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  1. Verapamil induced ventricular hypertrophy in conscious dogs.

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    French, W J; Garner, D; Adomian, G E; Averill, W; Laks, M M

    1989-08-01

    Verapamil is used clinically in the treatment of various cardiac diseases including hypertrophic cardiomyopathy. Its long term effects on ventricular mass are not well known. In 11 conscious dogs heart rate, aortic and left ventricular pressures, cardiac output, a methoxamine induced stress ventricular function test and left ventriculography were performed. These variables were measured prior to and following a mean 7.2 month infusion of verapamil at 0.005 or 0.01 mg.kg-1.min-1 using a subcutaneously implanted pump. Resting haemodynamic variables and left ventricular ejection fraction [60(SD 6) v 55(6)%] were unchanged between baseline and chronic verapamil studies, but the slope of the methoxamine induced stress ventricular function test decreased from 3.9(0.8) to 2.1 (1.3). After verapamil was discontinued the mean slope of the stress ventricular function test returned to the baseline 4.0(1.7). Total ventricular weight increased 22% from 176.1(17.5) g.m-2 in controls to 215.6(29.5) g.m-2 (p less than 0.01) in the verapamil animals. The right ventricular weight increased 25% from 46(5.9) to 57.6(9.1) g.m-2 (p less than 0.01); the septum weight increased 26% from 42.5(4.1) to 53.7(7.2) g.m-2 (p less than 0.001); and the left ventricular free wall weight increased 19% from 87.4(9.8) to 103.9(15.7) g.m-2 (p less than 0.01). The increase in ventricular weights was not due to fibrosis or oedema since hydroxyproline contents and wet/dry ratios were not increased. In conclusion, a chronic infusion of verapamil in conscious dogs caused no change in resting haemodynamic variables but produced reversible depression of stress ventricular function and biventricular and septal hypertrophy.

  2. Left Ventricular Hypertrophy

    Science.gov (United States)

    ... need to restrict certain physical activities, such as weightlifting, which may temporarily raise your blood pressure. The ... Accessed April 6, 2015. Chatterjee S, et al. Meta-analysis of left ventricular hypertrophy and sustained arrhythmias. American ...

  3. Ventricular hypertrophy in cardiomyopathy.

    Science.gov (United States)

    Oakley, C

    1971-01-01

    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

  4. Uni- or bi-ventricular hypertrophy and susceptibility to drug-induced torsades de pointes.

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    Panyasing, Yaowalak; Kijtawornrat, Anusak; Del Rio, Carlos; Carnes, Cynthia; Hamlin, Robert L

    2010-01-01

    Cardiac hypertrophy is an independent risk factor for torsades de pointes (TdP), a polymorphic ventricular tachycardia that is often drug-induced, that may evolve into ventricular fibrillation and sudden death. Therefore this study was designed to determine if right (RVH), left (LVH), or biventricular (BVH) hypertrophy increases susceptibility to drug-induced TdP. Rabbits were separated into 4 groups: control or RVH, LVH, BVH (studied 8weeks after banding of one or both great arteries). ECGs were recorded continuously under anesthesia after baseline and after rabbits received escalating doses of torsadogens (dofetilide, clofilium and terfenadine) or non-torsadogens (cilobradine, diltiazem and vehicle). The following parameters were measured [RR, PQ, QRS and QT] or calculated [QTc (F), short term variability of QT interval]. Generally, torsadogenicity for the compounds tested was dofetilide>clofilium>terfenadine, and there was no TdP following cilobradine, diltiazem or vehicle. In general the susceptibility to TdP was RVH>BVH>LVH>control. Rabbits with RVH developed TdP much more prevalently than for those with either LVH or BVH (p<0.05). At the low dose of dofetilide, LVH was actually protective. Rabbits with any form of hypertrophy develop prolongation of QT, QTc and increased QT instability. Rabbits with any form of hypertrophy are more prone to arrhythmia than normals in response to known torsadogens. 2010 Elsevier Inc. All rights reserved.

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

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    Tillmanns Harald H

    2007-02-01

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

  6. Preservation of diastolic function in monocrotaline-induced right ventricular hypertrophy in rats.

    Science.gov (United States)

    Lamberts, Regis R; Caldenhoven, Eric; Lansink, Mirian; Witte, Gerrit; Vaessen, Rob J; St Cyr, John A; Stienen, Ger J M

    2007-09-01

    During ischemic heart diseases and when heart failure progresses depletion of myocardial energy stores occurs. D-Ribose (R) has been shown to improve cardiac function and energy status after ischemia. Folic acid (FA) is an essential cofactor in the formation of adenine nucleotides. Therefore, we assessed whether chronic R-FA administration during the development of hypertrophy resulted in an improved cardiac function and energy status. In Wistar rats (n = 40) compensatory right ventricular (RV) hypertrophy was induced by monocrotaline (30 mg/kg; MCT), whereas saline served as control. Both groups received a daily oral dose of either 150 mg.kg(-1).day(-1) dextrose (placebo) or R-FA (150 and 40 mg.kg(-1).day(-1), respectively). In Langendorff-perfused hearts, RV and left ventricular (LV) pressure development and collagen content as well as total RV adenine nucleotides (TAN), creatine content, and RV and LV collagen content were determined. In the control group R-FA had no effect. In the MCT-placebo group, TAN and creatine content were reduced, RV and LV diastolic pressure-volume relations were steeper, RV systolic pressures were elevated, RV and LV collagen content was increased, and RV-LV diastolic interaction was altered compared with controls. In the MCT-R-FA group, TAN, RV and LV diastolic stiffness, RV and LV collagen content, and RV-LV diastolic interaction were normalized to the values in the control group while creatine content remained depressed and RV systolic function remained elevated. In conclusion, the depression of energy status in compensated hypertrophic myocardium observed was partly prevented by chronic R-FA administration and accompanied by a preservation of diastolic function and collagen deposition.

  7. Electrophysiological characteristics of pressure overload-induced cardiac hypertrophy and its influence on ventricular arrhythmias.

    Science.gov (United States)

    Chen, Xiaowei; Qin, Mu; Jiang, Weifeng; Zhang, Yu; Liu, Xu

    2017-01-01

    To explore the cardiac electrophysiological characteristics of cardiac hypertrophy and its influence on the occurrence of ventricular tachyarrhythmias. Adult C57BL6 mice were randomly divided into a surgery group and a control group. Thoracic aortic constriction was performed on mice in the surgery group, and cardiac anatomical and ultrasonic evaluations were performed to confirm the success of the cardiac hypertrophy model 4 weeks after the operation. Using the Langendorff method of isolated heart perfusion, monophasic action potentials (MAPs) and the effective refractory period (ERP) at different parts of the heart (including the epi- and endo-myocardium of the left and right ventricles) were measured, and the induction rate of ventricular tachyarrhythmias was observed under programmed electrical stimulus (PES) and burst stimulus. Whole-cell patch-clamp was used to obtain the I-V characteristics of voltage-gated potassium channels in cardiomyocytes of different parts of the heart (including the epi- and endo-myocardium of the left and right ventricles) as well as the channels' properties of steady-state inactivation and recovery from inactivation. The ratio of heart weight to body weight and the ratio of left ventricular weight to body weight in the surgery group were significantly higher than those in the control group (P cardiac hypertrophy, and the spatially heterogeneous changes of the channels may increase the occurrence of ventricular arrhythmias that accompany cardiac hypertrophy.

  8. Correlations of Serum Cyclophilin A and Melatonin Concentrations with Hypertension-induced Left Ventricular Hypertrophy.

    Science.gov (United States)

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

    2017-12-14

    Cyclophilin A (CyPA) is an abundantly expressed pro-inflammatory cytokine and a major secreted oxidative stress-induced factor (SOXF). Melatonin is an important chronobiological regulatory molecule that is mainly released from the pineal gland and exerts antioxidant effects by acting as a radical scavenger. Based on accumulating evidence, both CyPA and melatonin play important roles in cardiovascular diseases. However, further investigations are required to determine whether CyPA and melatonin are associated with hypertension-induced left ventricular hypertrophy (LVH). A total of 135 patients with essential hypertension were divided into an LVH (+) group and an LVH (-) group according to Doppler echocardiography results. Clinical data of the two groups were evaluated. High CyPA levels and low melatonin levels are independent risk factors for LVH (p = 0.000). In addition, body mass index (BMI) and systolic blood pressure (SBP) are correlated with the risk of LVH (p = 0.000). However, other factors did not display statistically significant associations (p >0.05). The Pearson correlation and linear regression analyses show that BMI, SBP, and CyPA levels were positively correlated with left ventricular mass (LVM) and the left ventricular mass index (LVMI) (p <0.05), whereas melatonin levels were negatively correlated with LVM and the LVMI (p = 0.000). Furthermore, according to the results of the Pearson correlation analysis, CyPA levels were negatively correlated with melatonin levels (p <0.01) in subjects with LVH. Based on these results, both CyPA and melatonin are closely related to the pathogenesis of LVH. As CyPA was negatively correlated with melatonin in patients with LVH, additional studies are required to determine whether melatonin may partially protect the myocardium by decreasing CyPA levels. Copyright © 2017 IMSS. Published by Elsevier Inc. All rights reserved.

  9. Exercise training does not improve cardiac function in compensated or decompensated left ventricular hypertrophy induced by aortic stenosis.

    Science.gov (United States)

    van Deel, Elza D; de Boer, Martine; Kuster, Diederik W; Boontje, Nicky M; Holemans, Patricia; Sipido, Karin R; van der Velden, Jolanda; Duncker, Dirk J

    2011-06-01

    There is ample evidence that regular exercise exerts beneficial effects on left ventricular (LV) hypertrophy, remodeling and dysfunction produced by ischemic heart disease or systemic hypertension. In contrast, the effects of exercise on pathological LV hypertrophy and dysfunction produced by LV outflow obstruction have not been studied to date. Consequently, we evaluated the effects of 8 weeks of voluntary wheel running in mice (which mitigates post-infarct LV dysfunction) on LV hypertrophy and dysfunction produced by mild (mTAC) and severe (sTAC) transverse aortic constriction. mTAC produced ~40% LV hypertrophy and increased myocardial expression of hypertrophy marker genes but did not affect LV function, SERCA2a protein levels, apoptosis or capillary density. Exercise had no effect on global LV hypertrophy and function in mTAC but increased interstitial collagen, and ANP expression. sTAC produced ~80% LV hypertrophy and further increased ANP expression and interstitial fibrosis and, in contrast with mTAC, also produced LV dilation, systolic as well as diastolic dysfunction, pulmonary congestion, apoptosis and capillary rarefaction and decreased SERCA2a and ryanodine receptor (RyR) protein levels. LV diastolic dysfunction was likely aggravated by elevated passive isometric force and Ca(2+)-sensitivity of myofilaments. Exercise training failed to mitigate the sTAC-induced LV hypertrophy and capillary rarefaction or the decreases in SERCA2a and RyR. Exercise attenuated the sTAC-induced increase in passive isometric force but did not affect myofilament Ca(2+)-sensitivity and tended to aggravate interstitial fibrosis. In conclusion, exercise had no effect on LV function in compensated and decompensated cardiac hypertrophy produced by LV outflow obstruction, suggesting that the effect of exercise on pathologic LV hypertrophy and dysfunction depends critically on the underlying cause. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Chuanyu Wei

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

  11. Left Ventricular Hypertrophy

    Science.gov (United States)

    ... AskMayoExpert. What tests are needed to confirm the diagnosis of hypertrophic cardiomyopathy (HCM) and what is the role of genetic testing? Rochester, Minn.: Mayo Foundation for Medical Education and Research; ... diagnosis in patients with hypertrophied left ventricles. Heart. 2014; ...

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

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    Hui Pang

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

  13. Development of nonfibrotic left ventricular hypertrophy in an ANG II-induced chronic ovine hypertension model

    DEFF Research Database (Denmark)

    Klatt, Niklas; Scherschel, Katharina; Schad, Claudia

    2016-01-01

    Hypertension is a major risk factor for many cardiovascular diseases and leads to subsequent concomitant pathologies such as left ventricular hypertrophy (LVH). Translational approaches using large animals get more important as they allow the use of standard clinical procedures in an experimental...... setting. Therefore, the aim of this study was to establish a minimally invasive ovine hypertension model using chronic angiotensin II (ANG II) treatment and to characterize its effects on cardiac remodeling after 8 weeks. Sheep were implanted with osmotic minipumps filled with either vehicle control (n...

  14. Electrophysiological characteristics of pressure overload-induced cardiac hypertrophy and its influence on ventricular arrhythmias.

    Directory of Open Access Journals (Sweden)

    Xiaowei Chen

    Full Text Available To explore the cardiac electrophysiological characteristics of cardiac hypertrophy and its influence on the occurrence of ventricular tachyarrhythmias.Adult C57BL6 mice were randomly divided into a surgery group and a control group. Thoracic aortic constriction was performed on mice in the surgery group, and cardiac anatomical and ultrasonic evaluations were performed to confirm the success of the cardiac hypertrophy model 4 weeks after the operation. Using the Langendorff method of isolated heart perfusion, monophasic action potentials (MAPs and the effective refractory period (ERP at different parts of the heart (including the epi- and endo-myocardium of the left and right ventricles were measured, and the induction rate of ventricular tachyarrhythmias was observed under programmed electrical stimulus (PES and burst stimulus. Whole-cell patch-clamp was used to obtain the I-V characteristics of voltage-gated potassium channels in cardiomyocytes of different parts of the heart (including the epi- and endo-myocardium of the left and right ventricles as well as the channels' properties of steady-state inactivation and recovery from inactivation.The ratio of heart weight to body weight and the ratio of left ventricular weight to body weight in the surgery group were significantly higher than those in the control group (P < 0.05. Ultrasonic evaluation revealed that both interventricular septal diameter (IVSD and left ventricle posterior wall diameter (LVPWD in the surgery group were significantly larger than those in the control group (P < 0.05. Under PES and burst stimuli, the induction rates of arrhythmias in the surgery group significantly increased, reaching 41.2% and 23.5%, respectively. Both the QT interval and action potential duration (APD in the surgery group were significantly longer than in the control group (P<0.01, and the changes showed obvious spatial heterogeneity. Whole-cell patch-clamp recordings demonstrated that the surgery group

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

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    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

    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. © 2014 American Heart Association, Inc.

  16. Left ventricular hypertrophy, geometric patterns and clinical ...

    African Journals Online (AJOL)

    Background: Left ventricular hypertrophy can be due to various reasons including hypertension. It constitutes an increased cardiovascular risk. Various left ventricular geometric patterns occur in hypertension and may affect the cardiovascular risk profile of hypertensive subjects. Methods: One hundred and eighty eight ...

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

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    Ana Helena M Pereira

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

  18. Reversal of left ventricular hypertrophy by propranolol in ...

    African Journals Online (AJOL)

    Background: Hypertension contributes significantly to the development of left ventricular hypertrophy. Left ventricular hypertrophy is associated with increased incidence of sudden cardiac death. Recognition and management of hypertension is, therefore, imperative. Objective: To establish whether propranolol can reverse ...

  19. Diosmin prevents left ventricular hypertrophy, adenosine triphosphatases dysfunction and electrolyte imbalance in experimentally induced myocardial infarcted rats.

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    Sabarimuthu, Sharmila Queenthy; Ponnian, Stanely Mainzen Prince; John, Babu

    2017-11-05

    Currently, there has been an increased interest globally to identify natural compounds that are pharmacologically potent and have low or no adverse effects for use in preventive medicine. Myocardial infarction is a vital pathological feature resulting in high levels of mortality and morbidity. Left ventricular hypertrophy (LVH), adenosine triphosphatases (ATPases) dysfunction and electrolyte imbalance play a vital role in the pathogenesis of myocardial infarction. This study aims to evaluate the preventive effects of diosmin on LVH, ATPases dysfunction and electrolyte imbalance in isoproterenol induced myocardial infarcted rats. Male albino Wistar rats were pretreated orally with diosmin (10mg/kg body weight) daily for a period of 10 days. After pretreatment, isoproterenol (100mg/kg body weight) was injected subcutaneously into the rats twice at an interval of 24h to induce myocardial infarction. Isoproterenol induced myocardial infarcted rats showed increased LVH, altered levels/ concentrations of serum cardiac troponin-T, heart ATPases, heart sodium ion, calcium ion and potassium ion, and increased myocardial infarct size. Pretreatment with diosmin revealed preventive effects on LVH, and all the above mentioned biochemical parameters evaluated in isoproterenol induced myocardial infarcted rats. The 2, 3, 5-triphenyl tetrazolium chloride staining on myocardial infarct size confirmed the prevention of myocardial infarction. Further, the 1, 1 diphenyl-2- picryl-hydrazyl (DPPH) radical in vitro study revealed a potent DPPH free radical scavenging action of diosmin. Thus, the observed effects of diosmin are due to its antihypertrophic and free radical scavenging activities in isoproterenol induced myocardial infarcted rats. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Left ventricular hypertrophy : virtuous intentions, malign consequences

    NARCIS (Netherlands)

    Pokharel, S; Sharma, UC; Pinto, YM

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

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

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

    2015-10-01

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

  2. Endothelial Nitric Oxide Synthase-Induced Hypertrophy and Vascular Dysfunction Contribute to the Left Ventricular Dysfunction in Caveolin-1-/- Mice.

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    Ebner, Annette; Kuerbis, Nadine; Brandt, Aljoscha; Zatschler, Birgit; Weinert, Sönke; Poitz, David M; Ebner, Bernd; Augstein, Antje; Wunderlich, Carsten; El-Armouche, Ali; Strasser, Ruth H

    2017-12-01

    Caveolin-1 (Cav1)-/- mice display impaired development of left ventricular pressure and increased left ventricular wall thickness but no dilated ventricle; these are typical findings in patients with heart failure with preserved ejection fraction (HfpEF). Aiming to clarify if dysfunctional endothelial nitric oxide synthase (eNOS) influences cardiomyocyte contractility, cardiac conduction system, or afterload/vascular resistance, we studied Cav1-/-/eNOS-/- mice. Cardiac function was assessed in vivo by pressure-volume-catheterization of the left ventricle, echocardiography and electrocardiography. In addition, isolated tissue experiments were performed to evaluate cardiomyocyte contractility (atria) and vessel morphology and function (aorta). Histology, immunoblotting and quantitative polymerase chain reaction were applied to characterise radical formation and oxidative stress in the heart. Cardiac hypertrophy was completely reversed in Cav1-/-/eNOS-/- mice. The impaired pump function in Cav1-/- mice was significantly improved in Cav1-/-/eNOS-/- mice, but no complete alignment with eNOS-/- controls was achieved, indicating an additional eNOS-independent mechanism contributing to HFpEF in Cav1-/- mice. It is unlikely that frequently occurring arrhythmias contributed to HFpEF in Cav1-/- mice. In contrast, numerous eNOS-dependent and eNOS-independent vascular abnomalities could explain the cardiac phenotypes of Cav1-/- mice. Synergistic effects between eNOS-related cardiac hypertrophy and vascular hypercontractility appear to underlie the left ventricular dysfunction in Cav1-/-mice. These findings provide insights relevant to the poorly understood pathophysiology of HFpEF. Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  3. Effects of a pure alpha/beta-adrenergic receptor blocker on monocrotaline-induced pulmonary arterial hypertension with right ventricular hypertrophy in rats.

    Science.gov (United States)

    Ishikawa, Masaya; Sato, Naoki; Asai, Kuniya; Takano, Teruo; Mizuno, Kyoichi

    2009-12-01

    It is unclear how much the sympathetic nervous system is involved in the development of pulmonary arterial hypertension (PAH). The present study examined whether or not a pure alpha/beta-adrenergic receptor blocker (arotinolol) could prevent the development of PAH and right ventricular hypertrophy (RVH) in a rat model of monocrotaline (MCT)-induced PAH. The heart rate, arterial blood pressure (BP), left ventricular pressure, pulmonary artery pressure (PAP), and right ventricular pressure (RVP) were measured after administration of arotinolol or saline for 2 weeks. Ventricular weight and myocyte size were also measured. Mean PAP was increased less in the arotinolol group (n=6), (53 +/-9 vs 21 +/-2 mmHg in the control (n=6); Parotinolol group (41 +/-3 vs 91 +/-14 mmHg in the control, Parotinolol group. The pure alpha/beta-blocker arotinolol prevented the progression of MCT-induced PAH and RVH in rats, suggesting that sympathetic nervous activation might play a role in the development of PAH.

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

    DEFF Research Database (Denmark)

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

    2009-01-01

    BACKGROUND AND AIM: Diabetes is associated with left ventricular hypertrophy (LVH) and impaired systolic function in hypertensive patients, but less is known about its impact on LVH regression and functional improvement during antihypertensive treatment. METHODS AND RESULTS: We performed annual...... echocardiography in 730 non-diabetic and 93 diabetic patients (aged 55-80 years) with hypertension and electrocardiographic LVH during 4.8-year losartan- or atenolol-based treatment in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. Baseline mean blood pressure (BP) and LV mass did...... shortening (both phypertensive patients with LVH, diabetes is associated with more residual LVH and less improvement in systolic LV function by echocardiography over 4.8 years of antihypertensive treatment....

  5. Ventricular arrhythmias and left ventricular hypertrophy in hypertrophic cardiomyopathy.

    Science.gov (United States)

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

    2013-05-01

    In hypertrophic cardiomyopathy (HCM), the degree of left ventricular hypertrophy (LVH) could influence the development of ventricular arrhythmias. In HCM, analyze the association between the occurrence of ventricular arrhythmias determined by Holter electrocardiogram (ECG-Holter) and the degree of LVH determined by maximum wall thickness (MWT) in echocardiography and body mass index (BMI). Fifty-four consecutive patients with HCM underwent 24-hour ECG-Holter and echocardiography for assessment of level of LVH through MWT and BMI. Two levels were established for the occurrence of Ventricular Arrhythmias: I - alone or paired extrasystoles and II - Non- Sustained Ventricular Tachycardia (NSVT). In 13 patients (24%) with NSVT (level II), there was a higher frequency of MWT of the left ventricle (LV) > 21 mm (n = 10, 77%, 25 ± 4 mm) and LLLV = 144 g/m² (n = 10, 77%, 200 ± 30 g/m²), in comparison with those presenting with extrasystole arrhythmias (level I) (n = 41, 76%), in which these measures were identified in, respectively, 37 % (n= 15, 23 ± 1 mm), p = 0.023, and 39% (n = 16, 192 ± 53 g / m²) of the cases (p = 0.026). The cut-off values mentioned were determined by the ROC curve with a confidence interval of 95%. NSVT was more common in patients with MWTLV > 21 mm and LLLV > 144 g/m² (8 of 13, 62%) than in those with (4 of 13, 31%) or without (1 of 13; 8%) echocardiographic variables above cut-off values (p = 0.04). In HCM, occurrence of ventricular arrhythmias by Holter was associated with the degree of LVH assessed by echocardiography through MWT and BMI.

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

    Directory of Open Access Journals (Sweden)

    Yoichiro Kusakari

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

  7. Ablation of biglycan attenuates cardiac hypertrophy and fibrosis after left ventricular pressure overload.

    Science.gov (United States)

    Beetz, Nadine; Rommel, Carolin; Schnick, Tilman; Neumann, Elena; Lother, Achim; Monroy-Ordonez, Elsa Beatriz; Zeeb, Martin; Preissl, Sebastian; Gilsbach, Ralf; Melchior-Becker, Ariane; Rylski, Bartosz; Stoll, Monika; Schaefer, Liliana; Beyersdorf, Friedhelm; Stiller, Brigitte; Hein, Lutz

    2016-12-01

    Biglycan, a small leucine-rich proteoglycan, has been shown to play an important role in stabilizing fibrotic scars after experimental myocardial infarction. However, the role of biglycan in the development and regression of cardiomyocyte hypertrophy and fibrosis during cardiac pressure overload and unloading remains elusive. Thus, the aim of the present study was to assess the effect of biglycan on cardiac remodeling in a mouse model of left ventricular pressure overload and unloading. Left ventricular pressure overload induced by transverse aortic constriction (TAC) in mice resulted in left ventricular dysfunction, fibrosis and increased biglycan expression. Fluorescence- and magnetic-assisted sorting of cardiac cell types revealed upregulation of biglycan in the fibroblast population, but not in cardiomyocytes, endothelial cells or leukocytes after TAC. Removal of the aortic constriction (rTAC) after short-term pressure overload (3weeks) improved cardiac contractility and reversed ventricular hypertrophy but not fibrosis in wild-type (WT) mice. Biglycan ablation (KO) enhanced functional recovery but did not resolve cardiac fibrosis. After long-term TAC for 9weeks, ablation of biglycan attenuated the development of cardiac hypertrophy and fibrosis. In vitro, biglycan induced hypertrophy of neonatal rat cardiomyocytes and led to activation of a hypertrophic gene program. Putative downstream mediators of biglycan signaling include Rcan1, Abra and Tnfrsf12a. These genes were concordantly induced by TAC in WT but not in biglycan KO mice. Left ventricular pressure overload induces biglycan expression in cardiac fibroblasts. Ablation of biglycan improves cardiac function and attenuates left ventricular hypertrophy and fibrosis after long-term pressure overload. In vitro biglycan induces hypertrophy of cardiomyocytes, suggesting that biglycan may act as a signaling molecule between cell types to modulate cardiac remodeling. Copyright © 2016 Elsevier Ltd. All rights

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  9. Relationship between coronary artery size and ventricular hypertrophy.

    Science.gov (United States)

    Liau, C S; Chen, M F; Chen, W J; Lee, C M; Peng, J Y; Lee, Y T

    1989-02-01

    The relationship between coronary blood flow and ventricular hypertrophy has been studied in animal models. But, this relationship in the human body is scarcely evaluated. In this study we measured coronary arterial sizes by coronary arteriograms and correlated them with ventricular hypertrophy. Patients who underwent cardiac catheterization and coronary arteriography and showed no significant coronary arterial lesions were included in this study. There were 131 patients, 75 men and 56 women, with a mean age of 53 +/- 10 years (S.D.). After evaluation with electrocardiograms, echocardiograms and left ventriculograms these patients were divided into 4 groups: (1) the non-hypertrophy (NVH) group, 50 cases; (2) the left ventricular hypertrophy (LVH) group, 38 cases; (3) the right ventricular hypertrophy (RVH) group, 23 cases; and (4) the biventricular hypertrophy (BVH) group, 20 cases. The proximal portion of the 3 major coronary arteries and the left main stem were measured from coronary arteriograms with the catheter tip as a size reference. The results showed that the left main stem was larger than the 3 major coronary arteries in the NVH, LVH and BVH groups. But in the RVH group, the left main stem was not significantly larger than the right coronary artery. In all 4 groups the left circumflex coronary artery was the smallest while the left anterior descending coronary artery and the right coronary artery were similar in size. Patients with LVH showed dilatation of all 3 left coronary measurements (left main stem, left anterior descending coronary artery and left circumflex coronary artery) as compared with the NVH patients and the RVH patients.(ABSTRACT TRUNCATED AT 250 WORDS)

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

    Directory of Open Access Journals (Sweden)

    Richard E. Katholi

    2011-01-01

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

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

    Science.gov (United States)

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

    2015-03-01

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

  12. Glomerular alterations in pulmonary hypertension and right ventricular hypertrophy

    OpenAIRE

    Cadillo Alfaro, Mario; Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú

    2014-01-01

    The purpose of this work was to study the renal abnormalities in patients with pulmonary hypertension, irrespective of their origin (unless there is evidence of a mitral lesion) and in those not taking full evidence of pulmonary hypertension, right ventricular hypertrophy was found present. Little has been written on this topic, even the poorest are conclusions, not knowing until now the pathogenic factors of renal impairment; least of their pathophysiological significance. El objeto del p...

  13. Role of ubiquitin-proteasome system (UPS) in left ventricular hypertrophy (LVH).

    Science.gov (United States)

    Cacciapuoti, Federico

    2014-01-01

    Cardiac hypertrophy is a key compensatory mechanism acting in response to pressure or volume overload, involving some alterations in signaling transduction pathways and transcription factors-regulation. These changes result in enhanced proteins' synthesis leading to Left Ventricular Hypertrophy (LVH). It is known that the main function of Ubiquitin-Proteasome System (UPS) is to prevent accumulation of damaged, misfolded and mutant proteins by proteolysis. But emerging evidences suggest that UPS also attends to the cells' growth, favoring proteins' synthesis, subsequently evolving in LVH. The role of the proteasome in to favor cellular hypertrophy consists in upregulation of the catalytic proteasome subunit, with prevalence of proteins-synthesis on proteins degradation. It is also evident that UPS inhibition may prevent cells' growth opposing to the hypertrophy. In fact in several experimental models, UPS inhibition demonstrated to be able to prevent or reverse cardiac hypertrophy induced by abdominal aortic banding (AAB). That can happen with several proteasome inhibitors acting by multifactorial mechanisms. These evidences induce to hypothesize that, in the future, in patients with the increased volume overload by systemic hypertension, some proteasome-inhibitors could be used to antagonize or prevent LVH without reducing peripheral high blood pressure levels too.

  14. Electrocardiographic Left Ventricular Hypertrophy Among Gambian Diabetes Mellitus Patients.

    Science.gov (United States)

    Jobe, M; Kane, A; Jones, J C; Pessinaba, S; Nkum, B C; Abdou Ba, S; Nyan, O A

    2015-03-01

    The global prevalence of diabetes and its complications is increasing worldwide. Its role in coronary heart disease has been linked with the presence of left ventricular hypertrophy (LVH). The present study aims to determine the prevalence of electrocardiographic left ventricular hypertrophy (ECG-LVH) in adult diabetic subjects, its epidemiological and clinical correlates. A descriptive cross-sectional study involving 534 patients was conducted at the Edward Francis Small Teaching Hospital (formerly Royal Victoria Teaching Hospital), The Gambia. Four hundred and forty patients were included using a standard questionnaire. Anthropometry, laboratory investigations and electrocardiogram were carried out. We used the Lewis, Cornell, and Sokolow-Lyon Voltage criteria to define ECG-LVH. Minitab™ statistical software version 13.20 was used for analysis. 146 (35.2%) patients had ECG-LVH using all 3 criteria and this prevalence was higher among women being 116 (79.5%). A generally high prevalence of overweight (155/37.4%) and obesity (119/28.6%) was observed among study participants, and both clinic-day systolic and diastolic blood pressure (BP) were significantly higher in those with ECG-LVH. Poor diabetes control was observed in both groups. There was a high prevalence of ECG-LVH and it is especially so with combining multiple criteria, hence the need for screening. Clinic-day hypertension was associated with ECG-LVH hence the need for diagnosing and aggressive treatment of hypertension in patients with diabetes mellitus.

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Celso Ferreira Filho

    2010-01-01

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

  17. Antiandrogenic therapy with finasteride attenuates cardiac hypertrophy and left ventricular dysfunction.

    Science.gov (United States)

    Zwadlo, Carolin; Schmidtmann, Elisa; Szaroszyk, Malgorzata; Kattih, Badder; Froese, Natali; Hinz, Hebke; Schmitto, Jan Dieter; Widder, Julian; Batkai, Sandor; Bähre, Heike; Kaever, Volkhard; Thum, Thomas; Bauersachs, Johann; Heineke, Joerg

    2015-03-24

    In comparison with men, women have a better prognosis when experiencing aortic valve stenosis, hypertrophic cardiomyopathy, or heart failure. Recent data suggest that androgens like testosterone or the more potent dihydrotestosterone contribute to the development of cardiac hypertrophy and failure. Therefore, we analyzed whether antiandrogenic therapy with finasteride, which inhibits the generation of dihydrotestosterone by the enzyme 5-α-reductase, improves pathological ventricular remodeling and heart failure. We found a strongly induced expression of all 3 isoforms of the 5-α-reductase (Srd5a1 to Srd5a3) in human and mouse hearts with pathological hypertrophy, which was associated with increased myocardial accumulation of dihydrotestosterone. Starting 1 week after the induction of pressure overload by transaortic constriction, mice were treated with finasteride for 2 weeks. Cardiac function, hypertrophy, dilation, and fibrosis were markedly improved in response to finasteride treatment in not only male, but also in female mice. In addition, finasteride also very effectively improved cardiac function and mortality after long-term pressure overload and prevented disease progression in cardiomyopathic mice with myocardial Gαq overexpression. Mechanistically, finasteride, by decreasing dihydrotestosterone, potently inhibited hypertrophy and Akt-dependent prohypertrophic signaling in isolated cardiac myocytes, whereas the introduction of constitutively active Akt blunted these effects of finasteride. Finasteride, which is currently used in patients to treat prostate disease, potently reverses pathological cardiac hypertrophy and dysfunction in mice and might be a therapeutic option for heart failure. © 2015 American Heart Association, Inc.

  18. Anti-Hypertensive Drugs Have Different Effects on Ventricular Hypertrophy Regression

    Science.gov (United States)

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

    2010-01-01

    OBJECTIVES: There is a direct relationship between the regression of left ventricular hypertrophy (LVH) and a decreased risk of mortality. This investigation aimed to describe the effects of anti-hypertensive drugs on cardiac hypertrophy through a meta-analysis of the literature. METHODS: The Medline (via PubMed), Lilacs and Scielo databases were searched using the subject keywords cardiac hypertrophy, antihypertensive and mortality. We aimed to analyze the effect of anti-hypertensive drugs on ventricle hypertrophy. RESULTS: The main drugs we described were enalapril, verapamil, nifedipine, indapamina, losartan, angiotensin-converting enzyme inhibitors and atenolol. These drugs are usually used in follow up programs, however, the studies we investigated used different protocols. Enalapril (angiotensin-converting enzyme inhibitor) and verapamil (Ca++ channel blocker) caused hypertrophy to regress in LVH rats. The effects of enalapril and nifedipine (Ca++ channel blocker) were similar. Indapamina (diuretic) had a stronger effect than enalapril, and losartan (angiotensin II receptor type 1 (AT1) receptor antagonist) produced better results than atenolol (selective β1 receptor antagonist) with respect to LVH regression. CONCLUSION: The anti-hypertensive drugs induced various degrees of hypertrophic regression. PMID:20668631

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    with larger left ventricular diameter and higher left ventricular mass index (both P hypertrophy was greater (84 vs. 64%; P cardiac output......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......, transmitral peak E velocities and peak A velocities; and lower E/A ratio (all P hypertrophy, but normal left ventricular chamber systolic function with increased...

  20. Mitochondrial Reprogramming Induced by CaMKIIδ Mediates Hypertrophy Decompensation

    Science.gov (United States)

    Westenbrink, B. Daan; Ling, Haiyun; Divakaruni, Ajit; Gray, Charles B. B.; Zambon, Alexander C.; Dalton, Nancy D.; Peterson, Kirk L.; Gu, Yusu; Matkovich, Scot J.; Murphy, Anne; Miyamoto, Shigeki; Dorn, Gerald W.; Brown, Joan Heller

    2015-01-01

    Rationale Sustained activation of Gq signaling during pressure overload causes cardiac hypertrophy that ultimately progresses to dilated cardiomyopathy. The molecular events that drive hypertrophy decompensation are incompletely understood. Ca2+/calmodulin-dependent protein kinase II delta (CaMKIIδ) is activated downstream of Gq and overexpression of Gq and CaMKIIδ recapitulates hypertrophy decompensation. Objective To determine whether CaMKIIδ contributes to hypertrophy decompensation provoked by Gq. Methods and Results Compared to Gαq transgenic (Gq) mice, compound Gq/CaMKIIδ knockout (KO) (Gq/KO) mice developed a similar degree of cardiac hypertrophy but exhibited significantly improved left ventricular function, less cardiac fibrosis and cardiomyocyte apoptosis, and fewer ventricular arrhythmias. Markers of oxidative stress were elevated in mitochondria from Gq vs. WT mice and respiratory rates were lower; these changes in mitochondrial function were restored by CaMKIIδ deletion. Gq-mediated increases in mitochondrial oxidative stress, compromised membrane potential and cell death were recapitulated in NRVMs infected with constitutively active Gq and attenuated by CaMKII inhibition. Deep RNA sequencing revealed altered expression of 41 mitochondrial genes in Gq hearts, with normalization of ~40% of these genes by CaMKIIδ deletion. Uncoupling protein 3 (UCP3) was markedly downregulated in Gq or by Gq expression in NRVMs and reversed by CaMKIIδ deletion or inhibition, as was Peroxisome proliferator-activated receptor alpha (PPAR-α). The protective effects of CaMKIIδ inhibition on ROS generation and cell death were abrogated by knock down of UCP3. Conversely, restoration of UCP3 expression attenuated ROS generation and cell death induced by CaMKIIδ. Our in vivo studies further demonstrated that pressure overload induced decreases in PPAR-α and UCP3, increases in mitochondrial protein oxidation, and hypertrophy decompensation which were attenuated by Ca

  1. Identifying the aetiology of left ventricular hypertrophy in an athlete: importance of lifestyle modification.

    Science.gov (United States)

    Ball, Miriam Jane; Keenan, Niall; Lynch, Mary; Prasad, Sanjay; Gorog, Diana A

    2009-01-01

    The aetiology of left ventricular hypertrophy (LVH) in an athlete is often difficult to identify. We describe a 29-year-old fitness instructor who was referred for investigation of syncope. He gave a history of intensive weight lifting and anabolic steroid use at supra-therapeutic doses for the preceding 6 years. Electrocardiography showed inferolateral repolarisation abnormalities and a transthoracic echocardiogram demonstrated asymmetrical LVH with reduced left ventricular cavity dimensions. There was no left ventricular outflow tract obstruction or systolic motion of the anterior mitral valve leaflet. These findings were confirmed on cardiac magnetic resonance imaging (CMR). The differential diagnosis included athlete's heart, steroid-induced cardiomyopathy and non-obstructive hypertrophic cardiomyopathy. The patient was advised to discontinue both steroid use and intensive training. After 3 years of steroid abstinence but continued training, the syncopal episodes and the ECG abnormalities completely resolved, associated with regression of LVH on echocardiography and CMR.

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

    Science.gov (United States)

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

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

    DEFF Research Database (Denmark)

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

    2004-01-01

    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......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...

  4. Calcium Signaling Regulates Ventricular Hypertrophy During Development Independent of Contraction or Blood Flow

    Science.gov (United States)

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

    2014-01-01

    In utero interventions aimed at restoring left ventricular hemodynamic forces in fetuses with prenatally diagnosed hypoplastic left heart syndrome failed to stimulate ventricular myocardial growth during gestation, suggesting chamber growth during development may not rely upon fluid forces. We therefore hypothesized that ventricular hypertrophy during development may depend upon fundamental Ca2+-dependent growth pathways that function independent of hemodynamic forces. To test this hypothesis, zebrafish embryos were treated with inhibitors or activators of Ca2+ signaling in the presence or absence of contraction during the period of chamber development. Abolishment of contractile function alone in the setting of preserved Ca2+ signaling did not impair ventricular hypertrophy. In contrast, inhibition of L-type voltage-gated Ca2+ influx abolished contraction and led to reduced ventricular hypertrophy, whereas increasing L-type voltage-gated Ca2+ influx led to enhanced ventricular hypertrophy in either the presence or absence of contraction. Similarly, inhibition of the downstream Ca2+-sensitive phosphatase calcineurin, a known regulator of adult cardiac hypertrophy, led to reduced ventricular hypertrophy in the presence or absence of contraction, whereas hypertrophy was rescued in the absence of L-type voltage-gated Ca2+ influx and contraction by expression of a constitutively active calcineurin. These data suggest ventricular cardiomyocyte hypertrophy during chamber formation is dependent upon Ca2+ signaling pathways that are unaffected by heart function or hemodynamic forces. Disruption of Ca2+-dependent hypertrophy during heart development may therefore represent one mechanism for impaired chamber formation that is not related to impaired blood flow. PMID:25536179

  5. Factors associated with diagnostic discrepancy for left ventricular hypertrophy between electrocardiography and echocardiography

    DEFF Research Database (Denmark)

    Sandager Petersen, Søren; Reinholdt Pedersen, Line; Pareek, Manan

    2017-01-01

    OBJECTIVE: To investigate the influence of cardiovascular risk factors, including fasting plasma glucose (FPG), on the association between electrocardiographic (ECG) and echocardiographic left ventricular hypertrophy (LVH) in an elderly population. METHODS: We tested cross-sectional associations ...

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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

    Science.gov (United States)

    Wong, Raymond Ching-Chiew; Tan, Kong Bing

    2014-12-01

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

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  9. Hydroxysafflor yellow A (HSYA) attenuates hypoxic pulmonary arterial remodelling and reverses right ventricular hypertrophy in rats.

    Science.gov (United States)

    Li, Lei; Dong, Pengda; Hou, Congjia; Cao, Fangyuan; Sun, Shouli; He, Fa; Song, Yanping; Li, Sen; Bai, Yuhua; Zhu, Daling

    2016-06-20

    Carthamus tinctorius L. is a traditional herbal medicine native to China with properties of promoting blood circulation and removing blood stasis, which is used for the treatment of cerebrovascular and cardiovascular diseases. Hydroxysafflor yellow A (HSYA) is the main constituent isolated from the flower of Carthamus tinctorius L. which is used as a marker substance in the quality control of Carthamus tinctorius L. in Chinese Pharmacopeia. This study is to investigate the hypertension attenuating effect of HSYA on hypoxia-induced pulmonary artery hypertension model rats, and the possible mechanism. The animal models were made by treating adult male Wistar rats (of the same age with the same weight of 200±25g) under hypoxia 24h per day for 9 days with or without administration of HSYA. The pulmonary arterial pressure of rats was measured after anesthetization; The right ventricular hypotrophy was evaluated by the right ventricular hypotrophy index (RVHI=[RV/(LV+S)]) as well as histomorphology assay with Hematoxylin and Eosin (HE) staining; The reducing of pulmonary artery remodelling was evaluated by histomorphology assay with HE staining; The proliferation of pulmonary artery smooth muscle cells (PASMCs) was evaluated by immunohistochemistry assays (PCNA and Ki67) and MTT assay. Cell cycle analysis and Weston-blot analysis were also performed in the study. HSYA reduced the mean right ventricular systolic pressure (RVSP) of rats with hypoxic pulmonary arterial hypertension (HPH) in a manner of concentration dependency. It significantly inhibited the PASMCs proliferation and attenuated the remodelling of the pulmonary artery and right ventricular hypertrophy. These findings suggested that HSYA protected against hypoxic induced pulmonary hypertension by reversing the remodelling of the pulmonary artery through inhibiting the proliferation and hypertrophy of PASMCs. This is in accordance with our previous finding that HSYA protects against the pulmonary artery

  10. Left ventricular hypertrophy as a predictor of cardiovascular risk.

    Science.gov (United States)

    Gosse, Philippe

    2005-04-01

    Left ventricular hypertrophy (LVH) is a potent, independent predictor of cardiovascular events, particularly in hypertension, in which it dramatically increases the risk of stroke, coronary heart disease and heart failure. LVH is predominantly a surrogate marker for the effects of other risk factors integrated over time, but it may also contribute directly to cardiovascular disease through pathological changes in cardiac structure. The influence of blood pressure is central to LVH pathology, with 24-h blood pressure being more predictive of LVH than single clinic measurements. Blood pressure variation throughout the day is also emerging as an important correlate of LVH, and a strong association has been found between the early morning blood pressure rise and increased left ventricular mass. Antihypertensive treatment can reverse LVH, and preliminary studies suggest that this improves cardiovascular outcome and long-term prognosis. Most classes of antihypertensive agent show some effect on LVH regression, with the notable exceptions of minoxidil and hydralazine. However, many of the data regarding LVH regression come from small, poor-quality trials or from meta-analyses of these studies. In the few well-conducted studies that are available, certain classes of antihypertensive drugs are more effective than others. Those that target angiotensin II, such as the angiotensin II receptor blockers, appear to have a specific action on LVH that is independent of blood pressure reduction. Further high-quality studies are needed to define how LVH predicts cardiovascular risk, which agents are most effective at eliciting LVH regression and how such reversal can affect cardiovascular outcome.

  11. Comparison of Electrocardiographic Criteria for Identifying Left Ventricular Hypertrophy in Athletes from Different Sports Modalities

    Directory of Open Access Journals (Sweden)

    Nelson Samesima

    Full Text Available OBJECTIVES: In athletes, isolated electrocardiogram high voltage criteria are widely used to evaluate left ventricular hypertrophy, but positive findings are thought to represent normal electrocardiogram alterations. However, which electrocardiogram criterion can best detect left ventricular hypertrophy in athletes of various sport modalities remains unknown. METHODS: Five electrocardiogram criteria used to detect left ventricular hypertrophy were tested in 180 male athletes grouped according to their sport modality: 67% low-static and high-dynamic components and 33% high-static and high-dynamic components of exercise. The following echocardiogram parameters are the gold standard for diagnosing left ventricular hypertrophy: left ventricular mass index ≥134 g.m-2, relative wall thickness ≥0.42 mm, left ventricular diastolic diameter index ≥32 mm.m-2, septum wall thickness ≥13 mm, and posterior wall thickness ≥13 mm. Results for the various criteria were compared using the kappa coefficient. Significance was established at p<0.05. RESULTS: Fifty athletes (28% presented with left ventricular hypertrophy according to electrocardiogram findings, with the following sensitivities and specificities, respectively: 38-53% and 79-83% (Perugia, 22-40% and 89-91% (Cornell, 24-29% and 90% (Romhilt-Estes, 68-87% and 20-23% (Sokolow-Lyon, and 0% and 99% (Gubner. The Perugia and Cornell criteria had higher negative predictive values for the low-static and high-dynamic subgroup. Kappa coefficients were higher for Romhilt-Estes, Cornell and Perugia criteria than for Sokolow-Lyon and Gubner criteria. CONCLUSION: All five evaluated criteria are inadequate for detecting left ventricular hypertrophy, but the Perugia, Cornell and Romhilt-Estes criteria are useful for excluding its presence. The Perugia and Cornell criteria were more effective at excluding left ventricular hypertrophy in athletes involved in a sport modality with low-static and high

  12. p38 MAPK Inhibition Improves Heart Function in Pressure-Loaded Right Ventricular Hypertrophy.

    Science.gov (United States)

    Kojonazarov, Baktybek; Novoyatleva, Tatyana; Boehm, Mario; Happe, Chris; Sibinska, Zaneta; Tian, Xia; Sajjad, Amna; Luitel, Himal; Kriechling, Philipp; Posern, Guido; Evans, Steven M; Grimminger, Friedrich; Ghofrani, Hossein A; Weissmann, Norbert; Bogaard, Harm J; Seeger, Werner; Schermuly, Ralph T

    2017-11-01

    Although p38 mitogen-activated protein kinase (MAPK) is known to have a role in ischemic heart disease and many other diseases, its contribution to the pathobiology of right ventricular (RV) hypertrophy and failure is unclear. Therefore, we sought to investigate the role of p38 MAPK in the pathophysiology of pressure overload-induced RV hypertrophy and failure. The effects of the p38 MAPK inhibitor PH797804 were investigated in mice with RV hypertrophy/failure caused by exposure to hypoxia or pulmonary artery banding. In addition, the effects of p38 MAPK inhibition or depletion (by small interfering RNA) were studied in isolated mouse RV fibroblasts. Echocardiography, invasive hemodynamic measurements, immunohistochemistry, collagen assays, immunofluorescence staining, and Western blotting were performed. Expression of phosphorylated p38 MAPK was markedly increased in mouse and human hypertrophied/failed RVs. In mice, PH797804 improved RV function and inhibited cardiac fibrosis compared with placebo. In isolated RV fibroblasts, p38 MAPK inhibition reduced transforming growth factor (TGF)-β-induced collagen production as well as stress fiber formation. Moreover, p38 MAPK inhibition/depletion suppressed TGF-β-induced SMAD2/3 phosphorylation and myocardin-related transcription factor A (MRTF-A) nuclear translocation, and prevented TGF-β-induced cardiac fibroblast transdifferentiation. Moreover, p38 MAPK inhibition in mice exposed to pulmonary artery banding led to diminished nuclear levels of MRTF-A and phosphorylated SMAD3 in RV fibroblasts. Together, our data indicate that p38 MAPK inhibition significantly improves RV function and inhibits RV fibrosis. Inhibition of p38 MAPK in RV cardiac fibroblasts, resulting in coordinated attenuation of MRTF-A cytoplasmic-nuclear translocation and SMAD3 deactivation, indicates that p38 MAPK signaling contributes to distinct disease-causing mechanisms.

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

    Directory of Open Access Journals (Sweden)

    V. N. Poptsov

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Seyyed Mohsen Hosseini

    2014-01-01

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

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

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    Reneta Yovcheva Koycheva

    2015-12-01

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

  16. Inflammation, Left Ventricular Hypertrophy, and Mortality in End-stage Renal Disease.

    Science.gov (United States)

    Cafka, Majlinda; Rroji, Merita; Seferi, Saimir; Barbullushi, Myftar; Burazeri, Genc; Spahia, Nereida; Idrizi, Alma; Likaj, Erjola; Seiti, Joana; Lazaj, Jonida; Goda, Artan

    2016-07-01

    The aim of this study was to evaluate ventricular geometry, its relationship with the inflammatory markers, and mortality of patients with end-stage renal disease on peritoneal and hemodialysis treatment. We enrolled adult patients on long-term dialysis (hemodialysis and peritoneal dialysis) for more than 3 months. Two-dimensional echocardiography was performed by an experienced cardiologist who was blinded to all clinical details of patients. Cardiovascular mortality was assessed during a 2-year follow-up period. There were 129 participants, of whom 86 (66%) were on hemodialysis. Left ventricular hypertrophy was present in 86.7%; concentric hypertrophy was found in 64 (49.1%) and eccentric hypertrophy in 48 patients (37.2%). Patients with left ventricular hypertrophy were further divided into tertiles according to their left ventricular mass index. Logistic regression found pulse pressure as an independent risk factor associated with left ventricular mass index (odds ratio [OR], 1.04; 95% confidence interval (CI), 1.01 to 1.19; P = .047). Cardiovascular mortality rate was 15.5%. Multivariable analysis showed that C-reactive protein (OR, 1.06; 95% CI, 1.01 to 1.10; P = .01), pulse pressure (OR, 1.01; 95% CI, 1.0 to 1.26; P = .046), and left ventricular mass index (OR, 1.03; 95% CI, 1.01 to 1.21; P = .03) were independent risk factors for cardiovascular mortality. Concentric hypertrophy is the most frequent left ventricular geometry model in patients with chronic kidney disease. Inflammation, pulse pressure, and  left ventricular hypertrophy are interrelated and all contribute to mortality and cardiovascular death risk among dialysis patients.

  17. Salubrinal attenuates right ventricular hypertrophy and dysfunction in hypoxic pulmonary hypertension of rats.

    Science.gov (United States)

    He, Yun-Yun; Liu, Chun-Lei; Li, Xin; Li, Rui-Jun; Wang, Li-Li; He, Kun-Lun

    2016-12-01

    The phosphorylation of eukaryotic translation initiation factor 2 alpha (p-eIF2α) is essential for cell survival during hypoxia. The aim of this study was to investigate whether salubrinal, an inhibitor of p-eIF2α dephosphorylation could attenuate pulmonary arterial hypertension (PAH) and right ventricular (RV) hypertrophy in rats exposed to hypobaric hypoxia. PAH of rats was induced by hypobaric hypoxia. Salubrinal supplemented was randomized in either a prevention or a reversal protocol. At the end of the follow-up point, we measured echocardiography, hemodynamics, hematoxylin-eosin and Masson's trichrome stainings. RNA-seq analysis is explored to identify changes in gene expression associated with hypobaric hypoxia with or without salubrinal. Compared with vehicle-treatment rats exposed to hypobaric hypoxia, salubrinal prevented and partly reversed the increase of the mean pulmonary artery pressure and RV hypertrophy. What's more, salubrinal reduced the percentage wall thickness (WT%) of pulmonary artery and RV collagen volume fraction (CVF) in both prevention and reversal protocols. We also found that salubrinal was capable of reducing endoplasmic reticulum stress and oxidative stress. The result of RNA-seq analysis revealed that chronic hypoxia stimulated the differential expression of a series of genes involved in cell cycle regulation and ventricular hypertrophy and so on. Some of these genes could be ameliorated by salubrinal. These results indicate that salubrinal could prevent and reverse well-established RV remodeling, and restore the genes and pathways altered in the right ventricles of rats exposed to hypobaric hypoxia. Copyright © 2016. Published by Elsevier Inc.

  18. An increased TREK-1-like potassium current in ventricular myocytes during rat cardiac hypertrophy.

    Science.gov (United States)

    Wang, Weiping; Zhang, Man; Li, Pingping; Yuan, Hui; Feng, Nan; Peng, Ying; Wang, Ling; Wang, Xiaoliang

    2013-04-01

    To elucidate the expression and identify the functional changes of 2 pore domain potassium channel TREK-1 during cardiac hypertrophy in rats, left ventricular hypertrophy was induced by subcutaneous injection with isoproterenol. Western blot was used to detect the expression of TREK-1 channel protein, and inside-out and whole-cell recordings were used to record TREK-1 currents. The results showed that TREK-1 protein expression in endocardium was slightly higher than that in epicardium in control left ventricles. However, it was obviously upregulated by 89.8% during hypertrophy, 2.3-fold higher than in epicardium. Mechanical stretch, intracellular acidification, and arachidonic acid could activate a TREK-1-like current in cardiomyocytes. The slope conductances of cardiac TREK-1 and CHO/TREK-1 channels were 123 ± 7 and 113 ± 17 pS, respectively. The TREK-1 inhibitor L-3-n-butylphthalide (10 μM) reduced the currents in CHO/TREK-1 cells, normal cardiomyocytes, and hypertrophic cardiomyocytes by 48.5%, 54.3%, and 55.5%, respectively. The percentage of L-3-n-butylphthalide-inhibited outward whole-cell current in hypertrophic cardiomyocytes (23.7%) was larger than that in normal cardiomyocytes (14.2%). The percentage of chloroform-activated outward whole-cell current in hypertrophic cardiomyocytes (58.3%) was also larger than normal control (40.2%). Our results demonstrated that in hypertrophic rats, TREK-1 protein expression in endocardium was specifically increased and the ratio of TREK-1 channel current in cardiac outward currents was also enhanced. TREK-1 might balance potassium ion flow during hypertrophy and might be a potential drug target for heart protection.

  19. MiR-30-regulated autophagy mediates angiotensin II-induced myocardial hypertrophy.

    Directory of Open Access Journals (Sweden)

    Wei Pan

    Full Text Available Dysregulated autophagy may lead to the development of disease. Role of autophagy and the diagnostic potential of microRNAs that regulate the autophagy in cardiac hypertrophy have not been evaluated. A rat model of cardiac hypertrophy was established using transverse abdominal aortic constriction (operation group. Cardiomyocyte autophagy was enhanced in rats from the operation group, compared with those in the sham operation group. Moreover, the operation group showed up-regulation of beclin-1 (an autophagy-related gene, and down-regulation of miR-30 in cardiac tissue. The effects of inhibition and over-expression of the beclin-1 gene on the expression of hypertrophy-related genes and on autophagy were assessed. Angiotensin II-induced myocardial hypertrophy was found to be mediated by over-expression of the beclin-1 gene. A dual luciferase reporter assay confirmed that beclin-1 was a target gene of miR-30a. miR-30a induced alterations in beclin-1 gene expression and autophagy in cardiomyocytes. Treatment of cardiomyocytes with miR-30a mimic attenuated the Angiotensin II-induced up-regulation of hypertrophy-related genes and decreased in the cardiomyocyte surface area. Conversely, treatment with miR-30a inhibitor enhanced the up-regulation of hypertrophy-related genes and increased the surface area of cardiomyocytes induced by Angiotensin II. In addition, circulating miR-30 was elevated in patients with left ventricular hypertrophy, and circulating miR-30 was positively associated with left ventricular wall thickness. Collectively, these above-mentioned results suggest that Angiotensin II induces down-regulation of miR-30 in cardiomyocytes, which in turn promotes myocardial hypertrophy through excessive autophagy. Circulating miR-30 may be an important marker for the diagnosis of left ventricular hypertrophy.

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

    DEFF Research Database (Denmark)

    Wachtell, K; Smith, G; Gerdts, E

    2000-01-01

    Abnormal left ventricular (LV) filling may exist in early stages of hypertension. Whether this finding is related to LV hypertrophy is currently controversial. This study was undertaken to assess relations between abnormal diastolic LV filling and LV geometry in a large series of hypertensive pat...

