-sun

2012-01-01

5

Signaling responses after exposure to 5 alpha-dihydrotestosterone or 17 beta-estradiol in norepinephrine-induced hypertrophy of neonatal rat ventricular myocytes.  

Science.gov (United States)

Androgens appear to enhance, whereas estrogens mitigate, cardiac hypertrophy. However, signaling pathways in cells for short (3 min) and longer term (48 h) treatment with 17beta-estradiol (E2) or 5 alpha-dihydrotestosterone (DHT) are understudied. We compared the effect of adrenergic stimulation by norepinephrine (NE; 1 microM) alone or in combination with DHT (10 nM) or E2 (10 nM) treatment in neonatal rat ventricular myocytes (NRVMs) by cell area, protein synthesis, sarcomeric structure, gene expression, phosphorylation of extracellular signal-regulated (ERK), and focal adhesion kinases (FAK), and phospho-FAK nuclear localization. NE alone elicited the expected hypertrophy and strong sarcomeric organization, and DHT alone gave a similar but more modest response, whereas E2 did not alter cell size. Effects of NE dominated when used with either E2 or DHT with all combinations. Both sex hormones alone rapidly activated FAK but not ERK. Long-term or brief exposure to E2 attenuated NE-induced FAK phosphorylation, whereas DHT had no effect. Neither hormone altered NE-elicited ERK activation. Longer term exposure to E2 alone reduced FAK phosphorylation and reduced nuclear phospho-FAK, whereas its elevation was seen in the presence of NE with both sex hormones. The mitigating effects of E2 on the NE-elicited increase in cell size and the hypertrophic effect of DHT in NRVMs are in accordance with results observed in whole animal models. This is the first report of rapid, nongenomic sex hormone signaling via FAK activation and altered FAK trafficking to the nucleus in heart cells. PMID:20044473

Koshman, Yevgeniya E; Piano, Mariann R; Russell, Brenda; Schwertz, Dorie W

2010-03-01

6

Chronic coronary artery constriction leads to moderate myocyte loss and left ventricular dysfunction and failure in rats.  

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Coronary artery narrowing, ranging from 19% to 61%, was induced in rats and ventricular performance, myocardial damage, and myocyte hypertrophy were examined 1 mo later. Animals were separated into two groups, exhibiting ventricular dysfunction and failure, respectively. Dysfunction consisted of a 2.4-fold increase in left ventricular end diastolic pressure (LVEDP), 15% decrease in left ventricular peak systolic pressure (LVPSP), 24% reduction in developed pressure (DP), and a 16% depression ...

Anversa, P.; Zhang, X.; Li, P.; Capasso, J. M.

1992-01-01

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Multiscale modeling in rodent ventricular myocytes.  

Science.gov (United States)

There is a growing body of experimental evidence suggesting that the Ca(2+) signaling in ventricular myocytes is characterized by a high gradient near the cell membrane and a more uniform Ca(2+) distribution in the cell interior [1]--[7]. An important reason for this phenomenon might be that in these cells the t-tubular system forms a network of extracellular space, extending deep into the cell interior. This allows the electrical signal, that propagates rapidly along the cell membrane, to reach the vicinity of the sarcoplasmic reticulum (SR), where intracellular Ca(2+) required for myofilament activation is stored [1], [8]--[11]. Early studies of cardiac muscle showed that the t-tubules are found at intervals of about 2 lm along the longitudinal cell axis in close proximity to the Z-disks of the sarcomeres [12]. Subsequent studies have demonstrated that the t-tubular system has also longitudinal extensions [9]--[11], [13]. PMID:19349251

Lu, Shaoying; Michailova, Anushka; Saucerman, Jeffrey; Cheng, Yuhui; Yu, Zeyun; Kaiser, Timothy; Li, Wilfred; Bank, Randolph; Holst, Michael; McCammon, J; Hayashi, Takeharu; Hoshijima, Masahiko; Arzberger, Peter; McCulloch, Andrew

2009-01-01

8

Post-translational modifications of tubulin and microtubule stability in adult rat ventricular myocytes and immortalized HL-1 cardiomyocytes.  

Science.gov (United States)

Little is known about the subcellular distribution and the dynamics of tubulins in adult cardiac myocytes although both are modified during cardiac hypertrophy and heart failure. Using confocal microscopy, we examined post-translational modifications of tubulin in fully differentiated ventricular myocytes isolated from adult rat hearts, as well as in immortalized and dividing HL-1 cardiomyocytes. Detyrosinated Glu-alpha-tubulin was the most abundant post-translationally modified tubulin found in ventricular myocytes, while acetylated- and delta2-alpha-tubulins were found in lower amounts or absent. In contrast, dividing HL-1 cardiomyocytes exhibited high levels of tyrosinated or acetylated alpha-tubulins. A mild nocodazole treatment (0.1 microM, 1 h) disrupted microtubules in HL-1 myocytes, but not in adult ventricular myocytes. A stronger treatment (10 microM, 2 h) was required to disassemble tubulins in adult myocytes. Glu-alpha-tubulin containing microtubules were more resistant to nocodazole treatment in HL-1 cardiomyocytes than in ventricular myocytes. Endogenous activation of the cAMP pathway with the forskolin analog L858051 (20 microM) or the beta-adrenergic agonist isoprenaline (10 microM) disrupted the most labile microtubules in HL-1 cardiomyocytes. In contrast, isoprenaline (10 microM), cholera toxin (200 ng/ml, a G(S)-protein activator), L858051 (20 microM) or forskolin (10 microM) had no effect on the microtubule network in ventricular myocytes. In addition, intracellular Ca2+ accumulation induced either by thapsigargin (2 microM) or caffeine (10 mM) did not modify microtubule stability in ventricular myocytes. Our data demonstrate the unique stability of the microtubule network in adult cardiac myocytes. We speculate that microtubule stability is required to support cellular integrity during cardiac contraction. PMID:15030168

Belmadani, Souad; Poüs, Christian; Fischmeister, Rodolphe; Méry, Pierre-François

2004-03-01

9

Trichostatin A accentuates doxorubicin-induced hypertrophy in cardiac myocytes  

Science.gov (United States)

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

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

2010-01-01

10

Transient Severe Isolated Right Ventricular Hypertrophy in Neonates  

Science.gov (United States)

Isolated right ventricular hypertrophy (RVH) is a rare form of hypertrophic cardiomyopathy and premature closure of the patent ductus arteriosus in utero is a probable etiologic factor. We reported transient isolated RVH in three neonates and ventricular hypertrophy resolved within 8-10 weeks period without any specific therapy in all cases.

Alp, Hayrullah; Karatas, Zehra; Baysal, Tamer

2014-01-01

11

Left ventricular diastolic performance of left ventricular hypertrophy  

International Nuclear Information System (INIS)

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

12

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

13

Stochastic Simulation of Cardiac Ventricular Myocyte Calcium Dynamics and Waves  

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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 ...

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

2011-01-01

14

Instability of myocardial repolarization in patients with left ventricular hypertrophy  

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Background: Left ventricular hypertrophy (LVH) is known to increase the incidence of sudden cardiac death. The pathophysiological backround is supposed to be an increased vulnerability of the heart for ventricular arrhythmias. The same connection is known of alterated myocardial repolarisation as indicated by a prolongated electrocardiographic qt interval. The aim of this study was to investigate whether there is a direct correlation between LVH (as indicated by the left ventricular...

Fehrendt, Stefanie

2010-01-01

15

Calcium-independent phospholipase A2 in rabbit ventricular myocytes.  

Science.gov (United States)

We have previously reported that the majority of phospholipase A2 (PLA2) activity in rabbit ventricular myocytes is membrane-associated, calcium-independent (iPLA2), selective for arachidonylated plasmalogen phospholipids and inhibited by the iPLA2-selective inhibitor bromoenol lactone (BEL). Here, we identified the presence of iPLA2 in rabbit ventricular myocytes, determined the full length sequences for rabbit iPLA2beta and iPLA2gamma and compared their homology to the human isoforms. Rabbit iPLA2beta encoded a protein with a predicated molecular mass of 74 kDa that is 91% identical to the human iPLA2beta short isoform. Full length iPLA2gamma protein has a predicated molecular mass of 88 kDa and is 88% identical to the human isoform. Immunoblot analysis of iPLA2beta and gamma in membrane and cytosolic fractions from rabbit and human cardiac myocytes demonstrated a similar pattern of distribution with both isoforms present in the membrane fraction, but no detectable protein in the cytosol. Membrane-associated iPLA2 activity was inhibited preferentially by the R enantiomer of bromoenol lactone [(R)-BEL], indicating that the majority of activity is due to iPLA2gamma. PMID:18574607

Beckett, Caroline S; McHowat, Jane

2008-09-01

16

Apical aneurysm and left ventricular hypertrophy  

Directory of Open Access Journals (Sweden)

Full Text Available A 59-year-old woman presented with an embolic transient ischemic attack and a history of controlled hypertension for 16 years. Both echocardiogram and MRI showed severe biventricular hypertrophy and an apical aneurysm with a thrombus. The occurrence of an apical aneurysm in the presence of cardiac hypertrophy is a rare finding and has been described in patients with hypertrophic cardiomyopathy. However, it has not been reported in patients with systemic arterial hypertension. In this patient the lack of a relationship between the severity of the hypertrophy and the levels of blood pressure, together with the presence of histologic disorganization of myocardial cardiac muscle cells by endomyocardial biopsy suggested the diagnosis of hypertrophic cardiomyopathy.

Helena Nogueira Soufen

2000-08-01

17

Thyroid status and potassium currents in rat ventricular myocytes.  

Science.gov (United States)

The size and rate dependence of the transient (Ito) and steady-state (Iss) outward potassium currents were investigated in isolated rat ventricular myocytes obtained from euthyroid, hyperthyroid, and hypothyroid rats, using the whole cell, suction electrode voltage-clamp method. Under hypothyroid conditions Ito was reduced in size, with no significant change in Iss. In hypothyroid cells, the rate dependence of both currents was greatly enhanced, resulting in a much larger attenuation with increasing stimulation rates. A significant slowing of the recovery kinetics of Ito was observed. These effects of hypothyroidism were reversed by physiological triiodothyronine (T3) replacement. These current changes were reflected in an altered rate dependence of the action potential configuration in hypothyroid myocytes. Under hyperthyroid conditions no significant changes were observed in the amplitude or time course of recovery of Ito. Iss amplitude was increased, but no changes were found in its rate dependence. These results are discussed in terms of hormonal, long-term modulation of potassium currents, and in terms of cardiac pathology under conditions of altered thyroid status. PMID:7864182

Shimoni, Y; Severson, D L

1995-02-01

18

Skeletal myocyte hypertrophy requires mTOR kinase activity and S6K1  

International Nuclear Information System (INIS)

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

19

Mitochondrial metabolic adaptation in right ventricular hypertrophy and failure  

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Right ventricular failure (RVF) is the leading cause of death in pulmonary arterial hypertension (PAH). Some patients with pulmonary hypertension are adaptive remodelers and develop RV hypertrophy (RVH) but retain RV function; others are maladaptive remodelers and rapidly develop RVF. The cause of RVF is unclear and understudied and most PAH therapies focus on regressing pulmonary vascular disease. Studies in animal models and human RVH suggest that there is reduced glucose oxidation and incr...

Piao, Lin; Marsboom, Glenn; Archer, Stephen L.

2010-01-01

20

Inhibition of Angiotensin II-Induced Cardiac Hypertrophy and Associated Ventricular Arrhythmias by a p21 Activated Kinase 1 Bioactive Peptide  

Science.gov (United States)

Cardiac hypertrophy increases the risk of morbidity and mortality of cardiovascular disease and thus inhibiting such hypertrophy is beneficial. In the present study, we explored the effect of a bioactive peptide (PAP) on angiotensin II (Ang II)-induced hypertrophy and associated ventricular arrhythmias in in vitro and in vivo models. PAP enhances p21 activated kinase 1 (Pak1) activity by increasing the level of phosphorylated Pak1 in cultured neonatal rat ventricular myocytes (NRVMs). Such PAP-induced Pak1 activation is associated with a significant reduction of Ang II-induced hypertrophy in NRVMs and C57BL/6 mice, in vitro and in vivo, respectively. Furthermore, PAP antagonizes ventricular arrhythmias associated with Ang II-induced hypertrophy in mice. Its antiarrhythmic effect is likely to be involved in multiple mechanisms to affect both substrate and trigger of ventricular arrhythmogenesis. Thus our results suggest that Pak1 activation achieved by specific bioactive peptide represents a potential novel therapeutic strategy for cardiac hypertrophy and associated ventricular arrhythmias. PMID:25014109

Lin, Wee K.; Zhang, Yanmin; Liu, Wei; Huang, Kai; Terrar, Derek A.; Solaro, R. John; Wang, Xin; Ke, Yunbo; Lei, Ming

2014-01-01

 
 
 
 
21

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

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Right ventricular hypertrophy (RVH is an important complication of chronic lung disease. However, the signal transduction pathways involved as well as the physiological changes to the right ventricle have not been investigated. Emphysema was produced in male, Syrian Golden hamsters by intra-tracheal instillation of 250 IU/kg elastase (Emp, n = 17. Saline treated animals served as controls (Con, n = 15. Results Nine months later, Emp hamsters had 75% greater lung volume, and evidence of RVH at the gross and myocyte level (RV:tibia length Emp 6.84 ± 1.18 vs. Con 5.14 ± 1.11 mg/mm; myocyte cross sectional area Emp 3737 vs. Con 2695 ?m2, but not left ventricular hypertrophy. Serial echocardiographic analysis from baseline to nine months after induction of emphysema revealed increasing right ventricular internal dimension and decreased pulmonary artery acceleration time only in Emp hamsters. There was an increase in translocation of PKC ?I and PKC ? from cytosolic to membranous cell fractions in RV of Emp hamsters. Phosphorylation of PKC ? was unchanged. Translocation of PKC ? and ?II were unchanged. Emp animals had a 22% increase in phospho-ERK 1/2, but no change in levels of total ERK 1/2 compared to Con. Conclusion These data suggest that PKC ?I, ? and ERK 1/2 may play a role in mediating compensated RVH secondary to emphysema and may have clinical relevance in the pathogenesis of RVH.

Litwin Sheldon E

2005-05-01

22

L-type calcium current in right ventricular outflow tract myocytes of rabbit heart.  

Science.gov (United States)

The mechanism of idiopathic ventricular tachycardia originating from the right ventricular outflow tract (RVOT) is not clear. Many clinical reports have suggested a mechanism of triggered activity. However, there are few studies investigating this because of the technical difficulties associated with examining this theory. The L-type calcium current (I (Ca-L)), an important inward current of the action potential (AP), plays an important role in arrhythmogenesis. The aim of this study was to explore differences in the APs of right ventricular (RV) and RVOT cardiomyocytes, and differences in electrophysiological characteristics of the ICa-L in these myocytes. Rabbit RVOT and RV myocytes were isolated and their AP and I (Ca-L) were investigated using the patch-clamp technique. RVOT cardiomyocytes had a wider range of AP duration (APD) than RV cardiomyocytes, with some markedly prolonged APDs and markedly shortened APDs. The markedly shortened APDs in RVOT myocytes were abolished by treatment with 4-AP, an inhibitor of the transient outward potassium current, but the markedly prolonged APDs remained, with some myocytes with a long AP plateau not repolarizing to resting potential. In addition, early afterdepolarization (EAD) and second plateau responses were seen in RVOT myocytes but not in RV myocytes. RVOT myocytes had a higher current density for I (Ca-L) than RV myocytes (RVOT (13.16±0.87) pA pF(-1), RV (8.59±1.97) pA pF(-1); PRVOT myocytes than in RV myocytes, which is one of the basic factors involved in arrhythmogenesis. The higher current density for I (Ca-L) is one of the factors causing prolongation of the APD in RVOT myocytes. The combination of EAD with prolonged APD may be one of the mechanisms of RVOT-VT generation. PMID:22314490

Liang, Shenghui; Lin, Chenhui; Li, Yuan; Liu, Taifeng; Wang, Yan

2012-01-01

23

How to estimate left ventricular hypertrophy in hypertensive patients.  

Science.gov (United States)

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

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

2014-06-01

24

Modeling CICR in rat ventricular myocytes: voltage clamp studies  

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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.

Palade Philip T

2010-11-01

25

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

Science.gov (United States)

A case is presented revealing the common phenomenon of heart rate-dependent diagnosis of electrocardiographic (ECG) diagnosis of left ventricular hypertrophy (LVH), which consists of satisfaction of LVH criteria only at faster rates whereas ECGs with a slow heart rate do not satisfy such criteria. The mechanism of the phenomenon has been attributed to the tachycardia-mediated underfilling of the left ventricle bringing the electrical "centroid" of the heart closer to the recording electrodes, which results in augmentation of the amplitude of QRS complexes, particularly in leads V2-V4. PMID:22519574

Madias, John E

2013-05-01

26

Changes of Ventricular Myocytes Membrane Capacitance in Rabbit with Myocardial Infarction and Effects of Carvedilol  

DEFF Research Database (Denmark)

Objective: To investigate effects of long-term treatment of oral Carvedilol on ventricular myocytes membrane capacitance in HMI. Methods: 30 rabbits were randomly assigned in three groups: HMI group, ligation of circumflex coronary artery; Carvedilol group, with operation the same as HMI group, and administration of oral Carvedilol 0.33 mg/kg×3 months beginning on the day of operation; Sham group, left thoracotomy with no coronary artery ligation. 3 months after surgery, rabbits were harvested. Myocytes were isolated by enzymatic method. The cell membrane capacitance was recorded by using the whole cell patch clamp technique. Results: The membrane capacitance of myocytes in CVD group was reduced significantly as compared with those in HMI group which was larger than those in Sham group (P<0.05). Conclusion: Long-term treatment of oral Carvedilol may reverse the increase of ventricular myocytes membrane capacitance.

Niu, Hui-Yan; Liang, Bo

2005-01-01

27

Tissue characteristics in left ventricular hypertrophy using magnetic resonance imaging  

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

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

1988-06-01

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17 Beta-Estradiol Differentially Affects Left Ventricular and Cardiomyocyte Hypertrophy Following Myocardial Infarction and Pressure Overload  

Science.gov (United States)

Background We have shown previously that 17?-estradiol (E2) increases left ventricular (LV) and cardiomyocyte hypertrophy following myocardial infarction (MI). However, E2 decreases hypertrophy in pressure overload models. We hypothesized that the effect of estrogen on cardiac hypertrophy was dependent on the type of hypertrophic stimulus. Methods Ovariectomized wild type female mice (n=192) were given vehicle or E2 treatment followed by coronary ligation (MI), transverse aortic constriction (TAC), or sham operation. Signaling pathway activation was studied at 3, 24, and 48 hours while echocardiography and hemodynamic studies were performed at 14 days. Results MI induced early but transient activation of p38 and p42/44 MAPK pathways, whereas TAC induced sustained activation of both pathways. E2 had no effect on these pathways, but increased Stat3 activation following MI while decreasing Stat3 activation following TAC. MI caused LV dilation, and decreased fractional shortening (FS), that were unaltered by E2. TAC caused LV dilation, reduced FS, and increased LV mass, but in this model, E2 improved these parameters. Following MI, E2 led to increases in myocyte cross-sectional area, atrial natriuretic peptide (ANP) and ?-myosin heavy chain (MHC) gene expression, but E2 diminished TAC-induced increases ANP and ?-MHC gene expression. Conclusions These data demonstrate that the effects of E2 on LV and myocyte remodeling depend on the nature of the hypertrophic stimulus. The opposing influence of E2 on hypertrophy in these models may, in part, result from differential effects of E2 on Stat3 activation. Further work will be necessary to explore this and other potential mechanisms by which estrogen affects hypertrophy in these models. PMID:18381189

Patten, Richard D.; Pourati, Isaac; Aronovitz, Mark J.; Alsheikh-Ali, Alawi; Eder, Sarah; Force, Thomas; Mendelsohn, Michael E.; Karas, Richard H.

2014-01-01

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

Directory of Open Access Journals (Sweden)

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.

Yang Zhen-Yu

2010-04-01

30

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%) fnd 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)

31

Resveratrol protects rabbit ventricular myocytes against oxidative stress-induced arrhythmogenic activity and Ca2+ overload  

Science.gov (United States)

Aim: To investigate whether resveratrol suppressed oxidative stress-induced arrhythmogenic activity and Ca2+ overload in ventricular myocytes and to explore the underlying mechanisms. Methods: Hydrogen peroxide (H2O2, 200 ?mol/L)) was used to induce oxidative stress in rabbit ventricular myocytes. Cell shortening and calcium transients were simultaneously recorded to detect arrhythmogenic activity and to measure intracellular Ca2+ ([Ca2+]i). Ca2+/calmodulin-dependent protein kinases II (CaMKII) activity was measured using a CaMKII kit or Western blotting analysis. Voltage-activated Na+ and Ca2+ currents were examined using whole-cell recording in myocytes. Results: H2O2 markedly prolonged Ca2+ transient duration (CaTD), and induced early afterdepolarization (EAD)-like and delayed afterdepolarization (DAD)-like arrhythmogenic activity in myocytes paced at 0.16 Hz or 0.5 Hz. Application of resveratrol (30 or 50 ?mol/L) dose-dependently suppressed H2O2-induced EAD-like arrhythmogenic activity and attenuated CaTD prolongation. Co-treatment with resveratrol (50 ?mol/L) effectively prevented both EAD-like and DAD-like arrhythmogenic activity induced by H2O2. In addition, resveratrol markedly blunted H2O2-induced diastolic [Ca2+]i accumulation and prevented the myocytes from developing hypercontracture. In whole-cell recording studies, H2O2 significantly enhanced the late Na+ current (INa,L) and L-type Ca2+ current (ICa,L) in myocytes, which were dramatically suppressed or prevented by resveratrol. Furthermore, H2O2-induced ROS production and CaMKII activation were significantly prevented by resveratrol. Conclusion: Resveratrol protects ventricular myocytes against oxidative stress-induced arrhythmogenic activity and Ca2+ overload through inhibition of INa,L/ICa,L, reduction of ROS generation, and prevention of CaMKII activation. PMID:23912472

Li, Wei; Wang, Yue-peng; Gao, Ling; Zhang, Peng-pai; Zhou, Qing; Xu, Quan-fu; Zhou, Zhi-wen; Guo, Kai; Chen, Ren-hua; Yang, Huang-tian; Li, Yi-gang

2013-01-01

32

Mitochondrial ROS production and subsequent ERK phosphorylation are necessary for temperature preconditioning of isolated ventricular myocytes  

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Hypothermia and hypothermic preconditioning are known to be profoundly cardioprotective, but the molecular mechanisms of this protection have not been fully explained. In this study, temperature preconditioning (16?°C) was found to be cardioprotective in isolated adult rat ventricular myocytes, enhancing contractile recovery and preventing calcium dysregulation after oxidative stress. Hypothermic preconditioning preserved mitochondrial function by delaying the pathological opening of the m...

Bhagatte, Y.; Lodwick, D.; Storey, N.

2012-01-01

33

Hypoxia alters the subcellular distribution of protein kinase C isoforms in neonatal rat ventricular myocytes.  

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Cardiac myocytes coexpress multiple protein kinase C (PKC) isoforms which likely play distinct roles in signaling pathways leading to changes in contractility, hypertrophy, and ischemic preconditioning. Although PKC has been reported to be activated during myocardial ischemia, the effect of ischemia/hypoxia on individual PKC isoforms has not been determined. This study examines the effect of hypoxia on the subcellular distribution of individual PKC isoforms in cultured neonatal rat ventricula...

Goldberg, M.; Zhang, H. L.; Steinberg, S. F.

1997-01-01

34

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)

35

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

International Nuclear Information System (INIS)

Echocardiography was used for the study of prevalence of left ventricular hypertrophy in 839 liquidators of consequences of the Chernobyl accident. Prevalence of left ventricular hypertrophy (left ventricular myocardial mass 134 g/m2) was 10.3, 13.4 and 22.5 % in liquidators with normal blood pressure, borderline hypertension and hypertension, respectively. Liquidators with normal blood pressure had significantly greater left ventricular myocardial mass than normotensive men from general population while liquidators and non liquidators with hypertension had equal values of this parameter

36

Anti-Hypertensive Drugs Have Different Effects on Ventricular Hypertrophy Regression  

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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 o...

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

2010-01-01

37

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

Directory of Open Access Journals (Sweden)

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.

Rosa Eduardo Cantoni

2002-01-01

38

Calcium influx through If channels in rat ventricular myocytes  

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The Hyperpolarization-activated, Cyclic Nucleotide-gated (HCN) channels, or If/Ih channels, are conventionally considered as monovalent-selective channels. Recently we discovered that Ca2+ ions can permeate through HCN4 and Ih channels in neurons. This raises the possibility of Ca2+ permeation in If, the Ih counterpart in cardiac myocytes, due to their structural homology. We performed simultaneous measurement of fura-2 Ca2+ signals and whole-cell currents produced by HCN2 and HCN4 channels (...

Yu, Xiao; Chen, Xiao-wei; Zhou, Peng; Yao, Lijun; Liu, Tao; Zhang, Bo; Li, Ying; Zheng, Hui; Zheng, Liang-hong; Zhang, Claire Xi; Bruce, Iain; Ge, Jun-bo; Wang, Shi-qiang; Hu, Zhi-an; Yu, Han-gang

2007-01-01

39

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

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

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

1991-01-01

40

PKC-? mediates multiple endothelin-1 actions on systolic Ca2+ and contractility in ventricular myocytes.  

Science.gov (United States)

Endothelin-1 (ET-1) induces positive inotropy (enhanced contractility) in cardiac muscle, but establishing underlying cellular mechanisms has been controversial in part because of a growing number of signaling pathways and end effectors targeted by ET-1. Here we present evidence that ET-1 induces positive inotropism in ventricular tissue by increasing both systolic Ca2+ and myofilament Ca2+ sensitivity. To examine the roles of PKC-? and PKC-? in these acute responses to ET-1, kinase inactive dominant negative PKC (dn-PKC) constructs were expressed in adult rat ventricular myocytes. Yellow fluorescent protein (YFP) was fused to dn-PKC constructs to visualize expression and localization of dn-PKC in living myocytes. Due to an alanine to glutamate mutation in the pseudosubstrate site, dn-PKCs constitutively translocated to anchoring sites and were unaffected by agonist or phorbol ester treatment. Dn-PKC-?-YFP mainly distributed at Z-lines and at intercalated disks in adult myocytes, whereas dn-PKC-?-YFP stained the surface sarcolemma, T-tubules/Z-lines and perinuclear region. Myocytes expressing dn-PKC-?-YFP showed normal systolic Ca2+ and contractile responses to ET-1. In contrast, the entire ensemble of ET-1 responses was blocked in myocytes expressing dn-PKC-?-YFP including increased Ca2+ transients, enhanced myofilament Ca2+ sensitivity, and positive inotropy. This report provides direct evidence that PKC-? is activated early and robustly following ET-1 stimulation and thus mediates multiple intracellular changes underlying the acute actions of ET-1 on myocardium. PMID:22699119

Kang, Misuk; Chung, Ka Young

2012-07-01

 
 
 
 
41

Remodeling of myocyte dimensions in hypertrophic and atrophic rat hearts.  

Science.gov (United States)

Changes in hemodynamic load cause alterations in cardiac myocyte size, with regional variations in myocyte size distribution possible within the ventricular wall. We studied regional changes in cellular dimensions and their distribution in two models of cardiac hypertrophy and in cardiac atrophy in the rat. Combined volume-pressure overload was produced by 3,3',5-triiodo-L-thyronine (T3) treatment; atrophy was produced by heterotopic isotransplantation. Our previous data from long-term pressure overload after aortic constriction were used for comparison. Isolated ventricular myocytes were obtained after in vitro coronary perfusion with collagenase. Cell volume and its distribution were determined; cell length was directly measured by image analysis, and cross-sectional area was estimated from the cell volume/cell length ratio, assuming a cylindrical model. Myocyte hypertrophy resulting from hyperthyroidism and aortic constriction was primarily due to increased cross-sectional area. In both cases, the relative response was greater in the right ventricle than in the left ventricle. Within the left ventricle, epimyocardial myocytes enlarged the most. Aortic constriction and T3 treatment predominantly increased the size of smaller myocytes. Heterogeneity in myocyte size increased after constriction but remained relatively unaffected after T3 treatment. Atrophy of left ventricular myocytes was due to a proportional decrease in cell length and cross-sectional area, with the greatest decrease in the left ventricular endomyocardium. Atrophy predominantly affected larger myocytes, resulting in a more homogeneous overall population of smaller myocytes. We conclude that various alterations in load lead to diverse remodeling in the myocyte population throughout the ventricular wall. In general, smaller myocytes show the highest growth potential, whereas larger myocytes exhibit the highest potential to atrophy. PMID:1826234

Campbell, S E; Korecky, B; Rakusan, K

1991-04-01

42

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

Scientific Electronic Library Online (English)

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

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

2013-01-01

43

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

Scientific Electronic Library Online (English)

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

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

2013-03-01

44

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

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

Han, Shu-ying; Chu, Jin-xiu; Li, Guang-min; Zhu, Li-sha; Shi, Rui-fang

2010-01-01

45

Effects of pressure overload, left ventricular hypertrophy on beta-adrenergic receptors, and responsiveness to catecholamines.  

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Pressure overload left ventricular (LV) hypertrophy was produced by banding the ascending aorta of puppies and allowing them to grow to adulthood. LV free wall weight per body weight increased by 87% from a normal value of 3.23 +/- 0.19 g/kg. Hemodynamic studies of conscious dogs with LV hypertrophy and of normal, conscious dogs without LV hypertrophy showed similar base-line values for mean arterial pressure, heart rate, and LV end-diastolic pressure and diameter. LV systolic pressure was si...

Vatner, D. E.; Homcy, C. J.; Sit, S. P.; Manders, W. T.; Vatner, S. F.

1984-01-01

46

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

DEFF Research Database (Denmark)

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

Gerdts, E.; Cramariuc, D.

2008-01-01

47

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

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

Woo, Sun-hee; Morad, Martin

2001-01-01

48

Relationship between serum leptin levels and left ventricular hypertrophy  

Directory of Open Access Journals (Sweden)

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

Ozgur Kartal

2008-10-01

49

Dinitrophenol pretreatment of rat ventricular myocytes protects against damage by metabolic inhibition and reperfusion.  

Science.gov (United States)

We have investigated the protective effects of pretreatment with the mitochondrial uncoupler 2,4-dinitrophenol on the cellular damage induced by metabolic inhibition (with cyanide and iodoacetic acid) and reperfusion in freshly isolated adult rat ventricular myocytes. Damage was assessed from changes in cell length and morphology measured using video microscopy. Intracellular Ca(2+), mitochondrial membrane potential, and NADH were measured using fura-2, tetramethylrhodamine ethyl ester and autofluorescence, respectively. During metabolic inhibition myocytes developed rigor, and on reperfusion 73.6+/-8.1% hypercontracted and 10.8+/-6.7% recovered contractile function in response to electrical stimulation. Intracellular Ca(2+) increased substantially, indicated by a rise in the fura-2 ratio (340/380 nm) on reperfusion from 0.86+/-0.04 to 1.93+/-0.18. Myocytes pretreated with substrate-free Tyrode containing 50 microm dinitrophenol showed reduced reperfusion injury: 29.0+/-7.4% of cells hypercontracted and 65.3+/-7.3% recovered contractile function (Pglucose and pyruvate reduced these effects, and abolished the protection against damage by metabolic inhibition and reperfusion. However protection was unaffected by block of ATP-sensitive potassium channels. Thus the protective effects of pretreatment with dinitrophenol may result from a reduction in NADH in response to mitochondrial depolarisation. PMID:12056859

Rodrigo, G C; Lawrence, C L; Standen, N B

2002-05-01

50

Metabolic inhibition activates a non-selective current through connexin hemichannels in isolated ventricular myocytes.  

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Intracellular Na(+)accumulation and K(+)loss play important roles in the pathogenesis of arrhythmias and injury in the ischemic heart. We investigated the role of metabolically sensitive connexin hemichannels as a potential route for Na(+)influx and K(+)efflux during ischemia, using dye uptake and electrophysiological measurements to assay hemichannel activity in isolated rabbit ventricular myocytes. Consistent with the known size selectivity of connexin hemichannels,;50% of myocytes exposed to either low extracellular Ca(2+)(an established method for opening connexin hemichannels) or to metabolic inhibitors (a recently described method for opening hemichannels) accumulated fluorescent dyes with <1000 MW (propidium iodide and calcein), but excluded a larger dye with 1500-3000 MW (dextran-rhodamine). Using the whole cell patch clamp technique, we found that metabolic inhibitors activated a non-selective current permeant to both small and large cations, and blocked by La(3+), similar to the properties of connexin 43 when overexpressed in human embryonic kidney (HEK) cells. These findings indicate that isolated cardiac myocytes endogenously express metabolically-sensitive connexin hemichannels. If activated during ischemia, these hemichannels could contribute significantly to altered ionic fluxes promoting arrhythmias and myocardial injury. PMID:11013130

Kondo, R P; Wang, S Y; John, S A; Weiss, J N; Goldhaber, J I

2000-10-01

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Echocardiographic assessment of global ventricular function using the myocardial performance index in rats with hypertrophy.  