  1. Frequent left ventricular hypertrophy independent of blood pressure in 1851 pre-western Inuit

    DEFF Research Database (Denmark)

    Andersen, Stig; Kjærgaard, Marie; Jørgensen, Marit Eika

    2011-01-01

    BACKGROUND: Elevated blood pressure is a risk factor for cardiovascular disease and may be detected by left ventricular hypertrophy (LVH) in electrocardiogram (ECG). Pre-western Inuit had frequent signs of LVH in ECG predominantly in the 3rd decade while a low occurrence of ischemic heart disease....... METHODS: We evaluated the association between blood pressures and ECG signs of LVH, cardiac auscultation, and symptoms related to heart disease in the recently recovered data from the survey of 1851 Inuit conducted in 1962-1964 in East Greenland. RESULTS: The participation rate was 97%. Among the 812...... only after the age of 40 years in pre-western Inuit. Left ventricular hypertrophy peaked among 30-year olds and was independent of elevated blood pressure. It may be speculated that the common left ventricular hypertrophy was due to marked physical activity that contributed to the low occurrence...

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

    DEFF Research Database (Denmark)

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

    1993-01-01

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

  3. Normalization of cardiac substrate utilization and left ventricular hypertrophy precede functional recovery in heart failure regression.

    Science.gov (United States)

    Byrne, Nikole J; Levasseur, Jody; Sung, Miranda M; Masson, Grant; Boisvenue, Jamie; Young, Martin E; Dyck, Jason R B

    2016-05-15

    Impaired cardiac substrate metabolism plays an important role in heart failure (HF) pathogenesis. Since many of these metabolic changes occur at the transcriptional level of metabolic enzymes, it is possible that this loss of metabolic flexibility is permanent and thus contributes to worsening cardiac function and/or prevents the full regression of HF upon treatment. However, despite the importance of cardiac energetics in HF, it remains unclear whether these metabolic changes can be normalized. In the current study, we investigated whether a reversal of an elevated aortic afterload in mice with severe HF would result in the recovery of cardiac function, substrate metabolism, and transcriptional reprogramming as well as determined the temporal relationship of these changes. Male C57Bl/6 mice were subjected to either Sham or transverse aortic constriction (TAC) surgery to induce HF. After HF development, mice with severe HF (% ejection fraction hypertrophy/HF were returned to values observed in healthy controls. Interestingly, pressure-overload-induced left ventricular hypertrophy (LVH) and cardiac substrate metabolism were restored at 1-week post-DB, which preceded functional recovery. The regression of severe HF is associated with early and dramatic improvements in cardiac energy metabolism and LVH normalization that precede restored cardiac function, suggesting that metabolic and structural improvements may be critical determinants for functional recovery. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    BACKGROUND: Persistence or development of ECG left ventricular hypertrophy (LVH) by Cornell product criteria is associated with an increased risk of developing heart failure compared with regression or continued absence of LVH. We postulated that this association might be in part mediated via worse...... in ECG LVH are associated with the changing risk of developing heart failure. CLINICAL TRIALS REGISTRATION: http://clinicaltrials.gov/ct/show/NCT00338260?order=1....... left ventricular systolic function in patients with new or persistent ECG LVH. METHODS: Baseline and year-3 ECG LVH and left ventricular midwall shortening (MWS) were examined in 725 hypertensive patients in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) echocardiographic...

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

    Science.gov (United States)

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

    2018-01-01

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

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

    Science.gov (United States)

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

    2011-01-01

    Cardiac hypertrophy develops most commonly in response to hypertension and is an independent risk factor for the development of heart failure. The mechanisms by which cardiac hypertrophy may be reversed to reduce this risk have not been fully determined to the point where mechanism-specific therapies have been developed. Recently, proteases in the calpain family have been implicated in regulating the development of cardiac hypertrophy in preclinical animal models. In this review, we summarize the molecular mechanisms by which calpain inhibition has been shown to modulate the development of cardiac (specifically ventricular) hypertrophy. The context within which calpain inhibition might be developed for therapeutic intervention of cardiac hypertrophy is then discussed. PMID:21817165

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

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

    DEFF Research Database (Denmark)

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

    2005-01-01

    BACKGROUND: Left ventricular hypertrophy (LVH) is an independent risk factor for myocardial ischaemia, cardiac arrhythmia, sudden death, and heart failure, all common findings in patients with type 2 diabetes. AIM: To determine the prevalence of, and risk factors for, LVH in normoalbuminuric type 2...... h. RESULTS: The prevalence of LVH indexed to height(2.7) was 43% (95%CI 38-50%), and was similar in men and women. BMI, HbA(1c) and log urinary albumin excretion were significantly associated with left ventricular hypertrophy in a logistic regression model, whereas sex, age, known duration...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-08-15

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Wolfe, C.L.; Kennedy, P.L.; Kulkarni, P.V.; Jansen, D.E.; Gabliani, G.I.; Corbett, J.R. (Univ. of Texas Health Science Center (USA))

    1990-06-01

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

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

    Science.gov (United States)

    Wolfe, C L; Kennedy, P L; Kulkarni, P V; Jansen, D E; Gabliani, G I; Corbett, J R

    1990-06-01

    Regional alterations in myocardial substrate uptake and/or utilization have been demonstrated in rats with hypertension. To determine whether alterations in left ventricular fatty acid uptake and/or utilization are present in patients with left ventricular hypertrophy (LVH), we compared the results of rest and exercise iodine-123 phenylpentadecanoic acid (IPPA) myocardial scintigraphy in 10 patients with hypertension who had concentric LVH without evidence of coronary artery disease and in 15 normal subjects. Patients with LVH had more heterogeneous left ventricular activity of IPPA compared to normal subjects after exercise but not at rest (23 +/- 8% versus 13 +/- 5% difference in maximum segmental activity at 4 minutes after exercise; p = 0.005). Although IPPA clearance was similar in both patients with LVH and normal subjects, postexercise washout in segments showing decreased initial IPPA uptake was reduced compared to washout at rest in patients with LVH (11.7 +/- 7.5% versus 21.5 +/- 8.4% at 20 minutes after injection, n = 15; p = 0.005). Exercise thallium-201 (TI-201) scintigraphy was normal in all seven patients with LVH tested. Patients with LVH showed significantly greater heterogeneity in IPPA uptake compared to TI-201 uptake immediately after exercise (25 +/- 5% versus 16 +/- 6%; p = 0.013). We conclude that (1) compared to normal subjects, patients with LVH show heterogeneous myocardial IPPA activity after exercise but not at rest; (2) postexercise washout of IPPA was decreased in segments with reduced uptake after exercise in patients with LVH; and (3) the distribution of IPPA is more heterogeneous than that of TI-201 immediately after exercise in patients with concentric LVH. The postexercise heterogeneity in IPPA uptake and delayed washout in segments with reduced initial uptake is consistent with exercise-induced myocardial ischemia in patients with LVH.

  12. Echocardiography-based left ventricular mass estimation. How should we define hypertrophy?

    Directory of Open Access Journals (Sweden)

    Rohde Luis EP

    2005-06-01

    Full Text Available Abstract Left ventricular hypertrophy is an important risk factor in cardiovascular disease and echocardiography has been widely used for diagnosis. Although an adequate methodologic standardization exists currently, differences in measurement and interpreting data is present in most of the older clinical studies. Variability in border limits criteria, left ventricular mass formulas, body size indexing and other adjustments affects the comparability among these studies and may influence both the clinical and epidemiologic use of echocardiography in the investigation of the left ventricular structure. We are going to review the most common measures that have been employed in left ventricular hypertrophy evaluation in the light of some recent population based echocardiographic studies, intending to show that echocardiography will remain a relatively inexpensive and accurate tool diagnostic tool.

  13. Transient receptor potential vanilloid 2 function regulates cardiac hypertrophy via stretch-induced activation.

    Science.gov (United States)

    Koch, Sheryl E; Mann, Adrien; Jones, Shannon; Robbins, Nathan; Alkhattabi, Abdullah; Worley, Mariah C; Gao, Xu; Lasko-Roiniotis, Valerie M; Karani, Rajiv; Fulford, Logan; Jiang, Min; Nieman, Michelle; Lorenz, John N; Rubinstein, Jack

    2017-03-01

    Hypertension (increased afterload) results in cardiomyocyte hypertrophy leading to left ventricular hypertrophy and subsequently, heart failure with preserved ejection fraction. This study was performed to test the hypothesis that transient receptor potential vanilloid 2 subtype (TRPV2) function regulates hypertrophy under increased afterload conditions. We used functional (pore specific) TRPV2 knockout mice to evaluate the effects of increased afterload-induced stretch on cardiac size and function via transverse aortic constriction (TAC) as well as hypertrophic stimuli including adrenergic and angiotensin stimulation via subcutaneous pumps. Wild-type animals served as control for all experiments. Expression and localization of TRPV2 was investigated in wild-type cardiac samples. Changes in cardiac function were measured in vivo via echocardiography and invasive catheterization. Molecular changes, including protein and real-time PCR markers of hypertrophy, were measured in addition to myocyte size. TRPV2 is significantly upregulated in wild-type mice after TAC, though not in response to beta-adrenergic or angiotensin stimulation. TAC-induced stretch stimulus caused an upregulation of TRPV2 in the sarcolemmal membrane. The absence of functional TRPV2 resulted in significantly reduced left ventricular hypertrophy after TAC, though not in response to beta-adrenergic or angiotensin stimulation. The decreased development of hypertrophy was not associated with significant deterioration of cardiac function. We conclude that TRPV2 function, as a stretch-activated channel, regulates the development of cardiomyocyte hypertrophy in response to increased afterload.

  14. Eccentric Left Ventricular Hypertrophy and Sudden Death in Patients with End-Stage Kidney Disease

    NARCIS (Netherlands)

    De Roij Van Zuijdewijn, Camiel L M; Hansildaar, Romy; Bots, Michiel L.; Blankestijn, Peter J.; Van Den Dorpel, Marinus A.; Grooteman, Muriel P C; Kamp, Otto; Ter Wee, Piet M.; Nubé, Menso J.

    2015-01-01

    Background/Aims: Both all-cause and cardiovascular mortality risks are extremely high in patients with end-stage kidney disease (ESKD). Sudden death accounts for approximately one-quarter of all fatal events. Left ventricular hypertrophy (LVH) is a known risk factor for mortality and can be divided

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    We conducted a 1:2 matched case-control study in order to evaluate whether the prevalence of coronary artery calcium (CAC) and electrocardiographic left ventricular hypertrophy (LVH) or strain was higher in patients with uncontrolled hypertension than in subjects from the general population...

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

    Directory of Open Access Journals (Sweden)

    Xiao-Bing Ji

    2015-07-01

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

  17. BMP type I receptor ALK2 is required for angiotensin II-induced cardiac hypertrophy

    Science.gov (United States)

    Spagnolli, Ester; Ernande, Laura; Thoonen, Robrecht; Kolodziej, Starsha A.; Leyton, Patricio A.; Cheng, Juan; Tainsh, Robert E. T.; Mayeur, Claire; Rhee, David K.; Wu, Mei. X.; Scherrer-Crosbie, Marielle; Buys, Emmanuel S.; Zapol, Warren M.; Bloch, Kenneth D.; Bloch, Donald B.

    2016-01-01

    Bone morphogenetic protein (BMP) signaling contributes to the development of cardiac hypertrophy. However, the identity of the BMP type I receptor involved in cardiac hypertrophy and the underlying molecular mechanisms are poorly understood. By using quantitative PCR and immunoblotting, we demonstrated that BMP signaling increased during phenylephrine-induced hypertrophy in cultured neonatal rat cardiomyocytes (NRCs), as evidenced by increased phosphorylation of Smads 1 and 5 and induction of Id1 gene expression. Inhibition of BMP signaling with LDN193189 or noggin, and silencing of Smad 1 or 4 using small interfering RNA diminished the ability of phenylephrine to induce hypertrophy in NRCs. Conversely, activation of BMP signaling with BMP2 or BMP4 induced hypertrophy in NRCs. Luciferase reporter assay further showed that BMP2 or BMP4 treatment of NRCs repressed atrogin-1 gene expression concomitant with an increase in calcineurin protein levels and enhanced activity of nuclear factor of activated T cells, providing a mechanism by which BMP signaling contributes to cardiac hypertrophy. In a model of cardiac hypertrophy, C57BL/6 mice treated with angiotensin II (A2) had increased BMP signaling in the left ventricle. Treatment with LDN193189 attenuated A2-induced cardiac hypertrophy and collagen deposition in left ventricles. Cardiomyocyte-specific deletion of BMP type I receptor ALK2 (activin-like kinase 2), but not ALK1 or ALK3, inhibited BMP signaling and mitigated A2-induced cardiac hypertrophy and left ventricular fibrosis in mice. The results suggest that BMP signaling upregulates the calcineurin/nuclear factor of activated T cell pathway via BMP type I receptor ALK2, contributing to cardiac hypertrophy and fibrosis. PMID:26873969

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

    Directory of Open Access Journals (Sweden)

    Aleksandra Zebrowska

    2009-03-01

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

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

    African Journals Online (AJOL)

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

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    The predictive value of changes in the severity of electrocardiographic left ventricular hypertrophy (ECG-LVH) during antihypertensive therapy remains unclear in isolated systolic hypertension (ISH). In a Losartan Intervention For Endpoint reduction in hypertension substudy, we included 1320...

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

    Directory of Open Access Journals (Sweden)

    Paulo de Tarso Müller

    2015-10-01

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

  2. Correlation between ankle brachial index, carotid intima media thickness and left ventricular hypertrophy in patients on maintenance hemodialysis

    OpenAIRE

    Hayam A. Hebah; Khaled A. Fouad

    2012-01-01

    Introduction: Left ventricular hypertrophy (LVH) is a major cardiovascular risk factor in patients on maintenance hemodialysis (HD). The aim of our study is to find correlation between ankle brachial index (ABI), carotid intima media thickness (IMT) and left ventricular hypertrophy in this population. Patient and methods: Twenty consecutive patients on maintenance hemodialysis were studied, all clinical data were included and laboratory data recorded, three most recent pre-dialysis blood p...

  3. Lack of regression of left ventricular hypertrophy is associated with higher incidence of revascularization in hypertension: The LIFE Study

    DEFF Research Database (Denmark)

    Søraas, Camilla L; Wachtell, Kristian; Okin, Peter M

    2010-01-01

    Regression of left ventricular (LV) hypertrophy and albuminuria in hypertension has previously been shown to reduce clinical cardiovascular events and death. We aimed to investigate the associations of regression of electrocardiographic (ECG) LV hypertrophy and albuminuria with the incidence of r...

  4. Lack of regression of left ventricular hypertrophy is associated with higher incidence of revascularization in hypertension: The LIFE Study

    DEFF Research Database (Denmark)

    Søraas, Camilla L; Wachtell, Kristian; Okin, Peter M

    2010-01-01

    Regression of left ventricular (LV) hypertrophy and albuminuria in hypertension has previously been shown to reduce clinical cardiovascular events and death. We aimed to investigate the associations of regression of electrocardiographic (ECG) LV hypertrophy and albuminuria with the incidence of r...... of revascularization....

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

    Directory of Open Access Journals (Sweden)

    Bastiaan J van Nierop

    Full Text Available BACKGROUND: Left ventricular (LV and right ventricular (RV function have an important impact on symptom occurrence, disease progression and exercise tolerance in pressure overload-induced heart failure, but particularly RV functional changes are not well described in the relevant aortic banding mouse model. Therefore, we quantified time-dependent alterations in the ventricular morphology and function in two models of hypertrophy and heart failure and we studied the relationship between RV and LV function during the transition from hypertrophy to heart failure. METHODS: MRI was used to quantify RV and LV function and morphology in healthy (n = 4 and sham operated (n = 3 C57BL/6 mice, and animals with a mild (n = 5 and a severe aortic constriction (n = 10. RESULTS: Mice subjected to a mild constriction showed increased LV mass (P0.05. Animals with a severe constriction progressively developed LV hypertrophy (P<0.001, depressed LVEF (P<0.001, followed by a declining RVEF (P<0.001 and the development of pulmonary remodeling, as compared to controls during a 10-week follow-up. Myocardial strain, as a measure for local cardiac function, decreased in mice with a severe constriction compared to controls (P<0.05. CONCLUSIONS: Relevant changes in mouse RV and LV function following an aortic constriction could be quantified using MRI. The well-controlled models described here open opportunities to assess the added value of new MRI techniques for the diagnosis of heart failure and to study the impact of new therapeutic strategies on disease progression and symptom occurrence.

  6. Long-Term Prognosis after Myectomy in Hypertrophic Obstructive Cardiomyopathy with Severe Left Ventricular Hypertrophy.

    Science.gov (United States)

    An, Shuoyan; Fan, Chaomei; Yang, Yinjian; Hang, Fei; Wang, Zhimin; Zhang, Yuhui; Zhang, Jian

    2018-01-05

    Patients with hypertrophic obstructive cardiomyopathy (HOCM) and severe left ventricular hypertrophy (maximal left ventricular wall thickness ≥30 mm) are at high risk of sudden cardiac death (SCD). In this study, we aimed to determine whether HOCM patients with severe hypertrophy had a lower incidence of SCD after myectomy. HOCM patients with severe hypertrophy were consecutively enrolled from Fuwai Hospital in China between 2000 and 2013. Long-term outcomes were retrospectively compared between the 2 groups, namely the myectomy group and medical group. A total of 244 patients (118 in the myectomy group and 126 in the medical group) were involved. The mean follow-up durations for the myectomy and medical groups were 5.07 ± 3.73 and 6.23 ± 4.15 years, respectively. During the follow-up period, the annual cardiovascular mortality rate was 0.84% in the myectomy group and 2.04% in the medical group (p = 0.041). The annual SCD rate was 0.33% in the myectomy group and 1.40% in the medical group (p = 0.040). Multivariate Cox regression analysis showed that myectomy was independently associated with lower rates of cardiovascular death and SCD. In HOCM patients with severe hypertrophy, those that underwent myectomy had a lower risk of cardiovascular death and SCD than those treated with medicines only. © 2018 S. Karger AG, Basel.

  7. [Preliminary Study of Necroptosis in Cardiac Hypertrophy Induced by Pressure Overload].

    Science.gov (United States)

    Zhao, Mingyue; Qin, Yupei; Lu, Lihui; Tang, Xiaoju; Wu, Wenchao; Fu, Hua; Liu, Xiaojing

    2015-06-01

    The aim of this study was to observe whether necroptosis is involved in the process of cardiac hypertrophy induced by pressure overload. SD rats underwent transverse abdominal aortic constriction (TAC) operation for establishing cardiac hypertrophy model. The structure and function of the left ventricle of rats were evaluated via echocardiography, left ventricular mass index, the expression of markers of cardiac hypertrophy and histological detection. Real-time PCR and Western blot were used to measure the gene and protein expression of receptor interacting protein kinase 1 and 3 (RIPK1 and RIPK3, the necroptosis markers) respectively. Four weeks after TAC operation, rat model for cardiac hypertrophy was established. The experimental data showed that the gene and protein expressions of RIPK1 and RIPK3 in the rat heart hypertrophic tissues after TAC for 4 weeks were increased significantly compared with those in the sham group. HE staining showed cardiomyocytes injury and hypertrophy in the hearts of TAC rat models. By transmission electron microscope, we observed that mitochondria of cardiomyocytes were damaged seriously in the TAC models. Treatment with losartan used, the selective antagonist of angiotensin II type I receptor could improve the cardiac function of TAC rats. Moreover, losartan treatment decreased the expression of RIPK1 and RIPK3 in heart tissues of TAC rats. The results suggest that necroptosis occurrs in the process of cardiac hypertrophy with pressure overload, and losartan could alleviate the cardiac hypertrophy and inhibit necroptosis.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1999-09-01

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

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

    DEFF Research Database (Denmark)

    Wachtell, Kristian; Palmieri, Vittorio; Gerdts, Eva

    2010-01-01

    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...... was strongly associated with a reduced risk for hospitalization for heart failure.......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...

  10. Regression of left ventricular hypertrophy in children following the Ross procedure.

    Science.gov (United States)

    Lehoux, Juan; Swartz, Michael F; Atallah-Yunes, Nader; Cholette, Jill M; Alfieris, George M

    2014-05-01

    Left ventricular hypertrophy (LVH) frequently accompanies the progression of aortic valve disease in children. The extent of LVH regression following surgical relief of aortic valve disease in children has not been clearly elucidated. We hypothesized that significant regression of LVH will occur in children following the Ross procedure. We examined LVH over time in children Ross procedure. Left ventricular mass index (LVMI) and corresponding z scores were calculated based on height, age and gender. Left ventricular hypertrophy was defined as an LVMI of > 39 g/m(2.7) and a z score of >1.6. Twenty-five children underwent the Ross procedure. The left ventricular mass increased proportionally with the growth of the child from baseline to the latest follow-up at 7.3 ± 2.9 years (121.1 ± 81.5 vs 133.1 ± 79.8 g, P = 0.4). However, 96% (24/25) of children demonstrated LVMI regression from baseline. Mean LVMI decreased from 70.8 ± 31.2 to 41.8 ± 16.6 g/m(2.7) (P Freedom from LVH was 83% at 10 years. Examination of LVMI and z scores over time demonstrated that the largest decrease occurred after the first year, with continued gradual decline over 10 years of follow-up. The Ross procedure is effective in reversing LVH in children with aortic valve disease.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2000-01-01

    The pathophysiologic process in patients with electrocardiographic left ventricular hypertrophy with ST, T changes but without echocardiographic abnormalities was investigated by myocardial perfusion imaging and fatty acid metabolic imaging. Exercise stress {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)

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

    Science.gov (United States)

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

    2011-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Hao Xue

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

  14. Dual effects of amiodarone on pacemaker currents in hypertrophied ventricular myocytes isolated from spontaneously hypertensive rats.

    Science.gov (United States)

    Li, Hongxia; Zhou, Yafeng; Jiang, Bin; Zhao, Xin; Li, Xun; Yang, Xiangjun; Jiang, Wenping

    2014-09-01

    The pacemaker current If conducted by hyperpolarization-activated cyclic nucleotide-gated (HCN) channels plays a critical role in the regulation of cardiac automaticity, with If density increased in hypertrophied ventricular myocytes. Amiodarone, a highly effective anti-arrhythmic agent, blocks human HCN currents and native If under normal conditions. To determine the effects of amiodarone under pathological conditions, we monitored If under after both acute (0.01, 0.1, 1, 10 and 100 μmol/L) and chronic (10 μmol/L) amiodarone treatment in ventricular myocytes from spontaneously hypertensive rats (SHR) with left ventricular hypertrophy using the whole-cell patch-clamp technique. The If current density was significantly greater in SHR ventricular myocytes than in cells from healthy normotensive control Wistar-Kyoto (WKY) rats. Acute application of amiodarone significantly decreased If density in myocytes from both SHR and WKY rats. The inhibition was concentration dependent with an IC50 of 4.9 ± 1.2 and 6.9 ± 1.3 μmol/L in myocytes from SHR and WKY rats, respectively. Amiodarone increased the activation and deactivation times of If in myocytes from SHR, although it did not alter the relationship of voltage-dependent activation and the reversal potential of If in myocytes from SHR. Chronic exposure of myocytes from SHR to amiodarone potently inhibited If and downregulated HCN2 and HCN4, the major channel subtypes underlying native If , at both the mRNA and protein level. These findings indicate that amiodarone inhibits If under hypertrophied conditions through dual mechanisms: (i) direct channel blockade of If currents; and (ii) indirect suppression via negative regulation of HCN channel gene expression. These unique properties of amiodarone may contribute to its anti-arrhythmic properties under pathological conditions. © 2014 Wiley Publishing Asia Pty Ltd.

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

    Science.gov (United States)

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

    2015-01-01

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

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

    African Journals Online (AJOL)

    elevation of hypoxia inducible factor (HIF), which in turn leads to increases in levels of VEGF and other angiogenic factors. This adaptive response delays progression from pathological cardiac hypertrophy to heart failure. In early cardiac hypertrophy, stability of HIF-1 promotes glycolysis, which improves glucose utilization ...

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    ); higher hemoglobin (6.3 ± 2.2 vs. 6.0 ± 2.7 mmol/l) and prevalence of diabetes (20.6 vs. 12.8%, P ≤ 0.004) than patients without psoriasis. In multivariable Cox analysis, adjusting for age, sex, hemoglobin, diabetes, time-varying SBP, heart rate, study treatment and Sokolow-Lyon hypertrophy, psoriasis...... has a similar prevalence in hypertensive patients as in the general population. Psoriasis independently predicted new-onset atrial fibrillation despite lower age and electrocardiographic LVH in psoriasis patients than in patients without psoriasis.......BACKGROUND: Inflammation contributes to the pathogenesis of psoriasis as well as atrial fibrillation. The impact of psoriasis and its association with new-onset atrial fibrillation was assessed in hypertensive patients with left ventricular hypertrophy (LVH). METHODS: The predictive value...

  18. The effects of candesartan on left ventricular hypertrophy and function in nonobstructive hypertrophic cardiomyopathy: a pilot, randomized study.

    Science.gov (United States)

    Penicka, Martin; Gregor, Pavel; Kerekes, Roman; Marek, Dan; Curila, Karol; Krupicka, Jiri

    2009-01-01

    Hypertrophic cardiomyopathy is caused by mutations in the genes that encode sarcomeric proteins and is primarily characterized by unexplained left ventricular hypertrophy, impaired cardiac function, reduced exercise tolerance, and a relatively high incidence of sudden cardiac death, especially in the young. The extent of left ventricular hypertrophy is one of the major determinants of disease prognosis. Angiotensin II has trophic effects on the heart and plays an important role in the development of myocardial hypertrophy. Here in a double-blind, placebo-controlled, randomized study, we show that the long-term administration of the angiotensin II type 1 receptor antagonist candesartan in patients with hypertrophic cardiomyopathy was associated with the significant regression of left ventricular hypertrophy, improvement of left ventricular function, and exercise tolerance. The magnitude of the treatment effect was dependent on specific sarcomeric protein gene mutations that had the greatest responses on the carriers of ss-myosin heavy chain and cardiac myosin binding protein C gene mutations. These data indicate that modulating the role of angiotensin II in the development of hypertrophy is specific with respect to both the affected sarcomeric protein gene and the affected codon within that gene. Thus, angiotensin II type 1 receptor blockade has the potential to attenuate myocardial hypertrophy and may, therefore, provide a new treatment option to prevent sudden cardiac death in patients with hypertrophic cardiomyopathy.

  19. Inhibition of Cardiac Hypertrophy Effects in D-Galactose-Induced Senescent Hearts by Alpinate Oxyphyllae Fructus Treatment

    Directory of Open Access Journals (Sweden)

    Yung-Ming Chang

    2017-01-01

    Full Text Available Aging is a complex physiological phenomenon accelerated by ROS accumulation, with multisystem decline and increasing vulnerability to degenerative diseases and death. Cardiac hypertrophy is a key pathophysiological component that accompanies the aging process. Alpinate Oxyphyllae Fructus (Alpinia oxyphylla MIQ, AOF is a traditional Chinese medicine, which provides cardioprotective activity against aging, hypertension, and cerebrovascular disorders. In this study, we found the protective effect of AOF against cardiac hypertrophy in D-galactose-induced aging rat model. The results showed that treating rats with D-galactose resulted in pathological hypertrophy as evident from the morphology change, increased left ventricular weight/whole heart weight, and expression of hypertrophy-related markers (MYH7 and BNP. Both concentric and eccentric cardiac hypertrophy signaling proteins were upregulated in aging rat model. However, these pathological changes were significantly improved in AOF treated group (AM and AH in a dose-dependent manner. AOF negatively modulated D-galactose-induced cardiac hypertrophy signaling mechanism to attenuate ventricular hypertrophy. These enhanced cardioprotective activities following oral administration of AOF reflect the potential use of AOF for antiaging treatments.

  20. Left ventricular hypertrophy in mild essential hypertension. Its progression, prediction and treatment strategy.

    Science.gov (United States)

    Doba, N; Tomiyama, H; Yoshida, H; Kihara, Y; Watanabe, G; Hinohara, S

    1996-07-01

    Since the pathogenesis of left ventricular hypertrophy (LVH) in hypertension is thought to be multifactorial, the antihypertensive strategy also has to be multifaceted. Diagnosis of LVH is more reliable than ever with echocardiography either of the M-mode or 2D method. Diagnostic criteria have already been proposed by Ganau et al who classified LV morphology into 4 different sectors based on the standard values of left ventricular mass index (LVMI) and relative wall thickness in diastole (RWTd); normal, concentric remodeling, concentric hypertrophy and eccentric hypertrophy. The concentric hypertrophy pattern is the most risky with regard to prognosis. Therefore, its detection and prediction for further progression have to be conducted with relatively easy routine work-up procedures such as echocardiography and maximal exercise testing. The prediction of LVH progression has already been proposed based on several studies conducted in patients with borderline or mild hypertension. The following two predictors were defined as LVMI > 124 g/m2 and peak Ps at maximal exercise testing > 200 mmHg. Therefore, the patient who meets these criteria has to be treated with medications that are appropriately selected on an individualized basis. Both hyperinsulinemia and insulin resistance are thought to be involved in the initiation, promotion and potentiation of remodeling of the LV in hypertension. Physical fitness also seems to be decreased in a parallel manner. Selection of the most appropriate drug for a given patient has to be individually determined based on the risks that have to be corrected. Finally, arteriosclerosis, which is almost always initiated and progresses in concert with hypertension, must also be targeted with regard to such prognostic aspects as cardiovascular morbidity and mortality. Arteriosclerosis is pathogenetically independent from hypertension, but usually behaves in concert with it. Selection of medication must be focussed on an individualized basis

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

    Science.gov (United States)

    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

    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-1α), PPAR-α and ERR-α. The expression of multiple PCG-1α target genes required for fatty acid oxidation (FAO) was similarly decreased. Decreased PGC-1α 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-1α, 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

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

    Science.gov (United States)

    Mirza, Sumbul Javed; Radaideh, Ghazi Ahmad

    2013-01-01

    To explore the pattern of left ventricular hypertrophy caused by hypertension and to compare it with idiopathic hypertrophiccardiomyopathy. 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 > 15 mm) 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. 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 diametre in 4 (36%) cases. 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.

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

    DEFF Research Database (Denmark)

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

    2007-01-01

    AIM: To examine the association of left ventricular hypertrophy (LVH) on admission electrocardiography with adverse outcomes in acute coronary syndrome (ACS) patients. METHODS AND RESULTS: A total of 7443 non-ST-elevation ACS patients in Global Utilization of STrategies to Open occluded arteries......-depression >or= 0.5 mm, elevated C-reactive protein and N-terminal pro-brain naturetic peptide (NT-proBNP), and lower troponin T. Invasive procedures occurred less often in LVH patients (cardiac catheterization: 31 vs. 38%, P = 0.001; percutaneous coronary intervention: 12 vs. 20%, P

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

    Science.gov (United States)

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

    2016-06-01

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

  5. Marked Regression of Left Ventricular Hypertrophy after Outflow Desobliteration in HOCM

    Directory of Open Access Journals (Sweden)

    Zisis Dimitriadis

    2012-01-01

    Full Text Available We present an HOCM patient in whom marked regression of left ventricular hypertrophy occurred within two years following outflow desobliteration by percutaneous septal ablation. Maximum wall thickness (initially documented by both echo and MRI decreased from 34 mm to 22 mm (followup by echo only due to presence of the ICD, crossing the threshold value of 30 mm which was one of the risk markers that had triggered the primary prophylactic ICD implantation in this case prior to septal ablation.

  6. Prevalence of left ventricular hypertrophy in Type I diabetic patients with diabetic nephropathy

    DEFF Research Database (Denmark)

    Sato, A; Tarnow, L; Parving, H H

    1999-01-01

    The increased mortality of patients with diabetic nephropathy is mainly due to cardiovascular disease and end stage renal failure. Left ventricular hypertrophy is an independent risk factor for myocardial ischaemia and sudden death. The aim of our cross-sectional study was to evaluate left...... ventricular structure and function in Type I (insulin-dependent) diabetic patients with diabetic nephropathy. M-mode and Doppler echocardiography were done on 105 Type I diabetic patients with diabetic nephropathy [61 men, age (means +/- SD) 44+/-9 years, and albuminuria [median(range)] 567(10-8188) mg/24 h......, serum creatinine 109 (53-558) micromol/l], and 140 Type I diabetic patients with persistent normoalbuminuria [79 men, 47+/-10 years, urinary albumin excretion rate 8 (0-30) mg/24 h, and serum creatinine 81 (55-121) micromol/l]. Patients with and without nephropathy were comparable with respect to sex...

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

    Science.gov (United States)

    Zhang, Hong-Shan; Wu, Qing-Yu; Xu, Ming; Zhou, Yu-Xiang; Shui, Chao-Xiang

    2012-07-01

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

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

    Directory of Open Access Journals (Sweden)

    Mohammad T. Elnakish

    2015-01-01

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

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

    Science.gov (United States)

    Elnakish, Mohammad T.; Ahmed, Amany A. E.; Mohler, Peter J.; Janssen, Paul M. L.

    2015-01-01

    Cardiac hypertrophy is the most documented cardiomyopathy following hyperthyroidism in experimental animals. Thyroid hormone-induced cardiac hypertrophy is described as a relative ventricular hypertrophy that encompasses the whole heart and is linked with contractile abnormalities in both right and left ventricles. The increase in oxidative stress that takes place in experimental hyperthyroidism proposes that reactive oxygen species are key players in the cardiomyopathy frequently reported in this endocrine disorder. The goal of this review is to shed light on the effects of thyroid hormones on the development of oxidative stress in the heart along with the subsequent cellular and molecular changes. In particular, we will review the role of thyroid hormone-induced oxidative stress in the development of cardiomyocyte hypertrophy and associated cardiac dysfunction, as well as the potential effectiveness of antioxidant treatments in attenuating these hyperthyroidism-induced abnormalities in experimental animal models. PMID:26146529

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

    DEFF Research Database (Denmark)

    Wachtell, Kristian; Palmieri, Vittorio; Gerdts, Eva

    2010-01-01

    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......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...

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    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...... 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...

  12. Albuminuria Is Associated with Left Ventricular Hypertrophy in Patients with Early Diabetic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Nan Wu

    2014-01-01

    Full Text Available Aims. Left ventricular hypertrophy (LVH and albuminuria are both markers for cardiovascular diseases (CVDs in patients with type 2 diabetes mellitus (T2DM. We speculate that albuminuria in T2DM patients with early diabetic kidney disease (DKD could predict LVH. Methods. 333 diabetic patients (219 non-DKD and 114 early DKD were enrolled. The association between albuminuria and LVMI was examined using multivariate linear regression and logistic regression. Results. The rate of LVH was significantly higher in patients with early DKD versus those without DKD (57.0% versus 32.9%; P<0.001. Multivariate linear regression analysis demonstrated that albuminuria status (no, micro-, and macroalbuminuria; P<0.001, age (P<0.001, systolic blood pressure (P=0.0578, and the use of ACEI/ARB drug (P<0.001 were independently associated with LVMI. The risks were substantially higher for LVH in the microalbuminuria group (odds ratio 2.473 (95% confidence interval 1.370–4.464 and macroalbuminuria group (odds ratio 3.940 (95% confidence interval 1.553–9.993 compared with that in non-DKD group. Concentric hypertrophy was the most common geometric pattern in patients with early DKD (36.0%, followed by eccentric hypertrophy (21.0%. Conclusions. Albuminuria is associated with higher LVMI and higher rate of LVH in patients with early phase DKD.

  13. [Microalbuminuria and left ventricular hypertrophy in essential arterial hypertension. A study in non-diabetic patients].

    Science.gov (United States)

    Berrut, G; Chameau, A M; Bouhanick, B; Page, J D; Hallab, M; Richard, C; Girault, A; Fressinaud, P; Marre, M

    To evaluate the relationship between urinary albumin excretion and left ventricular hypertrophy in essential hypertension, we studied, cross-sectionally, 64 subjects with essential hypertension and no diabetes. Urinary albumin excretion and Sokolow index correlated significantly (r = 0.483; P = 0.0001). Five subjects were positive for microalbuminuria (> 30 mg/24 h) and Sokolow index (> 35 mm); 43 were negative for both, with a concordance rate of 77 percent (chi-squared test 11.1; P = 0.0009). Stepwise multivariate regression analysis indicated two independent determinants for urinary albumin excretion: Sokolow index (F = 18.29), and diastolic blood pressure (F = 12.23). The relationships between urinary albumin excretion, Sokolow index, and blood pressure were not different in the 18 subjects taking angiotensin I-converting enzyme inhibitors and in the 46 others. The close relationship between urinary albumin excretion and Sokolow index observed in this study suggests that left ventricular hypertrophy due to hypertension may account for the increased cardiovascular mortality observed in non diabetic subjects with microalbuminuria.

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

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    Diego Valarezo-Sevilla

    2013-03-01

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

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

    Science.gov (United States)

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

    2016-09-01

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

  16. Effects of losartan on left ventricular hypertrophy and fibrosis in patients with nonobstructive hypertrophic cardiomyopathy.

    Science.gov (United States)

    Shimada, Yuichi J; Passeri, Jonathan J; Baggish, Aaron L; O'Callaghan, Caitlin; Lowry, Patricia A; Yannekis, Gia; Abbara, Suhny; Ghoshhajra, Brian B; Rothman, Richard D; Ho, Carolyn Y; Januzzi, James L; Seidman, Christine E; Fifer, Michael A

    2013-12-01

    The aim of this study was to evaluate the effects of losartan on left ventricular (LV) hypertrophy and fibrosis in patients with nonobstructive hypertrophic cardiomyopathy (HCM). Despite evidence that myocardial hypertrophy and fibrosis are mediated by angiotensin II and are important determinants of morbidity and mortality in patients with HCM, no prior studies have evaluated the effects of angiotensin receptor blockers on LV hypertrophy and fibrosis with cardiac magnetic resonance imaging. In double-blind fashion, 20 patients (3 women, 17 men; age: 51 ± 13 years) with HCM were randomly assigned to receive placebo (n = 9) or losartan 50 mg twice a day (n = 11) for 1 year. Cardiac magnetic resonance imaging was performed at baseline and 1 year to measure LV mass and extent of fibrosis as assessed by late gadolinium enhancement. There was a trend toward a significant difference in the percent change in LV mass (median [interquartile range]: +5% [-4% to +21%] with placebo vs. -5% [-11% to -0.9%] with losartan; p = 0.06). There was a significant difference in the percent change in extent of late gadolinium enhancement, with the placebo group experiencing a larger increase (+31% ± 26% with placebo vs. -23% ± 45% with losartan; p = 0.03). This pilot study suggests attenuation of progression of myocardial hypertrophy and fibrosis with losartan in patients with nonobstructive HCM. Confirmation of these results in a larger trial is required to confirm a place for angiotensin receptor blockers in the management of patients with HCM. (Effect of Losartan in Patients With Nonobstructive Hypertrophic Cardiomyopathy; NCT01150461). Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  17. Myocardial reverse remodeling after pressure unloading is associated with maintained cardiac mechanoenergetics in a rat model of left ventricular hypertrophy.

    Science.gov (United States)

    Ruppert, Mihály; Korkmaz-Icöz, Sevil; Li, Shiliang; Németh, Balázs Tamás; Hegedűs, Péter; Brlecic, Paige; Mátyás, Csaba; Zorn, Markus; Merkely, Béla; Karck, Matthias; Radovits, Tamás; Szabó, Gábor

    2016-09-01

    Pressure unloading represents the only effective therapy in increased afterload-induced left ventricular hypertrophy (LVH) as it leads to myocardial reverse remodeling (reduction of increased left ventricular mass, attenuated myocardial fibrosis) and preserved cardiac function. However, the effect of myocardial reverse remodeling on cardiac mechanoenergetics has not been elucidated. Therefore, we aimed to provide a detailed hemodynamic characterization in a rat model of LVH undergoing pressure unloading. Pressure overload was induced in Sprague-Dawley rats by abdominal aortic banding for 6 (AB 6th wk) or 12 wk (AB 12th wk). Sham-operated animals served as controls. Aortic debanding procedure was performed after the 6th experimental week (debanded 12th wk) to investigate the regression of LVH. Pressure unloading resulted in significant reduction of LVH (heart weight-to-tibial length ratio: 0.38 ± 0.01 vs. 0.58 ± 0.02 g/mm, cardiomyocyte diameter: 18.3 ± 0.1 vs. 24.1 ± 0.8 μm debanded 12th wk vs. AB 12th wk, P cardiac mechanoenergetics. Copyright © 2016 the American Physiological Society.

  18. Role of Osteoprotegerin and Its Gene Polymorphisms in the Occurrence of Left Ventricular Hypertrophy in Essential Hypertensive Patients

    Science.gov (United States)

    Shen, Anna; Hou, Xuwei; Yang, Deguang; Liu, Tingrong; Zheng, Dezhong; Deng, Liehua; Zhou, Tao

    2014-01-01

    Abstract The aim of the study was to investigate the role of osteoprotegerin (OPG) in left ventricular hypertrophy (LVH) development in patients with essential hypertension (EH). A total of 1092 patients diagnosed with EH were recruited. The LVHs were determined and OPG gene polymorphisms were genotyped. Patients with LVH had a significantly higher mean serum OPG level than those without LVH. The 1181CC genotype carriers had significantly lower risk for LVH compared with GC and GG genotype carriers. The serum OPG level and OPG 1181 G>C polymorphism were found to be independent risk factors for the occurrence of LVH in hypertensive patients. In vitro study shows that OPG overexpression upregulates cell surface size, protein synthesis per cell, and hypertrophy- and fibrosis-related proteins in both cardiomyocytes and cardiac fibroblasts, whereas OPG inhibition can abolish the above-mentioned changes. Consistent with the in vitro data, our in vivo study revealed that the OPG administration induced the LVH in hypertensive rats. This study is the first to report the close association between OPG and LVH development in EH patients and the regulatory effect of OPG on cardiomyocytes and cardiac fibroblasts. PMID:25546658

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

    Directory of Open Access Journals (Sweden)

    Yuki Fujimura

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

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

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    Dorota Drożdż

    2016-01-01

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

  1. Cardiac hypertrophy and dysfunction induced by overexpression of miR-214 in vivo.

    Science.gov (United States)

    Yang, Tao; Gu, Haihua; Chen, Xiaofan; Fu, Shaozhi; Wang, Cheng; Xu, Hongfei; Feng, Qiang; Ni, Yiming

    2014-12-01

    An increasing number of studies have demonstrated the critical role of microRNAs in the pathogenesis of cardiac hypertrophy and dysfunction. This study evaluated whether miR-214 plays a pivotal role in the development of cardiac hypertrophy and heart failure. In human tissues, miR-214 overexpression was determined to promote cardiac hypertrophy. We predicted miR-214 direct target by bioinformatics database and verifed it using luciferase dual reporting system. We silenced miR-214 using a specific antagomir in a pressure-overload mouse model of heart failure. Analysis of transgenic mice with cardiomyocyte-specific overexpression of miR-214 indicated that their hearts were 21% heavier than wild-type hearts and expressed several biochemical and functional markers consistent with dilated cardiomyopathy. These findings include enlarged left ventricular internal diameters, wall thinning, reduced ejection fraction, fractional shortening, and an increased fetal gene expression. The enhancer of zeste homolog 2 (EZH2) was confirmed as a direct target of miR-214 in cardiomyocytes. In vivo silencing of miR-214 using a specific antagomir rescued cardiac EZH2 expression and prevented cardiac hypertrophy and dysfunction. Taken together, these results suggest that miR-214 may induce pathologic cardiac hypertrophy in part by reducing EZH2 messenger RNA levels. MiR-214 may therefore be a potential therapeutic target for treating certain cardiac disease states. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Diagnostic accuracy of computer-assisted electrocardiography in the diagnosis of left ventricular hypertrophy in left bundle branch block.

    Science.gov (United States)

    Rodríguez-Padial, Luis; Rodríguez-Picón, Blanca; Jerez-Valero, Miguel; Casares-Medrano, Julio; Akerström, Finn O; Calderon, Alberto; Barrios, Vivencio; Sarría-Santamera, Antonio; González-Juanatey, José R; Coca, Antonio; Andrés, Josep; Ruiz-Baena, Jessica

    2012-01-01

    Left ventricular hypertrophy has important prognostic implications. Although electrocardiography is the technique most often recommended in the diagnosis of hypertrophy, its diagnostic accuracy is hampered in the presence of a left bundle branch block. In 1875 consecutive patients (56±16 years) undergoing studies to rule out heart disease and/or hypertension, 2-dimensional echocardiography and electrocardiography were performed simultaneously in an outpatient clinic. Digitized electrocardiograms were interpreted using an online computer-assisted platform (ELECTROPRES). Sensitivity, specificity, likelihood ratios, and predictive values of standard electrocardiographic criteria and of some diagnostic algorithms for left ventricular hypertrophy were determined and compared with the findings in patients with neither left bundle branch block nor myocardial infarction. Left bundle branch block was present in 233 (12%) patients. Left ventricular hypertrophy was detected more frequently in patients with left bundle branch block (60% vs 31%). In patients with left bundle branch block, sensitivities were low but similar to those observed in patients without it, and ranged from 6.4% to 70.9%, whereas specificities were high, ranging from 57.6% to 100%. Positive likelihood ratios ranged from 1.33 to 4.94, and negative likelihood ratios from 0.50 to 0.98. Diagnostic algorithms, voltage-duration products, and certain compound criteria had the best sensitivities. Left ventricular hypertrophy can be diagnosed in the presence of left bundle branch block with an accuracy at least similar to that observed in patients without this conduction defect. Computer-assisted interpretation of the electrocardiogram may be useful in the diagnosis of left ventricular hypertrophy as it enables the implementation of more accurate algorithms. Copyright © 2011 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

  3. [Hypertrophic cardiomyopathy with ventricular septal hypertrophy localized to the apical region of the left ventricle (apical ASH)].

    Science.gov (United States)

    Koga, Y; Takahashi, H; Ifuku, M; Itaya, M; Adachi, K; Toshima, H

    1984-08-01

    Clinical and morphologic features are described in a subgroup of 22 patients with hypertrophic cardiomyopathy, who showed ventricular septal hypertrophy localized to the apical region (apical asymmetric septal hypertrophy: apical ASH). All patients had ventricular septal thickness of 17 mm or less with an average of 13 +/- 3 mm in the M-mode echocardiograms. In contrast, the two-dimensional echocardiograms demonstrated septal hypertrophy localized to the apical region, with an average septal thickness of 20 +/- 3 mm at the mitral valve and papillary muscle levels. On the left ventriculogram, 82% of patients with apical ASH showed inward concavity of the right-inferior wall of the left ventricle, indicating hypertrophy of the ventricular septum. However, no patient showed spade-like appearance of the left ventricle and only two showed giant T wave inversion exceeding 10 mm. Echocardiographic examination performed in eight affected relatives revealed typical asymmetric septal hypertrophy (ASH) in four relatives, one of them showing a resting pressure gradient of 30 mmHg in the left ventricle. The remaining four relatives showed similar apical ASH. When compared with patients of typical ASH, patients with apical ASH demonstrated significantly greater cardiac size, left ventricular end-diastolic pressure, left atrial and left ventricular diameters and significantly lower percent fractional shortening. Atrial fibrillation, B bump of the mitral echogram and heart failure were more frequent in this subgroup of patients. Thus, apical ASH appeared to be a part of the morphologic spectrum of hypertrophic cardiomyopathy with ASH and to be a separate disease entity from apical hypertrophy previously described in Japan. Severely impaired diastolic performances associated with mild to moderately depressed systolic function of the left ventricle were the characteristic clinical features of the subgroup of patients with apical ASH.

  4. Exacerbated pulmonary arterial hypertension and right ventricular hypertrophy in animals with loss of function of extracellular superoxide dismutase.

    Science.gov (United States)

    Xu, Dachun; Guo, Haipeng; Xu, Xin; Lu, Zhongbing; Fassett, John; Hu, Xinli; Xu, Yawei; Tang, Qizhu; Hu, Dayi; Somani, Arif; Geurts, Aron M; Ostertag, Eric; Bache, Robert J; Weir, E Kenneth; Chen, Yingjie

    2011-08-01

    Studies have demonstrated that increased oxidative stress contributes to the pathogenesis and the development of pulmonary artery hypertension (PAH). Extracellular superoxide dismutase (SOD3) is essential for removing extracellular superoxide anions, and it is highly expressed in lung tissue. However, it is not clear whether endogenous SOD3 can influence the development of PAH. Here we examined the effect of SOD3 knockout on hypoxia-induced PAH in mice and a loss-of-function SOD3 gene mutation (SOD3(E124D)) on monocrotaline (40 mg/kg)-induced PAH in rats. SOD3 knockout significantly exacerbated 2 weeks of hypoxia-induced right ventricular (RV) pressure and RV hypertrophy, whereas RV pressure in SOD3 knockout mice under normoxic conditions is similar to wild-type controls. In untreated control rats at age of 8 weeks, there was no significant difference between wild-type and SOD3(E124D) rats in RV pressure and the ratio of RV weight:left ventricular weight (0.25±0.02 in wild-type rats versus 0.25±0.01 in SOD3(E124D) rats). However, monocrotaline caused significantly greater increases of RV pressure in SOD3(E124D) rats (48.6±1.8 mm Hg in wild-type versus 57.5±3.1 mm Hg in SOD3(E124D) rats), of the ratio of RV weight:left ventricular weight (0.41±0.01 versus 0.50±0.09; Prats (55.2±2.3% versus 69.9±2.6%; P<0.05). Together, these findings indicate that the endogenous SOD3 has no role in the development of PAH under control conditions but plays an important role in protecting the lung from the development of PAH under stress conditions.

  5. Amlodipine-induced reversible gum hypertrophy

    Directory of Open Access Journals (Sweden)

    Gutch Manish

    2016-01-01

    Full Text Available Gingival hypertrophy is a common manifestation of any pathology affecting gingival and periodontal regions. It commonly follows inflammatory disorders, Vitamin C deficiency, leukemia and due to drugs such as anticonvulsants, immunosuppressants, and calcium channel blockers. Amlodipine is a third generation dihydropyridine derived calcium channel blocker commonly used to treat hypertension. Here, we describe the case of a 45-year-old hypertensive woman who was on amlodipine for 1 year and subsequently developed one of its rarest adverse effects, i.e., gingival hypertrophy.

  6. Non-gated computed tomography of left ventricular hypertrophy. Comparison with vectorcardiogram

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    Harada, Junta (Jikei Univ., Tokyo (Japan). School of Medicine)

    1983-08-01

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

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

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

    DEFF Research Database (Denmark)

    Kjaer, Andreas; Meyer, Christian; Wachtell, Kristian

    2005-01-01

    Myocardial perfusion (MP) may differ in physiologic and pathologic left ventricular hypertrophy (LVH). We compared MP in LVH in elite athletes and patients with hypertension with healthy, age-matched subjects. We included 12 rowers with LVH, 19 patients with hypertension with LVH, and 2 age...

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    PURPOSE:: To improve risk stratification for development of ischaemic heart disease, several markers have been proposed. Both the presence of coronary artery calcification (CAC) and ECG pattern of left ventricular hypertrophy/strain have been shown to provide independent prognostic information. I...... with nonhypertensive individuals (21 vs. 14%, P ...

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

    DEFF Research Database (Denmark)

    Paul, David S; Grevengoed, Trisha J; Pascual, Florencia

    2014-01-01

    In mice with temporally-induced cardiac-specific deficiency of acyl-CoA synthetase-1 (Acsl1(H-/-)), the heart is unable to oxidize long-chain fatty acids and relies primarily on glucose for energy. These metabolic changes result in the development of both a spontaneous cardiac hypertrophy...... of sarco/endoplasmic reticulum calcium ATPase and phospholamban showed no difference between genotypes. To determine the role of mTOR in the development of cardiac hypertrophy, we treated Acsl1(H-/-) mice with rapamycin. Six to eight week old Acsl1(H-/-) mice and their littermate controls were given i.......p. tamoxifen to eliminate cardiac Acsl1, then concomitantly treated for 10weeks with i.p. rapamycin or vehicle alone. Rapamycin completely blocked the enhanced ventricular S6K phosphorylation and cardiac hypertrophy and attenuated the expression of hypertrophy-associated fetal genes, including α-skeletal actin...

  11. Anti-hypertensive drugs and left ventricular hypertrophy: a clinical update.

    Science.gov (United States)

    Milan, Alberto; Caserta, Mimma A; Avenatti, Eleonora; Abram, Sara; Veglio, Franco

    2010-12-01

    Structural remodelling of the heart, known as left ventricular hypertrophy (LVH), is a consequence of systemic hypertension, and is associated with an increased risk of cardiovascular morbidity and mortality. Therefore, particular attention should be paid to the identification, prevention and treatment of this condition in hypertensive patients. LVH seems to benefit from all classes of anti-hypertensive drugs; however, antagonists of the renin-angiotensin-aldosterone system (RAAS) have demonstrated an additional benefit in the inhibition and reversal of myocardial interstitial fibrosis. Nevertheless, in evaluating the degree of arterial hypertension and organ damage, many neuro-hormonal systems are involved, primarily the sympathetic nervous system, thereby explaining the use of different classes of anti-hypertensive drugs to prevent or reduce LVH. The RAAS antagonists are actually the recommended anti-hypertensive agents to prevent organ damage in hypertensive subjects or in hypertensives with evidence of LVH to reduce cardiovascular mortality and morbidity.

  12. Clenbuterol induces cardiac myocyte hypertrophy via paracrine signalling and fibroblast-derived IGF-1.

    Science.gov (United States)

    Bhavsar, Pankaj K; Brand, Nigel J; Felkin, Leanne E; Luther, Pradeep K; Cullen, Martin E; Yacoub, Magdi H; Barton, Paul J R

    2010-12-01

    The β(2)-selective adrenoreceptor agonist clenbuterol promotes both skeletal and cardiac muscle hypertrophy and is undergoing clinical trials in the treatment of muscle wasting and heart failure. We have previously demonstrated that clenbuterol induces a mild physiological ventricular hypertrophy in vivo with normal contractile function and without induction of α-skeletal muscle actin (αSkA), a marker of pathological hypertrophy. The mechanisms of this response remain poorly defined. In this study, we examine the direct action of clenbuterol on cardiocyte cultures in vitro. Clenbuterol treatment resulted in increased cell size of cardiac myocytes with increased protein accumulation and myofibrillar organisation characteristic of hypertrophic growth. Real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) revealed elevated mRNA expression of ANP and brain natriuretic peptide (BNP) but without change in αSkA, consistent with physiological hypertrophic growth. Clenbuterol-treated cultures also showed elevated insulin-like growth factor I (IGF-1) mRNA and activation of the protein kinase Akt. Addition of either IGF-1 receptor-blocking antibodies or LY294002 in order to inhibit phosphatidylinositol 3-kinase, a downstream effector of the IGF-1 receptor, inhibited the hypertrophic response indicating that IGF-1 signalling is required. IGF-1 expression localised primarily to the minor population of cardiac fibroblasts present in the cardiocyte cultures. Together these data show that clenbuterol acts to induce mild cardiac hypertrophy in cardiac myocytes via paracrine signalling involving fibroblast-derived IGF-1.

  13. Cucurbitacin B Protects Against Pressure Overload Induced Cardiac Hypertrophy.

    Science.gov (United States)

    Xiao, Yang; Yang, Zheng; Wu, Qing-Qing; Jiang, Xiao-Han; Yuan, Yuan; Chang, Wei; Bian, Zhou Yan; Zhu, Jin Xiu; Tang, Qi-Zhu

    2017-11-01

    Lack of effective anti-cardiac hypertrophy drugs creates a major cause for the increasing prevalence of heart failure. In the present study, we determined the anti-hypertrophy and anti-fibrosis potential of a natural plant triterpenoid, Cucurbitacin B both in vitro and in vivo. Aortic banding (AB) was performed to induce cardiac hypertrophy. After 1 week of surgery, mice were receive cucurbitacin B treatment (Gavage, 0.2 mg/kg body weight/2 day). After 4 weeks of AB, cucurbitacin B demonstrated a strong anti-hypertrophy and -fibrosis ability as evidenced by decreased of heart weight, myocardial cell cross-sectional area and interstitial fibrosis, ameliorated of systolic and diastolic abnormalities, normalized in gene expression of hypertrophic and fibrotic markers, reserved microvascular density in pressure overload induced hypertrophic mice. Cucurbitacin B also showed significant hypertrophy inhibitory effect in phenylephrine stimulated cardiomyocytes. The Cucurbitacin B-mediated mitigated cardiac hypertrophy was attributable to the increasing level of autophagy, which was associated with the blockade of Akt/mTOR/FoxO3a signal pathway, validated by SC79, MK2206, and 3-MA, the Akt agonist, inhibitor and autophagy inhibitor in vitro. The overexpression of constitutively active Akt completely abolished the Cucurbitacin B-mediated protection of cardiac hypertrophy in human cardiomyocytes AC16. Collectively, our findings suggest that cucurbitacin B protects against cardiac hypertrophy through increasing the autophagy level in cardiomyocytes, which is associated with the inhibition of Akt/mTOR/FoxO3a signal axis. J. Cell. Biochem. 118: 3899-3910, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

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

    Directory of Open Access Journals (Sweden)

    Degui eZhi

    2012-05-01

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

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

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    Elena Ulasova

    2013-01-01

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

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

    Science.gov (United States)

    Gentille-Lorente, Delicia; Salvadó-Usach, Teresa

    2016-01-01

    Sigmoid septum and hypertrophic cardiomyopathy presenting with left ventricular hypertrophy and, although they appear to be different entities, often involve problems in the differential diagnosis. This study was carried out to assess the prevalence and characteristics of the echocardiographic sigmoid septum and its differential findings regarding hypertrophic cardiomyopathy. Descriptive, observational and prospective study. A total of 1,770 patients were studied by echocardiography. Sigmoid septum (focal and isolated hypertrophy of the basal interventricular septum≥13mm in men and ≥12mm in women, exceeding ≥50% of the median septum thickness) was classified as «Type 1» (≤14mm) and «Type 2» (≥15mm). There were 59 cases of sigmoid septum (prevalence of 3.3%): 26 (1.5%) patients with type 1 (50% male) and 33 (1.9%) patients with type 2 (72.7% male); there were 25 (1.4%) cases of hypertrophic cardiomyopathy (76% male). The group with type 2 sigmoid septum differed from hypertrophic cardiomyopathy in: was older (73±10.5years; Phypertrophic cardiomyopathy, patients with type 2 sigmoid septum are older and generally hypertensive; otherwise, often they have no clear differences in their clinical, electrocardiographic or echocardiographic characteristics. Therefore, cardiac resonance is helpful in the differential diagnosis. Copyright © 2016 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

  17. [Study on tissue Doppler imaging in diagnosis of right ventricular hypertrophy in patients with silicosis complicated by chronic pulmonary heart disease].

    Science.gov (United States)

    Chen, Gongquan

    2014-12-01

    To investigate the value of tissue Doppler imaging (TDI) in the diagnosis of right ventricular hypertrophy in patients with silicosis complicated by chronic pulmonary heart disease. A total of 50 cases of silicosis complicated by chronic pulmonary heart disease in our hospital underwent conventional electrocardiography (ECG) and TDI. The detection rates for right ventricular hypertrophy by two methods were compared. Of 50 cases of silicosis complicated by chronic pulmonary heart disease, 19 were diagnosed with right ventricular hypertrophy by ECG, with a detection rate of 38.0%; 29 were diagnosed with right ventricular hypertrophy by TDI, with a detection rate off 58.0%. Statistical analysis suggested that TDI leads to a significantly higher detection rate for right ventricular hypertrophy in patients with silicosis complicated by chronic pulmonary heart disease (χ² = 4.006, P = 0.036). Both TDI and ECG can be used for detecting right ventricular hypertrophy in patients with silicosis complicated by chronic pulmonary heart disease, but the detection rate is higher when TDI is employed. In addition, ECG cannot directly reflect the increase in pulmonary artery pressure. Therefore, TDI is more suitable for the diagnosis of right ventricular hypertrophy in patients with silicosis complicated by chronic pulmonary heart disease and provides a strong diagnostic basis for the clinical treatment of silicosis complicated by pulmonary heart disease.

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

    Science.gov (United States)

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

    2014-03-20

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

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

    Science.gov (United States)

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

    2013-08-01

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

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

    Directory of Open Access Journals (Sweden)

    Shu-ichi Fujita

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

  1. Modeling and visualization of the activation wavefront propagation to improve understanding the QRS complex changes indicating left ventricular hypertrophy.

    Science.gov (United States)

    Svehlikova, Jana; Zelinka, Jan; Bacharova, Ljuba; Tysler, Milan

    2016-01-01

    Activation wavefront propagation was computed and visualized in a geometrical heart model for pathological cases of reduced velocity of propagation, left ventricular hypertrophy and their combination. Selected parameters of a multiple dipole equivalent heart generator were computed and compared for three heart geometries and several degrees and extents of reduction of propagation velocity. First, the influence of geometrical changes modeling the left ventricular hypertrophy at reference propagation velocity was compared with reduction of the propagation velocity in the reference heart geometry. Reduced propagation velocity yielded similar or greater changes of the magnitude of the (electrical) heart vector representing the activation wavefront than the geometrical changes. Observations of the wavefront propagation with reduced velocity revealed longer presence of a large extent of the wavefront during depolarization which resulted in increased magnitude of the heart vector. The duration of depolarization was significantly prolonged only when the propagation velocity was decreased to 25% of its normal value. Changes of the direction of the maximal heart vector were dependent on the position of the region where the propagation velocity was reduced. Then the combination of the left ventricular hypertrophy and reduced propagation velocity was studied. Such combination enhanced the enlargement of the electrical heart vector and significantly prolonged the duration of depolarization. The influence of reduced activation velocity on the observed parameters was greater than the effect of the enlargement of the left ventricular mass. The presented study showed that intramyocardial conduction disturbances might cause increase of the actual surface area of propagation wavefront leading to changes of the amplitudes of ECG signals comparable with the changes resulting from the left ventricular hypertrophy. Intramyocardial conduction disturbances, as well as the modeled 50

  2. Human paraoxonase gene cluster overexpression alleviates angiotensin II-induced cardiac hypertrophy in mice.

    Science.gov (United States)

    Pei, Jian-Fei; Yan, Yun-Fei; Tang, Xiaoqiang; Zhang, Yang; Cui, Shen-Shen; Zhang, Zhu-Qin; Chen, Hou-Zao; Liu, De-Pei

    2016-11-01

    Cardiac hypertrophy is the strongest predictor of the development of heart failure, and anti-hypertrophic treatment holds the key to improving the clinical syndrome and increasing the survival rates for heart failure. The paraoxonase (PON) gene cluster (PC) protects against atherosclerosis and coronary artery diseases. However, the role of PC in the heart is largely unknown. To evaluate the roles of PC in cardiac hypertrophy, transgenic mice carrying the intact human PON1, PON2, and PON3 genes and their flanking sequences were studied. We demonstrated that the PC transgene (PC-Tg) protected mice from cardiac hypertrophy induced by Ang II; these mice had reduced heart weight/body weight ratios, decreased left ventricular wall thicknesses and increased fractional shortening compared with wild-type (WT) control. The same protective tendency was also observed with an Apoe -/- background. Mechanically, PC-Tg normalized the disequilibrium of matrix metalloproteinases (MMPs)/tissue inhibitors of MMPs (TIMPs) in hypertrophic hearts, which might contribute to the protective role of PC-Tg in cardiac fibrosis and, thus, protect against cardiac remodeling. Taken together, our results identify a novel anti-hypertrophic role for the PON gene cluster, suggesting a possible strategy for the treatment of cardiac hypertrophy through elevating the levels of the PON gene family.

  3. The relationship of hyperinsulinemic state to left ventricular hypertrophy, microalbuminuria, and physical fitness in borderline and mild hypertension.

    Science.gov (United States)

    Tomiyama, H; Doba, N; Kushiro, T; Yamashita, M; Kanmatsuse, K; Kajiwara, N; Yoshida, H; Hinohara, S

    1997-06-01

    The relationship of the hyperinsulinemic state to left ventricular hypertrophy, left ventricular geometric patterns, microalbuminuria, and physical fitness were studied in 52 middle-aged unmedicated men with borderline and mild hypertension. Left ventricular mass index and relative wall thickness were assessed by echocardiography. Physical fitness was determined by symptom-limited maximal treadmill stress testings. The urinary concentration of microalbumin and C-peptide was measured in 24-h urine samples by radioimmunoassey. The 24-h urinary C-peptide excretion rate was correlated with left ventricular mass index (r = 0.46), relative wall thickness (r = 0.41), treadmill time (r = -0.35), normalized treadmill time (r = -0.52), systolic blood pressure at peak exercise (r = 0.29), and 24-h urinary microalbumin excretion (r = 0.48). Stepwise multiple regression analysis identified the left ventricular mass index, the 24-h urinary albumin excretion, and the normalized treadmill time as variables in the equation for the 24-h urinary C-peptide excretion. Thus, the hyperinsulinemic state is related to left ventricular hypertrophy, microalbuminuria, and impaired physical fitness in patients with borderline and mild hypertension.

  4. Sarcomeric lesions and remodeling proximal to intercalated disks in overload-induced cardiac hypertrophy.

    Science.gov (United States)

    Kebir, Sied; Orfanos, Zacharias; Schuld, Julia; Linhart, Markus; Lamberz, Christian; van der Ven, Peter F M; Schrickel, Jan; Kirfel, Gregor; Fürst, Dieter O; Meyer, Rainer

    2016-10-15

    Pressure overload induces cardiac remodeling involving both the contractile machinery and intercalated disks (IDs). Filamin C (FlnC) and Xin actin-binding repeat-containing proteins (XIRPs) are multi-adapters localizing in IDs of higher vertebrates. Knockout of the gene encoding Xin (Xirp1) in mice leads to a mild cardiac phenotype with ID mislocalization. In order to amplify this phenotype, we performed transverse aortic constriction (TAC) on control and Xirp1-deficient mice. TAC induced similar left ventricular hypertrophy in both genotypes, suggesting that the lack of Xin does not lead to higher susceptibility to cardiac overload. However, in both genotypes, FlnC appeared in "streaming" localizations across multiple sarcomeres proximal to the IDs, suggesting a remodeling response. Furthermore, FlnC-positive areas of remodeling, reminiscent of sarcomeric lesions previously described for skeletal muscles (but so far unreported in the heart), were also observed. These adaptations reflect a similarly strong effect of the pressure induced by TAC in both genotypes. However, 2 weeks post-operation TAC-treated knockout hearts had reduced levels of connexin43 and slightly increased incidents of ventricular tachycardia compared to their wild-type (WT) counterparts. Our findings highlight the FlnC-positive sarcomeric lesions and ID-proximal streaming as general remodeling responses in cardiac overload-induced hypertrophy. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Periodontitis and myocardial hypertrophy.

    Science.gov (United States)

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

    2017-04-01

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

  6. Supra-physiological dose of testosterone induces pathological cardiac hypertrophy.

    Science.gov (United States)

    Pirompol, Prapawadee; Teekabut, Vassana; Weerachatyanukul, Wattana; Bupha-Intr, Tepmanas; Wattanapermpool, Jonggonnee

    2016-04-01

    Testosterone and androgenic anabolic steroids have been misused for enhancement of physical performance despite many reports on cardiac sudden death. Although physiological level of testosterone provided many regulatory benefits to human health, including the cardiovascular function, supra-physiological levels of the hormone induce hypertrophy of the heart with unclear contractile activation. In this study, dose- and time-dependent effects of high-testosterone treatment on cardiac structure and function were evaluated. Adult male rats were divided into four groups of testosterone treatment for 0, 5, 10, and 20 mg/kg BW for 4, 8, or 12 weeks. Increases in both percentage heart:body weight ratio and cardiomyocyte cross-sectional area in representing hypertrophy of the heart were significantly shown in all testosterone-treated groups to the same degree. In 4-week-treated rats, physiological cardiac hypertrophy was apparent with an upregulation of α-MHC without any change in myofilament contractile activation. In contrast, pathological cardiac hypertrophy was observed in 8- and 12-week testosterone-treated groups, as indicated by suppression of myofilament activation and myocardial collagen deposition without transition of MHC isoforms. Only in 12-week testosterone-treated group, eccentric cardiac hypertrophy was demonstrated with unaltered myocardial stiffness, but significant reductions in the phosphorylation signals of ERK1/2 and mTOR. Results of our study suggest that the outcome of testosterone-induced cardiac hypertrophy is not dose dependent but is rather relied on the factor of exposure to duration in inducing maladaptive responses of the heart. © 2016 Society for Endocrinology.

  7. Eccentric Left Ventricular Hypertrophy and Sudden Death in Patients with End-Stage Kidney Disease.

    Science.gov (United States)

    de Roij van Zuijdewijn, Camiel L M; Hansildaar, Romy; Bots, Michiel L; Blankestijn, Peter J; van den Dorpel, Marinus A; Grooteman, Muriel P C; Kamp, Otto; ter Wee, Piet M; Nubé, Menso J

    2015-01-01

    Both all-cause and cardiovascular mortality risks are extremely high in patients with end-stage kidney disease (ESKD). Sudden death accounts for approximately one-quarter of all fatal events. Left ventricular hypertrophy (LVH) is a known risk factor for mortality and can be divided in 2 types: concentric and eccentric. This study evaluated possible differences in all-cause mortality, cardiovascular mortality and sudden death between prevalent ESKD patients with concentric and eccentric LVH. Participants of the CONvective TRAnsport STudy (CONTRAST) who underwent transthoracic echocardiography (TTE) at baseline were analyzed. In patients with LVH, a relative wall thickness of ≤0.42 was considered eccentric and >0.42 was considered concentric hypertrophy. Cox proportional hazards models, adjusted for potential confounders, were used to calculate hazard ratios (HRs) of patients with eccentric LVH versus patients with concentric LVH for all-cause mortality, cardiovascular mortality and sudden death. TTE was performed in 328 CONTRAST participants. LVH was present in 233 participants (71%), of which 87 (37%) had concentric LVH and 146 (63%) eccentric LVH. The HR for all-cause mortality of eccentric versus concentric LVH was 1.14 (p = 0.52), 1.79 (p = 0.12) for cardiovascular mortality and 4.23 (p = 0.02) for sudden death in crude analyses. Propensity score-corrected HR for sudden death in patients with eccentric LVH versus those with concentric LVH was 5.22 (p = 0.03). (1) The hazard for all-cause mortality, cardiovascular mortality and sudden death is markedly increased in patients with LVH. (2) The sudden death risk is significantly higher in ESKD patients with eccentric LVH compared to subjects with concentric LVH. © 2015 S. Karger AG, Basel.

  8. Left Atrial Performance in the Course of Hypertrophic Cardiomyopathy: Relation to Left Ventricular Hypertrophy and Fibrosis.

    Science.gov (United States)

    Kowallick, Johannes T; Silva Vieira, Miguel; Kutty, Shelby; Lotz, Joachim; Hasenfu, Gerd; Chiribiri, Amedeo; Schuster, Andreas

    2017-03-01

    Hypertrophic cardiomyopathy (HCM) is associated with left atrial (LA) functional abnormalities. The determinants and the degree of LA dysfunction in the course of HCM are not fully understood. We aimed to characterize LA mechanics in HCM, according to the extent of left ventricular (LV) hypertrophy and fibrosis. Seventy-three HCM patients and 23 age- and sex-matched controls underwent cardiovascular magnetic resonance imaging including late gadolinium enhancement (LGE). LA reservoir, conduit, and contractile functions were quantified by fractional volume changes and cardiovascular magnetic resonance feature-tracking-derived strain and strain rate. In multivariable regression, LA mechanics were associated with the extent of LV LGE (P = 0.033 to P < 0.001), but not with the LV mass extent or maximum wall thickness (P = 0.108 to P = 0.964). Left atrial function decreased according to the increase in extent of LV fibrosis (non-LGE; mild LGE ≤ 10%; intermediate LGE 11%-19%; severe LGE ≥ 20%). Compared with healthy controls, LA conduit function was impaired in HCM with no LGE already (LA emptying fraction conduit: 32% ± 7% vs 26 ± 14, P = 0.037). Conversely, LA contractile booster pump function was impaired in HCM with severe LGE only (LA emptying fraction booster: 40% ± 8% vs 20% ± 10%, P < 0.001; for controls vs LGE ≥ 20%, respectively). Left atrial functional abnormalities are associated with LV fibrosis, but not with LV hypertrophy. While LA conduit function is impaired in early HCM stages as represented by mild or absent LV fibrosis, LA contractile function is impaired later in the course of disease progression as demonstrated by the presence of severe LV fibrosis only. These novel markers of LA performance may potentially proof useful for disease staging and early detection of cardiac deterioration.

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    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 ...

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

    Science.gov (United States)

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

    2017-09-01

    Lysyl oxidase (LOX) controls matrix remodeling, a key process that underlies cardiovascular diseases and heart failure; however, a lack of suitable animal models has limited our knowledge with regard to the contribution of LOX to cardiac dysfunction. Here, we assessed the impact of LOX overexpression on ventricular function and cardiac hypertrophy in a transgenic LOX (TgLOX) mouse model with a strong cardiac expression of human LOX. TgLOX mice exhibited high expression of the transgene in cardiomyocytes and cardiofibroblasts, which are associated with enhanced LOX activity and H2O2 production and with cardiofibroblast reprogramming. LOX overexpression promoted an age-associated concentric remodeling of the left ventricle and impaired diastolic function. Furthermore, LOX transgenesis aggravated angiotensin II (Ang II)-induced cardiac hypertrophy and dysfunction, which triggered a greater fibrotic response that was characterized by stronger collagen deposition and cross-linking and high expression of fibrotic markers. In addition, LOX transgenesis increased the Ang II-induced myocardial inflammatory infiltrate, exacerbated expression of proinflammatory markers, and decreased that of cardioprotective factors. Mechanistically, LOX overexpression enhanced oxidative stress and potentiated the Ang II-mediated cardiac activation of p38 MAPK while reducing AMPK activation. Our findings suggest that LOX induces an age-dependent disturbance of diastolic function and aggravates Ang II-induced hypertrophy, which provides novel insights into the role of LOX in cardiac performance.-Galán, M., Varona, S., Guadall, A., Orriols, M., Navas, M., Aguiló, S., de Diego, A., Navarro, M. A., García-Dorado, D., Rodríguez-Sinovas, A., Martínez-González, J., Rodriguez, C. Lysyl oxidase overexpression accelerates cardiac remodeling and aggravates angiotensin II-induced hypertrophy. © FASEB.

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

    OpenAIRE

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

    2011-01-01

    Chlorthalidone (CTD) reduces 24-hour blood pressure more effectively than hydrochlorothiazide (HCTZ), but whether this influences electrocardiographic left ventricular hypertrophy (LVH) is uncertain. One source of comparative data is the Multiple Risk Factor Intervention Trial (MRFIT), which randomly assigned 8,012 hypertensive men to special intervention (SI) or usual care (UC). SI participants could use CTD or HCTZ initially; previous analyses have grouped clinics by their main diuretic use...

  12. Left ventricular hypertrophy and antiarrhythmic drugs in atrial fibrillation: impact on mortality.

    Science.gov (United States)

    Chung, Roy; Houghtaling, Penny L; Tchou, Michael; Niebauer, Mark J; Lindsay, Bruce D; Tchou, Patrick J; Chung, Mina K

    2014-10-01

    Despite sparse clinical data, current atrial fibrillation (AF) guidelines favor amiodarone as a drug of choice for patients with left ventricular hypertrophy (LVH). This study tested the hypothesis that patients with persistent AF and LVH on nonamiodarone antiarrhythmics have higher mortality compared to patients on amiodarone. In an observational cohort analysis of patients who underwent cardioversion for AF, patients with LVH, defined as left ventricular wall thickness ≥1.4 cm, by echocardiogram prior to their first cardioversion, were included; clinical data, including antiarrhythmic drugs and ejection fraction (LVEF), were collected. Mortality, determined via the Social Security Death Index, was analyzed using Kaplan-Meier and Cox proportional hazards models to determine whether antiarrhythmic drugs were associated with higher mortality. In 3,926 patients, echocardiographic wall thickness was available in 1,399 (age 66.8 ± 11.8 years, 67% male, LVEF 46 ± 15%, septum 1.3 ± 0.4, posterior wall 1.2 ± 0.2 cm), and 537 (38%) had LVH ≥1.4 cm. Among 537 patients with LVH, mean age was 67.5 ± 11.7 years, 76.4% were males, and mean LVEF was 48.3 ± 13.3%. Amiodarone was associated with lower survival (log rank P = 0.001), including after adjusting for age, LVEF, and coronary artery disease (P = 0.023). In propensity-score matched cohorts with LVH treated with no drugs, nonamiodarone antiarrhythmic drugs (non-AADs), or amiodarone (N = 65 each group), there was early lower survival in patients on amiodarone (P = 0.05). Patients with persistent AF and LVH on non-AADs do not have higher mortality compared to patients on amiodarone. Importantly, these findings do not support amiodarone as a superior choice in patients with LVH. ©2014 Wiley Periodicals, Inc.

  13. Left ventricular hypertrophy detected by echocardiography in HIV-infected patients.

    Science.gov (United States)

    Pombo, Marta; Olalla, Julián; Del Arco, Alfonso; De La Torre, Javier; Urdiales, Daniel; Aguilar, Ana; Prada, José Luis; García-Alegría, Javier; Ruiz-Mateas, Francisco

    2013-09-01

    Left ventricular hypertrophy (LVH) is a predictor of overall mortality in the general population. The most sensitive diagnostic method is transthoracic echocardiography (TTE). In this study, we describe the prevalence of LVH, and the factors associated with it, in a group of patients with HIV infection. TTE was offered to all patients attending the outpatient clinic of the Hospital Costa del Sol (Marbella, Spain) between 1 December 2009 and 28 February 2011. The corresponding demographic and clinical data were obtained. The left ventricular mass (LVM) was calculated and indexed by height(2.7). LVH was defined as LVM >48g/m(2.7) in men or >44g/m(2.7) in women. We examined 388 individuals (75.5% male, mean age 45.38years). Of these, 76.1% were receiving HAART; 11.9% had hypertension, 6.2% had diabetes mellitus, 23.2% had dyslipidaemia and 53.6% were tobacco users. The risk of cardiovascular disease at 10years (RV10) was 12.15% (95%CI: 10.99-13.31%). 19.1% of these patients had a high RV10. A total of 69 patients (19.8%) presented high LVM. Age, hypertension, dyslipidaemia, RV10 and the use of nevirapine were associated with a greater presence of LVH in the univariate analysis. In the logistic regression analysis performed, the factors retained in the model were the presence of high RV10 (OR: 2.92, 95%CI: 1.39-6.15) and the use of nevirapine (OR 2.20, 95%CI: 1.18-4.14). In this group of patients, the use of nevirapine and the presence of high RV10 were associated with LVH. The use of nevirapine might be related to its prescription for patients with higher RV10. Copyright © 2013 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  14. Factors associated with diagnostic discrepancy for left ventricular hypertrophy between electrocardiography and echocardiography.

    Science.gov (United States)

    Petersen, Søren Sandager; Pedersen, Line Reinholdt; Pareek, Manan; Nielsen, Mette Lundgren; Diederichsen, Søren Zöga; Leósdóttir, Margrét; Nilsson, Peter M; Diederichsen, Axel Cosmus Pyndt; Olsen, Michael Hecht

    2017-02-01

    To investigate the influence of cardiovascular risk factors, including fasting plasma glucose (FPG), on the association between electrocardiographic (ECG) and echocardiographic left ventricular hypertrophy (LVH) in an elderly population. We tested cross-sectional associations between electrocardiographic and echocardiographic LVH, defining LVH according to the Sokolow-Lyon voltage combination, Cornell voltage-duration product, or left ventricular mass index (LVMI). Differences between standardized LVMI and Sokolow-Lyon voltage combination or Cornell voltage-duration product (absolute value/cut-off value for LVH) were used as outcome variables in order to identify explanatory variables associated with diagnostic discrepancies between ECG and echocardiography. Of the 1382 subjects included, 77% did not display any signs of LVH, 6% had LVH defined by ECG only, 13% had LVH defined by echocardiography only, and 5% had LVH on both ECG and echocardiography. Older subjects and those with higher blood pressure and RWT were more likely to have a relatively greater LVMI on echocardiography than that predicted on ECG (odds ratio: 1.65 per 10 years (95% confidence interval (CI): 1.27-2.15), p = .0002, odds ratio: 1.17 per 10 mmHg (95% CI: 1.09-1.25), p < .0001, and odds ratio: 1.21 per 0.10 (95% CI: 1.02-1.42), p = .03). In addition, discrepancy was also seen in females and subjects receiving antihypertensive medication (odds ratio: 1.41 (95% CI: 1.04-1.89), p = .03 and odds ratio: 1.41 (95% CI: 1.06-1.87), p = .02), but FPG did not independently influence discrepancy between ECG and echocardiography. Age, blood pressure, female sex, greater RWT and use of antihypertensive medication were associated with a greater risk of non-consistency between LVH determined by ECG and echocardiography.

  15. The clinical features, outcomes and genetic characteristics of hypertrophic cardiomyopathy patients with severe right ventricular hypertrophy.

    Directory of Open Access Journals (Sweden)

    Xiying Guo

    Full Text Available Severe right ventricular hypertrophy (SRVH is a rare phenotype in hypertrophic cardiomyopathy (HCM for which limited information is available. This study was undertaken to investigate the clinical, prognostic and genetic characteristics of HCM patients with SRVH.HCM with SRVH was defined as HCM with a maximum right ventricular wall thickness ≥10 mm. Whole-genome sequencing (WGS was performed in HCM patients with SRVH. Multivariate Cox proportional hazards regression models were used to identify risk factors for cardiac death and events in HCM with SRVH. Patients with apical hypertrophic cardiomyopathy (ApHCM were selected as a comparison group. The clinical features and outcomes of 34 HCM patients with SRVH and 273 ApHCM patients were compared.Compared with the ApHCM group, the HCM with SRVH group included younger patients and a higher proportion of female patients and also displayed higher cardiovascular morbidity and mortality. The multivariate Cox proportional hazards regression models identified 2 independent predictors of cardiovascular death in HCM patients with SRVH, a New York Heart Association class ≥III (hazard ratio [HR] = 8.7, 95% confidence interval (CI: 1.43-52.87, p = 0.019 and an age at the time of HCM diagnosis ≤18 (HR = 5.5, 95% CI: 1.24-28.36, p = 0.026. Among the 11 HCM patients with SRVH who underwent WGS, 10 (90.9% were identified as carriers of at least one specific sarcomere gene mutation. MYH7 and TTN mutations were the most common sarcomere mutations noted in this study. Two or more HCM-related gene mutations were observed in 9 (82% patients, and mutations in either other cardiomyopathy-related genes or ion-channel disease-related genes were found in 8 (73% patients.HCM patients with SRVH were characterized by poor clinical outcomes and the presentation of multiple gene mutations.

  16. Cardiovascular Disease Risk Factors and Left Ventricular Hypertrophy in Girls and Boys With CKD

    Science.gov (United States)

    Ruebner, Rebecca L.; Ng, Derek; Mitsnefes, Mark; Foster, Bethany J.; Meyers, Kevin; Warady, Bradley

    2016-01-01

    Background and objectives Prior studies suggested that women with CKD have higher risk for cardiovascular disease (CVD) and mortality than men, although putative mechanisms for this higher risk have not been identified. We assessed sex differences in (1) CVD risk factors and left ventricular hypertrophy (LVH), and (2) the relationship of left ventricular mass (LVM) with different measures of body size in children with CKD. Design, setting, participants, and measurements The study population comprised 681 children with CKD from the Chronic Kidney Disease in Children cohort, contributing 1330 visits. CVD risk factors were compared cross-sectionally by sex. LVH was defined as LVM/height2.7 >95th percentile and LVM relative to estimated lean body mass (eLBM) >95th percentile for age and sex. Differences in LVM by sex were assessed by adjusting for age, weight, height, and eLBM using bivariate and multivariate regression models. Results Girls were less likely to have uncontrolled hypertension (26% versus 38%, P=0.001), had lower diastolic BP z-scores (+0.3 versus +0.6, P=0.001), and had lower prevalence of high triglycerides (38% versus 47%, P=0.03) compared with boys. When LVH was defined by LVM indexed to height, girls had higher prevalence of LVH (16% versus 9%, P=0.01); when LVH was defined by LVM relative to eLBM, prevalence of LVH was similar between girls and boys (18% versus 17%, P=0.92). In regression models adjusting for eLBM, no sex differences in LVM were observed. Conclusions Despite lack of increased prevalence of CVD risk factors, indexing LVM to height showed a higher proportion of LVH among girls, while estimates of LVH based on eLBM showed no sex differences. Indexing LVM to eLBM may be an alternative to height indexing in children with CKD. PMID:27630183

  17. Screening for left ventricular hypertrophy in patients with type 2 diabetes mellitus in the community

    Directory of Open Access Journals (Sweden)

    Bagg Warwick

    2011-04-01

    Full Text Available Abstract Background Left ventricular hypertrophy (LVH is a strong predictor of cardiovascular disease and is common among patients with type 2 diabetes. However, no systematic screening for LVH is currently recommended for patients with type 2 diabetes. The purpose of this study was to determine whether NT-proBNP was superior to 12-lead electrocardiography (ECG for detection of LVH in patients with type 2 diabetes. Methods Prospective cross-sectional study comparing diagnostic accuracy of ECG and NT-proBNP for the detection of LVH among patients with type 2 diabetes. Inclusion criteria included having been diagnosed for > 5 years and/or on treatment for type 2 diabetes; patients with Stage 3/4 chronic kidney disease and known cardiovascular disease were excluded. ECG LVH was defined as either the Sokolow-Lyon or Cornell voltage criteria. NT-proBNP level was measured using the Roche Diagnostics Elecsys assay. Left ventricular mass was assessed from echocardiography. Receiver operating characteristic curve analysis was carried out and area under the curve (AUC was calculated. Results 294 patients with type 2 diabetes were recruited, mean age 58 (SD 11 years, BP 134/81 ± 18/11 mmHg, HbA1c 7.3 ± 1.5%. LVH was present in 164 patients (56%. In a logistic regression model age, gender, BMI and a history of hypertension were important determinants of LVH (p Conclusions LVH was highly prevalent in asymptomatic patients with type 2 diabetes. ECG was an inadequate test to identify LVH and while NT-proBNP was superior to ECG it remained unsuitable for detecting LVH. Thus, there remains a need for a screening tool to detect LVH in primary care patients with type 2 diabetes to enhance risk stratification and management.

  18. Left Ventricular Hypertrophy and Antiarrhythmic Drugs In Atrial Fibrillation: Impact On Mortality

    Science.gov (United States)

    Chung, Roy; Houghtaling, Penny L.; Tchou, Michael; Niebauer, Mark J.; Lindsay, Bruce D.; Tchou, Patrick J.; Chung, Mina K.

    2015-01-01

    Background Despite sparse clinical data, current atrial fibrillation (AF) guidelines favor amiodarone as a drug of choice for patients with left ventricular hypertrophy (LVH). Objective This study tested the hypothesis that patients with persistent AF and LVH on nonamiodarone antiarrhythmics have higher mortality compared to patients on amiodarone. Methods In an observational cohort analysis of patients who underwent cardioversion for AF, patients with LVH, defined as left ventricular wall thickness ≥1.4 cm, by echocardiogram prior to their first cardioversion were included; clinical data, including antiarrhythmic drugs and ejection fraction (LVEF) were collected. Mortality, determined via the Social Security Death Index, was analyzed using Kaplan-Meier and Cox proportional hazards models to determine whether antiarrhythmic drugs were associated with higher mortality. Results In 3926 patients, echocardiographic wall thickness was available in 1399 (age 66.8±11.8 years, 67% male, LVEF 46±15%, septum 1.3±0.4, posterior wall 1.2±0.2 cm), and 537(38%) had LVH≥1.4cm. Among 537 patients with LVH, mean age was 67.5±11.7 years, 76.4% were males, and mean LVEF was 48.3±13.3%. Amiodarone was associated with lower survival (log rank p=0.001), including after adjusting for age, LVEF and CAD (p=0.023). In propensity-score matched cohorts with LVH treated with no drugs, non-amiodarone antiarrhythmic drugs or amiodarone (N=65 each group), there was early lower survival in patients on amiodarone (p=0.05). Conclusions Patients with persistent AF and LVH on non-amiodarone antiarrhythmic drugs do not have higher mortality compared to patients on amiodarone. Importantly, these findings do not support amiodarone as a superior choice in patients with LVH. PMID:24831860

  19. Assessment of voltage criteria for left ventricular hypertrophy in adult hypertensives in south-western Nigeria.

    Science.gov (United States)

    Ogunlade, Oluwadare; Akintomide, Anthony Olubunmi

    2013-03-01

    Left ventricular hypertrophy (LVH) is a common pathophysiological consequence of hypertension. Various voltage (ECG) criteria exist for evaluation of LVH. This study assessed the performance of 4 commonly used ECG criteria in south-western Nigeria. A cross-sectional descriptive study of adult hypertensive subjects. Participants were assessed for LVH using 4 ECG criteria: Sokolow-Lyon, Araoye code system, Cornell voltage, and Gubner-Ungerleider criteria. Echocardiography was used to determine the left ventricular mass index for the participants, and a value greater than 125 g/m(2) was used as the cut-off point for LVH. The sensitivity, specificity, accuracy, positive and negative predictive values were determined for each of the ECG criteria. 90 subjects (45 males, 45 females) participated in the study. The prevalence of LVH by echocardiography was 32.2%. The prevalence of LVH by voltage criteria were: 45.6%, 42.2%, 34.4%, 13.3% by Sokolow-Lyon, Araoye code system, Cornell, and Gubner-Ungerleider criteria, respectively. The sensitivity and specificity respectively of the ECG criteria were 58.62% and 60.66% (Sokolow-Lyon), 48.28% and 60.65% (Araoye code system), 51.72% and 73.77% (Cornell), and 13.79% and 86.89% (Gubner-Ungerleider). Out of the 4 ECG criteria, Araoye code system, Cornell and Sokolow-Lyon criteria compared favorably well with echocardiography and may be used in the initial assessment of LVH in adult hypertensive subjects. However, a combination of any of the 3 criteria with Gubner-Ungerleider criterion will be more clinically useful.

  20. Improvements in ECG accuracy for diagnosis of left ventricular hypertrophy in obesity.

    Science.gov (United States)

    Rider, Oliver J; Ntusi, Ntobeko; Bull, Sacha C; Nethononda, Richard; Ferreira, Vanessa; Holloway, Cameron J; Holdsworth, David; Mahmod, Masliza; Rayner, Jennifer J; Banerjee, Rajarshi; Myerson, Saul; Watkins, Hugh; Neubauer, Stefan

    2016-10-01

    The electrocardiogram (ECG) is the most commonly used tool to screen for left ventricular hypertrophy (LVH), and yet current diagnostic criteria are insensitive in modern increasingly overweight society. We propose a simple adjustment to improve diagnostic accuracy in different body weights and improve the sensitivity of this universally available technique. Overall, 1295 participants were included-821 with a wide range of body mass index (BMI 17.1-53.3 kg/m(2)) initially underwent cardiac magnetic resonance evaluation of anatomical left ventricular (LV) axis, LV mass and 12-lead surface ECG in order to generate an adjustment factor applied to the Sokolow-Lyon criteria. This factor was then validated in a second cohort (n=520, BMI 15.9-63.2 kg/m(2)). When matched for LV mass, the combination of leftward anatomical axis deviation and increased BMI resulted in a reduction of the Sokolow-Lyon index, by 4 mm in overweight and 8 mm in obesity. After adjusting for this in the initial cohort, the sensitivity of the Sokolow-Lyon index increased (overweight: 12.8% to 30.8%, obese: 3.1% to 27.2%) approaching that seen in normal weight (37.8%). Similar results were achieved in the validation cohort (specificity increased in overweight: 8.3% to 39.1%, obese: 9.4% to 25.0%) again approaching normal weight (39.0%). Importantly, specificity remained excellent (>93.1%). Adjusting the Sokolow-Lyon index for BMI (overweight +4 mm, obesity +8 mm) improves the diagnostic accuracy for detecting LVH. As the ECG, worldwide, remains the most widely used screening tool for LVH, implementing these findings should translate into significant clinical benefit. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  1. Home versus office blood pressure: longitudinal relations with left ventricular hypertrophy: the Finn-Home study.

    Science.gov (United States)

    Sivén, Sam S E; Niiranen, Teemu J; Langén, Ville L J; Puukka, Pauli J; Kantola, Ilkka M; Jula, Antti M

    2017-02-01

    Electrocardiographically assessed left-ventricular hypertrophy (ECG-LVH) is a particularly high-risk phenomenon that is a part of every hypertensive patient's initial work-up. Several cross-sectional studies have demonstrated that home blood pressure (BP) has a stronger relation to LVH than office BP. However, longitudinal evidence on the association between home BP and target organ damage is scarce to nonexistent. We studied in a sample of 615 community-dwelling participants (mean age at baseline 53.7 ± 7.2, 58% women) whether change in home BP is more strongly associated with change in ECG-LVH than change in office BP over an 11-year follow-up. Pearson's correlation coefficients between changes in home/office SBP and changes in Sokolow-Lyon index, Cornell voltage, Cornell product and R wave amplitude in aVL were 0.21/0.18, 0.28/0.17, 0.25/0.16, and 0.32/0.20, respectively (asterisk indicates P home/office DBP and change in the aforementioned ECG-LVH indexes, the correlations were 0.12/0.12, 0.20/0.15, 0.16/0.12, and 0.28/0.19. Multivariable-adjusted regression modelling provided similar results. No clinically significant increase in correlations between home BP and ECG-LVH indexes occurred after the fourth day of home BP measurement. Our study demonstrates for the first time the superiority of home BP over office BP in the follow-up of left ventricular mass. The results of this and previous studies underline the importance of using out-of-office BP measurements as the primary method for assessing blood pressure levels.

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

    Science.gov (United States)

    Yan, Ling; Bowman, Marion A Hofmann

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

  3. TGFβ Inducible Early Gene-1 (TIEG1) and Cardiac Hypertrophy: Discovery and Characterization of a Novel Signaling Pathway

    Science.gov (United States)

    Rajamannan, Nalini M.; Subramaniam, Malayannan; Abraham, Theodore P.; Vasile, Vlad C.; Ackerman, Michael J.; Monroe, David G.; Chew, Teng-Leong; Spelsberg, Thomas C.

    2014-01-01

    Cellular mechanisms causing cardiac hypertrophy are currently under intense investigation. We report a novel finding in the TGFβ inducible early gene (TIEG) null mouse implicatingTIEG1 in cardiac hypertrophy. The TIEG−/− knock-out mouse was studied. Male mice age 4–16 months were characterized (N = 86 total) using echocardiography, transcript profiling by gene microarray, and immunohistochemistry localized upregulated genes for determination of cellular mechanism. The female mice (N =40) did not develop hypertrophy or fibrosis. The TIEG −/− knock-out mouse developed features of cardiac hypertrophy including asymmetric septal hypertrophy, an increase in ventricular size at age 16 months, an increase (214%) in mouse heart/weight body weight ratio TIEG−/−, and an increase in wall thickness in TIEG−/− mice of (1.85 ±0.21 mm), compared to the control (1.13 ±0.15 mm, PMasson Trichrome staining demonstrated evidence of myocyte disarray and myofibroblast fibrosis. Microarray analysis of the left ventricles demonstrated that TIEG−/− heart tissues expressed a 13.81-fold increase in pituitary tumor-transforming gene-1 (Pttg1). An increase in Pttg1 and histone H3 protein levels were confirmed in the TIEG−/− mice hearts tissues. We present evidence implicating TIEG and possibly its target gene, Pttg1, in the development of cardiac hypertrophy in the TIEG null mouse. PMID:16888812

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

    Science.gov (United States)

    Diederichsen, Søren Z; Pareek, Manan; Nielsen, Mette L; D'Souza, Maria; Leósdóttir, Margrét; Nilsson, Peter M; Olsen, Michael H

    2015-06-01

    To evaluate relationships between fasting plasma glucose (FPG), other cardiovascular risk markers and left ventricular hypertrophy (LVH) as detected by electrocardiography. Subjects were selected randomly from groups defined by FPG. Traditional risk markers were assessed. LVH was defined by either Cornell voltage-duration product (CP) or Sokolow-Lyon voltage combination (SL), and univariate and multivariable regressions were performed in search of explanatory factors for the presence of LVH and the values of CP and SL. Of the 1759 subjects included, 1007 had a history of cardiovascular disease and/or medical treatment, while 752 subjects appeared to be healthy. We found an independent association between FPG and LVH (odds ratio 1.152, p = 0.042] as well as continuous CP (beta = 0.126, p = 0.007) in healthy men. As expected, we found an association between systolic blood pressure and LVH (odds ratio 1.020, p < 0.001) among healthy subjects, but only in subjects with FPG < 6 mmol/l (p = 0.04 for interaction). We found an independent association between FPG and LVH in healthy men, and no potentiating effect by FPG on the impact of hypertension.

  5. Pressor hormone profile during stress in hypertension: does vasopressin interfere with left ventricular hypertrophy?

    Science.gov (United States)

    Manolis, A; Athanasopoulos, G; Karatasakis, G; Gavras, I; Bresnahan, M; Cokkinos, D V; Gavras, H

    1993-05-01

    Neurohormonal factors may account for the fact that patients with similar severity and duration of hypertension develop different degrees of left ventricular hypertrophy (LVH). The purpose of this work was to compare the pressor hormone profiles of hypertensive subjects off medication during exercise testing. Nineteen patients, stratified according to echocardiographically diagnosed absence (Group I n = 6) or presence (Group II n = 13) of LVH, underwent testing on the treadmill according to the Bruce protocol. Both groups were comparable in age, severity and duration of hypertension and reached similar double product at peak exercise. Measurements of plasma renin activity (PRA), plasma catecholamines and vasopressin (AVP) at baseline, peak exercise and post exercise revealed significant differences between groups: Group I had suppressed PRA levels throughout and had significantly higher baseline AVP levels, which increased further at peak effort. Group II had significantly higher baseline PRA levels, which tended to increase further at peak effort, and had suppressed AVP levels throughout. There was a significant negative correlation between percent increments in AVP and increments in double product. Norepinephrine increased significantly with effort in both groups, but the levels attained were higher in Group I. In view of the known negative inotropic action of AVP and the trophic effect of angiotensin, we speculate that lower baseline AVP and higher PRA, together with inability of AVP to increase with effort, may be causally related to development of LVH.

  6. Computational modeling of the electromechanical response of a ventricular ber a ected by eccentric hypertrophy

    Directory of Open Access Journals (Sweden)

    Bianco Fabrizio Del

    2017-12-01

    Full Text Available The aim of this work is to study the effects of eccentric hypertrophy on the elec- tromechanics of a single myocardial ventricular fiber by means of a one-dimensional finite-element strongly-coupled model. The electrical current ow model is written in the reference configuration and it is characterized by two geometric feedbacks, i.e. the conduction and convection ones, and by the mechanoelectric feedback due to stretch- activated channels. First, the inuence of such feedbacks is investigated for both a healthy and a hypertrophic fiber in case of isometric simulations. No relevant discrepancies are found when disregarding one or more feedbacks for both fibers. Then, all feedbacks are taken into account while studying the electromechanical responses of fibers. The results from isometric tests do not point out any notable difference between the healthy and hypertrophic fibers as regards the action potential duration and conduction velocity. The length-tension relationships show increased stretches and reduced peak values for tension instead. The tension-velocity relationships derived from afterloaded isotonic and quick- release tests depict higher values of contraction velocity at smaller afterloads. Moreover, higher maximum shortenings are achieved during the isotonic contraction. In conclusion, our simulation results are innovative in predicting the electromechanical behavior of eccentric hypertrophic fibers.

  7. Electrocardiographic left ventricular hypertrophy Cornell product is a feasible predictor of cardiac prognosis in patients with chronic heart failure.

    Science.gov (United States)

    Otaki, Yoichiro; Takahashi, Hiroki; Watanabe, Tetsu; Kadowaki, Shinpei; Narumi, Taro; Honda, Yuki; Hasegawa, Hiromasa; Honda, Shintaro; Funayama, Akira; Nishiyama, Satoshi; Arimoto, Takanori; Shishido, Tetsuro; Miyashita, Takehiko; Miyamoto, Takuya; Kubota, Isao

    2014-04-01

    Left ventricular hypertrophy (LVH) is an independent risk factor for cardiovascular disease and is associated with heart failure development. The Cornell product is an easily measured electrocardiographic parameter for assessing LVH. However, it is undetermined whether the Cornell product can predict the cardiac prognosis of chronic heart failure (CHF) patients. We performed standard 12-lead electrocardiography and calculated the Cornell product in 432 consecutive CHF patients. LV geometry was assessed as normal, concentric remodeling, concentric or eccentric hypertrophy. The Cornell product was significantly higher in patients with eccentric hypertrophy, and increased with advancing New York Heart Association functional class. During a median follow-up of 660 days, there were 121 cardiac events including 36 cardiac deaths and 85 re-hospitalizations for worsening heart failure. Multivariate Cox proportional hazard analysis showed that the Cornell product was an independent predictor of cardiac events in CHF patients. Patients in the highest quartile of Cornell product had a higher prevalence of LV eccentric hypertrophy (22, 29, 33 and 67 % for quartiles one through four). Kaplan-Meier analysis demonstrated that the highest quartile of Cornell product was associated with the greatest risk among CHF patients. The Cornell product is associated with LV eccentric hypertrophy and can be used to predict future cardiac events in CHF patients.

  8. Cinnamaldehyde attenuates pressure overload-induced cardiac hypertrophy.

    Science.gov (United States)

    Yang, Liu; Wu, Qing-Qing; Liu, Yuan; Hu, Zhe-Fu; Bian, Zhou-Yan; Tang, Qi-Zhu

    2015-01-01

    Cinnamaldehyde is a major bioactive compound isolated from the leaves of Cinnamomum osmophloeum. Studies have demonstrated that cinnamaldehyde has anti-bacterial activity, anti-tumorigenic effect, immunomodulatory effect, anti-fungal activity, anti-oxidative effect, anti-inflammatory and anti-diabetic effect. It has been proven that Cinnamaldehyde improves ischemia/reperfusion injury of pre-treatment. However, little is known about the effect of cinnamaldehyde on cardiac hypertrophy. Aortic banding (AB) was performed to induce cardiac hypertrophy in mice. Cinnamaldehyde premixed in diets was administered to mice after one week of AB. Echocardiography and catheter-based measurements of hemodynamic parameters were performed at week 7 after starting cinnamaldehyde (8 weeks after surgery). The extent of cardiac hypertrophy was evaluated by pathological and molecular analyses of heart samples. Meanwhile, the effect of cinnamaldehyde on myocardial hypertrophy, fibrosis and dysfunction induced by AB was investigated, as was assessed by heart weigh/body weight, lung weight/body weight, heart weight/tibia length, echocardiographic and haemodynamic parameters, histological analysis, and gene expression of hypertrophic and fibrotic markers. Our data demonstrated that echocardiography and catheter-based measurements of hemodynamic parameters at week 7 revealed the amelioration of systolic and diastolic abnormalities by cinnamaldehyde intervention. Cardiac fibrosis in AB mice was also decreased by cinnamaldehyde. Moreover, the beneficial effect of cinnamaldehyde was associated with the normalization in gene expression of hypertrophic and fibrotic markers. Further studies showed that pressure overload significantly induced the activation of extracellular signal-regulated kinase (ERK) signaling pathway, which was blocked by cinnamaldehyde. Cinnamaldehyde may be able to retard the progression of cardiac hypertrophy and fibrosis, probably via blocking ERK signaling pathway.

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

    Science.gov (United States)

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

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

  10. Prevalence and correlates of echocardiographic determined left ventricular hypertrophy in 2318 asymptomatic middle-aged men: the ECCIS project. Epidemiolgia e Clinica della Cardiopatia Ischemica Silente.

    Science.gov (United States)

    Antoniucci, D; Seccareccia, F; Menotti, A; Dovellini, E V; Prati, P L; Rovelli, F; Fazzini, P F

    1997-04-01

    It is well established that left ventricular hypertrophy is a strong and independent risk factor for cardiovascular morbidity and mortality. This study was designed to determine the prevalence and correlates of left ventricular hypertrophy (LVH) among a sample population of 2318 totally asymptomatic men aged 40-59. This sample is a subset of the participants in the ECCIS Project. Left ventricular mass was estimated by echocardiography. The following individual variables were employed in the multiple linear regression analyses: age, diastolic and systolic blood pressure at rest and at peak exercise, body mass index, body surface area, conditioning physical activity. Three indexes of left ventricular mass were used: left ventricular mass/height, left ventricular mass/body surface area and "adjusted left ventricular mass" derived from adjustment, using a regression model, of left ventricular mass by age, body mass index and body surface area. The sample was subdivided in 3 blood pressure classes; normotensive (n = 1605), borderline (n = 390) and hypertensive (n = 323). All the variables considered with the exception of diastolic blood pressure both at rest and peak exercise were significantly correlated with left ventricular mass. Upper normal limits for left ventricular mass indexed to height and body surface area and of adjusted left ventricular mass were 143 g/m, 129 g/m2, and 245 g respectively. The prevalences of left ventricular hypertrophy, as determined by the reference standard of left ventricular mass/height, left.ventricular mass/body surface area and adjusted left ventricular mass, ranged 2.7-3.2% in the normotensive group, 4.2-5.4% in the borderline group and 11.8-14.5% in the hypertensive group, and were lower using adjusted left ventricular mass index. The results of this study show that the prevalence of left ventricular hypertrophy using adjustment by age, body surface area and body mass index reduces variability of left ventricular mass associated

  11. Diuretics prevent thiazolidinedione-induced cardiac hypertrophy without compromising insulin-sensitizing effects in mice.

    Science.gov (United States)

    Chang, Cherng-Shyang; Tsai, Pei-Jane; Sung, Junne-Ming; Chen, Ju-Yi; Ho, Li-Chun; Pandya, Kumar; Maeda, Nobuyo; Tsai, Yau-Sheng

    2014-02-01

    Much concern has arisen regarding critical adverse effects of thiazolidinediones (TZDs), including rosiglitazone and pioglitazone, on cardiac tissue. Although TZD-induced cardiac hypertrophy (CH) has been attributed to an increase in plasma volume or a change in cardiac nutrient preference, causative roles have not been established. To test the hypothesis that volume expansion directly mediates rosiglitazone-induced CH, mice were fed a high-fat diet with rosiglitazone, and cardiac and metabolic consequences were examined. Rosiglitazone treatment induced volume expansion and CH in wild-type and PPARγ heterozygous knockout (Pparg(+/-)) mice, but not in mice defective for ligand binding (Pparg(P465L/+)). Cotreatment with the diuretic furosemide in wild-type mice attenuated rosiglitazone-induced CH, hypertrophic gene reprogramming, cardiomyocyte apoptosis, hypertrophy-related signal activation, and left ventricular dysfunction. Similar changes were observed in mice treated with pioglitazone. The diuretics spironolactone and trichlormethiazide, but not amiloride, attenuated rosiglitazone effects on volume expansion and CH. Interestingly, expression of glucose and lipid metabolism genes in the heart was altered by rosiglitazone, but these changes were not attenuated by furosemide cotreatment. Importantly, rosiglitazone-mediated whole-body metabolic improvements were not affected by furosemide cotreatment. We conclude that releasing plasma volume reduces adverse effects of TZD-induced volume expansion and cardiac events without compromising TZD actions in metabolic switch in the heart and whole-body insulin sensitivity. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  12. Changes in T-Tubules and Sarcoplasmic Reticulum in Ventricular Myocytes in Early Cardiac Hypertrophy in a Pressure Overload Rat Model

    Directory of Open Access Journals (Sweden)

    Perla Pérez-Treviño

    2015-10-01

    Full Text Available Background/Aims: Pressure-overload (PO causes cardiac hypertrophy (CH, and eventually leads to heart failure (HF. HF ventricular myocytes present transverse-tubules (TT loss or disarrangement and decreased sarcoplasmic reticulum (SR density, and both contribute to altered Ca2+ signaling and heart dysfunction. It has been shown that TT remodeling precedes HF, however, it is unknown whether SR structural and functional remodeling also starts early in CH. Methods: Using confocal microscopy, we assessed TT (with Di-8-ANNEPS and SR (with SR-trapped Mag-Fluo-4 densities, as well as SR fluorophore diffusion (fluorescence recovery after photobleach; FRAP, cytosolic Ca2+ signaling and ex vivo cardiac performance in a PO rat hypertrophy model induced by abdominal aortic constriction (at 6 weeks. Results: Rats developed CH, while cardiac performance, basal and upon β-adrenergic stimulation, remained unaltered. TT density decreased by ∼14%, without spatial disarrangement, while SR density decreased by ∼7%. More important, FRAP was ∼30% slower, but with similar maximum recovery, suggesting decreased SR interconnectivity. Systolic and diastolic Ca2+ signaling and SR Ca2+ content were unaltered. Conclusion: SR remodeling is an early CH event, similar to TT remodeling, appearing during compensated hypertrophy. Nevertheless, myocytes can withstand those moderate structural changes in SR and TT, preserving normal Ca2+ signaling and contractility.

  13. Effects of losartan on left ventricular mass: a three-year follow-up in elderly hypertensives with myocardial hypertrophy despite successful conventional antihypertensive treatment.

    Science.gov (United States)

    Moroni, C; Tolone, S; Lopreiato, F; Scrofani, A R; Bossini, A; Affricano, C; Cassone, R; Gaudio, C

    2017-03-01

    Reversal of left ventricular hypertrophy (LVH) in hypertensive patients appears to be a desirable goal to the reduction cardiac risk. The Renin-Angiotensin System (RAS) seems to play a major role in the establishment and maintenance of LVH through the activated systemic RAS and the Intracardiac Angiotensin System (IAS). We focused on the effects of a three-year treatment with losartan supplement in hypertensive patients with LVH not responding to eight years of an effective previous antihypertensive pharmacological treatment. Two groups of 28 sex-, age- and therapy-matched subjects with essential hypertension and LVH were taken into consideration. The two groups were in effective pharmacological treatment (BP losartan (100 mg/die) on-top treatment, whereas patients of Group B continued the follow-up of the previous conventional therapy. Both groups were submitted to an echocardiographic follow-up. Group A, showed a significant reduction of the mean LVH since the first step at six months with a further significant trend during the whole period (variance analysis: p losartan in hypertensive and hypertrophic patients are in agreement with the results of LIFE Trial. However, the reduction of left ventricular hypertrophy in our patients seems to be related to changes inducted by losartan on the IAS, since no further hemodynamic effects were observed. Losartan induced both a significant reduction of LVH and an improvement of LV diastolic function with a subsequent expected beneficial shift on the prognosis.

  14. Left ventricular hypertrophy by ECG versus cardiac MRI as a predictor for heart failure.

    Science.gov (United States)

    Oseni, Abdullahi O; Qureshi, Waqas T; Almahmoud, Mohamed F; Bertoni, Alain G; Bluemke, David A; Hundley, William G; Lima, Joao A C; Herrington, David M; Soliman, Elsayed Z

    2017-01-01

    To determine if there is a significant difference in the predictive abilities of left ventricular hypertrophy (LVH) detected by ECG-LVH versus LVH ascertained by cardiac MRI-LVH in a model similar to the Framingham Heart Failure Risk Score (FHFRS). This study included 4745 (mean age 61±10 years, 53.5% women, 61.7% non-whites) participants in the Multi-Ethnic Study of Atherosclerosis. ECG-LVH was defined using Cornell voltage product while MRI-LVH was derived from left ventricular mass. Cox proportional hazard regression was used to examine the association between ECG-LVH and MRI-LVH with incident heart failure (HF). Harrell's concordance C-index was used to estimate the predictive ability of the model when either ECG-LVH or MRI-LVH was included as one of its components. ECG-LVH was present in 291 (6.1%), while MRI-LVH was present in 499 (10.5%) of the participants. Both ECG-LVH (HR 2.25, 95% CI 1.38 to 3.69) and MRI-LVH (HR 3.80, 95% CI 1.56 to 5.63) were predictive of HF. The absolute risk of developing HF was 8.81% for MRI-LVH versus 2.26% for absence of MRI-LVH with a relative risk of 3.9. With ECG-LVH, the absolute risk of developing HF 6.87% compared with 2.69% for absence of ECG-LVH with a relative risk of 2.55. The ability of the model to predict HF was better with MRI-LVH (C-index 0.871, 95% CI 0.842 to 0.899) than with ECG-LVH (C-index 0.860, 95% CI 0.833 to 0.888) (p<0.0001). ECG-LVH and MRI-LVH are predictive of HF. Substituting MRI-LVH for ECG-LVH improves the predictive ability of a model similar to the FHFRS. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  15. Telmisartan reduces mortality and left ventricular hypertrophy with sympathoinhibition in rats with hypertension and heart failure.