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Myocardial hypertrophy is the hallmark of chronic pressure overload and the myocardial performance index (MPI) is an easily recordable measurement of Doppler time intervals. In this study, the utility of using MPI to assess the progression of hypertrophy in the aortic-banded rat model was evaluated. Male Wistar rats (70-90 g) underwent ascending aorta constriction (n = 4) or a sham operation (n = 5). High-resolution echocardiography was performed 4, 7, 10, and 12 weeks after the surgery. Over this follow-up interval, animals in the aortic-banded group demonstrated an increase in their mean left ventricular (LV) mass and MPI compared with controls. MPI reflects ventricular performance in small animals with LV hypertrophy, showing alterations early after aorta constriction. PMID:15084191

Salemi, Vera M C; Pires, Mara D; Cestari, Ismar N; Cestari, Idágene A; Picard, Michael H; Leirner, Adolfo A; Mady, Charles

2004-04-01

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Docosahexaenoic Acid Reduces the Incidence of Early Afterdepolarizations caused by Oxidative Stress in Rabbit Ventricular Myocytes  

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Full Text Available Accumulating evidence has suggested that ?3-polyunsaturated fatty acids (?3-PUFAs may have beneficial effects in the prevention/treatment of cardiovascular diseases, while controversies still remain regarding their antiarrhythmic potential. It is not clear yet whether ?-3 PUFAs can suppress early afterdepolarizations (EADs induced by oxidative stress. In the present study, we recorded action potentials (APs using the the patch-clamp technique in ventricular myocytes isolated from rabbit hearts. The treatment of myocytes with H2O2 (200 ?M prolonged AP durations (APDs and induced EADs, which were significantly suppressed by docosahexaenoic acid (DHA, 10 or 25 µM (n = 8. To reveal the ionic mechanisms, we examined the effects of DHA on L-type calcium currents (ICa.L, late sodium (INa, and transient outward potassium currents (Ito in ventricular myocytes pretreated with H2O2. H2O2 (200 ?M increased ICa.L by 46.4% from control (-8.4 ±1.4 pA/pF to a peak level (-12.3±1.8 pA/pF, n=6, p < 0.01 after 6 min of H2O2 perfusion. H2O2-enhanced ICa.L was significantly reduced by DHA (25 ?M (-7.1 ± 0.9 pA/pF, n = 6, p < 0.01. Similarly, H2O2 increased the late INa (-3.2 ± 0.3 pC from control level (-0.7 ± 0.1 pC. DHA (25 ?M completely reversed the H2O2-induced increase in late INa (to -0.8 ± 0.2 pC, n=5. H2O2 also increased the peak amplitude of and the steady state Ito from 8.9 ±1.0 and 2.16 ± 0.25 pA/pF to 12.8 ±1.21 and 3.13 ± 0.47 pA/pF respectively (n=6, p < 0.01, however, treatment with DHA (25 ?M did not produce significant effects on current amplitudes and dynamics of Ito altered by H2O2. In addition, DHA (25 ?M did not affect the increase of intracellular reactive oxygen species (ROS levels induced by H2O2 in rabbit ventricular myocytes. These findings demonstrate that DHA suppresses exogenous H2O2-induced EADs mainly by modulating membrane ion channel functions, while its direct effect on ROS may play less prominent role.

ZhenghangZhao

2012-07-01

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

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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

Wachtell, K; Smith, G

2000-01-01

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Resolution of hyposmotic stress in isolated mouse ventricular myocytes causes sealing of t-tubules.  

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It has recently been shown that various stress-inducing manipulations in isolated ventricular myocytes may lead to significant remodelling of t-tubules. Osmotic stress is one of the most common complications in various experimental and clinical settings. This study was therefore designed to determine the effects of a physiologically relevant type of osmotic stress, hyposmotic challenge, to the integrity of the t-tubular system in mouse ventricular myocytes using the following two approaches: (1) electrophysiological measurements of membrane capacitance and inward rectifier (IK1) tail currents originating from K(+) accumulation in t-tubules; and (2) confocal microscopy of fluorescent dextrans trapped in sealed t-tubules. Importantly, we found that removal of '0.6 Na' (60% NaCl) hyposmotic solution, but not its application to myocytes, led to a ?27% reduction in membrane capacitance, a ?2.5-fold reduction in the amplitude of the IK1 tail current and a ?2-fold reduction in the so-called IK1 'inactivation' (due to depletion of t-tubular K(+)) at negative membrane potentials; all these data were consistent with significant detubulation. Confocal imaging experiments also demonstrated that extracellularly applied dextrans become trapped in sealed t-tubules only upon removal of hyposmotic solutions, i.e. during the shrinking phase, but not during the initial swelling period. In light of these data, relevant previous studies, including those on excitation-contraction coupling phenomena during hyposmotic stress, may need to be reinterpreted, and the experimental design of future experiments should take into account the novel findings. PMID:23585327

Moench, I; Meekhof, K E; Cheng, L F; Lopatin, A N

2013-07-01

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PGE2 release from tryptase-stimulated rabbit ventricular myocytes is mediated by calcium-independent phospholipase A2?.  

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Inflammation is associated with cardiovascular disease, including myocardial infarction, atherosclerosis, myocarditis and congestive heart failure. Mast cells have been implicated in inflammation, but their precise role in cardiac inflammation remains unclear. Mast cells contain a variety of pre-formed granule-associated mediators, including tryptase. We have previously demonstrated that the majority of the phospholipase A(2) (PLA(2)) activity in isolated rabbit ventricular myocytes is membrane-associated, calcium-independent and selective for plasmalogen phospholipids. We hypothesized that tryptase stimulation of rabbit ventricular myocytes would increase iPLA(2) activity, leading to increased arachidonic acid and prostaglandin E(2) (PGE(2)) release. Isolated rabbit ventricular myocytes were stimulated with tryptase and iPLA(2) activity, arachidonic acid and PGE(2) release were measured. Tryptase stimulation increased iPLA(2) activity after 5 min. Activation of iPLA(2) was accompanied by increased arachidonic acid and PGE(2) release in tryptase-stimulated myocytes. However no increase in platelet activating factor was observed with tryptase stimulation. To distinguish between different iPLA(2) isoforms in the myocardium, we pretreated ventricular myocytes with the (R)- and (S)-enantiomers of bromoenol lactone (BEL) to selectively inhibit iPLA(2)? and ? respectively. Pretreatment with (R)-BEL resulted in complete inhibition of tryptase-stimulated iPLA(2) activity, arachidonic acid and PGE(2) release, suggesting the iPLA(2)? is the predominant myocardial isoform activated by tryptase. These studies demonstrate that PGE(2) release from tryptase stimulated rabbit ventricular myocytes is mediated primarily by iPLA(2)?. PMID:21461868

Sharma, Janhavi; McHowat, Jane

2011-05-01

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Left ventricular hypertrophy in Turner syndrome : a prospective echocardiographic study  

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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.

Mortensen, Kristian Havmand; Gravholt, Claus HØjbjerg

2012-01-01

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

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

Chinali, M.; Simone, G. de

2008-01-01

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Pressure mediated hypertrophy and mechanical stretch up-regulate expression of the long form of leptin receptor (ob-Rb in rat cardiac myocytes  

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Full Text Available Abstract Background Hyperleptinemia is known to participate in cardiac hypertrophy and hypertension, but the relationship between pressure overload and leptin is poorly understood. We therefore examined the expression of leptin (ob and the leptin receptor (ob-R in the pressure-overloaded rat heart. We also examined gene expressions in culture cardiac myocytes to clarify which hypertension-related stimulus induces these genes. Results Pressure overload was produced by ligation of the rat abdominal aorta, and ob and ob-R isoform mRNAs were measured using a real-time polymerase chain reaction (PCR. We also measured these gene expressions in neonatal rat cardiac myocytes treated with angiotensin II (ANGII, endothelin-1 (ET-1, or cyclic mechanical stretch. Leptin and the long form of the leptin receptor (ob-Rb gene were significantly increased 4?weeks after banding, but expression of the short form of the leptin receptor (ob-Ra was unchanged. ob-Rb protein expression was also detected by immunohistochemistry in hypertrophied cardiac myocytes after banding. Meanwhile, plasma leptin concentrations were not different between the control and banding groups. In cultured myocytes, ANGII and ET-1 increased only ob mRNA expression. However, mechanical stretch activated both ob and ob-Rb mRNA expression in a time-dependent manner, but ob-Ra mRNA was unchanged by any stress. Conclusions We first demonstrated that both pressure mediated hypertrophy and mechanical stretch up-regulate ob-Rb gene expression in heart and cardiac myocytes, which are thought to be important for leptin action in cardiac myocytes. These results suggest a new local mechanism by which leptin affects cardiac remodeling in pressure-overloaded hearts.

Matsui Hiroki

2012-12-01

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Effects of nifedipine on left ventricular systolic and diastolic functions in patients with left ventricular hypertrophy  

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The effect of nifedpine on left ventricular (LV) systolic and diastolic function was studied in 10 patients with hypertrophic cadiomyopathy(HCM), 8 patients with hypertensive hypertrophy(HT) and 9 normal subjects. Multigated cardiac blood pool imaging with Tc-99m were obtained at 40-degree left anterior oblique position before and after nifedipine administration (10 mg, sublingually). As systolic indices, we obtained LV ejection fraction and mean first third ejection rate. And as diastolic indices, mean filling rate during first third of diastole (1/3 FRsub(mean)) and diastolic maximal filling rate were calculated. Before nifedipine, systolic indices were significantly superior in HCM group than in other 2 groups, and diastolic indices were significantly lower in HCM and HT groups than in normal. After nifedipine, systolic indices improved in HT group but they did not change in other 2 groups. Diastolic indices improved significantly in HCM and HT groups after nifedpine. In HCM group, 1/3 FRsub(mean) improved more markedly in symptomatic patients than in asymptomatic patients. The ratio of diastolic function to systolic function (1/3 FRsub(mean)/1/3 ERsub(mean)) did not change in normal and HT groups but it increased significantly in HCM group. There we a slight increase in heart rate (HR) and decrease in systemic arterial pressure (BP). The increase in HR was similar among 3 groups but the decrease in BP was significantly greater in HT group in whom control BP was siater in HT group in whom control BP was significantly higher than other groups. LV end-diastolic volume did not change in 3 groups by nifedipine administration. These data suggested that abnormal diastolic function in HCM and HT was faborably modified by nifedipine, but their mechanisms were different. In HT, it was considered to relate with improved systolic function due to LV afterload reduction, while in HCM, it was not related to the peripheral hemodynamic effects nor improved systolic function. (author)

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

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Alcohol consumption may result in electrocardiographic changes and arrhythmias. Important role of modifications of the inward rectifier potassium current IK1 in arrhythmogenesis is well established. Considering lack of relevant data, we aimed at studying the effect of 0.2-200 mM ethanol on IK1 in enzymatically isolated rat right ventricular myocytes using the whole cell patch-clamp technique at 23±1°C. Ethanol reversibly affected IK1 in a dual way. At a very low concentration of 0.8 mM (?~0.004%), ethanol significantly decreased IK1 by 6.9±2.7%. However, at concentrations of ethanol ?20 mM (?0.09%), IK1 was conversely significantly increased (by 16.6±4.0% at 20 mM and 24.5±2.4% at 80 mM). The steady-state IK1 increase was regularly preceded by its transient decrease at the beginning of ethanol application. Under 2 and 8 mM ethanol, IK1 was decreased at the steady-state in some cells but increased in others. Both effects were voltage-independent. In agreement with the observed effects of ethanol on IK1, a transient action potential (AP) prolongation followed by its final shortening were observed after the application of ethanol in a low concentration of 8 mM (?0.04%). Under the effect of 0.8 mM ethanol, only AP prolongation was apparent which agreed well with the above described IK1 decrease. Other AP characteristics remained unaltered in both concentrations. These observations corresponded with the results of mathematical simulations in a model of the rat ventricular myocyte. To summarize, changes of the cardiac IK1 under ethanol at concentrations relevant to the current alcohol consumption were first demonstrated in ventricular myocytes in this study. The observed dual ethanol effect suggests at least two underlying mechanisms that remain to be clarified. The ethanol-induced IK1 changes might contribute to the reported alterations of cardiac electrophysiology related to alcohol consumption. PMID:25179082

Bebarova, M; Matejovic, P; Pasek, M; Simurdova, M; Simurda, J

2014-08-01

 
 
 
 
61

[Vector-echocardiographic correlations in type B right ventricular hypertrophy].  

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The correlation between the right posterior surface of the QRS complex in the horizontal plane and the various parameters characterizing the right ventricle on TM and 2D echocardiography on left parasternal longitudinal sections and subcostal sections was investigated by the Chi-square independence test and Student's t test in 185 cases of heart disease due to various aetiologies. The right posterior surface (Octant III) of the QRS complex in the horizontal plane is independent of the diastolic thickness of the right ventricular posterior wall (RVPW); the diastolic thickness of the right ventricular anterior wall (RVAW); the right ventricular ejection fraction (RVEF); the systolic diameter and diastolic diameter of the right ventricle; the percentage thickening of the RVPW and the RVAW; and, finally, there is no significant relationship between the diastolic thickness of the RVPW and that of the RVAW. Its variance according to the presence or absence and the nature of an associated conduction disorder (RBBB, RIBBB, RBBB + LAHB, LAHB, LBBB, LIBBB or Kent) was not significant for a risk of error of 5% and 1%. The right posterior surface (Octant III) of the QRS complex in the horizontal plane is significantly correlated with the right ventricular mass (RVM), calculated from the diastolic thickness of the right ventricular posterior wall (RVPW): alpha RVDD + 2 RVPW)3. The correlation between these last two quantitative parameters is borderline significant r = 0.11 t = 1.25, 0.20 < alpha < 0.30 according to a linear regression equation: y = 55.15-34.71 x; Po = 549 t = 1.48, increasing from 0 to 0.137 and decreasing beyond 0.137, linearity hypothesis: admissible, p = 0.04. PMID:8763647

Hayat, J C

1996-05-01

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Prevalence and correlates of left ventricular hypertrophy in the African American Study of Kidney Disease Cohort Study.  

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African Americans with hypertensive renal disease represent a high-risk population for cardiovascular events. Although left ventricular hypertrophy is a strong predictor of adverse cardiac outcome, the prevalence and associated factors of left ventricular hypertrophy in this patient population are not well described. The African American Study of Kidney Disease Cohort Study is a prospective, observational study that is an extension of the African American Study of Kidney Disease randomized clinical trial that was conducted from 1994 to 2001 in African Americans with hypertension and mild-to-moderate renal dysfunction. Echocardiograms and 24-hour ambulatory blood pressure monitoring were performed at the baseline visit of the cohort. Of 691 patients enrolled in the cohort study, 599 patients had interpretable baseline echocardiograms and ambulatory blood pressure data. Left ventricular hypertrophy was defined using a cut point for left ventricular mass index >49.2 g/m(2.7) in men and >46.7 m/m(2.7) in women. The majority of patients had left ventricular hypertrophy (66.7% of men and 73.9% of women). In a multiple regression analysis, higher average day and nighttime systolic blood pressure, younger age, and lower predicted glomerular filtration rate were associated with left ventricular hypertrophy, but albuminuria was not. These data demonstrate a striking prevalence of left ventricular hypertrophy in the African American Study of Kidney Disease Cohort and identify potential targets for prevention and therapeutic intervention in this high-risk patient population. PMID:17968003

Peterson, Gail E; de Backer, Tine; Gabriel, Avril; Ilic, Vladimir; Vagaonescu, Tudor; Appel, Lawrence J; Contreras, Gabriel; Kendrick, Cindy; Rostand, Stephen; Phillips, Robert A

2007-12-01

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

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Summary Background Early development of cardiac hypertrophy may be beneficial but sustained hypertrophic activation leads to myocardial dysfunction. Regulation of the repolarizing currents can be modulated by the activation of humoral factors, such as angiotensin II (ANG II) through protein kinases. The aim of this work is to assess the regulation of IK and IK1 by ANG II through the PI3-K pathway in hypertrophied ventricular myocytes. Material/Methods Cardiac eccentric hypertrophy was induced through volume-overload in adult male rats by aorto-caval shunt (3 weeks). After one week half of the rats were given captopril (2 weeks; 0.5 g/l/day) and the other half served as control. The voltage-clamp and western blot techniques were used to measure the delayed outward rectifier potassium current (IK) and the instantaneous inward rectifier potassium current (IK1) and Akt activity, respectively. Results Hypertrophied cardiomyocytes showed reduction in IK and IK1. Treatment with captopril alleviated this difference seen between sham and shunt cardiomyocytes. Acute administration of ANG II (10?6M) to cardiocytes treated with captopril reduced IK and IK1 in shunts, but not in sham. Captopril treatment reversed ANG II effects on IK and IK1 in a PI3-K-independent manner. However in the absence of angiotensin converting enzyme inhibition, ANG II increased both IK and IK1 in a PI3-K-dependent manner in hypertrophied cardiomyocytes. Conclusions Thus, captopril treatment reveals a negative effect of ANG II on IK and IK1, which is PI3-K independent, whereas in the absence of angiotensin converting enzyme inhibition IK and IK1 regulation is dependent upon PI3-K. PMID:21709626

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

2011-01-01

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Comparison of sarcoplasmic reticulum calcium content in atrial and ventricular myocytes of three fish species.  

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Ryanodine (Ry) sensitivity of cardiac contraction differs between teleost species, between atrium and ventricle, and according to the thermal history of the fish. The hypothesis that variability in Ry sensitivity of contraction is due to species-specific, chamber-specific, and temperature-related differences in the sarcoplasmic reticulum (SR) Ca(2+) content, was tested by comparing steady-state (SS) and maximal (Max) Ca(2+) loads of the SR in three teleost fish, rainbow trout (Oncorhynchus mykiss), burbot (Lota lota), and crucian carp (Carassius carassius), which differ in the extent of SR contribution to excitation-contraction coupling. Fish were acclimated at 4 degrees C (cold-acclimation, CA) or 18 degrees C (warm-acclimation, WA), and SR Ca(2+) content was released by a rapid application of 10 mM caffeine to single cardiac myocytes; its amount was determined from the Na(+)-Ca(2+) exchange current at 18 degrees C. SS Ca(2+) load was larger in atrial (304-915 micromol/l) than ventricular (224-540 micromol/l) myocytes in all fish species (P burbot heart, but contrary to the hypothesis, temperature acclimation did not affect SR Ca(2+) content in rainbow trout and crucian carp hearts. Furthermore, there was an inverse relation between SR Ca(2+) content and Ry sensitivity of contraction force: the species with the smallest SR Ca(2+) content (burbot) is most sensitive to Ry. Collectively, these findings show that SR Ca(2+) content of fish cardiac myocytes is several times larger than that in mammalian cardiac SR. PMID:19692664

Haverinen, Jaakko; Vornanen, Matti

2009-10-01

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Mitochondrial ROS production and subsequent ERK phosphorylation are necessary for temperature preconditioning of isolated ventricular myocytes  

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Hypothermia and hypothermic preconditioning are known to be profoundly cardioprotective, but the molecular mechanisms of this protection have not been fully explained. In this study, temperature preconditioning (16?°C) was found to be cardioprotective in isolated adult rat ventricular myocytes, enhancing contractile recovery and preventing calcium dysregulation after oxidative stress. Hypothermic preconditioning preserved mitochondrial function by delaying the pathological opening of the mitochondrial permeability transition pore (mPTP), whereas transient mPTP flickering remained unaltered. For the first time, reactive oxygen species (ROS) from the mitochondria are shown to be released exclusively during the hypothermic episodes of the temperature-preconditioning protocol. Using a mitochondrially targeted ROS biosensor, ROS release was shown during the brief bursts to 16?°C of temperature preconditioning. The ROS scavenger N-(2-mercaptopropionyl) glycine attenuated ROS accumulation during temperature preconditioning, abolishing the protective delay in mPTP opening. Temperature preconditioning induces ROS-dependant phosphorylation of the prosurvival kinase extracellular signal-regulated kinase (ERK)1/2. ERK1/2 activation was shown to be downstream of ROS release, as the presence of a ROS scavenger during temperature preconditioning completely blocked ERK1/2 activation. The cardioprotective effects of temperature preconditioning on mPTP opening were completely lost by inhibiting ERK1/2 activation. Thus, mitochondrial ROS release and ERK1/2 activation are both necessary to signal the cardioprotective effects of temperature preconditioning in cardiac myocytes. PMID:22764104

Bhagatte, Y; Lodwick, D; Storey, N

2012-01-01

66

Excitation-contraction coupling gain in ventricular myocytes: insights from a parsimonious model  

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We present a minimal mathematical model of Ca2+ spark triggering under voltage-clamp conditions in ventricular myocytes. The model predicts changes in excitation–contraction coupling ‘gain’ that result from diverse experimental interventions. We compare model results to several sets of data, and, in so doing, place apparent constraints on physiologically relevant model parameters. Specifically, the analysis suggests that many L-type Ca2+ channel openings can potentially trigger each Ca2+ spark, but the probability that an individual opening will trigger a spark is low. This procedure helps to reconcile contradictory results obtained in recent studies; moreover, this new model should be a useful tool for understanding changes in gain that occur physiologically and in disease. PMID:19153162

Sobie, Eric A; Ramay, Hena R

2009-01-01

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

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

Chiranjivi Potu

2012-02-01

68

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

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Reverse rate dependence is a problematic property of antiarrhythmic drugs that prolong the cardiac action potential (AP). The prolongation caused by reverse rate dependent agents is greater at slow heart rates, resulting in both reduced arrhythmia suppression at fast rates and increased arrhythmia risk at slow rates. The opposite property, forward rate dependence, would theoretically overcome these parallel problems, yet forward rate dependent (FRD) antiarrhythmics remain elusive. Moreover, there is evidence that reverse rate dependence is an intrinsic property of perturbations to the AP. We have addressed the possibility of forward rate dependence by performing a comprehensive analysis of 13 ventricular myocyte models. By simulating populations of myocytes with varying properties and analyzing population results statistically, we simultaneously predicted the rate-dependent effects of changes in multiple model parameters. An average of 40 parameters were tested in each model, and effects on AP duration were assessed at slow (0.2 Hz) and fast (2 Hz) rates. The analysis identified a variety of FRD ionic current perturbations and generated specific predictions regarding their mechanisms. For instance, an increase in L-type calcium current is FRD when this is accompanied by indirect, rate-dependent changes in slow delayed rectifier potassium current. A comparison of predictions across models identified inward rectifier potassium current and the sodium-potassium pump as the two targets most likely to produce FRD AP prolongation. Finally, a statistical analysis of results from the 13 models demonstrated that models displaying minimal rate-dependent changes in AP shape have little capacity for FRD perturbations, whereas models with large shape changes have considerable FRD potential. This can explain differences between species and between ventricular cell types. Overall, this study provides new insights, both specific and general, into the determinants of AP duration rate dependence, and illustrates a strategy for the design of potentially beneficial antiarrhythmic drugs. PMID:24675446

Cummins, Megan A; Dalal, Pavan J; Bugana, Marco; Severi, Stefano; Sobie, Eric A

2014-03-01

69

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

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

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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 blood 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...

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

2000-01-01

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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)

72

Body size adjustments for left ventricular mass by cardiovascular magnetic resonance and their impact on left ventricular hypertrophy classification  

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Methods to index left ventricular (LV) mass, measured by cardiovascular magnetic resonance (CMR), for body size have not been investigated. The purposes of this study were to develop allometric indices for LV mass measured by CMR and compare estimates of the prevalence and predictive value of LV hypertrophy defined by a new allometric height-weight index, LV mass/body surface area (BSA), height indices (a new allometric height index; and previously derived indices from echocardiographic measurements: LV mass/height2, LV mass/height2.7), and non-indexed LV mass. 5,004 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) with CMR measurements of LV mass and no clinical cardiovascular disease at baseline were followed for a median of 4.1 years. The new indices and limits for hypertrophy (95th percentile) were derived from 822 normal-weight, normotensive, non-diabetic MESA participants. 107 events (coronary heart disease or stroke) were observed. The estimated prevalence of hypertrophy at baseline and hazard ratio for event associated with hypertrophy were 8% and 2.4 with the new allometric height-weight index, 11% and 2.2 with LV mass/BSA, 23–24% and 2.0–2.1 with height indices, and 20% and 1.7 with non-indexed LV mass. A statistically significant difference was detected between the hazard ratios based on the new height-weight index and non-indexed LV mass. The prevalence of hypertrophy is higher for indices that do not account for weight. The predictive value of hypertrophy is significantly better with the new allometric height-weight index than with non-indexed LV mass and may be better than indices without weight. PMID:20107905

Kronmal, Richard; Heckbert, Susan R.; Ni, Hanyu; Hundley, W. Gregory; Lima, Joao A.; Bluemke, David A.

2011-01-01

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

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

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

2003-01-01

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

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It has been known for a long time that healthy athletes can develop left ventricular hypertrophy with typical electrocardiographic and echocardiographic findings which lead to the definition of the athlete's heart, as a separate physiological feature. In some cases it is difficult to distinguish between pathological versus physiological myocardial hypertrophy. Diastolic dysfunction is an early sign in the temporal sequence of ischemic events in coronary heart disease. Similar changes occur in other types of heart disease due to arterial hypertension or inflammation processes. Diastolic function is changed even in idiopathic hypertrophic cardiomyopathies. In contrast to these groups of patients, diastolic function remains unchanged or is improved in healthy athletes depending on the type of training (isotonic or isometric exercise). In cases with borderline changes, examinations during physical stress (exercise testing) which provokes an oxygen demand/supply imbalance and consecutively impairs early diastolic filling could clarify if an underlying heart disease is present. Although the physiology of diastolic function is complex, the factors contributing to diastolic disturbances can be differentiated into intrinsic and extrinsic left ventricular (LV) abnormalities. Intrinsic mechanisms include a) impaired LV relaxation, b) increased overall chamber stiffness, c) increased myocardial stiffness and d) increased LV asynchrony. All these factors are part of pathological LV hypertrophy. Factors extrinsic to the LV causing diastolic disorders include a) increased central blood volume, which will increase left ventricular pressure without altering the LV pressure-volume relation, and b) ventricular interaction mediated by pericardial restraint, which may cause a parallel upward shift of the diastolic LV pressure-volume curve. Improved understanding of LV relaxation and filling helps to differentiate pathological and physiological myocardial hypertrophy. Ongoing heart disease of different types can be diagnosed early by stress Doppler echocardiography in relation to other clinical findings and symptoms of the patient. PMID:9119541

Möckel, M; Störk, T

1996-11-01

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Economic benefits of left ventricular hypertrophy regression in patients with arterial hypertension  

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Aim. To evaluate by modelling the economic benefits of left ventricular hypertrophy (LVH) regression in patients with arterial hypertension (HT) due to therapy with fixed combination of valsartan/amlodipine.Material and methods. 20 patients (15 females and 5 males, aged 18 to 70 years) with essential HT accompanied by metabolic syndrome with a history of previous ineffective antihypertensive therapy were included into the study. All patients were treated with fixed combination of amlodipine/v...

Tarlovskaya, E. I.; Maksimchuk, N. S.; Malchicova, S. V.; Avksentieva, M. V.; Sapozhnikova, I. E.; Balandina, Y. A.

2011-01-01

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

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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...

Sm, Ching; Yc, Chia; Wa, Wan Azman

2012-01-01

77

Anti-hypertensive drugs have different effects on ventricular hypertrophy regression  

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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.

Celso Ferreira Filho

2010-01-01

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Anti-hypertensive drugs have different effects on ventricular hypertrophy regression  

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

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.

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Microtubule proliferation in right ventricular myocytes of rats with monocrotaline-induced pulmonary hypertension.  

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Microtubules are components of the cardiac cytoskeleton that can proliferate in response to pressure-overload in animal and human heart failure. We wished to test whether there was a proliferation of the microtubule cytoskeleton in the right ventricle of rats with pulmonary hypertension induced by monocrotaline (MCT) and whether this contributed to contractile dysfunction. Male Wistar rats were injected with 60mg/kg of MCT in saline or an equivalent volume of saline (CON). MCT produced clinical signs of heart failure within 4weeks of injection. Expression of right ventricular mRNA for ?-tubulin was measured by real-time reverse transcription polymerase chain reaction. Free and polymerised fractions of ?-tubulin protein were assessed using Western blot analysis and immunofluorescence microscopy was used to assess tyrosinated and acetylated (stabilized) microtubules. Right ventricular myocyte contraction was measured in response to the microtubule de-polymeriser colchicine (10?mol/l for at least 1h). Compared to CON, in MCT right ventricles there was a small but statistically significant increase in the expression of mRNA for ?-tubulin (P0.05) or affect their response to increased stimulation frequency. Our observations support the hypothesis that microtubule proliferation is a common response to pulmonary hypertension in failing right ventricles but suggest that the effect this has on contraction depends upon the specific experimental or clinical conditions that prevail and the subsequent level of microtubule proliferation. PMID:23261965

Stones, Rachel; Benoist, David; Peckham, Michelle; White, Ed

2013-03-01

80

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

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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 Deviation of the means of heart periods over five-minute intervals (SDANN) were significantly reduced in BHT with LVH but not in BHT without LVH. No significant differences of short-term variability measures were detectable, although a progressive decrease among control subjects and BHT with and without LVH was observed. Diastolic left ventricular compliance evaluated by early to late transmitral flow velocity ratio (E/A ratio) significantly declined from normotensive subjects to BHT with LVH. There was a significant positive correlation between E/A and SDNN and SDANN throughout all studied groups. This indicates that BHT with LVH has a reduced HRV compared to other groups. This impairment is probably related to left ventricular mass and left ventricular filling abnormalities. PMID:11270591

Martini, G; Rabbia, F; Gastaldi, L; Riva, P; Sibona, M P; Morra di Cella, S; Chiandussi, L; Veglio, F

2001-01-01

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

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

Narita, Michihiro; Kurihara, Tadashi [Sumitomo Hospital, Osaka (Japan)

2000-01-01

82

Degradation of [125I]-atrial natriuretic peptide by a soluble metallopeptidase isolated from rat ventricular myocytes  

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Atrial natriuretic peptide is rapidly degraded by a soluble, heat labile peptidase isolated from ventricular myocytes. Degradation of [125I]-ANP is antagonized by unlabelled ANP, bradykinin, glucagon, 1,10-phenanthroline, PCMB, EDTA and the bacterial antibiotic bacitracin, but not by phenylmethylsulphonyl fluoride, aprotinin, phosphoramidon, E-64, amastatin or the ACE inhibitor SQ 20881 and bradykinin potentiator C. In addition neither bovine serum albumin nor caesin afforded any protection against degradation. Peptidase activity was optimal at pH values above 8.5. The peptidase is likely to be of intracellular origin and may contribute to the extensive ANP degradative activity found in various ventricular muscle preparations

83

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

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

84

Vulnerable Myocardial Interstitium in Patients With Isolated Left Ventricular Hypertrophy and Sudden Cardiac Death: A Postmortem Histological Evaluation  

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Background Concentric left ventricular hypertrophy (LVH) is independently associated with increased risk of sudden cardiac death (SCD). Some animal models of LVH display specific alterations of the myocardial interstitium that could increase myocardial vulnerability to ventricular arrhythmias, but these merit evaluation in humans with LVH and SCD. Methods and Results Twelve consecutive patients with isolated LVH and SCD (LVH+SCD) in the absence of hypertrophic cardiomyopathy, coronary disease, or other cardiac structural abnormality were ascertained in the Oregon Sudden Unexpected Death Study. Detailed postmortem comparisons were conducted with 18 controls who had isolated LVH and unnatural deaths (Control Group A) and 6 controls who had structurally normal hearts and unnatural deaths (Control Group B). Postmortem left ventricular myocardial sections were obtained for measurement of collagen volume fraction, characterization of gap junctions, and quantification of collagen subtypes. Heart weight normalized to body weight was higher in LVH+SCD cases (6.9±1.2 g/kg) than in Control Group A (5.3±1.4 g/kg) and Control Group B (4.2±0.3 g/kg); P=0.001. Collagen volume fraction was also higher in LVH+SCD cases (3.1±0.4) than in Control Group A (2.3±0.4) and Control Group B (1.6±0.3); P=0.0002. The relative amount of collagen III was significantly higher in LVH+SCD cases (33.0±4.4%) than in Control Group A (20.9±4.3%) and Control Group B (13.4±3.5%); P=0.0001. There was an overall increase in the number of connexin 43–labeled gap junctions with increasing myocyte size. No subject was found to have high-risk hypertrophic cardiomyopathy mutations. Conclusions In addition to the expected increase in myocardial mass and overall collagen content, SCD with isolated LVH was associated with relative abundance of type III collagen, a novel finding that warrants further mechanistic evaluation. (J Am Heart Assoc. 2012;1:e001511 doi: 10.1161/JAHA.111.001511.) PMID:23130141

Tamarappoo, Balaji K.; John, Benjamin T.; Reinier, Kyndaron; Teodorescu, Carmen; Uy-Evanado, Audrey; Gunson, Karen; Jui, Jonathan; Chugh, Sumeet S.

2012-01-01

85

Evaluation of left ventricular eccentric hypertrophy by /sup 201/Tl-myocardial scintigraphy  

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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.

Yamazaki, Junichi; Kawamura, Yasuaki; Okuzumi, Ichio; Morishita, Takeshi; Koyama, Nobuya; Komatsu, Hisashi; Ohsawa, Hidefumi; Yabe, Yoshimasa

1989-03-01

86

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)

87

Metabolic Gene Remodeling and Mitochondrial Dysfunction in Failing Right Ventricular Hypertrophy due to Pulmonary Arterial Hypertension  

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Background Right ventricular dysfunction (RVD) is the most frequent cause of death in patients with pulmonary arterial hypertension. Whereas abnormal energy substrate utilization has been implicated in the development of chronic left heart failure, data describing such metabolic remodeling in RVD remain incomplete. Thus, we sought to characterize metabolic gene expression changes and mitochondrial dysfunction in functional and dysfunctional RV hypertrophy. Methods and Results Two different rat models of RV hypertrophy were studied. The model of RVD (SU5416/hypoxia) exhibited a significantly decreased gene expression of PPAR-gamma coactivator-1 alpha (PGC-1?), PPAR-? and ERR-?. The expression of multiple PCG-1? target genes required for fatty acid oxidation (FAO) was similarly decreased. Decreased PGC-1? expression was also associated with a net loss of mitochondrial protein and oxidative capacity. Reduced mitochondrial number was associated with a downregulation of TFAM and other genes required for mitochondrial biogenesis. Electron microscopy demonstrated that in RVD tissue, mitochondria had abnormal shape and size. Lastly, respirometric analysis demonstrated that mitochondria isolated from RVD-tissue had a significantly reduced ADP-stimulated (state 3) rate for complex I. Conversely, functional RV hypertrophy in the pulmonary artery banding (PAB) model showed normal expression of PGC-1?, whereas the expression of FAO genes was either preserved or unregulated. Moreover, PAB-RV tissue exhibited preserved TFAM expression and mitochondrial respiration despite elevated RV pressure-overload. Conclusions Right ventricular dysfunction, but not functional RV hypertrophy in rats, demonstrates a gene expression profile compatible with a multilevel impairment of fatty acid metabolism and significant mitochondrial dysfunction, partially independent of chronic pressure-overload. PMID:23152488

Gomez-Arroyo, Jose; Mizuno, Shiro; Szczepanek, Karol; Van Tassell, Benjamin; Natarajan, Ramesh; dos Remedios, Cristobal G.; Drake, Jennifer I.; Farkas, Laszlo; Kraskauskas, Donatas; Wijesinghe, Dayanjan S.; Chalfant, Charles E.; Bigbee, John; Abbate, Antonio; Lesnefsky, Edward J.; Bogaard, Harm J.; Voelkel, Norbert F.