    Science.gov (United States)

    Kishi, Takuya; Hirooka, Yoshitaka; Sunagawa, Kenji

    2014-02-01

    Angiotensin II type 1 receptor (AT1R) blockers have various benefits on hypertension and/or heart failure. We demonstrated that telmisartan (TLM), an AT1R blocker, causes sympathoinhibition by reduction of reactive oxygen species (ROS) in the rostral ventrolateral medulla (RVLM) of stroke-prone spontaneously hypertensive rats (SHRSPs). The aim of this study was to determine whether TLM improves survival in rats with hypertension and heart failure. Angiotensin II-infused and salt-loaded SHRSPs were divided into TLM-treated, candesartan cilexetil (CAN)-treated, and control groups. We determined the dose of TLM or CAN with similar depressor effects. We examined survival, urinary norepinephrine excretion (uNE) as a parameter of sympathoexcitation, ROS in the RVLM, and left ventricular (LV) end-diastolic pressure (LVEDP). LV hypertrophy (LVH) was assessed by echocardiography and heart/body weight. Compared with the control group, TLM improved survival to a greater extent than CAN. At 4 weeks after treatment, ROS in the RVLM and uNE were significantly lower in the TLM-treated group than in the CAN-treated group, despite the similar depressor effects. At 8 weeks after the treatments, LVH and LVEDP were attenuated in the TLM-treated group compared with the CAN-treated group. Our results suggest that TLM has the potential to reduce mortality, LVH, and LVEDP and that enhanced sympathoinhibition by reduction of ROS in the RVLM might be one of the mechanisms contributing to the beneficial actions of TLM in a model of rats with severe hypertension and heart failure.

  16. Left ventricular hypertrophy is associated with obesity, male gender, and symptoms in healthy adolescents.

    Science.gov (United States)

    Movahed, Mohammad Reza; Martinez, Adolfo; Greaves, Jeff; Greaves, Seaneen; Morrell, Holly; Hashemzadeh, Mehrtash

    2009-03-01

    Obesity has been found to be associated with left ventricular (LV) hypertrophy (LVH). However, the occurrence of LVH in obese teenagers who are involved in sport programs has not been studied. The objective of this study was to evaluate the prevalence of LVH and its correlation with obesity, gender, and symptoms in teenage athletes. We used echocardiographic database of 1,500 adolescences between the ages of 12 and 20 years who were actively involved in school sport programs. We evaluated associations between obesity and LVH (defined as LV wall thickness (LVWT)) >12 mm, or LV mass (LVM) >215 g or relative wall thickness (RWT) >0.43) and physical symptoms. Using univariate and multivariate analysis, male gender was associated with increased LVWT (multivariate odds ratio (OR) 4.87, confidence interval (CI) 2.41-9.82). Obesity was associated with parameters of LVH using univariate and multivariate analysis. (LVM > 215 g) occurred in 10.32% of obese athletes vs. 0.2% (1/445) of controls, (OR 51.33, CI 6.05-433.8), P 12 mm occurred in 16.5% of obese students vs. 3.6% of controls (OR 5.2, CI 2.7-10.1, P 0.43 occurred in 41.4% of obese students vs. 15.7% of controls (OR 3.78, CI 2.11-6.76, P obese students and in students with LVH. In conclusion obesity is associated with LVH in a population of healthy teenagers actively involved in sport programs. Furthermore, the presence of LVH was independently associated with many physical symptoms suggesting negative effect of LVH on myocardial function.

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

    Science.gov (United States)

    Bacharova, Ljuba; Ugander, Martin

    2014-11-01

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

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

    Science.gov (United States)

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

    2014-11-01

    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 40 mm excluded HC with sensitivity of 92% and specificity of 71% (p <0.001). 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 <0.001), with values <11.5 cm/second yielding sensitivity of 81% and specificity of 61% for the diagnosis of HC (p <0.001). Absence of diffuse T-wave inversion on electrocardiography (specificity 92%) and negative family history for HC (specificity 100%) also proved useful for excluding HC. In conclusion, in 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 <54 mm useful for differentiation from 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. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Low serum 25-hydroxyvitamin D levels are associated with left ventricular hypertrophy in essential hypertension.

    Science.gov (United States)

    Fallo, F; Catena, C; Camozzi, V; Luisetto, G; Cosma, C; Plebani, M; Lupia, M; Tona, F; Sechi, L A

    2012-10-01

    Low serum 25-hydroxyvitamin D [25(OH)D] levels may have an important role in predisposing to hypertension and myocardial disease. We investigated the relationship between 25(OH)D and left ventricular (LV) structure and function, assessed by echocardiography, in a series of patients with essential hypertension (EH). Sixty-two newly diagnosed never-treated patients (32 male/30 female), aged 18-65 years, with grade 1-2 hypertension, no diabetes, no obesity, no hyperlipidemia, and no cardiopulmonary, renal, or hepatic disease, were studied. Twenty-four healthy normotensive sex-, age-, BMI-matched subjects served as controls. Hypertensive patients with 25(OH)D deficiency, defined as serum 25(OH)D levels <50 nmol/L, had higher prevalence of LV hypertrophy (LVH) than their 25(OH)D-sufficient counterparts (57.1 vs 17.6%, P = 0.02); no differences between the two groups were found in blood pressure levels as well as in other biochemical and hormone parameters. There was an inverse correlation between LV mass index and 25(OH)D levels (r = -0.366, P < 0.003) and a direct correlation between LV mass index and BMI (r = 0.333, P < 0.006) in the entire hypertensive population. The two variables remained independently associated with LVH at multivariable logistic regression analysis (OR 1.05, P < 0.005 and OR 1.25, P = 0.03, respectively). Prevalence of 25(OH)D deficiency was similar in EH patients and controls (45.1 vs 41.6%, P = 0.89), whereas no correlation between echocardiographic parameters and hormone levels was found. In the absence of major cardiovascular risk factors, 25(OH)D deficiency is a frequent finding in EH patients and is independently associated with LVH. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. [Importance of hypertensive left ventricular hypertrophy in patients with ischemic events of the heart or brain].

    Science.gov (United States)

    Castilla-Guerra, L; Fernández-Moreno, M C; Aguilera-Saborido, A; Solanella-Soler, J

    2016-01-01

    Hypertensive left ventricular hypertrophy (H-LVH) is a potentially modifiable vascular risk factor (VRF) often overlooked in clinical practice. We aimed to evaluate the frequency of H-LVH in patients with coronary heart disease (CHD) or ischemic stroke (IS). We retrospectively assessed all the echocardiography studies of patients admitted with the diagnosis CHD or IS over a 4-year period. We studied 533 patients, 330 with CHD and 203 with IS. Mean age was 69 (±11) years, 61.5% males. Hypertension was the most common RF: 362 patients (67.9%) (CHD vs. IS: 70 vs. 64.5%; P=NS). H-LVH was seen in 234 patients (43.9%) (CHD vs. IS: 44.8 vs. 42.3%; P=NS). Patients with H-LVH were older and received a greater number of antihypertensive drugs at discharge. Half of patients with hypertension presented H-LVH (184 patients; 50.8%), with similar frequency in both groups (CHD vs. IS: 50.6 vs. 51.1%; P=NS). Neither patients' characteristics nor VRF with the exception of hypertension (P=.0001) were associated with H-LVH. H-LVH is a major VRF in patients with ischemic events in the heart and brain. Nearly half the patients present H-LVH, with a similar frequency in both groups. It is important to identify H-LVH in these patients to optimize treatment and improve long-term prognosis. Copyright © 2015 SEHLELHA. Published by Elsevier España, S.L.U. All rights reserved.

  1. T-wave axis deviation and left ventricular hypertrophy interaction in diabetes and hypertension.

    Science.gov (United States)

    Assanelli, Deodato; Di Castelnuovo, Augusto; Rago, Livia; Badilini, Fabio; Vinetti, Giovanni; Gianfagna, Francesco; Salvetti, Massimo; Zito, Francesco; Donati, Maria Benedetta; de Gaetano, Giovanni; Iacoviello, Licia

    2013-01-01

    Electrocardiographic signs of left ventricular hypertrophy (ECG-LVH) and T-wave axis (TA) deviation are independent predictors of fatal and non fatal events. We assessed the prevalence of ECG-LVH, TA abnormalities and their combination according to the presence or absence of diabetes and/or hypertension in a large sample of the adult general Italian population. Data from 10,184 women (54 ± 11 years) and 8775 men (54 ± 11 years) were analyzed from the Moli-sani cohort, a database of randomly recruited adults (age >35) from the general population of Molise, a central region of Italy that includes collection of standard 12-lead resting ECG. Subjects with previous myocardial infarction, angina, cerebrovascular disease or left bundle brunch block or missing values for TA or ECG-LVH have been excluded. TA was measured from the standard 12-lead ECG and it was defined as the rotation of the T wave in the frontal plane as computed by a proprietary algorithm (CalECG/Bravo, AMPS-LLC, NY). ECG-LVH was defined as Sokolow Lyon voltage (SLv) >35 mm or Cornell voltage duration Product (CP) >= 2440 mm*ms. Among subjects with ECG-LVH, prevalence of hypertension was 59.0% and 49.7%, respectively for men and women, whereas that of diabetes was 10.7% and 5.7%. In hypertensives, TA was normal in 72.3% of subjects, borderline in 24.8% and abnormal in 2.9%. In diabetics, TA was normal in 70.4% of subjects, borderline in 26.5% and abnormal in 3.1%. In both hypertensive and diabetic subjects, the prevalence of ECG-LVH, was significantly greater in subjects with borderline or abnormal TA. Hypertension was an independent predictor of abnormal TA (odd ratio: 1.38, P = .025). These results suggest that hypertension might play a relevant role in the pathogenesis of TA deviation. © 2013.

  2. ECG is an inefficient screening-tool for left ventricular hypertrophy in normotensive African children population

    Directory of Open Access Journals (Sweden)

    Giuseppe Di Gioia

    2016-09-01

    Full Text Available Background Left ventricular hypertrophy (LVH is a marker of pediatric hypertension and predicts development of cardiovascular events. Electrocardiography (ECG screening is used in pediatrics to detect LVH thanks to major accessibility, reproducibility and easy to use compared to transthoracic echocardiography (TTE, that remains the standard technique. Several diseases were previously investigated, but no data exists regarding our study population. The aim of our study was to evaluate the relationship between electrocardiographic and echocardiographic criteria of LVH in normotensive African children. Methods We studied 313 children (mean age 7,8 ± 3 yo, in north-Madagascar. They underwent ECG and TTE. Sokolow-Lyon index was calculated to identify ECG-LVH (>35 mm. Left ventricle mass (LVM with TTE was calculated and indexed by height2.7 (LVMI2.7 and weight (LVMIw. We report the prevalence of TTE-LVH using three methods: (1 calculating percentiles age- and sex- specific with values >95th percentile identifying LVH; (2 LVMI2.7 >51 g/m2.7; (3 LVMIw >3.4 g/weight. Results 40 (13% children showed LVMI values >95th percentile, 24 children (8% an LVMI2.7 >51 g/m2.7 while 19 children (6% an LVMIw >3.4 g/kg. LVH-ECG by Sokolow-Lyon index was present in five, three and three children respectively, with poor values of sensitivity (ranging from 13 to 16%, positive predictive value (from 11 to 18% and high values of specificity (up to 92%. The effects of anthropometrics parameters on Sokolow-Lyon were analyzed and showed poor correlation. Conclusion ECG is a poor screening test for detecting LVH in children. In clinical practice, TTE remains the only tool to be used to exclude LVH.

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

    Science.gov (United States)

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

    2017-08-01

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

  4. Increased myocardial vulnerability to ischemia-reperfusion injury in the presence of left ventricular hypertrophy

    DEFF Research Database (Denmark)

    Mølgaard, Søren; Faricelli, Barbara; Salomonsson, Max

    2016-01-01

    .  Conclusion: Hearts from hypertensive (SHR-SP) rats with left ventricle hypertrophy appeared more vulnerable to ischemia-reperfusion injury, as supported by a more profound infarct development and an earlier loss of postconditioning by Exe-4. Mitochondrial complexes III and IV were identified among possible...... loci of this increased, hypertrophy-associated vulnerability....

  5. T1 measurements identify extracellular volume expansion in hypertrophic cardiomyopathy sarcomere mutation carriers with and without left ventricular hypertrophy.

    Science.gov (United States)

    Ho, Carolyn Y; Abbasi, Siddique A; Neilan, Tomas G; Shah, Ravi V; Chen, Yucheng; Heydari, Bobak; Cirino, Allison L; Lakdawala, Neal K; Orav, E John; González, Arantxa; López, Begoña; Díez, Javier; Jerosch-Herold, Michael; Kwong, Raymond Y

    2013-05-01

    Myocardial fibrosis is a hallmark of hypertrophic cardiomyopathy (HCM) and a potential substrate for arrhythmias and heart failure. Sarcomere mutations seem to induce profibrotic changes before left ventricular hypertrophy (LVH) develops. To further evaluate these processes, we used cardiac magnetic resonance with T1 measurements on a genotyped HCM population to quantify myocardial extracellular volume (ECV). Sarcomere mutation carriers with LVH (G+/LVH+, n=37) and without LVH (G+/LVH-, n=29), patients with HCM without mutations (sarcomere-negative HCM, n=11), and healthy controls (n=11) underwent contrast cardiac magnetic resonance, measuring T1 times pre- and postgadolinium infusion. Concurrent echocardiography and serum biomarkers of collagen synthesis, hemodynamic stress, and myocardial injury were also available in a subset. Compared with controls, ECV was increased in patients with overt HCM, as well as G+/LVH- mutation carriers (ECV=0.36±0.01, 0.33±0.01, 0.27±0.01 in G+/LVH+, G+/LVH-, controls, respectively; P≤0.001 for all comparisons). ECV correlated with N-terminal probrain natriuretic peptide levels (r=0.58; P60% of overt patients with HCM but absent from G+/LVH- subjects. Both ECV and late gadolinium enhancement were more extensive in sarcomeric HCM than sarcomere-negative HCM. Myocardial ECV is increased in HCM sarcomere mutation carriers even in the absence of LVH. These data provide additional support that fibrotic remodeling is triggered early in disease pathogenesis. Quantifying ECV may help characterize the development of myocardial fibrosis in HCM and ultimately assist in developing novel disease-modifying therapy, targeting interstitial fibrosis.

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

    DEFF Research Database (Denmark)

    Fyhrquist, Frej; Eriksson, Anders; Saijonmaa, Outi

    2013-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  8. Low agreement between cardiologists diagnosing left ventricular hypertrophy in children with end-stage renal disease.

    Science.gov (United States)

    Schoenmaker, Nikki J; van der Lee, Johanna H; Groothoff, Jaap W; van Iperen, Gabrielle G; Frohn-Mulder, Ingrid M E; Tanke, Ronald B; Ottenkamp, Jaap; Kuipers, Irene M

    2013-08-02

    Monitoring of the appearance of left ventricular hypertrophy (LVH) by echocardiography is currently recommended for in the management of children with End-stage renal disease (ESRD). In order to investigate the validity of this method in ESRD children, we assessed the intra- and inter-observer reproducibility of the diagnosis LVH. Echocardiographic measurements in 92 children (0-18 years) with ESRD, made by original analysists, were reassessed offline, twice, by 3 independent observers. Smallest detectable changes (SDC) were calculated for continuous measurements of diastolic interventricular septum (IVSd), Left ventricle posterior wall thickness (LVPWd), Left ventricle end-diastolic diameter (LVEDd), and Left ventricle mass index (LVMI). Cohen's kappa was calculated to assess the reproducibility of LVH defined in two different ways. LVH(WT) was defined as Z-value of IVSd and/or LVPWd>2 and LVH(MI) was defined as LVMI> 103 g/m² for boys and >84 g/m² for girls. The intra-observer SDCs ranged from 1.6 to 1.7 mm, 2.0 to 2.6 mm and 17.7 to 30.5 g/m² for IVSd, LVPWd and LVMI, respectively. The inter-observer SDCs were 2.6 mm, 2.9 mm and 24.6 g/m² for IVSd, LVPWd and LVMI, respectively. Depending on the observer, the prevalence of LVH(WT) and LVH(MI) ranged from 2 to 30% and from 8 to 25%, respectively. Kappas ranged from 0.4 to 1.0 and from 0.1 to 0.5, for intra-and inter- observer reproducibility, respectively. Changes in diastolic wall thickness of less than 1.6 mm or LVMI less than 17.7 g/m² cannot be distinguished from measurement error in individual children, even when measured by the same observer. This limits the use of echocardiography to detect changes in wall thickness in children with ESRD in routine practice.

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

    Science.gov (United States)

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

    2015-05-01

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

  10. Atorvastatin induced increase in homologous angiotensin I converting enzyme (ACE2) mRNA is associated to decreased fibrosis and decreased left ventricular hypertrophy in a rat model of diabetic cardiomyopathy

    OpenAIRE

    Aguilar, Cristian; Departamento de Anatomía Patológica, Hospital Nacional Edgardo Rebagliati Martins. Lima, Perú. Médico, Residente de Anatomía Patológica, HNERM.; Ventura, Freddy; Departamento de Ciencias Básicas, facultad de Medicina, Universidad Nacional de Trujillo. Trujillo, Perú. Químico farmacéutico, Magíster en fisiología y Biofísica.; Rodríguez-Delfín, Luis; Departamento de Anatomía Patológica, Hospital Nacional Edgardo Rebagliati Martins. Lima, Perú. Laboratorio de Biología Molecular, Facultad de Biología, Universidad Nacional Pedro Ruiz Gallo. Chiclayo, Perú. Investigación y Diagnóstico en Genética y Biología Molecular “GEN MOL”. Trujillo, Perú. Biólogo, Doctor en Ciencias, área de Genética.

    2011-01-01

    Objectives. This study has investigated the effect of atorvastatin on the progression of cardiac remodelling and ACE- 2 expression in diabetic myocardium in rats. Materials and Methods. Diabetes was induced in Holtzman rats with an intraperitoneal injection of streptozotocin. The animals were divided into 3 groups: (1) normal control rats, (2) diabetic rats and (3) diabetic rats treated orally with atorvastatin (50 mg/kg/day). After eight weeks of treatment, the hearts were removed for morpho...

  11. Prophylactic amiodarone in patients with severe aortic stenosis and left ventricular hypertrophy undergoing aortic valve replacement: Silencing the rebels

    Directory of Open Access Journals (Sweden)

    Mohammed Abd Al Jawad

    2017-12-01

    Conclusions: Prophylactic use of a single dose amiodarone through the pump circuit before cross clamp release reduces the incidence of reperfusion induced ventricular fibrillation and subsequent defibrillation therapy needed.

  12. Loss of mitochondrial exo/endonuclease EXOG affects mitochondrial respiration and induces ROS-mediated cardiomyocyte hypertrophy.

    Science.gov (United States)

    Tigchelaar, Wardit; Yu, Hongjuan; de Jong, Anne Margreet; van Gilst, Wiek H; van der Harst, Pim; Westenbrink, B Daan; de Boer, Rudolf A; Silljé, Herman H W

    2015-01-15

    Recently, a locus at the mitochondrial exo/endonuclease EXOG gene, which has been implicated in mitochondrial DNA repair, was associated with cardiac function. The function of EXOG in cardiomyocytes is still elusive. Here we investigated the role of EXOG in mitochondrial function and hypertrophy in cardiomyocytes. Depletion of EXOG in primary neonatal rat ventricular cardiomyocytes (NRVCs) induced a marked increase in cardiomyocyte hypertrophy. Depletion of EXOG, however, did not result in loss of mitochondrial DNA integrity. Although EXOG depletion did not induce fetal gene expression and common hypertrophy pathways were not activated, a clear increase in ribosomal S6 phosphorylation was observed, which readily explains increased protein synthesis. With the use of a Seahorse flux analyzer, it was shown that the mitochondrial oxidative consumption rate (OCR) was increased 2.4-fold in EXOG-depleted NRVCs. Moreover, ATP-linked OCR was 5.2-fold higher. This increase was not explained by mitochondrial biogenesis or alterations in mitochondrial membrane potential. Western blotting confirmed normal levels of the oxidative phosphorylation (OXPHOS) complexes. The increased OCR was accompanied by a 5.4-fold increase in mitochondrial ROS levels. These increased ROS levels could be normalized with specific mitochondrial ROS scavengers (MitoTEMPO, mnSOD). Remarkably, scavenging of excess ROS strongly attenuated the hypertrophic response. In conclusion, loss of EXOG affects normal mitochondrial function resulting in increased mitochondrial respiration, excess ROS production, and cardiomyocyte hypertrophy. Copyright © 2015 the American Physiological Society.

  13. Growth hormone-releasing hormone attenuates cardiac hypertrophy and improves heart function in pressure overload-induced heart failure.

    Science.gov (United States)

    Gesmundo, Iacopo; Miragoli, Michele; Carullo, Pierluigi; Trovato, Letizia; Larcher, Veronica; Di Pasquale, Elisa; Brancaccio, Mara; Mazzola, Marta; Villanova, Tania; Sorge, Matteo; Taliano, Marina; Gallo, Maria Pia; Alloatti, Giuseppe; Penna, Claudia; Hare, Joshua M; Ghigo, Ezio; Schally, Andrew V; Condorelli, Gianluigi; Granata, Riccarda

    2017-11-07

    It has been shown that growth hormone-releasing hormone (GHRH) reduces cardiomyocyte (CM) apoptosis, prevents ischemia/reperfusion injury, and improves cardiac function in ischemic rat hearts. However, it is still not known whether GHRH would be beneficial for life-threatening pathological conditions, like cardiac hypertrophy and heart failure (HF). Thus, we tested the myocardial therapeutic potential of GHRH stimulation in vitro and in vivo, using GHRH or its agonistic analog MR-409. We show that in vitro, GHRH(1-44)NH 2 attenuates phenylephrine-induced hypertrophy in H9c2 cardiac cells, adult rat ventricular myocytes, and human induced pluripotent stem cell-derived CMs, decreasing expression of hypertrophic genes and regulating hypertrophic pathways. Underlying mechanisms included blockade of Gq signaling and its downstream components phospholipase Cβ, protein kinase Cε, calcineurin, and phospholamban. The receptor-dependent effects of GHRH also involved activation of Gα s and cAMP/PKA, and inhibition of increase in exchange protein directly activated by cAMP1 (Epac1). In vivo, MR-409 mitigated cardiac hypertrophy in mice subjected to transverse aortic constriction and improved cardiac function. Moreover, CMs isolated from transverse aortic constriction mice treated with MR-409 showed improved contractility and reversal of sarcolemmal structure. Overall, these results identify GHRH as an antihypertrophic regulator, underlying its therapeutic potential for HF, and suggest possible beneficial use of its analogs for treatment of pathological cardiac hypertrophy. Copyright © 2017 the Author(s). Published by PNAS.

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

    DEFF Research Database (Denmark)

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

    2007-01-01

    BACKGROUND: Sudden cardiac death (SCD) occurs more often in patients with ECG left ventricular (LV) hypertrophy. However, whether LV hypertrophy regression is associated with a reduced risk of SCD remains unclear. METHODS AND RESULTS: The Losartan Intervention for End Point Reduction in Hypertens...... 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......-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...

  15. Association of left ventricular dilatation and hypertrophy with chronotropic incompetence in the Framingham Heart Study.

    Science.gov (United States)

    Lauer, M S; Larson, M G; Evans, J C; Levy, D

    1999-05-01

    Chronotropic incompetence and left ventricular (LV) dilatation have both been shown to be markers of an adverse cardiovascular prognosis. Chronotropic incompetence has been described in patients with symptomatic LV dilatation and dysfunction, but the effect of asymptomatic LV dilatation and hypertrophy on exercise heart rate response has not been well characterized. Members of the Framingham Offspring Study underwent M-mode echocardiography and graded exercise testing as part of a routine evaluation. Subjects receiving beta-blockers and digitalis and subjects with preexisting coronary heart disease, heart failure, and baseline ST-segment abnormalities were excluded. Chronotropic incompetence was assessed in 2 ways: (1) failure to achieve an age--predicted target heart rate and (2) a low chronotropic index, a measure of heart rate response that takes into account effects of age, resting heart rate, and physical fitness. Echocardiographic variables studied included LV diastolic and systolic dimensions, LV wall thickness, LV mass, and fractional shortening. There were 1414 men and 1601 women eligible for analyses; failure to reach target heart rate occurred in 20% of men and 23% of women; a low chronotropic index was noted in 14% of men and 12% of women. In unadjusted categorical analyses, an abnormally high LV mass, as defined by exceeding the 90th percentile predicted value of a healthy reference group, was associated with failure to achieve target heart rate in men (31% vs 18%, odds ratio [OR] 2.05, 95% confidence interval [CI] 1.49 to 2.83) and women (34% vs 20%, OR 2.09, 95% CI 1.63 to 2.69). Similarly, an abnormally high LV mass was predictive of a low chronotropic index in men (18% vs 13%, OR 1. 47, 95% CI 1.01 to 2.14) and women (17% vs 10%, OR 1.78, 95% CI 1.29 to 2.45). When considered as a continuous variable, LV diastolic dimension predicted failure to achieve target heart rate in men (ageadjusted OR for 1 SD increase 1.30, 95% CI 1.00 to 1.33) and in

  16. Cardiac hypertrophy induced by active Raf depends on Yorkie-mediated transcription.

    Science.gov (United States)

    Yu, Lin; Daniels, Joseph P; Wu, Huihui; Wolf, Matthew J

    2015-02-03

    Organ hypertrophy can result from enlargement of individual cells or from cell proliferation or both. Activating mutations in the serine-threonine kinase Raf cause cardiac hypertrophy and contribute to Noonan syndrome in humans. Cardiac-specific expression of activated Raf also causes hypertrophy in Drosophila melanogaster. We found that Yorkie (Yki), a transcriptional coactivator in the Hippo pathway that regulates organ size, is required for Raf-induced cardiac hypertrophy in flies. Although aberrant activation of Yki orthologs stimulates cardiac hyperplasia in mice, cardiac-specific expression of an activated mutant form of Yki in fruit flies caused cardiac hypertrophy without hyperplasia. Knockdown of Yki caused cardiac dilation without loss of cardiomyocytes and prevented Raf-induced cardiac hypertrophy. In flies, Yki-induced cardiac hypertrophy required the TEA domain-containing transcription factor Scalloped, and, in mammalian cells, expression of mouse Raf(L613V), an activated form of Raf with a Noonan syndrome mutation, increased Yki-induced Scalloped activity. Furthermore, overexpression of Tgi (a Tondu domain-containing Scalloped-binding corepressor) in the fly heart abrogated Yki- or Raf-induced cardiac hypertrophy. Thus, crosstalk between Raf and Yki occurs in the heart and can influence Raf-mediated cardiac hypertrophy. Copyright © 2015, American Association for the Advancement of Science.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-07-15

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

  18. Predictors of the left ventricular dysfunction induced by ventricular arrhythmia

    Directory of Open Access Journals (Sweden)

    А. І. Vytryhovskiy

    2016-08-01

    Full Text Available The most powerful predictor of life-threatening arrhythmia risk is a combination of low heart rate variability with low ejection fraction (EF of the left ventricle. Aim. To identify predictors of left ventricle dysfunction which is induced by ventricular arrhythmia. Materials and methods. To diagnose structural changes of left ventricular functional capacity and reserves in patients with previous myocardial infarction and patients with high and very high cardiovascular risk by SCORE scale and for establishment the relationship between morphological heart changes and pathological phenomenon of heart turbulence echocardiography and study of heart rate turbulence variability were performed. 603 patients were selected for the research. All patients were divided into groups: group 1 – patients with coronary heart disease, but without associated risk factors, such as smoking, obesity, metabolic syndrome; group 2 – patients who smoke tobacco more than 2 years (very high cardiovascular risk by scale SCORE; group 3 – patients with metabolic syndrome without coronary heart disease or arterial hypertension (very high cardiovascular risk by scale SCORE. The control group consisted of 149 persons. Results. The feature of structural changes in patients with myocardial infarction and in patients with a high cardiovascular risk by SCORE with heart rate turbulence compared with cases without НRT is considerably thickening of the left interventricular septum in systole. Based on this, it can be argued that the emergence of ventricular arrhythmia and accordingly phenomenon of heart rate turbulence in patients with existing cardiovascular diseases and risk factors has both morphological and functional character. Significant difference of echocardioscopy parameters in patients with postinfarction cardiosclerosis and risk factors by the SCORE system was established by index of intraventricular septum thickness in systole, and in persons with high risk – in

  19. Long-Term Excessive Body Weight and Adult Left Ventricular Hypertrophy Are Linked Through Later-Life Body Size and Blood Pressure: The Bogalusa Heart Study.

    Science.gov (United States)

    Zhang, Huijie; Zhang, Tao; Li, Shengxu; Guo, Yajun; Shen, Wei; Fernandez, Camilo; Harville, Emily; Bazzano, Lydia A; Urbina, Elaine M; He, Jiang; Chen, Wei

    2017-05-12

    Childhood adiposity is associated with cardiac structure in later life, but little is known regarding to what extent childhood body weight affects adult left ventricular geometric patterns through adult body size and blood pressure (BP). Determine quantitatively the mediation effect of adult body weight and BP on the association of childhood body mass index (BMI) with adult left ventricular (LV) hypertrophy. This longitudinal study consisted of 710 adults, aged 26 to 48 years, who had been examined for BMI and BP measured ≥4× during childhood and ≥2× during adulthood, with a mean follow-up period of 28.0 years. After adjusting for age, race, and sex, adult BMI had a significant mediation effect (76.4%; Padult LV mass index association. The mediation effects of adult systolic BP (15.2%), long-term burden (12.1%), and increasing trends of systolic BP (7.9%) were all significant (Padult LV hypertrophy, eccentric hypertrophy, and concentric hypertrophy. Importantly, the mediation effects of adult BMI were all significantly stronger than those of adult systolic BP on LV mass index, LV hypertrophy, and LV remodeling patterns (Padult cardiac structure, and early life excessive body weight and adult LV hypertrophy are linked through later life excessive body weight and elevated BP. © 2017 American Heart Association, Inc.

  20. [Left ventricular hypertrophy in black African subjects with artery hypertension: Results of a cross-sectional survey conducted in semi-rural area in Senegal].

    Science.gov (United States)

    Mbaye, A; Dodo, B; Ngaïde, A A; Sy, N F; Babaka, K; Mingou, J S; Faye, M; Niang, K; Sarr, S A; Dioum, M; Bodian, M; Ndiaye, M B; Kane, A D; Ndour-Mbaye, M; Diao, M; Diack, B; Kane, M; Diagne-Sow, D; Thiaw, I; Kane, A

    2017-09-01

    To assess the prevalence of left ventricular hypertrophy according to electrocardiographic and echocardiographic criteria among hypertensive patients living in semi-rural Senegalese area. According to the World Health Organization STEPSwise approach, we conducted, in November 2012, a cross-sectional and exhaustive study in the population aged at least 35 years old and living for at least six months in the semi-rural area of Guéoul. We researched electrocardiographic and echocardiographic left ventricular hypertrophy in hypertensive subjects. Data were analyzed with SPSS 18.0 software version. The significance level was agreed for a value of P<0.05. We examined 1411 subjects aged on average of 48.5±12.7 years. In total, 654 subjects were hypertensive and screening of left ventricular hypertrophy (LVH) was effective in 515 of them. According to Sokolow-Lyon index, 86 subjects (16.7%) presented electrocardiographic LVH, more frequently in men (P=0.002). According to Cornell index and Cornell product, LVH was founded respectively in 66 (12.8%) and 52 subjects (10.1%), more frequently in female (P=0.0001; P=0.004). It was more common in grade 3 of hypertension however criteria. In echocardiography, prevalence of LVH was 2.2% (13 cases) according to the left ventricular mass, 9.3% (48 cases) according to the left ventricular mass indexed to body surface area and 8.2% (42 cases) according to the left ventricular mass indexed to height 2.7 . LVH was significantly correlated with the electrocardiographic LVH according to Sokolow-Lyon index (P<0.0001) and the grade 3 of hypertension (P=0.003). Although rare in hypertensive Senegalese living in semi-rural area, left ventricular hypertrophy is correlated with severity of grade of hypertension. Screening by electrocardiogram will allow better follow-up of these hypertensive subjects. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

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

    DEFF Research Database (Denmark)

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

    1993-01-01

    The objective of this study was to analyze the long-term hemodynamic effects of the calcium antagonist isradipine in mild hypertension compared with those of the beta 1-selective adrenoceptor antagonist atenolol, focusing in particular on the development of cardiac hypertrophy. Ten male patients ...

  3. [Metoprolol attenuates pressure overload-induced myocardial hypertrophy through modulating Dryk1A-ASF-CaMKIIδ signaling pathways].

    Science.gov (United States)

    Yao, Jian; Sheng, Hong-zhuan; Lu, Xiao-chen; Gu, Qing-qing; Zhu, Jian-hua

    2013-12-01

    Previous study showed that the signaling pathway of dual-specificity tyrosine-phosphorylated and regulated kinase 1A (Dyrk1A)-alternative splicing factor (ASF)- alternative splicing of Ca(2+)/calmodulin-dependent protein kinase IIδ (CaMKIIδ) is related to myocardial hypertrophy. The aim of present study was to determine the effect and related mechamism of metoprolol on pressure overload induced myocardial hypertrophy. Pressure overload-induced hypertension was induced by coarctation of suprarenal abdominal aorta in rats. Rats were randomly divided into sham-operated control, hypertension and hypertension plus metoprolol (30 mg×kg(-1)×d(-1)) groups (n = 10 each). Blood pressure, the left ventricular weight to body weight ratio and cardiomyocytes area were measured, the protein expression of Dyrk1A and ASF were determined by Western blot and mRNA expression of alternative splicing of CaMKIIδ was detected by RT-PCR. Four weeks after coarctation, cardiac hypertrophy was evidenced in rats of hypertensive group, and the protein expression of Dyrk1A was significantly upregulated, while the expression of ASF was significantly downregulated, the mRNA expression of CaMKIIδ A and B were significantly upregulated and mRNA expression of CaMKIIδ C was significantly downregulated compared to those in sham-operated control rats (all P ASF, and alternative splicing of CaMKIIδ (all P ASF-CaMKIIδ signaling pathways.

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    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......, 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...

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

    DEFF Research Database (Denmark)

    Boman, Kurt; Gerdts, Eva; Wachtell, Kristian

    2009-01-01

    BACKGROUND: Exercise lowers blood pressure and improves cardiovascular function, but little is known about whether exercise impacts cardiovascular morbidity and mortality independent of left ventricular hypertrophy (LVH) and LV geometry. DESIGN: Observational analysis of prospectively obtained...... (never exercise), intermediate (30 min twice/week). During 4.8-year follow-up, 105 patients suffered the primary composite endpoint of myocardial infarction (MI), stroke, or cardiovascular death. MI occurred in 39, stroke in 60, and cardiovascular death in 33 patients. RESULTS: Sedentary individuals (n...... echocardiographic data within the context of a randomized trial of antihypertensive treatment. METHODS: A total of 937 hypertensive patients with ECG LVH were studied by echocardiography in the Losartan Intervention For Endpoint reduction in hypertension study. Baseline exercise status was categorized as sedentary...

  6. Candesartan abrogates G protein-coupled receptors agonist-induced MAPK activation and cardiac myocyte hypertrophy

    Directory of Open Access Journals (Sweden)

    Djamel Lebeche

    2001-03-01

    Full Text Available The renin-angiotensin-aldosterone system (RAAS has been identified as a major contributor to the development of cardiac hypertrophy and the subsequent transition to heart failure. G protein-coupled receptors agonists such as angiotensin II (Ang II, endothelin-1 (ET-1 and phenylephrine (PE have been implicated in hypertrophic responses in ventricular myocytes through the activation of several families of MAP kinases. In this study we examined the effect of candesartan, an Ang II type 1-(AT1-receptor antagonist, on cardiac hypertrophy by using cultured neonatal rat cardiomyocytes. Stimulation with Ang II (100 nM, ET-1 (100 nM or PE (1 µM induced marked increases in [3H]Leucine incorporation (≥ 50%, compatible with enhanced protein synthesis. The addition of candesartan abrogated the increase in [3H]Leucine incorporation in response not only to Ang II but also to ET-1 and PE. To elucidate the mechanisms involved in this antihypertrophic effect of candesartan, we studied the activation of p38-MAPK, extracellular signal-regulated kinases (ERK1/2 and stress-activated protein kinases (SAPKs. Ang II, ET-1 and PE increased the phosphorylation levels of ERK1/2, p54 SAPK and p46SAPK and p38 in a time-dependent manner. This activation was completely blocked in the case of Ang II by pretreatment with candesartan. ET-1-induced activation of ERKs, SAPKs and p38 was also partially, but significantly, reduced by candesartan. PE-induced activation of SAPKs, but not ERKs and p38, was also reduced by candesartan. These results suggest that the hypertrophic response to ET-1 and PE, along with Ang II, is dependent upon a functioning AT1-receptor and may be mediated by AT 1 activation of the MAP kinases.

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

    Science.gov (United States)

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

    2015-03-15

    Diagnosis of apical HCM utilizes conventional wall thickness criteria. The normal left ventricular wall thins towards the apex such that normal values are lower in the apical versus the basal segments. The impact of this on the diagnosis of apical hypertrophic cardiomyopathy has not been evaluated. We performed a retrospective review of 2662 consecutive CMR referrals, of which 75 patients were identified in whom there was abnormal T-wave inversion on ECG and a clinical suspicion of hypertrophic cardiomyopathy. These were retrospectively analyzed for imaging features consistent with cardiomyopathy, specifically: relative apical hypertrophy, left atrial dilatation, scar, apical cavity obliteration or apical aneurysm. For comparison, the same evaluation was performed in 60 healthy volunteers and 50 hypertensive patients. Of the 75 patients, 48 met conventional HCM diagnostic criteria and went on to act as another comparator group. Twenty-seven did not meet criteria for HCM and of these 5 had no relative apical hypertrophy and were not analyzed further. The remaining 22 patients had relative apical thickening with an apical:basal wall thickness ratio >1 and a higher prevalence of features consistent with a cardiomyopathy than in the control groups with 54% having 2 or more of the 4 features. No individual in the healthy volunteer group had more than one feature and no hypertension patient had more than 2. A cohort of individuals exist with T wave inversion, relative apical hypertrophy and additional imaging features of HCM suggesting an apical HCM phenotype not captured by existing diagnostic criteria. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Boersma Hester

    2009-04-01

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

  9. Normal Limits of Electrocardiogram and Cut-Off Values for Left Ventricular Hypertrophy in Young Adult Nigerians.

    Science.gov (United States)

    Ayoka, A O; Ogunlade, O; Akintomide, A O; Akomolafe, R O; Ajayi, O E

    2014-06-19

    This study assessed healthy young adults to determine the normal limits for electrocardiographic variables and cut-off values for left ventricular hypertrophy. It was a cross sectional descriptive study in which the participants were evaluated clinically by standard 12-lead resting electrocardiogram (ECG) at 25 mm/s during quiet respiration. The heart rate, P wave duration, axis and amplitude, PR and QT intervals, QRS duration, axis and amplitude and T wave axis were assessed. Three hundred and twenty four (324) volunteers comprising of 175 males and 149 females aged 20 to 30 years (mean, 23.01 ± 2.88 years) participated in the study. The normal limits for heart rate, P wave duration, amplitude and axis in lead II, QRS duration and axis, T wave axis, PR interval, QT interval and QTc respectively were; 61-93 beats per minute,0.08-0.12s,1.00-2.00 mm,22.00-79.000,78.00-106.00 ms,15.50-81.000, 24.25-69.000,0.12-0.19s, 0.32-0.40s and 0.36-0.44s. The cut-off values for Sokolow-Lyon, Cornell and Araoye criteria for assessment of left ventricular hypertrophy (LVH) were higher than those previously in use in medical practice. Gender difference exists in some cut-off values for LVH. This study defined the normal limits for electrocardiographic variables for young adult Nigerians. Racial factor should be taken into consideration in interpretation of ECG.

  10. A Novel HRAS Mutation Independently Contributes to Left Ventricular Hypertrophy in a Family with a Known MYH7 Mutation.

    Directory of Open Access Journals (Sweden)

    Maria Elena Sana

    Full Text Available Several genetic conditions can lead to left ventricular hypertrophy (LVH. Among them, hypertrophic cardiomyopathy (HCM, caused by mutations in sarcomere genes, is the most common inherited cardiac disease. Instead, RASopathies, a rare class of disorders characterized by neuro-cardio-facial-cutaneous abnormalities and sometimes presenting with LVH, are caused by mutations in the RAS-MAPK pathway. We report on a 62-years-old male who presented isolated severe obstructive LVH but did not carry the sarcomere mutation previously identified in his affected relatives. By exome sequencing, we detected a novel mutation in HRAS gene (NM_005343.2:p.Arg68Trp, present also in the proband's daughter, who showed mild LVH and severe intellectual disability. The cardiac phenotype was indistinguishable between family members carrying either mutation. In silico studies suggested that the mutated HRAS protein is constitutionally activated. Consistently, functional characterization in vitro confirmed elevated HRAS-GTP accumulation and downstream RAS-MAPK pathway activation that are known to drive cell proliferation in LVH. Our study emphasizes the role of RAS signaling in cardiac hypertrophy and highlights the complexity in differential diagnosis of RASopathies. In fact, the mild features of RASopathy and the recurrence of sarcomeric HCM in this family delayed the correct diagnosis until comprehensive genetic testing was performed.

  11. A Novel HRAS Mutation Independently Contributes to Left Ventricular Hypertrophy in a Family with a Known MYH7 Mutation.

    Science.gov (United States)

    Sana, Maria Elena; Quilliam, Lawrence A; Spitaleri, Andrea; Pezzoli, Laura; Marchetti, Daniela; Lodrini, Chiara; Candiago, Elisabetta; Lincesso, Anna Rita; Ferrazzi, Paolo; Iascone, Maria

    2016-01-01

    Several genetic conditions can lead to left ventricular hypertrophy (LVH). Among them, hypertrophic cardiomyopathy (HCM), caused by mutations in sarcomere genes, is the most common inherited cardiac disease. Instead, RASopathies, a rare class of disorders characterized by neuro-cardio-facial-cutaneous abnormalities and sometimes presenting with LVH, are caused by mutations in the RAS-MAPK pathway. We report on a 62-years-old male who presented isolated severe obstructive LVH but did not carry the sarcomere mutation previously identified in his affected relatives. By exome sequencing, we detected a novel mutation in HRAS gene (NM_005343.2:p.Arg68Trp), present also in the proband's daughter, who showed mild LVH and severe intellectual disability. The cardiac phenotype was indistinguishable between family members carrying either mutation. In silico studies suggested that the mutated HRAS protein is constitutionally activated. Consistently, functional characterization in vitro confirmed elevated HRAS-GTP accumulation and downstream RAS-MAPK pathway activation that are known to drive cell proliferation in LVH. Our study emphasizes the role of RAS signaling in cardiac hypertrophy and highlights the complexity in differential diagnosis of RASopathies. In fact, the mild features of RASopathy and the recurrence of sarcomeric HCM in this family delayed the correct diagnosis until comprehensive genetic testing was performed.

  12. Genetic variation in angiotensin II type 2 receptor gene influences extent of left ventricular hypertrophy in hypertrophic cardiomyopathy independent of blood pressure.

    Science.gov (United States)

    Carstens, Nadia; van der Merwe, Lize; Revera, Miriam; Heradien, Marshall; Goosen, Althea; Brink, Paul A; Moolman-Smook, Johanna C

    2011-09-01

    Hypertrophic cardiomyopathy (HCM), an inherited primary cardiac disorder mostly caused by defective sarcomeric proteins, serves as a model to investigate left ventricular hypertrophy (LVH). HCM manifests extreme variability in the degree and distribution of LVH, even in patients with the same causal mutation. Genes coding for renin-angiotensin-aldosterone system components have been studied as hypertrophy modifiers in HCM, with emphasis on the angiotensin (Ang) II type 1 receptor (AT(1)R). However, Ang II binding to Ang II type 2 receptors (AT(2)R) also has hypertrophy-modulating effects. We investigated the effect of the functional +1675 G/A polymorphism (rs1403543) and additional single nucleotide polymorphisms in the 3' untranslated region of the AT(2)R gene (AGTR2) on a heritable composite hypertrophy score in an HCM family cohort in which HCM founder mutations segregate. We find significant association between rs1403543 and hypertrophy, with each A allele decreasing the average wall thickness by ~0.5 mm, independent of the effects of the primary HCM causal mutation, blood pressure and other hypertrophy covariates (p = 0.020). This study therefore confirms a hypertrophy-modulating effect for AT(2)R also in HCM and implies that +1675 G/A could potentially be used in a panel of markers that profile a genetic predisposition to LVH in HCM.

  13. The ATP-binding cassette transporter ABCG2 protects against pressure overload-induced cardiac hypertrophy and heart failure by promoting angiogenesis and antioxidant response.

    Science.gov (United States)

    Higashikuni, Yasutomi; Sainz, Julie; Nakamura, Kazuto; Takaoka, Minoru; Enomoto, Soichiro; Iwata, Hiroshi; Tanaka, Kimie; Sahara, Makoto; Hirata, Yasunobu; Nagai, Ryozo; Sata, Masataka

    2012-03-01

    ATP-binding cassette transporter subfamily G member 2 (ABCG2), expressed in microvascular endothelial cells in the heart, has been suggested to regulate several tissue defense mechanisms. This study was performed to elucidate its role in pressure overload-induced cardiac hypertrophy. Pressure overload was induced in 8- to 12-week-old wild-type and Abcg2-/- mice by transverse aortic constriction (TAC). Abcg2-/- mice showed exaggerated cardiac hypertrophy and ventricular remodeling after TAC compared with wild-type mice. In the early phase after TAC, functional impairment in angiogenesis and antioxidant response in myocardium was found in Abcg2-/- mice. In vitro experiments demonstrated that ABCG2 regulates transport of glutathione, an important endogenous antioxidant, from microvascular endothelial cells. Besides, glutathione transported from microvascular endothelial cells in ABCG2-dependent manner ameliorated oxidative stress-induced cardiomyocyte hypertrophy. In vivo, glutathione levels in plasma and the heart were increased in wild-type mice but not in Abcg2-/- mice after TAC. Treatment with the superoxide dismutase mimetic ameliorated cardiac hypertrophy in Abcg2-/- mice after TAC to the same extent as that in wild-type mice, although cardiac dysfunction with impaired angiogenesis was observed in Abcg2-/- mice. ABCG2 protects against pressure overload-induced cardiac hypertrophy and heart failure by promoting angiogenesis and antioxidant response.

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

    Directory of Open Access Journals (Sweden)

    Aureliusz Kolonko

    2014-01-01

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

  15. El aumento de la expresión del ARNm de la enzima convertidora de angiotensina I homóloga (ECA-2 inducido por atorvastatina se asocia a menor fibrosis e hipertrofia ventricular izquierda en un modelo de cardiomiopatía diabética Atorvastatin induced increase in homologous angiotensin i converting enzyme (ACE2 mRNA is associated to decreased fibrosis and decreased left ventricular hypertrophy in a rat model of diabetic cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Cristian Aguilar

    2011-06-01

    Full Text Available Objetivos. Evaluar el efecto de atorvastatina sobre la progresión del remodelado cardiaco y la expresión de ECA-2 en el miocardio de ratas diabéticas. Materiales y métodos. La diabetes fue inducida en ratas Holtzman con una inyección intraperitoneal de estreptozotocina. Los animales fueron divididos en tres grupos: (1 ratas control, (2 ratas diabéticas y (3 ratas diabéticas tratadas con atorvastatina (50 mg/kg/día. Después de ocho semanas de tratamiento, los corazones fueron extraídos para el análisis morfométrico, la cuantificación de colágeno y la determinación de los niveles de ARNm de ECA y ECA-2. Resultados. El índice de hipertrofia ventricular y el depósito de colágeno se incrementaron significativamente en las ratas diabéticas. La administración de atorvastatina previno estos cambios sin modificar los niveles de colesterol. La hiperglicemia produjo un incremento significativo en los niveles del ARNm de ECA y una marcada disminución en la expresión de ECA-2 en el miocardio de ratas diabéticas. La administración de atorvastatina indujo la expresión del ARNm de ECA-2 e inhibió la sobreexpresión del ARNm de ECA en el miocardio de las ratas diabéticas. Conclusiones. Nuestros resultados indican que la atorvastatina, independientemente de su capacidad para disminuir el colesterol, normaliza la relación de la expresión de ECA/ECA-2 y atenúa el desarrollo del remodelado adverso en el corazón diabético.Objectives. This study has investigated the effect of atorvastatin on the progression of cardiac remodelling and ACE- 2 expression in diabetic myocardium in rats. Materials and Methods. Diabetes was induced in Holtzman rats with an intraperitoneal injection of streptozotocin. The animals were divided into 3 groups: (1 normal control rats, (2 diabetic rats and (3 diabetic rats treated orally with atorvastatin (50 mg/kg/day. After eight weeks of treatment, the hearts were removed for morphometric studies, collagen

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

    Science.gov (United States)

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

    2011-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2002-12-01

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

  18. Factors associated with left ventricular hypertrophy in adults with surgically repaired coarctation of the aorta

    Directory of Open Access Journals (Sweden)

    Daniel Rinnström

    2013-01-01

    Conclusion: Increased LVM is a common late finding after surgically repaired CoA. This study showed that LVM was associated with modifiable factors; systolic blood pressure and aortic valve disease. As most patients are young, and increased LVM will eventually affect ventricular function, close attention to blood pressure optimization may be of particular importance in the surgically repaired CoA population.

  19. Left ventricular hypertrophy in non-insulin-dependent diabetic patients with and without diabetic nephropathy

    DEFF Research Database (Denmark)

    Nielsen, F S; Ali, S; Rossing, P

    1997-01-01

    The aim of our cross-sectional case-control study was to evaluate putative mechanisms of the increased cardiac morbidity and mortality in NIDDM patients with or without diabetic nephropathy. Fifty-one NIDDM patients with diabetic nephropathy (38 males, age 61 +/- 8 years, group 1), 53 NIDDM...... determined by echocardiography. LVMI was elevated, mean +/- SE, in group 1: 157 +/- 6 g m(-2), and in group 2: 139 +/- 7 g m(-2), as compared with group 3: 95 +/- 5 g m(-2) (p hypertrophy (LVH) (LVMI...... systolic function which may constitute independent risk factors for fatal and non-fatal cardiac events....

  20. A functional insulin-like growth factor receptor is not necessary for load-induced skeletal muscle hypertrophy

    National Research Council Canada - National Science Library

    Espen E. Spangenburg; Derek Le Roith; Chris W. Ward; Sue C. Bodine

    2008-01-01

    ...-I), which is thought to be a critical step in the induction of muscle hypertrophy. To determine the role of the IGF-I receptor in load-induced skeletal muscle hypertrophy, we utilized a transgenic mouse model (MKR...

  1. [The value of RV(6) > RV(5) of ECG in diagnosis of pneumocardiac disease complicated by left ventricular hypertrophy in coal-workers with pneumoconiosis].

    Science.gov (United States)

    Bao, Ying

    2012-09-01

    This thesis will discuss the value of RV(6) > RV(5) of ECG in diagnosis of pneumocardiac disease complicated by left ventricular hypertrophy in coal-workers with pneumoconiosis through the analysis of the ECG characteristics in the postmortem examination of coal-workers with pneumoconiosis. Three data groups will be formed on the basis of the ECG data in the case 47 postmortem examination of coal-workers with pneumocardiac disease complicated by left ventricular hypertrophy, and they are right deviation group with ECG cardiac electric axis more than 90 degrees (case 16), no deviation group with ECG cardiac electric axis between 30 degrees and 90 degrees (case 16) and left deviation group with ECG cardiac electric axis between 30 degrees and -30 degrees (case 15). The method that this thesis adopted is to compare the thickness of the right and left ventricle walls of the three groups, their ratio and the detectable ratio of ECG RV(6) > RV(5). The detectable rate of the thickness of right ventricle front wall, the thickness of the left ventricle wall, the thickness of the left ventricle wall to the thickness of right ventricle wall and ECG RV(6) > RV(5) in left deviation group is obviously higher than those of the no deviation group and right deviation group. The differences between the three groups are of statistics significance (P left ventricle wall, the thickness of the left ventricle wall to the thickness of right ventricle wall and ECG RV(6) > RV(5) in no deviation group is obviously higher than those of the right deviation group. The differences are of statistics significance (P left ventricular hypertrophy in coal-workers with pneumoconiosis, the ECG shows 20 cases of ECG RV(6) > RV(5). There are altogether 3 kinds of ECG types: (1) 14 cases of ECG RV(6) > RV(5); (2) 4 cases of left ventricular hypertrophy; (3) 2 cases of right ventricular hypertrophy. The left deviation of ECG cardiac electric axis and ECG RV(6) > RV(5) can be used as indications to

  2. Qiliqiangxin Attenuates Phenylephrine-Induced Cardiac Hypertrophy through Downregulation of MiR-199a-5p

    Directory of Open Access Journals (Sweden)

    Haifeng Zhang

    2016-05-01

    Full Text Available Background/Aims: Qiliqiangxin (QL, a traditional Chinese medicine, has long been used to treat chronic heart failure. Previous studies demonstrated that QL could prevent cardiac remodeling and hypertrophy in response to hypertensive or ischemic stress. However, little is known about whether QL could modulate cardiac hypertrophy in vitro, and (if so whether it is through modulation of specific hypertrophy-related microRNA. Methods: The primary neonatal rat ventricular cardiomyocytes were isolated, cultured, and treated with phenylephrine (PE, 50 µmol/L, 48 h to induce hypertrophy in vitro, in the presence or absence of pretreatment with QL (0.5 µg/ml, 48 h. The cell surface area was determined by immunofluorescent staining for α-actinin. The mRNA levels of hypertrophic markers including atrial natriuretic peptide (ANP, brain natriuretic peptide (BNP, and β-myosin heavy chain (MYH7 were assayed by qRT-PCRs. The protein synthesis of cardiomyocytes was determined by the protein/DNA ratio. The miR-199a-5p expression level was quantified in PE-treated cardiomyocytes and heart samples from acute myocardial infarction (AMI mouse model. MiR-199a-5p overexpression was used to determine its role in the anti-hypertrophic effect of QL on cardiomyocytes. Results: PE induced obvious enlargement of cell surface in cardiomyocytes, paralleling with increased ANP, BNP, and MYH7 mRNA levels and elevated protein/DNA ratio. All these changes were reversed by the treatment with QL. Meanwhile, miR-199a-5p was increased in AMI mouse heart tissues. Of note, the increase of miR-199a-5p in PE-treated cardiomyocytes was reversed by the treatment with QL. Moreover, overexpression of miR-199a-5p abolished the anti-hypertrophic effect of QL on cardiomyocytes. Conclusion: QL prevents PE-induced cardiac hypertrophy. MiR-199a-5p is increased in cardiac hypertrophy, while reduced by treatment with QL. miR-199a-5p suppression is essential for the anti-hypertrophic effect of QL

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

    Science.gov (United States)

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

    2013-07-30

    Hypertension, a strong determinant of cardiovascular disease risk, has been documented among elite, professional American-style football (ASF) players. The risk of increased blood pressure (BP) and early adulthood hypertension among the substantially larger population of collegiate ASF athletes is not known. We conducted a prospective, longitudinal study to examine BP, the incidence of hypertension, and left ventricular remodeling among collegiate ASF athletes. Resting BP and left ventricular structure were assessed before and after a single season of competitive ASF participation in 6 consecutive groups of first-year university athletes (n=113). ASF participation was associated with significant increases in systolic BP (116±8 versus 125±13 mm Hg; Plife cardiovascular health outcomes in this population.

  4. Role of Nodal-PITX2C signaling pathway in glucose-induced cardiomyocyte hypertrophy.

    Science.gov (United States)

    Su, Dongmei; Jing, Sun; Guan, Lina; Li, Qian; Zhang, Huiling; Gao, Xiaobo; Ma, Xu

    2014-06-01

    Pathological cardiac hypertrophy is a major cause of morbidity and mortality in cardiovascular disease. Recent studies have shown that cardiomyocytes, in response to high glucose (HG) stimuli, undergo hypertrophic growth. While much work still needs to be done to elucidate this important mechanism of hypertrophy, previous works have showed that some pathways or genes play important roles in hypertrophy. In this study, we showed that sublethal concentrations of glucose (25 mmol/L) could induce cardiomyocyte hypertrophy with an increase in the cellular surface area and the upregulation of the atrial natriuretic peptide (ANP) gene, a hypertrophic marker. High glucose (HG) treatments resulted in the upregulation of the Nodal gene, which is under-expressed in cardiomyocytes. We also determined that the knockdown of the Nodal gene resisted HG-induced cardiomyocyte hypertrophy. The overexpression of Nodal was able to induce hypertrophy in cardiomyocytes, which was associated with the upregulation of the PITX2C gene. We also showed that increases in the PITX2C expression, in response to Nodal, were mediated by the Smad4 signaling pathway. This study is highly relevant to the understanding of the effects of the Nodal-PITX2C pathway on HG-induced cardiomyocyte hypertrophy, as well as the related molecular mechanisms.

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

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    Ping-Chun Li

    2012-01-01

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

  6. Effect of carvedilol on pulse pressure and left ventricular hypertrophy in spontaneously hypertensive rats with adriamycin nephropathy.

    Science.gov (United States)

    Jovanovic, Dijana; Jovovic, Djurdjica; Mihailovic-Stanojevic, Nevena; Miloradovic, Zoran; Naumovic, Radomir; Dimitrijevic, Jovan; Maksic, Nebojsa; Djukanovic, Ljubica

    2009-09-01

    Recent studies indicated pulse pressure as a risk factor for left ventricular hypertrophy, myocardial infarction, congestive heart failure and stroke as well as chronic renal failure progression. The present study examined the effects of carvedilol and its combination with captopril on blood pressure, left ventricular hypertrophy, kidney vascular changes and kidney function in spontaneously hypertensive rats with adriamycin nephropathy. Four groups of 20 SHR each were involved: (1) control group: SHR; (2) ADR group: SHR treated with ADR (2mg/kg i.v. twice in 20 days); (3) ADR-C group: SHR treated with ADR and carvedilol (30 mg/kg/day) and (4) ADR-CC group: SHR treated with ADR and carvedilol (30 mg/kg/day) and captopril (60 mg/kg/day). Systolic-, diastolic- and mean-pressures and pulse pressure were determined at weeks 6 and 12 after the second ADR injection; and body weight, creatinine clearance and proteinuria at weeks -3, 6 and 12. The rats were sacrificed at week 6 or 12, the weights of the left and right ventricles and kidneys measured and the kidney vascular index was calculated as described by Bader and Mayer. Both carvedilol alone and combined with captopril significantly reduced systemic blood pressure but the effect of the latter was more pronounced and registered from week 4 till the end of the study. Carvedilol and its combination with captopril significantly decreased SBP, DBP and MAP. They also decreased PP, prevented the development of LVH, and renal vascular changes and slowed the progression of chronic renal failure and these effects were stronger in the ADR-CC group than in the ADR-C group. The antihypertensive drugs failed to prevent proteinuria in ADR SHR. Significant positive correlations were found between PP (but not SBP, DBP and MAP) and both proteinuria and Ccr in all groups of rats. In conclusion, carvedilol alone, but more strongly in combination with captopril, significantly reduced blood pressure, PP, LVH, renal blood vessel changes and

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

    DEFF Research Database (Denmark)

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

    2017-01-01

    Background--Approximately one third of patients with ST-segment elevation myocardial infarction (STEMI) have left ventricular hypertrophy (LVH), which is associated with impaired outcome. However, the causal association between LVH and outcome in STEMI is unknown. We evaluated the association...... between LVH and: myocardial infarct size, area at risk, myocardial salvage, microvascular obstruction, left ventricular (LV) function (all determined by cardiac magnetic resonance [CMR]), and all-cause mortality and readmission for heart failure in STEMI patients treated with primary percutaneous coronary...

  8. Kallikrein-related peptidase 8 is expressed in myocardium and induces cardiac hypertrophy

    Science.gov (United States)

    Cao, Buqing; Yu, Qing; Zhao, Wei; Tang, Zhiping; Cong, Binghai; Du, Jiankui; Lu, Jianqiang; Zhu, Xiaoyan; Ni, Xin

    2016-01-01

    The tissue kallikrein-related peptidase family (KLK) is a group of trypsin- and chymotrypsin-like serine proteases that share a similar homology to parent tissue kallikrein (KLK1). KLK1 is identified in heart and has anti-hypertrophic effects. However, whether other KLK family members play a role in regulating cardiac function remains unknown. In the present study, we demonstrated for the first time that KLK8 was expressed in myocardium. KLK8 expression was upregulated in left ventricle of cardiac hypertrophy models. Both intra-cardiac adenovirus-mediated and transgenic-mediated KLK8 overexpression led to cardiac hypertrophy in vivo. In primary neonatal rat cardiomyocytes, KLK8 knockdown inhibited phenylephrine (PE)-induced cardiomyocyte hypertrophy, whereas KLK8 overexpression promoted cardiomyocyte hypertrophy via a serine protease activity-dependent but kinin receptor-independent pathway. KLK8 overexpression increased epidermal growth factor (EGF) production, which was blocked by the inhibitors of serine protease. EGF receptor (EGFR) antagonist and EGFR knockdown reversed the hypertrophy induced by KLK8 overexpression. KLK8-induced cardiomyocyte hypertrophy was also significantly decreased by blocking the protease-activated receptor 1 (PAR1) or PAR2 pathway. Our data suggest that KLK8 may promote cardiomyocyte hypertrophy through EGF signaling- and PARs-dependent but a kinin receptor-independent pathway. It is implied that different KLK family members can subtly regulate cardiac function and remodeling. PMID:26823023

  9. Vascular smooth muscle cell hypertrophy induced by glycosylated human oxyhaemoglobin.

    Science.gov (United States)

    Peiró, C; Angulo, J; Rodríguez-Mañas, L; Llergo, J L; Vallejo, S; Cercas, E; Sánchez-Ferrer, C F

    1998-10-01

    1. Nonenzymatic protein glycosylation is a possible mechanism contributing to oxidative stress and vascular disease in diabetes. In this work, the influence of 14%-glycosylated human oxyhaemoglobin (GHHb), compared to the non-glycosylated protein (HHb), was studied on several growth parameters of rat cultured vascular smooth muscle cells (VSMC). A role for reactive oxygen species was also analysed. 2. Treatment of VSMC for 48 h with GHHb, but not with HHb, increased planar cell surface area in a concentration dependent manner. The threshold concentration was 10 nM, which increased cell size from 7965+/-176 to 9411+/-392 microm2. Similarly, only GHHb enhanced protein content per well in VSMC cultures. 3. The planar surface area increase induced by 10 nM GHHb was abolished by superoxide dismutase (SOD; 50 200 u ml(-1)), deferoxamine (100 nM-100 microM), or dimethylthiourea (1 mM), while catalase (50 200 u ml(-1)) or mannitol (1 mM) resulted in a partial inhibition of cell size enhancement. 4. When a known source of oxygen free radicals was administered to VSMC, the xanthine/xanthine oxidase system, the results were analogous to those produced by GHHb. Indeed, enhancements of cell size were observed, which were inhibited by SOD, deferoxamine, or catalase. 5. These results indicate that, at low concentrations, GHHb induces hypertrophy in VSMC, this effect being mediated by superoxide anions, hydrogen peroxide, and/or hydroxyl radicals. Therefore, glycosylated proteins can have a role in the development of the structural vascular alterations associated to diabetes by enhancing oxidative stress.

  10. Vascular smooth muscle cell hypertrophy induced by glycosylated human oxyhaemoglobin

    Science.gov (United States)

    Peiró, Concepción; Angulo, Javier; Rodríguez-Mañas, Leocadio; Llergo, José L; Vallejo, Susana; Cercas, Elena; Sánchez-Ferrer, Carlos F

    1998-01-01

    Nonenzymatic protein glycosylation is a possible mechanism contributing to oxidative stress and vascular disease in diabetes. In this work, the influence of 14%-glycosylated human oxyhaemoglobin (GHHb), compared to the non-glycosylated protein (HHb), was studied on several growth parameters of rat cultured vascular smooth muscle cells (VSMC). A role for reactive oxygen species was also analysed.Treatment of VSMC for 48 h with GHHb, but not with HHb, increased planar cell surface area in a concentration dependent manner. The threshold concentration was 10 nM, which increased cell size from 7965±176 to 9411±392 μm2. Similarly, only GHHb enhanced protein content per well in VSMC cultures.The planar surface area increase induced by 10 nM GHHb was abolished by superoxide dismutase (SOD; 50–200 u ml−1), deferoxamine (100 nM–100 μM), or dimethylthiourea (1 mM), while catalase (50–200 u ml−1) or mannitol (1 mM) resulted in a partial inhibition of cell size enhancement.When a known source of oxygen free radicals was administered to VSMC, the xanthine/xanthine oxidase system, the results were analogous to those produced by GHHb. Indeed, enhancements of cell size were observed, which were inhibited by SOD, deferoxamine, or catalase.These results indicate that, at low concentrations, GHHb induces hypertrophy in VSMC, this effect being mediated by superoxide anions, hydrogen peroxide, and/or hydroxyl radicals. Therefore, glycosylated proteins can have a role in the development of the structural vascular alterations associated to diabetes by enhancing oxidative stress. PMID:9831896

  11. Expression of periodontal inflammation into left ventricular hypertrophy in Type 2 diabetes mellitus: A cross-sectional study

    Directory of Open Access Journals (Sweden)

    Trupti Sarda

    2016-01-01

    Full Text Available Background: Chronic periodontitis, an inflammatory disease, is closely related to certain systemic conditions such as cardiovascular diseases, obesity, and Type 2 diabetes mellitus. These conditions, occurring as comorbidities, synergically affect periodontal tissues. Aim: This study aims to examine whether chronic gingivitis and chronic generalized severe periodontitis in patients with Type 2 diabetes mellitus are associated with increased left ventricular mass (LVM. Materials and Methods: A total of 45 patients affected with Type 2 diabetes mellitus were recruited and divided into three groups with 15 patients each according to their periodontal status: Group I consisting of healthy individuals, Group II consisting of chronic gingivitis, and Group III consisting of chronic generalized severe periodontitis. They were assessed clinically, biochemically, and echocardiographically. LVM was calculated according to Devereux formula and was indexed to height. Results: The differences in the means for LVM and LVM index (LVMI were statistically significant in three groups with a P = 0.006 and 0.014, respectively. After adjusting for the confounders, the mean values of LVM in Group I, II, and III were 149.35 ± 35.51 g, 147.95 ± 31.59 g, and 156.36 ± 36.57 g, respectively and for LVMI, the mean values were 43.61 ± 12.16 g/m 2.7 (Group I, 47.12 ± 10.84 g/m 2.7 (Group II, and 46.34 ± 12.55 g/m 2.7 (Group III. Conclusions: A positive association between chronic generalized severe periodontitis and increased LVM in Type 2 DM patients was observed, suggesting the role of periodontal disease in the left ventricular hypertrophy.

  12. Expression of periodontal inflammation into left ventricular hypertrophy in Type 2 diabetes mellitus: A cross-sectional study.

    Science.gov (United States)

    Sarda, Trupti; Rathod, Surekha; Kolte, Abhay; Bodhare, Girish; Modak, Anil

    2016-01-01

    Chronic periodontitis, an inflammatory disease, is closely related to certain systemic conditions such as cardiovascular diseases, obesity, and Type 2 diabetes mellitus. These conditions, occurring as comorbidities, synergically affect periodontal tissues. This study aims to examine whether chronic gingivitis and chronic generalized severe periodontitis in patients with Type 2 diabetes mellitus are associated with increased left ventricular mass (LVM). A total of 45 patients affected with Type 2 diabetes mellitus were recruited and divided into three groups with 15 patients each according to their periodontal status: Group I consisting of healthy individuals, Group II consisting of chronic gingivitis, and Group III consisting of chronic generalized severe periodontitis. They were assessed clinically, biochemically, and echocardiographically. LVM was calculated according to Devereux formula and was indexed to height. The differences in the means for LVM and LVM index (LVMI) were statistically significant in three groups with a P = 0.006 and 0.014, respectively. After adjusting for the confounders, the mean values of LVM in Group I, II, and III were 149.35 ± 35.51 g, 147.95 ± 31.59 g, and 156.36 ± 36.57 g, respectively and for LVMI, the mean values were 43.61 ± 12.16 g/m(2.7) (Group I), 47.12 ± 10.84 g/m(2.7) (Group II), and 46.34 ± 12.55 g/m(2.7) (Group III). A positive association between chronic generalized severe periodontitis and increased LVM in Type 2 DM patients was observed, suggesting the role of periodontal disease in the left ventricular hypertrophy.

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

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

    2009-05-15

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

  14. Impact of dry weight determined by calf bioimpedance ratio on carotid stiffness and left ventricular hypertrophy in hemodialysis patients.

    Science.gov (United States)

    Zhou, Yi-Lun; Liu, Jing; Ma, LiJie; Sun, Fang; Shen, Yang; Huang, Jing; Cui, TaiGen

    2014-04-01

    Our previous study has shown that modification of bioimpedance technique by the measurement of bioimpedance ratio in the calf (calf-BR) was a simple and practical method in assessing fluid status in hemodialysis patients. However, the consequences of periodical dry weight (DW) adjustment under the guidance of calf-BR on target organ damage have not been investigated. One hundred fifteen hemodialysis patients were enrolled in this pilot trial. Patients were divided into bioimpedance group and control group according to their dialysis schedule. In the bioimpedance group, DW was routinely adjusted under the guidance of calf-BR every 3 months. In the control group, the assessment of DW remained a clinical judgment. Carotid stiffness, left ventricular mass index (LVMI), and calf-BR were measured at baseline and at the 12th month in both groups. Home blood pressure (BP) was monitored monthly. Episodes of dialysis-related adverse events were recorded. No significant differences were observed in parameters between the two groups at baseline. Compared with the control group, the bioimpedance group had significantly lower values in terms of the annual averages of systolic home BP (147.4 ± 15.3 mm Hg vs. 152.6 ± 16.9 mm Hg, P = 0.019), carotid stiffness index β (10.7 ± 3.3 vs. 12.2 ± 3.1, P = 0.003), LVMI (155.21 ± 15.64 g/m(2) vs. 165.17 ± 16.76 g/m(2) , P measurement improved arterial stiffness and left ventricular hypertrophy with good tolerability in hemodialysis patients. © 2013 Wiley Periodicals, Inc. and International Center for Artificial Organs and Transplantation.

  15. ST segment/heart rate hysteresis improves the diagnostic accuracy of ECG stress test for coronary artery disease in patients with left ventricular hypertrophy.

    Science.gov (United States)

    Zimarino, Marco; Montebello, Elena; Radico, Francesco; Gallina, Sabina; Perfetti, Matteo; Iachini Bellisarii, Francesco; Severi, Silva; Limbruno, Ugo; Emdin, Michele; De Caterina, Raffaele

    2016-10-01

    The exercise electrocardiographic stress test (ExET) is the most widely used non-invasive diagnostic method to detect coronary artery disease. However, the sole ST depression criteria (ST-max) have poor specificity for coronary artery disease in patients with left ventricular hypertrophy. We hypothesised that ST-segment depression/heart rate hysteresis, depicting the relative behaviour of ST segment depression during the exercise and recovery phase of the test might increase the diagnostic accuracy of ExET for coronary artery disease detection in such patients. In three cardiology centres, we studied 113 consecutive patients (mean age 66 ± 2 years; 88% men) with hypertension-related left ventricular hypertrophy at echocardiography, referred to coronary angiography after an ExET. The following ExET criteria were analysed: ST-max, chronotropic index, heart rate recovery, Duke treadmill score, ST-segment depression/heart rate hysteresis. We detected significant coronary artery disease at coronary angiography in 61 patients (53%). At receiver-operating characteristic analysis, ST-segment depression/heart rate hysteresis had the highest area under the curve value (0.75, P coronary artery disease than conventional criteria in patients with hypertension-related left ventricular hypertrophy. © The European Society of Cardiology 2016.

  16. Features of left ventricular hypertrophy in patients with metabolic syndrome with or without comparable blood pressure: a meta-analysis.

    Science.gov (United States)

    Li, Ning-Yin; Yu, Jing; Zhang, Xiao-Wei; Wang, Shi-Xiong; Chang, Peng; Ding, Qi; Ma, Rui-Xin; Chen, Qun-Fei; Zhao, Feng; Bai, Feng

    2013-06-01

    The prevalence of metabolic syndrome (MS) has been on the rise over the past few decades, and this is associated with an increased incidence of target organ damage such as left ventricular hypertrophy (LVH). This meta-analysis aims to evaluate the features of LVH in MS patients with or without high blood pressure (BP). PubMed, Cochrane Library, Embase, Science Citation Index, and China Biology Medicine Disc, WanFang data, China National Knowledge Infrastructure database, and VIP were searched. Cross-sectional studies which directly compared LVH in hypertensive patients with MS and those with hypertension alone were identified. The following parameters were analyzed: systolic blood pressure (SBP), diastolic blood pressure (DBP), left ventricular mass (LVM), left ventricular mass index (LVMI), left ventricular mass/height(2.7) (LVM/h(2.7)), interventricular septum thickness (IVSt), left ventricular end-diastolic diameter (LVEDd), left ventricular posterior wall (LVPW), ratio of early to late diastolic peak flow velocity (E/A), and relative wall thickness (RWT). Data were extracted and analyzed by Cochrane Collaboration's RevMan 5.0 software. 14 studies involving 5,994 patients were included. In four studies, MS patients with comparable level of BP had higher SBP (mmHg) [Mean Difference (MD) = 2.28, 95 % confidence intervals (CI): -0.58 to 5.13], DBP (mmHg) (MD = 1.32, 95 % CI: -0.23 to 2.87), LVM (g) (MD = 42.10, 95 % CI: 6.92-77.28), LVMI (g/m(2)) (MD = 8.93, 95 % CI: 5.29-12.57), LVM/h(2.7) (g/m(2.7)) (MD = 5.40, 95 % CI: 2.51-8.29), IVSt (mm) (MD = 0.49, 95 % CI: 0.28-0.71), LVEDd (mm) (MD = 1.04, 95 % CI: -1.10 to 3.18), LVPW (mm) (MD = 0.75, 95 % CI: 0.13-1.37), RWT (MD = 0.06, 95 % CI: -0.00 to 0.12), and lower E/A (MD = -0.08, 95 % CI: -0.18 to 0.02) when compared to the patients with hypertension alone. In other ten studies, the hypertensive patients with MS exhibited higher levels of SBP (mmHg) (MD = 4.67, 95 % CI: 2.72-6.62), DBP (mmHg) (MD = 2.03,95 % CI

  17. Ectopic expression of Cdk8 induces eccentric hypertrophy and heart failure.

    Science.gov (United States)

    Hall, Duane D; Ponce, Jessica M; Chen, Biyi; Spitler, Kathryn M; Alexia, Adrianne; Oudit, Gavin Y; Song, Long-Sheng; Grueter, Chad E

    2017-08-03

    Widespread changes in cardiac gene expression occur during heart failure, yet the mechanisms responsible for coordinating these changes remain poorly understood. The Mediator complex represents a nodal point for modulating transcription by bridging chromatin-bound transcription factors with RNA polymerase II activity; it is reversibly regulated by its cyclin-dependent kinase 8 (Cdk8) kinase submodule. Here, we identified increased Cdk8 protein expression in human failing heart explants and determined the consequence of this increase in cardiac-specific Cdk8-expressing mice. Transgenic Cdk8 overexpression resulted in progressive dilated cardiomyopathy, heart failure, and premature lethality. Prior to functional decline, left ventricular cardiomyocytes were dramatically elongated, with disorganized transverse tubules and dysfunctional calcium handling. RNA sequencing results showed that myofilament gene isoforms not typically expressed in adult cardiomyocytes were enriched, while oxidative phosphorylation and fatty acid biosynthesis genes were downregulated. Interestingly, candidate upstream transcription factor expression levels and MAPK signaling pathways thought to determine cardiomyocyte size remained relatively unaffected, suggesting that Cdk8 functions within a novel growth regulatory pathway. Our findings show that manipulating cardiac gene expression through increased Cdk8 levels is detrimental to the heart by establishing a transcriptional program that induces pathological remodeling and eccentric hypertrophy culminating in heart failure.

  18. Syndecan-4 Signaling Is Required for Exercise-Induced Cardiac Hypertrophy

    Science.gov (United States)

    Xie, Jun; He, Guixin; Chen, Qinhua; Sun, Jiayin; Dai, Qin; Lu, Jianrong; Li, Guannan; Wu, Han; Li, Ran; Chen, Jianzhou; Xu, Wei; Xu, Biao

    2016-01-01

    Cardiac hypertrophy can be broadly classified as either physiological or pathological. Physiological stimuli such as exercise cause adaptive cardiac hypertrophy and normal heart function. Pathological stimuli including hypertension and aortic valvular stenosis cause maladaptive cardiac remodeling and ultimately heart failure. Syndecan-4 (synd4) is a transmembrane proteoglycan identified as being involved in cardiac adaptation after injury, but whether it takes part in physiological cardiac hypertrophy is unclear. We observed upregulation of synd4 in exercise-induced hypertrophic myocardium. To evaluate the role of synd4 in the physiological form of cardiac hypertrophy, mice lacking synd4 (synd4–/–) were exercised by swimming for 4 wks. Ultrasonic cardiogram (UCG) and histological analysis revealed that swimming induced the hypertrophic phenotype but was blunted in synd4–/– compared with wild-type (WT) mice. The swimming-induced activation of Akt, a key molecule in physiological hypertrophy was also more decreased than in WT controls. In cultured cardiomyocytes, synd4 overexpression could induce cell enlargement, protein synthesis and distinct physiological molecular alternation. Akt activation also was observed in synd4-overexpressed cardiomyocytes. Furthermore, inhibition of protein kinase C (PKC) prevented the synd4-induced hypertrophic phenotype and Akt phosphorylation. This study identified an essential role of synd4 in mediation of physiological cardiac hypertrophy. PMID:26835698

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

    Science.gov (United States)

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

    2017-06-01

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

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

    Directory of Open Access Journals (Sweden)

    K. I. Pshenichkin

    2015-12-01

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

  1. Progression of left ventricular hypertrophy in children with early chronic kidney disease: 2-year follow-up study.

    Science.gov (United States)

    Mitsnefes, Mark M; Kimball, Thomas R; Kartal, Janis; Witt, Sandra A; Glascock, Betty J; Khoury, Philip R; Daniels, Stephen R

    2006-11-01

    To determine the prevalence and incidence of left ventricular hypertrophy (LVH) and LV geometry and identify variables associated with LV mass (LVM) growth and development of LVH in children and adolescents with chronic kidney disease (CKD). A 2-year longitudinal study of children with CKD (glomerular filtration rate [GFR] 15-89 mL/minute/1.73 m2). Thirty-one subjects had baseline and repeated echocardiography. Six (19%) of 31 children had LVH at baseline; the prevalence of LVH increased to 39% at 2-year follow-up. Eccentric LVH was the most common geometric pattern throughout the study. Among 25 children with initially normal LVM index, 8 (32%) developed new LVH. Children with incident LVH had significantly higher mean parathyroid hormone (iPTH), lower hemoglobin and calcium levels at baseline, and significantly larger increase in iPTH during a follow-up than children with normal LVM index. Stepwise regression analysis showed that lower initial LVM index and hemoglobin level and interval increase in iPTH and nighttime systolic blood pressure (SBP) load during a follow-up independently predicted interval increase in LVM index. LVH progresses in children during early stages of CKD. More aggressive control of anemia, BP, and hyperparathyroidism might be important in preventing the development of LVH in these patients.

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

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    B. Amarjagal

    2015-12-01

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

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

    Directory of Open Access Journals (Sweden)

    B. Amarjagal

    2007-01-01

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

  4. Relationship between Serum Bilirubin and Left Ventricular Hypertrophy in Patients with Essential Hypertension.

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    Tao Zhou

    Full Text Available Prospective studies have found low bilirubin levels were an important predictive factor of cardiovascular events. However, few have yet investigated possible association between serum bilirubin level and LVH in essential hypertension. The aim of the present study was to evaluate the relationship between serum bilirubin levels with LVH in newly diagnosed hypertension patients.The present study evaluated the relationship between serum total bilirubin level and left ventricle hypertrophy (LVH in newly diagnosed hypertensive patients with a sample size of 344. We divided subjects into LVH group (n=138 and non-LVH group (n=206. Physical examination, laboratory tests and echocardiography were conducted. The multivariate logistic regression model was used to verify the independent association between RDW and LVH.Our results found that patients with LVH had lower bilirubin levels than non-LVH ones. Stepwise multiple linear regression analysis showed total bilirubin level (B=-0.017, P=0.008 was negatively associated with left ventricle mass index (LVMI even adjusting for some confounders. The multiples logistic regression found total bilirubin level was independently related with of LVH, as a protective factors (OR=0.91, P=0.010.As a routine and quick laboratory examination index, serum bilirubin may be treated as novel marker for evaluating LVH risk in hypertensive patients. Cohort study with larger sample size are needed.

  5. Sulforaphane protects H9c2 cardiomyocytes from angiotensin II-induced hypertrophy.

    Science.gov (United States)

    Wu, Q-Q; Zong, J; Gao, L; Dai, J; Yang, Z; Xu, M; Fang, Y; Ma, Z-G; Tang, Q-Z

    2014-05-01

    Cardiac hypertrophy is an adaptive process of the heart in response to various stimuli, but sustained cardiac hypertrophy will finally lead to heart failure. Sulforaphane-extracted from cruciferous vegetables of the genus Brassica such as broccoli, brussels sprouts, and cabbage-has been evaluated for its anticarcinogenic and antioxidant effects. To investigate the effect of sulforaphane on angiotensin II (Ang II)-induced cardiac hypertrophy in vitro. Embryonic rat heart-derived H9c2 cells were co-incubated with sulforaphane and Ang II. The cell surface area and mRNA levels of hypertrophic markers were measured to clarify the effect of sulforaphane on cardiac hypertrophy. The underlying mechanism was further investigated by detecting the activation of Akt and NF-κB signaling pathways. We found that H9c2 cells pretreated with sulforaphane were protected from Ang II-induced hypertrophy. The increasing mRNA levels of ANP, BNP, and β-MHC in Ang II-stimulated cells were also down-regulated after sulforaphane treatment. Moreover, sulforaphane repressed the Ang II-induced phosphorylation of Akt, GSK3β, mTOR, eIF4e, as well as of IκBα and NF-κB. Based on our results, sulforaphane attenuates Ang II-induced hypertrophy of H9c2 cardiomyocytes mediated by the inhibition of intracellular signaling pathways including Akt and NF-κB.

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

    Science.gov (United States)

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

    2014-11-04

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

  7. Prognostic role of Sokolow-Lyon criterion in further development of the left ventricular concentric hypertrophy in adolescents with arterial hypertension

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    O. G. Ivanko

    2017-02-01

    Full Text Available Objective – to determine the possibility of Sokolow-Lyon criterion for forecast of the concentric Left Ventricular Hypertrophy (LVH development in young hypertensive patients. The investigation has been organized as a prospective support of teenagers aged 16-17 yr within 3 years. Materials and Methods. Methods of the study were multiple office blood pressure measurements, daily blood pressure monitoring with electronic device, ECG and ultrasound. 47 males and females teens with firstly diagnosed primary arterial hypertension not treated before were enrolled. Primary labile hypertension diagnosed in 10 males and 11 females and 18 males and 8 females had stable hypertension. For all patients the electrocardiographic study was performed. The positive Sokolow-Lyon criterion was considered as a sum in height of S1 and R5 or R6 waves in standard chest leads excessed34 mm. Watching teens conducted during 3 years. Results. Sokolow-Lyon criterion >34 mm (3.4 mV was identified as positive in 8 males with a stable and 6 with a labile hypertension, also it was the same in 6 females, all of them had stable hypertension. Morphological and functional left ventricular parameters in patients were minimal and appeared only as a mild thickening of the myocardial wall of the left ventricle. Only one girl who was positive by Sokolow-Lyon criterion had LVH and was excluded from the study. Repeated clinical and instrumental examination was carried out in 46 persons over 3 years to the age of 21 years. New ultrasound investigation showed the left ventricular hypertrophy development in 18 young men and 5 women with stable hypertension. The odds ratio for the development of concentric hypertrophy of the left ventricle during 3 years of the young people with diagnosed in adolescence index Sokolow-Lyon >34 mm was 8.906 with a 95% confidence interval 2.24-35.33 (p < 0.05. The sensitivity of Sokolow-Lyon criterion in predicting of the left ventricular hypertrophy during 3

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

    Science.gov (United States)

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

    1995-01-01

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

  9. Hypertrophied myocardium is vulnerable to ischemia reperfusion injury and refractory to rapamycin-induced protection due to increased oxidative/nitrative stress.

    Science.gov (United States)

    Ma, Lei-Lei; Yin, Pei-Pei; Li, Yang; Kong, Fei-Juan; Guo, Jun-Jie; Shi, Hong-Tao; Zhu, Jian-Bin; Zou, Yun-Zeng; Ge, Jun-Bo

    2017-11-24

    Left ventricular hypertrophy (LVH) is causally related to increased morbidity and mortality following acute myocardial infarction (AMI) via still unknown mechanisms. Although rapamycin exerts cardioprotective effects against myocardial ischemia/reperfusion (MI/R) injury in normal animals, whether rapamycin-elicited cardioprotection are altered in the presence of LVH has yet to be determined. Pressure overload-induced cardiac hypertrophied mice and sham-operated controls were exposed to AMI by coronary artery ligation, and treated with vehicle or rapamycin  10 min before reperfusion. Rapamycin produced marked cardioprotection in normal control mice, whereas pressure overload-induced cardiac hypertrophied mice manifested enhanced myocardial injury, and was refractory to rapamycin-elicited cardioprotection evidenced by augmented infarct size, aggravated cardiomyocytes apoptosis, and worsening cardiac function. Rapamycin alleviated MI/R injury via ERK-dependent antioxidative pathways in normal mice, whereas cardiac hypertrophied mice manifested markedly exacerbated oxidative/nitrative stress after MI/R evidenced by the increased iNOS/gp91phox expression, superoxide production, total NO metabolites and nitrotyrosine content. Moreover, scavenging superoxide or peroxynitrite by selective gp91phox assembly inhibitor gp91ds-tat or ONOO- scavenger EUK134 markedly ameliorated MI/R injury, as shown by reduced myocardial oxidative/nitrative stress, alleviated myocardial infarction, hindered cardiomyocytes apoptosis, and improved cardiac function in aortic-banded mice. However, no additional cardioprotective effects was achieved when we combined rapamycin and gp91ds-tat or EUK134 in ischemic reperfused hearts with or without LVH. These results suggest that cardiac hypertrophy attenuated rapamycin-induced cardioprotection by increasing oxidative/nitrative stress and scavenging superoxide/peroxynitrite protects the hypertrophied heart from MI/R. ©2017 The Author(s).

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

    African Journals Online (AJOL)

    Western blot was used to analyze the expression of some glycolytic proteins, including Glut-1, hexokinase (HXK-2), and enolase, while apoptosis of H9C2 was determined by flow cytometry. Results: PE caused hypertrophy in H9C2, which was ameliorated by HIF-1α. Compared to normal, under prolonged high glucose, the ...

  11. 19-Hydroxyeicosatetraenoic acid and isoniazid protect against angiotensin II-induced cardiac hypertrophy.

    Science.gov (United States)

    Elkhatali, Samya; El-Sherbeni, Ahmed A; Elshenawy, Osama H; Abdelhamid, Ghada; El-Kadi, Ayman O S

    2015-12-15

    We have recently demonstrated that 19-hydroxyeicosatetraenoic acid (19-HETE) is the major subterminal-HETE formed in the heart tissue, and its formation was decreased during cardiac hypertrophy. In the current study, we examined whether 19-HETE confers cardioprotection against angiotensin II (Ang II)-induced cardiac hypertrophy. The effect of Ang II, with and without 19-HETE (20 μM), on the development of cellular hypertrophy in cardiomyocyte RL-14 cells was assessed by real-time PCR. Also, cardiac hypertrophy was induced in Sprague-Dawley rats by Ang II, and the effect of increasing 19-HETE by isoniazid (INH; 200mg/kg/day) was assessed by heart weight and echocardiography. Also, alterations in cardiac cytochrome P450 (CYP) and their associated arachidonic acid (AA) metabolites were determined by real-time PCR, Western blotting and liquid-chromatography-mass-spectrometry. Our results demonstrated that 19-HETE conferred a cardioprotective effect against Ang II-induced cellular hypertrophy in vitro, as indicated by the significant reduction in β/α-myosin heavy chain ratio. In vivo, INH improved heart dimensions, and reversed the increase in heart weight to tibia length ratio caused by Ang II. We found a significant increase in cardiac 19-HETE, as well as a significant reduction in AA and its metabolite, 20-HETE. In conclusion, 19-HETE, incubated with cardiomyocytes in vitro or induced in the heart by INH in vivo, provides cardioprotection against Ang II-induced hypertrophy. This further confirms the role of CYP, and their associated AA metabolites in the development of cardiac hypertrophy. Copyright © 2015 Elsevier Inc. All rights reserved.

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

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    Güínever Eustáquio do Império

    2015-08-01

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

  13. Usefulness of Non-Anteroseptal Region Left Ventricular Hypertrophy Using Cardiac Magnetic Resonance to Predict Repeat Alcohol Septal Ablation for Refractory Obstructive Hypertrophic Cardiomyopathy.

    Science.gov (United States)

    Kitamura, Mitsunobu; Amano, Yasuo; Takayama, Morimasa; Shibuya, Junsuke; Matsuda, Junya; Sangen, Hideto; Nakamura, Shunichi; Takano, Hitoshi; Asai, Kuniya; Kumita, Shinichiro; Shimizu, Wataru

    2017-07-01

    We evaluated a cohort of patients treated with alcohol septal ablation (ASA) to identify predictive factors for repeat ASA. We compared 15 patients who underwent repeat ASA procedures (group R) with 69 patients not requiring repeat procedures (group S) in terms of clinical parameters and morphologic cardiac magnetic resonance. Group R showed higher number of hypertrophic segments (thickness ≥15 mm) in the basal left ventricular level (2.8 ± 1.7 vs 1.7 ± 0.8, p = 0.009) than group S. In the multivariate analysis, diuretics use (adjusted odds ratio 5.8, 95% confidential interval [CI] 1.04 to 32.2, p = 0.045) and the number of non-anteroseptal extended hypertrophy segments at the basal level were independent predictors of a repeat ASA procedure (adjusted odds ratio 3.64/segment, 95% CI 1.40 to 9.4, p = 0.008). One repeat ASA among 21 patients without non-anteroseptal hypertrophy and 1 repeat ASA among 29 patients without posteroseptal hypertrophy were observed; however, 7 of the 14 patients with ≥2 segments of non-anteroseptal hypertrophy received repeat ASA. In conclusion, cardiac magnetic resonance-based cross-sectional investigation elucidated non-anteroseptal hypertrophy (≥2 segments) to be a crucial predictor of repeat ASA. ASA is useful for patients with regional hypertrophy in the basal anteroseptal, but not posteroseptal region, and without heart failure requiring diuretics. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Assessment of pulmonary artery pressure and right ventricular function in children with adenotonsillar hypertrophy using different parameters.

    Science.gov (United States)

    Çetin, Mecnun; Yılmaz, Münevver; Özen, Serkan; Bozan, Nazım; Coşkun, Şenol

    2014-11-01

    Our aim was comparison of preoperative and postoperative right ventricular functions of children with adenotonsillar hypertrophy (ATH) who have findings of upper airway obstruction, using new echocardiographic parameters. Forty-one children who have admitted to our hospital with symptoms suggestive of upper airway obstruction, whose history and physical examination findings suggest upper airway obstruction and who have undergone adenoidectomy/adenotonsillectomy and 40 healthy children, all of whom between 2 and 12 years of age, were included in the study. Patient group was evaluated by pulsed wave tissue Doppler echocardiography as well as with conventional echocardiography before the operation and 6 months after the operation. Of 41 children in study group, 26 (63.4%) had adenotonsillectomy and 15 (36.6%) had adenoidectomy. Tricuspid annular plane systolic excursion (TAPSE) was significantly lower in preoperative group compared to control group (18.46±1.67, 19.77±1.62; p=0.000, respectively). Myocardial performance index (MPI) was significantly higher in preoperative group than postoperative and control group (0.40±0.07, 0.36±0.06, 0.35±0.07; p=0.032, respectively). Tricuspid isovolumic acceleration (TIVA) was significantly lower in preoperative group than preoperative and control group (2.97±0.8, 3.43±0.7, 3.43±0.9; p=0.020, respectively). Disappearance of this difference was found between postoperative and control groups (p=0.984). Pulmonary acceleration time (PAcT) was found to be significantly lower in preoperative group compared to postoperative and control group (109.68±18.03, 118.93±17.46, 120.0±14.07; p=0.010, respectively). Mean pulmonary artery pressure (mPAP) was significantly higher in preoperative group than control group (29.64±8.11, 24.95±6.33; p=0.010, respectively). In postoperative group mPAP was found to be similar to control group (25.48±7.85, 24.95±6.33; p=0.740, respectively). TAPSE, PAcT, MPI and TIVA are useful markers for

  15. UCH-L1 induces podocyte hypertrophy in membranous nephropathy by protein accumulation.

    Science.gov (United States)

    Lohmann, Frithjof; Sachs, Marlies; Meyer, Tobias N; Sievert, Henning; Lindenmeyer, Maja T; Wiech, Thorsten; Cohen, Clemens D; Balabanov, Stefan; Stahl, R A K; Meyer-Schwesinger, Catherine

    2014-07-01

    Podocytes are terminally differentiated cells of the glomerular filtration barrier that react with hypertrophy in the course of injury such as in membranous nephropathy (MGN). The neuronal deubiquitinase ubiquitin C-terminal hydrolase L1 (UCH-L1) is expressed and activated in podocytes of human and rodent MGN. UCH-L1 regulates the mono-ubiquitin pool and induces accumulation of poly-ubiquitinated proteins in affected podocytes. Here, we investigated the role of UCH-L1 in podocyte hypertrophy and in the homeostasis of the hypertrophy associated "model protein" p27(Kip1). A better understanding of the basic mechanisms leading to podocyte hypertrophy is crucial for the development of specific therapies in MGN. In human and rat MGN, hypertrophic podocytes exhibited a simultaneous up-regulation of UCH-L1 and of cytoplasmic p27(Kip1) content. Functionally, inhibition of UCH-L1 activity and knockdown or inhibition of UCH-L1 attenuated podocyte hypertrophy by decreasing the total protein content in isolated glomeruli and in cultured podocytes. In contrast, UCH-L1 levels and activity increased podocyte hypertrophy and total protein content in culture, specifically of cytoplasmic p27(Kip1). UCH-L1 enhanced cytoplasmic p27(Kip1) levels by nuclear export and decreased poly-ubiquitination and proteasomal degradation of p27(Kip1). In parallel, UCH-L1 increased podocyte turnover, migration and cytoskeletal rearrangement, which are associated with known oncogenic functions of cytoplasmic p27(Kip1) in cancer. We propose that UCH-L1 induces podocyte hypertrophy in MGN by increasing the total protein content through altered degradation and accumulation of proteins such as p27(Kip1) in the cytoplasm of podocytes. Modification of both UCH-L1 activity and levels could be a new therapeutic avenue to podocyte hypertrophy in MGN. Copyright © 2014 Elsevier B.V. All rights reserved.

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

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    Mungrue K

    2011-07-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2004-03-01

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

  18. Electrocardiographic measures of left ventricular hypertrophy in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.

    Science.gov (United States)

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

    2016-12-01

    Left ventricular hypertrophy (LVH) predicts cardiovascular risk in hypertensive patients. We analyzed baseline/follow-up electrocardiographies in 26,376 Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial participants randomized to amlodipine (A), lisinopril (L), or chlorthalidone (C). Prevalent/incident LVH was examined using continuous and categorical classifications of Cornell voltage. At 2 and 4 years, prevalence of LVH in the C group (5.57%; 6.14%) was not statistically different from A group (2 years: 5.47%; P = .806, 4 years: 6.54%; P = .857) or L group (2 years: 5.64%; P = .857, 4 years: 6.50%; P = .430). Incident LVH followed similarly, with no difference at 2 years for C (2.99%) compared to A (2.57%; P = .173) or L (3.16%; P = .605) and at 4 years (C = 3.52%, A = 3.29%, L = 3.71%; P = .521 C vs. A, P = .618 C vs. L). Mean Cornell voltage decreased comparably across treatment groups (Δ baseline, 2 years = +3 to -27 μV, analysis of variance P = .8612; 4 years = +10 to -17 μV, analysis of variance P = .9692). We conclude that risk reductions associated with C treatment in secondary end points of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial cannot be attributed to differential improvements in electrocardiography LVH. Copyright © 2016 American Society of Hypertension. All rights reserved.

  19. Office and Home Blood Pressures as Determinants of Electrocardiographic Left Ventricular Hypertrophy Among Black Nigerians Compared With White Flemish.

    Science.gov (United States)

    Odili, Augustine N; Thijs, Lutgarde; Yang, Wen-Yi; Ogedengbe, John O; Nwegbu, Maxwell M; Jacobs, Lotte; Wei, Fang-Fei; Feng, Ying-Mei; Zhang, Zhen-Yu; Kuznetsova, Tatiana; Nawrot, Tim S; Staessen, Jan A

    2017-11-01

    The association of electrocardiographic left ventricular hypertrophy (ECG-LVH) with blood pressure (BP) in Blacks living in sub-Saharan Africa remains poorly documented. In 225 Black Nigerians and 729 White Flemish, we analyzed QRS voltages and voltage-duration products and 12 criteria diagnostic of ECG-LVH in relation to office BP (mean of 5 consecutive readings) and home BP (duplicate morning and evening readings averaged over 1 week). In multivariable analyses, QRS voltage and voltage-duration indexes were generally higher in Blacks than Whites. By using any of 12 criteria, ECG-LVH was more prevalent among Black than White men (54.4% vs. 36.0%) with no ethnic difference among women (17.1%). Precordial voltages and voltage-duration products increased with office and home systolic BP (SBP), and increases were up to 3-fold steeper in Blacks. In Blacks vs. Whites, increases in the Sokolow-Lyon voltage associated with a 10-mm Hg higher SBP were 0.18 mV (95% confidence interval [CI], 0.09-0.26) vs. 0.06 mV (0.02-0.09) and 0.17 mV (0.07-0.28) vs. 0.11 mV (CI, 0.07-0.15) for office and home BP, respectively, with a significant ethnic gradient (P office and home BP in Blacks than Whites. Associations of ECG voltages and voltage-duration products and risk of ECG-LVH with BP are steeper in Black Nigerians compared with a White reference population. In resource-poor settings of sub-Saharan Africa, the ECG in combination with office and home BP is an essential instrument in risk stratification across the entire BP range.

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

    Directory of Open Access Journals (Sweden)

    Nabil Ghorayeb

    2005-09-01

    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

  1. Repeated blood flow restriction induces muscle fiber hypertrophy.

    Science.gov (United States)

    Sudo, Mizuki; Ando, Soichi; Kano, Yutaka

    2017-02-01

    We recently developed an animal model to investigate the effects of eccentric contraction (ECC) and blood flow restriction (BFR) on muscle tissue at the cellular level. This study clarified the effects of repeated BFR, ECC, and BFR combined with ECC (BFR+ECC) on muscle fiber hypertrophy. Male Wistar rats were assigned to 3 groups: BFR, ECC, and BFR+ECC. The contralateral leg in the BFR group served as a control (CONT). Muscle fiber cross-sectional area (CSA) of the tibialis anterior was determined after the respective treatments for 6 weeks. CSA was greater in the BFR+ECC group than in the CONT (P hypertrophy at the cellular level. Muscle Nerve 55: 274-276, 2017. © 2016 Wiley Periodicals, Inc.

  2. Expression profiling reveals differences in metabolic gene expression between exercise-induced cardiac effects and maladaptive cardiac hypertrophy

    DEFF Research Database (Denmark)

    Strøm, Claes C; Aplin, Mark; Ploug, Thorkil

    2005-01-01

    While cardiac hypertrophy elicited by pathological stimuli eventually leads to cardiac dysfunction, exercise-induced hypertrophy does not. This suggests that a beneficial hypertrophic phenotype exists. In search of an underlying molecular substrate we used microarray technology to identify cardiac...... by quantitative PCR. The exercise program resulted in cardiac hypertrophy without impaired cardiac function. Principal component analysis identified an exercise-induced change in gene expression that was distinct from the program observed in maladaptive hypertrophy. Statistical analysis identified 267 upregulated...... translocase (CD36). DNA microarray analysis of gene expression changes in exercise-induced cardiac hypertrophy suggests that a set of genes involved in fatty acid and glucose metabolism could be fundamental to the beneficial phenotype of exercise-induced hypertrophy, as these changes are absent or reversed...

  3. Relationship of left ventricular hypertrophy and diastolic function with cardiovascular and renal outcomes in African Americans with hypertensive chronic kidney disease.

    Science.gov (United States)

    Peterson, Gail E; de Backer, Tine; Contreras, Gabriel; Wang, Xuelei; Kendrick, Cynthia; Greene, Tom; Appel, Lawrence J; Randall, Otelio S; Lea, Janice; Smogorzewski, Miroslaw; Vagaonescu, Tudor; Phillips, Robert A

    2013-09-01

    African Americans with hypertension are at high risk for adverse outcomes from cardiovascular and renal disease. Patients with stage 3 or greater chronic kidney disease have a high prevalence of left ventricular (LV) hypertrophy and diastolic dysfunction. Our goal was to study prospectively the relationships of LV mass and diastolic function with subsequent cardiovascular and renal outcomes in the African American Study of Kidney Disease and Hypertension cohort study. Of 691 patients enrolled in the cohort, 578 had interpretable echocardiograms and complete relevant clinical data. Exposures were LV hypertrophy and diastolic parameters. Outcomes were cardiovascular events requiring hospitalization or causing death; a renal composite outcome of doubling of serum creatinine or end-stage renal disease (censoring death); and heart failure. We found strong independent relationships between LV hypertrophy and subsequent cardiovascular (hazard ratio, 1.16; 95% confidence interval, 1.05-1.27) events, but not renal outcomes. After adjustment for LV mass and clinical variables, lower systolic tissue Doppler velocities and diastolic parameters reflecting a less compliant LV (shorter deceleration time and abnormal E/A ratio) were significantly (Pfailure events. This is the first study to show a strong relationship among LV hypertrophy, diastolic parameters, and adverse cardiac outcomes in African Americans with hypertension and chronic kidney disease. These echocardiographic risk factors may help identify high-risk patients with chronic kidney disease for aggressive therapeutic intervention.

  4. Pharmacological interference of vascular smooth muscle cell hypertrophy induced by glycosylated human oxyhaemoglobin.

    Science.gov (United States)

    Peiró, C; Vallejo, S; Nevado, J; Angulo, J; Llergo, J L; Cercas, E; Rodríguez-Mañas, L; Sánchez-Ferrer, C F

    1999-12-15

    Nonenzymatically glycosylated human oxyhaemoglobin induces vascular smooth muscle cell hypertrophy by releasing reactive oxygen species. We analysed the ability of drugs with antihypertrophic properties for the vascular wall and/or antioxidant activity, such as captopril, losartan, and nifedipine, or gliclazide, carvedilol, and ascorbic acid, to interfere with 10 nM glycosylated human oxyhaemoglobin-induced increase in vascular smooth muscle cell size (118+/-0.5% of basal). Vascular smooth muscle cell hypertrophy was abolished concentration-dependently, with pD(2) values over a 100-fold interval: 6.4+/-0.3, 7.7+/-0.4, 7.3+/-0.4, 7.4+/-0.6, 8. 8+/-0.2, and 9.0+/-0.2 for captopril, losartan, nifedipine, ascorbic acid, carvedilol and gliclazide, respectively. Drugs with powerful antioxidant properties, especially carvedilol and gliclazide, are particularly effective in preventing glycosylated human oxyhaemoglobin-induced vascular smooth muscle cell hypertrophy.

  5. Systems Genetics Approach Identifies Gene Pathways and Adamts2 as Drivers of Isoproterenol-Induced Cardiac Hypertrophy and Cardiomyopathy in Mice.

    Science.gov (United States)

    Rau, Christoph D; Romay, Milagros C; Tuteryan, Mary; Wang, Jessica J-C; Santolini, Marc; Ren, Shuxun; Karma, Alain; Weiss, James N; Wang, Yibin; Lusis, Aldons J

    2017-01-25

    We previously reported a genetic analysis of heart failure traits in a population of inbred mouse strains treated with isoproterenol to mimic catecholamine-driven cardiac hypertrophy. Here, we apply a co-expression network algorithm, wMICA, to perform a systems-level analysis of left ventricular transcriptomes from these mice. We describe the features of the overall network but focus on a module identified in treated hearts that is strongly related to cardiac hypertrophy and pathological remodeling. Using the causal modeling algorithm NEO, we identified the gene Adamts2 as a putative regulator of this module and validated the predictive value of NEO using small interfering RNA-mediated knockdown in neonatal rat ventricular myocytes. Adamts2 silencing regulated the expression of the genes residing within the module and impaired isoproterenol-induced cellular hypertrophy. Our results provide a view of higher order interactions in heart failure with potential for diagnostic and therapeutic insights. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    McIver Lauren J

    2009-12-01

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

  7. Interleukin-6 deficiency attenuates angiotensin II-induced cardiac pathogenesis with increased myocyte hypertrophy.

    Science.gov (United States)

    Chen, Fan; Chen, Dandan; Zhang, Yubin; Jin, Liang; Zhang, Han; Wan, Miyang; Pan, Tianshu; Wang, Xiaochuan; Su, Yuheng; Xu, Yitao; Ye, Junmei

    2017-12-16

    Interleukin-6 (IL-6) signaling is critical for cardiomyocyte hypertrophy, while the role of IL-6 in the pathogenesis of myocardium hypertrophy remains controversial. To determine the essential role of IL-6 signaling for the cardiac development during AngII-induced hypertension, and to elucidate the mechanisms, wild-type (WT) and IL-6 knockout (IL-6 KO) mice were infused subcutaneously with either vehicle or AngII (1.5 μg/h/mouse) for 1 week. Immunohistological and serum studies revealed that the extents of cardiac fibrosis, inflammation and apoptosis were reduced in IL-6 KO heart during AngII-stimulation, while cardiac hypertrophy was obviously induced. To investigate the underlying mechanisms, by using myocardial tissue and neonatal cardiomyocytes, we observed that IL-6/STAT3 signaling was activated under the stimulation of AngII both in vivo and in vitro. Further investigation suggested that STAT3 activation enhances the inhibitory effect of EndoG on MEF2A and hampers cardiomyocyte hypertrophy. Our study is the first to show the important role of IL-6 in regulating cardiac pathogenesis via inflammation and apoptosis during AngII-induced hypertension. We also provide a novel link between IL-6/STAT3 and EndoG/MEF2A pathway that affects cardiac hypertrophy during AngII stimulation. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. The role of cytochrome P450 1B1 and its associated mid-chain hydroxyeicosatetraenoic acid metabolites in the development of cardiac hypertrophy induced by isoproterenol.

    Science.gov (United States)

    Maayah, Zaid H; Althurwi, Hassan N; El-Sherbeni, Ahmed A; Abdelhamid, Ghada; Siraki, Arno G; El-Kadi, Ayman O S

    2017-05-01

    Numerous experimental studies have demonstrated the role of cytochrome P450 1B1 (CYP1B1) and its associated mid-chain hydroxyeicosatetraenoic acids (mid-chain HETEs) metabolite in the pathogenesis of cardiac hypertrophy. However, the ability of isoproterenol (ISO) to induce cardiac hypertrophy through mid-chain HETEs has not been investigated yet. Therefore, we hypothesized that ISO induces cardiac hypertrophy through the induction of CYP1B1 and its associated mid-chain HETE metabolites. To test our hypothesis, Sprague-Dawley rats were treated with ISO (5 mg/kg i.p.) for 12 and 72 h whereas, human ventricular cardiomyocytes RL-14 cells were exposed to 100 μM ISO in the presence and absence of 0.5 μM tetramethoxystilbene (TMS) a selective CYP1B1 inhibitor, or 25 nM CYP1B1-siRNA. Moreover, RL-14 cells were transiently transfected with the CRISPR-CYP1B1 plasmid. Thereafter, real-time PCR, western blot analysis, and liquid chromatography-electrospray ionization mass spectroscopy were used to determine the level of gene expression, protein expression, and mid-chain HETEs, respectively. Our results showed that ISO induced CYP1B1 protein expression and the level of cardiac mid-chain HETEs in vivo at pre-hypertrophic and hypertrophic stage. In vitro, inhibition of CYP1B1 using TMS or CYP1B1-siRNA significantly attenuates ISO-induced hypertrophy. Furthermore, overexpression of CYP1B1 significantly induced cellular hypertrophy and mid-chain HETEs metabolite. Mechanistically, the protective effect of TMS against cardiac hypertrophy was mediated through the modulation of superoxide anion, mitogen-activated protein kinases (MAPKs), and nuclear factor-κB (NF-κB). In conclusion, our study provides the first evidence that CYP1B1 and its associated mid-chain HETE metabolites are directly involved in the ISO-induced cardiac hypertrophy.

  9. Diets containing corn oil, coconut oil and cholesterol alter ventricular hypertrophy, dilatation and function in hearts of rats fed copper-deficient diets.

    Science.gov (United States)

    Jenkins, J E; Medeiros, D M

    1993-06-01

    Cardiac hypertrophy and function were evaluated in rats fed diets containing deficient, marginal or adequate levels of copper. The fat concentration of the diets was either 10 g/100 g corn oil, 10 g/100 g coconut oil or 10 g/100 g coconut oil + 1 g/100 g added cholesterol. Left ventricular (LV) wall thickening of hearts in rats fed copper-deficient diets was characterized by greater (P oil. Rats fed the copper-deficient diet with coconut oil + cholesterol had LV chamber volumes that were twofold larger than those of rats fed the copper-deficient diet with coconut oil or corn oil. Copper deficiency reduced LV chamber volume only in rats fed coconut oil + cholesterol. Cardiac LV end diastolic pressure in rats fed copper-deficient diets was twofold larger than in copper-adequate and copper-marginal groups fed corn oil or coconut oil. Hearts from rats fed the copper-deficient diet with corn oil compared with those from rats fed the copper-deficient diet with coconut oil + cholesterol had greater right ventricular (RV) and LV end diastolic pressures, LV pressures and LV and RV maximal rates of positive pressure development. Our data suggest that cardiac adaptations in rats fed copper-deficient diets are influenced by dietary fat type: 1) hearts of rats fed the copper-deficient diet with corn oil were concentrically hypertrophied, whereas cardiac contractility was maintained in the presence of high preload; 2) preload and contractility in hearts of coconut oil-fed rats was greater than cardiac response to cholesterol addition to the coconut oil diet; 3) hearts in copper-deficient rats fed coconut oil + cholesterol exhibited eccentric hypertrophy and ventricular dysfunction.

  10. Effect of siRNA silencing of inducible co-stimulatory molecule on myocardial cell hypertrophy after cardiac infarction in rats.

    Science.gov (United States)

    Wang, W M; Liu, Z; Chen, G

    2016-05-20

    As the most common cardiac disease, myocardial infarction is followed by hypertrophy of cardiac myocytes and reconstruction of ventricular structure. The up-regulation of a series of factors including metalloproteinases, inflammatory factors, and growth factors after primary infarction lead to the hypertrophy, apoptosis, necrosis, and fibroblast proliferation in cardiac muscle tissues. Recent studies have reported on the potency of small interfering RNA (siRNA) in treating cardiac diseases. We thus investigated the efficacy of inducible co-stimulatory molecule (ICOS)-specific siRNA silencing in myocardial hypertrophy in a cardiac infarction rat model. This cardiac infarction model was prepared by ligating the left anterior descending coronary artery. ICOS-siRNA treatment was administered in parallel with non-sense siRNA. After 18 days, the cross-sectional area of cardiac muscle tissues and the left ventricle weight index were measured, along with ICOS mRNA and protein expression levels, and pathological staining. Compared to those in the control groups, in myocardial infarcted rats, the application of ICOS-siRNA effectively decreased the left ventricle weight index, as well as the surface area of cardiac myocytes. Both mRNA and protein levels of ICOS were also significantly decreased. HE staining was consistent with these results. In conclusion, ICOS-targeted siRNA can effectively silence gene expression of ICOS, and provided satisfactory treatment efficacy for myocardial cell hypertrophy after infarction.