2013-01-01

88

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

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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)

89

Sex differences in SR Ca(2+) release in murine ventricular myocytes are regulated by the cAMP/PKA pathway.  

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Previous studies have shown that ventricular myocytes from female rats have smaller contractions and Ca(2+) transients than males. As cardiac contraction is regulated by the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway, we hypothesized that sex differences in cAMP contribute to differences in Ca(2+) handling. Ca(2+) transients (fura-2) and ionic currents were measured simultaneously (37°C, 2Hz) in ventricular myocytes from adult male and female C57BL/6 mice. Under basal conditions, diastolic Ca(2+), sarcoplasmic reticulum (SR) Ca(2+) stores, and L-type Ca(2+) current did not differ between the sexes. However, female myocytes had smaller Ca(2+) transients (26% smaller), Ca(2+) sparks (6% smaller), and excitation-contraction coupling gain in comparison to males (23% smaller). Interestingly, basal levels of intracellular cAMP were lower in female myocytes (0.7±0.1 vs. 1.7±0.2fmol/?g protein; pforskolin abolished sex differences in cAMP levels, as well as differences in Ca(2+) transients, sparks, and gain. To determine if the breakdown of cAMP differed between the sexes, phosphodiesterase (PDE) mRNA levels were measured. PDE3 expression was similar in males and females, but PDE4B expression was higher in female ventricles. The inhibition of cAMP breakdown by PDE4 (10?M rolipram) abolished differences in Ca(2+) transients and gain. These findings suggest that female myocytes have lower levels of basal cAMP due, in part, to higher expression of PDE4B. Lower cAMP levels in females may attenuate PKA phosphorylation of Ca(2+) handling proteins in females, and may limit positive inotropic responses to stimulation of the cAMP/PKA pathway in female hearts. PMID:25066697

Parks, Randi J; Ray, Gibanananda; Bienvenu, Laura A; Rose, Robert A; Howlett, Susan E

2014-10-01

90

Change in conduction velocity due to fiber curvature in cultured neonatal rat ventricular myocytes.  

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Computer modeling of cardiac propagation suggests that curvature of muscle fibers modulates conduction velocity (CV). The effect could be involved in arrhythmogenesis by altering the dynamics of reentrant wavefronts or by causing propagation block. To verify the existence of this effect experimentally, we measured CV in anisotropic neonatal rat ventricular myocyte monolayers. The orientation of the cells was directed by scratches machined into plastic coverslips. Each substrate contained a region in which scratch radius of curvature varied from 0.25 to 1.0 cm. The CV anisotropy ratio (longitudinal CV/transverse CV in straight fiber regions) was 2.3 +/- 0.3 (n = 38). We initiated wavefronts transverse to fibers with the fibers either curving toward or away from the wavefronts. Action potentials were recorded using a potentiometric dye and a video camera. Propagation was faster (p = 0.0003) when fibers curved toward wavefronts than when fibers curved in the opposite direction. The mean CV difference was 0.38 +/- 0.44 cm/s (n = 24), which is 3.5% of nominal straight fiber transverse CV (11.0 +/- 3.2 cm/s). The effect was also present (p = 0.07) when pacing was slowed from 350 to 500 ms (n = 6). In a control group (n = 8) with uncurved fibers, CV was the same in both directions (p = NS). We conclude that fiber curvature is a factor in modulating cardiac propagation. PMID:19272891

Bourgeois, Elliot B; Fast, Vladimir G; Collins, Rueben L; Gladden, James D; Rogers, Jack M

2009-03-01

91

Frataxin deficiency in neonatal rat ventricular myocytes targets mitochondria and lipid metabolism.  

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Friedreich ataxia (FRDA) is a hereditary disease caused by deficient frataxin expression. This mitochondrial protein has been related to iron homeostasis, energy metabolism, and oxidative stress. Patients with FRDA experience neurologic alterations and cardiomyopathy, which is the leading cause of death. The specific effects of frataxin depletion on cardiomyocytes are poorly understood because no appropriate cardiac cellular model is available to researchers. To address this research need, we present a model based on primary cultures of neonatal rat ventricular myocytes (NRVMs) and short-hairpin RNA interference. Using this approach, frataxin was reduced down to 5 to 30% of control protein levels after 7 days of transduction. At this stage the activity and amount of the iron-sulfur protein aconitase, in vitro activities of several OXPHOS components, levels of iron-regulated mRNAs, and the ATP/ADP ratio were comparable to controls. However, NRVMs exhibited markers of oxidative stress and a disorganized mitochondrial network with enlarged mitochondria. Lipids, the main energy source of heart cells, also underwent a clear metabolic change, indicated by the increased presence of lipid droplets and induction of medium-chain acyl-CoA dehydrogenase. These results indicate that mitochondria and lipid metabolism are primary targets of frataxin deficiency in NRVMs. Therefore, they contribute to the understanding of cardiac-specific mechanisms occurring in FRDA and give clues for the design of cardiac-specific treatment strategies for FRDA. PMID:24751525

Obis, Èlia; Irazusta, Verónica; Sanchís, Daniel; Ros, Joaquim; Tamarit, Jordi

2014-08-01

92

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  

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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.

Juan René Llapur Milián

2009-06-01

93

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

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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.

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

1998-01-01

94

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)

95

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

DEFF Research Database (Denmark)

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.

Ravn, Nathja; Zois, Nora Elisabeth

2014-01-01

96

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

DEFF Research Database (Denmark)

The objective of this study was to analyze the long-term hemodynamic effects of the calcium antagonist isradipine in mild hypertension compared with those of the beta 1-selective adrenoceptor antagonist atenolol, focusing in particular on the development of cardiac hypertrophy. Ten male patients with mild essential hypertension were entered into a double-blind crossover study. Examinations were carried out after 2 weeks of placebo run-in, and after 6 and 12 months of active treatment. Mean resting blood pressure was reduced from 115 +/- 12 mm Hg to 106 +/- 12 mm Hg with atenolol, and to 107 +/- 8 mm Hg with isradipine. The increase in the product of heart rate times blood pressure was significantly greater during isradipine treatment, as was the maximum exercise capacity. Left ventricular mass was increased from 228 +/- 36 g to 305 +/- 68 g with atenolol whereas it remained unchanged with isradipine (254 +/- 55 g). The results indicate that antihypertensive treatment with isradipine as monotherapy may preventthe development of left ventricular hypertrophy whereas treatment with atenolol as monotherapy does not appear to offer this possibility.

Mehlsen, J; Fornitz, Gitte Gleerup

1993-01-01

97

Carotid intima-media thickness and left ventricular hypertrophy in hemodialysis patients  

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Full Text Available Introduction: Two principal findings of cardiovascular disease in end-stage renal disease patients undergoing regular hemodialysis are left ventricular hypertrophy (LVH and arterial disease due to rapidly progressive atherosclerotic vascular disease that can be characterized by an enlargement and hypertrophy of arteries (intima-media complex thickening; IMT.Objectives: In this study, we sought to evaluate the relationship between left ventricular hypertrophy with intima-media complex thickening in end-stage renal disease patients undergoing regular hemodialysis.Patients and Methods: Sixty-one patients with end-stage renal disease (ESRD who were undergoing regular and maintenance hemodialysis treatment (F=23, M=38 were studied. The subjects consisted of 50 non-diabetic hemodialysis patients (F=20, M=30 and 11 diabetic hemodialysis patients (F=3, M=8. For all the subjects, echocardiography and carotid intima-media thickness measuring by B-mode ultrasonography were performed.Results: In this study, there was a positive correlation between stages of LVH with duration of hemodialysis treatment, stages of hypertension (HTN, and with carotid-IMT. A positive correlation was also seen between stages of LVH and presence of chest pain, and more thickening of the intima-media complex was seen in the diabetic group. Diabetes mellitus was associated with the presence of chest pain, as was positive correlation between stages of HTN with IMT, and a reverse correlation was observed between IMT with the percent of cardiac ejection fraction.Conclusion: Prevalence of thickening in intima-media complex is more evident in hemodialysis subjects with LVH. When there is LVH, IMT is similar in severity to the LVH.

Rafieian-Kopaei Mahmoud

2013-10-01

98

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

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Patients with hypertension and left ventricular (LV) hypertrophy commonly have impaired diastolic filling. However, it remains unknown whether changes in LV diastolic filling variables are associated with cardiovascular morbidity and mortality. In this study, 778 patients with hypertension with electrocardiographic LV hypertrophy who underwent echocardiography at baseline and annually thereafter during randomized losartan- or atenolol-based antihypertensive treatment were followed for a mean of 4.6 years. The composite cardiovascular end point was the first occurrence of fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, and cardiovascular mortality. Antihypertensive therapy resulted in an increase in the prevalence of normal transmitral flow pattern from 28% to 46% of patients. Although antihypertensive treatment often resulted in a marked increase in the prevalence of normal mitral valve flow pattern, this was not associated with reduced cardiovascular morbidity and mortality when adjusting for blood pressure, left atrial diameter, LV mass index, and treatment in time-varying Cox analyses. In contrast, lower in-treatment E/A ratios and shorter mitral valve deceleration times were associated with less risk for heart failure. Similarly, normal in-treatment transmitral flow pattern was strongly associated with less risk for heart failure (hazard ratio 0.22, 95% confidence interval 0.05 to 0.98, p = 0.048), even when taking in-treatment left atrial diameter and blood pressure into account. In conclusion, antihypertensive treatment in patients with hypertension with electrocardiographic LV hypertrophy resulted in significant improvement in transmitral flow patterns; this was not associated with reduced cardiovascular morbidity and mortality. However, normal in-treatment LV filling was strongly associated with a reduced risk for hospitalization for heart failure.

Wachtell, Kristian; Palmieri, Vittorio

2010-01-01

99

Effect of partial blockade of the Na(+)/Ca(2+)-exchanger on Ca(2+) handling in isolated rat ventricular myocytes.  

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SEA0400 is a selective inhibitor of the Na(+)/Ca(2+) exchanger having equal potencies to suppress both the forward and reverse mode operation of the Na(+)/Ca(2+) exchanger. Present experiments were designed to study the effect of partial blockade of Na(+)/Ca(2+) exchanger on Ca(2+) handling in isolated rat ventricular myocytes. Intracellular Ca(2+) transient and cell shortening were measured in ventricular myocytes loaded with Fura-2-AM fluorescent dye. Partial blockade of Na(+)/Ca(2+) exchanger was induced by superfusion of the cells with SEA0400 at a concentration of 0.3 microM. Amplitude of the intracellular Ca(2+) transient and cell shortening was significantly increased by SEA0400 in both field stimulated and voltage clamped myocytes, without significant elevation of diastolic Ca(2+) level and the decay time constant of the Ca(2+) transient. In patch clamped myocytes the SEA0400 induced increase in the Ca(2+) transient and cell shortening was accompanied by significant reduction of peak L-type Ca(2+) current. These effects can be explained by the autoregulative nature of cardiac Ca(2+) handling, as the reduced Ca(2+) efflux from the cell results in an increased Ca(2+) load to the sarcoplasmic reticulum leading to increased Ca(2+) release, which in turn may decrease the L-type Ca(2+) current by accelaration of Ca(2+) dependent inactivation of L-type Ca(2+) current. Our results suggest that complex changes in the Ca(2+) cycling can occur after selective pharmacological inhibition of the Na(+)/Ca(2+) exchanger. PMID:17727839

Acsai, Károly; Kun, Attila; Farkas, Attila S; Fülöp, Ferenc; Nagy, Norbert; Balázs, Marianna; Szentandrássy, Norbert; Nánási, Péter P; Papp, Julius Gy; Varró, András; Tóth, András

2007-12-01

100

Quantitative comparison of cardiac ventricular myocyte electrophysiology and response to drugs in human and nonhuman species.  

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Explanations for arrhythmia mechanisms at the cellular level are usually based on experiments in nonhuman myocytes. However, subtle electrophysiological differences between species may lead to different rhythmic or arrhythmic cellular behaviors and drug response given the nonlinear and highly interactive cellular system. Using detailed and quantitatively accurate mathematical models for human, dog, and guinea pig ventricular action potentials (APs), we simulated and compared cell electrophysiology mechanisms and response to drugs. Under basal conditions (absence of ?-adrenergic stimulation), Na(+)/K(+)-ATPase changes secondary to Na(+) accumulation determined AP rate dependence for human and dog but not for guinea pig where slow delayed rectifier current (I(Ks)) was the major rate-dependent current. AP prolongation with reduction of rapid delayed rectifier current (I(Kr)) and I(Ks) (due to mutations or drugs) showed strong species dependence in simulations, as in experiments. For humans, AP prolongation was 80% following I(Kr) block. It was 30% for dog and 20% for guinea pig. Under basal conditions, I(Ks) block was of no consequence for human and dog, but for guinea pig, AP prolongation after I(Ks) block was severe. However, with ?-adrenergic stimulation, I(Ks) played an important role in all species, particularly in AP shortening at fast rate. Quantitative comparison of AP repolarization, rate-dependence mechanisms, and drug response in human, dog, and guinea pig revealed major species differences (e.g., susceptibility to arrhythmogenic early afterdepolarizations). Extrapolation from animal to human electrophysiology and drug response requires great caution. PMID:22159993

O'Hara, Thomas; Rudy, Yoram

2012-03-01

 
 
 
 
101

Calcium homeostasis in rabbit ventricular myocytes. Disruption by hypochlorous acid and restoration by dithiothreitol.  

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Hypochlorous acid (HOCl) is a toxic oxidant produced by neutrophils at sites of cardiac inflammation. To examine the effect of this oxidant on Ca2+ homeostasis in the heart, isolated rabbit ventricular myocytes were iontophoretically loaded with the Ca2+ indicator fura 2 and superfused with 100 microM HOCl under voltage-clamp conditions. Ca2+ transients and the corresponding Ca2+ currents were elicited by 300-msec depolarizing pulses from -40 to 0 mV. Within 200 seconds after HOCl addition, the amplitude of the Ca2+ transients was reduced from 402 +/- 89 to 82 +/- 29 nM (p less than 0.01) while intracellular free ([Ca2+]i increased from 78 +/- 16 to 265 +/- 48 nM (p less than 0.01). During this time, the amplitude of the slow inward currents increased by 10%, while steady-state holding current remained stable. This sustained steady-state rise in [Ca2+]i occurred even in the absence of extracellular Ca2+ but was virtually abolished by a 20-second preexposure to 10 mM caffeine, suggesting that the major source of this Ca2+ was the sarcoplasmic reticulum. Although washout of HOCl failed to induce recovery, subsequent exposure to the dithiol reducing agent dithiothreitol caused a rapid restoration of both the steady-state [Ca2+]i and Ca2+ transient amplitude. We conclude that 1) HOCl caused a rise of [Ca2+]i by inducing the release of Ca2+ from internal stores and impairing cellular extrusion mechanisms and 2) these effects occur through alteration of protein thiol redox status. PMID:1657437

Eley, D W; Korecky, B; Fliss, H; Désilets, M

1991-10-01

102

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

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

Hikmet Selçuk Gedik

2012-02-01

103

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

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

Xin Li

2013-06-01

104

Developmental analysis reveals mismatches in the expression of K+ channel alpha subunits and voltage-gated K+ channel currents in rat ventricular myocytes  

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In the experiments here, the developmental expression of the functional Ca(2+)-independent, depolarization-activated K+ channel currents, Ito and IK, and of the voltage-gated K+ channel (Kv) alpha subunits, Kv1.2, Kv1.4, Kv1.5, Kv2.1, and Kv4.2 in rat ventricular myocytes were examined quantitatively. Using the whole-cell patch clamp recording method, the properties and the densities of Ito and IK in ventricular myocytes isolated from postnatal day 5 (P5), 10 (P10), 15 (P15), 20 (P20), 25 (P2...

1996-01-01

105

Acceleration of the wavefront of myocardial necrosis by chronic hypertension and left ventricular hypertrophy in dogs.  

Science.gov (United States)

Previous studies have shown that hypertension and left ventricular hypertrophy (HT-LVH) increase completed infarct size. Myocardial infarction progresses in a wavefront of myocardial necrosis from the subendocardium to the subepicardium. We tested two hypotheses: First, HT-LVH accelerates the wavefront of myocardial necrosis when compared with normotensive animals; and second, lowering of arterial pressure by infusing nitroprusside 1 hour after coronary artery occlusion exerts a salutary effect on infarct size. To test these hypotheses, systemic hypertension (mean aortic pressure = 141 +/- 3 mm Hg) and left ventricular hypertrophy (18% increase in left ventricular mass) were induced in dogs using a single-kidney, single-clip model. Seventeen adult mongrel dogs were used as controls. We measured mean aortic pressure, heart rate, left atrial pressure, and myocardial perfusion (microspheres) in several groups of normal and HT-LVH awake dogs. In two groups (normal and HT-LVH), 1 hour of circumflex coronary artery occlusion was followed by 4 hours of reperfusion. In two additional groups (normal and HT-LVH), 3 hours of circumflex coronary artery occlusion was followed by 90 minutes of reperfusion. In another group with HT-LVH, nitroprusside was infused to reduce mean arterial pressure to 100 mm Hg beginning 1 hour after occlusion and was continued for the duration of reperfusion period (HT-LVH + N). Infarct size was assessed using triphenyltetrazolium chloride stain and risk area was determined using postmortem barium angiography. Fifteen of 17 (88%) control animals survived coronary artery occlusion, whereas only 17 of 42 (40%) dogs with HT-LVH survived coronary occlusion (p less than 0.05). Infarct-to-risk ratios in the various layers of the left ventricular wall were determined for survivors in all groups. After 1 hour of coronary occlusion more than twice as much mid-wall and epicardium was infarcted in the HT-LVH group compared with the control group. After 3 hours of coronary occlusion significantly more endocardium, mid-wall, and epicardium was infarcted in the dogs with HT-LVH. In the nitroprusside-treated HT-LVH dogs, the infarct sizes were similar to control animals. From these data we conclude: 1) the rate of infarction is accelerated in animals with HT-LVH; 2) nitroprusside infused 1 hour after coronary artery occlusion and continued throughout the reperfusion period exerts beneficial effect on infarct size when compared with control animals; and 3) acute coronary artery occlusion in animals with HT-LVH is associated with significantly greater mortality when compared with control animals. PMID:2968195

Dellsperger, K C; Clothier, J L; Hartnett, J A; Haun, L M; Marcus, M L

1988-07-01

106

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

Scientific Electronic Library Online (English)

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

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

2000-02-01

107

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

Scientific Electronic Library Online (English)

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

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

108

The cytosolic calcium transient modulates the action potential of rat ventricular myocytes.  

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1. The modulation of the action potential by the cytosolic Ca2+ (Cai2+) transient was studied in single isolated rat ventricular myocytes loaded with the acetoxymethyl ester form of the Ca(2+)-sensitive fluorescent dye Indo-1. Stimulation following rest and exposure to ryanodine were used to change the amount of Ca2+ released from the sarcoplasmic reticulum and thus the size of the Cai2+ transient. The Cai2+ transient was measured as the change, upon stimulation, in the ratio of Indo-1 fluorescence at 410 nm to that at 490 nm (410/490) and action potentials or membrane currents were recorded using patch-type microelectrodes. 2. When stimulation was initiated following rest, the magnitude of the Cai2+ transient decreased in a beat-dependent manner until a steady state was reached. The negative staircase in the Cai2+ transient was accompanied by a similar beat-dependent decrease in the duration of the action potential, manifested primarily as a gradual loss of the action potential plateau (approximately -45 mV). A slow terminal phase of repolarization of a few millivolts in amplitude was found to parallel the terminal decay of the Cai2+ transient. 3. The terminal portion of phase-plane loops of membrane potential (Vm) vs. Indo-1 ratio from all of the beats of a stimulus train followed a common linear trajectory even though the individual beats differed markedly in the duration and amplitude of the action potential and Cai2+ transient. 4. When the stimulation dependence of the Cai2+ transient was titrated away with submaximal exposure to ryanodine, the stimulation-dependent changes in the action potential plateau and terminal phase of repolarization were also eliminated. The same effect was noted in cells which, fortuitously, did not show a staircase in the Cai2+ transient following a period of rest. 5. When action potentials were triggered immediately following spontaneous release of Ca2+ from the sarcoplasmic reticulum, which results in a small depolarization at the resting potential, phase-plane loops (Vm vs. Indo-1 ratio) of the spontaneous events followed the same linear trajectory as the terminal phase of repolarization in the loops of the stimulated beats. 6. Following repolarization from brief voltage clamp pulses (to minimize time and voltage-dependent currents associated with depolarization), an inward current was observed that rose and fell in phase with the Cai2+ transient. This current was present at -70 mV, near the resting potential, and at -40 mV, a potential relevant to the plateau of the action potential.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:2061836

duBell, W H; Boyett, M R; Spurgeon, H A; Talo, A; Stern, M D; Lakatta, E G

1991-05-01

109

Determinants of beat-to-beat variability of repolarization duration in the canine ventricular myocyte: a computational analysis.  

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Beat-to-beat variability of repolarization duration (BVR) is an intrinsic characteristic of cardiac function and a better marker of proarrhythmia than repolarization prolongation alone. The ionic mechanisms underlying baseline BVR in physiological conditions, its rate dependence, and the factors contributing to increased BVR in pathologies remain incompletely understood. Here, we employed computer modeling to provide novel insights into the subcellular mechanisms of BVR under physiological conditions and during simulated drug-induced repolarization prolongation, mimicking long-QT syndromes type 1, 2, and 3. We developed stochastic implementations of 13 major ionic currents and fluxes in a model of canine ventricular-myocyte electrophysiology. Combined stochastic gating of these components resulted in short- and long-term variability, consistent with experimental data from isolated canine ventricular myocytes. The model indicated that the magnitude of stochastic fluctuations is rate dependent due to the rate dependence of action-potential (AP) duration (APD). This process (the "active" component) and the intrinsic nonlinear relationship between membrane current and APD ("intrinsic component") contribute to the rate dependence of BVR. We identified a major role in physiological BVR for stochastic gating of the persistent Na(+) current (INa) and rapidly activating delayed-rectifier K(+) current (IKr). Inhibition of IKr or augmentation of INa significantly increased BVR, whereas subsequent ?-adrenergic receptor stimulation reduced it, similar to experimental findings in isolated myocytes. In contrast, ?-adrenergic stimulation increased BVR in simulated long-QT syndrome type 1. In addition to stochastic channel gating, AP morphology, APD, and beat-to-beat variations in Ca(2+) were found to modulate single-cell BVR. Cell-to-cell coupling decreased BVR and this was more pronounced when a model cell with increased BVR was coupled to a model cell with normal BVR. In conclusion, our results provide new insights into the ionic mechanisms underlying BVR and suggest that BVR reflects multiple potentially proarrhythmic parameters, including increased ion-channel stochasticity, prolonged APD, and abnormal Ca(2+) handling. PMID:23990775

Heijman, Jordi; Zaza, Antonio; Johnson, Daniel M; Rudy, Yoram; Peeters, Ralf L M; Volders, Paul G A; Westra, Ronald L

2013-01-01

110

Clustering of protein kinase A-dependent CFTR chloride channels in the sarcolemma of guinea-pig ventricular myocytes.  

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Cardiac myocytes express protein kinase A-dependent Cl(-) (Cl(PKA)) channels that are thought to represent cardiac expression of CFTR. In the present study, the 'Smart' patch clamp technique was used to investigate the distribution of Cl(PKA) channels at the cell surface of isolated guinea-pig ventricular myocytes. Imaging the cell surface using scanning ion conductance microscopy allowed the identification of the mouths to t-tubules and lateral z-grooves with a spacing of 1.86 microm. Cell-attached patch clamp recordings were made from specified locations within the imaged area. Perfusion of the cells with an activating cocktail of isoprenaline (5 microM), forskolin (10 microM) and isobutylmethylxanthine (50 microM) activated large, noisy anion-selective currents in which unitary channel currents could not be identified. Currents were recorded both from within z-grooves and in the inter-groove region but not at the mouths of t-tubules. Power spectral and noise analyses indicated the involvement of 13.5pS channels occurring in clusters of >50 channels. Channel activity was lost on excision of the patch from the cell but could be recovered in inside-out excised patches by application of the catalytic subunit of PKA. These results suggest that CFTR Cl(PKA) channels occur in clusters in the sarcolemma of guinea-pig ventricular myocytes; there was no evidence of a heterogeneous distribution of clusters between the z-grooves and the inter-groove region. PMID:19945434

James, Andrew F; Sabirov, Razshan Z; Okada, Yasunobu

2010-01-01

111

Cerium oxide nanoparticles attenuate monocrotaline induced right ventricular hypertrophy following pulmonary arterial hypertension.  

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Cerium oxide (CeO2) nanoparticles have been posited to exhibit potent anti-oxidant activity which may allow for the use of these materials in biomedical applications. Herein, we investigate whether CeO2 nanoparticle administration can diminish right ventricular (RV) hypertrophy following four weeks of monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH). Male Sprague Dawley rats were randomly divided into three groups: control, MCT only (60 mg/kg), or MCT + CeO2 nanoparticle treatment (60 mg/kg; 0.1 mg/kg). Compared to the control group, the RV weight to body weight ratio was 45% and 22% higher in the MCT and MCT + CeO2 groups, respectively (p < 0.05). Doppler echocardiography demonstrated that CeO2 nanoparticle treatment attenuated monocrotaline-induced changes in pulmonary flow and RV wall thickness. Paralleling these changes in cardiac function, CeO2 nanoparticle treatment also diminished MCT-induced increases in right ventricular (RV) cardiomyocyte cross sectional area, ?-myosin heavy chain, fibronectin expression, protein nitrosylation, protein carbonylation and cardiac superoxide levels. These changes with treatment were accompanied by a decrease in the ratio of Bax/Bcl2, diminished caspase-3 activation and reduction in serum inflammatory markers. Taken together, these data suggest that CeO2 nanoparticle administration may attenuate the hypertrophic response of the heart following PAH. PMID:25224369

Kolli, Madhukar B; Manne, Nandini D P K; Para, Radhakrishna; Nalabotu, Siva K; Nandyala, Geeta; Shokuhfar, Tolou; He, Kun; Hamlekhan, Azhang; Ma, Jane Y; Wehner, Paulette S; Dornon, Lucy; Arvapalli, Ravikumar; Rice, Kevin M; Blough, Eric R

2014-12-01

112

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

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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.

Han Li

2013-01-01

113

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)

114

Cardiac myocyte nuclear size and ploidy status decrease after mechanical support.  

Science.gov (United States)

Two patients with end-stage dilated cardiomyopathy of ischemic and idiopathic origin were treated with a left ventricular assist device (LVAD) as a bridge for heart transplantation. Myocardial tissue was collected during LVAD insertion and from the left ventricular apex of the explanted hearts. The myocyte diameter, nuclear area and DNA content of myocyte nuclei were measured by static cytomorphometry in tissue sections and in isolated myocytes with a digital analysis system. The presence of apoptotic nuclei was investigated by the TdT mediated X-dUTP nick end labeling technique (TUNEL). The prolonged use of a LVAD was associated with a reduction in myocyte diameter, indicating that the LVAD may induce a reversion of myocyte hypertrophy, a process described as "reverse remodeling." In addition, unloading of the heart induced a reduction in the size and DNA content of myocyte nuclei. These results suggest that the cardiomyocyte nuclei are in a dynamic state and, as it occurs with cell hypertrophy, nuclear hypertrophy and polyploidization may be a reversible phenomenon. PMID:11425598

Rivello, H G; Meckert, P C; Vigliano, C; Favaloro, R; Laguens, R P

2001-01-01

115

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

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

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

2011-02-15

116

Actions of cADP-ribose and its antagonists on contraction in guinea pig isolated ventricular myocytes. Influence of temperature.  

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Although it is becoming widely accepted that cADP-ribose (cADPR) can regulate calcium release from the endoplasmic reticulum in sea urchin eggs and in a variety of mammalian cell types, it remains controversial whether this substance might influence calcium release during excitation-contraction coupling in cardiac muscle. We have investigated possible actions of cADPR in intact cells isolated from guinea pig ventricle, paying particular attention to the possible influence of temperature. At 36 degrees C, myocyte contraction was influenced by cytosolic application of cADPR in a concentration-dependent manner (showing an approximately 30% increase in contraction with 5 mumol/L cADPR applied via a patch pipette in myocytes stimulated to fire action potentials at 1 Hz). Calcium transients measured with fura 2 were also increased by 5 mumol/L cADPR. Antagonists of cADPR reduced contraction at 36 degrees C (by approximately 35% with either 50 mumol/L 8-Br-cADPR or 5 mumol/L 8-amino-cADPR applied via the patch pipette). At room temperature (approximately 20 degrees C to 24 degrees C), no significant effects on contraction were detected with either cADPR or its antagonists. At 36 degrees C, treatment of the cells with a mixture of 2 mumol/L ryanodine and 1 mumol/L thapsigargin to suppress function of the sarcoplasmic reticulum stores of calcium prevented the action of 5 mumol/L cADPR applied via a patch pipette. These observations are consistent with an action of cytosolic cADPR to enhance calcium-induced calcium release from the sarcoplasmic reticulum in guinea pig ventricular myocytes at 36 degrees C. The observed influence of temperature under the conditions of our experiments is one factor that might help to account for failure to detect actions of cADPR and its analogues in some previous studies. PMID:9351463

Iino, S; Cui, Y; Galione, A; Terrar, D A

1997-11-01

117

Economic benefits of left ventricular hypertrophy regression in patients with arterial hypertension  

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

E.I. Tarlovskaya

2011-01-01

118

Effects of coronary artery occlusion in animals with hypertension and left ventricular hypertrophy.  

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Chronic arterial hypertension (HT) and left ventricular hypertrophy (LVH) increase the morbidity and mortality of acute myocardial infarction in patients. In this article, we discuss earlier studies from Koyanagi et al. in our laboratory that showed that when animals with chronic HT and LVH (HT-LVH) were subjected to acute coronary artery occlusion (CAO), there was a 3.5-fold increase in mortality and a 35% increase in infarct size expressed as a percent of the area at risk. We subsequently determined the effect of HT-LVH on the wavefront of myocardial infarction. Dogs were made hypertensive using a single-kidney, single-clip model of renovascular hypertension that produced mean arterial blood pressure (BP) = 141 +/- 3 mm Hg and left ventricular:body weight = 5.8 +/- 0.1 g/kg (p less than 0.05 vs. control animals). Conscious animals with HT-LVH and control animals were subjected to 1 or 3 h of CAO. Infarct and risk areas were measured using triphenyltetrazolium chloride (TTC) stain and barium angiography, respectively. The results suggested that the wavefront of infarction was accelerated in animals with HT-LVH. Further studies suggested that the wavefront of myocardial infarction could be markedly retarded by normalizing blood pressure (nitroprusside) 1 h following CAO. Recent studies in an animal model of HT-LVH suggested that electrophysiological abnormalities occur when these animals were subjected to CAO. Sixty-five percent of animals with HT-LVH had sudden death during CAO compared to 27% of the control group. We studied whether chronic beta-adrenergic blockade would reduce mortality associated with CAO in animals with HT-LVH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1715484

Dellsperger, K C; Clothier, J L; Koyanagi, S; Inou, T; Marcus, M L

1991-01-01

119

Electrocardiographic left ventricular hypertrophy and the risk of adverse cardiovascular events: a critical appraisal.  

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This review covers selected electrocardiographic left ventricular hypertrophy (ECG-LVH) studies which have evaluated their prognostic value for adverse cardiovascular (CVD) events. Most ECG-LVH studies have used echocardiographic left ventricular mass (Echo-LVM) as the gold standard for evaluating ECG-LVH criteria. More recently, LVM from magnetic resonance imaging (MRI-LVM) has evolved as the new gold standard. The reported risk of adverse CVD events is generally highest for ECG-LVH criteria which combine high amplitude QRS criteria with repolarization abnormalities such as in LV strain pattern. Evolving coronary heart disease (CHD) may account in part for the increased risk for ECG-LVH. However, one large coronary arteriography study found that 5-year survival was significantly lower in coronary artery disease (CAD) patients with ECG-LVH than without LVH regardless of CAD status. The utility of Echo-LVH as a standard is limited by the large intra- and inter-reader variability and the lack of standardization of allometric formulations for adjustment of LVM to body size. Newer evaluation data with MRI-LVM as the standard show that for most ECG criteria CVD event rates are significantly higher for study subgroups with ECG-LVH than those without ECG-LVH. However, the performance results differ when comparing the risk for CVD events from those for the overall LVH classification accuracy according to sensitivity and specificity. Large short-term variability of ECG amplitudes due to electrode placement variability is a common limiting factor for ECG-LVH criteria performance regardless of the gold standard. Clinical trials for hypertension control rely largely on monitoring Echo-LVH rather than ECG-LVH. PMID:25012077

Rautaharju, Pentti M; Soliman, Elsayed Z

2014-01-01

120

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

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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.

Lu, Luyao; Xia, Ling; Ye, Xuesong; Cheng, Heping

2010-06-01

 
 
 
 
121

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

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Cardiac ion channels are membrane-spanning proteins that allow the passive movement of ions across the cell membrane along its electrochemical gradient, which regulates the resting membrane potential as well as the shape and duration of the cardiac action potential. Additionally, they have been recognized as potential targets for the actions of neurotransmitters, hormones and drugs of cardiac diseases. Spider venoms contain high abundant of toxins that target diverse ion channels and have been considered as a potential resource of new constituents with speci?c pharmacological properties. However, few peptides from spider venoms were detected as cardiac channel antagonists. In order to explore the effects of the venom of Ornithoctonus hainana on the action potential and ionic currents of neonatal rat ventricular myocytes (NRVMs), whole cell patch clamp technique was used to record action potential duration (APD), sodium current (INa), L calcium current (ICaL), rapidly activating and inactivating transient outward currents (Ito1), rapid (IKr) and slow (IKs) components of the delayed rectifier currents and the inward rectifier currents (IK1). Our results showed that 100 ?g/mL venom obviously prolonged APDs. Signi?cantly, the venom could inhibit INa and ICaL effectively, while no evident inhibitory effects on cardiac K(+) channels (Ito1, Iks, Ikr and Ik1) were observed, suggesting that the venom represented a multifaceted pharmacological profile. The effect of venom on Na(+) and Ca(2+) currents of ventricular myocytes revealed that the hainan venom as a rich resource of cardiac channel antagonists might be valuable tools for the investigation of both channels and drug development. PMID:24930961

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

2014-09-01

122

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

123

Triggering the succinate receptor GPR91 enhances pressure overload-induced right ventricular hypertrophy  

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Background: Pulmonary arterial hypertension (PAH) leads to pressure overload in the right ventricle (RV) and induces right ventricular hypertrophy (RVH). GPR91 is an orphan G-protein-coupled receptor (GPCR) that has been characterized as a receptor for succinate, which increases in RVH; however, its role remains unknown. Methods and results: We studied succinate-GPR91 signaling in a pulmonary arterial banding (PAB) model of RVH in the SD rats due to pressure overload. We report that GPR91 was located in cardiomyocytes. We found that the expressions of GPR91 and p-Akt in the RV significantly increased in the PAB model compared with the sham. In the PAB rats, the treatment of succinate further increased the p-Akt levels and aggravated RVH in vivo. In in vitro studies, succinate stimulated the up-regulation of the hypertrophic gene marker anp. All these effects were inhibited by the antagonist of PI3K, wortmannin, both in vivo and in vitro. Finally, we found that the GPR91-PI3K/Akt axis was also up-regulated compared with the sham in human RVH. Conclusions: Our results suggest that succinate-GPR91 is involved in RVH via PI3K/Akt signaling in vivo and in vitro. GPR91 may be a novel therapeutic target for RVH induced by pressure overload.

Yang, Lei; Yu, Di; Fan, Huan-Huan; Feng, Yu; Hu, Liang; Zhang, Wei-Yan; Zhou, Kai; Mo, Xu-Ming

2014-01-01

124

Differentiating left ventricular hypertrophy in athletes from that in patients with hypertrophic cardiomyopathy.  

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Identification of hypertrophic cardiomyopathy (HC) in young athletes is challenging when left ventricular (LV) wall thickness is between 13 and 15 mm. The aim of this study was to revise the ability of simple echocardiographic and clinical variables for the differential diagnosis of HC versus athlete's heart. Twenty-eight athletes free of cardiovascular disease were compared with 25 untrained patients with HC, matched for LV wall thickness (13 to 15 mm), age, and gender. Clinical, electrocardiographic, and echocardiographic variables were compared. Athletes had larger LV cavities (60 ± 3 vs 45 ± 5 mm, p athlete's heart with the highest sensitivity and specificity (both 100%, p 40 mm excluded HC with sensitivity of 92% and specificity of 71% (p Athletes showed higher e' velocity by tissue Doppler imaging than patients with HC (12.5 ± 1.9 vs 9.3 ± 2.3 cm/second, p athletes with LV hypertrophy in the "gray zone" with HC, LV cavity size appears the most reliable criterion to help in diagnosis, with a cut-off value of athlete's heart. Other criteria, including LV diastolic dysfunction, absence of T-wave inversion on electrocardiography, and negative family history, further aid in the differential diagnosis. PMID:25217454

Caselli, Stefano; Maron, Martin S; Urbano-Moral, Josè A; Pandian, Natesa G; Maron, Barry J; Pelliccia, Antonio

2014-11-01

125

Effects of calcium on mitochondrial NAD(P)H in paced rat ventricular myocytes.  

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The response of the steady-state level of mitochondrial NAD(P)H of individual cardiac myocytes to substrate and to pharmacological alteration of intracellular calcium was investigated using a defined pacing protocol. Rapid pacing (5 Hz) reversibly decreased the NAD(P)H level and increased oxygen consumption whereas phosphocreatine and ATP levels did not change significantly. Verapamil plus NiCl2 blockade of calcium channels abolished contractions. Ryanodine, which prevents calcium-induced cal...

White, R. L.; Wittenberg, B. A.

1995-01-01

126

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)

Full Text Available SciELO Mexico | Language: English Abstract in spanish 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

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

127

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  

Scientific Electronic Library Online (English)

Full Text Available SciELO Chile | Language: Spanish Abstract in spanish 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' Abstract in english 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 M [...] ethods: 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

Luigi, Gabrielli; Fernando, Yañez; María Paz, Ocaranza; Iván, Godoy; Pablo, Castro; Douglas, Greig; Claudia, Hernández; Silvana, Llevaneras; Jorge, Jalil.

2009-04-01

128

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

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

Ikuo Yokoyama

2002-12-01

129

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

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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 blood 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<0.05, from 147±3.8 to 133±2.8 in the losartan group (p<0.05, and from 146±3.0 to 116±4.0 in the enalapril+losartan group (p<0.05. However, the percent reduction of LVMI was significantly greater (p<0.01 in the enalapril+losartan group (20.5±5.0% than in enalapril (12.4±3.2% and the losartan (9.1±2.1% groups. Normalization of LVMI was obtained in 10 out of the 16 patients who received enalapril+ losartan, in 6 out of the 15 patients who received only enalapril and in 4 out of the 15 patients treated with losartan. CONCLUSION: The combination of an angiotensin-converting enzyme inhibitor and an angiotensin II receptor antagonist (AT1 receptor antagonist in patients produced an additional effect on the reduction of left ventricular hypertrophy. This finding may depend on a more complete inhibition of the cardiac renin-angiotensin.

Antônio Carlos Avanza Jr

2000-02-01

130

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

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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

Aleksandra Zebrowska

2009-03-01

131

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

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

MichaelNivala

2012-05-01

132

Altered expression of troponin T isoforms in mild left ventricular hypertrophy in the rabbit.  

Science.gov (United States)

Alterations in troponin T (TnT) isoforms have been reported in severe human and experimental heart failure (HF), and may play a role in the depressed myofibrillar ATPase activity observed in this condition. It is unclear whether these alterations reflect very severe hemodynamic derangement or are a component of mild hypertrophic stress. Therefore, we studied the expression of TnT isoforms (SDS-PAGE, Western blots), myosin isoforms, myofibrillar ATPase activity, and left ventricular (LV) mechanoenergetics (rbc perfused, isovolumically contracting isolated heart) in a rabbit model of mild hypertrophy (LVH) due to gradual hypertension caused by 12 weeks of cellophane wrap of the kidneys (n=12). LV/body weight ratio increased by 28% in LVH compared to shams (P<0.001); no animals had evidence of HF. In LVH, the percentage of TnT2 was modestly but significantly increased compared to shams [6.2+/-1.9 (+/-S.D. ) v 3.7+/-1.0%, P<0.05], mainly as a consequence of a parallel decrease in TnT4 (P=0.07). Sham hearts ranged from 75-100% V3 isomyosin, whereas all LVH hearts had 100% of the V3 form. There were no significant differences in myofibrillar ATPase activity or mechanical variables, including contraction and relaxation rates. The slope of the VO2-pressure-volume-area relation (a measure of the energy conversion efficiency of the contractile machinery) was also unchanged. We conclude that in the rabbit, shifts in TnT isoforms toward a more "fetal" pattern occur during mild LVH and, therefore, are likely to be a general feature of the response to hemodynamic stress, rather than a phenomenon confined to end-stage disease. These modest shifts are not associated with major alterations in LV myofibrillar ATPase activity or mechanoenergetics. PMID:9299358

Chen, Z; Higashiyama, A; Yaku, H; Bell, S; Fabian, J; Watkins, M W; Schneider, D J; Maughan, D W; LeWinter, M M

1997-09-01

133

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)

Full Text Available SciELO Cuba | Language: Spanish Abstract in spanish 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.

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

2010-12-01

134

Slowly inactivating component of sodium current in ventricular myocytes is decreased by diabetes and partially inhibited by known Na(+)-H(+)Exchange blockers.  

Science.gov (United States)

Recent evidence has suggested a major role for a slowly inactivating component of Na(+)current (I(NaL)) as a contributor to ischemic Na(+)loading. The purposes of this study were to investigate veratrine and lysophosphatidylcholine (LPC)-induced I(NaL)in single ventricular myocytes of normal and diabetic rats and to analyse the effects on this current of three pharmacological agents, known as Na(+)/H(+)exchange inhibitors, whose selectivity has been questioned in several studies. A decrease in Na(+)/H(+)exchange activity has been previously shown to be associated with diabetes, and this has been found to confer some protection to the diabetic heart after an episode of ischemia/reperfusion. Recordings were made using the whole-cell patch-clamp technique. I(NaL)was stimulated either by veratrine (100 mg/ml) or by LPC (10 micromol/l) applied extracellularly. Veratrine as well as LPC-induced I(NaL)was found to be significantly decreased in ventricular myocytes isolated from diabetic rat hearts. Veratrine- and LPC-induced I(NaL)in ventricular myocytes of normal rats was significantly (in the range 10(-7)to 10(-4)mol/l) inhibited by the Na(+)/H(+)exchange blockers HOE 694, EIPA and HOE 642. HOE 694 was the most potent inhibitor, followed by the amiloride derivative EIPA and HOE 642. The sensitivity of veratrine-induced I(NaL)to inhibition by HOE 694 and EIPA was markedly reduced in diabetic ventricular myocytes, with no observed inhibition by HOE 642. These data may have important implications as to the protection that may be afforded against ischemic and reperfusion injury, especially during ischemia and when ischemia occurs in a diabetic situation. PMID:10860762

Chattou, S; Coulombe, A; Diacono, J; Le Grand, B; John, G; Feuvray, D

2000-07-01

135

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

Science.gov (United States)

Endothelial dysfunction can lead to congestive heart failure and the activation of endothelial ATP-sensitive potassium (KATP) channels may contribute to endothelial protection. Therefore, the present study was carried out to investigate the hypothesis that natakalim, a novel KATP channel opener, ameliorates post-infarction left ventricular remodeling and failure by correcting endothelial dysfunction. The effects of myocardial infarction were assessed 8 weeks following left anterior descending coronary artery occlusion in male Wistar rats. Depressed blood pressure, cardiac dysfunction, evidence of left ventricular remodeling and congestive heart failure were observed in the rats with myocardial infarction. Treatment with natakalim at daily oral doses of 1, 3 or 9 mg/kg/day for 8 weeks prevented these changes. Natakalim also prevented the progression to cardiac failure, which was demonstrated by the increase in right ventricular weight/body weight (RVW/BW) and relative lung weight, signs of cardiac dysfunction, as well as the overexpression of atrial and brain natriuretic peptide mRNAs. Our results also demonstrated that natakalim enhanced the downregulation of endothelium-derived nitric oxide, attenuated the upregulation of inducible nitric oxide synthase-derived nitric oxide (NO), inhibited the upregulated endothelin system and corrected the imbalance between prostacyclin and thromboxane A2. Overall, our findings suggest that natakalim prevents post-infarction hypertrophy and cardiac failure by restoring the coordinated balance between endothelial function and cardiac hypertrophy. PMID:25215478

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

2014-11-01

136

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

DEFF Research Database (Denmark)

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

Wachtell, K.; Devereux, R.B.

2008-01-01

137

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)

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.

Luigi Gabrielli

2009-04-01

138

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

Scientific Electronic Library Online (English)

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

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

139

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

Science.gov (United States)

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 training 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. PMID:25296357

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

2014-11-01

140

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

Scientific Electronic Library Online (English)

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

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.

 
 
 
 
141

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

Scientific Electronic Library Online (English)

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

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.

2014-08-29

142

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

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Objectives: The aim of this study was to analyze the antihypertensiveeffect of Valsartan and Nebivolol and their effects on QT dispersion and left ventricular hypertrophy (LVH) in the treatment of naive hypertensive patients.Methods: A prospective study with a six-month follow-up was conducted on hypertensive patients with LVH and mild/ moderate essential hypertension. The patients were randomly assigned to Valsartan (80 to 160 mg/day) or Nebivolol (5 to 10 mg/day) groups. The study group con...

Luminita L??ea; Negrea, S?tefania L.; Bolboaca?, Sorana D.

2010-01-01

143

Inhibitory effects of glycyrrhetinic Acid on the delayed rectifier potassium current in Guinea pig ventricular myocytes and HERG channel.  

Science.gov (United States)

Background. Licorice has long been used to treat many ailments including cardiovascular disorders in China. Recent studies have shown that the cardiac actions of licorice can be attributed to its active component, glycyrrhetinic acid (GA). However, the mechanism of action remains poorly understood. Aim. The effects of GA on the delayed rectifier potassium current (I K), the rapidly activating (I Kr) and slowly activating (I Ks) components of I K, and the HERG K(+) channel expressed in HEK-293 cells were investigated. Materials and Methods. Single ventricular myocytes were isolated from guinea pig myocardium using enzymolysis. The wild type HERG gene was stably expressed in HEK293 cells. Whole-cell patch clamping was used to record I K (I Kr, I Ks) and the HERG K(+) current. Results. GA (1, 5, and 10? ? M) inhibited I K (I Kr, I Ks) and the HERG K(+) current in a concentration-dependent manner. Conclusion. GA significantly inhibited the potassium currents in a dose- and voltage-dependent manner, suggesting that it exerts its antiarrhythmic action through the prolongation of APD and ERP owing to the inhibition of I K (I Kr, I Ks) and HERG K(+) channel. PMID:24069049

Wu, Delin; Jiang, Linqing; Wu, Hongjin; Wang, Shengqi; Zheng, Sidao; Yang, Jiyuan; Liu, Yuna; Ren, Jianxun; Chen, Xianbing

2013-01-01

144

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

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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, com 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.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 of 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.

Mirella Pessoa Sant'Anna

2012-02-01

145

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

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: Portuguese Abstract in portuguese 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.

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

2012-02-01

146

Caveolin contributes to the modulation of basal and ?-adrenoceptor stimulated function of the adult rat ventricular myocyte by simvastatin: a novel pleiotropic effect.  

Science.gov (United States)

The number of people taking statins is increasing across the globe, highlighting the importance of fully understanding statins' effects on the cardiovascular system. The beneficial impact of statins extends well beyond regression of atherosclerosis to include direct effects on tissues of the cardiovascular system ('pleiotropic effects'). Pleiotropic effects on the cardiac myocyte are often overlooked. Here we consider the contribution of the caveolin protein, whose expression and cellular distribution is dependent on cholesterol, to statin effects on the cardiac myocyte. Caveolin is a structural and regulatory component of caveolae, and is a key regulator of cardiac contractile function and adrenergic responsiveness. We employed an experimental model in which inhibition of myocyte HMG CoA reductase could be studied in the absence of paracrine influences from non-myocyte cells. Adult rat ventricular myocytes were treated with 10 µM simvastatin for 2 days. Simvastatin treatment reduced myocyte cholesterol, caveolin 3 and caveolar density. Negative inotropic and positive lusitropic effects (with corresponding changes in [Ca2+]i) were seen in statin-treated cells. Simvastatin significantly potentiated the inotropic response to ?2-, but not ?1-, adrenoceptor stimulation. Under conditions of ?2-adrenoceptor stimulation, phosphorylation of phospholamban at Ser16 and troponin I at Ser23/24 was enhanced with statin treatment. Simvastatin increased NO production without significant effects on eNOS expression or phosphorylation (Ser1177), consistent with the reduced expression of caveolin 3, its constitutive inhibitor. In conclusion, statin treatment can reduce caveolin 3 expression, with functional consequences consistent with the known role of caveolae in the cardiac cell. These data are likely to be of significance, particularly during the early phases of statin treatment, and in patients with heart failure who have altered ?-adrenoceptor signalling. In addition, as caveolin is ubiquitously expressed and has myriad tissue-specific functions, the impact of statin-dependent changes in caveolin is likely to have many other functional sequelae. PMID:25211146

Pugh, Sara D; MacDougall, David A; Agarwal, Shailesh R; Harvey, Robert D; Porter, Karen E; Calaghan, Sarah

2014-01-01

147

Caveolin Contributes to the Modulation of Basal and ?-Adrenoceptor Stimulated Function of the Adult Rat Ventricular Myocyte by Simvastatin: A Novel Pleiotropic Effect  

Science.gov (United States)

The number of people taking statins is increasing across the globe, highlighting the importance of fully understanding statins' effects on the cardiovascular system. The beneficial impact of statins extends well beyond regression of atherosclerosis to include direct effects on tissues of the cardiovascular system (‘pleiotropic effects’). Pleiotropic effects on the cardiac myocyte are often overlooked. Here we consider the contribution of the caveolin protein, whose expression and cellular distribution is dependent on cholesterol, to statin effects on the cardiac myocyte. Caveolin is a structural and regulatory component of caveolae, and is a key regulator of cardiac contractile function and adrenergic responsiveness. We employed an experimental model in which inhibition of myocyte HMG CoA reductase could be studied in the absence of paracrine influences from non-myocyte cells. Adult rat ventricular myocytes were treated with 10 µM simvastatin for 2 days. Simvastatin treatment reduced myocyte cholesterol, caveolin 3 and caveolar density. Negative inotropic and positive lusitropic effects (with corresponding changes in [Ca2+]i) were seen in statin-treated cells. Simvastatin significantly potentiated the inotropic response to ?2-, but not ?1-, adrenoceptor stimulation. Under conditions of ?2-adrenoceptor stimulation, phosphorylation of phospholamban at Ser16 and troponin I at Ser23/24 was enhanced with statin treatment. Simvastatin increased NO production without significant effects on eNOS expression or phosphorylation (Ser1177), consistent with the reduced expression of caveolin 3, its constitutive inhibitor. In conclusion, statin treatment can reduce caveolin 3 expression, with functional consequences consistent with the known role of caveolae in the cardiac cell. These data are likely to be of significance, particularly during the early phases of statin treatment, and in patients with heart failure who have altered ?-adrenoceptor signalling. In addition, as caveolin is ubiquitously expressed and has myriad tissue-specific functions, the impact of statin-dependent changes in caveolin is likely to have many other functional sequelae. PMID:25211146

Agarwal, Shailesh R.; Harvey, Robert D.; Porter, Karen E.; Calaghan, Sarah

2014-01-01

148

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

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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

Wachtell, Kristian; Okin, Peter M

2007-01-01

149

Hydrogen sulfide endothelin-induced myocardial hypertrophy in rats and the mechanism involved.  

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The aim of the study was to evaluate the clinical efficacy of hydrogen sulfide (H2S) treatment on the endothelin-induced cardiac hypertrophy. Sixty-four adult male rats, weighing from 180 to 200 g, were randomly divided into four groups: ten in normal group, ten in sham group, 44 in model group established by inducing the myocardial hypertrophy with endothelin. The myocardial hypertrophy model rats were randomly divided into two groups: 22 in the simple myocardial hypertrophy model group and 22 in the H2S treatment group. Rats in normal group were given 2 ml pure water by gavage per day, those in the sham group and simple cardiac hypertrophy model group were given 2 ml of saline by gavage per day, and rats in the pure cardiac hypertrophy with H2S treatment were given intraperitoneal injections of 2 ml NaHS saline per day for a period of 4 weeks. Left ventricular mass index, myocyte hypertrophy, volume fraction of myocardial interstitial collagen, myocardial hydroxyproline content and other indicators of cardiac hypertrophy were observed after 4 weeks. (1) There were significant differences on the ventricular mass between the treatment group and the cardiac hypertrophy group: The left ventricular mass decreased 21.4 % and the left ventricular mass index decreased 5.97 % (P treatment group compared to the cardiac hypertrophy group; (3) the volume fraction of myocardial interstitial collagen and the myocardial hydroxyproline content decreased 22.3 and 31.3 % in treatment group compared with the cardiac hypertrophy group, respectively (P < 0.05). H2S had a good clinical efficacy in reducing left ventricular mass fraction and myocardial collagen levels, improving myocardial hypertrophy and decrease myocardial fibrosis. It is worthy for further clinical studies. PMID:24980860

Yang, Fengyong; Liu, Zhen; Wang, Yajing; Li, Zhaoxin; Yu, Haichu; Wang, Qixin

2014-12-01

150

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

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

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

2014-12-01

151

Altered Spatiotemporal Dynamics of the Mitochondrial Membrane Potential in the Hypertrophied Heart  

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Abstract Chronically elevated levels of oxidative stress resulting from increased production and/or impaired scavenging of reactive oxygen species are a hallmark of mitochondrial dysfunction in left ventricular hypertrophy. Recently, oscillations of the mitochondrial membrane potential (??m) were mechanistically linked to changes in cellular excitability under conditions of acute oxidative stress produced by laser-induced photooxidation of cardiac myocytes in vitro. Here, we investigate the spatiotemporal dynamics of ??m within the intact heart during ischemia-reperfusion injury. We hypothesize that altered metabolic properties in left ventricular hypertrophy modulate ??m spatiotemporal properties and arrhythmia propensity. PMID:20483313

Jin, Hongwei; Nass, Robert D.; Joudrey, Paul J.; Lyon, Alexander R.; Chemaly, Elie R.; Rapti, Kleopatra; Akar, Fadi G.

2010-01-01

152

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

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

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

2000-01-01

153

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

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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?

Gerke, Oke; Olsen, Michael Hecht

2013-01-01

154

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

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

Cesare Cuspidi

2008-03-01

155

Nifedipine Inhibits Cardiac Hypertrophy and Left Ventricular Dysfunction in Response to Pressure Overload  

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Pathological hypertrophy is commonly induced by activation of protein kinases phosphorylating class II histone deacetylases (HDACs) and de-suppression of transcription factors, such as NFAT. We hypothesized that nifedipine, an L-type Ca2+ channel blocker, inhibits Ca2+ -calmodulin dependent kinase II (CaMKII) and NFAT, thereby inhibiting pathological hypertrophy. Mice were subjected to sham operation or transverse aortic constriction (TAC) for 2 weeks with or without nifedipine (10 mg/kg/day)...

Ago, Tetsuro; Yang, Yanfei; Zhai, Peiyong; Sadoshima, Junichi

2010-01-01

156

Predicting Local SR Ca2+ Dynamics during Ca2+ Wave Propagation in Ventricular Myocytes  

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Abstract Of the many ongoing controversies regarding the workings of the sarcoplasmic reticulum (SR) in cardiac myocytes, two unresolved and interconnected topics are 1), mechanisms of calcium (Ca2+) wave propagation, and 2), speed of Ca2+ diffusion within the SR. Ca2+ waves are initiated when a spontaneous local SR Ca2+ release event triggers additional release from neighboring clusters of SR release channels (ryanodine receptors (RyRs)). A lack of consensus regarding the effective Ca2+ diffusion constant in the SR (DCa,SR) severely complicates our understanding of whether dynamic local changes in SR [Ca2+] can influence wave propagation. To address this problem, we have implemented a computational model of cytosolic and SR [Ca2+] during Ca2+ waves. Simulations have investigated how dynamic local changes in SR [Ca2+] are influenced by 1), DCa,SR; 2), the distance between RyR clusters; 3), partial inhibition or stimulation of SR Ca2+ pumps; 4), SR Ca2+ pump dependence on cytosolic [Ca2+]; and 5), the rate of transfer between network and junctional SR. Of these factors, DCa,SR is the primary determinant of how release from one RyR cluster alters SR [Ca2+] in nearby regions. Specifically, our results show that local increases in SR [Ca2+] ahead of the wave can potentially facilitate Ca2+ wave propagation, but only if SR diffusion is relatively slow. These simulations help to delineate what changes in [Ca2+] are possible during SR Ca2+release, and they broaden our understanding of the regulatory role played by dynamic changes in [Ca2+]SR. PMID:20513395

Ramay, Hena R.; Jafri, M. Saleet; Lederer, W. Jonathan; Sobie, Eric A.

2010-01-01

157

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

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

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

2014-05-01

158

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

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Objectives Left ventricular systolic wall motion abnormalities have prognostic value. Whether wall motion detected by serial echocardiographic examinations predicts prognosis in hypertensive patients with left ventricular hypertrophy ( LVH) without clinically recognized atherosclerotic disease has, however, never been investigated. We examined whether 'in- treatment' wall motion abnormalities predicted outcome in the Losartan Intervention For Endpoint ( LIFE) reduction in hypertension echocardiographic substudy. Methods We studied 749 patients without coronary artery disease, myocardial infarction ( MI), or stroke history. Echocardiographic segmental wall motion abnormalities at baseline and annual re-evaluations (' as time- varying covariate') were examined in relation to endpoints ( cardiovascular mortality, MI, stroke, and hospitalized heart failure). Adjusted Cox regression was used to analyze the primary composite endpoint of cardiovascular death, MI, or stroke and, separately, for fatal and nonfatal MI and hospitalized heart failure. Results During a mean follow-up of 4.8 years, an event was recorded in 67 ( 9%) patients. In Cox models after adjusting for age, gender, treatment, blood pressure lowering, and serial change of left ventricular mass index, ' in-treatment' segmental wall motion abnormalities were associated with subsequent composite endpoint [ hazard ratio =2.1, 95% confidence interval ( CI) 1.1-3.8; P=0.019] and MI [ hazard ratio =3.7 ( 1.5 - 8.9); P=0.004]. Conclusion In hypertensive patients with LVH and no history of cardiovascular disease, ' in- treatment' left ventricular wall motion abnormalities are associated with increased likelihood of subsequent cardiovascular events independent of age, gender, blood pressure lowering, treatment modality, and in- treatment left ventricular mass index Udgivelsesdato: 2008/4

Cicala, S.; Simone, G. de

2008-01-01

159

Increased reactive oxygen species, metabolic maladaptation, and autophagy contribute to pulmonary arterial hypertension-induced ventricular hypertrophy and diastolic heart failure.  

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Pulmonary arterial hypertension (PAH) is a debilitating and deadly disease with no known cure. Heart failure is a major comorbidity and a common cause of the premature death of patients with PAH. Increased asymmetrical right ventricular hypertrophy and septal wall thickening compress the left ventricular cavity and elicit diastolic heart failure. In this study, we used the Sugen5416/hypoxia/normoxia-induced PAH rat to determine whether altered pyridine nucleotide signaling in the failing heart contributes to 1) increased oxidative stress, 2) changes in metabolic phenotype, 3) autophagy, and 4) the PAH-induced failure. We found that increased reactive oxygen species, metabolic maladaptation, and autophagy contributed to the pathogenesis of right ventricular remodeling and hypertrophy that lead to left ventricular diastolic dysfunction. In addition, arterial elastance increased in PAH rats. Glucose-6-phosphate dehydrogenase is a major source of pyridine molecule (nicotinamide adenine dinucleotide phosphate), which is a substrate for nicotinamide adenine dinucleotide phosphate oxidases in the heart. Dehydroepiandrosterone, a 17-ketosteroid that reduces pulmonary hypertension and right ventricular hypertrophy, inhibited glucose-6-phosphate dehydrogenase, decreased oxidative stress, increased glucose oxidation and acetyl-coA, and reduced autophagy in the hearts of PAH rats. It also decreased arterial stiffness and improved left ventricular diastolic function. These findings demonstrate that pyridine nucleotide signaling, at least partly, mediates PAH-induced diastolic heart failure, and that reduction of glucose-6-phosphate dehydrogenase-derived nicotinamide adenine dinucleotide phosphate is beneficial to improve left ventricle diastolic function. PMID:25267798

Rawat, Dhawjbahadur K; Alzoubi, Abdallah; Gupte, Rakhee; Chettimada, Sukrutha; Watanabe, Makino; Kahn, Andrea G; Okada, Takao; McMurtry, Ivan F; Gupte, Sachin A

2014-12-01

160

p21-Activated kinase1 (Pak1) is a negative regulator of NADPH-oxidase 2 in ventricular myocytes.  

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Ischemic conditions reduce the activity of the p21-activated kinase (Pak1) resulting in increased arrhythmic activity. Triggered arrhythmic activity during ischemia is based on changes in cellular ionic balance and the cells Ca(2+) handling properties. In the current study we used isolated mouse ventricular myocytes (VMs) deficient for the expression of Pak1 (Pak1(-/-)) to determine the mechanism by which Pak1 influences the generation of arrhythmic activity during simulated ischemia. The Ca(2+) transient amplitude and kinetics did not significantly change in wild type (WT) and Pak1(-/-) VMs during 15 min of simulated ischemia. However, Pak1(-/-) VMs exhibited an exaggerated increase in [Ca(2+)]i, which resulted in spontaneous Ca(2+) release events and waves. The Ca(2+) overload in Pak1(-/-) VMs could be suppressed with a reverse mode blocker (KB-R7943) of the sodium calcium exchanger (NCX), a cytoplasmic scavenger of reactive oxygen species (ROS; TEMPOL) or a RAC1 inhibitor (NSC23766). Measurements of the cytoplasmic ROS levels revealed that decreased Pak1 activity in Pak1(-/-) VMs or VMs treated with the Pak1 inhibitor (IPA3) enhanced cellular ROS production. The Pak1 dependent increase in ROS was attenuated in VMs deficient for NADPH oxidase 2 (NOX2; p47(phox-/-)) or in VMs where NOX2 was inhibited (gp91ds-tat). Voltage clamp recordings showed increased NCX activity in Pak1(-/-) VMs that depended on enhanced NOX2 induced ROS production. The exaggerated Ca(2+) overload in Pak1(-/-) VMs could be mimicked by low concentrations of ouabain. Overall our data show that Pak1 is a critical negative regulator of NOX2 dependent ROS production and that a latent ROS dependent stimulation of NCX activity can predispose VMs to Ca(2+) overload under conditions where no significant changes in excitation-contraction coupling are yet evident. PMID:24380729

DeSantiago, Jaime; Bare, Dan J; Xiao, Lei; Ke, Yunbo; Solaro, R John; Banach, Kathrin

2014-02-01

 
 
 
 
161

Role of inositol-1,4,5-trisphosphate receptor in the regulation of calcium transients in neonatal rat ventricular myocytes.  

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This study determined the regulatory effect of inositol 1,4,5-trisphosphate receptors (IP3Rs) on the basal Ca(2+) transients in cardiomyocytes. In cultured neonatal rat ventricular myocytes (NRVMs) at different densities, we used confocal microscopy to assess the effect of IP3Rs on the endogenous spontaneous Ca(2+) oscillations through specific activation of IP3Rs with myo-IP3 hexakis (butyryloxymethyl) ester (IP3BM), a membrane permeable IP3, and interference of IP3R expression with shRNA. We found that NRVMs at the monolayer state displayed coordinated Ca(2+) transients with less rate, shorter duration, and higher amplitude compared to single NRVMs. In addition, monolayer NRVMs exhibited 4 or 10 times more increased Ca(2+) transients in response to phenylephrine, an ?-adrenergic receptor agonist, or IP3BM than single NRVMs did, while the transient pattern remained unaltered, suggesting that the sensitivity of intracellular Ca(2+) response to IP3R activation is different between single and monolayer NRVMs. However, interference of IP3R expression with shRNA reduced the frequency and amplitude of the spontaneous Ca(2+) fluctuates similarly in both densities of NRVMs, resembling the effects of ryanodine receptor inhibition by ryanodine or tetracaine. Our findings suggest that IP3Rs are involved, in part, in the regulation of native Ca(2+) transients, in profiles of their initiation and Ca(2+) release extent, in developing cardiomyocytes. In addition, caution should be paid in evaluating the behavior of Ca(2+) signaling in primary cultured cardiomyocytes at different densities. PMID:25242084

Zeng, Zheng; Zhang, Heping; Lin, Na; Kang, Man; Zheng, Yuanyuan; Li, Chen; Xu, Pingxiang; Wu, Yongquan; Luo, Dali

2014-09-20

162

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

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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.)

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

163

Fragmented QRS and Left Ventricular Geometry in Hypertensive Patients  

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Full Text Available Introduction: Fragmented QRS is a depolarization abnormality detected with routin ECG recording. It is related with conduction defect which occurs after myocardial fibrosis. In the left ventricular hypertrophy, an excessive amount of collagen accumulates in the interstitium when the myocytes became hypertrophied, resulting in myocardial fibrosis. In this study, we aimed to investigate the relationship of fragmented QRS which was detected on ECG recordings of the hypertensive patients with the left ventricular geometry.Patients and Methods: Essential hypertension patients referred to our hospital on outpatient bases were included in the study. 12-lead resting ECG was taken in all the patients. Left ventricular geometry defined using left ventricular mass index and relative wall thickness with transthorasic echocardiography.Results: Sixy seven patients with fragmented QRS and 63 patients without fragmented QRS included the study. We found that patients in the group with fragmented QRS detected have a wider mean left atrium diameter, greater left ventricular mass and left ventricular mass index compared with the group without fragmented QRS. Concentric and eccentric hypertrophy were more common in fragmented QRS group, while normal geometry and concentric remodelling have greater rates in the normal group.Conclusion: Left ventricular hypertrophy is observed more frequently in the patients with fragmented QRS than without fragmented QRS. This may be associated with the increased myocardial fibrosis in the left ventricular hypertrophy. Existence of fragmented QRS can be used for risk stratification in the hypertensive patients.