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

    Science.gov (United States)

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

    2016-04-01

    The changes that left ventricular hypertrophy (LVH) induces in depolarization and repolarization vectors are well known. We analyzed the performance of the electrocardiographic and vectorcardiographic transverse planes (TP in the ECG and XZ in the VCG) and frontal planes (FP in the ECG and XY in the VCG) to discriminate LVH patients from control subjects. In an age-balanced set of 58 patients, the directions and amplitudes of QRS-complexes and T-wave vectors were studied. The repolarization vector significantly decreased in modulus from controls to LVH in the transverse plane (TP: 0.45±0.17mV vs. 0.24±0.13mV, p<0.0005 XZ: 0.43±0.16mV vs. 0.26±0.11mV, p<0.005) while the depolarization vector significantly changed in angle in the electrocardiographic frontal plane (Controls vs. LVH, FP: 48.24±33.66° vs. 46.84±35.44°, p<0.005, XY: 20.28±35.20° vs. 19.35±12.31°, NS). Several LVH indexes were proposed combining such information in both ECG and VCG spaces. A subset of all those indexes with AUC values greater than 0.7 was further studied. This subset comprised four indexes, with three of them belonging to the ECG space. Two out of the four indexes presented the best ROC curves (AUC values: 0.78 and 0.75, respectively). One index belonged to the ECG space and the other one to the VCG space. Both indexes showed a sensitivity of 86% and a specificity of 70%. In conclusion, the proposed indexes can favorably complement LVH diagnosis

  12. MicroRNA-200c modulates DUSP-1 expression in diabetes-induced cardiac hypertrophy.

    Science.gov (United States)

    Singh, Gurinder Bir; Raut, Satish K; Khanna, Sanskriti; Kumar, Akhilesh; Sharma, Saurabh; Prasad, Rishikesh; Khullar, Madhu

    2017-01-01

    Mitogen-activated protein kinases (MAPKs) (ERK1/2, JNK, and p38) are upregulated in diabetic cardiomyopathy (DCM). Dual-specific phosphatase-1 (DUSP-1) has been reported to regulate the activity of MAPKs in cardiac hypertrophy; however, the role of DUSP-1 in regulating MAPKs activity in DCM is not known. MicroRNAs have been reported to regulate the expression of several genes in hypertrophied failing hearts. However, little is known about the microRNAs regulating DUSP-1 expression in diabetes-related cardiac hypertrophy. In the present study, we investigated the role of DUSP-1 and miR-200c in diabetes-induced cardiac hypertrophy. DCM was induced in Wistar rats by low-dose Streptozotocin high-fat diet for 12 weeks. Cardiac expression of ERK, p-38, JNK, DUSP-1, miR-200c, and hypertrophy markers (ANP and β-MHC) was studied in DCM in control rats and in high-glucose (HG)-treated rat neonatal cardiomyocytes. miR-200c inhibition was performed to validate DUSP-1 as target. A significant increase in phosphorylated ERK, p38, and JNK was observed in DCM model and in HG-treated cardiomyocytes (p 1 was significantly decreased in diabetes group and in HG-treated cardiomyocytes (p 1 causing decreased expression of phosphorylated ERK, p38, and JNK and attenuated cardiomyocyte hypertrophy in HG-treated cardiomyocytes. miR-200c plays a role in diabetes-associated cardiac hypertrophy by modulating expression of DUSP-1.

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

    NARCIS (Netherlands)

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

    2013-01-01

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

  14. Urocortin-induced cardiomyocytes hypertrophy is associated with regulation of the GSK-3β pathway.

    Science.gov (United States)

    Gruson, Damien; Ginion, Audrey; Decroly, Noémie; Lause, Pascale; Vanoverschelde, Jean-Louis; Ketelslegers, Jean-Marie; Bertrand, Luc; Thissen, Jean-Paul

    2012-03-01

    Urocortin-1 (UCN), a member of the corticotropin-releasing factor, is a cardioprotective peptide, and is also involved in cardiac hypertrophy. The involvement of GSK-3β, a pivotal kinase in cardiac hypertrophy, in response to UCN is not yet documented. Cardiomyocytes from adult rats were stimulated for 48 h with UCN. Cell size, protein, and DNA contents were determined. Phosphorylated and total forms GSK-3β and the total amount of β-catenin were quantified by Western immunoblots. The effects of astressin, a UCN competitive receptor antagonist, were also evaluated. UCN increased cell size and the protein-to-DNA ratio, in accordance with a hypertrophic response. This effect was associated with increased phosphorylation of GSK-3β and marked accumulation of β-catenin, a downstream element to GSK-3β. All these effects were prevented by astressin and LY294002, an inhibitor of the phosphatidyl-inositol-3-kinase. UCN-induced cardiomyocytes hypertrophy is associated with regulation of GSK-3β, a pivotal kinase involved in cardiac hypertrophy, in a PI3K-dependent manner. Furthermore, the pharmacological blockade of UCN receptors was able to prevent UCN-induced hypertrophy, which leads to inhibition of the Akt/GSK-3β pathway.

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    In hypertensive patients with left ventricular hypertrophy, antihypertensive treatment induces changes in left ventricular structure and function. However, less is known about gender differences in this response. Baseline and annual echocardiograms until the end of study or a primary end point...... hypertrophy regression during long-term antihypertensive treatment Udgivelsesdato: 2008/4...

  16. Antioxidant and cardioprotective effects of Danshensu (3-(3, 4-dihydroxyphenyl)-2-hydroxy-propanoic acid from Salvia miltiorrhiza) on isoproterenol-induced myocardial hypertrophy in rats.

    Science.gov (United States)

    Tang, Yiqun; Wang, Minhui; Le, Xiaoyong; Meng, Jianing; Huang, Lu; Yu, Peng; Chen, Jia; Wu, Ping

    2011-09-15

    Myocardial hypertrophy has been linked to the development of a variety of cardiovascular diseases, and is a risk factor for myocardial ischemia, arrhythmias, and sudden cardiac death. The objective of the present study was to evaluate the cardioprotective effects of Danshensu (DSS), a water-soluble active component of Danshen, on cardiac hypertrophy in rats. We are the first to report that DSS reversed Cx43 down-regulation in ventricular tissue. Cardiomyopathy in rats was produced using isoproterenol (Iso) treatment (2.5 mg/kg/d, s.c.) for seven days. DSS (3 and 10 mg/kg/d, i.p.) and Valsartan (Val) (10 mg/kg, i.g.) were administered on days 4-7 of Iso-treatment. Heart weight index, hemodynamic parameters, and ECG II parameters were monitored and recorded; protein expression of left ventricular connexin 43 (Cx43) and the activity of the redox system were assayed, and arrhythmias were produced using a coronary ligation/reperfusion procedure. The results demonstrated that DSS treatment significantly decreased heart weight/body weight (HW/BW) and left ventricular weight/body weight (LVW/BW) ratios. The protective role of DSS against Iso-induced myocardial hypertrophy was further confirmed using ECG. The incidences of ventricular tachycardia and ventricular fibrillation (VT, VF) and arrhythmic scores were higher in the model group and were suppressed by DSS. DSS decreased the serum and myocardium levels of creatine kinase, lactate dehydrogenase, and malondialdehyde (CK, LDH, and MDA) and increased serum activity of superoxide dismutase (SOD) in a dose-dependent manner. Cx43 expression in the left ventricle was down-regulated, and there was significant oxidative stress in this model of cardiomyopathy. DSS reversed the down-regulated Cx43 protein levels and showed potent anti-oxidative activities and cellular protection. These data demonstrate that DSS can prevent cardiac I/R injury and improve cardiac function in a rat model of hypertrophy, the effects partially

  17. Left-Ventricular Energetics in Pulmonary Arterial Hypertension-Induced Right-Ventricular Hypertrophic Failure.

    Science.gov (United States)

    Han, June-Chiew; Guild, Sarah-Jane; Pham, Toan; Nisbet, Linley; Tran, Kenneth; Taberner, Andrew J; Loiselle, Denis S

    2017-01-01

    Pulmonary arterial hypertension (PAH) alters the geometries of both ventricles of the heart. While the right ventricle (RV) hypertrophies, the left ventricle (LV) atrophies. Multiple lines of clinical and experimental evidence lead us to hypothesize that the impaired stroke volume and systolic pressure of the LV are a direct consequence of the effect of pressure overload in the RV, and that atrophy in the LV plays only a minor role. In this study, we tested this hypothesis by examining the mechanoenergetic response of the atrophied LV to RV hypertrophy in rats treated with monocrotaline. Experiments were performed across multiple-scales: the whole-heart in vivo and ex vivo , and its trabeculae in vitro . Under the in vivo state where the RV was pressure-overloaded, we measured reduced systemic blood pressure and LV ventricular pressure. In contrast, under both ex vivo and in vitro conditions, where the effect of RV pressure overload was circumvented, we found that LV was capable of developing normal systolic pressure and stress. Nevertheless, LV atrophy played a minor role in that LV stroke volume remained lower, thereby contributing to lower LV mechanical work output. Concomitantly lower oxygen consumption and change of enthalpy were observed, and hence LV energy efficiency was unchanged. Our internally consistent findings between working-heart and trabecula experiments explain the rapid improvement of LV systolic function observed in patients with chronic pulmonary hypertension following surgical relief of RV pressure overload.

  18. Resveratrol Attenuated Low Ambient Temperature-Induced Myocardial Hypertrophy via Inhibiting Cardiomyocyte Apoptosis

    OpenAIRE

    Kun Yin; Liang Zhao; Dan Feng; Wenya Ma; Yu Liu; Yang Wang; Jing Liang; Fan Yang; Chongwei Bi; Hongyang Chen; Xingda Li; Yanjie Lu; Benzhi Cai

    2015-01-01

    Background/Aims: Low ambient temperature is an important risk factor for cardiovascular diseases, and has been shown to lead to cardiac hypertrophy. In this study, we aim to investigate if Resveratrol may inhibit cold exposure-induced cardiac hypertrophy in mice, and if so to clarify its molecular mechanism. Methods: Adult male mice were randomly assigned to Control group (kept at room temperature), Cold group (kept at low air temperature range from 3°C to 5°C) and Resveratrol treatment group...

  19. Pressure load: the main factor for altered gene expression in right ventricular hypertrophy in chronic hypoxic rats.

    Directory of Open Access Journals (Sweden)

    Jonas D Baandrup

    Full Text Available BACKGROUND: The present study investigated whether changes in gene expression in the right ventricle following pulmonary hypertension can be attributed to hypoxia or pressure loading. METHODOLOGY/PRINCIPAL FINDINGS: To distinguish hypoxia from pressure-induced alterations, a group of rats underwent banding of the pulmonary trunk (PTB, sham operation, or the rats were exposed to normoxia or chronic, hypobaric hypoxia. Pressure measurements were performed and the right ventricle was analyzed by Affymetrix GeneChip, and selected genes were confirmed by quantitative PCR and immunoblotting. Right ventricular systolic blood pressure and right ventricle to body weight ratio were elevated in the PTB and the hypoxic rats. Expression of the same 172 genes was altered in the chronic hypoxic and PTB rats. Thus, gene expression of enzymes participating in fatty acid oxidation and the glycerol channel were downregulated. mRNA expression of aquaporin 7 was downregulated, but this was not the case for the protein expression. In contrast, monoamine oxidase A and tissue transglutaminase were upregulated both at gene and protein levels. 11 genes (e.g. insulin-like growth factor binding protein were upregulated in the PTB experiment and downregulated in the hypoxic experiment, and 3 genes (e.g. c-kit tyrosine kinase were downregulated in the PTB and upregulated in the hypoxic experiment. CONCLUSION/SIGNIFICANCE: Pressure load of the right ventricle induces a marked shift in the gene expression, which in case of the metabolic genes appears compensated at the protein level, while both expression of genes and proteins of importance for myocardial function and remodelling are altered by the increased pressure load of the right ventricle. These findings imply that treatment of pulmonary hypertension should also aim at reducing right ventricular pressure.

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

    Directory of Open Access Journals (Sweden)

    Javier Duran

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

  1. Identification of genes regulated during mechanical load-induced cardiac hypertrophy

    Science.gov (United States)

    Johnatty, S. E.; Dyck, J. R.; Michael, L. H.; Olson, E. N.; Abdellatif, M.; Schneider, M. (Principal Investigator)

    2000-01-01

    Cardiac hypertrophy is associated with both adaptive and adverse changes in gene expression. To identify genes regulated by pressure overload, we performed suppressive subtractive hybridization between cDNA from the hearts of aortic-banded (7-day) and sham-operated mice. In parallel, we performed a subtraction between an adult and a neonatal heart, for the purpose of comparing different forms of cardiac hypertrophy. Sequencing more than 100 clones led to the identification of an array of functionally known (70%) and unknown genes (30%) that are upregulated during cardiac growth. At least nine of those genes were preferentially expressed in both the neonatal and pressure over-load hearts alike. Using Northern blot analysis to investigate whether some of the identified genes were upregulated in the load-independent calcineurin-induced cardiac hypertrophy mouse model, revealed its incomplete similarity with the former models of cardiac growth. Copyright 2000 Academic Press.

  2. The role of echocardiography in the differential diagnosis between training induced myocardial hypertrophy versus cardiomyopathy.

    Science.gov (United States)

    Venckunas, Tomas; Mazutaitiene, Birute

    2007-01-01

    Increased myocardial mass due to regular high-volume intense exercise training (so-called athlete's heart) is not uncommon. Although directly correlated with the extent of training loads, myocardial hypertrophy is not present exclusively in well-trained or elite athletes. Athlete's heart is considered a physiological phenomenon with no known harmful consequences. However, extreme forms of myocardial hypertrophy due to endurance training resemble a structural heart disease such as hypertrophic cardiomyopathy, a condition associated with substantially increased risk of cardiac event. Endurance sports such as rowing and road cycling, rather than strength/power training, are most commonly associated with left ventricular (LV) wall thickness compatible with hypertrophic cardiomyopathy. The differentiation between physiological and maladaptive cardiac hypertrophy in athletes is undoubtedly important, since untreated cardiac abnormality often possesses a real threat of premature death due to heart failure during intense physical exertion. Luckily, the distinction from pathological hypertrophy is usually straightforward using transthoracic echocardiography, as endurance athletes, in addition to moderately and proportionally thickened LV walls with normal acoustic density, tend to possess increased LV diameter. In more uncertain cases, a detailed evaluation of myocardial function using (tissue) Doppler and contrast echocardiography is effective. When a doubt still remains, knowledge of an athlete's working capacity may be useful in evaluating whether the insidious cardiac pathology is absent. In such cases cardiopulmonary exercise testing typically resolves the dilemma: indices of aerobic capacity are markedly higher in healthy endurance athletes compared to patients. Other characteristics such as a decrease of LV mass due to training cessation are also discussed in the article. Key pointsTransthoracic echocardiography is still the most common relevant differentiation

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

    Science.gov (United States)

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

    1999-10-15

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

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

    Directory of Open Access Journals (Sweden)

    Yang Xiaomin

    2015-01-01

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

  5. THE ROLE OF ECHOCARDIOGRAPHY IN THE DIFFERENTIAL DIAGNOSIS BETWEEN TRAINING INDUCED MYOCARDIAL HYPERTROPHY VERSUS CARDIOMYOPATHY

    Directory of Open Access Journals (Sweden)

    Tomas Venckunas

    2007-06-01

    Full Text Available Increased myocardial mass due to regular high-volume intense exercise training (so-called athlete's heart is not uncommon. Although directly correlated with the extent of training loads, myocardial hypertrophy is not present exclusively in well-trained or elite athletes. Athlete's heart is considered a physiological phenomenon with no known harmful consequences. However, extreme forms of myocardial hypertrophy due to endurance training resemble a structural heart disease such as hypertrophic cardiomyopathy, a condition associated with substantially increased risk of cardiac event. Endurance sports such as rowing and road cycling, rather than strength/power training, are most commonly associated with left ventricular (LV wall thickness compatible with hypertrophic cardiomyopathy. The differentiation between physiological and maladaptive cardiac hypertrophy in athletes is undoubtedly important, since untreated cardiac abnormality often possesses a real threat of premature death due to heart failure during intense physical exertion. Luckily, the distinction from pathological hypertrophy is usually straightforward using transthoracic echocardiography, as endurance athletes, in addition to moderately and proportionally thickened LV walls with normal acoustic density, tend to possess increased LV diameter. In more uncertain cases, a detailed evaluation of myocardial function using (tissue Doppler and contrast echocardiography is effective. When a doubt still remains, knowledge of an athlete's working capacity may be useful in evaluating whether the insidious cardiac pathology is absent. In such cases cardiopulmonary exercise testing typically resolves the dilemma: indices of aerobic capacity are markedly higher in healthy endurance athletes compared to patients. Other characteristics such as a decrease of LV mass due to training cessation are also discussed in the article

  6. Identification of a core set of genes that signifies pathways underlying cardiac hypertrophy

    DEFF Research Database (Denmark)

    Strom, C.C.; Kruhoffer, M.; Knudsen, Steen

    2004-01-01

    gene expression, using microarray technology in multiple models of cardiac hypertrophy, including aortic banding, myocardial infarction, an arteriovenous shunt and pharmacologically induced hypertrophy, would uncover networks of conserved hypertrophy-specific genes and identify novel genes involved...... in hypertrophic signalling. From gene expression analyses (8740 probe sets, n = 46) of rat ventricular RNA, we identified a core set of 139 genes with consistent differential expression in all hypertrophy models as compared to their controls, including 78 genes not previously associated with hypertrophy and 61...... genes whose altered expression had previously been reported. We identified a single common gene program underlying hypertrophic remodelling, regardless of how the hypertrophy was induced. These genes constitute the molecular basis for the existence of one main form of cardiac hypertrophy and may...

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

    Directory of Open Access Journals (Sweden)

    Cameron J Mitchell

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

  8. Loss of TRADD attenuates pressure overload-induced cardiac hypertrophy through regulating TAK1/P38 MAPK signalling in mice.

    Science.gov (United States)

    Wu, Lianpin; Cao, Zhiyong; Ji, Ling; Mei, Liqin; Jin, Qike; Zeng, Jingjing; Lin, Jiafeng; Chu, Maoping; Li, Lei; Yang, Xiangjun

    2017-02-05

    We investigated the role of tumour necrosis factor receptor (TNFR)-associated death domain (TRADD) on pressure overload-induced cardiac hypertrophy and the underlying molecular mechanisms by using a TRADD deficiency mice model. 6-8 weeks wild-type and TRADD knockout mice were performed to transverse aorta constriction (TAC) or sham operation (6-8 mice for each group). 14 days after TAC, cardiac function was measured by echocardiography, as well as by pathological and molecular analyses of heart samples. The expressions of cardiac hypertrophic and fibrotic markers were detected by qPCR. Phosphorylated and total TAK1, Akt, and p38 MAPK levels were examined by Western blotting. The ratios of lung or heart/body weight, wall thickness/chamber diameter of left ventricular and cross area of cardiomyocyte were significantly reduced in TRADD knockout (KO) mice than those of wild-type mice after TAC. Moreover, cardiac hypertrophic and fibrotic markers were downregulated in TRADD knockout mice than those of wild-type mice following TAC. Protein expression analysis showed phosphorylated TAK1, p38 MAPK and AKT were upregulated after TAC in both wild-type and TRADD KO mice, phosphorylation of TAK1 and p38 MAPK was reduced more remarkably after TRADD deficiency, while phosphorylated AKT expression was similar between TRADD KO and wild-type mice following TAC. Our data suggest that TRADD KO blunts pressure overload-induced cardiac hypertrophy through mediating TAK1/p38 MAPK but not AKT phosphorylation in mice. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    DEFF Research Database (Denmark)

    Wachtell, K.; Palmieri, V.; Olsen, M.H.

    2002-01-01

    in a large hypertensive population. Methods The urine albumin/creatinine ratio (UACR) and echocardiographic measures of LV structure and function were obtained in 833 patients with stage I to III hypertension and LV hypertrophy determined by electrocardiogram (ECG) (Cornell voltage-duration or Sokolow......-Lyon voltage criteria) after 14 days of placebo treatment. Results Patients’ mean ages were 66 years, 42% were women, 23% had microalbuminuria, and 5% had macroalbuminuria. Patients with eccentric or concentric LV hypertrophy had higher prevalences of microalbuminuria (average 26%-30% vs 9%, P ... regression analysis higher UACR was associated with higher LV mass (β = .169, Phypertrophy, abnormal LV...

  10. Polyamine Depletion Attenuates Isoproterenol-Induced Hypertrophy and Endoplasmic Reticulum Stress in Cardiomyocytes

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    Yan Lin

    2014-10-01

    Full Text Available Background/Aim: Polyamines (putrescine, spermidine and spermine play an essential role in cell growth, differentiation and apoptosis. Hypertrophy is accompanied by an increase in polyamine synthesis and endoplasmic reticulum stress (ERS in cardiomyocytes. The present study was undertaken to elucidate the molecular interactions between polyamines, ERS and cardiac hypertrophy. Methods: Myocardial hypertrophy was simulated by incubating cultured neonatal rat cardiomyocytes in 100 nM isoproterenol (ISO. Polyamine deletion was achieved using 0.5 mM difluoromethylornithine (DFMO. Hypertrophy was estimated using cell surface area measurements, total protein concentrations and atrial natriuretic peptide (ANP gene expression. Apoptosis was measured using flow cytometry and transmission electron microscopy. Expression of ornithine decarboxylase (ODC and spermidine/spermine N1-acetyltransferase (SSAT were analyzed via real-time PCR and Western blotting. Protein expression of ERS and apoptosis factors were analyzed using Western blotting. Results: DFMO (0.5 mM and 2 mM treatments significantly attenuated hypertrophy and apoptosis induced by ISO in cardiomyocytes. DFMO also decreased lactate dehydrogenase (LDH and malondialdehyde (MDA level in the culture medium. In addition, DFMO (0.5 mM down regulated the expression of ODC, glucose-regulated protein 78 (GRP78, C/EBP homologous protein (CHOP, cleaved caspase-12, and Bax and up regulated the expression of SSAT and Bcl-2. Finally, these changes were partly reversed by the addition of exogenous putrescine (0.5 mM. Conclusion: The data presented here suggest that polyamine depletion could inhibit cardiac hypertrophy and apoptosis, which is closely related to the ERS pathway.

  11. C-C Motif Chemokine Receptor 9 Exacerbates Pressure Overload-Induced Cardiac Hypertrophy and Dysfunction.

    Science.gov (United States)

    Xu, Zhengxi; Mei, Fanghua; Liu, Hanning; Sun, Cheng; Zheng, Zhe

    2016-05-04

    Maladaptive cardiac hypertrophy is a major risk factor for heart failure, which is the leading cause of death worldwide. C-C motif chemokine receptor 9 (CCR9), a subfamily of the G protein-coupled receptor supergene family, has been highlighted as an immunologic regulator in the development and homing of immune cells and in immune-related diseases. Recently, CCR9 was found to be involved in the pathogenesis of other diseases such as cardiovascular diseases; however, the effects that CCR9 exerts in cardiac hypertrophy remain elusive. We observed significantly increased CCR9 protein levels in failing human hearts and in a mouse or cardiomyocyte hypertrophy model. In loss- and gain-of-function experiments, we found that pressure overload-induced hypertrophy was greatly attenuated by CCR9 deficiency in cardiac-specific CCR9 knockout mice, whereas CCR9 overexpression in cardiac-specific transgenic mice strikingly enhanced cardiac hypertrophy. The prohypertrophic effects of CCR9 were also tested in vitro, and a similar phenomenon was observed. Consequently, we identified a causal role for CCR9 in pathological cardiac hypertrophy. Mechanistically, we revealed a lack of difference in the expression levels of mitogen-activated protein kinases between groups, whereas the phosphorylation of AKT/protein kinase B and downstream effectors significantly decreased in CCR9 knockout mice and increased in CCR9 transgenic mice after aortic binding surgery. The prohypertrophic effects of CCR9 were not attributable to the mitogen-activated protein kinase signaling pathway but rather to the AKT-mammalian target of rapamycin-glycogen synthase kinase 3β signaling cascade. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  12. Cardiomyopathy induced by incessant fascicular ventricular tachycardia.

    Science.gov (United States)

    Velázquez-Rodríguez, Enrique; Rodríguez-Piña, Horacio; Pacheco-Bouthillier, Alex; Deras-Mejía, Luz María

    2013-01-01

    A 12-year-old girl with symptoms of fatigue, decreased exercise tolerance and progressive dyspnea (New York Heart Association functional class III) with a possible diagnosis of dilated cardiomyopathy secondary to viral myocarditis. Because of incessant wide QRS tachycardia refractory to antiarrhythmic drugs, she was referred for electrophysiological study. The diagnosis was idiopathic left ventricular tachycardia involving the posterior fascicle of the left bundle branch. After successful treatment with radiofrequency catheter ablation guided by a Purkinje potential radiological and echocardiographic evaluation showed complete reversal of left ventricular function in the first 3 months and no recurrence of arrhythmia during 2 years of follow up. Copyright © 2012 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

  13. Smad Nuclear Interacting Protein 1 Acts as a Protective Regulator of Pressure Overload-Induced Pathological Cardiac Hypertrophy.

    Science.gov (United States)

    Lu, Yu-Yan; Xu, Da-Chun; Zhao, Yi-Fan; Zhu, Guo-Fu; Zhu, Meng-Yun; Liu, Wei-Jing; Yu, Xue-Jing; Chen, Wei; Liu, Zheng; Xu, Ya-Wei

    2016-10-26

    Smad nuclear interacting protein 1 (SNIP1) plays a critical role in cell proliferation, transformation of embryonic fibroblasts, and immune regulation. However, the role of SNIP1 in cardiac hypertrophy remains unclear. Here we examined the role of SNIP1 in pressure overload-induced cardiac hypertrophy and its mechanisms. Our results demonstrated that SNIP1 expression was downregulated in human dilated cardiomyopathic hearts, aortic banding-induced mice hearts, and angiotensin II-treated cardiomyocytes. Accordingly, SNIP1 deficiency significantly exacerbated aortic banding-induced cardiac hypertrophy, fibrosis, and contractile dysfunction, whereas cardiac-specific overexpression of SNIP1 markedly recovered pressure overload-induced cardiac hypertrophy and fibrosis. Besides that, SNIP1 protected neonatal rat cardiomyocytes against angiotensin II-induced hypertrophy in vitro. Moreover, we identified that SNIP1 suppressed nuclear factor-κB signaling during pathological cardiac hypertrophy, and inhibition of nuclear factor-κB signaling by a cardiac-specific conditional inhibitor of κB S 32A/S36A transgene blocked these adverse effects of SNIP1 deficiency on hearts. Together, our findings demonstrated that SNIP1 had protective effects in pressure overload-induced pathological cardiac hypertrophy via inhibition of nuclear factor-κB signaling. Thus, SNIP1 may be a novel approach for the treatment of heart failure. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  14. Angiotensin II Facilitates Matrix Metalloproteinase-9-Mediated Myosin Light Chain Kinase Degradation in Pressure Overload-Induced Cardiac Hypertrophy

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    Shun Wang

    2017-12-01

    Full Text Available Background/Aims: Angiotensin II (Ang II has been shown to promote cardiac remodeling during the process of hypertrophy. Myosin light chain kinase (MLCK, a specific kinase for the phosphorylation of myosin light chain 2 (MLC2, plays an important role in regulating cardiac muscle contraction and hypertrophy. However, whether Ang II could facilitate cardiac hypertrophy by altering the expression of MLCK remains unclear. This study aimed to investigate this effect and the underlying mechanisms. Methods: Cardiac hypertrophy was induced via pressure overload in rats, which were then evaluated via histological and biochemical measurements and echocardiography. Angiotensin-converting enzyme inhibitor (ACEI was used to inhibit Ang II. Neonatal rat cardiomyocytes were stimulated with Ang II to induce hypertrophy and were treated with a matrix metalloproteinase 9 (MMP9 inhibitor. Myocyte hypertrophy was evaluated using immunofluorescence and qRT-PCR. Degradation of recombinant human MLCK by recombinant human MMP9 was tested using a cleavage assay. The expression levels of MLCK, MLC2, phospho-myosin light chain 2 (p-MLC2, myosin phosphatase 2 (MYPT2, and calmodulin (CaM were measured using western blotting. Results: ACEI improved cardiac function and remodeling and increased the levels of MLCK and p-MLC2 as well as reduced the expression of MMP9 in pressure overload-induced cardiac hypertrophy. Moreover, the MMP9 inhibitor alleviated myocyte hypertrophy and upregulated the levels of MLCK and p-MLC2 in Ang II-induced cardiomyocyte hypertrophy. Recombinant human MLCK was concentration- and time-dependently degraded by recombinant human MMP9 in vitro, and this process was prevented by the MMP9 inhibitor. Conclusion: Our results suggest that Ang II is involved in the degradation of MLCK in pressure overload-induced cardiac hypertrophy and that this process was mediated by MMP9.

  15. Rapamycin Attenuated Cardiac Hypertrophy Induced by Isoproterenol and Maintained Energy Homeostasis via Inhibiting NF-κB Activation

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    Xi Chen

    2014-01-01

    Full Text Available Rapamycin, also known as sirolimus, is an immunosuppressant drug used to prevent rejection organ (especially kidney transplantation. However, little is known about the role of Rapa in cardiac hypertrophy induced by isoproterenol and its underlying mechanism. In this study, Rapa was administrated intraperitoneally for one week after the rat model of cardiac hypertrophy induced by isoproterenol established. Rapa was demonstrated to attenuate isoproterenol-induced cardiac hypertrophy, maintain the structure integrity and functional performance of mitochondria, and upregulate genes related to fatty acid metabolism in hypertrophied hearts. To further study the implication of NF-κB in the protective role of Rapa, cardiomyocytes were pretreated with TNF-α or transfected with siRNA against NF-κB/p65 subunit. It was revealed that the upregulation of extracellular circulating proinflammatory cytokines induced by isoproterenol was able to be reversed by Rapa, which was dependent on NF-κB pathway. Furthermore, the regression of cardiac hypertrophy and maintaining energy homeostasis by Rapa in cardiomyocytes may be attributed to the inactivation of NF-κB. Our results shed new light on mechanisms underlying the protective role of Rapa against cardiac hypertrophy induced by isoproterenol, suggesting that blocking proinflammatory response by Rapa might contribute to the maintenance of energy homeostasis during the progression of cardiac hypertrophy.

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

    Science.gov (United States)

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

    2017-12-01

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

  17. Role of α1D -adrenoceptors in vascular wall hypertrophy during angiotensin II-induced hypertension.

    Science.gov (United States)

    Gallardo-Ortíz, I A; Rodríguez-Hernández, S N; López-Guerrero, J J; Del Valle-Mondragón, L; López-Sánchez, P; Touyz, R M; Villalobos-Molina, R

    2015-09-01

    The in vivo effect of continuous angiotensin II (Ang II) infusion on arterial blood pressure, vascular hypertrophy and α1 -adrenoceptors (α1 -ARs) expression was explored. Alzet(®) minipumps filled with Ang II (200 ng kg(-1)  min(-1) ) were subcutaneously implanted in male Wistar rats (3 months-old). Groups of rats were also treated with losartan, an AT1 R antagonist, or with BMY 7378, a selective α1D -AR antagonist. Blood pressure was measured by tail-cuff; after 2 or 4 weeks of treatment, vessels were isolated for functional and structural analyses. Angiotensin II increased systolic blood pressure. Phenylephrine-induced contraction in aorta was greater (40% higher) in Ang II-treated rats than in the controls, and similar effect occurred with KCl 80 mm. Responses in tail arteries were not significantly different among the different groups. Angiotensin II decreased α1D -ARs without modifying the other α1 -ARs and induced an increase in media thickness (hypertrophy) in aorta, while no structural change occurred in tail artery. Losartan prevented and reversed hypertension and hypertrophy, while BMY 7378 prevented and reversed the aorta's hypertrophic response, without preventing or reversing hypertension. Findings indicate that Ang II-induced aortic hypertrophic response involves Ang II-AT1 Rs and α1D -ARs. Angiotensin II-induced α1D -AR-mediated vascular remodeling occurs independently of hypertension. Findings identify a α1D -AR-mediated process whereby Ang II influences aortic hypertrophy independently of blood pressure elevation. © 2016 John Wiley & Sons Ltd.

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

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    Hakalahti Anna E

    2010-08-01

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

  19. NF-κB (p65) negatively regulates myocardin-induced cardiomyocyte hypertrophy through multiple mechanisms.

    Science.gov (United States)

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

    2014-12-01

    Myocardin is well known to play a key role in the development of cardiomyocyte hypertrophy. But the exact molecular mechanism regulating myocardin stability and transactivity to affect cardiomyocyte hypertrophy has not been studied clearly. We now report that NF-κB (p65) can inhibit myocardin-induced cardiomyocyte hypertrophy. Then we explore the molecular mechanism of this response. First, we show that p65 can functionally repress myocardin transcriptional activity and also reduce the protein expression of myocardin. Second, the function of myocardin can be regulated by epigenetic modifications. Myocardin sumoylation is known to transactivate cardiac genes, but whether p65 can inhibit SUMO modification of myocardin is still not clear. Our data show that p65 weakens myocardin transcriptional activity through attenuating SUMO modification of myocardin by SUMO1/PIAS1, thereby impairing myocardin-mediated cardiomyocyte hypertrophy. Furthermore, the expression of myocardin can be regulated by several microRNAs, which play important roles in the development and function of the heart and muscle. We next investigated potential role of miR-1 in cardiac hypotrophy. Our results show that p65 can upregulate the level of miR-1 and miR-1 can decrease protein expression of myocardin in cardiac myocytes. Notably, miR-1 expression is also controlled by myocardin, leading to a feedback loop. These data thus provide important and novel insights into the function that p65 inhibits myocardin-mediated cardiomyocyte hypertrophy by downregulating the expression and SUMO modification of myocardin and enhancing the expression of miR-1. Copyright © 2014 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2001-03-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-02-15

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

  2. Early NADPH oxidase-2 activation is crucial in phenylephrine-induced hypertrophy of H9c2 cells.

    Science.gov (United States)

    Hahn, Nynke E; Musters, René J P; Fritz, Jan M; Pagano, Patrick J; Vonk, Alexander B A; Paulus, Walter J; van Rossum, Albert C; Meischl, Christof; Niessen, Hans W M; Krijnen, Paul A J

    2014-09-01

    Reactive oxygen species (ROS) produced by different NADPH oxidases (NOX) play a role in cardiomyocyte hypertrophy induced by different stimuli, such as angiotensin II and pressure overload. However, the role of the specific NOX isoforms in phenylephrine (PE)-induced cardiomyocyte hypertrophy is unknown. Therefore we aimed to determine the involvement of the NOX isoforms NOX1, NOX2 and NOX4 in PE-induced cardiomyocyte hypertrophy. Hereto rat neonatal cardiomyoblasts (H9c2 cells) were incubated with 100 μM PE to induce hypertrophy after 24 and 48h as determined via cell and nuclear size measurements using digital imaging microscopy, electron microscopy and an automated cell counter. Digital-imaging microscopy further revealed that in contrast to NOX1 and NOX4, NOX2 expression increased significantly up to 4h after PE stimulation, coinciding and co-localizing with ROS production in the cytoplasm as well as the nucleus. Furthermore, inhibition of NOX-mediated ROS production with apocynin, diphenylene iodonium (DPI) or NOX2 docking sequence (Nox2ds)-tat peptide during these first 4h of PE stimulation significantly inhibited PE-induced hypertrophy of H9c2 cells, both after 24 and 48h of PE stimulation. These data show that early NOX2-mediated ROS production is crucial in PE-induced hypertrophy of H9c2 cells. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. [The value of terminal force of P wave in V1 lead in the diagnosis of coal-worker's pneumoconiosis with pulmonary heart disease complicated by left ventricular hypertrophy].

    Science.gov (United States)

    Bao, Ying

    2012-01-01

    To determine the value of terminal force of P wave in V1 lead (Ptf-V1) in the diagnosis of coal-workers' pneumoconiosis with pulmonary heart disease complicated by left ventricular hypertrophy. Select the coal-worker with pneumoconiosis postmortem examination cases which were pathologically diagnosed as pulmonary heart disease complicated by left ventricular hypertrophy and can measure Ptf-V1. Select 14 cases with ECG left axis deviation, no deviation and right axis deviation. Measure and analyze the Ptf-V1 value, the thickness of left and right ventricular wall. There's obvious discrepancy in ventricular wall thickness mean in ECG left axis deviation, no deviation and right axis deviation groups, the discrepancy have statistical significance (F1 = 32.18, P left ventricular wall is thicker in ECG left axis deviation group [(1.81 +/- 0.18) cm] than in no deviation [(1.47 +/- 0.15) cm] and right axis deviation groups [(1.39 +/- 0.10) cm], the discrepancy have statistical significance with (P left axis deviation group [(0.79 +/- 0.14) cm] than in no deviation group [(0.58 +/- 0.14) cm], the discrepancy have statistical significance with (P axis deviation group [(0.71 +/- 0.14) cm] than in no deviation group, the discrepancy have statistical significance with (P left axis deviation Ptf-V1 relevance ratio 85.71% is higher than in no deviation (35.70%) and right axis deviation groups (28.57%), the discrepancy have statistical significance with (P left ventricular wall thickness in ECG left axis deviation and no deviation groups (r1 = 0.92, P left ventricular morphosis and function especially left atrium loading change. ECG Ptf-V1 combined with ECG left axis deviation is valuable to the diagnosis of coal-workers with pneumoconiosis complicated by left ventricular hypertrophy.

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    was superior to atenolol-based treatment for reducing new-onset AF and complications, especially stroke, associated with new-onset or pre-existing AF. Potential mechanisms of AF prevention by angiotensin receptor blockade supported by LIFE results include greater reduction in left atrial size and LV...... 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...

  5. Simvastatin prevents isoproterenol-induced cardiac hypertrophy through modulation of the JAK/STAT pathway

    Directory of Open Access Journals (Sweden)

    Al-Rasheed NM

    2015-06-01

    Full Text Available Nouf M Al-Rasheed,1 Maha M Al-Oteibi,1 Reem Z Al-Manee,1 Sarah A Al-Shareef,1 Nawal M Al-Rasheed,1 Iman H Hasan,1 Raeesa A Mohamad,2 Ayman M Mahmoud3 1Department of Pharmacology, Faculty of Pharmacy, 2Department of Anatomy, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 3Physiology Division, Department of Zoology, Faculty of Science, Beni-Suef University, Egypt Abstract: Simvastatin (SIM is a lipid-soluble inhibitor of hydroxy-3-methylglutaryl coenzyme A reductase with multiple reported therapeutic benefits. The present study was designed to investigate the effect of pretreatment with SIM on isoproterenol (ISO-induced cardiac hypertrophy in rats. Twenty-four male albino Wistar rats weighing 180–200 g were divided into four groups. Groups I and III received normal saline while groups II and IV received SIM (10 mg/kg body weight for 30 days per gavage. In the last 7 days, rats of groups III and IV were administered ISO (5 mg/kg intraperitoneally to induce cardiac hypertrophy. Administration of ISO induced an increase in heart-to-body weight (HW/BW ratio, an increase in serum interleukin-6, and elevated systolic and diastolic blood pressure. Serum levels of lipids, cardiovascular risk indices, and cardiac troponin I and creatine phosphokinase-MB showed significant increase in ISO-induced hypertrophic rats. Histopathological examination of heart tissue revealed focal areas of subendocardium degeneration, mononuclear cellular infiltrations, fibrous tissue deposition, and increased thickness of the myocardium of left ventricle. In addition, ISO-administered rats exhibited significant upregulation of cardiac Janus kinase, phosphorylated signal transducer and activator of transcription, and nuclear factor-kappa B. Pretreatment with SIM significantly prevented ISO-induced cardiac hypertrophy, alleviated the altered biochemical parameters, and improved the heart architecture. In conclusion, our study provides evidence that SIM

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

    Science.gov (United States)

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

    2015-03-01

    Hyperpolarization-activated cyclic nucleotide-gated channels (HCNs) are expressed in the ventricles of fetal hearts but are normally down-regulated as development progresses. In the hypertrophied heart, however, these channels are re-expressed and generate a hyperpolarization-activated, nonselective cation current (Ih), which evidence suggests may increase susceptibility to arrhythmia. To test this hypothesis, we generated and analyzed transgenic mice overexpressing HCN2 specifically in their hearts (HCN2-Tg). Under physiological conditions, HCN2-Tg mice exhibited no discernible abnormalities. After the application of isoproterenol (ISO), however, ECG recordings from HCN2-Tg mice showed intermittent atrioventricular dissociation followed by idioventricular rhythm. Consistent with this observation, 0.3 μmol/L ISO-induced spontaneous action potentials (SAPs) in 76% of HCN2-Tg ventricular myocytes. In the remaining 24%, ISO significantly depolarized the resting membrane potential (RMP), and the late repolarization phase of evoked action potentials (APs) was significantly longer than in WT myocytes. Analysis of membrane currents revealed that these differences are attributable to the Ih tail current. These findings suggest HCN2 channel activity reduces the repolarization reserve of the ventricular action potential and increases ectopic automaticity under pathological conditions such as excessive β-adrenergic stimulation. Copyright © 2015. Published by Elsevier Ltd.

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

    Science.gov (United States)

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

    2015-01-01

    Follistatin, a physiological inhibitor of myostatin, induces a dramatic increase in skeletal muscle mass, requiring the type 1 IGF-I receptor/Akt/mTOR pathway. The aim of the present study was to investigate the role of IGF-I and insulin, two ligands of the IGF-I receptor, in the follistatin hypertrophic action on skeletal muscle. In a first step, we showed that follistatin increases muscle mass while being associated with a downregulation of muscle IGF-I expression. In addition, follistatin retained its full hypertrophic effect toward muscle in hypophysectomized animals despite very low concentrations of circulating and muscle IGF-I. Furthermore, follistatin did not increase muscle sensitivity to IGF-I in stimulating phosphorylation of Akt but, surprisingly, decreased it once hypertrophy was present. Taken together, these observations indicate that increased muscle IGF-I production or sensitivity does not contribute to the muscle hypertrophy caused by follistatin. Unlike low IGF-I, low insulin, as obtained by streptozotocin injection, attenuated the hypertrophic action of follistatin on skeletal muscle. Moreover, the full anabolic response to follistatin was restored in this condition by insulin but also by IGF-I infusion. Therefore, follistatin-induced muscle hypertrophy requires the activation of the insulin/IGF-I pathway by either insulin or IGF-I. When insulin or IGF-I alone is missing, follistatin retains its full anabolic effect, but when both are deficient, as in streptozotocin-treated animals, follistatin fails to stimulate muscle growth. PMID:26219865

  8. Gene reprogramming in exercise-induced cardiac hypertrophy in swine: A transcriptional genomics approach.

    Science.gov (United States)

    Kuster, Diederik W D; Merkus, Daphne; Blonden, Lau A; Kremer, Andreas; van IJcken, Wilfred F J; Verhoeven, Adrie J M; Duncker, Dirk J

    2014-12-01

    Cardiac hypertrophy of the left ventricle (LV) in response to dynamic exercise-training (EX) is a beneficial adaptation to increased workload, and is thought to result from genetic reprogramming. We aimed to determine which transcription factors (TFs) are involved in this genetic reprogramming of the LV in swine induced by exercise-training. Swine underwent 3-6 weeks of dynamic EX, resulting in a 16% increase of LV weight/body weight ratio compared to sedentary animals (P=0.03). Hemodynamic analysis showed an increased stroke volume index (stroke volume/body weight +35%; P=0.02). Microarray-analysis of LV tissue identified 339 upregulated and 408 downregulated genes (false discovery rate1.5-fold (P2-fold were observed for 23 TF-specific DNA probes. Matching results in TFBS and protein/DNA array analyses were obtained for transcription factors YY1 (Yin Yang 1), PAX6 (paired box 6) and GR (glucocorticoid receptor). Notably, PAX6 and GR show lower signals in TFBS and protein/DNA array analyses upon exercise-training, whereas we previously showed higher signals for these factors in the remodeled LV of swine post-myocardial infarction (MI). In conclusion, we have identified transcription factors that may drive the genetic reprogramming underlying exercise-training induced LV hypertrophy in swine. PAX6 and GR are among the transcription factors that are oppositely regulated in LV hypertrophy after exercise-training and MI. These proteins may be at the base of the differences between pathological and physiological hypertrophy. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Effects of candesartan versus amlodipine on home-measured blood pressure, QT dispersion and left ventricular hypertrophy in high-risk hypertensive patients.

    Science.gov (United States)

    Matsuno, Yasunari; Minatoguchi, Shinya; Fujiwara, Hisayoshi

    2011-04-01

    The GIFU substudy of the Candesartan Antihypertensive Survival Evaluation in Japan (CASE-J) trial was conducted to compare the long-term effects of candesartan and amlodipine on office- and home-measured blood pressure (BP), QTc dispersion and left ventricular mass index (LVMI) in high-risk Japanese patients with hypertension. We used a prospective, randomized, open-label design with blinded assessment of endpoints. Patients were assigned to candesartan-based therapy up to 12 mg/day (n = 100) or amlodipine-based therapy up to 10 mg/day (n = 101) and followed for 3 years. LVMI was assessed by echocardiography and QTc dispersion was obtained from electrocardiograms. Both candesartan and amlodipine lowered and controlled office- and home-measured BP levels with no significant between-treatment differences. In patients diagnosed with left ventricular hypertrophy (LVH) at baseline, both candesartan and amlodipine significantly regressed LVMI after 3 years. However, candesartan (41.7 ± 15.1 ms at baseline vs 32.9 ± 16.6 ms after 3 years, p candesartan effect will translate into improved prognosis in terms of cardiovascular mortality and morbidity.

  10. Sphaeranthus indicus attenuates testosterone induced prostatic hypertrophy in albino rats.

    Science.gov (United States)

    Nahata, Alok; Dixit, Vinod Kumar

    2011-12-01

    The present study reports the attenuating effect of Sphaeranthus indicus extracts (SI) on prostatic hyperplasia induced by testosterone in albino rats. In vitro studies were conducted to assess the 5α-reductase inhibitory potential of the petroleum ether, ethanolic and aqueous extracts of SI. A biochemical marker, β-sitosterol, was isolated and extracts were characterized utilizing HPTLC. Testosterone (3 mg/kg s.c.) was administered to the rats along with the test extracts and isolated β-sitosterol for a period of 28 days. The weight of the rats, the urine output, serum testosterone concentrations and prostate-specific antigen (PSA) levels were recorded. The prostate/body weight ratio (P/BW) was calculated and histological studies were performed to observe the changes in the histoarchitecture of the prostate. Finasteride was used as a positive control (1 mg/kg p.o.). Sphaeranthus indicus extracts attenuated the increase in the P/BW ratio induced by testosterone in the treated groups. The petroleum ether extract exhibited the best activity, although the ethanol and aqueous extracts also exhibited significant activity. Urine output was also improved significantly, demonstrating the clinical implications of the study. Histological studies, testosterone levels which were measured weekly and PSA levels measured at the end of the study also support claims for the potential use of Sphaeranthus indicus in the treatment of prostatic hyperplasia. Copyright © 2011 John Wiley & Sons, Ltd.

  11. Loperamide Induced Life Threatening Ventricular Arrhythmia

    Directory of Open Access Journals (Sweden)

    Ankit Upadhyay

    2016-01-01

    Full Text Available Loperamide is over-the-counter antidiarrheal agent acting on peripherally located μ opioid receptors. It is gaining popularity among drug abusers as opioid substitute. We report a case of a 46-year-old male that was presented after cardiac arrest. After ruling out ischemia, cardiomyopathy, pulmonary embolism, central nervous system pathology, sepsis, and other drug toxicity, we found out that patient was using around 100 mg of Loperamide to control his chronic diarrhea presumably because of irritable bowel syndrome for last five years and consumed up to 200 mg of Loperamide daily for last two days before the cardiac arrest. We hypothesize that the patient’s QTc prolongation and subsequent cardiac arrest are due to Loperamide toxicity. Patient experienced gradual resolution of tachyarrhythmia and gradual decrease in QTc interval during hospitalization which supports the evidence of causal relationship between Loperamide overdose and potentially fatal arrhythmias. It also provided the clue that patient may have congenital long QT syndrome which was unmasked by Loperamide causing ventricular arrhythmias. This case adds one more pearl in the literature to support that Loperamide overdose related cardiac toxicity does exist and it raises concerns over Loperamide abuse in the community.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-02-01

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

  13. Testosterone induces cardiomyocyte hypertrophy through mammalian target of rapamycin complex 1 pathway.

    Science.gov (United States)

    Altamirano, Francisco; Oyarce, César; Silva, Patricio; Toyos, Marcela; Wilson, Carlos; Lavandero, Sergio; Uhlén, Per; Estrada, Manuel

    2009-08-01

    Elevated testosterone concentrations induce cardiac hypertrophy but the molecular mechanisms are poorly understood. Anabolic properties of testosterone involve an increase in protein synthesis. The mammalian target of rapamycin complex 1 (mTORC1) pathway is a major regulator of cell growth, but the relationship between testosterone action and mTORC1 in cardiac cells remains unknown. Here, we investigated whether the hypertrophic effects of testosterone are mediated by mTORC1 signaling in cultured cardiomyocytes. Testosterone increases the phosphorylation of mTOR and its downstream targets 40S ribosomal protein S6 kinase 1 (S6K1; also known as RPS6KB1) and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1). The S6K1 phosphorylation induced by testosterone was blocked by rapamycin and small interfering RNA to mTOR. Moreover, the hormone increased both extracellular-regulated kinase (ERK1/2) and protein kinase B (Akt) phosphorylation. ERK1/2 inhibitor PD98059 blocked the testosterone-induced S6K1 phosphorylation, whereas Akt inhibition (Akt-inhibitor-X) had no effect. Testosterone-induced ERK1/2 and S6K1 phosphorylation increases were blocked by either 1,2-bis(2-aminophenoxy)ethane-N,N,N,N-tetraacetic acid-acetoxymethylester or by inhibitors of inositol 1,4,5-trisphosphate (IP(3)) pathway: U-73122 and 2-aminoethyl diphenylborate. Finally, cardiomyocyte hypertrophy was evaluated by, the expression of beta-myosin heavy chain, alpha-skeletal actin, cell size, and amino acid incorporation. Testosterone increased all four parameters and the increase being blocked by mTOR inhibition. Our findings suggest that testosterone activates the mTORC1/S6K1 axis through IP(3)/Ca(2+) and MEK/ERK1/2 to induce cardiomyocyte hypertrophy.

  14. Early development of calcific aortic valve disease and left ventricular hypertrophy in a mouse model of combined dyslipidemia and type 2 diabetes mellitus.

    Science.gov (United States)

    Le Quang, Khai; Bouchareb, Rihab; Lachance, Dominic; Laplante, Marc-André; El Husseini, Diala; Boulanger, Marie-Chloé; Fournier, Dominique; Fang, Xiang Ping; Avramoglu, Rita Kohen; Pibarot, Philippe; Deshaies, Yves; Sweeney, Gary; Mathieu, Patrick; Marette, André

    2014-10-01

    This study aimed to determine the potential impact of type 2 diabetes mellitus on left ventricular dysfunction and the development of calcified aortic valve disease using a dyslipidemic mouse model prone to developing type 2 diabetes mellitus. When compared with nondiabetic LDLr(-/-)/ApoB(100/100), diabetic LDLr(-/-)/ApoB(100/100)/IGF-II mice exhibited similar dyslipidemia and obesity but developed type 2 diabetes mellitus when fed a high-fat/sucrose/cholesterol diet for 6 months. LDLr(-/-)/ApoB(100/100)/IGF-II mice showed left ventricular hypertrophy versus C57BL6 but not LDLr(-/-)/ApoB(100/100) mice. Transthoracic echocardiography revealed significant reductions in both left ventricular systolic fractional shortening and diastolic function in high-fat/sucrose/cholesterol fed LDLr(-/-)/ApoB(100/100)/IGF-II mice when compared with LDLr(-/-)/ApoB(100/100). Importantly, we found that peak aortic jet velocity was significantly increased in LDLr(-/-)/ApoB(100/100)/IGF-II mice versus LDLr(-/-)/ApoB(100/100) animals on the high-fat/sucrose/cholesterol diet. Microtomography scans and Alizarin red staining indicated calcification in the aortic valves, whereas electron microscopy and energy dispersive x-ray spectroscopy further revealed mineralization of the aortic leaflets and the presence of inflammatory infiltrates in diabetic mice. Studies showed upregulation of hypertrophic genes (anp, bnp, b-mhc) in myocardial tissues and of osteogenic genes (spp1, bglap, runx2) in aortic tissues of diabetic mice. We have established the diabetes mellitus -prone LDLr(-/-)/ApoB(100/100)/IGF-II mouse as a new model of calcified aortic valve disease. Our results are consistent with the growing body of clinical evidence that the dysmetabolic state of type 2 diabetes mellitus contributes to early mineralization of the aortic valve and calcified aortic valve disease pathogenesis. © 2014 American Heart Association, Inc.

  15. Expression of periodontal inflammation into left ventricular hypertrophy in Type 2 diabetes mellitus: A cross-sectional study

    OpenAIRE

    Trupti Sarda; Surekha Rathod; Abhay Kolte; Girish Bodhare; Anil Modak

    2016-01-01

    Background: Chronic periodontitis, an inflammatory disease, is closely related to certain systemic conditions such as cardiovascular diseases, obesity, and Type 2 diabetes mellitus. These conditions, occurring as comorbidities, synergically affect periodontal tissues. Aim: This study aims to examine whether chronic gingivitis and chronic generalized severe periodontitis in patients with Type 2 diabetes mellitus are associated with increased left ventricular mass (LVM). Materials and Methods: ...

  16. The influence of aldosterone on the development of left ventricular geometry and hypertrophy in patients with essential hypertension.

    Science.gov (United States)

    Soylu, Ahmet; Temizhan, Ahmet; Duzenli, Mehmet Akif; Sokmen, Gulizar; Koylu, Oznur; Telli, Hasan Huseyin

    2004-09-01

    The identification of risk factors for the initiation of left ventricle hypertrophy (LVH), which is an independent risk factor for cardiovascular mortality and morbidity in hypertensive patients, is very important. The objective of the present study was to identify the relationship of aldosterone with LVH and different geometrical patterns of left ventricle that develop in patients with essential hypertension. A total of 83 patients with essential hypertension (44 females, mean age, 51 +/- 8 years, 39 males, mean age, 57 +/- 10 years) were included in this study. Thirty-two had LVH. When evaluated according to the geometrical patterns of LVH, 18 patients had concentric LVH, 14 had eccentric LVH, and 17 had concentric remodeling. Thirty-four patients had normal left ventricle geometry. Two weeks after the cessation of antihypertensive medications, sodium, potassium, and proteinuria in 24-hour urine samples and plasma aldosterone levels and plasma renin activity were measured. Plasma aldosterone levels of the patients with LVH were found to be significantly higher (9.92 +/- 6.34 ng/dL versus 5.83 +/- 3.5 ng/dL, P < 0.01). The difference between plasma renin activities was not statistically significant. Linear regression analysis revealed that plasma aldosterone level and age were independent parameters increasing left ventricle mass index. The plasma aldosterone levels of patients with concentric hypertrophy of the left ventricle were significantly higher than those of patients with normal geometry and concentric remodeling. There was no significant difference between plasma renin activities. Twenty-four hour urine protein concentrations of the patients with LVH were found to be significantly higher and sodium to be significantly lower. Plasma aldosterone levels seem to be correlated with LVH especially with concentric hypertrophy of the left ventricle in patients with essential hypertension.

  17. Thyroid Hormone-Induced Hypertrophy in Mesenchymal Stem Cell Chondrogenesis Is Mediated by Bone Morphogenetic Protein-4

    Science.gov (United States)

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

    2014-01-01

    Chondrogenic differentiating mesenchymal stem cells (MSCs) express markers of hypertrophic growth plate chondrocytes. As hypertrophic cartilage undergoes ossification, this is a concern for the application of MSCs in articular cartilage tissue engineering. To identify mechanisms that elicit this phenomenon, we used an in vitro hypertrophy model of chondrifying MSCs for differential gene expression analysis and functional experiments with the focus on bone morphogenetic protein (BMP) signaling. Hypertrophy was induced in chondrogenic MSC pellet cultures by transforming growth factor β (TGFβ) and dexamethasone withdrawal and addition of triiodothyronine. Differential gene expression analysis of BMPs and their receptors was performed. Based on these results, the in vitro hypertrophy model was used to investigate the effect of recombinant BMP4 and the BMP inhibitor Noggin. The enhancement of hypertrophy could be shown clearly by an increased cell size, alkaline phosphatase activity, and collagen type X deposition. Upon induction of hypertrophy, BMP4 and the BMP receptor 1B were upregulated. Addition of BMP4 further enhanced hypertrophy in the absence, but not in the presence of TGFβ and dexamethasone. Thyroid hormone induced hypertrophy by upregulation of BMP4 and this induced enhancement of hypertrophy could be blocked by the BMP antagonist Noggin. BMP signaling is an important modulator of the late differentiation stages in MSC chondrogenesis and the thyroid hormone induces this pathway. As cartilage tissue engineering constructs will be exposed to this factor in vivo, this study provides important insight into the biology of MSC-based cartilage. Furthermore, the possibility to engineer hypertrophic cartilage may be helpful for critical bone defect repair. PMID:23937304

  18. Regional Stress-Induced Ischemia in Non-fibrotic Hypertrophied Myocardium in Young HCM Patients.

    Science.gov (United States)

    Jablonowski, Robert; Fernlund, Eva; Aletras, Anthony H; Engblom, Henrik; Heiberg, Einar; Liuba, Petru; Arheden, Håkan; Carlsson, Marcus

    2015-12-01

    The relationship between hypertrophy, perfusion abnormalities and fibrosis is unknown in young patients with hypertrophic cardiomyopathy (HCM). Since mounting evidence suggests causal relationship between myocardial ischemia and major adverse cardiac events, we sought to investigate whether (1) regional myocardial perfusion is decreased in young HCM patients and in individuals at risk of HCM, and (2) hypoperfused areas are larger than areas with fibrosis. HCM patients (n = 12), HCM-risk subjects (n = 15) and controls (n = 9) were imaged on a 1.5 T MRI scanner. Myocardial hypertrophy was assessed on cine images. Perfusion images were acquired during adenosine hyperemia and at rest. Maximum upslope ratios of perfusion (stress/rest) were used for semiquantitative analysis. Fibrosis was assessed by late gadolinium enhancement (LGE). Results are presented as median and range. Perfusion in HCM-risk subjects and in non-hypertrophied segments in HCM patients showed no difference compared to controls (P = ns). Hypertrophic segments in HCM patients without LGE showed decreased perfusion compared to segments without hypertrophy [1.5 (1.1-2.3) vs. 2.0 (1.8-2.6), P myocardium in HCM patients during adenosine exceeded the extent of fibrosis on LGE [20 (0-48) vs. 4 (0-7) % slice area, P myocardium and is lowest in fibrotic myocardium in young HCM patients but does not discriminate HCM-risk subjects from controls. The stress-induced hypoperfused regions exceed regions with LGE, indicating that hypoperfusion precedes fibrosis and may be a more sensitive marker of diseased myocardium in HCM.