Lütfü Bekar

2013-08-01

164

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

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

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

2014-10-01

165

Properties of palytoxin-induced whole cell current in single rat ventricular myocytes.  

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We examined the properties of the current induced by palytoxin in single ventricular cells of rats. The current was measured by a whole cell voltage clamp method. When the cell was held at -75 mV, palytoxin induced a sustained inward current in a concentration-dependent manner (2-100 pmol/l). The time-course of the inward current paralleled that of the depolarization. At a holding potential of +50 mV, it caused an outward current. Palytoxin-induced current reversed at 0 mV and its current-voltage relation was almost linear at either negative or positive voltage. Substitution of external NaCl with choline-Cl suppressed the palytoxin-induced inward current but not the outward current, by shifting the reversal potential to levels more negative than -50 mV. A cardiac glycoside, cymarin (10 and 100 mumol/l) partially inhibited the palytoxin-induced current without changing the reversal potential, only when applied before palytoxin. Palytoxin decreased the nicardipine-sensitive Ca2+ current. These data suggest that palytoxin-induced inward current is carried by extracellular Na+ and the outward current is carried mainly by intracellular K+, and that the inward current is responsible for the toxin's depolarizing action. The antagonism by cysmarin indicates that the site of action of palytoxin is in the vicinity of the binding site of cardiac glycosides. PMID:1719436

Kinoshita, K; Ikeda, M; Ito, K

1991-08-01

166

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

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

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

2012-03-01

167

Blocking effect of methylflavonolamine on human NaV1.5 channels expressed in Xenopus laevis oocytes and on sodium currents in rabbit ventricular myocytes  

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Aim: To investigate the blocking effects of methylflavonolamine (MFA) on human NaV1.5 channels expressed in Xenopus laevis oocytes and on sodium currents (INa) in rabbit ventricular myocytes. Methods: Human NaV1.5 channels were expressed in Xenopus oocytes and studied using the two-electrode voltage-clamp technique. INa and action potentials in rabbit ventricular myocytes were studied using the whole-cell recording. Results: MFA and lidocaine inhibited human NaV1.5 channels expressed in Xenopus oocytes in a positive rate-dependent and concentration-dependent manner, with IC50 values of 72.61 ?mol/L and 145.62 ?mol/L, respectively. Both of them markedly shifted the steady-state activation curve of INa toward more positive potentials, shifted the steady-state inactivation curve of INa toward more negative potentials and postponed the recovery of the INa inactivation state. In rabbit ventricular myocytes, MFA inhibited INa with a shift in the steady-state inactivation curve toward more negative potentials, thereby postponing the recovery of the INa inactivation state. This shift was in a positive rate-dependent manner. Under current-clamp mode, MAF significantly decreased action potential amplitude (APA) and maximal depolarization velocity (Vmax) and shortened action potential duration (APD), but did not alter the resting membrane potential (RMP). The demonstrated that the kinetics of sodium channel blockage by MFA resemble those of class I antiarrhythmic agents such as lidocaine. Conclusion: MFA protects the heart against arrhythmias by its blocking effect on sodium channels. PMID:20173760

Fan, Xin-rong; Ma, Ji-hua; Zhang, Pei-hua; Xing, Jun-lian

2010-01-01

168

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

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

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

169

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

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

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

170

Carbonic anhydrase II promotes cardiomyocyte hypertrophy.  

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Pathological cardiac hypertrophy, the maladaptive remodelling of the myocardium, often progresses to heart failure. The sodium-proton exchanger (NHE1) and chloride-bicarbonate exchanger (AE3) have been implicated as important in the hypertrophic cascade. Carbonic anhydrase II (CAII) provides substrates for these transporters (protons and bicarbonate, respectively). CAII physically interacts with NHE1 and AE3, enhancing their respective ion transport activities by increasing the concentration of substrate at their transport sites. Earlier studies found that a broad-spectrum carbonic anhydrase inhibitor prevented cardiomyocyte hypertrophy (CH), suggesting that carbonic anhydrase is important in the development of hypertrophy. Here we investigated whether cytosolic CAII was the CA isoform involved in hypertrophy. Neonatal rat ventricular myocytes (NRVMs) were transduced with recombinant adenoviral constructs to over-express wild-type or catalytically inactive CAII (CAII-V143Y). Over-expression of wild-type CAII in NRVMs did not affect CH development. In contrast, CAII-V143Y over-expression suppressed the response to hypertrophic stimuli, suggesting that CAII-V143Y behaves in a dominant negative fashion over endogenous CAII to suppress hypertrophy. We also examined CAII-deficient (Car2) mice, whose hearts exhibit physiological hypertrophy without any decrease in cardiac function. Moreover, cardiomyocytes from Car2 mice do not respond to prohypertrophic stimulation. Together, these findings support a role of CAII in promoting CH. PMID:23210439

Brown, Brittany F; Quon, Anita; Dyck, Jason R B; Casey, Joseph R

2012-12-01

171

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

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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.

Boersma Hester

2009-04-01

172

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

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Full Text Available SciELO Brazil | Language: Portuguese Abstract in portuguese A doença cardiovascular (DCV) permanece sendo uma das maiores causas de morte em pacientes com doença renal crônica (DRC). A hipertrofia ventricular esquerda (HVE) está presente em 75% dos pacientes ao iniciarem diálise, sugerindo que esta deve estar presente precocemente no curso da DRC. Poucos est [...] udos avaliaram a prevalência de HVE na pré-diálise. Foram avaliados 309 pacientes clinicamente estáveis em acompanhamento por pelo menos três meses em cinco Centros no Brasil. Perfil bioquímico e marcadores inflamatórios foram avaliados. Dados são apresentados como media ± DP. Observamos que a HVE esteve presente em 53% dos pacientes, idade = 60 ± 13 anos, e 55 ± 14 anos para aqueles sem HVE. Diabetes mellitus como doença de base esteve presente em 35% dos pacientes em ambos os grupos. Filtração glomerular estimada foi 30 ± 11 e 32 ± 12 mL/min para pacientes com HVE e sem, respectivamente (p = 0,19). A distribuição de pacientes mostrou que 60% com HVE se encontravam no estágio 4. Análise logística multivariada mostrou que eram determinantes independentes para HVE: idade (p Abstract in english Cardiovascular disease (CVD) remains the major cause of death in patients with chronic kidney disease (CKD). Left ventricular hypertrophy (LVH) is present in 75% of patients starting dialysis, suggesting that LVH might be present from an early stage of CKD. Few studies have addressed the predialysis [...] prevalence of LVH. This study evaluated 309 clinically stable patients under treatment for at least three months at five Brazilian centers. Biochemical profile and inflammatory markers were assessed. Data were shown as mean ± SD. Left ventricular hypertrophy was present in 53% of the patients, whose mean age was 60 ± 13years. The mean age of those without LVH was 55 ± 14 years. Diabetes mellitus was the underlying disease in 35% of the patients in both groups. Estimated glomerular filtration rate was 30 ± 11 and 32 ± 12 mL/min for patients with and without LVH, respectively (p = 0.19). The distribution of patients showed that 60% of those with LVH were in stage 4. Multivariate logistic regression analysis indicated the following independent determinants for LVH: age (p

Rachel, Bregman; Carla, Lemos; Roberto, Pecoits Filho; Hugo, Abensur; Sergio, Draibe; Marcus Gomes, Bastos; Maria Eugênia, Canziani.

2010-03-01

173

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

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

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

1998-04-01

174

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

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

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

175

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

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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

Cabral A.M.

1998-01-01

176

Sarcolemmal ion currents and sarcoplasmic reticulum Ca2+ content in ventricular myocytes from the cold stenothermic fish, the burbot (Lota lota).  

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The burbot (Lota lota) is a cold stenothermic fish species whose heart is adapted to function in the cold. In this study we use whole-cell voltage-clamp techniques to characterize the electrophysiological properties of burbot ventricular myocytes and to test the hypothesis that changes in membrane currents and intracellular Ca2+ cycling associated cold-acclimation in other fish species are routine for stenothermic cold-adapted species. Experiments were performed at 4 degrees C, which is the body temperature of burbot for most of the year, and after myocytes were acutely warmed to 11 degrees C, which is in the upper range of temperatures experienced by burbot in nature. Results on K+ channels support our hypothesis as the relative density of K-channel conductances in the burbot heart are similar to those found for cold-acclimated cold-active fish species. I(K1) conductance was small (39.2+/-5.4 pS pF(-1) at 4 degrees C and 71.4+/-1.7 pS pF(-1) at 11 degrees C) and I(Kr) was large (199+/-27 pS pF(-1) at 4 degrees C and 320.3+/-8 pS pF(-1) at 11 degrees C) in burbot ventricular myocytes. We found high Na+-Ca2+ exchange (NCX) activity (35.9+/-6.3 pS pF(-1) at 4 degrees C and 58.6+/-8.4 pS pF(-1) at 11 degrees C between -40 and 20 mV), suggesting that it may be the primary pathway for sarcolemmal (SL) Ca2+ influx in this species. In contrast, the density (I(Ca), 0.81+/-0.13 pA pF(-1) at 4 degrees C, and 1.35+/-0.18 pA pF(-1) at 11 degrees C) and the charge (Q(Ca), 0.24+/-0.043 pC pF(-1) at 4 degrees C and 0.21+/-0.034 pC pF(-1) at 11 degrees C) carried by the L-type Ca2+ current was small. Our results on sarcolemmal ion currents in burbot ventricular myocytes suggest that cold stenothermy and compensative cold-acclimation involve many of the same subcellular adaptations that culminate in enhanced excitability in the cold. PMID:16888058

Shiels, Holly A; Paajanen, Vesa; Vornanen, Matti

2006-08-01

177

The impact of change in volume and left-ventricular hypertrophy on left-ventricular mechanical dyssynchrony in children with end-stage renal disease.  

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Left-ventricular dyssynchrony (LVD) adversely affects systolic performance and has not been previously evaluated in children with end-stage renal disease (ESRD). We hypothesized (1) that LVD in children with ESRD would be significantly increased compared with controls and (2) that volume load and left-ventricular hypertrophy (LVH) would be associated with increased LVD. This was a prospective observational study in which real-time three-dimensional echocardiographic data were acquired in 27 stable children with ESRD (13 peritoneal dialysis [PD] and 14 hemodialysis [HD]) and 29 normal controls. Data were acquired before and after an HD session. Dyssynchrony index (SDI) was defined per standard formulae and was normalized to cardiac cycle duration (SDIp). Left-ventricular mass (LVM) was obtained from M-mode echocardiography and was normalized to height(2.7) (LVM index). The mean age (13.8 vs. 11.3 years) and SDI, SDIp, LVM, and LVM index were significantly greater among children with ESRD than among controls (p SDIp 16 segments, and LVM were significantly greater in the HD group. SDI and SDIp 16 segments improved after an HD session (p < 0.05); LVM and LVM index remained unchanged. LVD was significantly greater in patients with LVH compared with those without LVH. Children with ESRD had significant LVD and increased LVM compared with controls. Increased LVD in those undergoing HD rather than PD, as well as the improvement in synchrony after HD, suggest that volume may modulate LVD. LVD was increased in children with LVH. LVD in children with ESRD may have pathogenic implications. PMID:22441563

Kobayashi, Daisuke; Patel, Sheetal R; Mattoo, Tej K; Valentini, Rudolph P; Aggarwal, Sanjeev

2012-10-01

178

Bilirubin Level is Associated with Left Ventricular Hypertrophy Independent of Blood Pressure in Previously Untreated Hypertensive Patients  

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Background and Objectives Left ventricular hypertrophy (LVH), a sign of subclinical cardiovascular disease, is an important predictor of cardiovascular morbidity and mortality. The aim of our study was to determine the association of left ventricular mass (LVM) with possible causative anthropometric and biochemical parameters as well as carotid intima-media thickness (CIMT) and brachial flow-mediated dilation (FMD) as surrogates of atherosclerosis and endothelial dysfunction, respectively, in previously untreated hypertensive patients. Subjects and Methods Our study included 114 consecutive previously untreated hypertensive patients who underwent echocardiography and ultrasonography to evaluate their vascular status and function via brachial artery CIMT and FMD. Results Among all study parameters, age, systolic blood pressure (BP), diastolic BP, pulse pressure, plasma glucose, uric acid, total bilirubin, direct bilirubin, hemoglobin, and CIMT were positively correlated with the LVM index. Multiple logistic regression analysis revealed that office systolic BP, age, male gender, and total bilirubin were independent predictors of LVH. Conclusion Bilirubin seems to be related to LVM and LVH. The positive association of bilirubin with these parameters is novel and requires further research.

Ayaz, Teslime; Kocaman, Sinan Altan; Durakoglugil, Tugba; Erdogan, Turan; Sahin, Osman Zikrullah; Sahin, Serap Baydur; Cicek, Yuksel; Satiroglu, Omer

2014-01-01

179

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

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

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

2000-05-01

180

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

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Cardiovascular disease is the leading cause of death in the United States and worldwide. High incidence of cardiovascular diseases has been linked to populations with elevated arsenic content in their drinking water. Although this correlation has been established in many epidemiological studies, a lack of experimental models to study mechanisms of arsenic-related cardiovascular pathogenesis has limited our understanding of how arsenic exposure predisposes for development of hypertension and increased cardiovascular mortality. Our studies show that mice chronically exposed to drinking water containing 100 parts per billion (ppb) sodium arsenite for 22 weeks show an increase in both systolic and diastolic blood pressure. Echocardiographic analyses as well as histological assessment show concentric left ventricular hypertrophy, a primary cardiac manifestation of chronic hypertension. Live imaging by echocardiography shows a 43% increase in left ventricular mass in arsenic-treated animals. Relative wall thickness (RWT) was calculated showing that all the arsenic-exposed animals show an RWT greater than 0.45, indicating concentric hypertrophy. Importantly, left ventricular hypertrophy, although often associated with chronic hypertension, is an independent risk factor for cardiovascular-related mortalities. These results suggest that chronic low-level arsenite exposure promotes the development of hypertension and the comorbidity of concentric hypertrophy. PMID:22215511

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

2012-04-01

 
 
 
 
181

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

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

182

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

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

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

2002-12-01

183

[Left ventricular efficiency of hypertensive without hypertrophy: echographic study with modelisation of left ventricular-aortic coupling].  

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Because the functional interaction between the LV and arterial systems, termed ventricular-arterial coupling, is recognized as a key determinant of LV performance, the objective of the present study was to assess the impact of uncomplicated HT without LVH on LV performance using simultaneously echocardiography and carotid tonometry. LV maximal power (PmaxVG), cardiac power output (CPO), LV efficiency (CPO/PmaxVG), input aortic and output LV elastance (Ea and Ees) were assessed in 20 normotensive control subjects (NT) and 10 patients with untreated HT. PmaxVG was calculated according to the integral of the product of LV wall stress with strain rate (as an index of gradient velocity). Cyclic variation of wall thickness and SR were measured by speckel-tracking. Ea and Ees were derived and modelized from the pressure-volume curve. No difference in age, BMI and sex ratio was observed between NT and HT. Systolic BP (160±18 vs. 119±10mmHg), LV mass (99±15 vs. 76±12g/m(2)), PWV (9.7±2 vs. 6.9±1m/s) were significantly higher (P<0.01) in HT when compared to NT. In HT increased of CPO and Ea was compensated by an increase of LV (15±4 vs. 12±3%, P<0.02) and Ees (5.5±2 vs. 4.5±1.5mmHg/mL), which are significantly elevated in HT (P<0.05). No difference was observed in Ea/Ees between NT and HT. In conclusion at the early phase of HT, in patients without LVH, LV performance and ventricular-arterial coupling were adapted to post-load elevation. This adaptation may be the result of an increased of LV contractility. PMID:24952676

Bonnet, B; Jourdan, F; du Cailar, G; Mimran, A; Fesler, P

2014-06-01

184

A novel mouse model of X-linked cardiac hypertrophy.  

Science.gov (United States)

We recovered a novel mouse mutant exhibiting neonatal lethality associated with severe fetal cardiac hypertrophy and with some adult mice dying suddenly with left ventricular hypertrophic cardiomyopathy. Using Doppler echocardiography, we screened surviving adult mice in this mutant line for cardiac hypertrophy. Cardiac dimensions were obtained either from two-dimensional images collected using a novel ECG-gated ultra-high-frequency ultrasound system or by traditional M-mode imaging on a clinical ultrasound system. These analyses identified, among the littermates, two populations of mice: those with apparent cardiac hypertrophy with hypercontractile function characterized by ejection fraction of 75-80%, and normal littermates with ejection fraction of 53-55%. Analysis of the ECG-gated two-dimensional cines indicated that the hypertrophy was of the nonobstructive type. Further analysis of heart-to-body weight ratio confirmed the ultrasound diagnosis of left ventricular hypertrophic cardiomyopathy. Histopathology showed increased ventricular wall thickness, enlarged myocyte size, and mild myofiber disarray. Ultrastructural analysis by electron microscopy revealed mitochondria hyperproliferation and dilated sarcoplasmic reticulum. Genome scanning using microsatellite DNA markers mapped the mutation to the X chromosome. DNA sequencing showed no mutations in the coding regions of several candidate genes on the X chromosome, including several known to be associated with left ventricular hypertrophic cardiomyopathy. These findings suggest that this mouse line may harbor a mutation in a novel gene causing X-linked cardiomyopathy. PMID:18424640

Leatherbury, L; Yu, Q; Chatterjee, B; Walker, D L; Yu, Z; Tian, X; Lo, C W

2008-06-01

185

Usefulness of QRS voltage correction by body mass index to improve electrocardiographic detection of left ventricular hypertrophy in patients with systemic hypertension.  

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Obesity reduces the accuracy of voltage-based electrocardiographic (ECG) criteria for diagnosis of left ventricular (LV) hypertrophy. We developed a new ECG score for diagnosis of LV hypertrophy, defined either by a typical strain pattern or a product of the Cornell voltage (R wave height in lead aVL plus S wave depth in lead V3) by body mass index >604 mm?kg/m(2). We examined a population of 2,747 untreated hypertensive subjects (mean age 49 ± 11 years) with good quality ECG and echocardiographic tracings. Several traditional ECG criteria for LV hypertrophy were compared with the new score, with echocardiographic LV mass taken as reference. Among the tested criteria, the highest sensitivity combined with specificity was yielded by the new score (sensitivity 36.1%, 95% confidence interval [CI] 32.9 to 39.4; specificity 90.5%, 95% CI 89.1 to 91.8; and accuracy 73.1%, 95% CI 71.5 to 74.8). Prevalence of ECG LV hypertrophy with the new score was 18%. On the basis of comparisons between areas under the receiver operating characteristic curves, the best performance was achieved by the new score with respect to other ECG criteria for LV hypertrophy (all p <0.0001). In conclusion, correction of Cornell voltage by body mass index as a marker of obesity improves the performance of traditional electrocardiography for diagnosis of LV hypertrophy in patients with hypertension. PMID:24934758

Angeli, Fabio; Verdecchia, Paolo; Iacobellis, Gianluca; Reboldi, Gianpaolo

2014-08-01

186

Increased Apoptosis and Myocyte Enlargement with Decreased Cardiac Mass; Distinctive Features of the Aging Male, but not Female, Monkey Heart  

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We studied gender-specific changes in aging cardiomyopathy in a primate model, Macaca fascicularis, free of the major human diseases, complicating the interpretation of data specific to aging in humans. Left ventricular (LV) weight/body weight decreased, p<0.05, in old males, but did not change in old females. However, despite the decrease in LV weight, mean myocyte cross-sectional area in the old males increased by 51%. This increase in myocyte size was not uniform in old males, i.e., it was manifest in only 20–30% of all the myocytes from old males. In old males there was a 4-fold increase in frequency of myocyte apoptosis without any increase in proliferation-capable myocytes assessed by Ki-67 expression. Apoptosis was unchanged in old female monkey hearts, whereas the frequency of myocytes expressing Ki-67 declined 90%. These results, opposite to findings from rodent studies, indicate distinct differences in which male and female monkeys maintain functional heart mass during aging. The old male hearts demonstrated increased apoptosis, which more than offset the myocyte hypertrophy, which interestingly was not uniform, without a significant increase in myocyte proliferation. PMID:17720187

Zhang, Xiao-Ping; Vatner, Stephen F.; Shen, You-Tang; Rossi, Franco; Tian, Yimin; Peppas, Athanasios; Resuello, Ranillo R.G.; Natividad, Filipinas F.; Vatner, Dorothy E.

2009-01-01

187

Presystolic mitral closure sound in aortic regurgitation with left ventricular hypertrophy and first degree heart block.  

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We report a patient who developed aortic regurgitation and first degree atrioventricular block caused by infective endocarditis complicating aortic valve stenosis. There was premature closure of the mitral valve and, in the absence of an Austin Flint murmur, a simultaneous high frequency sound was audible which we regard as a presystolic first heart sound. That such a sound may be associated with valve closure, even though this precedes electrical and mechanical ventricular systole, provides ...

Traill, T. A.; Fortuin, N. J.

1982-01-01

188

Right ventricular myocardial performance index is decreased with severe pressure-overload cardiac hypertrophy in young rats.  

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Although the right ventricular (RV) myocardial performance index (MPI) usually is increased in the presence of RV dysfunction and pressure overload, debate continues over the correlation between the RV MPI and functional derangement in patients with RV pressure-overload congenital heart disease (CHD). To address this controversy, this study took serial measurements of the RV MPI in addition to invasive RV hemodynamic measurements during the acute stage of mild to severe pressure overload. Right ventricle pressure overload was induced by partial pulmonary arterial banding (PAB) in 3-week-old rats. The rats were divided into two groups: mild pulmonary stenosis (PS) group (20-40 % stenosis; n = 20) and severe PS group (40-70 % stenosis; n = 28). Sham-treated animals (sham group; n = 30) underwent the same surgical procedure without PAB. Pressure-overload RV hypertrophy was documented by weighing the heart, by evaluating echocardiograms, and by evaluating cardiac hypertrophy-associated gene expression. The RV MPI was checked 1, 2, 3, 5, and 8 weeks after PAB. The MPI was calculated as the sum of the isovolumic contraction time and the isovolumic relaxation time (IRT) divided by the ejection time. The RV MPI of the mild PS group did not differ significantly from that of the sham group. The RV MPI of the severe PS group, however, was lower than that of the sham group (0.27 ± 0.01 vs 0.29 ± 0.01) 2 to 8 weeks after PAB: 0.19 ± 0.01 at 2 weeks (P overload condition. PMID:23467728

Ko, Jeong-Hyeon; Eom, Gwang Hyeon; Cho, Hwa Jin; Nam, Kwang-Il; Ma, Jae Sook; Kook, Hyun; Cho, Young Kuk

2013-10-01

189

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)

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

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

2007-12-01

190

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

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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 do...

Tarlovskaya, Ye I.; Maksimchuk, N. S.; Ye Sapozhnikova, I.; Malchikova, S. V.

2010-01-01

191

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

DEFF Research Database (Denmark)

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

Andersen, Asger; Nielsen, Jan MØller

2013-01-01

192

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.)

193

The Value of Chest Radiogram and Electrocardiogram in the Assessment of Left Ventricular Hypertrophy among Adult Hypertensives  

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Full Text Available The objective of the study was to assess the relative contributions and benefits of chest radiogram and electrocardiogram in detecting left ventricular hypertrophy among adult hypertensives. Seventy consecutive, newly diagnosed hypertensive patients with forty age and sex comparable healthy controls were recruited for the study at the University of Maiduguri Teaching Hospital, Northeast, Nigeria. The echocardiographic mean Left Ventricular Mass (LVM was 260.8 ± 72.9 g (range 109.8 to 429.8 g and 136.9 ± 18.1 g (range 104 to 188.9 g in patients and controls respectively (p<0.001. Echocardiographic LVM correlated fairly with Cardiothoracic Ratio (CTR on chest X-ray (r = 0.43, p<0.01 followed by SV 2 + RV6 with a correlation of 0.39 (p<0.01. However, in terms of sensitivity, specificity and accuracy in comparison with ECHO LVM, SV2 + RV6 had better indices than CTR. The sensitivity, specificity and accuracy indices were 0.60, 0.93 and 0.67 for SV2 + RV6 as compared to 0.53, 0.87 and 0.60 for CTR, respectively. Though previous studies had noted echocardiography as the gold standard in this form of assessment, however most centres in the developing world lacked facility for this purpose. In contrast radiography and electrocardiography are uniformly available. In view of the results, we recommend that chest X-ray and electrocardiograms might be simple screening procedures in the management of hypertensive heart disease where echocardiography is inaccessible.

F. Buba

2008-01-01

194

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

Science.gov (United States)

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

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

2012-12-01

195

Sensitivity and specificity of frequently used electrocardiographic criteria for left ventricular hypertrophy in patients with anterior wall myocardial infarction  

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Electrocardiographic left ventricular hypertrophy (LVH) strongly predicts mortality in patients with myocardial infarction (MI). However, the validity of LVH voltage criteria in this context has not been assessed. Reviewing the coded database of echocardiographic studies performed at one institution, we performed a retrospective analysis of 49 patients who had anterior akinesis on the echocardiogram and anterior wall MI on the electrocardiogram. Results showed that, compared with the sensitivities and specificities of the electrocardiographic voltage criteria in historical cohorts, Cornell criteria were less sensitive and specific for the diagnosis of LVH in patients with anterior wall MI. The sensitivity was reduced in the presence of an associated lateral wall MI, and the specificity was reduced in the absence of a lateral wall MI (overall sensitivity in case of anterior wall MI, with or without an associated lateral wall MI, 21% vs 41%, P = 0.049; overall specificity 84% vs 98%, P = 0.003). All criteria, except for S in V1 + R in V5 or V6 >3.5 mV, had a significantly reduced specificity in the case of anterior wall MI not associated with lateral wall MI, and all criteria, except for R in V6 > R in V5, had reduced sensitivity in the presence of a lateral wall MI. In conclusion, anterior wall MI reduces the sensitivity and the specificity of the most commonly used LVH voltage criteria. PMID:20157497

Glancy, D. Luke; Oral, Evrim

2010-01-01

196

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.)

197

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

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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.

K.I. Pshenichkin

2007-01-01

198

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

International Nuclear Information System (INIS)

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

199

Tissue Doppler imaging of longitudinal movement of a fibrous ring of mitral valve during isovolumic periods in left ventricular hypertrophy  

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

B. Amarjagal

2007-01-01

200

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 ive 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

 
 
 
 
201

Protein kinase C(epsilon) modulates apoptosis induced by beta -adrenergic stimulation in adult rat ventricular myocytes via extracellular signal-regulated kinase (ERK) activity.  

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Beta-adrenergic stimulation of ventricular myocytes has been shown to induce apoptosis; however, the cellular mechanisms involved in this pathway have not been completely characterized. This study examines the role of protein kinase C (PKC) in the signaling cascade that mediates beta-adrenergic stimulation-induced apoptosis. Stimulation of beta-adrenergic receptors using isoproterenol (ISO, 1-10 microm, 24 h) induced apoptosis in cultured adult rat ventricular myocytes (ARVM) in a dose-dependent manner. Treatment with ISO significantly resulted in the membrane translocation of PKC(epsilon), but not of PKC alpha or delta in ARVM. The activation of PKC(epsilon) by ISO was confirmed using an immune complex kinase assay. To address whether PKC(epsilon) is involved in the mechanism of ISO-induced apoptosis, we used the PKC(epsilon)-specific translocation inhibitor peptide, epsilonV1-2. Peptide epsilonV1-2 significantly blocked the translocation of PKC(epsilon), as well as the enzymatic action of PKC(epsilon), resulting from ISO stimulation. The inhibition of PKC(epsilon) attenuated ISO-induced apoptosis as measured by terminal deoxynucleotidyltransferase nick-end labeling (TUNEL) assay (18.2+/-3.8%v 49.0+/-2.4%Pdelta-specific peptide translocation inhibitor (delta V1-1) failed to do so (39.8+/-7.8%). In the presence of ISO, PKC(epsilon) inhibition by epsilonV1-2 was found to significantly enhance activity of ERK, but not that of Akt/PKB. Inhibition of ERK activation by PD 98059 (10-50 microm) attenuated the epsilonV1-2 peptide-mediated anti-apoptotic effect, thus suggesting that ERK activation is involved in this anti-apoptotic effect. Therefore, our results suggest that activation of PKC(epsilon) downstream of beta-adrenergic stimulation promotes apoptosis largely via inhibition of an ERK activation-dependent anti-apoptotic effect. PMID:11603922

Shizukuda, Y; Buttrick, P M

2001-10-01

202

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)

Full Text Available SciELO Argentina | Language: Spanish Abstract in portuguese 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

Daniel, Piskorz; Alicia, Tommasi.

203

Cytosolic H2O2 mediates hypertrophy, apoptosis, and decreased SERCA activity in mice with chronic hemodynamic overload.  

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Oxidative stress in the myocardium plays an important role in the pathophysiology of hemodynamic overload. The mechanism by which reactive oxygen species (ROS) in the cardiac myocyte mediate myocardial failure in hemodynamic overload is not known. Accordingly, our goals were to test whether myocyte-specific overexpression of peroxisomal catalase (pCAT) that localizes in the sarcoplasm protects mice from hemodynamic overload-induced failure and prevents oxidation and inhibition of sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA), an important sarcoplasmic protein. Chronic hemodynamic overload was caused by ascending aortic constriction (AAC) for 12 wk in mice with myocyte-specific transgenic expression of pCAT. AAC caused left ventricular hypertrophy and failure associated with a generalized increase in myocardial oxidative stress and specific oxidative modifications of SERCA at cysteine 674 and tyrosine 294/5. pCAT overexpression ameliorated myocardial hypertrophy and apoptosis, decreased pathological remodeling, and prevented the progression to heart failure. Likewise, pCAT prevented oxidative modifications of SERCA and increased SERCA activity without changing SERCA expression. Thus cardiac myocyte-restricted expression of pCAT effectively ameliorated the structural and functional consequences of chronic hemodynamic overload and increased SERCA activity via a post-translational mechanism, most likely by decreasing inhibitory oxidative modifications. In pressure overload-induced heart failure cardiac myocyte cytosolic ROS play a pivotal role in mediating key pathophysiologic events including hypertrophy, apoptosis, and decreased SERCA activity. PMID:24633550

Qin, Fuzhong; Siwik, Deborah A; Pimentel, David R; Morgan, Robert J; Biolo, Andreia; Tu, Vivian H; Kang, Y James; Cohen, Richard A; Colucci, Wilson S

2014-05-15

204

Hipertrofia ventricular esquerda do atleta: resposta adaptativa fisiológica do coração / Left ventricular hypertrophy of athletes: adaptative physiologic response of the heart  

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: Portuguese Abstract in portuguese OBJETIVO: Verificar se a hipertrofia ventricular esquerda (HVE) de atletas competitivos de resistência (maratonistas) representa processo adaptativo, puramente fisiológico, ou se pode envolver aspectos patológicos em suas características anatômicas e funcionais. MÉTODOS: De novembro de 1999 a dezemb [...] ro de 2000, foram separados consecutivamente de 30 maratonistas em atividade esportiva plena, idade inferior a 50 anos, com HVE, previamente documentada, e sem cardiopatia subjacente. Foram submetidos aos exames: clínico, eletrocardiograma, ecodopplercardiograma, e teste ergométrico (TE). Quinze foram sorteados para realizar, também, teste ergoespirométrico e ressonância magnética (RM) do coração. RESULTADOS: Nos TE, todos apresentavam boa capacidade física cardiopulmonar, sem evidências de resposta isquêmica ao exercício, sintomas ou arritmias. No ecodopplercardiograma, os valores do diâmetro e espessura diastólica da parede posterior do ventrículo esquerdo (VE), do septo interventricular, massa do VE e diâmetro do átrio esquerdo, foram significativamente maiores que os do grupo de não atletas, com idades e medidas antropométricas semelhantes. A média da massa do VE dos atletas indexada à superfície corpórea (126 g/m2) foi significativamente maior que a do grupo controle (70 g/m2) (p Abstract in english OBJECTIVE: To verify whether left ventricular hypertrophy (LVH) of elite competition athletes (marathoners) represents a purely physiological, adaptative process, or it may involve pathological aspects in its anatomical and functional characteristics. METHODS: From November 1999 to December 2000, co [...] nsecutive samples from 30 under 50-year-old marathoners in full sportive activity, with previously documented LVH and absence of cardiopathy were selected. They were submitted to clinical exams, electrocardiogram, color Doppler echocardiogram and exercise treadmill test (ETT). Fifteen were assorted to be also submitted to ergoespirometric test and heart magnetic resonance imaging (MRI). RESULTS: In ETT, all of them showed good physical pulmonary capacity, with no evidences of ischemic response to exercise, symptoms or arrhythmias. In Doppler echocardiogram, values of diameter and diastolic thickness of LV posterior wall, interventricular septum, LV mass and left atrium diameter, were significantly higher when compared to non-athlete control group, with similar ages and anthropometric measurements. The mean of LV mass of athletes indexed to body surface (126 g/m2) was significantly greater than the one in control group (70 g/m2) (p

Nabil, Ghorayeb; Michel, Batlouni; Ibraim M. F, Pinto; Giuseppe S, Dioguardi.

205

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)

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

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

2012-12-01

206

The degree of albuminuria is related to left ventricular hypertrophy in hypertensive diabetics and is associated with abnormal left ventricular filling: a pilot study.  