  19. Fenofibrate unexpectedly induces cardiac hypertrophy in mice lacking MuRF1.

    Science.gov (United States)

    Parry, Traci L; Desai, Gopal; Schisler, Jonathan C; Li, Luge; Quintana, Megan T; Stanley, Natalie; Lockyer, Pamela; Patterson, Cam; Willis, Monte S

    2016-01-01

    The muscle-specific ubiquitin ligase muscle ring finger-1 (MuRF1) is critical in regulating both pathological and physiological cardiac hypertrophy in vivo. Previous work from our group has identified MuRF1's ability to inhibit serum response factor and insulin-like growth factor-1 signaling pathways (via targeted inhibition of cJun as underlying mechanisms). More recently, we have identified that MuRF1 inhibits fatty acid metabolism by targeting peroxisome proliferator-activated receptor alpha (PPARα) for nuclear export via mono-ubiquitination. Since MuRF1-/- mice have an estimated fivefold increase in PPARα activity, we sought to determine how challenge with the PPARα agonist fenofibrate, a PPARα ligand, would affect the heart physiologically. In as little as 3 weeks, feeding with fenofibrate/chow (0.05% wt/wt) induced unexpected pathological cardiac hypertrophy not present in age-matched sibling wild-type (MuRF1+/+) mice, identified by echocardiography, cardiomyocyte cross-sectional area, and increased beta-myosin heavy chain, brain natriuretic peptide, and skeletal muscle α-actin mRNA. In addition to pathological hypertrophy, MuRF1-/- mice had an unexpected differential expression in genes associated with the pleiotropic effects of fenofibrate involved in the extracellular matrix, protease inhibition, hemostasis, and the sarcomere. At both 3 and 8 weeks of fenofibrate treatment, the differentially expressed MuRF1-/- genes most commonly had SREBP-1 and E2F1/E2F promoter regions by TRANSFAC analysis (54 and 50 genes, respectively, of the 111 of the genes >4 and cardiac hypertrophy, and hemostasis. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. ZNF307 (Zinc Finger Protein 307) Acts as a Negative Regulator of Pressure Overload-Induced Cardiac Hypertrophy.

    Science.gov (United States)

    Yu, Chang-Jiang; Liang, Chen; Li, Yu-Xia; Hu, Qing-Qing; Zheng, Wei-Wan; Niu, Na; Yang, Xu; Wang, Zi-Rui; Yu, Xiao-Di; Zhang, Bao-Long; Song, Bin-Lin; Zhang, Zhi-Ren

    2017-04-01

    Pathological cardiac hypertrophy is a key risk factor for heart failure. We found that the protein expression levels of the ZNF307 (zinc finger protein 307) were significantly increased in heart samples from both human patients with dilated cardiomyopathy and mice subjected to aortic banding. Therefore, we aimed to elucidate the role of ZNF307 in the development of cardiac hypertrophy and to explore the signal transduction events that mediate the effect of ZNF307 on cardiac hypertrophy, using cardiac-specific ZNF307 transgenic (ZNF307-TG) mice and ZNF307 global knockout (ZNF307-KO) mice. The results showed that the deletion of ZNF307 potentiated aortic banding-induced pathological cardiac hypertrophy, fibrosis, and cardiac dysfunction; however, the aortic banding-induced cardiac hypertrophic phenotype was dramatically diminished by ZNF307 overexpression in mouse heart. Mechanistically, the antihypertrophic effects mediated by ZNF307 in response to pathological stimuli were associated with the direct inactivation of NF-κB (nuclear factor-κB) signaling and blockade of the nuclear translocation of NF-κB subunit p65. Furthermore, the overexpression of a degradation-resistant mutant of IκBα (IκBα S32A/S36A ) reversed the exacerbation of cardiac hypertrophy, fibrosis, and dysfunction shown in aortic banding-treated ZNF307-KO mice. In conclusion, our findings demonstrate that ZNF307 ameliorates pressure overload-induced cardiac hypertrophy by inhibiting the activity of NF-κB-signaling pathway. © 2017 American Heart Association, Inc.

  1. Identifying non-inducible ventricular tachycardia origin utilizing defibrillator electrograms.

    Science.gov (United States)

    Tschabrunn, Cory M; Anter, Elad; Marchlinski, Francis E

    2013-04-01

    Developing an ablation strategy when the clinical arrhythmia cannot be induced is a challenge. A 72-year-old man is transferred to our facility for ventricular tachycardia (VT) storm. Endocardial and epicardial voltage mapping was normal and program stimulation failed to induce any arrhythmias. Implantable cardioverter-defibrillators (ICD) electrograms (EGMs) were recorded while pacing and compared to the stored clinical events. Ablation lesions were delivered across a narrow area of matching ICD EGM pace maps. The patient has remained arrhythmia free for 11 months. ICD EGMs may be useful in facilitating successful VT ablation when the clinical arrhythmia cannot be induced in the EP lab.

  2. Tanshinone IIA Prevents Leu27IGF-II-Induced Cardiomyocyte Hypertrophy Mediated by Estrogen Receptor and Subsequent Akt Activation.

    Science.gov (United States)

    Weng, Yueh-Shan; Wang, Hsueh-Fang; Pai, Pei-Ying; Jong, Gwo-Ping; Lai, Chao-Hung; Chung, Li-Chin; Hsieh, Dennis Jine-Yuan; HsuanDay, Cecilia; Kuo, Wei-Wen; Huang, Chih-Yang

    2015-01-01

    IGF-IIR plays important roles as a key regulator in myocardial pathological hypertrophy and apoptosis, which subsequently lead to heart failure. Salvia miltiorrhiza Bunge (Danshen) is a traditional Chinese medicinal herb used to treat cardiovascular diseases. Tanshinone IIA is an active compound in Danshen and is structurally similar to 17[Formula: see text]-estradiol (E[Formula: see text]. However, whether tanshinone IIA improves cardiomyocyte survival in pathological hypertrophy through estrogen receptor (ER) regulation remains unclear. This study investigates the role of ER signaling in mediating the protective effects of tanshinone IIA on IGF-IIR-induced myocardial hypertrophy. Leu27IGF-II (IGF-II analog) was shown in this study to specifically activate IGF-IIR expression and ICI 182,780 (ICI), an ER antagonist used to investigate tanshinone IIA estrogenic activity. We demonstrated that tanshinone IIA significantly enhanced Akt phosphorylation through ER activation to inhibit Leu27IGF-II-induced calcineurin expression and subsequent NFATc3 nuclear translocation to suppress myocardial hypertrophy. Tanshinone IIA reduced the cell size and suppressed ANP and BNP, inhibiting antihypertrophic effects induced by Leu27IGF-II. The cardioprotective properties of tanshinone IIA that inhibit Leu27IGF-II-induced cell hypertrophy and promote cell survival were reversed by ICI. Furthermore, ICI significantly reduced phospho-Akt, Ly294002 (PI3K inhibitor), and PI3K siRNA significantly reduced the tanshinone IIA-induced protective effect. The above results suggest that tanshinone IIA inhibited cardiomyocyte hypertrophy, which was mediated through ER, by activating the PI3K/Akt pathway and inhibiting Leu27IGF-II-induced calcineurin and NFATC3. Tanshinone IIA exerted strong estrogenic activity and therefore represented a novel selective ER modulator that inhibits IGF-IIR signaling to block cardiac hypertrophy.

  3. Relative Importance of Aortic Stiffness and Volume as Predictors of Treatment-Induced Improvement in Left Ventricular Mass Index in Dialysis.

    Directory of Open Access Journals (Sweden)

    Panagiotis I Georgianos

    Full Text Available This study aimed to explore the relative contribution of aortic stiffness and volume in treatment-induced change of left ventricular mass in dialysis. Hypertension in Hemodialysis Patients Treated with Atenolol or Lisinopril trial compared the effect of lisinopril versus atenolol in reducing left ventricular mass index; 179 patients with echo measurements of aortic pulse wave velocity and left ventricular mass at baseline were included. In unadjusted analysis, overall reductions of 26.24 g/m2 (95% CI: -49.20, -3.29 and 35.67 g/m2 (95% CI: -63.70, -7.64 in left ventricular mass index were noted from baseline to 6 and 12 months respectively. Volume control emerged as an important determinant of regression of left ventricular mass index due to the following reasons: (i additional control for change in ambulatory systolic blood pressure mitigated the reduction in left ventricular mass index in the statistical model above [6-month visit: -18.6 g/m2 (95% CI: -43.7, 6.5; 12-month visit: -22.1 g/m2 (95% CI: -52.2, 8.0] (ii regression of left ventricular hypertrophy was primarily due to reduction in left ventricular chamber and not wall thickness and (iii adjustment for inferior vena cava diameter (as a proxy for volume removed the effect of time on left ventricular mass index reduction [6-month visit: -6.6 g/m2 (95% CI: (-41.6, 28.4; 12-month visit: 0.6 g/m2 (95% CI: -39.5, 40.7]. In contrast, aortic pulse wave velocity was neither a determinant of baseline left ventricular mass index nor predictor of its reduction. Among dialysis patients, ambulatory systolic pressure, a proxy for volume expansion, but not aortic stiffness is more important predictor of reduction in left ventricular mass index. Improving blood pressure control via adequate volume management appears as an effective strategy to improve left ventricular hypertrophy in dialysis.

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

    Science.gov (United States)

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

    2014-04-01

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

  5. Left Ventricular Outflow Tract Obstruction in Hypertrophic Cardiomyopathy Patients Without Severe Septal Hypertrophy: Implications of Mitral Valve and Papillary Muscle Abnormalities Assessed Using Cardiac Magnetic Resonance and Echocardiography.

    Science.gov (United States)

    Patel, Parag; Dhillon, Ashwat; Popovic, Zoran B; Smedira, Nicholas G; Rizzo, Jessica; Thamilarasan, Maran; Agler, Deborah; Lytle, Bruce W; Lever, Harry M; Desai, Milind Y

    2015-07-01

    In patients with hypertrophic cardiomyopathy and left ventricular outflow tract (LVOT) obstruction, but without basal septal hypertrophy, we sought to identify mitral valve (MV) and papillary muscle (PM) abnormalities that predisposed to LVOT obstruction, using echo and cardiac magnetic resonance. We studied 121 patients with hypertrophic cardiomyopathy hypertrophic cardiomyopathy (age, 49±17 years; 60% men; 57% on β-blockers) with a basal septal thickness of ≤1.8 cm who underwent echocardiography (rest+stress) and cine cardiac magnetic resonance. Echo measurements included maximal LVOT gradient (rest/provocable), MV leaflet length (parasternal long, 4 and 3-chamber views), and abnormal chordal attachment to mid/base of anterior MV. Cine cardiac magnetic resonance measurements included basal septal thickness, number/area of PM heads, and bifid PM mobility (in systole and diastole). Mean basal septal thickness, LVOT gradient, and LV ejection fraction were 1.5±0.3 cm, 72±54 mm Hg, and 61±6%, respectively. The number of anterolateral and posteromedial PM heads was 2.7±0.7 and 2.6±0.7, respectively. Anterolateral and posteromedial PM areas were 19.9±7 cm(2) and 17.1±6 cm(2), respectively. PM mobility was 11±6°. On multivariable analysis, predictors of maximal LVOT gradient were basal septal thickness, bifid PM mobility, anterior mitral leaflet length, and abnormal chordal attachment to base of anterior mitral leaflet. Forty-five patients underwent surgery to relieve LVOT obstruction, of which 52% needed an additional nonmyectomy (MV repair/replacement or PM reorientation) approach. In hypertrophic cardiomyopathy patients without significant LV hypertrophy, in addition to basal septal thickness, anterior MV length, abnormal chordal attachment, and bifid PM mobility are associated with LVOT obstruction. In such patients, additional procedures on MV and PM (±myectomy) could be considered. © 2015 American Heart Association, Inc.

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

    Science.gov (United States)

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

    2012-04-01

    Whether the left ventricular (LV) mass index (LVMI) and LV volumetric parameters are associated independently with natriuretic peptide levels is unclear in hypertrophic cardiomyopathy (HCM). Therefore, we investigated which parameters have an independent relationship with N-terminal pro-B type natriuretic peptide (NT-proBNP) levels in HCM patients using echocardiography and cardiac magnetic resonance imaging (CMR). A total of 103 patients with HCM (82 men, age 53 ± 12 years) were evaluated. Echocardiographic evaluations included left atrial volume index (LAVI) and early diastolic mitral inflow E velocity to early annular Ea velocity ratio (E/Ea). LVMI, maximal wall thickness and LV volumetric parameters were measured using CMR. The median value of NT-proBNP level was 387.0 pg/ml. The mean NT-proBNP level in patients with non-apical HCM (n = 69; 36 patients with asymmetric septal hypertrophy, 11 with diffuse, and 22 with mixed type) was significantly higher than in those with apical HCM (n = 34, P < 0.001). NT-proBNP level was negatively correlated with LV end-diastolic volume (LVEDV) (r = -0.263, P = 0.007) and positively with LVMI (r = 0.225, P = 0.022) and maximal wall thickness (r = 0.495, P < 0.001). Among the echocardiographic variables, LAVI (r = 0.492, P < 0.001) and E/Ea (r = 0.432, P < 0.001) were correlated with NT-proBNP. On multivariable analysis, non-apical HCM, increased maximal wall thickness and LAVI were independently related with NT-proBNP. Severity of LV hypertrophy and diastolic parameters might be important in the elevation of NT-proBNP level in HCM. Therefore, further evaluation of these parameters in HCM might be warranted.

  7. NMNAT3 is involved in the protective effect of SIRT3 in Ang II-induced cardiac hypertrophy.

    Science.gov (United States)

    Yue, Zhongbao; Ma, Yunzi; You, Jia; Li, Zhuoming; Ding, Yanqing; He, Ping; Lu, Xia; Jiang, Jianmin; Chen, Shaorui; Liu, Peiqing

    2016-10-01

    Pathological cardiac hypertrophy is a maladaptive response in a variety of organic heart disease (OHD), which is characterized by mitochondrial dysfunction that results from disturbed energy metabolism. SIRT3, a mitochondria-localized sirtuin, regulates global mitochondrial lysine acetylation and preserves mitochondrial function. However, the mechanisms by which SIRT3 regulates cardiac hypertrophy remains to be further elucidated. In this study, we firstly demonstrated that expression of SIRT3 was decreased in Angiotension II (Ang II)-treated cardiomyocytes and in hearts of Ang II-induced cardiac hypertrophic mice. In addition, SIRT3 overexpression protected myocytes from hypertrophy, whereas SIRT3 silencing exacerbated Ang II-induced cardiomyocyte hypertrophy. In particular, SIRT3-KO mice exhibited significant cardiac hypertrophy. Mechanistically, we identified NMNAT3 (nicotinamide mononucleotide adenylyltransferase 3), the rate-limiting enzyme for mitochondrial NAD biosynthesis, as a new target and binding partner of SIRT3. Specifically, SIRT3 physically interacts with and deacetylates NMNAT3, thereby enhancing the enzyme activity of NMNAT3 and contributing to SIRT3-mediated anti-hypertrophic effects. Moreover, NMNAT3 regulates the activity of SIRT3 via synthesis of mitochondria NAD. Taken together, these findings provide mechanistic insights into the negative regulatory role of SIRT3 in cardiac hypertrophy. Copyright © 2016. Published by Elsevier Inc.

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

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

    2009-10-09

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

  9. The effect of raloxifene on left ventricular hypertrophy in postmenopausal women: A prospective, randomized, and controlled study.

    Science.gov (United States)

    Bal, Uğur Abbas; Atar, İlyas; Öktem, Mesut; Zeyneloğlu, Hulusi B; Yıldırır, Aylin; Kuşcu, Esra; Müderrisoğlu, Haldun

    2015-06-01

    In healthy women, there is a progressive age-related increase in myocardial mass that is not seen in their male counterparts and occurs primarily in postmenopausal women. Raloxifene is a selective estrogen receptor modulator that has estrogenic actions on bone and the cardiovascular system. The aim of this study was to investigate the effect of raloxifene on myocardial hypertrophy in postmenopausal patients. A total of 22 postmenopausal osteoporotic women were included in this open-label, randomized, prospective, controlled study. Patients were randomized into two groups: 11 of the patients (group 1) were treated with raloxifene 60 mg/day, and the other 11 patients
(group 2) were defined as the control group. Quantitative 2-dimensional and M-mode echocardiographic examination was performed in all patients at the beginning and repeated at the end of the 6-month follow-up period. Left ventricle mass (LVM) and left ventricle mass index (LVMI) were calculated for all patients. The mean age of the patients was 57.2±3.9 years, and baseline clinical characteristics and echocardiographic parameters were similar between the two groups. After 6 months of raloxifene treatment, there was no difference in echocardiographic parameters of LVM and LVMI compared with the control group (201.2±25.9 gr vs. 169.7±46.2 gr, p=0.14 and 120.4±25.9 gr/m2 vs. 105.5±26.3 gr/m2, p=0.195, respectively). There was also no significant difference in LVM and LVMI in the within-group analysis of both groups. Raloxifene therapy does not affect myocardial hypertrophy in postmenopausal women after 6 months of treatment.

  10. Androgen interacts with exercise through the mTOR pathway to induce skeletal muscle hypertrophy

    Directory of Open Access Journals (Sweden)

    Fanxing Zeng

    2017-12-01

    Full Text Available This study was designed to investigate the effects of exogenous androgen and resistance exercise on skeletal muscle hypertrophy and the role of the mammalian target of rapamycin (mTOR signalling during the process. A total of 24 male Sprague-Dawley rats were randomly assigned to sham operation and dihydrotestosterone (DHT implantation groups with subgroups subjected to sedentary conditions or resistance exercise (SHAM+SED, SHAM+EX, DHT+SED, and DHT+EX. The experimental procedure lasted for 10 days. The mRNA expression of androgen receptor (AR and insulin-like growth factor I (IGF-I, the expression of myosin heavy chain (MHC, as well as the phosphorylation statuses of AR, mTOR, p70 ribosomal S6 kinase (p70S6K, and eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1 were determined in the white gastrocnemius muscle. The cross sectional area and wet mass of the muscle were also measured. The cross sectional area and MHC expression were significantly higher in SHAM+EX, DHT+SED, and DHT+EX than in SHAM+SED. There was no significant difference among groups in muscle mass. The mRNA expression of AR and IGF-I and the phosphorylation of mTOR, p70S6K, and 4EBP1 were significantly increased in DHT+SED and SHAM+EX and were significantly enhanced in DHT+EX compared with either DHT or exercise alone. These data show that DHT causes hypertrophy in skeletal muscle and that exercise has a synergistic effect on DHT-induced hypertrophy. Exercise enhances androgen-induced rapid anabolic action, which involves activation of the mTOR pathway.

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

    Science.gov (United States)

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

    2017-02-01

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

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

    Science.gov (United States)

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

    1999-01-01

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

  13. Cardiac magnetic resonance feature tracking: a novel method to assess myocardial strain. Comparison with echocardiographic speckle tracking in healthy volunteers and in patients with left ventricular hypertrophy.

    Science.gov (United States)

    Orwat, Stefan; Kempny, Aleksander; Diller, Gerhard-Paul; Bauerschmitz, Pia; Bunck, Alexander Ch; Maintz, David; Radke, Robert M; Baumgartner, Helmut

    2014-01-01

    Left ventricular longitudinal strain (LV-LS) and strain rate (SR) are sensitive markers of early systolic dysfunction. To evaluate the feasibility of a novel, cardiac magnetic resonance (CMR) based method known as feature tracking (FT) for the assessment of strain and SR, and to compare the CMR based results to those obtained on standard transthoracic echocardiography (TTE) in healthy volunteers and in patients with left ventricular hypertrophy cardiomyopathy (HCM). Overall, 20 healthy volunteers (ten male, mean age 24 ± 3 years) and 20 consecutive patients with HCM (12 male, mean age 47 ± 19 years) were included. Longitudinal and circumferential strain and SR of the left ventricle were measured on CMR at 1.5 Tesla and TTE and interobserver variability was assessed. FT measurements were feasible in all subjects. A good agreement between global LV-LS measured on CMR (controls: 20.8 ± 3.0; HCM: 17.6 ± 3.8) and TTE (controls: 19.4 ± 2.1; HCM: 16.6 ± 2.9) was found, while the agreement was worse for circumferential strain and all SR measurements. For the left and right ventricles, interobserver reproducibility was higher for strain measurements compared to SR. Coefficients of variation were lowest for LV-LS (13.2%) by CMR. FT analysis is a novel CMR based method for the analysis of myocardial strain and SR that is simple and correlates well with the echocardiographic measurements. Since CMR is unaffected by inadequate acoustic windows, FT may represent an attractive alternative to echocardiography in assessing the increasingly important parameters of myocardial deformation.

  14. The effect of atenolol on NT-proBNP and troponin in asymptomatic cats with severe left ventricular hypertrophy because of hypertrophic cardiomyopathy: a pilot study.

    Science.gov (United States)

    Jung, S W; Kittleson, M D

    2011-01-01

    Atenolol often is used empirically in cats with hypertrophic cardiomyopathy (HCM) before the onset of heart failure, although evidence of efficacy is lacking. Cardiac biomarkers play a critical role in the early detection of subclinical cardiac disease, in the prediction of long-term prognosis, and in monitoring the response to therapy in humans. Circulating concentrations of the biomarkers N-terminal pro-B type natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) will decrease after chronic administration of atenolol PO to cats with severe HCM but no signs of heart failure. Six Maine Coon or Maine Coon cross cats with severe HCM. Cats were treated with atenolol (12.5 mg PO q12 h) for 30 days. No cat had left ventricular dynamic outflow tract obstruction caused by systolic anterior motion of the mitral valve. The concentrations of NT-proBNP and cTnI were assayed before and on the last day of drug administration. There was no statistically significant change in NT-proBNP (median before, 394 pmol/L; range, 71-1,500 pmol/L; median after, 439 pmol/L; range, 24-1,500 pmol/L; P = .63) or in cTnI (median before, 0.24 ng/mL; range, 0.10-0.97 ng/mL; median after, 0.28 ng/mL; range, 0.09-1.0 ng/mL; P = .69) after administration of atenolol. Atenolol administration did not decrease NT-proBNP or cTnI concentrations in cats with severe left ventricular hypertrophy caused by hypertrophic cardiomyopathy. These results suggest that atenolol did not decrease myocardial ischemia and myocyte death in these cats. A larger clinical trial is warranted to verify these findings. Copyright © 2011 by the American College of Veterinary Internal Medicine.

  15. Association of Left Ventricular Hypertrophy With a Faster Rate of Renal Function Decline in Elderly Patients With Non-End-Stage Renal Disease.

    Science.gov (United States)

    Shi, Hong-tao; Wang, Xiao-jing; Li, Jun; Song, Gui-fang; Huang, Zhe-yong; Guo, Xiang-yu; Guo, Jun-jie; Lv, Zhi-yang; Li, Hong-wei; Ge, Jun-bo; Cui, Jie; Qi, Guan-ming

    2015-11-09

    Several studies have indicated that chronic kidney disease is independently associated with the presence of left ventricular hypertrophy (LVH). However, little clinical data are currently available regarding the detailed correlation between LVH and renal function in elderly patients with non-end-stage renal disease. A total of 300 in- and outpatients (more than 60 years of age, non-end-stage renal disease), 251 with LVH and 49 without LVH, seen at Beijing Friendship Hospital from January 2000 to December 2010 were included in this retrospective study. One observation period of 12 months was used to detect rapid kidney function decline. The evaluations of cardiac structure and function were performed via echocardiography. The multivariable logistic analysis showed patients with LVH had a much higher risk of rapid kidney function decline than those without LVH. Additionally, the baseline left ventricular mass index was 140 (125-160) g/m(2) in the non-chronic kidney disease group, 152 (130-175) g/m(2) in the mild chronic kidney disease group (estimated glomerular filtration rate (eGFR)≥60 ml/min/1.73 m(2)), and 153 (133-183) g/m(2) in the severe chronic kidney disease group (eGFRrenal function decline contributes to pathological LVH in non-end-stage renal disease elderly patients and that LVH is positively associated with renal function decline followed by an increased risk of rapid kidney function decline. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  16. Effects of chronic treprostinil treatment on experimental right heart hypertrophy and failure.

    Science.gov (United States)

    Axelgaard, Sofie; Holmboe, Sarah; Ringgaard, Steffen; Hillgaard, Thomas K; Andersen, Stine; Hansen, Mona S; Andersen, Asger; Nielsen-Kudsk, Jens E

    2017-01-01

    Right heart function is an important predictor of morbidity and mortality in pulmonary arterial hypertension and many CHD. We investigated whether treatment with the prostacyclin analogue treprostinil could prevent pressure overload-induced right ventricular hypertrophy and failure. Male Wistar rats were randomised to severe pulmonary trunk banding with a 0.5-mm banding clip (n=41), moderate pulmonary trunk banding with a 0.6-mm banding clip (n=36), or sham procedure (n=10). The banded rats were randomised to 6 weeks of treatment with a moderate dose of treprostinil (300 ng/kg/minute), a high dose of treprostinil (900 ng/kg/minute), or vehicle. Pulmonary trunk banding effectively induced hypertrophy, dilatation, and decreased right ventricular function. The severely banded animals presented with decompensated heart failure with extracardial manifestations. Treatment with treprostinil neither reduced right ventricular hypertrophy nor improved right ventricular function. In the pulmonary trunk banding model of pressure overload-induced right ventricular hypertrophy and failure, moderate- and high-dose treatment with treprostinil did not improve right ventricular function neither in compensated nor in decompensated right heart failure.

  17. Nobiletin, a Polymethoxy Flavonoid, Protects Against Cardiac Hypertrophy Induced by Pressure-Overload via Inhibition of NAPDH Oxidases and Endoplasmic Reticulum Stress

    OpenAIRE

    Ning Zhang; Wen-Ying Wei; Zheng Yang; Yan Che; Ya-Ge Jin; Hai-Han Liao; Sha-sha Wang; Wei Deng; Qi-Zhu Tang

    2017-01-01

    Background/Aims: An increase in oxidative stress has been implicated in the pathophysiology of pressure-overload induced cardiac hypertrophy. Nobiletin (NOB), extracted from the fruit peel of citrus, possesses anti-oxidative property. Our study aimed to investigate the protective role of NOB in the progression of cardiac hypertrophy in vivo and in vitro. Methods: Mice received aortic banding (AB) operation to induce cardiac hypertrophy. Experimental groups were as follows: sham+vehicle (VEH/S...

  18. Does exercise-induced muscle damage play a role in skeletal muscle hypertrophy?

    Science.gov (United States)

    Schoenfeld, Brad J

    2012-05-01

    Exercise-induced muscle damage (EIMD) occurs primarily from the performance of unaccustomed exercise, and its severity is modulated by the type, intensity, and duration of training. Although concentric and isometric actions contribute to EIMD, the greatest damage to muscle tissue is seen with eccentric exercise, where muscles are forcibly lengthened. Damage can be specific to just a few macromolecules of tissue or result in large tears in the sarcolemma, basal lamina, and supportive connective tissue, and inducing injury to contractile elements and the cytoskeleton. Although EIMD can have detrimental short-term effects on markers of performance and pain, it has been hypothesized that the associated skeletal muscle inflammation and increased protein turnover are necessary for long-term hypertrophic adaptations. A theoretical basis for this belief has been proposed, whereby the structural changes associated with EIMD influence gene expression, resulting in a strengthening of the tissue and thus protection of the muscle against further injury. Other researchers, however, have questioned this hypothesis, noting that hypertrophy can occur in the relative absence of muscle damage. Therefore, the purpose of this article will be twofold: (a) to extensively review the literature and attempt to determine what, if any, role EIMD plays in promoting skeletal muscle hypertrophy and (b) to make applicable recommendations for resistance training program design.

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

    Science.gov (United States)

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

    2003-12-01

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

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

    Directory of Open Access Journals (Sweden)

    F.S. Evangelista

    2003-12-01

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

  1. Transarterial versus transhepatic portal vein embolization to induce selective hepatic hypertrophy: a comparative study in swine.

    Science.gov (United States)

    Madoff, David C; Gupta, Sanjay; Pillsbury, Edmund P; Kan, Zuxing; Tinkey, Peggy T; Stephens, L Clifton; Ensor, Joe E; Hicks, Marshall E; Wright, Kenneth C

    2007-01-01

    Portal vein embolization (PVE) is used to induce liver hypertrophy for surgical candidates with marginal future liver remnant (FLR) volumes. We compared the feasibility, safety, and effectiveness of a transarterial approach for PVE (TA-PVE) with those of a transhepatic approach for PVE (TH-PVE) in a swine model. Ten experimental pigs (TA-PVE, n = 5; TH-PVE, n = 5) and six controls (TA, n = 3; TH, n = 3) were studied. For TA-PVE, a microcatheter was advanced into arteries supplying the left and left middle hepatic lobes. A 3 to 1 Ethiodol-ethanol mixture was infused into selected arteries to cross the arterioportal peribiliary plexus and remain within the portal veins (PVs). For TH-PVE, PVs in the same lobar distribution were embolized with 355- to 500-micro m polyvinyl alcohol particles and coils. Controls were similarly catheterized for saline infusion. Computed tomography with volumetry was performed before and 7, 14, 21, and 28 days after PVE to assess FLR hypertrophy (absolute FLR volume change and FLR/total liver volume [TLV]). Computed tomographic volumetry, laboratory data, and histopathology were compared between groups. All procedures were technically successful. The increases in mean absolute FLR volume (TA-PVE, 148 +/- 84 cm(3); TH-PVE, 62 +/- 19 cm(3); P = .082), mean FLR hypertrophy (TA-PVE, 93.2%; TH-PVE, 48.4%; P = .178), and mean FLR/TLV (TA-PVE, 31.0%; TH-PVE, 16.2%; P = .130) from day 0 to day 28 between experimental groups were better for TA-PVE. Changes in laboratory data among all groups were minimal. Two complications occurred from TA-PVE (right gastric artery embolization [n = 2] without sequela) and two from TH-PVE (acute segmental right PV thrombosis [n = 1]; death 3 weeks after PVE of unknown cause [n = 1]). Transarterial portal vein embolization is feasible, safe, and effective for inducing future liver remnant hypertrophy in swine and may represent an improvement over previously reported transhepatic portal vein embolization methods.

  2. Kruppel-like Factor 4 Protein Regulates Isoproterenol-induced Cardiac Hypertrophy by Modulating Myocardin Expression and Activity*

    Science.gov (United States)

    Yoshida, Tadashi; Yamashita, Maho; Horimai, Chihiro; Hayashi, Matsuhiko

    2014-01-01

    Kruppel-like factor 4 (KLF4) plays an important role in vascular diseases, including atherosclerosis and vascular injury. Although KLF4 is expressed in the heart in addition to vascular cells, the role of KLF4 in cardiac disease has not been fully determined. The goals of this study were to investigate the role of KLF4 in cardiac hypertrophy and to determine the underlying mechanisms. Cardiomyocyte-specific Klf4 knockout (CM Klf4 KO) mice were generated by the Cre/LoxP technique. Cardiac hypertrophy was induced by chronic infusion of the β-adrenoreceptor agonist isoproterenol (ISO). Results showed that ISO-induced cardiac hypertrophy was enhanced in CM Klf4 KO mice compared with control mice. Accelerated cardiac hypertrophy in CM Klf4 KO mice was accompanied by the augmented cellular enlargement of cardiomyocytes as well as the exaggerated expression of fetal cardiac genes, including atrial natriuretic factor (Nppa). Additionally, induction of myocardin, a transcriptional cofactor regulating fetal cardiac genes, was enhanced in CM Klf4 KO mice. Interestingly, KLF4 regulated Nppa expression by modulating the expression and activity of myocardin, providing a mechanical basis for accelerated cardiac hypertrophy in CM Klf4 KO mice. Moreover, we showed that KLF4 mediated the antihypertrophic effect of trichostatin A, a histone deacetylase inhibitor, because ISO-induced cardiac hypertrophy in CM Klf4 KO mice was attenuated by olmesartan, an angiotensin II type 1 antagonist, but not by trichostatin A. These results provide novel evidence that KLF4 is a regulator of cardiac hypertrophy by modulating the expression and the activity of myocardin. PMID:25100730

  3. Kruppel-like factor 4 protein regulates isoproterenol-induced cardiac hypertrophy by modulating myocardin expression and activity.

    Science.gov (United States)

    Yoshida, Tadashi; Yamashita, Maho; Horimai, Chihiro; Hayashi, Matsuhiko

    2014-09-19

    Kruppel-like factor 4 (KLF4) plays an important role in vascular diseases, including atherosclerosis and vascular injury. Although KLF4 is expressed in the heart in addition to vascular cells, the role of KLF4 in cardiac disease has not been fully determined. The goals of this study were to investigate the role of KLF4 in cardiac hypertrophy and to determine the underlying mechanisms. Cardiomyocyte-specific Klf4 knockout (CM Klf4 KO) mice were generated by the Cre/LoxP technique. Cardiac hypertrophy was induced by chronic infusion of the β-adrenoreceptor agonist isoproterenol (ISO). Results showed that ISO-induced cardiac hypertrophy was enhanced in CM Klf4 KO mice compared with control mice. Accelerated cardiac hypertrophy in CM Klf4 KO mice was accompanied by the augmented cellular enlargement of cardiomyocytes as well as the exaggerated expression of fetal cardiac genes, including atrial natriuretic factor (Nppa). Additionally, induction of myocardin, a transcriptional cofactor regulating fetal cardiac genes, was enhanced in CM Klf4 KO mice. Interestingly, KLF4 regulated Nppa expression by modulating the expression and activity of myocardin, providing a mechanical basis for accelerated cardiac hypertrophy in CM Klf4 KO mice. Moreover, we showed that KLF4 mediated the antihypertrophic effect of trichostatin A, a histone deacetylase inhibitor, because ISO-induced cardiac hypertrophy in CM Klf4 KO mice was attenuated by olmesartan, an angiotensin II type 1 antagonist, but not by trichostatin A. These results provide novel evidence that KLF4 is a regulator of cardiac hypertrophy by modulating the expression and the activity of myocardin. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. Toll-Like Receptor 4 Inhibition Improves Oxidative Stress and Mitochondrial Health in Isoproterenol-Induced Cardiac Hypertrophy in Rats

    Directory of Open Access Journals (Sweden)

    Parmeshwar B. Katare

    2017-06-01

    Full Text Available BackgroundInflammation remains a crucial factor for progression of cardiac diseases and cardiac hypertrophy remains an important cause of cardiac failure over all age groups. As a key regulator of inflammation, toll-like receptor 4 (TLR4 plays an important role in pathogenesis of cardiac diseases. Being an important regulator of innate immunity, the precise pathway of TLR4-mediated cardiac complications is yet to be established. Therefore, the primary objective of the present study was to find the role of TLR4 in cardiac hypertrophy and the molecular mechanism thereof.MethodsCardiac hypertrophy was induced with administration of isoproterenol (5 mg/kg/day, sc. TLR4 receptor inhibitor RS-LPS (lipopolysaccharide from the photosynthetic bacterium Rhodobacter sphaeroides; 5 μg/day and agonist lipopolysaccharide (LPS (from Escherichia coli; 3.12 μg/day were administered through osmotic pump along with isoproterenol. Cardiac hypertrophy as well as oxidative stress and mitochondrial parameters were evaluated.ResultsCardiac hypertrophy was confirmed with increased heart weight/body weight ratio as well as assessment of hypertrophic markers in heart. There was a marked increase in the TLR4 expression and oxidative stress along with mitochondrial dysfunction in ISO group. TLR4 inhibition significantly decreased heart weight/body weight ratio and ANP, collagen, and β-MHC expression and restored the disturbed cellular antioxidant flux. The mitochondrial perturbations that were observed in hypertrophy heart was normalized after administration of TLR4 inhibitor but not with the agonist. TLR4 agonism further exaggerated the oxidative stress in heart and hence accelerated the disease development and progression.ConclusionOur data show that increased TLR4 ligand pool in cardiac hypertrophy may exaggerate the disease progression. However, inhibition of TLR4 attenuated cardiac hypertrophy through reduced cardiac redox imbalance and mitochondrial

  5. AVE 0991 attenuates cardiac hypertrophy through reducing oxidative stress.

    Science.gov (United States)

    Ma, Yuedong; Huang, Huiling; Jiang, Jingzhou; Wu, Lingling; Lin, Chunxi; Tang, Anli; Dai, Gang; He, Jiangui; Chen, Yili

    2016-06-10

    AVE 0991, the nonpeptide angiotensin-(1-7) (Ang-(1-7)) analog, is recognized as having beneficial cardiovascular effects. However, the mechanisms have not been fully elucidated. This study was designed to investigate the effects of AVE 0991 on cardiac hypertrophy and the mechanisms involved. Mice were underwent aortic banding to induce cardiac hypertrophy followed by the administration of AVE 0991 (20 mg kg·day (-1)) for 4 weeks. It was shown that AVE 0991 reduced left ventricular hypertrophy and improved heart function, characterized by decreases in left ventricular weight and left ventricular end-diastolic diameter, and increases in ejection fraction. Moreover, AVE 0991 significantly down-regulated mean myocyte diameter and attenuate the gene expression of the hypertrophic markers. Furthermore, AVE 0991 inhibited the expression of NOX 2 and NOX 4, meaning that AVE 0991 reduced oxidative stress of cardiac hypertrophy mice. Our data showed that AVE 0991 treatment could attenuate cardiac hypertrophy and improve heart function, which may be due to reduce oxidative stress. Copyright © 2016. Published by Elsevier Inc.

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

    DEFF Research Database (Denmark)

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

    2009-01-01

    infarction, or stroke. We measured total and high-density lipoprotein cholesterol at baseline and annually during 4.8 years of losartan-based compared with atenolol-based treatment in 8611 patients with hypertension and left ventricular hypertrophy. RESULTS: Patients randomized to losartan-based or atenolol......-based treatment had similar baseline total (6.04 +/- 1.12 vs. 6.05 +/- 1.13 mmol/l, NS) and high-density lipoprotein (HDL) cholesterol (1.50 +/- 0.44 vs. 1.49 +/- 0.44 mmol/l, NS). Total cholesterol decreased significantly but equally (-0.37 +/- 1.05 vs. -0.34 +/- 1.09 mmol/l, NS), whereas HDL cholesterol......OBJECTIVE: Beta-blockers and angiotensin II receptor blockers have different effects on lipids. METHODS: We examined lipid levels in the Losartan Intervention For Endpoint reduction in hypertension study and their impact on the primary composite endpoint of cardiovascular death, myocardial...

  7. The importance of frontal QRS-T angle for predicting non-dipper status in hypertensive patients without left ventricular hypertrophy.

    Science.gov (United States)

    Tanriverdi, Zulkif; Unal, Baris; Eyuboglu, Mehmet; Bingol Tanriverdi, Tugba; Nurdag, Abdullah; Demirbag, Recep

    2017-09-26

    Frontal QRS-T angle is a novel marker of myocardial repolarization, and an increased frontal QRS-T angle associated with adverse cardiac outcomes. Non-dipper hypertension is also associated with adverse cardiac outcomes. This study aimed to investigate the relationship between frontal QRS-T angle and non-dipper status in hypertensive patients without left ventricular hypertrophy (LVH). This study included 122 hypertensive patients without LVH. Patients were divided into two groups: dipper hypertension and non-dipper hypertension. The frontal QRS-T angle was calculated from 12-lead electrocardiography. Frontal QRS-T angle (47.9° ± 29.7° vs. 26.7° ± 19.6°, P angle was positively correlated with sleeping systolic (r = 0.211, P = 0.020), and diastolic (r = 0.199, P = 0.028) blood pressures (BP), even if they were weak. Multivariate analysis showed that the frontal QRS-T angle was independent predictor of non-dipper status (QR: 1.037, 95% CI: 1.019-1.056, P angle is independent predictor of non-dipper status in hypertensive patients without LVH.

  8. Does QRS Voltage Correction by Body Mass Index Improve the Accuracy of Electrocardiography in Detecting Left Ventricular Hypertrophy and Predicting Cardiovascular Events in a General Population?

    Science.gov (United States)

    Cuspidi, Cesare; Facchetti, Rita; Bombelli, Michele; Sala, Carla; Tadic, Marijana; Grassi, Guido; Mancia, Giuseppe

    2016-05-01

    The authors assessed the value of body mass index (BMI) correction of two electrocardiographic criteria in improving detection of left ventricular hypertrophy (LVH) and prediction of cardiovascular and all-cause mortality in the Italian study Pressioni Arteriose Monitorate E Loro Associazioni (PAMELA) population. At entry, 1549 patients underwent diagnostic tests, 24-hour ambulatory blood pressure (BP) monitoring, standard electrocardiography, and echocardiography. The BMI-corrected Cornell voltage and Sokolow-Lyon voltage criteria provided better results for detection of echocardiographic LVH as compared with unadjusted electrocardiographic parameters. Cornell voltage index, but not Sokolow-Lyon index, was associated with an increased risk of cardiovascular events (and all-cause mortality). The adjusted risk of cardiovascular events related to one-standard deviation increment of BMI-corrected Cornell voltage was similar to that conferred by the uncorrected criterion in the total population, but outperformed in obese participants. These findings show that correction for BMI may improve the diagnostic accuracy of Cornell voltage index in detecting LVH and prediction of cardiovascular mortality in obese individuals. © 2015 Wiley Periodicals, Inc.

  9. Addition of N-terminal pro-B-type natriuretic peptide levels to electrocardiography criteria for detection of left ventricular hypertrophy: the ARIRANG study.

    Science.gov (United States)

    Ahn, Min-Soo; Yoo, Byung-Su; Lee, Ji Hyun; Lee, Jun-Won; Youn, Young Jin; Ahn, Sung Gyun; Kim, Jang-Young; Lee, Seung-Hwan; Yoon, Junghan; Park, Jong-Ku; Ahn, Song Vogue; Choi, Eunhee

    2015-04-01

    The utility of electrocardiography (ECG) in screening for left ventricular hypertrophy (LVH) in general populations is limited mainly because its low sensitivity. B-type natriuretic peptide (BNP) is released due to the remodeling processes of LVH and could improve the diagnostic accuracy for the ECG criteria for LVH. We hypothesized that addition of BNP levels to ECG criteria could aid LVH detection compared with ECG alone in a general population. We enrolled consecutive 343 subjects from a community-based cohort. LVH was defined as LV mass index > 95 g/m(2) for females and > 115 g/m(2) for males according to echocardiography. The area under the receiver operator characteristic (ROC) curve to detect LVH was 0.55 (95% confidence interval [CI], 0.50-0.61) in Sokolow-Lyon criteria and 0.53 (0.47-0.59) in the Cornell voltage criteria. After addition of N-terminal-proBNP levels to the model, the corresponding areas under the ROC were 0.63 (0.58-0.69) and 0.64 (0.59-0.69), respectively. P values for the comparison in areas under the ROC for models with and without N-terminal-proBNP levels were < 0.001. These data suggest that addition of N-terminal-proBNP levels to ECG criteria could significantly improve the diagnostic accuracy of LVH in general populations.

  10. Early marker of regional left ventricular deformation in patients with hypertrophic cardiomyopathy evaluated by MRI tissue tracking: The effects of myocardial hypertrophy and fibrosis.

    Science.gov (United States)

    Xu, Hua-Yan; Chen, Jing; Yang, Zhi-Gang; Li, Rui; Shi, Ke; Zhang, Qin; Liu, Xi; Xie, Lin-Jun; Jiang, Li; Guo, Ying-Kun

    2017-11-01

    To evaluate the regional left ventricular (LV) myocardial strain of early stage hypertrophic cardiomyopathy (HCM) patients by magnetic resonance (MR) tissue tracking. In all, 114 adult HCM patients classified as NYHA I or II and 32 healthy volunteers were enrolled and underwent 3.0T MR examination. Vertical 2-chamber long axis, horizontal 4-chamber, and short axis cine sequence as well as late gadolinium enhancement images (LGE) were scanned. The cardiac function, regional LV tissue tracking variables, end-diastolic wall thickness (EDTH), and LGE extent were measured. In the HCM group, 38 were NYHA I and 76 were NYHA II. By regional analysis, peak strain (PS) and peak displacement (PD) with radial, circumferential direction of hypertrophic segments (n = 283) were significantly lower than nonhypertrophic segments (n = 1541) (all P hypertrophic and fibrotic segments of early-stage HCM patients can be measured by MR tissue tracking based on routine cine images. Moreover, myocardial strain may decrease with the increasing of myocardial hypertrophy as well as fibrosis. 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017;46:1368-1376. © 2017 International Society for Magnetic Resonance in Medicine.

  11. Voltage dependent potassium channel remodeling in murine intestinal smooth muscle hypertrophy induced by partial obstruction.

    Directory of Open Access Journals (Sweden)

    Dong-Hai Liu

    Full Text Available Partial obstruction of the small intestine causes obvious hypertrophy of smooth muscle cells and motility disorder in the bowel proximate to the obstruction. To identify electric remodeling of hypertrophic smooth muscles in partially obstructed murine small intestine, the patch-clamp and intracellular microelectrode recording methods were used to identify the possible electric remodeling and Western blot, immunofluorescence and immunoprecipitation were utilized to examine the channel protein expression and phosphorylation level changes in this research. After 14 days of obstruction, partial obstruction caused obvious smooth muscle hypertrophy in the proximally located intestine. The slow waves of intestinal smooth muscles in the dilated region were significantly suppressed, their amplitude and frequency were reduced, whilst the resting membrane potentials were depolarized compared with normal and sham animals. The current density of voltage dependent potassium channel (KV was significantly decreased in the hypertrophic smooth muscle cells and the voltage sensitivity of KV activation was altered. The sensitivity of KV currents (IKV to TEA, a nonselective potassium channel blocker, increased significantly, but the sensitivity of IKv to 4-AP, a KV blocker, stays the same. The protein levels of KV4.3 and KV2.2 were up-regulated in the hypertrophic smooth muscle cell membrane. The serine and threonine phosphorylation levels of KV4.3 and KV2.2 were significantly increased in the hypertrophic smooth muscle cells. Thus this study represents the first identification of KV channel remodeling in murine small intestinal smooth muscle hypertrophy induced by partial obstruction. The enhanced phosphorylations of KV4.3 and KV2.2 may be involved in this process.

  12. Augmented sphingosine 1 phosphate receptor-1 signaling in cardiac fibroblasts induces cardiac hypertrophy and fibrosis through angiotensin II and interleukin-6

    Science.gov (United States)

    Ohkura, Sei-ichiro; Takashima, Shin-ichiro; Yoshioka, Kazuaki; Okamoto, Yasuo; Inagaki, Yutaka; Sugimoto, Naotoshi; Kitano, Teppei; Takamura, Masayuki; Wada, Takashi; Kaneko, Shuichi; Takuwa, Yoh

    2017-01-01

    Background: Cardiac fibroblasts, together with cardiomyocytes, occupy the majority of cells in the myocardium and are involved in myocardial remodeling. The lysophospholipid mediator sphigosine-1-phosphate (S1P) regulates functions of cardiovascular cells through multiple receptors including S1PR1–S1PR3. S1PR1 but not other S1P receptors was upregulated in angiotensin II-induced hypertrophic hearts. Therefore, we investigated a role of S1PR1 in fibroblasts for cardiac remodeling by employing transgenic mice that overexpressed S1PR1 under the control of α-smooth muscle actin promoter. In S1PR1-transgenic mouse heart, fibroblasts and/or myofibroblasts were hyperplastic, and those cells as well as vascular smooth muscle cells overexpressed S1PR1. Transgenic mice developed bi-ventricular hypertrophy by 12-week-old and diffuse interstitial fibrosis by 24-week-old without hemodynamic stress. Cardiac remodeling in transgenic mice was associated with greater ERK phosphorylation, upregulation of fetal genes, and systolic dysfunction. Transgenic mouse heart showed increased mRNA expression of angiotensin-converting enzyme and interleukin-6 (IL-6). Isolated fibroblasts from transgenic mice exhibited enhanced generation of angiotensin II, which in turn stimulated IL-6 release. Either an AT1 blocker or angiotensin-converting enzyme inhibitor prevented development of cardiac hypertrophy and fibrosis, systolic dysfunction and increased IL-6 expression in transgenic mice. Finally, administration of anti-IL-6 antibody abolished an increase in tyrosine phosphorylation of STAT3, a major signaling molecule downstream of IL-6, in the transgenic mouse heart and prevented development of cardiac hypertrophy in transgenic mice. These results demonstrate a promoting role of S1PR1 in cardiac fibroblasts for cardiac remodeling, in which angiotensin II—AT1 and IL-6 are involved. PMID:28771545

  13. Coronary artery disease, left ventricular hypertrophy and diastolic dysfunction are associated with stroke in patients affected by persistent non-valvular atrial fibrillation: a case-control study

    Directory of Open Access Journals (Sweden)

    Andrea Passantino

    2009-04-01

    Full Text Available Persistent non-valvular atrial fibrillation (NVAF is associated with an increased risk of cardiovascular events such as stroke, and its rate is expected to rise because of the ageing population. The absolute rate of stroke depends on age and comorbidity. Risk stratification for stroke in patients with NVAF derives from populations enrolled in randomized clinical trials. However, participants in clinical trials are often not representative of the general population. Many stroke risk stratification scores have been used, but they do not include transthoracic echocardiogram (TTE, pulsate wave Doppler (PWD and tissue Doppler imaging (TDI, simple and non-invasive diagnostic tools. The role of TTE, PWD and TDI findings has not been previously determined. Our study goal was to determine the association between TTE and PWD findings and stroke prevalence in a population of NVAF prone outpatients. Patients were divided into two groups: P for stroke prone and F for stroke free. There were no statistically significant differences between the two groups concerning cardiovascular risk factors, age (p=0.2, sex (p=0.2, smoking (p=0.3, diabetes (p=0.1 and hypercholesterolemia (p=0.2; hypertension was statistically significant (p less than 0.001. There were statistically significant differences concerning coronary artery disease, previous acute myocardial infarction (AMI (p less than 0.05 and non- AMI coronaropathy (p less than 0.04, a higher rate being in the P group. Concerning echo-Doppler findings, a higher statistically significant rate of left ventricular hypertrophy (LVH (p less than  0.05 and left ventricular diastolic dysfunction (p less than 0.001 was found in the P group and dilated left atrium (p Cardiac Specific, Inducible ClC-3 Gene Deletion Eliminates Native Volume-Sensitive Chloride Channels and Produces Myocardial Hypertrophy in Adult Mice

    Science.gov (United States)

    Xiong, Dazhi; Heyman, Nathanael S.; Airey, Judith; Zhang, Mi; Singer, Cherie A.; Rawat, Shanti; Ye, Linda; Evans, Rebecca; Burkin, Dean J.; Tian, Honglin; McCloskey, Diana T; Valencik, Maria; Britton, Fiona C.; Duan, Dayue; Hume, Joseph R.

    2009-01-01

    Native volume-sensitive outwardly rectifying anion channels (VSOACs) play a significant role in cell volume homeostasis in mammalian cells. However, the molecular correlate of VSOACs has been elusive to identify. The short isoform of ClC-3 (sClC-3) is a member of the mammalian ClC gene family and has been proposed to be a molecular candidate for VSOACs in cardiac myocytes and vascular smooth muscle cells. To directly test this hypothesis, and assess the physiological role of ClC-3 in cardiac function, we generated a novel line of cardiac specific inducible ClC-3 knock-out mice. These transgenic mice were maintained on a doxycycline diet to preserve ClC-3 expression; removal of doxycycline activates Cre recombinase to inactivate the Clcn3 gene. Echocardiography revealed dramatically reduced ejection fraction and fractional shortening, and severe signs of myocardial hypertrophy and heart failure in the knock-out mice at both 1.5 and 3 weeks off doxycycline. In mice off doxyclycline, time-dependent inactivation of ClC-3 gene expression was confirmed in atrial and ventricular cells by qRT-PCR and Western blot analysis. Electrophysiological examination of native VSOACs in isolated atrial and ventricular myocytes 3 weeks off doxycycline revealed a complete elimination of the currents, whereas at 1.5 weeks, VSOAC current densities were significantly reduced, compared to age-matched control mice maintained on doxycycline. These results indicate that ClC-3 is a key component of native VSOACs in mammalian heart and plays a significant cardioprotective role against cardiac hypertrophy and failure. PMID:19615374

  14. Cardiac-specific, inducible ClC-3 gene deletion eliminates native volume-sensitive chloride channels and produces myocardial hypertrophy in adult mice.

    Science.gov (United States)

    Xiong, Dazhi; Heyman, Nathanael S; Airey, Judith; Zhang, Mi; Singer, Cherie A; Rawat, Shanti; Ye, Linda; Evans, Rebecca; Burkin, Dean J; Tian, Honglin; McCloskey, Diana T; Valencik, Maria; Britton, Fiona C; Duan, Dayue; Hume, Joseph R

    2010-01-01

    Native volume-sensitive outwardly rectifying anion channels (VSOACs) play a significant role in cell volume homeostasis in mammalian cells. However, the molecular correlate of VSOACs has been elusive to identify. The short isoform of ClC-3 (sClC-3) is a member of the mammalian ClC gene family and has been proposed to be a molecular candidate for VSOACs in cardiac myocytes and vascular smooth muscle cells. To directly test this hypothesis, and assess the physiological role of ClC-3 in cardiac function, we generated a novel line of cardiac-specific inducible ClC-3 knock-out mice. These transgenic mice were maintained on a doxycycline diet to preserve ClC-3 expression; removal of doxycycline activates Cre recombinase to inactivate the Clcn3 gene. Echocardiography revealed dramatically reduced ejection fraction and fractional shortening, and severe signs of myocardial hypertrophy and heart failure in the knock-out mice at both 1.5 and 3 weeks off doxycycline. In mice off doxycycline, time-dependent inactivation of ClC-3 gene expression was confirmed in atrial and ventricular cells by qRT-PCR and Western blot analysis. Electrophysiological examination of native VSOACs in isolated atrial and ventricular myocytes 3 weeks off doxycycline revealed a complete elimination of the currents, whereas at 1.5 weeks, VSOAC current densities were significantly reduced, compared to age-matched control mice maintained on doxycycline. These results indicate that ClC-3 is a key component of native VSOACs in mammalian heart and plays a significant cardioprotective role against cardiac hypertrophy and failure. Copyright 2009 Elsevier Inc. All rights reserved.

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    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......, 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...... 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...

  16. Cardiomyocyte Overexpression of FABP4 Aggravates Pressure Overload-Induced Heart Hypertrophy.

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    Ji Zhang

    Full Text Available Fatty acid binding protein 4 (FABP4 is a member of the intracellular lipid-binding protein family, responsible for the transportation of fatty acids. It is considered to express mainly in adipose tissues, and be strongly associated with inflammation, obesity, diabetes and cardiovasculardiseases. Here we report that FABP4 is also expressed in cardiomyocytes and plays an important role in regulating heart function under pressure overload. We generated heart-specific transgenic FABP4 (FABP4-TG mice using α myosin-heavy chain (α-MHC promoter and human FABP4 sequence, resulting in over-expression of FABP4 in cardiomyocytes. The FABP4-TG mice displayed normal cardiac morphology and contractile function. When they were subjected to the transverse aorta constriction (TAC procedure, the FABP4-TG mice developed more cardiac hypertrophy correlated with significantly increased ERK phosphorylation, compared with wild type controls. FABP4 over-expression in cardiomyocytes activated phosphor-ERK signal and up-regulate the expression of cardiac hypertrophic marker genes. Conversely, FABP4 induced phosphor-ERK signal and hypertrophic gene expressions can be markedly inhibited by an ERK inhibitor PD098059 as well as the FABP4 inhibitor BMS309403. These results suggest that FABP4 over-expression in cardiomyocytes can aggravate the development of cardiac hypertrophy through the activation of ERK signal pathway.