Science.gov (United States)

The association of albuminuria and left ventricular (LV) hypertrophy (LVH) in diabetics aggravates the prognosis. The authors studied the relation between LVH and the degree of albuminuria in diabetics and investigated the relationship of albuminuria to LV filling. A comparison was made between 30 hypertensive diabetics, 10 of whom had microalbuminuria (MIC) and 20 had macroalbuminuria (MAC), and 18 diabetics who were normotensive and normalbuminuric (NOR). LV mass index (LVMI) and LV ejection fraction (LVEF) were measured during echocardiography. LV filling pattern at rest and at peak standardized isometric exercise (IME) using handgrip was assessed by measuring E/A (peak velocity of the early/atrial filling waves) of the transmitral flow during Doppler and echocardiography. Each patient underwent a stress ECG test. LVMI was higher in MAC (132.3 +/- 55.4) than in MIC (115.6 +/- 32.5) or NOR (90.0 +/- 31.8) (p<0.01). There were more patients in MAC with LVH (n = 13) and abnormal filling (n = 9 at rest and 16 with IME) than in MIC (LVH = 5, abnormal filling = 1 at rest and 10 during IME) or NOR (LVH = 3, abnormal filling = 1 at rest and 9 during IME) (p < 0.02). LVMI was not related to LVEF. Although blood pressure was not different between MAC and MIC groups, it was significantly higher than in the NOR group. This study suggests that a high degree of albuminuria in hypertensive diabetics is associated with greater value for LVMI and an increased incidence of LVH independent of blood pressure level or systolic LV function. LVH is associated with abnormal LV filling. The degree of albuminuria may predict LVMI and LVH, which are associated with abnormal LV filling. This association of abnormal LV filling with albuminuria in hypertensive diabetic patients may account for their high risk of cardiovascular events. PMID:14666955

Salmasi, Abdul-Majeed; Jepson, Ewart; Grenfell, Ana; Kirollos, Camelia; Dancy, Mark

2003-01-01

207

Differential inhibition by the Rho kinase inhibitor Y-27632 of the increases in contractility and Ca2+ transients induced by endothelin-1 in rabbit ventricular myocytes.  

Science.gov (United States)

The role of Rho kinase activation in the regulation of cardiac contractility and Ca(2+) signaling remains unclear, whereas its role in smooth muscle regulation has been well documented. To study the potential role of Rho kinase in the regulation of cardiac contractility and Ca(2+) transients induced by endothelin-1 (ET-1) and isoproterenol, we used the Rho kinase inhibitor Y-27632 in rabbit ventricular myocardium and myocytes loaded with indo-1/AM. Y-27632 (3-30 microM) inhibited significantly the baseline contractility and Ca(2+) transients. Furthermore, Y-27632 suppressed the increase in contractility and Ca(2+) transients induced by ET-1 in a concentration-dependent manner, when it was used in a concentration at which it did not affect the effects of isoproterenol via beta-adrenoceptors. In the presence of Y-27632, ET-1 increased cell shortening in the absence of an increase in Ca(2+) transients. This is an indication that the increase in myofilament Ca(2+) sensitivity induced by ET-1 is less susceptible to the inhibitory action of Y-27632. These findings imply that the Rho kinase activation may partially contribute to the ET-1-induced regulation of contractility, primarily due to an ET-1-induced increase in Ca(2+) transients in rabbit ventricular myocardium. PMID:15900512

Chu, Li; Norota, Ikuo; Endoh, Masao

2005-03-01

208

Associations of Left Ventricular Hypertrophy with Prevalent and Incident Valve Calcification: The Multi-Ethnic Study of Atherosclerosis  

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Objectives We aim to evaluate the relationship between percent of predicted left ventricular mass (%PredLVM) and valve calcification in the Multi-Ethnic Study of Atherosclerosis (MESA). Background Cardiac valve calcification has been associated with left ventricular hypertrophy (LVH), which portends cardiovascular events. However, this relationship and its mediators are poorly understood. Methods MESA is a longitudinal cohort study of men and women aged 45-84 years without clinical cardiovascular disease in whom serial cardiac magnetic resonance and computed tomography imaging were performed. The relationships between baseline %PredLVM and the prevalence, severity, and incidence of aortic valve (AVC) and mitral annulus calcification (MAC) were determined by regression modeling. Results Prevalent AVC was observed in 630 and MAC in 442 of 5,042 subjects (median 55.9 and 71.1 Agatston units, respectively). After adjustment for age, gender, body mass index, ethnicity, socioeconomic status, physical activity, diabetes, cholesterol levels, blood pressure, smoking, kidney function, serum lipids, and antihypertensive and statin medications, %PredLVM was associated with prevalent AVC (OR=1.18 per SD increase in %PredLVM [95%CI 1.08 – 1.30]; p=0.0004) and MAC (OR=1.18 [95%CI 1.06 – 1.32]; p=0.002). Similarly, %PredLVM was associated with increased severity of prevalent AVC (risk difference = 0.26 [95%CI 0.15 – 0.38]; pAVC and 198 (5%) MAC. %PredLVM was associated with incident AVC (OR=1.24 [95%CI 1.04 – 1.47]; p=0.02) and MAC (OR=1.18 [1.01-1.40]; p=0.04). Further adjustment for inflammatory markers and coronary artery calcification did not attenuate these associations. Specifically, concentric LVH most strongly predicted incident valve calcification. Conclusions Within the MESA cohort, LVH was associated with prevalence, severity, and incidence of valve calcification independent of hypertension and other identified confounders. PMID:22897991

Elmariah, Sammy; Delaney, Joseph A. C.; Bluemke, David A; Budoff, Matthew J.; O’Brien, Kevin D.; Fuster, Valentin; Kronmal, Richard A.; Halperin, Jonathan L.

2012-01-01

209

Prevalence and long-term predictors of left ventricular hypertrophy, late hypertension, and hypertensive response to exercise after successful aortic coarctation repair.  

Science.gov (United States)

Controversial data exist about the long-term results of aortic coarctation (AC) repair. This study explored the prevalence and predictors of left ventricular (LV) hypertrophy, late hypertension, and hypertensive response to exercise in 48 subjects (age, 15.1 ± 9.7 years) currently followed in the authors' tertiary care hospital after successful AC repair. Data on medical history, clinical examination, rest and exercise echocardiography, and ambulatory blood pressure monitoring were collected. The time from AC repair to follow-up evaluation was 12.9 ± 9.2 years. The prevalence of LV hypertrophy ranged from 23 to 38 %, based on the criteria used to identify LV hypertrophy, and that of concentric geometry was 17 %. One sixth of the patients without residual hypertension experienced late-onset hypertension. One fourth of those who remained normotensive without medication showed a hypertensive response to exercise. Age at AC repair was the strongest independent predictor of LV hypertrophy, defined using indexation either for body surface area (odds ratio [OR], 1.03; p = 0.0090) or for height(2.7) (OR 1.02; p = 0.029), and it was the only predictor of late hypertension (OR 1.06; p = 0.0023) and hypertensive response to exercise (OR 1.09; p = 0.029). The risk of LV hypertrophy was 25 % for repair at the age of 3.4 years but rose to 50 and 75 % for repair at the ages of 5.9 and 8.4 years, respectively. Similar increases were found for the risk of late-onset hypertension and hypertensive response to exercise. A considerable risk of LV hypertrophy, late hypertension, and hypertensive response to exercise exists after successful AC repair. Older age at intervention is the most important predictor of these complications. PMID:23052661

Bocelli, Arianna; Favilli, Silvia; Pollini, Iva; Bini, Roberta Margherita; Ballo, Piercarlo; Chiappa, Enrico; Zuppiroli, Alfredo

2013-03-01

210

Effect of left ventricular hypertrophy on long-term survival of patients with coronary artery disease following percutaneous coronary intervention  

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Full Text Available The impact of left ventricular hypertrophy (LVH on survival among patients with established coronary artery disease (CAD is not well understood. We sought to evaluate the effect of LVH on the survival of patients with CAD following percutaneous coronary intervention (PCI. Three hospitals in New York City contributed prospectively defined data on 4284 consecutive patients undergoing PCI. All-cause mortality at a mean follow-up of three years was the primary endpoint. LVH was present in 383 patients (8.9%. LVH patients had a greater prevalence of hypertension (88% vs. 68%, p<0.001, vascular disease (21% vs. 6.6%, p=0.001, and prior heart failure (10% vs. 5.5%, p<0.001. LVH patients presented less often with one-vessel disease (38% vs. 50%, p=0.040 and more often with two- (34% vs. 29%, p=0.014 or three-vessel (22% vs. 18%, p=0.044 disease. Ejection fractions and angiographic success were similar in both groups. In-hospital mortality did not differ between groups. At three-year follow-up, the survival rate for patients with LVH was 86% vs. 91% in patients without LVH (log-rank p=0.001. However, after adjustment for differences in baseline characteristics using Cox proportional hazards analysis, LVH was found not to be an independent predictor of mortality (hazard ratio, 0.93; 95% confidence interval, 0.68-1.28; p=0.67. We conclude that LVH at the time of PCI is not independently associated with an increase in the hazard of death at three years.

David L. Brown

2009-04-01

211

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

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

Luminita L??ea

2010-06-01

212

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

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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.)

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

213

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

International Nuclear Information System (INIS)

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

214

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

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

Chae, S. C.; Chun, K. A.; Park, H. S.; Lee, J.; Jun, J. E.; Park, W. H.; Lee, K. B. [College of Medicine, Kyungpook National Univ., Taegu (Korea, Republic of)

1997-07-01

215

Prediction of carotid plaques in hypertensive patients by risk factors, left ventricular hypertrophy, and epicardial adipose tissue thickness.  

Science.gov (United States)

Hypertension and other risk factors (RFs) predispose to carotid plaques (CPs). An association between left ventricular hypertrophy (LVH) or epicardial adipose tissue (EAT) and CPs has also been reported. The aim of the study was to evaluate whether the assessment of LVH and EAT thickness, beyond RFs, would be of additive value in predicting CPs in hypertensive subjects. We studied 548 hypertensive patients aged ? 50 years without carotid bruit. LVH and CPs were evaluated and defined according to standard criteria. EAT was measured by echocardiography above the free wall of the right ventricle at end diastole. The presence of LVH and EAT thickness above the median value (3.9 mm) together significantly increased prevalence of CPs in subjects with 0-1 risk factor, but not in those with ? 2 RFs who showed high prevalence of CPs independently of LVH and/or EAT. Receiver operating characteristic curve analysis showed that the addition of LVH and higher EAT thickness together significantly improved prediction of CPs in patients with 0-1 risk factor. Indeed, the area under the curve improved from 0.63 (0.56-0.69) to 0.73 (0.67-0.79), which was significantly higher (p < 0.05). In patients with ? 2 RFs, the addition of LVH and EAT did not significantly improve prediction of CPs. This study shows that the presence of LVH and higher EAT thickness together improves prediction of CPs in hypertensive patients with 0-1 risk factor and that those with ? 2 RFs show high prevalence of CPs independently of LVH and/or EAT. PMID:22427251

Pierdomenico, Sante D; Mancini, Mariantonietta; Cuccurullo, Chiara; Guglielmi, Maria D; Pierdomenico, Anna M; Di Nicola, Marta; Di Carlo, Silvio; Lapenna, Domenico; Cuccurullo, Franco

2013-05-01

216

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)

Full Text Available SciELO Brazil | Language: Portuguese Abstract in portuguese 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.

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.

217

Hipertrofia ventricular esquerda do atleta: resposta adaptativa fisiológica do coração Left ventricular hypertrophy of athletes: adaptative physiologic response of the heart  

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Full Text Available OBJETIVO: Verificar se a hipertrofia ventricular esquerda (HVE de atletas competitivos de resistência (maratonistas representa processo adaptativo, puramente fisiológico, ou se pode envolver aspectos patológicos em suas características anatômicas e funcionais. MÉTODOS: De novembro de 1999 a dezembro de 2000, foram separados consecutivamente de 30 maratonistas em atividade esportiva plena, idade inferior a 50 anos, com HVE, previamente documentada, e sem cardiopatia subjacente. Foram submetidos aos exames: clínico, eletrocardiograma, ecodopplercardiograma, e teste ergométrico (TE. Quinze foram sorteados para realizar, também, teste ergoespirométrico e ressonância magnética (RM do coração. RESULTADOS: Nos TE, todos apresentavam boa capacidade física cardiopulmonar, sem evidências de resposta isquêmica ao exercício, sintomas ou arritmias. No ecodopplercardiograma, os valores do diâmetro e espessura diastólica da parede posterior do ventrículo esquerdo (VE, do septo interventricular, massa do VE e diâmetro do átrio esquerdo, foram significativamente maiores que os do grupo de não atletas, com idades e medidas antropométricas semelhantes. A média da massa do VE dos atletas indexada à superfície corpórea (126 g/m2 foi significativamente maior que a do grupo controle (70 g/m2 (pOBJECTIVE: To verify whether left ventricular hypertrophy (LVH of elite competition athletes (marathoners represents a purely physiological, adaptative process, or it may involve pathological aspects in its anatomical and functional characteristics. METHODS: From November 1999 to December 2000, consecutive samples from 30 under 50-year-old marathoners in full sportive activity, with previously documented LVH and absence of cardiopathy were selected. They were submitted to clinical exams, electrocardiogram, color Doppler echocardiogram and exercise treadmill test (ETT. Fifteen were assorted to be also submitted to ergoespirometric test and heart magnetic resonance imaging (MRI. RESULTS: In ETT, all of them showed good physical pulmonary capacity, with no evidences of ischemic response to exercise, symptoms or arrhythmias. In Doppler echocardiogram, values of diameter and diastolic thickness of LV posterior wall, interventricular septum, LV mass and left atrium diameter, were significantly higher when compared to non-athlete control group, with similar ages and anthropometric measurements. The mean of LV mass of athletes indexed to body surface (126 g/m2 was significantly greater than the one in control group (70 g/m2 (p<0.001. Magnetic resonance imaging (MRI showed there was not impairment of contractile strength or LV performance, and values of end diastolic volume, end systolic volume and EF within limits of normality. On the other hand, average ventricular parietal mass, 162.93±17.90 g, and LV parietal thickness, 13.67±2.13 mm, at the end of diastole in athlete group, differed significantly from control group: 110±14.2 g (p=0.0001 and 8±0.9 mm, respectively (p=0.0001. The same happened to the thickness at the end of systole, which was 18.87±3.40 mm (control group: 10±1.80 mm, p=0.0001. CONCLUSION: Results allowed for concluding that LVH in marathoners in full sportive activity period, assessed by non-invasive methods, represents an adaptative response to intensive and prolonged physical training, with purely physiological characteristics.

Nabil Ghorayeb

2005-09-01

218

The novel regulations of MEF2A, CAMKK2, CALM3, and TNNI3 in ventricular hypertrophy induced by arsenic exposure in rats.  

Science.gov (United States)

Arsenic is a ubiquitous toxic compound that exists naturally in many sources such as soil, groundwater, and food; in which vast majority forms are arsenite (As(3+)) or arsenate (As(5+)). The mechanism of arsenic detoxification in humans still remains obscured. Epidemiologic studies documented that arsenic pollution caused black foot disease, cardiovascular diseases (hypertension, hypotension, cardiomyopathy), bladder cancer and skin cancer in many countries in which Taiwan is considered as high arsenic exposure country for long time ago. However, the effects of arsenic to cardiac functions still lacked of investigation while some studies mainly focus on inflammatory and cancer mechanisms. In the present study, we found cardiac hypertrophy signaling may be the most significant pathway for up regulated genes in arsenic exposed patients via bioinformatics approach. To verify our bioinformatics prediction, arsenic was fed orally to rats at different concentration based on previous studies in Taiwan. Using hemodynamic method as the main tool to measure the changes in blood pressure, left ventricular pressure and left ventricular contractility index, the findings suggest that highly exposure to arsenic lead to hypertension; elevated left ventricular diastolic pressure and alteration in cardiac contractility which are supposed to be the interaction between arsenic and cardiac nerves activity via the changing in calcium homeostasis. Collectively, based on our real-time PCR and western blot data strongly suggest that calcium homeostasis may also go through MEF2A, TNNI3, CAMKK2, CALM3 and cardiac hypertrophy relative signaling pathway. PMID:25089838

Phan, Nam Nhut; Wang, Chih-Yang; Lin, Yen-Chang

2014-10-01

219

Ca(2+) influx through L-type Ca(2+) channels and transient receptor potential channels activates pathological hypertrophy signaling.  

Science.gov (United States)

Common cardiovascular diseases such as hypertension and myocardial infarction require that myocytes develop greater than normal force to maintain cardiac pump function. This requires increases in [Ca(2+)]. These diseases induce cardiac hypertrophy and increases in [Ca(2+)] are known to be an essential proximal signal for activation of hypertrophic genes. However, the source of "hypertrophic" [Ca(2+)] is not known and is the topic of this study. The role of Ca(2+) influx through L-type Ca(2+) channels (LTCC), T-type Ca(2+) channels (TTCC) and transient receptor potential (TRP) channels on the activation of calcineurin (Cn)-nuclear factor of activated T cells (NFAT) signaling and myocyte hypertrophy was studied. Neonatal rat ventricular myocytes (NRVMs) and adult feline ventricular myocytes (AFVMs) were infected with an adenovirus containing NFAT-GFP, to determine factors that could induce NFAT nuclear translocation. Four millimolar Ca(2+) or pacing induced NFAT nuclear translocation. This effect was blocked by Cn inhibitors. In NRVMs Nifedipine (Nif, LTCC antagonist) blocked high Ca(2+)-induced NFAT nuclear translocation while SKF-96365 (TRP channel antagonist) and Nickel (Ni, TTCC antagonist) were less effective. The relative potency of these antagonists against Ca(2+) induced NFAT nuclear translocation (Nif>SKF-96365>Ni) was similar to their effects on Ca(2+) transients and the LTCC current. Infection of NRVM with viruses containing TRP channels also activated NFAT-GFP nuclear translocation and caused myocyte hypertrophy. TRP effects were reduced by SKF-96365, but were more effectively antagonized by Nif. These experiments suggest that Ca(2+) influx through LTCCs is the primary source of Ca(2+) to activate Cn-NFAT signaling in NRVMs and AFVMs. While TRP channels cause hypertrophy, they appear to do so through a mechanism involving Ca(2+) entry via LTCCs. PMID:22921230

Gao, Hui; Wang, Fang; Wang, Wei; Makarewich, Catherine A; Zhang, Hongyu; Kubo, Hajime; Berretta, Remus M; Barr, Larry A; Molkentin, Jeffery D; Houser, Steven R

2012-11-01

220

Left ventricular hypertrophy in hypertensive adolescents: analysis of risk by 2004 National High Blood Pressure Education Program Working Group staging criteria.  

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The National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents recently recommended staging hypertension (HTN) in children and adolescents based on blood pressure severity. The use of blood pressure staging and its corresponding therapeutic approach was examined in this pooled analysis assessing the risk for end-organ damage, specifically left ventricular hypertrophy among hypertensive adolescents stratified by working group criteria. Newly diagnosed hypertensive adolescents and normotensive control subjects similar in age, race/ethnicity, gender, and body mass index completed casual and 24-hour ambulatory blood pressure measurements, M-mode echocardiography, and fasting serum laboratories. Hypertensive subjects had higher insulin and cholesterol but similar glucose levels as compared with control subjects. Among subjects with stage 1 HTN by casual blood pressure, 34% had white-coat HTN as opposed to 15% of stage 2 hypertensive subjects. Of the subjects with normal casual measurements, 20% had HTN by ambulatory monitoring. Subjects with stage 2 HTN by casual measurement alone (odds ratio: 4.13; 95% CI: 1.04 to 16.48) and after 24-hour ambulatory confirmation (odds ratio: 7.23; 95% CI: 1.28 to 40.68) had increased odds for left ventricular hypertrophy. In addition, the risk for left ventricular hypertrophy was similar for subjects with masked and confirmed stage 1 HTN, whereas subjects with white-coat HTN had a risk comparable to normotensive subjects. Thus, recommendations that adolescents with stage 2 HTN by casual measurements alone receive medication initially along with therapeutic lifestyle counseling are reasonable, though ambulatory blood pressure monitoring remains a valuable tool for evaluating children with stage 2 HTN, because >10% have white-coat HTN. PMID:17592068

McNiece, Karen L; Gupta-Malhotra, Monesha; Samuels, Joshua; Bell, Cynthia; Garcia, Kathleen; Poffenbarger, Timothy; Sorof, Jonathan M; Portman, Ronald J

2007-08-01

 
 
 
 
221

Autocrine A2 in the T-system of ventricular myocytes creates transmural gradients in ion transport: a mechanism to match contraction with load?  

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Transmural heterogeneities in Na/K pump current (IP), transient outward K(+)-current (Ito), and Ca(2+)-current (ICaL) play an important role in regulating electrical and contractile activities in the ventricular myocardium. Prior studies indicated angiotensin II (A2) may determine the transmural gradient in Ito, but the effects of A2 on IP and ICaL were unknown. In this study, myocytes were isolated from five muscle layers between epicardium and endocardium. We found a monotonic gradient in both Ip and Ito, with the lowest currents in ENDO. When AT1Rs were inhibited, EPI currents were unaffected, but ENDO currents increased, suggesting endogenous extracellular A2 inhibits both currents in ENDO. IP- and Ito-inhibition by A2 yielded essentially the same K0.5 values, so they may both be regulated by the same mechanism. A2/AT1R-mediated inhibition of IP or Ito or stimulation of ICaL persisted for hours in isolated myocytes, suggesting continuous autocrine secretion of A2 into a restricted diffusion compartment, like the T-system. Detubulation brought EPI IP to its low ENDO value and eliminated A2 sensitivity, so the T-system lumen may indeed be the restricted diffusion compartment. These studies showed that 33-50% of IP, 57-65% of Ito, and a significant fraction of ICaL reside in T-tubule membranes where they are transmurally regulated by autocrine secretion of A2 into the T-system lumen and activation of AT1Rs. Increased AT1R activation regulates each of these currents in a direction expected to increase contractility. Endogenous A2 activation of AT1Rs increases monotonically from EPI to ENDO in a manner similar to reported increases in passive tension when the ventricular chamber fills with blood. We therefore hypothesize load is the signal that regulates A2-activation of AT1Rs, which create a contractile gradient that matches the gradient in load. PMID:24896115

Gao, Junyuan; Sun, Xiurong; Potapova, Irina A; Cohen, Ira S; Mathias, Richard T; Kim, Jeremy H

2014-06-01

222

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

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

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

2014-09-01

223

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.

224

Transplantation-induced atrophy of normal and hypertrophic rat hearts: effect on cardiac myocytes and capillaries.  

Science.gov (United States)

Changes in tissue structure of hearts undergoing atrophy following heterotopic isotransplantation were studied. Both normal and hypertrophic hearts were used, originating from male and female rats. Aortic constriction produced in newborn rats, resulted in an 86 and 155% increase of left ventricular mass in male and female rats, respectively. On day 50, control and experimental animals were killed, half of their hearts were analysed morphometrically, while remaining hearts were transplanted into the abdominal cavity of recipient rats. Transplantation resulted in significantly decreased cardiac mass in control hearts (approximately 50% decrease compared to values at transplantation), and an even more pronounced decrease in hypertrophic hearts. Cardiac hypertrophy was characterized by significant decreases in capillary and myocyte densities. While myocyte density simply reflected changes in cell size, evidence for additional capillary growth was found (the aggregate length of capillaries per left ventricle increased by 57-88%). Cardiac atrophy resulted in increased capillary density, despite evidence of some capillary involution in transplanted hearts (aggregate length of capillaries decreased by 30-35% and 52-64% for transplants of normal and of hypertrophic hearts, respectively). Myocyte density increased due to a proportional decrease in the size of cardiac myocytes. In transplanted hearts, an increasing number of myocytes containing nuclei located close to the nearest capillary, suggests that changes in myocyte size are not symmetrical. The present study demonstrated the remarkable plasticity of the heart in neonatal animals; they were capable of large increases and decreases in cardiac mass within a few weeks, with more pronounced changes in female rats. These changes were accompanied by changes in myocardial structure, indicating some capillary growth in cardiac hypertrophy, and involution of coronary capillaries in cardiac atrophy. PMID:9152865

Rakusan, K; Heron, M I; Kolar, F; Korecky, B

1997-03-01

225

Model study of ATP and ADP buffering, transport of Ca(2+) and Mg(2+), and regulation of ion pumps in ventricular myocyte  

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We extended the model of the ventricular myocyte by Winslow et al. (Circ. Res 1999, 84:571-586) by incorporating equations for Ca(2+) and Mg(2+) buffering and transport by ATP and ADP and equations for MgATP regulation of ion transporters (Na(+)-K(+) pump, sarcolemmal and sarcoplasmic Ca(2+) pumps). The results indicate that, under normal conditions, Ca(2+) binding by low-affinity ATP and diffusion of CaATP may affect the amplitude and time course of intracellular Ca(2+) signals. The model also suggests that a fall in ATP/ADP ratio significantly reduces sarcoplasmic Ca(2+) content, increases diastolic Ca(2+), lowers systolic Ca(2+), increases Ca(2+) influx through L-type channels, and decreases the efficiency of the Na(+)/Ca(2+) exchanger in extruding Ca(2+) during periodic voltage-clamp stimulation. The analysis suggests that the most important reason for these changes during metabolic inhibition is the down-regulation of the sarcoplasmic Ca(2+)-ATPase pump by reduced diastolic MgATP levels. High Ca(2+) concentrations developed near the membrane might have a greater influence on Mg(2+), ATP, and ADP concentrations than that of the lower Ca(2+) concentrations in the bulk myoplasm. The model predictions are in general agreement with experimental observations measured under normal and pathological conditions.

Michailova, A.; McCulloch, A.

2001-01-01

226

[Structural-geometric changes of the myocardium and the state of central hemodynamics during left ventricular remodeling after myocardial infarction].  

Science.gov (United States)

Intergroup analysis of parameters of central hemodynamics in the process of increase of left ventricular dimensions has shown that changes of pump function of the heart correspond to stages of left ventricular remodeling after myocardial infarction. Decreases of ejection fraction and cardiac output occur in patients with postinfarction aneurysm. At various stages of pathogenesis of remodeling multiple factors facilitate adaptation to novel conditions of functioning. They include structural reorganization of ventricular wall, hypertrophy of myocytes, and augmentation of muscular mass without wall thickening (exocentric hypertrophy). At other equal conditions characteristic for the patients studied starting point of maladaptational left ventricular remodeling and consequent development of cardiac failure can be value of left ventricular diastolic volume 182.7+/-3.28 ml. This volume according to data obtained by the authors represents a threshold over which 'rescue' for the body Staring law is not able to maintain adequate stroke volume and cardiac output. PMID:12891282

Belov, Iu V; Varaksin, V A

2003-01-01

227

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)

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.

Larstorp, Anne Cecilie K; Ariansen, Inger

2012-01-01

228

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

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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...

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

2000-01-01

229

Angiotensin II-induced cardiomyocyte hypertrophy and cardiac fibrosis in stroke-prone spontaneously hypertensive rats.  

Science.gov (United States)

Angiotensin-converting enzyme inhibitors (ACEIs) cause regression of hypertensive left ventricular hypertrophy (LVH) by reducing angiotensin II, increasing bradykinin, or both. The mechanisms of these cardioprotective effects remain controversial. The aims of this study were to determine whether the cardioprotective effects of ACEIs are mediated by reducing angiotensin II and whether ACEIs ameliorate the morphologic, physiologic, and biochemical changes in the hearts of stroke-prone spontaneously hypertensive rats (SHRSPs). Male SHRSPs were treated with hydralazine, captopril, or candesartan, an angiotensin II type 1 receptor (AT1R) antagonist, from age 12 to 24 weeks. We measured systolic blood pressure (SBP), left ventricular weight (LVW), left ventricular (LV) myocyte cross-sectional area (myocyte size), LV Interstitial collagen volume fraction (ICVF), perivascular collagen area/luminal area ratio (PVCA/LA), the medial area to luminal area ratio (MA/LA), the relative amount of V3 myosin heavy chain (MHCV3), and coronary reserve maximum (coronary flow max/ventricular weight (CFmax/VW)). These parameters were compared with those of untreated SHRSPs and Wistar-Kyoto rats (WKYs). SHRSPs exhibited decreased coronary reserve and LVH with an increase in myocyte size, PVCA/LA, MA/LA, and MHCV3 at 12 weeks of age. In addition to these changes, 24-week-old SHRSPs showed an increase in ICVF. The LVW, coronary reserve, myocyte size, PVCA/LA, ICVF, and MHCV3 of SHRSPs treated with captopril or candesartan all approached control values. In contrast, hydralazine decreased only ICVF. These results suggest that ACEIs regress LVH and normalize coronary reserve by modulating the effects of angiotensin II via AT1R on the induction of cardiomyocyte hypertrophy, perivascular fibrosis, and medial thickening of intramyocardial coronary arteries in SHRSPs. We concluded that these effects, in addition to the reduction of SBP, are important in causing the regression of LVH. PMID:10779052

Ikeda, Y; Nakamura, T; Takano, H; Kimura, H; Obata, J E; Takeda, S; Hata, A; Shido, K; Mochizuki, S; Yoshida, Y

2000-04-01

230

Effects of Huoxue Qianyang Formula on expressions of proto-oncogenes c-fos and c-myc in spontaneous hypertensive rats with ventricular hypertrophy  

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Full Text Available Objective: To explore the possible mechanism of Huoxue Qianyang Formula (HXQYF, a compound traditional Chinese herbal medicine, in reversing the left ventricular hypertrophy (LVH of spontaneous hypertensive rats (SHRs by analyzing the expressions of mRNAs and proteins of proto-oncogenes c-fos and c-myc in left ventricular muscle.Methods: The experimental study was carried out in SHRs, the sex- and age-matched Wistar-Kyoto (WKY rats were served as normal control (n=5, normal saline 10 ml/kg daily. Twenty-five SHRs were randomly divided into five groups: untreated group (n=5, normal saline 10 ml/kg daily, high-dose HXQYF-treated group (n=5, 0.84 g/ml HXQYF, 10 ml/kg daily, medium-dose HXQYF-treated group (n=5, 0.42 g/ml HXQYF, 10 ml/kg daily, low-dose HXQYF-treated group (n=5, 0.21 g/ml HXQYF, 10 ml/kg daily and cilazapril-treated group (n=5, 1 mg/ml cilazapril, 10 ml/kg daily. The drugs were intragastrically administered once daily for 14 weeks. The expressions of mRNAs and proteins of proto-oncogenes c-fos and c-myc in left ventricular muscle were detected separately by in situ hybridization histochemical method and immunohistochemical method.Results: Compared with the normal control group, the expressions of mRNAs and proteins of proto-oncogenes c-fos and c-myc in left ventricular muscle were significantly increased in untreated group (P<0.01. After treatment, the expressions of c-fos and c-myc mRNAs in left ventricular muscle in HXQYF-treated groups were significantly down-regulated as compared with those of the untreated group (P<0.05. The expressions of c-myc protein were also significantly decreased in high- and medium-dose HXQYF-treated groups as compared with the untreated group (P<0.05, but it had no significant effects in protein expression of c-fos in the three HXQYF-treated groups.Conclusion: HXQYF can inhibit the expression of c-myc in ventricular hypertrophy tissue, which may be the mechanism in treating LVH of hypertention.

De-yu FU

2008-04-01

231

The cardiac ryanodine receptor luminal Ca2+ sensor governs Ca2+ waves, ventricular tachyarrhythmias and cardiac hypertrophy in calsequestrin-null mice.  

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CASQ2 (cardiac calsequestrin) is commonly believed to serve as the SR (sarcoplasmic reticulum) luminal Ca2+ sensor. Ablation of CASQ2 promotes SCWs (spontaneous Ca2+ waves) and CPVT (catecholaminergic polymorphic ventricular tachycardia) upon stress but not at rest. How SCWs and CPVT are triggered by stress in the absence of the CASQ2-based luminal Ca2+ sensor is an important unresolved question. In the present study, we assessed the role of the newly identified RyR2 (ryanodine receptor 2)-resident luminal Ca2+ sensor in determining SCW propensity, CPVT susceptibility and cardiac hypertrophy in Casq2-KO (knockout) mice. We crossbred Casq2-KO mice with RyR2 mutant (E4872Q+/-) mice, which lack RyR2-resident SR luminal Ca2+ sensing, to generate animals with both deficiencies. Casq2+/- and Casq2-/- mice showed stress-induced VTs (ventricular tachyarrhythmias), whereas Casq2+/-/E4872Q+/- and Casq2-/-/E4872Q+/- mice displayed little or no stress-induced VTs. Confocal Ca2+ imaging revealed that Casq2-/- hearts frequently exhibited SCWs after extracellular Ca2+ elevation or adrenergic stimulation, whereas Casq2-/-/E4872Q+/- hearts had few or no SCWs under the same conditions. Cardiac hypertrophy developed and CPVT susceptibility increased with age in Casq2-/- mice, but not in Casq2-/-/E4872Q+/- mice. However, the amplitudes and dynamics of voltage-induced Ca2+ transients in Casq2-/- and Casq2-/-/E4872Q+/- hearts were not significantly different. Our results indicate that SCWs, CPVT and hypertrophy in Casq2-null cardiac muscle are governed by the RyR2-resident luminal Ca2+ sensor. This implies that defects in CASQ2-based lumi-nal Ca2+ sensing can be overridden by the RyR2-resident luminal Ca2+ sensor. This makes this RyR2-resident sensor a promising molecular target for the treatment of Ca2+-mediated arrhythmias. PMID:24758151

Zhang, Jingqun; Chen, Biyi; Zhong, Xiaowei; Mi, Tao; Guo, Ang; Zhou, Qiang; Tan, Zhen; Wu, Guogen; Chen, Alexander W; Fill, Michael; Song, Long-Sheng; Chen, S R Wayne

2014-07-01

232

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

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

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

2014-09-01

233

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

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The purpose of this study was to identify and explain changes in ventricular and cellular function that contribute to aging-associated cardiovascular disease in aging F344 rats. Three groups of female F344 rats, aged 6, 18, and 22 mo, were studied. Echocardiographic measurements in isoflurane-anesthetized animals showed an increase in peak left ventricular torsion between the 6- and the 18-mo-old groups that was partially reversed in the 22-mo-old animals (P 75 cells for each of the nine age-region groups). The decay time of the Ca2+ transient and the time required for 50% length relaxation both increased with age but not uniformly across the three regions (P 50% reduction in troponin I phosphoprotein content in 22-mo-old epicardium relative to the other regions. These data suggest that between 18 and 22 mo of age (before the onset of heart failure), F344 rats display epicardial-specific myofilament-level modifications that 1) break from the progression observed between 6 and 18 mo and 2) coincide with aberrant patterns of cardiac torsion. PMID:23792678

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

2013-01-01

234

PROGRESSIVE REGRESSION OF LEFT VENTRICULAR HYPERTROPHY TWO YEARS AFTER BARIATRIC SURGERY: AN UNEXPECTED DISSOCIATION WITH THE BODY MASS INDEX  

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Background Obesity is a systemic disorder associated with an increase in left ventricular mass and premature death and disability from cardiovascular disease. Although bariatric surgery reverses many of the hormonal and hemodynamic derangements, the long-term collective effects on body composition and left ventricular mass have not been considered before. Hypothesis The decline in fat mass and lean mass after weight loss surgery is associated with a decline in left ventricular mass. Methods Fifteen severely obese women (mean body mass index or BMI: 46.7 ± 1.7 kg/m2) with medically controlled hypertension underwent bariatric surgery. Left ventricular mass and plasma markers of systemic metabolism, together with BMI, waist and hip circumferences, body composition (fat mass and lean mass), and resting energy expenditure (REE) were measured at 0, 3, 9, 12 and 24 months. Results Left ventricular mass continued to decline linearly over the entire period of observation, while rates of weight-loss, loss of lean mass, loss of fat mass, and REE all plateaued at 9 months (p<0.001 for all). Parameters of systemic metabolism normalized by 9 months, and showed no further change at 24 months after surgery. Conclusions Even though parameters of obesity, including BMI and body composition, plateau, the benefits of bariatric surgery on systemic metabolism and left ventricular mass are sustained. We propose that the progressive decline of left ventricular mass after weight loss surgery is regulated by neurohumoral factors, and may contribute to improved long-term survival. PMID:20569762

Algahim, Mohamed F.; Lux, Thomas R.; Leichman, Joshua G.; Boyer, Anthony F.; Miller, Charles C.; Laing, Susan T.; Wilson, Erik B.; Scarborough, Terry; Yu, Sherman; Snyder, Brad; Wolin-Riklin, Carol; Kyle, Ursula G.; Taegtmeyer, Heinrich

2010-01-01

235

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  

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Full Text Available SciELO Cuba | Language: Spanish Abstract in spanish 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.

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

2013-09-01

236

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

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

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

237

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

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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.

Bassani R.A.

2003-01-01

238

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  

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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.

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

239

Effect of Glycemic Control on the Progress of Left Ventricular Hypertrophy and Diastolic Dysfunction in Children with Type I Diabetes Mellitus  

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Full Text Available The present research evaluated the progression of left ventricular structural and functional changes in children and adolescent patients with type I DM and the effect of glycemic control on these changes. A Prospective, case-controlled, observational study was carried out in tertiary referral hospital in Holly Makkah-KSA including 135 young patients with type I DM recruited from the endocrinology clinic and were followed up in the hospital cardiac center unit. Patients were divided into 2 groups: group composed of 46 patients with type I DM and left ventricular hypertrophy (LVH+ve group compared to another group, composed of 89 patients with type I DM but had a normal left ventricular echocardiographic parameters (LVH -ve group. All the studied patients were subjected to full history taking, clinical and cardiac examination. Electrocardiogram, laboratory tests for glycosylated hemoglobin, lipid profile, albuminuria and careful ecocardiographic examination were done. All patients were followed up and participated in a program for glycemic control. Echocardiographic follow-up was done thoroughly again for patients who had left ventricular hypertrophy (LVH after two years. Our results showed that echocardiographic parameters after 2 years follow up showed statistically significant difference regarding cardiac structural and functional parameters in favor for the patients in group who achieved glycemic control. Also comparing echocardiographic parameters of those patients who achieved glycemic control to their baseline results showed that mean value of interventricular septal dimension (IVSd decreased from 1.12cm to 1.03 (p = 0.04, posterior wall dimension (PWd decreased from 1.07-0.97 (p = 0.05 however diastolic dysfunction represented by isovolumic relaxation time (IVRT and E/A did not show a statistically significant change. Patients who did not achieve glycemic control showed worsening of their echocardiographic parameters: IVSd increased significantly (p = 0.01, E/A ratio showed a significant decrease (p = 0.006 and IVRT significantly increased (p = 0.04. We concluded that good glycemic control in diabetic patients could improve some structural parameters of the heart while failure to achieve glycemic control leads to deterioration in functional and structural parameters of the heart. Follow up and early detection of myocardial structural and functional changes in young patients with type I DM contribute to better knowledge of diabetic cardiomyopathy and may help to prevent the natural progression of the disease.

Inas Abdul-Sattar Saad

2007-01-01

240

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

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

Daniel, Piskorz; Alicia, Tommasi.

2011-03-01

 
 
 
 
241

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

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Background: Electrocardiogram (ECG) is a cost effective tool to evaluate left ventricular hypertrophy (LVH). However, its reliability is often questionable when compared to the gold standard - echocardiography.The validation of ECG as a tool to diagnose LVH would benefit centres that lack access to echocardiography. Aim: (1) To assess the efficacy of ECG criteria to screen for left ventricular hypertrophy in comparison to echocardiography. (2) To determine whether ECG can be used as a screening tool for LVH in rural primary health centres. Materials and Methods: Fifty hypertensive patients admitted to a tertiary level hospital fulfilling the inclusion and the exclusion criteria, were evaluated for LVH using ECG and echocardiography. Romhilt-Estes and Sokolow-Lyon criteria were applied to all subjects and their efficiency in detecting LVH was measured using Kappa statistics in comparison to echocardiography. Results: Among the 50 patients, 23 had LVH by echocardiography. In comparison to echocardiography, Romhilt-Estes and Sokolow-Lyon criteria were specific for LVH (96.3%, 88.9% respectively), but were poorly sensitive (43.5%, 43.5%). Combining both the criteria, raised the sensitivity to 60.9% and specificity to 85.2%. Kappa statistical analysis showed moderate to fair agreement of the Romhilt-Estes criteria with echocardiography. Both criteria had high positive predictive values (90.9%, 76.9%). Conclusion: Both Romhilt-Estes and Sokolow-Lyon ECG criteria are poor screening tools due to low sensitivity. But during routine screening of hypertensive patients with ECG alone, if any patient is positive by Romhilt-Estes criteria or both criteria, it would certainly warrant echocardiographic evaluation. As echocardiography cannot be recommended to screen every patient with hypertension in developing countries, initial evaluation using ECG can certainly help in selecting those who require echocardiography. PMID:24783082

Pinto, Jostol; George, Peter; Hegde, Narasimha

2014-01-01

242

Cardiac-specific Deletion of LKB1 Leads to Hypertrophy and Dysfunction  

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LKB1 encodes a serine/threonine kinase, which functions upstream of the AMP-activated protein kinase (AMPK) superfamily. To clarify the role of LKB1 in heart, we generated and characterized cardiac myocyte-specific LKB1 knock-out (KO) mice using ?-myosin heavy chain-Cre deletor strain. LKB1-KO mice displayed biatrial enlargement with atrial fibrillation and cardiac dysfunction at 4 weeks of age. Left ventricular hypertrophy was observed in LKB1-KO mice at 12 weeks but not 4 weeks of age. Col...

Ikeda, Yasumasa; Sato, Kaori; Pimentel, David R.; Sam, Flora; Shaw, Reuben J.; Dyck, Jason R. B.; Walsh, Kenneth

2009-01-01

243

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

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

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.

244

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

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

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

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

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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.

Paulo Ginefra

2003-07-01

246

The Role of SUMO-1 in Cardiac Oxidative Stress and Hypertrophy  

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Abstract Aims: Small ubiquitin-like modifier type 1 (SUMO-1) has been shown to play a critical role in the dysfunction of the cardiac isoform of sarcoplasmic reticulum calcium ATPase (SERCA2a) pump in the setting of heart failure. In cardiac hypertrophy, the role of SUMO-1 has not been defined and our study's goals were to examine the effects of modulating SUMO-1 on the hypertrophic response both in vitro and in vivo and to examine whether oxidative stress (during cardiac hypertrophy) is abrogated by SUMO-1 gene transfer. Results: In mice undergoing transverse aortic constriction (TAC), SUMO-1 levels increased slightly during the compensated stage of hypertrophy and then dropped sharply during the transition to heart failure. In isolated cardiomyocytes, SUMO-1 gene transfer inhibited the hypertrophic response in the presence of phenylephrine. Adeno-associated vector type 9 (AAV9) gene transfer of SUMO-1 prevented the heart from undergoing hypertrophy after TAC and prevented the development of left ventricular dysfunction. Furthermore, SUMO-1 gene transfer blocked the negative effects of H2O2 on SERCA2a activity in cardiac myocytes, while in vivo indices of oxidative stress were decreased by SUMO-1 in cardiac hypertrophy and heart failure. Innovation and Conclusion: The results of this study indicate that post-translational modifications of SERCA2a caused by the toxic environment of the hypertrophied and failing myocardium can be prevented by SUMO-1. Antioxid. Redox Signal. 21, 1986–2001. PMID:24893265

Lee, Ahyoung; Jeong, Dongtak; Mitsuyama, Shinichi; Oh, Jae Gyun; Liang, Lifan; Ikeda, Yoshiyuki; Sadoshima, Junichi

2014-01-01

247

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

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

De Luca Alessio

2009-10-01

248

The role of the Na(+)-Ca2+ exchanger in the rate-dependent increase in contraction in guinea-pig ventricular myocytes.  

Science.gov (United States)

1. The intracellular sodium activity (alpha Na1), contraction and membrane current were recorded simultaneously in voltage-clamped guinea-pig ventricular myocytes. 2. Increasing the frequency (from 0.5 to 3 Hz) of voltage clamp pulses to 0 mV from a holding potential of -80 mV led to an increase in both alpha Na1 and contraction. The rate-dependent increase in contraction was reduced by 25 microM tetrodotoxin (TTX) and abolished with a holding potential of -40 mV. There was no rate-dependent rise in alpha Na1 with a holding potential of -40 mV. These results suggest an important role for alpha Na1 and in particular Na+ influx via Na+ channels during rate-dependent changes in contraction. 3. After an increase in frequency from 0.5 to 3 Hz, membrane current at the end of voltage clamp pulses became progressively more outward and the tail current upon at repolarization became progressively more inward compared with those recorded at 0.5 Hz. TTX reduced the magnitude of both the outward and inward rate-dependent shifts of current. 4. The addition of extracellular CsCl blocked the inward rectifier potassium current (IK.1) and the delayed rectifier (IK), but did not change the rate-dependent shift in current. 5. The difference between current-voltage relationships at 0.5 and 3 Hz showed that the rate-dependent outward shift of current at the end of voltage clamp pulses was small at potentials negative to -20 mV, was larger at more positive potentials and was reduced by TTX at most potentials. The TTX-sensitive component reversed at -47 mV. 6. These results are consistent with a net increase in outward Na(+)-Ca2+ exchange current during a voltage clamp pulse in response to the rise of alpha Na1. The increase in outward current (resulting from either enhanced Ca2+ influx or reduced Ca2+ efflux) will augment the Ca2+ load of the cell and contribute to the rate-dependent increase in contraction. PMID:7738848

Harrison, S M; Boyett, M R

1995-01-01

249

Hyperglycemia and nocturnal systolic blood pressure are associatedwith left ventricular hypertrophy and diastolic dysfunction in hypertensive diabetic patients  

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Abstract Background The aim of this study was to determine if hypertensive type 2 diabetic patients, when compared to patients with essential hypertension have an increased left ventricular mass index (LVMI) and a worse diastolic function, and if this fact would be related to 24-h pressoric levels changes. Methods Ninety-one hypertensive patients with type 2 diabetes mellitus (DM) (group-1 [G1]), 59 essential hypertensive patients (group-2 [G2]) and 26 healthy c...

Felício João S; Pacheco Juliana T; Ferreira Sandra R; Plavnik Frida; Moisés Valdir A.; Kohlmann Oswaldo; Ribeiro Artur B; Zanella Maria T

2006-01-01

250

Comparative echocardiographic features of conditions presenting with symptomatic pulmonary hypertension and right ventricular hypertrophy in early infancy.  

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Echocardiographic dimensions in infants (less than 2 months) with pulmonary hypertension, associated with coarctation of the aorta in 21, total anomalous venous return in 10, and left-to-right shunts in 14 were compared with 10 infants with respiratory distress syndrome, seven with transient tachypnoea of the newborn, 20 normal children, and with each other. Distinguishing features of total anomalous pulmonary venous return were very significantly lower left atrial and left ventricular dimens...

Patel, R.; Rowland, D.; Bloom, K. R.; Williams, C. M.; Rowe, R. D.

1980-01-01

251

KMUP-1 inhibits hypertension-induced left ventricular hypertrophy through regulation of nitric oxide synthases, ERK1/2, and calcineurin.  

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Hypertension can induce left ventricular hypertrophy (LVH), and the nitric oxide (NO) pathway plays an important role in the pathogenesis of cardiac hypertrophy. This study aimed to examine whether KMUP-1, a novel xanthine-based derivative, could inhibit LVH in spontaneously hypertensive rats (SHRs) and to investigate potential mechanisms underlying its antihypertrophic effects. Two groups of animals with chronic or subacute LVH were treated. In the chronic LVH group, KMUP-1 (10 or 30 mg/kg/d orally) was administered for 28 days to both normotensive rats and SHRs. In the subacute LVH group, KMUP-1 (0.5 mg/kg/d intraperitoneally) or sildenafil (0.7 mg/kg/d intraperitoneally) was administered for 10 days with or without co-treatment with the nitric oxide synthase (NOS) inhibitor N-omega-nitro-l-arginine (L-NNA; 20 mg/L orally). After treatment, the effects of KMUP-1 or sildenafil on hypertension, cardiac hypertrophy, survival, expression of the NO/soluble guanylate cyclase (sGC)/protein kinase G (NO/sGC/PKG) pathway in the aorta andleft ventricle, and calcineurin A/extracellular signal-regulated kinase 1/2 (ERK1/2) signaling in the left ventricle were examined. In the chronic LVH group, the SHRs developed hypertension with LVH over the 28 days. KMUP-1 attenuated the hypertension and LVH, increased survival rate, enhanced endothelial NOS/cyclic guanosine monophosphate/PKG (eNOS/cGMP/PKG) and decreased inducible NOS (iNOS) expression in the aorta and left ventricle of the SHRs. In the subacute LVH group, both KMUP-1 and sildenafil administered for 10 days attenuated the LVH in SHRs, with enhanced eNOS/cGMP/PKG and suppressed iNOS/calcineurin A/ERK1/2 expression in the left ventricle. In addition, both KMUP-1 and sildenafil attenuated L-NNA-induced LVH. KMUP-1 inhibition of hypertension-induced LVH with associated upregulation of eNOS, downregulation of iNOS in both the aorta and left ventricle, and attenuation of calcineurin A and ERK1/2 signaling in the left ventricle. PMID:23140764

Yeh, Jwu-Lai; Liu, Chung-Pin; Hsu, Jong-Hau; Tseng, Ching-Jiunn; Wu, Ping-Ju; Wang, Yi-Ya; Wu, Jiunn-Ren; Chen, Ing-Jun

2012-11-01

252

Evolution of ventricular myocyte electrophysiology  

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The relative importance of regulatory versus structural evolution for the evolution of different biological systems is a subject of controversy. The primacy of regulatory evolution in the diversification of morphological traits has been promoted by many evolutionary developmental biologists. For physiological traits, however, the role of regulatory evolution has received less attention or has been considered to be relatively unimportant. To address this issue for electrophysiological systems,...

Rosati, Barbara; Dong, Min; Cheng, Lan; Liou, Shian-ren; Yan, Qinghong; Park, Ji Young; Shiang, Elaine; Sanguinetti, Michael; Wang, Hong-sheng; Mckinnon, David

2008-01-01

253

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

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

Pedro Ferreira de Albuquerque

2012-01-01

254

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

Scientific Electronic Library Online (English)

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

Pedro Ferreira de, Albuquerque; Pedro Henrique Oliveira de, Albuquerque; Gustavo Oliveira de, Albuquerque; Denise Maria, Servantes; Saskya Meneses de, Carvalho; Japy Angelini, Oliveira Filho.

255

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

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The relation between maximum systolic blood pressure (BP) during exercise and left ventricular (LV) mass is controversial. Physical activity also induces LV mass increase. The objective was to assess the relation between BP response to exercise and LV mass in normotensive men, taking into account physical activity practice. A cross-sectional study was performed. Three hundred eighteen healthy normotensive men, aged between 20 and 60 years, participated in this study. The Minnesota questionnaire was used to assess physical activity practice. An echocardiogram and a maximum exercise test were performed. LV mass was calculated and indexed to body surface area. LV hypertrophy was defined as a ventricular mass index > or =134 g/m2. BP was measured at the moment of maximum effort. Hypertensive response was considered when BP was > or =210 mm Hg. In the multiple linear regression model, maximum systolic BP was associated with LV mass index and correlation coefficient was 0.27 (SE 0.07). Physical activity practice and age were also associated with LV mass. An association between hypertensive response to exercise and LV hypertrophy was observed (odds ratio 3.16). Thus, BP response to exercise is associated with LV mass and men with systolic BP response > or =210 mm Hg present a 3-times higher risk of LV hypertrophy than those not reaching this limit. Physical activity practice is related to LV mass, but not to LV hypertrophy. PMID:10532505

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

1999-10-15

256

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

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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.

Ye.I. Tarlovskaya

2010-01-01

257

Functional contribution of ?1D-adrenoceptors in the renal vasculature of left ventricular hypertrophy induced with isoprenaline and caffeine in Wistar-Kyoto rats.  

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This study investigated the role of ?1D-adrenoceptor in the modulation of renal haemodynamics in rats with left ventricular hypertrophy (LVH). LVH was established in Wistar-Kyoto (WKY) rats with isoprenaline (5.0 mg·(kg body mass)(-1), by subcutaneous injection every 72 h) and caffeine (62 mg·L(-1) in drinking water, daily for 14 days). Renal vasoconstrictor responses were measured for noradrenaline (NA), phenylephrine (PE), and methoxamine (ME) before and immediately after low or high dose intrarenal infusions of BMY?7378, a selective ?1D-adrenoceptor blocker. The rats with LVH had higher mean arterial blood pressure and circulating NA levels, but lower renal cortical blood perfusion compared with the control group (all P group, the magnitude of the renal vasoconstrictor response to ME was blunted, but not the response to NA or PE (P group (LVH vs. C, 38% vs. 50%). The magnitude of the drop in the vasoconstrictor responses to NA, PE, and ME in the presence of a higher dose of BMY?7378 was significantly greater in the LVH group compared with the control group (LVH vs. C, 45% vs. 25% for NA, 52% vs. 33% for PE, 66% vs. 53% for ME, all P < 0.05). These findings indicate an impaired renal vasoconstrictor response to adrenergic agonists during LVH. In addition, the ?1D-adrenoceptor subtype plays a key role in the modulation of vascular responses in this diseased state. PMID:25403946

Ahmad, Ashfaq; Sattar, Munavvar A; Rathore, Hassaan A; Abdulla, Mohammad H; Khan, Safia A; Abdullah, Nor A; Kaur, Gurjeet; Johns, Edward J

2014-12-01

258

Bone morphogenetic protein-4 induces upregulation of Cav3.1 Ca(2+) channels in HL-1 atrial myocytes.  

Science.gov (United States)

Cardiac T-type Ca(2+) channels are reexpressed in atrial and ventricular myocytes under various pathological conditions such as post-myocardial infarction, hypertrophy, and heart failure, but relatively little is known about the mechanisms. Our previous study found that bone morphogenetic protein-4 (BMP4) was reexpressed in pathological cardiac hypertrophy models and BMP4-mediated cardiomyocyte hypertrophy. We hypothesized that BMP4 could upregulate cardiac T-type Ca(2+) channels in HL-1 atrial myocytes. The T-type Ca(2+) currents were recorded by using the patch-clamp technique, and the expressions of Cav3.1 and Cav3.2 were measured by real-time PCR method in HL-1 cells. BMP4 and Cav3.1 mRNA expressions increased in the left atrium from the pressure overload-induced hypertrophy of mice hearts. BMP4 treatment for 48 h induced increase of Cav3.1 but not Cav3.2 mRNA expression in HL-1 cells, and the increase was inhibited by BMP4 inhibitor noggin. Acute treatment with BMP4 did not affect T-type Ca(2+) currents, but chronic treatment (48 h) significantly increased the amplitude of T-type Ca(2+) currents in HL-1 cells. Chronic treatment with BMP4 induced upregulation of NADPH oxidase-4 (NOX4), increase of reactive oxygen species (ROS) level, and activation of mitogen-activated protein kinase (MAPK)-activated protein kinases c-jun N-terminal kinases (JNK) and p38. BMP4-induced upregulation of Cav3.1 mRNA was inhibited by NADPH oxidase inhibitor apocynin, the radical scavenger tempol, JNK inhibitor SP600125, and p38 inhibitor SB203580. In conclusion, BMP4 induces upregulation of Cav3.1 Ca(2+) channels and T-type Ca(2+) currents in HL-1 atrial myocytes through ROS/MAPK pathways. PMID:24510064

Hu, Chao-Wei; Li, Qi; Zhang, Ying; Li, Yu-Hong; Jiang, Hong-Chao; Liu, Ming-Yu; Li, Shan-Liang; Han, Wei; Dong, De-Li

2014-11-01

259

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)

Full Text Available SciELO Brazil | Language: Portuguese Abstract in portuguese 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.

José Antonio Dias, Garcia; Erika Kristina, Incerpi.

2008-06-01

260

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  

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Full Text Available SciELO Brazil | Language: Portuguese Abstract in portuguese 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

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

 
 
 
 
261

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  

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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.

Alessandra Ferri Casini

2006-02-01

262

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)

Full Text Available SciELO Brazil | Language: Portuguese Abstract in portuguese 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

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

2006-02-01

263

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

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Exercise ECG and myocardial single-photon emission tomography (SPET) are fundamental in the non-invasive evaluation of patients suspected of having coronary artery disease (CAD). The purpose of the present study was to investigate the influence of physiological left ventricular hypertrophy (LVH) on myocardial sestamibi SPET in healthy young and old athletes. Eighteen young male elite athletes (ten rowers, five power/weight lifters and three triathletes) and 14 well-trained elderly rowers were studied. All underwent a bicycle test as part of a 2-day sestamibi SPET protocol. Attenuation correction was not performed. The studies were evaluated visually and quantitatively analysed by the CEqual program with its reference files and with a file from a local non-athletic age-matched population. Echocardiographic LVH was an inclusion criterion in the young athletes. Exercise ECG was normal in all subjects. In at least three of the young athletes a reversible defect was observed by visual analysis. On quantitative analysis one-third of the young athletes had ``significant`` (>10 pixels) defects compared with both the local reference base and the CEqual reference population. Nearly all defects were found in the anterior or inferior wall. The remaining subjects, including all old rowers, had normal SPET findings. Anterior and inferior wall defects are so common in healthy athletes with physiological LVH that the specificity of myocardial SPET, in contrast to exercise ECG, seems to be too low for evaluation of chest pain in this group. The mechanism of anterior and inferior defects may be related to hot spots (papillary muscles?) in the lateral wall. The specificity of SPET is maintained in athletes without LVH. (orig.) With 1 fig., 26 tabs., 22 refs.

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

1998-09-01

264

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

International Nuclear Information System (INIS)

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

265

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

Science.gov (United States)

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

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

2014-09-01

266

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  

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Full Text Available SciELO Brazil | Language: Portuguese Abstract in portuguese 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.

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

1997-12-01

267

Adenoviral expression of calmodulin antisense reduces hypertrophy in cultured cardiomyocytes.  

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Sustained myocardial hypertrophy is associated with an increased risk of sudden death and progression to heart failure. Multiple signal pathways are involved in cardiac hypertrophy and understanding their interaction may point to new therapeutic targets. In this work, we tested the hypothesis that adenovirus-mediated calmodulin (CaM) antisense expression will reduce the intracellular availability of CaM and inhibit the hypertrophic response. Three recombinant adenoviruses were constructed: AdASCaM, containing the AntiSense sequence of CaM and the enhanced green fluorescent protein (GFP) coding sequence; AdCaM, containing the coding sequence of CaM and the GFP sequence; and the AdGFP, containing the GFP coding sequence. Neonatal rat ventricular cardiomyocytes were infected with AdASCaM, AdCaM, or AdGFP and stimulated with phenylephrine (PE, 50 microM) or angiotensin II (AngII, 10 microM) for 48 h and cell surface area measured with planimetry. After PE treatment, the surface areas of cardiomyocytes infected with AdASCaM or AdGFP were 411 +/- 174.3 micro(2) and 832.6 +/- 372.3 micro(2), respectively (P < 0.01). After AngII treatment, the surface areas of cardiomyocytes infected with AdASCaM or AdGFP were 441.5 +/- 149.2 micro(2) and 726 +/- 328.3 micro(2), respectively (P < 0.01). Adenoviral expression of the CaM antisense (AdASCaM) significantly inhibited PE or AngII-induced cardiomyocyte hypertrophy. Cardiomyocytes infected with the AdCaM showed increased area when compared with those infected with the AdGFP. These results suggest that adenovirus-mediated changes in CaM expression may alter hypertrophy in cardiac myocytes. PMID:17437495

Arruda, Ligia H; Cestari, Idágene A; Leirner, Adolfo A; Cestari, Ismar N

2007-04-01

268

Length and PKA Dependence of Force Generation and Loaded Shortening in Porcine Cardiac Myocytes  

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In healthy hearts, ventricular ejection is determined by three myofibrillar properties; force, force development rate, and rate of loaded shortening (i.e., power). The sarcomere length and PKA dependence of these mechanical properties were measured in porcine cardiac myocytes. Permeabilized myocytes were prepared from left ventricular free walls and myocyte preparations were calcium activated to yield ~50% maximal force after which isometric force was measured at varied sarcomere lengths. Por...

Mcdonald, Kerry S.; Hanft, Laurin M.; Domeier, Timothy L.; Emter, Craig A.

2012-01-01

269

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

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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.

Greve, Anders; Boman, Kurt

2012-01-01

270

123I-metaiodobenzylguanidine imaging of the heart in essential hypertension. The effect of left ventricular hypertrophy and performance reserve upon it  

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To study myocardial norepinephrine (NE) activity in essential hypertension (HT) and the effect of left ventricular (LV) hypertrophy and LV performance reserve upon it, myocardial imaging was performed with 123I-metaiodobenzylguanidine (123I-MIBG) and 201Tl at rest in 23 patients with HT and 10 normal subjects. Uptake Ratio (%Uptake of 123I-MIBG in delayed image divided by %Uptake of 201Tl) was calculated as the index of myocardial 123I-MIBG uptake. Reduction of myocardial 123I-MIBG during 3h (WOR) was also calculated. The defect from the Bull's-eye map was quantitatively assessed as Defect Score. Patients were divided into 2 groups according to the LV mass (LVM) by echocardiography. Uptake Ratio was lower in Group I (LVM>l30g/m2, n=16) than that Group II (LVM2, n=7). WOR was accelerated in Group I than Group II. Uptake Ratio and WOR were identical between Group II and normal subjects. The incidence of 123I-MIBG defect and Defect Score were significantly greater in Group I (incidence: 94%, Defect Score: 3.0±1.3) than Group II (incidence: 43%, Defect Score: 1.1±0.6). To study the effect of LV performance reserve, patients were divided into 2 groups according to LV ejection fraction (EF) responses to exercise stress (Ex) obtained by 99mTc blood pool imaging. LVEF increased by Ex in 13 patients (Group A) and decreased or did not change by Ex inand decreased or did not change by Ex in 7 (Group B). Uptake Ratio was significantly smaller and WOR was significantly accelerated in Group B than Group A and normal subjects. The incidence of 123I-MIBG defect and Defect Score were greater in Group B than Group A, with no significant difference. LVM and LVEF response seemed to influence upon myocardial NE kinetics independently. These results suggested that LVM and LV performance reserve influenced upon myocardial NE kinetics in HT patients and quantitative analysis of 123I-MIBG imaging may be helpful for assessing HT prognosis. (J.P.N.)

271

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)

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.

Ariansen, Inger; Reims, Henrik M

2012-01-01

272

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

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The aim of this study was to compare the accuracy of these two imaging modalities in conjunction with dobutamine stress test for the diagnosis of coronary artery disease in hypertensive patients with and without left ventricular hypertrophy. Dobutamine stress echocardiography in conjunction with sestamibi (MIBI) SPET was performed in 84 patients with the diagnosis of systemic hypertension who had been referred for evaluation of myocardial ischaemia. Significant coronary artery disease ({>=}50% luminal diameter stenosis) was detected in 66 patients (79%). The sensitivity, specificity and accuracy of the ischaemic pattern at echocardiography for the diagnosis of coronary artery disease were 73% (CI 63%-82%), 83% (CI 75%-91%) and 75% (CI 66%-84%), those for MIBI were 67% (CI 57%-77%), 83% (CI 75%-91%) and 70% (CI 60%-80%) respectively (P = NS vs echocardiography). Significant stenosis was detected in 123 (49%) of the 252 analysed coronary arteries. The sensitivity, specificity and accuracy of echocardiography for the regional diagnosis of coronary artery disease were 63% (CI 56%-69%), 90% (CI 86%-94%) and 77% (CI 72%-82%). Those for MIBI were 58% (CI 51%-64%), 91% (CI 87%-94%) and 75% (CI 69%-80) respectively (P = NS vs echocardiography). Left ventricular hypertrophy was detected in 59 patients (70%) by echocardiography and did not influence the overall or regional specificity of echocardiography or MIBI SPET.(orig./MG) (orig.) With 2 figs., 4 tabs., 39 refs.

Elhendy, A.; Geleijnse, M.L.; Van Domburg, R.T.; Bax, J.J.; Nierop, P.R.; Beerens, S.A.M.; Mohsen Ibrahim, M.; Roelandt, J.R.T.C. [Thoraxcenter, University Hospital Rotterdam-Dijkzigt, Rotterdam (Netherlands); Valkema, R.; Krenning, E.P. [Department of Nuclear Medicine, University Hospital Rotterdam-Dijkzigt, Rotterdam (Netherlands)

1998-01-01

273

Simvastatin Modulates Remodeling of Kv4.3 Expression in Rat Hypertrophied Cardiomyocytes  

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Full Text Available Objectives: Hypertrophy has been shown to be associated with arrhythmias which can be caused by abnormal remodeling of the Kv4-family of transient potassium channels. Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins have recently been shown to exert pleiotropic protective effects in cardiovascular diseases, including anti-arrhythmias. It is hypothesized that remodeling of Kv4.3 occurs in rat hypertrophied cardiomyocytes and is regulated by simvastatin.Methods: Male Sprague-Dawley rats and neonatal rat ventricular myocytes (NRVMs underwent abdominal aortic banding (AAB for 7 weeks and angiotensin II (AngII treatment, respectively, to induce cardiac hypertrophy. Kv4.3 expression by NRVMs and myocardium (subepicardial and subendocardial in the left ventricle was measured. The transient outward potassium current (Ito of NRVMs was recorded using a whole-cell patch-clamp method.Results: Expression of the Kv4.3 transcript and protein was significantly reduced in myocardium (subepicardial and subendocardial in the left ventricle and in NRVMs. Simvastatin partially prevented the reduction of Kv4.3 expression in NRVMs and subepicardial myocardium but not in the subendocardial myocardium. Hypertrophied NRVMs exhibited a significant reduction in the Ito current and this effect was partially reversed by simvastatin.Conclusions: Simvastatin alleviated the reduction of Kv4.3 expression, Ito currents in hypertrophied NRVMs and alleviated the reduced Kv4.3 expression in subepicardial myocardium from the hypertrophied left ventricle. It can be speculated that among the pleiotropic effects of simvastatin, the anti-arrhythmia effect is partly mediated by its effect on Kv4.3.

Feifei Su, Miaoqian Shi, Zhiqiang Yan, Dongbo Ou, Juntang Li, Zifan Lu, Qiangsun Zheng

2012-01-01

274

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)

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

275

Remodeling of the heart in hypertrophy in animal models with myosin essential light chain mutations  

Directory of Open Access Journals (Sweden)

Full Text Available Cardiac hypertrophy represents one of the most important cardiovascular problems yet the mechanisms responsible for hypertrophic remodeling of the heart are poorly understood. In this report we aimed to explore the molecular pathways leading to two different phenotypes of cardiac hypertrophy in transgenic mice carrying mutations in the human ventricular myosin essential light chain (ELC. Mutation-induced alterations in the heart structure and function were studied in two transgenic (Tg mouse models carrying the A57G (alanine to glycine substitution or lacking the N-terminal 43 amino acid residues (?43 from the ELC sequence. The first model represents an HCM disease as the A57G mutation was shown to cause malignant HCM outcomes in humans. The second mouse model is lacking the region of the ELC that was shown to be important for a direct interaction between the ELC and actin during muscle contraction. Our earlier studies demonstrated that >7 month old Tg-?43 mice developed substantial cardiac hypertrophy with no signs of histopathology or fibrosis. Tg mice did not show abnormal cardiac function compared to Tg-WT expressing the full length human ventricular ELC. Previously reported pathological morphology in Tg-A57G mice included extensive disorganization of myocytes and interstitial fibrosis with no abnormal increase in heart mass observed in >6 month-old animals. In this report we show that strenuous exercise can trigger hypertrophy and pathologic cardiac remodeling in Tg-A57G mice as early as 3 months of age. In contrast, no exercise-induced changes were noted for Tg-?43 hearts and the mice maintained a non-pathological cardiac phenotype. Based on our results, we suggest that exercise-elicited heart remodeling in Tg-A57G mice follows the pathological pathway leading to HCM, while it induces no abnormal response in Tg-?43 mice.

DanutaSzczesna-Cordary

2014-09-01

276

Remodeling of the heart in hypertrophy in animal models with myosin essential light chain mutations  

Science.gov (United States)

Cardiac hypertrophy represents one of the most important cardiovascular problems yet the mechanisms responsible for hypertrophic remodeling of the heart are poorly understood. In this report we aimed to explore the molecular pathways leading to two different phenotypes of cardiac hypertrophy in transgenic mice carrying mutations in the human ventricular myosin essential light chain (ELC). Mutation-induced alterations in the heart structure and function were studied in two transgenic (Tg) mouse models carrying the A57G (alanine to glycine) substitution or lacking the N-terminal 43 amino acid residues (?43) from the ELC sequence. The first model represents an HCM disease as the A57G mutation was shown to cause malignant HCM outcomes in humans. The second mouse model is lacking the region of the ELC that was shown to be important for a direct interaction between the ELC and actin during muscle contraction. Our earlier studies demonstrated that >7 month old Tg-?43 mice developed substantial cardiac hypertrophy with no signs of histopathology or fibrosis. Tg mice did not show abnormal cardiac function compared to Tg-WT expressing the full length human ventricular ELC. Previously reported pathological morphology in Tg-A57G mice included extensive disorganization of myocytes and interstitial fibrosis with no abnormal increase in heart mass observed in >6 month-old animals. In this report we show that strenuous exercise can trigger hypertrophy and pathologic cardiac remodeling in Tg-A57G mice as early as 3 months of age. In contrast, no exercise-induced changes were noted for Tg-?43 hearts and the mice maintained a non-pathological cardiac phenotype. Based on our results, we suggest that exercise-elicited heart remodeling in Tg-A57G mice follows the pathological pathway leading to HCM, while it induces no abnormal response in Tg-?43 mice.

Kazmierczak, Katarzyna; Yuan, Chen-Ching; Liang, Jingsheng; Huang, Wenrui; Rojas, Ana I.; Szczesna-Cordary, Danuta

2014-01-01

277

Local control of mitochondrial membrane potential, permeability transition pore and reactive oxygen species by calcium and calmodulin in rat ventricular myocytes.  

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Calmodulin (CaM) and Ca(2+)/CaM-dependent protein kinase II (CaMKII) play important roles in the development of heart failure. In this study, we evaluated the effects of CaM on mitochondrial membrane potential (DeltaPsi(m)), permeability transition pore (mPTP) and the production of reactive oxygen species (ROS) in permeabilized myocytes; our findings are as follows. (1) CaM depolarized DeltaPsi(m) dose-dependently, but this was prevented by an inhibitor of CaM (W-7) or CaMKII (autocamtide 2-related inhibitory peptide (AIP)). (2) CaM accelerated calcein leakage from mitochondria, indicating the opening of mPTP, however this was prevented by AIP. (3) Cyclosporin A (an inhibitor of the mPTP) inhibited both CaM-induced DeltaPsi(m) depolarization and calcein leakage. (4) CaM increased mitochondrial ROS, which was related to DeltaPsi(m) depolarization and the opening of mPTP. (5) Chelating of cytosolic Ca(2+) by BAPTA, the depletion of SR Ca(2+) by thapsigargin (an inhibitor of SERCA) and the inhibition of mitochondrial Ca(2+) uniporter by Ru360 attenuated the effects of CaM on mitochondrial function. (6) CaM accelerated Ca(2+) extrusion from mitochondria. We conclude that CaM/CaMKII depolarized DeltaPsi(m) and opened mPTP by increasing ROS production, and these effects were strictly regulated by the local increase in cytosolic Ca(2+) concentration, initiated by Ca(2+) releases from the SR. In addition, CaM was involved in the regulation of mitochondrial Ca(2+) homeostasis. PMID:19318235

Odagiri, Keiichi; Katoh, Hideki; Kawashima, Hirotaka; Tanaka, Takamitsu; Ohtani, Hayato; Saotome, Masao; Urushida, Tsuyoshi; Satoh, Hiroshi; Hayashi, Hideharu

2009-06-01

278

3,3?-Diindolylmethane Protects against Cardiac Hypertrophy via 5?-Adenosine Monophosphate-Activated Protein Kinase-?2  

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Purpose 3,3?-Diindolylmethane (DIM) is a natural component of cruciferous plants. It has strong antioxidant and anti-angiogenic effects and promotes the apoptosis of a variety of tumor cells. However, little is known about the critical role of DIM on cardiac hypertrophy. In the present study, we investigated the effects of DIM on cardiac hypertrophy. Methods Multiple molecular techniques such as Western blot analysis, real-time PCR to determine RNA expression levels of hypertrophic, fibrotic and oxidative stress markers, and histological analysis including H&E for histopathology, PSR for collagen deposition, WGA for myocyte cross-sectional area, and immunohistochemical staining for protein expression were used. Results In pre-treatment and reverse experiments, C57/BL6 mouse chow containing 0.05% DIM (dose 100 mg/kg/d DIM) was administered one week prior to surgery or one week after surgery, respectively, and continued for 8 weeks after surgery. In both experiments, DIM reduced to cardiac hypertrophy and fibrosis induced by aortic banding through the activation of 5?-adenosine monophosphate-activated protein kinase-?2 (AMPK?2) and inhibition of mammalian target of the rapamycin (mTOR) signaling pathway. Furthermore, DIM protected against cardiac oxidative stress by regulating expression of estrogen-related receptor-alpha (ERR?) and NRF2 etc. The cardioprotective effects of DIM were ablated in mice lacking functional AMPK?2. Conclusion DIM significantly improves left ventricular function via the activation of AMPK?2 in a murine model of cardiac hypertrophy. PMID:23326427

Zhou, Heng; Bian, Zhou-yan; Dai, Jia; Yuan, Yuan; Zhang, Jie-yu; Zhang, Rui; Zhang, Yan; Wu, Qing-qing; Guo, Hai-peng; Li, Hong-liang; Tang, Qi-zhu

2013-01-01

279

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

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

Huang YP

2014-09-01

280

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)

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

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

 
 
 
 
281

Relación entre hiperinsulinemia, disfunción diastólica e hipertrofia del ventrículo izquierdo en pacientes con hipertensión arterial sistémica / Association of hyperinsulinemia with left ventricular hypertrophy and diastolic dysfunction in patients with hypertension  

Scientific Electronic Library Online (English)

Full Text Available SciELO Chile | Language: Spanish Abstract in spanish [...] Abstract in english Background: Hypertension is the main independent cardiovascular risk factor. However, there are additional factors that induce organic damage. Aim: To assess the association between hyperinsulinemia, ventricular hypertrophy and left ventricular diastolic function. Patients and Methods: Seventy-four [...] patients aged 30 to 65 years, with mild or moderate systemic hypertension, with overweight or mild obesity and normal glucose tolerance curve (GTC), were studied. Serum insulin was measured during GTC. The maximum levels of insulin and glucose were observed 60 minutes after the oral glucose load and they were expressed as rG/1. Patients were stratified in three groups according to their glucose and insulin fasting levels (I0) and post-glucose challenge levels (rG/I): Group 1 (normoinsulinemic patients) I0 2 (2.45+0.4). Group 2 (post-prandial hyperinsulinemic patients) I0 1 (1.34+0.3). Group 3 (persistently hyperinsulinemic patients) I0 >17 mU/mL and

Ernesto Germán, Cardona-Muñoz; David, Cardona-Müller; Sylvia, Totsuka-Sutto; Carlos Martín, Nuño-Guzmán; Sara, Pascoe-González; Marina, Romero-Prado; Alejandra G, Miranda-Díaz.

1125-11-01

282

Relación entre hiperinsulinemia, disfunción diastólica e hipertrofia del ventrículo izquierdo en pacientes con hipertensión arterial sistémica / Association of hyperinsulinemia with left ventricular hypertrophy and diastolic dysfunction in patients with hypertension  

Scientific Electronic Library Online (English)

Full Text Available SciELO Chile | Language: Spanish Abstract in spanish [...] Abstract in english Background: Hypertension is the main independent cardiovascular risk factor. However, there are additional factors that induce organic damage. Aim: To assess the association between hyperinsulinemia, ventricular hypertrophy and left ventricular diastolic function. Patients and Methods: Seventy-four [...] patients aged 30 to 65 years, with mild or moderate systemic hypertension, with overweight or mild obesity and normal glucose tolerance curve (GTC), were studied. Serum insulin was measured during GTC. The maximum levels of insulin and glucose were observed 60 minutes after the oral glucose load and they were expressed as rG/1. Patients were stratified in three groups according to their glucose and insulin fasting levels (I0) and post-glucose challenge levels (rG/I): Group 1 (normoinsulinemic patients) I0 2 (2.45+0.4). Group 2 (post-prandial hyperinsulinemic patients) I0 1 (1.34+0.3). Group 3 (persistently hyperinsulinemic patients) I0 >17 mU/mL and

Ernesto Germán, Cardona-Muñoz; David, Cardona-Müller; Sylvia, Totsuka-Sutto; Carlos Martín, Nuño-Guzmán; Sara, Pascoe-González; Marina, Romero-Prado; Alejandra G, Miranda-Díaz.

283

Let-7 miRNA Profiles Are Associated With the Reversal of Left Ventricular Hypertrophy and Hypertension in Adult Male Offspring From Mothers Undernourished During Pregnancy After Preweaning Growth Hormone Treatment.  

Science.gov (United States)

Maternal undernutrition (UN) is known to cause cardiac hypertrophy, elevated blood pressure, and endothelial dysfunction in adult offspring. Maternal UN may also lead to disturbances in GH regulation in offspring. Because GH plays a key role in cardiac development, we used a model of maternal UN to examine the effects of neonatal GH treatment on cardiac hypertrophy, cardiac micro RNA (miRNA) profiles, and associated gene regulation in adult offspring. Female Sprague-Dawley rats were fed either a standard control diet (CON) or 50% of CON intake throughout pregnancy (UN). From neonatal day 3 until weaning (d 21), CON and UN pups received either saline (S) (CON-S, UN-S) or GH (2.5 ?g/g·d) (CON-GH, UN-GH). Heart structure was determined by hematoxylin and eosin staining, and miRNA was isolated from cardiac tissue and miRNA expression analyzed using Cardiovascular miRNA gene Arrays (SABiosciences Ltd). Maternal UN caused marked increases in cardiac hypertrophy and left ventricular cardiomyocyte area, which were reversed by preweaning GH treatment. Systolic blood pressure was increased in UN-S groups and normalized in UN-GH groups (CON-S 121 ± 2 mmHg, CON-GH 115 ± 3 mm Hg, UN-S 146 ± 3 mmHg, and UN-GH 127 ± 2 mmHg). GH treatment during early development facilitated a reversal of pathological changes in offspring hearts caused by UN during pregnancy. Specific cardiac miRNA profiles were exhibited in response to maternal UN, accompanied by up-regulation of the lethal-7 (LET-7) miRNA family in GH-treated offspring. miRNA target analysis revealed a number of genes associated with inflammation and cardiovascular development, which may be involved in the altered cardiac function of these offspring. Up-regulation of the LET-7 family of miRNAs observed in GH groups may mediate the reversal of cardiac hypertrophy observed in adult offspring males of UN mothers. PMID:25264936

Gray, Clint; Li, Minglan; Patel, Rachna; Reynolds, Clare M; Vickers, Mark H

2014-12-01

284

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)

Full Text Available SciELO Brazil | Language: English Abstract in portuguese 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

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

2012-11-01

285

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

Directory of Open Access Journals (Sweden)

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

Weihong Jiang

2012-11-01

286

Myocardial hypertrophy after pulmonary regurgitation and valve implantation in pigs  

DEFF Research Database (Denmark)

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.

Smith, Julie; Goetze, Jens Peter

2012-01-01

287

The anti-adrenergic effect of adenosine and its blockade by pertussis toxin: a comparative study in myocytes isolated from guinea-pig, rat and failing human hearts.  

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1. In intact ventricular preparation, adenosine has been shown to reduce the beta-adrenoceptor-induced increase in contraction (the anti-adrenergic effect). In the present study we have investigated this effect of adenosine on isolated ventricular myocytes from failing human heart and normal guinea-pig and rat heart. 2. Adenosine in the absence of beta-adrenoceptor-mediated stimulation had no effect on contraction in human and guinea-pig myocytes but produced a variable effect in rat myocytes...

Brown, L. A.; Humphrey, S. M.; Harding, S. E.

1990-01-01

288

Curcumin prevents and reverses murine cardiac hypertrophy.  

Science.gov (United States)

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 cardiac myocytes and fibroblasts as well as two well-established mouse models of cardiac hypertrophy. Curcumin blocked phenylephrin-induced (PE-induced) cardiac hypertrophy in vitro in a dose-dependent manner. Furthermore, curcumin both prevented and reversed mouse cardiac hypertrophy induced by aortic banding (AB) and PE infusion, as assessed by heart weight/BW and lung weight/BW ratios, echocardiographic parameters, and gene expression of hypertrophic markers. Further investigation demonstrated that curcumin abrogated histone acetylation, GATA4 acetylation, and DNA-binding activity through blocking p300-HAT activity. Curcumin also blocked AB-induced inflammation and fibrosis through disrupting p300-HAT-dependent signaling pathways. Our results indicate that curcumin has the potential to protect against cardiac hypertrophy, inflammation, and fibrosis through suppression of p300-HAT activity and downstream GATA4, NF-kappaB, and TGF-beta-Smad signaling pathways. PMID:18292803

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; Maekawa, Yuichiro; Zhang, Liyong; Leask, Andrew; Ghosh, Asish K; Kirshenbaum, Lorrie A; Liu, Peter P

2008-03-01

289

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)

Full Text Available SciELO Cuba | Language: Spanish Abstract in spanish 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

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

290

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

Scientific Electronic Library Online (English)

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

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

2007-10-01

291

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

Science.gov (United States)

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

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

2014-10-01

292

Factors affecting left ventricular remodeling after valve replacement for aortic stenosis. An overview  

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Full Text Available Abstract Although a small percentage of patients with critical aortic stenosis do not develop left ventricle hypertrophy, increased ventricular mass is widely observed in conditions of increased afterload. There is growing epidemiological evidence that hypertrophy is associated with excess cardiac mortality and morbidity not only in patients with arterial hypertension, but also in those undergoing aortic valve replacement. Valve replacement surgery relieves the aortic obstruction and prolongs the life of many patients, but favorable or adverse left ventricular remodeling is affected by a large number of factors whose specific roles are still a subject of debate. Age, gender, hemodynamic factors, prosthetic valve types, myocyte alterations, interstitial structures, blood pressure control and ethnicity can all influence the process of left ventricle mass regression, and myocardial metabolism and coronary artery circulation are also involved in the changes occurring after aortic valve replacement. The aim of this overview is to analyze these factors in the light of our experience, elucidate the important question of prosthesis-patient mismatch by considering the method of effective orifice area, and discuss surgical timings and techniques that can improve the management of patients with aortic valve stenosis and maximize the probability of mass regression.

Mhagna Zen

2006-06-01

293

Irregularly Appearing Early Afterdepolarizations in Cardiac Myocytes: Random Fluctuations or Dynamical Chaos?  

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Irregularly occurring early afterdepolarizations (EADs) in cardiac myocytes are traditionally hypothesized to be caused by random ion channel fluctuations. In this study, we combined 1), patch-clamp experiments in which action potentials were recorded at different pacing cycle lengths from isolated rabbit ventricular myocytes under several experimental conditions inducing EADs, including oxidative stress with hydrogen peroxide, calcium overload with BayK8644, and ionic stress with hypokalemia...

Sato, Daisuke; Xie, Lai-hua; Nguyen, Thao P.; Weiss, James N.; Qu, Zhilin

2010-01-01

294

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)

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

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

2010-08-01

295

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

International Nuclear Information System (INIS)

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

296

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

DEFF Research Database (Denmark)

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 myocytes had unstable depolarized membrane potentials that were sensitive to the holding current. We hypothesized that this is at least partly due to a small slope conductance of Im around the resting membrane potential in atrial myocytes. In accordance with this hypothesis, the slope conductance of Im was about sevenfold smaller in atrial than in ventricular myocytes. Interestingly, ACh increased Im at -120 mV from 4.3 pA/pF to 27 pA/pF with an EC50 of 45 nM in atrial myocytes. Moreover, 3 nM ACh increased the slope conductance of Im fourfold, shifted its reversal potential from -78 ± 3 to -84 ± 3 mV, and stabilized the resting membrane potential at -92 ± 4 mV. ACh also shortened the action potential in both atrial myocytes and tissue, and this effect was antagonized by atropine. When applied alone, atropine prolonged the action potential in atrial tissue but had no effect on membrane potential, action potential, or Im in isolated atrial myocytes. This suggests that ACh-mediated activation of an inwardly rectifying K+ current can modulate the membrane potential in the trout atrial myocytes and stabilize the resting membrane potential. teleost heart; IK,ACh; cholinergic modulation; action potential

Molina, C.E.; Gesser, Hans

2007-01-01

297

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

Scientific Electronic Library Online (English)

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

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

298

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

Scientific Electronic Library Online (English)

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

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

2008-01-01

299

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)

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

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

2001-12-01

300

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)

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

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

 
 
 
 
301

Histopathological study of the papillary muscles and apex cordis of the hypertrophied left ventricle.  

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Hypertrophy of the papillary muscle and apex cordis of the left ventricle was studied histopathologically using 84 hearts obtained at autopsy. The hearts were divided into three groups: a hypertrophy group (heart weight more than 350 g); a borderline group (heart weight between 350 and 300 g) and a control group (heart weight less than 300 g). The size of the papillary muscle increased with increase in heart weight. Derangement of myocyte linings and fibrosis at the papillary muscle base became apparent with hypertrophy. In addition derangement and fibrosis extented from the internal to middle layers of the free wall with progressing hypertrophy. Derangement seemed to precede hypertrophy and fibrosis. A cluster of huge myocyte-like Purkinje's cells were associated with the center of the derangement. At the apex, criss-cross derangement developed from right and left side derangement with increasing hypertrophy. It is speculated that the focal derangement plays an important role in producing hypertrophy in response to mechanical stress with subsequent development of hypertrophy and fibrosis with some asymmetry. PMID:2957524

Wakafuji, S; Shirai, T; Okada, R

1987-05-01

302

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

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

Mehmet Kanada?ý

2003-09-01

303

Alterations in cardiac structure and function in a modified rat model of myocardial hypertrophy.  

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This study was aimed to establish a stable animal model of left ventricular hypertrophy (LVH) to provide theoretical and experimental basis for understanding the development of LVH. The abdominal aorta of male Wistar rats (80-100 g) was constricted to a diameter of 0.55 mm between the branches of the celiac and anterior mesenteric arteries. Echocardiography using a linear phased array probe was performed as well as pathological examination and plasma B-type natriuretic peptide (BNP) measurement at 3, 4 and 6 weeks after abdominal aortic constriction (AAC). The results showed that the acute mortality rate (within 24 h) of this modified rat model was 8%. Animals who underwent AAC demonstrated significantly increased interventricular septal (IVS), LV posterior wall (LVPWd), LV mass index (LVMI), cross-sectional area (CSA) of myocytes, and perivascular fibrosis; the ejection fraction (EF), fractional shortening (FS), and cardiac output (CO) were consistently lower at each time point after AAC. Notably, differences in these parameters between AAC group and sham group were significant by 3 weeks and reached peaks at 4th week. Following AAC, the plasma BNP was gradually elevated compared with the sham group at 3rd and 6th week. It was concluded that this modified AAC model can develop LVH, both stably and safely, by week four post-surgery; echocardiography is able to assess changes in chamber dimensions and systolic properties accurately in rats with LVH. PMID:25318869

Dai, Wen-Jun; Dong, Qi; Chen, Min-Sheng; Zhao, Lu-Ning; Chen, Ai-Lan; Li, Zhen-Ci; Liu, Shi-Ming

2014-10-01

304

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

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Full Text Available FUNDAMENTO: A hipertrofia do ventrículo esquerdo (HVE detectada pela eletrocardiografia é um forte preditor de morbidade e mortalidade cardiovasculares. OBJETIVO: Analisar o desempenho dos critérios de Sokolow-Lyon-Rappaport (SLR e de Cornell, em amostra populacional, em relação ao diagnóstico de HVE à ecocardiografia. MÉTODOS: Entre os 682 participantes da segunda fase do Projeto MONICA-OMS/Vitória, 641 foram avaliados por meio de eletrocardiografia e ecocardiografia. O subgrupo de indivíduos saudáveis (n = 269 foi usado para gerar valores de referência da massa do ventrículo esquerdo (MVE. As sensibilidades e especificidades dos critérios eletrocardiográficos foram determinadas pela curva ROC (receptor-operator characteristics em relação ao diagnóstico de HVE definido pelo critério ecocardiográfico interno (MVE > 48 g/m2,7 e 46 g/m2,7 para homens e mulheres, respectivamente. RESULTADOS: A prevalência de HVE à ecocardiografia foi de 23,7% na amostra global, em que havia 49% de hipertensos. O critério de Cornell apresentou melhor associação com a MVE estimada pela ecocardiografia (r = 0,37; p BACKGROUND: Electrocardiographically-detected left ventricular hypertrophy (LVH is a strong predictor of cardiovascular morbidity and mortality. OBJECTIVE: To assess the performance of the Sokolow-Lyon-Rappaport (SLR and Cornell voltage criteria in a population sample regarding the diagnosis of LVH on echocardiogram (ECHO. METHODS: A total of 641 out of the 682 participants of the second phase of the MONICA-Vitória project were assessed using electrocardiogram and echocardiogram. A subgroup of healthy individuals (n=269 was used to generate reference values of LV mass (LVM. Sensitivities and specificities of the electrocardiographic criteria were determined by the ROC (receptor-operator characteristics curve in relation to the diagnosis of LVH, as defined by the internal echocardiographic criterion (LVM > 48 and 46 g/m2.7 for males and females, respectively. RESULTS: The prevalence of LVH as detected by ECHO was 23.7% in the total sample, in which 49% of the individuals were hypertensive. The Cornell criterion showed a better association with the LVM as estimated by ECHO (r= 0.37, p < 0.01 than the SLR criterion (r= 0.19 as well as a better performance in the analysis of the area under the ROC curve. The new cut-off points for the internally-defined Cornell voltage criterion (2.3 mV for males and 1.9 mV for females showed an acceptable combination of sensitivity (22.5 and 28% for males and females, respectively, with a high specificity (95%. CONLUSION: The classic SLR and Cornell voltage criteria showed a low performance in relation to LVH as detected by the ECHO. However, this accuracy may be improved by using the Cornell voltage criteria defined in the present study.

Sérgio Lamêgo Rodrigues

2008-01-01

305

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

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

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

1990-01-01

306

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

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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.

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

307

Magnesium homeostasis in cardiac myocytes of Mg-deficient rats.  

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To study possible modulation of Mg(2+) transport in low Mg(2+) 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 Mg(2+) concentration ([Mg(2+)]i) of ventricular myocytes was measured with the fluorescent indicator furaptra. Mg(2+) transport rates, rates of Mg(2+) influx and Mg(2+) efflux, were estimated from the rates of change in [Mg(2+)]i during Mg loading/depletion and recovery procedures. In Mg-deficient rats, the serum total Mg concentration (0.29±0.026 mM) was significantly lower than in control rats (0.86±0.072 mM) after 4-6 weeks of Mg deficiency. However, neither total Mg concentration in ventricular tissues nor [Mg(2+)]i of ventricular myocytes was significantly different between Mg-deficient rats and control rats. The rates of Mg(2+) influx and efflux were not significantly different in both groups. In addition, quantitative RT-PCR revealed that Mg deficiency did not substantially change mRNA expression levels of known Mg(2+) channels/transporters (TRPM6, TRPM7, MagT1, SLC41A1 and ACDP2) in heart and kidney tissues. These results suggest that [Mg(2+)]i as well as the total Mg content of cardiac myocytes, was well maintained even under chronic hypomagnesemia without persistent modulation in function and expression of major Mg(2+) channels/transporters in the heart. PMID:24039880

Tashiro, Michiko; Inoue, Hana; Konishi, Masato

2013-01-01

308

Abnormal contractile function due to induction of nitric oxide synthesis in rat cardiac myocytes follows exposure to activated macrophage-conditioned medium.  

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The mechanism by which soluble mediators of immune cell origin depress myocardial contractility, either globally as in systemic sepsis, or regionally in areas of inflammatory myocardial infiltrates, remains unclear. When freshly isolated ventricular myocytes from adult rat hearts were preincubated for at least 24 h in medium conditioned by endotoxin (LPS)-activated rat alveolar macrophages, their subsequent inotropic response to the beta-adrenergic agonist isoproterenol was reduced from 225 +/- 19% to 155 +/- 10% of the baseline amplitude of shortening (mean +/- SEM, P < 0.05). Neither baseline contractile function nor the contractile response to high extracellular calcium were affected. To determine whether an endogenous nitric-oxide (NO)-signaling pathway within ventricular myocytes was responsible for their decreased responsiveness to isoproterenol, the L-arginine analogue L-NMMA was added to the preincubation medium. While L-NMMA did not affect baseline contractile function or the response of control myocytes to isoproterenol, it completely restored the positive inotropic response to isoproterenol in myocytes preincubated in LPS-activated macrophage medium. Release of NO by ventricular myocytes following exposure to activated macrophage medium was detected as an increase in cGMP content in a reporter-cell (RFL-6) bioassay and also as increased nitrite content in myocyte-conditioned medium. Thus, the depressed contractile response of adult rat ventricular myocytes to beta-adrenergic agonists by a 24-h exposure to soluble inflammatory mediators is mediated at least in party by induction of an autocrine NO signaling pathway. Images PMID:8486792

Balligand, J L; Ungureanu, D; Kelly, R A; Kobzik, L; Pimental, D; Michel, T; Smith, T W

1993-01-01

309

Immunolocalization of KATP channel subunits in mouse and rat cardiac myocytes and the coronary vasculature  

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Full Text Available Abstract Background Electrophysiological data suggest that cardiac KATP channels consist of Kir6.2 and SUR2A subunits, but the distribution of these (and other KATP channel subunits is poorly defined. We examined the localization of each of the KATP channel subunits in the mouse and rat heart. Results Immunohistochemistry of cardiac cryosections demonstrate Kir6.1 protein to be expressed in ventricular myocytes, as well as in the smooth muscle and endothelial cells of coronary resistance vessels. Endothelial capillaries also stained positive for Kir6.1 protein. Kir6.2 protein expression was found predominantly in ventricular myocytes and also in endothelial cells, but not in smooth muscle cells. SUR1 subunits are strongly expressed at the sarcolemmal surface of ventricular myocytes (but not in the coronary vasculature, whereas SUR2 protein was found to be localized predominantly in cardiac myocytes and coronary vessels (mostly in smaller vessels. Immunocytochemistry of isolated ventricular myocytes shows co-localization of Kir6.2 and SUR2 proteins in a striated sarcomeric pattern, suggesting t-tubular expression of these proteins. Both Kir6.1 and SUR1 subunits were found to express strongly at the sarcolemma. The role(s of these subunits in cardiomyocytes remain to be defined and may require a reassessment of the molecular nature of ventricular KATP channels. Conclusions Collectively, our data demonstrate unique cellular and subcellular KATP channel subunit expression patterns in the heart. These results suggest distinct roles for KATP channel subunits in diverse cardiac structures.

Nakamura Tomoe Y

2005-01-01

310

Permissive Roles of Phosphatidyl Inositol 3-Kinase and Akt in Skeletal Myocyte Maturation  

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Skeletal muscle differentiation, maturation, and regeneration are regulated by interactions between signaling pathways activated by hormones and growth factors, and intrinsic genetic programs controlled by myogenic transcription factors, including members of the MyoD and myocyte enhancer factor 2 (MEF2) families. Insulin-like growth factors (IGFs) play key roles in muscle development in the embryo, and in the maintenance and hypertrophy of mature muscle in the adult, but the precise signaling...

Wilson, Elizabeth M.; Tureckova, Jolana; Rotwein, Peter

2004-01-01

311

Mechanical stress activates protein kinase cascade of phosphorylation in neonatal rat cardiac myocytes.  

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We have previously shown that stretching cardiac myocytes evokes activation of protein kinase C (PKC), mitogen-activated protein kinases (MAPKs), and 90-kD ribosomal S6 kinase (p90rsk). To clarify the signal transduction pathways from external mechanical stress to nuclear gene expression in stretch-induced cardiac hypertrophy, we have elucidated protein kinase cascade of phosphorylation by examining the time course of activation of MAP kinase kinase kinases (MAPKKKs), MAP kinase kinase (MAPKK...

Yamazaki, T.; Komuro, I.; Kudoh, S.; Zou, Y.; Shiojima, I.; Mizuno, T.; Takano, H.; Hiroi, Y.; Ueki, K.; Tobe, K.

1995-01-01

312

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

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

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

2009-11-01

313

[A case of right ventricular dilated cardiomyopathy, which involved left ventricle].  

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A case of right ventricular dilated cardiomyopathy which also involved the left ventricle was reported. On health screening, a 16-year old woman was pointed out to have multifocal PVC and cardiomegaly. Subsequently, she was admitted to our hospital because of general fatigue. CTR was enlarged to 54.9% on chest X-ray. ECG showed LBBB-type PVC, right axis deviation, low voltage and T wave changes. On UCG, RVdD was dilated to 40 mm and LVdD was 37 mm. There was no finding of abnormality of the tricuspid valve. On cardiac catheterization, there was no shunt disease. Intracardiac pressure was normal. The end-diastolic volume index (ml/m2) of RV and LV was 196.7 and 67.4, respectively. And ejection fraction (%) was 20 and 40. Ventriculography revealed diffuse dilatation of the right ventricle. And lowered contractility existed not only in the right ventricle but also in the anterior and apical segment of the left ventricle. T(1)201 myocardial perfusion imaging showed irregular perfusion defect of the left ventricle. Endomyocardial biopsy revealed marked hypertrophy, partial atrophy, disarrangement of myocyte and interstitial fibrosis of the right ventricle. This case was considered to be right ventricular dilated cardiomyopathy. It seemed to be an intermediate form of dilated cardiomyopathy since it also involved the left ventricle. It was an interesting case to illustrate the spectrum of expression of cardiomyopathy. PMID:2287824

Ishikawa, K; Yokoyama, K; Araki, T; Miura, T; Goto, T; Saito, H

1990-12-01

314

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

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

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

2000-01-01

315

In-treatment reduced left atrial diameter during antihypertensive treatment is associated with reduced new-onset atrial fibrillation in hypertensive patients with left ventricular hypertrophy: The LIFE Study  

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It is unclear whether improvement of left atrial (LA) and ventricular (LV) structure results in reduction in new-onset atrial fibrillation (AF). The aim of the present study was to examine whether changes in-treatment LA diameter were related to changes in risk of new-onset AF.

Wachtell, Kristian; Gerdts, Eva

2010-01-01

316

Muscarinic cholinergic regulation of cardiac myocyte ICa-L is absent in mice with targeted disruption of endothelial nitric oxide synthase  

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Cardiac myocytes have been shown to express constitutively endothelial nitric oxide synthase (eNOS) (nitric oxide synthase 3), the activation of which has been implicated in the regulation of myocyte L-type voltage-sensitive calcium channel current (ICa-L) and myocyte contractile responsiveness to parasympathetic nervous system signaling, although this implication remains controversial. Therefore, we examined the effect of the muscarinic cholinergic agonist carbachol (CCh) on ICa-L and contractile amplitude in isoproterenol (ISO)-prestimulated ventricular myocytes isolated from adult mice, designated eNOSnull mice, with targeted disruption of the eNOS gene. Although both eNOSnull and wild-type (WT) ventricular myocytes exhibited similar increases in ICa-L in response to ISO, there was no measurable suppression of ICa-L by CCh in cells from eNOSnull mice, in contrast to cells from WT mice. These results were reflected in the absence of an effect of CCh on the positive inotropic effect of ISO in eNOSnull myocytes. Also, unlike myocytes from WT animals, eNOSnull myocytes failed to exhibit an increase in cGMP content in response to CCh. Nevertheless, the pharmacologic nitric oxide donors 3-morpholino-sydnonimine and S-nitroso-acetyl-cystein increased cGMP generation and suppressed ISO-augmented ICa-L in eNOSnull cells, suggesting that the signal transduction pathway(s) downstream of eNOS remained intact. Of importance, activation of the acetylcholine-activated K+ channel by CCh was unaffected in atrial and ventricular eNOSnull myocytes. These results confirm the obligatory role of eNOS in coupling muscarinic receptor activation to cGMP-dependent control of ICa-L in cardiac myocytes. PMID:9600997

Han, Xinqiang; Kubota, Isao; Feron, Olivier; Opel, Douglas J.; Arstall, Margaret A.; Zhao, You-Yang; Huang, Paul; Fishman, Mark C.; Michel, Thomas; Kelly, Ralph A.

1998-01-01

317

Thyroid hormones induce unique and potentially beneficial changes in cardiac myocyte shape in hypertensive rats near heart failure.  

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We examined the effects of thyroid hormones (THs) on left ventricular (LV) function and myocyte remodeling in rats with spontaneously hypertensive heart failure (SHHF). SHHF rats were treated with three different TH doses from 20-21 mo of age. In terminal experiments, LV function (as determined by echocardiography and catheterization) and isolated myocyte shape were examined in SHHF rat groups and age-matched Wistar-Furth control animals. Compared with Wistar-Furth rats, the ratio of alpha- to beta-myosin was reduced in untreated SHHF rats. The alpha-to-beta-myosin ratio increased in all TH groups, which suggests a reversal of the fetal gene program. Low-dose TH produced no changes in LV myocyte size or function, but high-dose TH produced signs of hyperthyroidism (e.g., increased heart weight, tachycardia). The chamber diameter-to-wall thickness ratio declined with increasing dose due to reduced chamber diameter and increased wall thickness. This resulted in a 38% reduction in LV systolic wall stress in the middle- and high-dose groups despite sustained hypertension