  17. Nutritional interventions to augment resistance training-induced skeletal muscle hypertrophy

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    Robert W Morton

    2015-09-01

    Full Text Available Skeletal muscle mass is regulated by a balance between muscle protein synthesis (MPS and muscle protein breakdown (MPB. In healthy humans, MPS is more sensitive (varying 4-5 times more than MPB to changes in protein feeding and loading indicating that it is the primary locus determining gains in muscle mass. Performing resistance exercise (RE followed by the consumption of protein results in an augmentation of MPS and, over time, can lead to muscle hypertrophy. The magnitude of the RE-induced increase in MPS (and potentially subsequent hypertrophy is dictated by a variety of factors including: the dose of protein, source of protein, and possibly the distribution and timing of post-exercise protein ingestion. In addition, RE variables such as frequency of sessions, time under tension, volume, and training status play roles in regulating MPS. This review provides a brief overview of our current understanding of how RE and protein ingestion can influence gains in skeletal muscle mass in young, healthy individuals. It is the goal of this review to provide nutritional recommendations for optimal skeletal muscle adaptation. Specifically, we will focus on how the manipulation of protein intake during the recovery period following RE augments the adaptive response.

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

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    Rosana dos Santos e Silva Martin

    2012-01-01

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

  19. Renal ischemia/reperfusion-induced cardiac hypertrophy in mice: Cardiac morphological and morphometric characterization

    Science.gov (United States)

    Cirino-Silva, Rogério; Kmit, Fernanda V; Trentin-Sonoda, Mayra; Nakama, Karina K; Panico, Karine; Alvim, Juliana M; Dreyer, Thiago R; Martinho-Silva, Herculano

    2017-01-01

    Background Tissue remodeling is usually dependent on the deposition of extracellular matrix that may result in tissue stiffness and impaired myocardium contraction. Objectives We had previously demonstrated that renal ischemia/reperfusion (I/R) is able to induce development of cardiac hypertrophy in mice. Therefore, we aimed to characterize renal I/R-induced cardiac hypertrophy. Design C57BL/6 J mice were subjected to 60 minutes’ unilateral renal pedicle occlusion, followed by reperfusion (I/R) for 5, 8, 12 or 15 days. Gene expression, protein abundance and morphometric analyses were performed in all time points. Results Left ventricle wall thickening was increased after eight days of reperfusion (p < 0.05). An increase in the number of heart ventricle capillaries and diameter after 12 days of reperfusion (p < 0.05) was observed; an increase in the density of capillaries starting at 5 days of reperfusion (p < 0.05) was also observed. Analyses of MMP2 protein levels showed an increase at 15 days compared to sham (p < 0.05). Moreover, TGF-β gene expression was downregulated at 12 days as well TIMP 1 and 2 (p < 0.05). The Fourier-transform infrared spectroscopy analysis showed that collagen content was altered only in the internal section of the heart (p < 0.05); such data were supported by collagen mRNA levels. Conclusions Renal I/R leads to impactful changes in heart morphology, accompanied by an increase in microvasculature. Although it is clear that I/R is able to induce cardiac remodeling, such morphological changes is present in only a section of the heart tissue. PMID:28228941

  1. Renal ischemia/reperfusion-induced cardiac hypertrophy in mice: Cardiac morphological and morphometric characterization

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    Rogério Cirino-Silva

    2017-01-01

    Full Text Available Background Tissue remodeling is usually dependent on the deposition of extracellular matrix that may result in tissue stiffness and impaired myocardium contraction. Objectives We had previously demonstrated that renal ischemia/reperfusion (I/R is able to induce development of cardiac hypertrophy in mice. Therefore, we aimed to characterize renal I/R-induced cardiac hypertrophy. Design C57BL/6 J mice were subjected to 60 minutes’ unilateral renal pedicle occlusion, followed by reperfusion (I/R for 5, 8, 12 or 15 days. Gene expression, protein abundance and morphometric analyses were performed in all time points. Results Left ventricle wall thickening was increased after eight days of reperfusion (p < 0.05. An increase in the number of heart ventricle capillaries and diameter after 12 days of reperfusion (p < 0.05 was observed; an increase in the density of capillaries starting at 5 days of reperfusion (p < 0.05 was also observed. Analyses of MMP2 protein levels showed an increase at 15 days compared to sham (p < 0.05. Moreover, TGF-β gene expression was downregulated at 12 days as well TIMP 1 and 2 (p < 0.05. The Fourier-transform infrared spectroscopy analysis showed that collagen content was altered only in the internal section of the heart (p < 0.05; such data were supported by collagen mRNA levels. Conclusions Renal I/R leads to impactful changes in heart morphology, accompanied by an increase in microvasculature. Although it is clear that I/R is able to induce cardiac remodeling, such morphological changes is present in only a section of the heart tissue.

  2. Quantitative Positron Emission Tomography Imaging Detects Early Metabolic Remodeling in a Mouse Model of Pressure Overload Left Ventricular Hypertrophy in vivo

    Science.gov (United States)

    Zhong, Min; Alonso, Clayton E.; Taegtmeyer, Heinrich; Kundu, Bijoy K.

    2013-01-01

    We proposed that metabolic remodeling in the form of increased myocardial glucose analogue 2-[18F] fluoro-2deoxy-D-glucose (FDG) uptake precedes and triggers the onset of severe contractile dysfunction in pressure overload left ventricular hypertrophy (LVH) in vivo. To test this hypothesis we used a mouse model of transverse aortic constriction (TAC) together with Positron Emission Tomography (PET) and assessed serial changes in cardiac metabolism and function over 7 days. Methods PET scans of 16 C57BL/6 male mice were performed using a microPET scanner under sevofluorane anesthesia. A 10-minute transmission scan was followed by a 60-minute dynamic FDG-PET scan with cardiac and respiratory gating. Blood glucose levels were measured before and after the emission scan. Transverse aortic constriction (TAC) and sham surgeries were performed after baseline imaging. Osmotic mini-pumps containing either propranolol (5 mg/kg/day) or vehicle alone were implanted subcutaneously at the end of surgery. Subsequent scans were taken at days 1 and 7 after surgery. A compartment model, in which the blood input function with spill-over and partial volume corrections and the metabolic rate constants in a 3-compartment model are simultaneously estimated, was used to determine the net myocardial FDG influx constant, Ki. The rate of myocardial glucose use, rMGU, was also computed. Estimations of the ejection fractions (EF) were based on the high resolution gated PET images Results Mice undergoing TAC surgery exhibited an increase in the Ki (580%) and glucose usage the day after surgery indicating early adaptive response. On day 7 the EF had decreased by 24% indicating a maladaptive response. Average Ki increases were not linearly associated with increases in rMGU. Ki exceeded rMGU by 29% in the TAC mice. TAC Mice treated with propranolol attenuated rate of FDG uptake, diminished mismatch between Ki and rMGU (9%) and rescued cardiac function. Conclusions Metabolic maladaptation precedes

  3. C-Myc Induced Compensated Cardiac Hypertrophy Increases Free Fatty Acid Utilization for the Citric Acid Cycle

    Energy Technology Data Exchange (ETDEWEB)

    Olson, Aaron; Ledee, Dolena; Iwamoto, Kate; Kajimoto, Masaki; O' Kelly-Priddy, Colleen M.; Isern, Nancy G.; Portman, Michael A.

    2013-02-01

    The protooncogene C-Myc (Myc) regulates cardiac hypertrophy. Myc promotes compensated cardiac function, suggesting that the operative mechanisms differ from those leading to heart failure. Myc regulation of substrate metabolism is a reasonable target, as Myc alters metabolism in other tissues. We hypothesize that Myc-induced shifts in substrate utilization signal and promote compensated hypertrophy. We used cardiac specific Myc-inducible C57/BL6 male mice between 4-6 months old that develop hypertrophy with tamoxifen (tam). Isolated working hearts and 13Carbon (13C )-NMR were used to measure function and fractional contributions (Fc) to the citric acid cycle by using perfusate containing 13C-labeled free fatty acids, acetoacetate, lactate, unlabeled glucose and insulin. Studies were performed at pre-hypertrophy (3-days tam, 3dMyc), established hypertrophy (7-days tam, 7dMyc) or vehicle control (cont). Non-transgenic siblings (NTG) received 7-days tam or vehicle to assess drug effect. Hypertrophy was confirmed by echocardiograms and heart weights. Western blots were performed on key metabolic enzymes. Hypertrophy occurred in 7dMyc only. Cardiac function did not differ between groups. Tam alone did not affect substrate contribution in NTG. Substrate utilization was not significantly altered in 3dMyc versus cont. The free fatty acid FC was significantly greater in 7dMyc vs cont with decreased unlabeled Fc, which is predominately exogenous glucose. Free fatty acid flux to the citric acid cycle increased while lactate flux was diminished in 7dMyc compared to cont. Total protein levels of a panel of key metabolic enzymes were unchanged; however total protein O-GlcNAcylation was increased in 7dMyc. Substrate utilization changes did not precede hypertrophy; therefore they are not the primary signal for cardiac growth in this model. Free fatty acid utilization and oxidation increase at established hypertrophy. Understanding the mechanisms whereby this change maintained

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

    DEFF Research Database (Denmark)

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

    2005-01-01

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

  5. Perinatal DDT Exposure Induces Hypertension and Cardiac Hypertrophy in Adult Mice.

    Science.gov (United States)

    La Merrill, Michele A; Sethi, Sunjay; Benard, Ludovic; Moshier, Erin; Haraldsson, Borje; Buettner, Christoph

    2016-11-01

    Dichlorodiphenyltrichloroethane (DDT) was used extensively to control malaria, typhus, body lice, and bubonic plague worldwide, until countries began restricting its use in the 1970s. However, the use of DDT to control vector-borne diseases continues in developing countries. Prenatal DDT exposure is associated with elevated blood pressure in humans. We hypothesized that perinatal DDT exposure causes hypertension in adult mice. DDT was administered to C57BL/6J dams from gestational day 11.5 to postnatal day 5. Blood pressure (BP) and myocardial wall thickness were measured in male and female adult offspring. Adult mice were treated with an angiotensin converting enzyme (ACE) inhibitor, captopril, to evaluate sensitivity to amelioration of DDT-associated hypertension by ACE inhibition. We further assessed the influence of DDT exposure on the expression of mRNAs that regulate BP through renal ion transport. Adult mice perinatally exposed to DDT exhibited chronically increased systolic BP, increased myocardial wall thickness, and elevated expression of mRNAs of several renal ion transporters. Captopril completely reversed hypertension in mice perinatally exposed to DDT. These data demonstrate that perinatal exposure to DDT causes hypertension and cardiac hypertrophy in adult offspring. A key mechanism underpinning this hypertension is an overactivated renin angiotensin system because ACE inhibition reverses the hypertension induced by perinatal DDT exposure. Citation: La Merrill M, Sethi S, Benard L, Moshier E, Haraldsson B, Buettner C. 2016. Perinatal DDT exposure induces hypertension and cardiac hypertrophy in adult mice. Environ Health Perspect 124:1722-1727; http://dx.doi.org/10.1289/EHP164.

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

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    A. Medeiros

    2004-12-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  8. Fish protein intake induces fast-muscle hypertrophy and reduces liver lipids and serum glucose levels in rats.

    Science.gov (United States)

    Kawabata, Fuminori; Mizushige, Takafumi; Uozumi, Keisuke; Hayamizu, Kohsuke; Han, Li; Tsuji, Tomoko; Kishida, Taro

    2015-01-01

    In our previous study, fish protein was proven to reduce serum lipids and body fat accumulation by skeletal muscle hypertrophy and enhancing basal energy expenditure in rats. In the present study, we examined the precise effects of fish protein intake on different skeletal muscle fiber types and metabolic gene expression of the muscle. Fish protein increased fast-twitch muscle weight, reduced liver triglycerides and serum glucose levels, compared with the casein diet after 6 or 8 weeks of feeding. Furthermore, fish protein upregulated the gene expressions of a fast-twitch muscle-type marker and a glucose transporter in the muscle. These results suggest that fish protein induces fast-muscle hypertrophy, and the enhancement of basal energy expenditure by muscle hypertrophy and the increase in muscle glucose uptake reduced liver lipids and serum glucose levels. The present results also imply that fish protein intake causes a slow-to-fast shift in muscle fiber type.

  9. The impact of electrocardiographic left ventricular hypertrophy and bundle branch block on the triage and outcome of ED patients with a suspected acute coronary syndrome: a multicenter study.

    Science.gov (United States)

    Pope, J Hector; Ruthazer, Robin; Kontos, Michael C; Beshansky, Joni R; Griffith, John L; Selker, Harry P

    2004-05-01

    We studied the impact on triage and outcome of the presence of left ventricular hypertrophy (LVH) and left/right bundle branch block (LBBB/RBBB) on the initial ED electrocardiogram (ECG) for patients with symptoms suggestive of an acute coronary syndrome (ACS). Secondary analysis of data from a prospective clinical trial of patients with chest pain or other symptoms suggesting ACS in six U.S. hospitals comparing patient demographics, clinical variables, and outcomes was used. Of 5,324 study patients, 3% had ECG-LVH, 3% had LBBB, 3% had RBBB, and 43% had ischemic ST segment or T wave abnormalities. Compared with patients without ST segment or T wave abnormalities, patients with ECG-LVH or BBB were older and were more likely to have a chief complaint of shortness of breath or a history of cardiac or related diseases. Patients with ECG-LVH or BBB had more diagnoses of congestive heart failure (CHF) and ACS compared with patients without these ECG abnormalities and were just as likely to have ACS as their diagnosis compared with patients with ischemic ST segment or T wave abnormalities. Having ECG-LVH or BBB did not alter the true-positive rate for ACS but increased the false-positive rate by almost 50%. Patients with ECG-LVH had approximately 3.5 times the 30-day mortality rate as those without these ECG abnormalities. It appears that for patients with symptoms suggestive of ACS, the presence of ECG-LVH or BBB did not alter the ability of ED clinicians to identify patients with ACS but was associated with a 50% higher false-positive admission rate compared with similar patients without these ECG abnormalities. With a short-term mortality rate 3.5 times that for patients without ECG-LVH, selected patients with ECG-LVH and symptoms suggesting ACS might benefit from hospitalization for further evaluation.

  10. Prognostic usefulness of left ventricular hypertrophy by electrocardiography in patients with atrial fibrillation (from the Randomized Evaluation of Long-Term Anticoagulant Therapy Study).

    Science.gov (United States)

    Verdecchia, Paolo; Reboldi, Gianpaolo; Di Pasquale, Giuseppe; Mazzotta, Giovanni; Ambrosio, Giuseppe; Yang, Sean; Pogue, Janice; Wallentin, Lars; Ezekowitz, Michael D; Connolly, Stuart J; Yusuf, Salim

    2014-02-15

    It is unknown whether left ventricular hypertrophy (LVH) diagnosis by electrocardiography improves risk stratification in patients with atrial fibrillation (AF). We investigated the prognostic impact of LVH diagnosis by electrocardiography in a large sample of anticoagulated patients with AF included in the Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) Study. We defined electrographic LVH (ECG-LVH) by strain pattern or Cornell voltage (R wave in aVL plus S wave in V3) >2.0 mV (women) or >2.4 mV (men). LVH prevalence was 22.7%. During a median follow-up of 2.0 years, 303 patients developed a stroke, 778 died (497 from cardiovascular causes), and 140 developed a myocardial infarction. LVH was associated with a greater risk of stroke (1.99% vs 1.32% per year, hazard ratio [HR] 1.51, 95% confidence interval [CI] 1.18 to 1.93, p <0.001), cardiovascular death (4.52% vs 1.80% per year, HR 2.56, 95% CI 2.14 to 3.06, p <0.0001), all-cause death (6.03% vs 3.11% per year, HR 1.95, 95% CI 1.68 to 2.26, p <0.0001), and myocardial infarction (1.11% vs 0.55% per year, HR 2.07, 95% CI 1.47 to 2.92, p <0.0001). In multivariate analysis, the prognostic value of LVH was additive to CHA2DS2-VASc score and other covariates. The category-free net reclassification index and integrated discrimination improvement increased significantly after adding LVH to multivariate models. In conclusion, our study demonstrates for the first time that ECG-LVH, a simple and easily accessible prognostic indicator, improves risk stratification in anticoagulated patients with AF. Copyright © 2014 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2015-09-01

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

  12. Hypertrophic cardiomyopathy and left ventricular hypertrophy in hypertensive heart disease with mildly reduced or preserved ejection fraction: insight from altered mechanics and native T1 mapping.

    Science.gov (United States)

    Wu, L-M; An, D-A L; Yao, Q-Y; Ou, Y-R Z; Lu, Q; Jiang, M; Xu, J-R

    2017-10-01

    To explore the relationship between extracellular volume (ECV), native T1, and systolic strain in hypertrophic cardiomyopathy (HCM) and hypertensive patients with left ventricular hypertrophy (HTN LVH) with mildly reduced or preserved ejection fraction. T1 mapping was performed in 45 patients with late gadolinium enhancement positive (LGE+) HCM (mean age, 53±6 years), 11 patients with LGE- (LGE-) HCM (mean age, 56±5 years), and 20 patients with HTN LVH (mean age, 55±6 years) on at 3 T magnetic resonance imaging (MRI) using the modified look-locker inversion-recovery (MOLLI) pulse sequence. Mean T1 value, ECV and circumferential strain parameters were determined for each patient. Overall, the HCM patients had higher native T1 values (1242.92±68.94) and ECV (0.31±0.05) in comparison to those of the HTN LVH patients (1197±46.80, 0.27±0.04; p<0.05). In the subgroup analysis, the HCM LGE+ patients had the highest native T1 values among the three groups. The HCM LGE+ patients had higher ECV than the LGE- patients. HCM LGE- patients had higher ECV than HTN LVH patients (p<0.05). Peak systolic circumferential strain and early diastolic strain rates were reduced in the HCM LGE+ patients in comparison to the HCM LGE- and HTN LVH patients (p<0.05). Reduced peak systolic and early diastolic circumferential strain rates were associated with increased levels of ECV and native T1 values among all the patients. HCM LGE+ patients had higher native T1 values, higher ECV, and an associated reduction in early diastolic strain rates and peak systolic circumferential strains when compared to the HCM LGE- and HTN LVH patients with mildly reduced or preserved ejection fraction. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  13. QT corrected for heart rate and qtc dispersion in Gujarati type 2 diabetics predominantly using preventive pharmacotherapy and with very low electrocardiogram left ventricular hypertrophy

    Directory of Open Access Journals (Sweden)

    Jayesh Dalpatbhai Solanki

    2017-01-01

    Full Text Available Background: There is a rising trend in the incidence of type 2 diabetes mellitus, and hyperglycaemia is known to cause cardiac dysautonomia, which may lead to life-threatening arrhythmias. It can be screened by simple electrocardiogram (ECG-based QTc (QT corrected for heart rate and QTd (QTc dispersion indicating cardiac repolarisation abnormality. We studied QTc and QTd intervals in treated type 2 diabetics (T2D, testing the effect of age, gender, duration and control of disease. Materials and Methods: We conducted a cross-sectional study in a tertiary care teaching hospital of Gujarat, India, on 199 T2D (67 males and 132 females. Standard 12-lead ECG was recorded to derive QTc by Bazett's formula, QTd and ECG left ventricular hypertrophy (LVH. QTc> 0.43 s in male and> 0.45 s in female, QTd> 80 msec were considered abnormal. Results: T2D (mean age 56 years, duration 6 years, coexisting hypertension 69%, glycaemic control 32% and use of β-blockers 56% had QTc and QTd abnormality prevalence 15% and 20% respectively with ECG LVH prevailing in 3%. Male gender, poor glycaemic control and increased duration had negative impact on QT parameters with statistical significance only for first two and not for all results. Conclusion: Our study showed low-to-moderate prevalence of prolonged QTc and QTd, qualitatively more than quantitatively, in T2D with very low LVH and high prevalence of preventive pharmacotherapy, associated with male gender and glycaemic control. It underscores high risk of repolarisation abnormality, though moderate, that can be further primarily prevented by early screening and strict disease control.

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

    Directory of Open Access Journals (Sweden)

    Wegscheider Karl

    2006-10-01

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

  15. Tempol improves lipid profile and prevents left ventricular hypertrophy in LDL receptor gene knockout (LDLr-/-) mice on a high-fat diet.

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    Viana Gonçalves, Igor Cândido; Cerdeira, Cláudio Daniel; Poletti Camara, Eduardo; Dias Garcia, José Antônio; Ribeiro Pereira Lima Brigagão, Maísa; Bessa Veloso Silva, Roberta; Bitencourt Dos Santos, Gérsika

    2017-09-01

    Dyslipidemia is associated with increased risk of cardiovascular disease and atherosclerosis, and hence with high morbidity and mortality. This study investigated the effects of the nitroxide 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (Tempol) on lipid profile and cardiac morphology in low-density lipoprotein (LDL) receptor gene knockout (LDLr-/-) mice. Male LDLr-/- mice (three months old, approximately 22 g weight) were divided into the following groups: controls, including (1) standard chow (SC, n=8) and (2) high-fat diet (HFD, n=8); and treatment, including (3) standard chow + Tempol (SC+T, n=8) (30 mg/kg administered by gavage, once daily) and (4) high-fat diet + Tempol (HFD+T, n=8) (30 mg/kg). After 30 days of the diet/treatment, whole blood was collected for analysis of biochemical parameters (total cholesterol, triglycerides [TG], high-density lipoprotein [HDL], LDL, and very low-density lipoprotein [VLDL]). The heart was removed through thoracotomy and histological analysis of the left ventricle was performed. A significant increase in TG, LDL, and VLDL and marked left ventricular hypertrophy (LVH) were demonstrated in the HFD group relative to the SC group (p<0.05), while Tempol treatment (HFD+T group) significantly (p<0.05) prevented increases in the levels of these lipid profile markers and attenuated LVH compared with the HFD group. In this study, Tempol showed potential for the prevention of events related to serious diseases of the cardiovascular system. Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. The association of left ventricular hypertrophy with metabolic syndrome is dependent on body mass index in hypertensive overweight or obese patients.

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    Federico Guerra

    Full Text Available BACKGROUND: Overweight (Ow and obesity (Ob influence blood pressure (BP and left ventricular hypertrophy (LVH. It is unclear whether the presence of metabolic syndrome (MetS independently affects echocardiographic parameters in hypertension. METHODS: 380 Ow/Ob essential hypertensive patients (age ≤ 65 years presenting for referred BP control-related problems. MetS was defined according to NCEP III/ATP with AHA modifications and LVH as LVM/h(2.7 ≥ 49.2 g/m(2.7 in males and ≥ 46.7 g/m(2.7 in females. Treatment intensity score (TIS was used to control for BP treatment as previously reported. RESULTS: Hypertensive patients with MetS had significantly higher BMI, systolic and mean BP, interventricular septum and relative wall thickness and lower ejection fraction than those without MetS. LVM/h(2.7 was significantly higher in MetS patients (59.14 ± 14.97 vs. 55.33 ± 14.69 g/m(2.7; p = 0.022. Hypertensive patients with MetS had a 2.3-fold higher risk to have LVH/h(2.7 after adjustment for age, SBP and TIS (OR 2.34; 95%CI 1.40-3.92; p = 0.001, but MetS lost its independent relationship with LVH when BMI was included in the model. CONCLUSIONS: In Ow/Ob hypertensive patients MetS maintains its role of risk factor for LVH independently of age, SBP, and TIS, resulting in a useful predictor of target organ damage in clinical practice. However, MetS loses its independent relationship when BMI is taken into account, suggesting that the effects on MetS on LV parameters are mainly driven by the degree of adiposity.

  17. Polyphenol rich ethanolic extract from Boerhavia diffusa L. mitigates angiotensin II induced cardiac hypertrophy and fibrosis in rats.

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    A, Prathapan; Varghese, Mathews V; S, Abhilash; P, Salin Raj; Mathew, Anil K; Nair, Anupama; Nair, R Harikumaran; K G, Raghu

    2017-03-01

    Boerhavia diffusa is a renowned edible medicinal plant extensively used against different ailments including heart diseases in the traditional system of medicine in several countries. The present study aims to evaluate the therapeutic efficacy of ethanolic extract of Boerhavia diffusa (BDE) on cardiac hypertrophy and fibrosis induced by angiotensin II (Ang II) in male wistar rats and to identify the active components present in it. A substantial increase of hypertrophy markers such as cardiac mass index, concentration of ANP and BNP, cardiac injury markers like CK-MB, LDH and SGOT, has been observed in hypertrophied groups whereas BDE treatment attenuated these changes when compared to hypertrophied rats. Moreover, Ang II induced myocardial oxidative stress was reduced by BDE which was apparent from diminished level of lipid and protein oxidation products, increased activities of membrane bound ATPases and endogenous antioxidant enzymes along with enhanced translocation of Nrf2 from the cytosol to nucleus. It appears that BDE evokes its antioxidant effects by attenuating lipid peroxidation, enhancing the translocation of Nrf2 from the cytoplasm to nucleus as well as by regulating the metabolism of glutathione. The extent of fibrosis during cardiac hypertrophy was determined by histopathology analysis and the results revealed that BDE treatment considerably reduced the fibrosis in the heart. HPLC analysis of BDE leads to the identification of four compounds viz., quercetin, kaempferol, boeravinone B and caffeic acid. The study substantiate the effect of B. diffusa in protecting the heart from pathological hypertrophy and the attenuation of cardiac abnormalities may be partly attributed through the reduction of oxidative stress and cardiac fibrosis. Since the plant is widely used as a green leafy vegetable, incorporation of this plant in diet may be an alternative way for the prevention and better management of heart diseases and associated complications. Copyright

  18. Syndecan-4 is essential for development of concentric myocardial hypertrophy via stretch-induced activation of the calcineurin-NFAT pathway.

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    Alexandra V Finsen

    Full Text Available Sustained pressure overload leads to compensatory myocardial hypertrophy and subsequent heart failure, a leading cause of morbidity and mortality. Further unraveling of the cellular processes involved is essential for development of new treatment strategies. We have investigated the hypothesis that the transmembrane Z-disc proteoglycan syndecan-4, a co-receptor for integrins, connecting extracellular matrix proteins to the cytoskeleton, is an important signal transducer in cardiomyocytes during development of concentric myocardial hypertrophy following pressure overload. Echocardiographic, histochemical and cardiomyocyte size measurements showed that syndecan-4(-/- mice did not develop concentric myocardial hypertrophy as found in wild-type mice, but rather left ventricular dilatation and dysfunction following pressure overload. Protein and gene expression analyses revealed diminished activation of the central, pro-hypertrophic calcineurin-nuclear factor of activated T-cell (NFAT signaling pathway. Cardiomyocytes from syndecan-4(-/--NFAT-luciferase reporter mice subjected to cyclic mechanical stretch, a hypertrophic stimulus, showed minimal activation of NFAT (1.6-fold compared to 5.8-fold increase in NFAT-luciferase control cardiomyocytes. Accordingly, overexpression of syndecan-4 or introducing a cell-permeable membrane-targeted syndecan-4 polypeptide (gain of function activated NFATc4 in vitro. Pull-down experiments demonstrated a direct intracellular syndecan-4-calcineurin interaction. This interaction and activation of NFAT were increased by dephosphorylation of serine 179 (pS179 in syndecan-4. During pressure overload, phosphorylation of syndecan-4 was decreased, and association between syndecan-4, calcineurin and its co-activator calmodulin increased. Moreover, calcineurin dephosphorylated pS179, indicating that calcineurin regulates its own binding and activation. Finally, patients with hypertrophic myocardium due to aortic stenosis had

  19. Resveratrol Attenuated Low Ambient Temperature-Induced Myocardial Hypertrophy via Inhibiting Cardiomyocyte Apoptosis

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    Kun Yin

    2015-04-01

    Full Text Available Background/Aims: Low ambient temperature is an important risk factor for cardiovascular diseases, and has been shown to lead to cardiac hypertrophy. In this study, we aim to investigate if Resveratrol may inhibit cold exposure-induced cardiac hypertrophy in mice, and if so to clarify its molecular mechanism. Methods: Adult male mice were randomly assigned to Control group (kept at room temperature, Cold group (kept at low air temperature range from 3°C to 5°C and Resveratrol treatment group (100mg/kg/day for eight weeks. HE staining, Masson staining and Transmission electron microscopy were employed to detect cardiac structure, fibrosis and myocardial ultrastructure, respectively. Echocardiogram was used to measure myocardial functions. Western blot was used to detect the expression of MAPK pathway and apoptotic proteins. TUENL assay was performed to evaluate cardiomyocyte apoptosis. qRT-PCR was employed to measure the mRNA level. Results: Cold-treated mice showed a higher heart/body weight ratio and heart weight/tibia length ratio compared with control mice, and Resveratrol treatment may suppress these changes in cold-treated mice. Myocardial cross-section area and cardiac collagen volume were larger in cold group than control group, which also can be attenuated by Resveratrol treatment. Also, Resveratrol improved the ultrastructure damage of myocardium such as myofibril disarray in cold group. Echocardiogram measurement showed that EF and FS values in cold group declined apparently as compared to control group, and Resveratrol may improve the reduction of heart functions. The expression of p-JNK, p-p38 and p-ERK relative to total JNK, p38 and ERK in cold group was not altered in cold group and Resveratrol group as compared to control group. Cold-treated mouse hearts also showed the upregulation of hypertrophy-related miRNA-miR-328 but not miR-23a, and Resveratrol treatment can inhibit the increase of miR-328. Finally, Resveratrol treatment

  20. Dual-specificity phosphatase 14 protects the heart from aortic banding-induced cardiac hypertrophy and dysfunction through inactivation of TAK1-P38MAPK/-JNK1/2 signaling pathway.

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    Li, Chang-Yi; Zhou, Qing; Yang, Ling-Chao; Chen, Yi-He; Hou, Jian-Wen; Guo, Kai; Wang, Yue-Peng; Li, Yi-Gang

    2016-03-01

    Dual-specificity phosphatase 14 (Dusp14), an important negative modulator of mitogen-activated protein kinase (MAPK) signaling pathways, has been implicated in inflammatory immune response, cancers, cell differentiation and proliferation. The role of Dusp14 in chronic pressure overload-induced cardiac hypertrophy has not been explored. Here we have shown that Dusp14-/- knockout mice and cardiac-specific Dusp14 transgenic mice were generated and subjected to aortic banding (AB) for 4 weeks. Our results demonstrated that genetic loss of Dusp14 significantly aggravated cardiac hypertrophy, fibrosis, ventricular dilation and dysfunction, whereas transgenic cardiac-specific Dusp14 overexpression significantly attenuated AB-induced cardiac dysfunction and remodeling. In vitro, adenoviral overexpression of constitutive Dusp14 blocked angiotensin II-induced hypertrophic growth of cardiomyocytes, while Dusp14 knockdown led to opposite effects. Mechanistically, excessive phosphorylation of TAK1, P38MAPK and JNK1/2 was evidenced in Dusp14-/- knockout mice post-AB and inactivation of TAK1-P38MAPK and -JNK1/2 signaling using TAK1 inhibitor 5Z-7-ox shares similar antihypertrophic effect as Dusp14 overexpression. Moreover, we show that Dusp14 directly interacted with TAK1. Results from present experiments indicate that Dusp14 protects the heart from AB-induced cardiac hypertrophy and dysfunction possibly through inactivation of TAK1-P38MAPK/-JNK1/2 signaling pathway. Future studies are warranted to test the feasibility of overexpressing Dusp14 as a therapeutic strategy to attenuate cardiac hypertrophy and failure.

  1. Mid-Ventricular Variant of Dobutamine-Induced Stress Cardiomyopathy.

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    Chandraprakasam, Satish; Kanuri, Swapna; Hunter, Claire

    2015-05-01

    Dobutamine stress testing is a commonly used modality in detecting and estimating the prognosis in coronary artery disease (CAD). Although it is well tolerated by most patients, adverse events have been reported. Rarely, transient wall motion abnormalities can occur in the absence of obstructive CAD to suggest stress cardiomyopathy. We report a 48-year-old female with intermittent chest pain. Her physical exam, cardiac enzymes and transthoracic echocardiogram were unremarkable. She underwent dobutamine stress echocardiogram to rule out obstructive CAD. After 40 micrograms (mcg)/kg/minute and 0.5 mg atropine, she complained of intense chest pain and became hypertensive. Stress echocardiogram demonstrated mid-anterior and mid-septal hypokinesis. Emergent coronary angiogram demonstrated normal coronaries. Left ventricular angiogram in the right anterior oblique projection revealed mid-ventricular ballooning during systole with apical and basal hypercontractility. Patient demonstrated excellent recovery with expectant management. The mechanism of mid-variant of Dobutamine-induced stress cardiomyopathy remains unclear. We think that multiple mechanisms are involved and this risk should be considered in patients with comorbid psychiatric conditions and with use of centrally acting stimulants.

  2. Epidermal growth factor and neurotensin induce microvillus hypertrophy following massive enterectomy.

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    Ryan, C K; Miller, J H; Seydel, A S; de Mesy Jensen, K; Sax, H C

    1997-01-01

    The compensatory hypertrophy that develops after massive enterectomy is rarely adequate to prevent the development of short bowel syndrome. Trophic hormones such as epidermal growth factor (EGF) and neurotensin (NT) may be useful in improving and accelerating this adaptive response. This study delineates the effects of NT and EGF on remnant small bowel at the microvillus cellular level, which is the prime determinant of surface area. New Zealand white rabbits (2 kg) underwent midgut transection (sham) or 70% jejunoileal resection. Alzet pumps containing saline solution (control), EGF (1.5 microg /kg/hr), or NT (900 microg/kg/day) were implanted in resected animals after which they underwent 1 week of infusion. A second group of EGF animals was killed 2 weeks after infusion completion to assess delayed effects (EGF-delayed). Proximal jejunum was fixed for light and electron microscopy; villus and microvillus parameters were read in a blinded fashion. EGF (2.17+/-0.05 microm), EGF-delayed (2.26+/-1.5 microm, and NT (1.96+/-0.02 microm) animals had significantly increased microvillus heights compared to the control group (1.49+/-0.04 microm). Calculated brush-border surface areas were increased in a similar fashion. EGF and NT failed to elicit increases in jejunal gross villus heights. EGF and NT induce enterocyte microvillus hypertrophy and increase absorptive surface area in remnant bowel after massive enterectomy. In addition, the trophic effects of EGF persist after cessation of infusion. These peptides may be useful in accelerating small bowel adaption and preventing the development of short gut syndrome.

  3. Omega-3-fatty acid adds to the protective effect of flax lignan concentrate in pressure overload-induced myocardial hypertrophy in rats via modulation of oxidative stress and apoptosis.

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    Ghule, Arvindkumar E; Kandhare, Amit D; Jadhav, Suresh S; Zanwar, Anand A; Bodhankar, Subhash L

    2015-09-01

    Objective of the present investigation was to study the effect of the flax lignan concentrate (FLC) and Omega-3-fatty acid (O-3-FA) on myocardial apoptosis, left ventricular (LV) contractile dysfunction and electrocardiographic abnormalities in pressure overload-induced cardiac hypertrophy. The rats were divided into five groups such as sham, aortic stenosis (AS), AS+FLC, AS+O-3-FA and AS+FLC+O-3-FA. Cardiac hypertrophy was produced in rats by abdominal aortic constriction. The rats were treated with FLC (400mg/kg, p.o.), O-3-FA (400mg/kg, p.o.) and FLC+O-3-FA orally per day for four weeks. The LV function, myocardial apoptosis, and oxidative stress were quantified. FLC+O-3-FA treatment significantly reduced hemodynamic changes, improved LV contractile dysfunction, reduced cardiomyocyte apoptosis and cellular oxidative stress. Moreover, it significantly up-regulated the VEGF expression and decreased TNF-alpha level in serum. The histological analysis also revealed that FLC+O-3-FA treatment markedly preserved the cardiac structure and inhibited interstitial fibrosis. In conclusion, FLC+O-3-FA treatment improved LV dysfunction, inhibited cardiomyocyte apoptosis, improved myocardial angiogenesis, conserved activities of membrane-bound phosphatase enzymes and suppressed inflammation through reduced oxidative stress in an additive manner than FLC alone and O-3-FA alone treatment in pressure overload-induced cardiac hypertrophy. Copyright © 2015 Elsevier B.V. All rights reserved.

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

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    Cameron J Mitchell

    Full Text Available Muscle hypertrophy following resistance training (RT involves activation of myofibrillar protein synthesis (MPS to expand the myofibrillar protein pool. The degree of hypertrophy following RT is, however, highly variable and thus we sought to determine the relationship between the acute activation of MPS and RT-induced hypertrophy. We measured MPS and signalling protein activation after the first session of resistance exercise (RE in untrained men (n = 23 and then examined the relation between MPS with magnetic resonance image determined hypertrophy. To measure MPS, young men (24±1 yr; body mass index  = 26.4±0.9 kg•m² underwent a primed constant infusion of L-[ring-¹³C₆] phenylalanine to measure MPS at rest, and acutely following their first bout of RE prior to 16 wk of RT. Rates of MPS were increased 235±38% (P<0.001 above rest 60-180 min post-exercise and 184±28% (P = 0.037 180-360 min post exercise. Quadriceps volume increased 7.9±1.6% (-1.9-24.7% (P<0.001 after training. There was no correlation between changes in quadriceps muscle volume and acute rates of MPS measured over 1-3 h (r = 0.02, 3-6 h (r = 0.16 or the aggregate 1-6 h post-exercise period (r = 0.10. Hypertrophy after chronic RT was correlated (r = 0.42, P = 0.05 with phosphorylation of 4E-BP1(Thr37/46 at 1 hour post RE. We conclude that acute measures of MPS following an initial exposure to RE in novices are not correlated with muscle hypertrophy following chronic RT.

  5. The PPARbeta/delta agonist GW0742 relaxes pulmonary vessels and limits right heart hypertrophy in rats with hypoxia-induced pulmonary hypertension.

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    Louise S Harrington

    2010-03-01

    Full Text Available Pulmonary vascular diseases are increasingly recognised as important clinical conditions. Pulmonary hypertension associated with a range of aetiologies is difficult to treat and associated with progressive morbidity and mortality. Current therapies for pulmonary hypertension include phosphodiesterase type 5 inhibitors, endothelin receptor antagonists, or prostacyclin mimetics. However, none of these provide a cure and the clinical benefits of these drugs individually decline over time. There is, therefore, an urgent need to identify new treatment strategies for pulmonary hypertension.Here we show that the PPARbeta/delta agonist GW0742 induces vasorelaxation in systemic and pulmonary vessels. Using tissue from genetically modified mice, we show that the dilator effects of GW0742 are independent of the target receptor PPARbeta/delta or cell surface prostacyclin (IP receptors. In aortic tissue, vascular relaxant effects of GW0742 were not associated with increases in cGMP, cAMP or hyperpolarisation, but were attributed to inhibition of RhoA activity. In a rat model of hypoxia-induced pulmonary hypertension, daily oral dosing of animals with GW0742 (30 mg/kg for 3 weeks significantly reduced the associated right heart hypertrophy and right ventricular systolic pressure. GW0742 had no effect on vascular remodelling induced by hypoxia in this model.These observations are the first to show a therapeutic benefit of 'PPARbeta/delta' agonists in experimental pulmonary arterial hypertension and provide pre-clinical evidence to favour clinical trials in man.

  6. Hemodialysis-Induced Regional Left Ventricular Systolic Dysfunction and Inflammation : A Cross-sectional Study

    NARCIS (Netherlands)

    Assa, Solmaz; Hummel, Yoran M.; Voors, Adriaan A.; Kuipers, Johanna; Westerhuis, Ralf; Groen, Henk; Bakker, Stephan J. L.; Muller Kobold, Anneke C.; van Oeveren, Wim; Struck, Joachim; de Jong, Paul E.; Franssen, Casper F. M.

    Background: Hemodialysis may acutely induce regional left ventricular (LV) systolic dysfunction, which is associated with increased mortality and progressive heart failure. We tested the hypothesis that hemodialysis-induced regional LV systolic dysfunction is associated with inflammation and

  7. Superoxide scavenging and Akt inhibition in myocardium ameliorate pressure overload-induced NF-κB activation and cardiac hypertrophy.

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    Hingtgen, Shawn D; Li, Zhenbo; Kutschke, William; Tian, Xin; Sharma, Ram V; Davisson, Robin L

    2010-04-01

    Recent studies from our laboratory and others have shown that increases in cytoplasmic superoxide (O(2)(·-)) levels and Akt activation play a key role in agonist-stimulated NF-κB activation and cardiomyocyte hypertrophy in vitro. In this study, we tested the hypothesis that adenovirus (Ad)-mediated intramyocardial gene transfer of cytoplasmic superoxide dismutase (AdCu/ZnSOD) or a dominant-negative form of Akt (AdDNAkt) in mice would attenuate pressure overload-induced increases in activation of the redox-sensitive transcription factor NF-κB and cardiac hypertrophy. Adult C57BL/6 mice were subjected to thoracic aortic banding (TAB) or sham surgery, and intramyocardial injections of viral vectors (AdCu/ZnSOD, AdDNAkt, or control) were performed. There was robust transgene expression in the heart, which peaked 6-7 days after injection and then declined to undetectable levels by 12-14 days. In mice injected with AdBgL II, TAB caused a significant increase in O(2)(·-) generation and cardiac mass at 1 wk, and these responses were markedly attenuated by AdCu/ZnSOD. In addition, TAB induced time-dependent activation of NF-κB in the myocardium as measured longitudinally by in vivo bioluminescent imaging of NF-κB-dependent luciferase expression. This was also abolished by intracardiac AdCu/ZnSOD or AdDNAkt, but not the control vector. The inhibition of Akt and O(2)(·-)-mediated NF-κB activation in TAB hearts was associated with an attenuation of cardiac hypertrophy. Since a direct cause-and-effect relationship between NF-κB activation and cardiomyocyte hypertrophy has been established previously, our data support the hypothesis that increased O(2)(·-) generation and Akt activation are key signaling intermediates in pressure overload-induced activation of NF-κB and cardiac hypertrophy.

  8. E2/ER β inhibit ISO-induced cardiac cellular hypertrophy by suppressing Ca2+-calcineurin signaling.

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    Tsai, Cheng-Yen; Kuo, Wei-Wen; Shibu, Marthandam Asokan; Lin, Yueh-Min; Liu, Chien-Nam; Chen, Yi-Hui; Day, Cecilia-Hsuan; Shen, Chia-Yao; Viswanadha, Vijaya Padma; Huang, Chih-Yang

    2017-01-01

    Cardiovascular incidences are markedly higher in men than in pre-menstrual women. However, this advantage in women declines with aging and therefore can be correlated with the sex hormone 17β-Estradiol (E2) which is reported to protect heart cells by acting though estrogen receptors (ERs). In this study we have determined the effect of E2/ERβ against ISO induced cellular hypertrophy in H9c2 cardiomyoblast cells. The results confirm that ISO induced cardiac-hypertrophy by elevating the levels of hypertrophy associated proteins, ANP and BNP and further by upregulating p-CaMKII, calcineurin, p-GATA4 and NFATc3 which was correlated with a significant enlargement of the H9c2 cardiomyoblast. However, overexpression of ERβ and/or administration of E2 inhibited ISO-induced hypertrophy in H9c2 cells. In addition, E2/ERβ also inhibited ISO-induced NFATc3 translocation, and reduced the protein level of downstream marker, BNP. Furthermore, by testing with the calcineurin inhibitor (CsA), it was confirmed that calcineurin acted as a key mediator for the anti-hypertrophic effect of E2/ERβ. In cells treated with calcium blocker (BATPA), the inhibitory effect of E2/ERβ on ISO-induced Ca2+ influx and hypertrophic effects were totally blocked suggesting that E2/ERβ inhibited calcineurin activity to activate I-1 protein and suppress PP1, then induce PLB protein phosphorylation and activation, resulting in Ca2+ reuptake into sarcoplasmic reticulum through SR Ca2+ cycling modification. In conclusion, E2/ERβ suppresses the Ca2+ influx and calcineurin activity induced by ISO to enhance the PLB protein activity and SR Ca2+ cycling.

  9. Fast diastolic swinging motion of the mitral valve as a clinical marker of familial hypertrophic cardiomyopathy in genetically affected young children without left ventricular hypertrophy: a new role for noninvasive imaging?

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    Udink ten Cate, Floris E A; Junghaenel, Shino; Brockmeier, Konrad; Sreeram, Narayanswami

    2013-08-01

    Structural mitral valve (MV) abnormalities are common in patients with hypertrophic cardiomyopathy (HCM). This is the first report demonstrating MV abnormalities in very young children as the sole overt clinical feature of a known HCM-causing sarcomere protein gene mutation. Due to MV leaflet elongation, we also noticed a typical fast diastolic swinging motion of the MV in our patients. This novel echocardiographic feature may be used as a clinical marker of HCM disease in the absence of left ventricular hypertrophy. © 2013, Wiley Periodicals, Inc.

  10. Selumetinib, an Oral Anti-Neoplastic Drug, May Attenuate Cardiac Hypertrophy via Targeting the ERK Pathway.

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    Li, Chen; Chen, Zhongxiu; Yang, Hao; Luo, Fangbo; Chen, Lihong; Cai, Huawei; Li, Yajiao; You, Guiying; Long, Dan; Li, Shengfu; Zhang, Qiuping; Rao, Li

    2016-01-01

    Although extracellular-regulated kinases (ERK) are a well-known central mediator in cardiac hypertrophy, no clinically available ERK antagonist has been tested for preventing cardiac hypertrophy. Selumetinib is a novel oral MEK inhibitor that is currently under Phase II and Phase III clinical investigation for advanced solid tumors. In this study, we investigated whether Selumetinib could inhibit the aberrant ERK activation of the heart in response to stress as well as prevent cardiac hypertrophy. In an in vitro model of PE-induced cardiac hypertrophy, Selumetinib significantly inhibited the ERK activation and prevented enlargement of cardiomyocytes or reactivation of certain fetal genes. In the pathologic cardiac hypertrophy model of ascending aortic constriction, Selumetinib provided significant ERK inhibition in the stressed heart but not in the other organs. This selective ERK inhibition prevented left ventricular (LV) wall thickening, LV mass increase, fetal gene reactivation and cardiac fibrosis. In another distinct physiologic cardiac hypertrophy model of a swimming rat, Selumetinib provided a similar anti-hypertrophy effect, except that no significant fetal gene reactivation or cardiac fibrosis was observed. Selumetinib, a novel oral anti-cancer drug with good safety records in a number of Phase II clinical trials, can inhibit ERK activity in the heart and prevent cardiac hypertrophy. These promising results indicate that Selumetinib could potentially be used to treat cardiac hypertrophy. However, this hypothesis needs to be validated in human clinical trials.

  11. Flecainide Therapy Reduces Exercise-Induced Ventricular Arrhythmias in Patients With Catecholaminergic Polymorphic Ventricular Tachycardia

    NARCIS (Netherlands)

    van der Werf, Christian; Kannankeril, Prince J.; Sacher, Frederic; Krahn, Andrew D.; Viskin, Sami; Leenhardt, Antoine; Shimizu, Wataru; Sumitomo, Naokata; Fish, Frank A.; Bhuiyan, Zahurul A.; Willems, Albert R.; van der Veen, Maurits J.; Watanabe, Hiroshi; Laborderie, Julien; Haïssaguerre, Michel; Knollmann, Björn C.; Wilde, Arthur A. M.

    2011-01-01

    Objectives This study evaluated the efficacy and safety of flecainide in addition to conventional drug therapy in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT). Background CPVT is an inherited arrhythmia syndrome caused by gene mutations that destabilize cardiac

  12. Pressure Overload by Transverse Aortic Constriction Induces Maladaptive Hypertrophy in a Titin-Truncated Mouse Model

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    Qifeng Zhou

    2015-01-01

    Full Text Available Mutations in the giant sarcomeric protein titin (TTN are a major cause for inherited forms of dilated cardiomyopathy (DCM. We have previously developed a mouse model that imitates a TTN truncation mutation we found in a large pedigree with DCM. While heterozygous Ttn knock-in mice do not display signs of heart failure under sedentary conditions, they recapitulate the human phenotype when exposed to the pharmacological stressor angiotensin II or isoproterenol. In this study we investigated the effects of pressure overload by transverse aortic constriction (TAC in heterozygous (Het Ttn knock-in mice. Two weeks after TAC, Het mice developed marked impairment of left ventricular ejection fraction (p<0.05, while wild-type (WT TAC mice did not. Het mice also trended toward increased ventricular end diastolic pressure and volume compared to WT littermates. We found an increase in histologically diffuse cardiac fibrosis in Het compared to WT in TAC mice. This study shows that a pattern of DCM can be induced by TAC-mediated pressure overload in a TTN-truncated mouse model. This model enlarges our arsenal of cardiac disease models, adding a valuable tool to understand cardiac pathophysiological remodeling processes and to develop therapeutic approaches to combat heart failure.

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

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    Roman Leischik

    2014-05-01

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

  14. CT-1-CP-induced ventricular electrical remodeling in mice.

    Science.gov (United States)

    Chen, Shu-fen; Wei, Tao-zhi; Rao, Li-ya; Xu, Ming-guang; Dong, Zhan-ling

    2015-02-01

    along with the time. The APD in four CT-1-CP-treat groups was prolonged mainly in middle to final repolarization phase. The difference among these groups became significant in middle phase (APD50) (F=6.076, PCP. The chronic action of CT-1-CP might induce the adapting alteration in cardiac conductivity and ventricular repolarization. The amplitude and the Vmax of the anterior LV epicardial MAP increased obviously, and the APD prolonged mainly in late and final phase of repolarization.

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

    Science.gov (United States)

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

    2016-03-01

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

  16. miR-34a Modulates Angiotensin II-Induced Myocardial Hypertrophy by Direct Inhibition of ATG9A Expression and Autophagic Activity

    Science.gov (United States)

    Huang, He; Ye, Jing; Pan, Wei; Zhong, Yun; Cheng, Chuanfang; You, Xiangyu; Liu, Benrong; Xiong, Longgen; Liu, Shiming

    2014-01-01

    Cardiac hypertrophy is characterized by thickening myocardium and decreasing in heart chamber volume in response to mechanical or pathological stress, but the underlying molecular mechanisms remain to be defined. This study investigated altered miRNA expression and autophagic activity in pathogenesis of cardiac hypertrophy. A rat model of myocardial hypertrophy was used and confirmed by heart morphology, induction of cardiomyocyte autophagy, altered expression of autophagy-related ATG9A, LC3 II/I and p62 proteins, and decrease in miR-34a expression. The in vitro data showed that in hypertrophic cardiomyocytes induced by Ang II, miR-34a expression was downregulated, whereas ATG9A expression was up-regulated. Moreover, miR-34a was able to bind to ATG9A 3′-UTR, but not to the mutated 3′-UTR and inhibited ATG9A protein expression and autophagic activity. The latter was evaluated by autophagy-related LC3 II/I and p62 levels, TEM, and flow cytometry in rat cardiomyocytes. In addition, ATG9A expression induced either by treatment of rat cardiomyocytes with Ang II or ATG9A cDNA transfection upregulated autophagic activity and cardiomyocyte hypertrophy in both morphology and expression of hypertrophy-related genes (i.e., ANP and β-MHC), whereas knockdown of ATG9A expression downregulated autophagic activity and cardiomyocyte hypertrophy. However, miR-34a antagonized Ang II-stimulated myocardial hypertrophy, whereas inhibition of miR-34a expression aggravated Ang II-stimulated myocardial hypertrophy (such as cardiomyocyte hypertrophy-related ANP and β-MHC expression and cardiomyocyte morphology). This study indicates that miR-34a plays a role in regulation of Ang II-induced cardiomyocyte hypertrophy by inhibition of ATG9A expression and autophagic activity. PMID:24728149

  17. Calpastatin overexpression in the skeletal muscle of mice prevents clenbuterol-induced muscle hypertrophy and phenotypic shift.

    Science.gov (United States)

    Douillard, Aymeric; Galbes, Olivier; Begue, Gwenaelle; Rossano, Bernadette; Levin, John; Vernus, Barbara; Bonnieu, Anne; Candau, Robin; Py, Guillaume

    2012-04-01

    Accumulating evidence suggests that the calpain/calpastatin system is involved in skeletal muscle remodelling induced by β(2) -adrenoceptor agonist treatment. In addition to other pathways, the Akt/mammalian target of rapamycin (mTOR) pathway, controlling protein synthesis, and the calcium/calmodulin-dependent protein kinase 2 (CamK2) and AMP-activated protein kinase (AMPK) pathways, recently identified as calpain substrates, could be relevant in β(2) -adrenoceptor agonist-induced skeletal muscle remodelling. In the present study we investigated muscle hypertrophy and phenotypic shifts, as well as the molecular response of components of the Akt/mTOR pathway (i.e. Akt, eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), ribosomal protein S6 (rpS6), CamK2 and AMPK), in response to calpastatin overexpression in the skeletal muscle of mice treated with 1 mg/kg per day clenbuterol for 21 days. Using gene electrotransfer of a calpastatin expression vector into the tibialis anterior of adult mice, we found that calpastatin overexpression attenuates muscle hypertrophy and phenotypic shifts induced by clenbuterol treatment. At the molecular level, calpastatin overexpression markedly decreased calpain activity, but was ineffective in altering the phosphorylation of Akt, 4E-BP1 and rpS6. In contrast, calpastatin overexpression increased the protein expression of both total AMPK and total CamK2. In conclusion, the results support the contention that the calpain/calpastatin system plays a crucial role in skeletal muscle hypertrophy and phenotypic shifts under chronic clenbuterol treatment, with AMPK and CamK2 probably playing a minor role. Moreover, the calpastatin-induced inhibition of hypertrophy under clenbuterol treatment was not related to a decreased mTOR-dependent initiation of protein translation. © 2012 The Authors Clinical and Experimental Pharmacology and Physiology © 2012 Blackwell Publishing Asia Pty Ltd.

  18. Nutritional interventions to augment resistance training-induced skeletal muscle hypertrophy.

    Science.gov (United States)

    Morton, Robert W; McGlory, Chris; Phillips, Stuart M

    2015-01-01

    Skeletal muscle mass is regulated by a balance between muscle protein synthesis (MPS) and muscle protein breakdown (MPB). In healthy humans, MPS is more sensitive (varying 4-5 times more than MPB) to changes in protein feeding and loading rendering it the primary locus determining gains in muscle mass. Performing resistance exercise (RE) followed by the consumption of protein results in an augmentation of MPS and, over time, can lead to muscle hypertrophy. The magnitude of the RE-induced increase in MPS is dictated by a variety of factors including: the dose of protein, source of protein, and possibly the distribution and timing of post-exercise protein ingestion. In addition, RE variables such as frequency of sessions, time under tension, volume, and training status play roles in regulating MPS. This review provides a brief overview of our current understanding of how RE and protein ingestion can influence gains in skeletal muscle mass in young, healthy individuals. It is the goal of this review to provide nutritional recommendations for optimal skeletal muscle adaptation. Specifically, we will focus on how the manipulation of protein intake during the recovery period following RE augments the adaptive response.

  19. Dorsal root ganglia hypertrophy as in vivo correlate of oxaliplatin-induced polyneuropathy.

    Directory of Open Access Journals (Sweden)

    Leonidas Apostolidis

    Full Text Available To investigate in vivo morphological and functional correlates of oxaliplatin-induced peripheral neuropathy (OXA-PNP by magnetic resonance neurography (MRN.Twenty patients (7 female, 13 male, 58.9±10.0 years with mild to moderate OXA-PNP and 20 matched controls (8 female, 12 male, 55.7±15.6 years were prospectively enrolled. All patients underwent a detailed neurophysiological examination prior to neuroimaging. A standardized imaging protocol at 3.0 Tesla included the lumbosacral plexus and both sciatic nerves and their branches using T2-weighted fat-saturated sequences and diffusion tensor imaging. Quantitative assessment included volumetry of the dorsal root ganglia (DRG, sciatic nerve normalized T2 (nT2 signal and caliber, and fractional anisotropy (FA, mean diffusivity (MD, axial (AD and radial diffusivity (RD. Additional qualitative evaluation of sciatic, peroneal, and tibial nerves evaluated the presence, degree, and distribution of nerve lesions.DRG hypertrophy in OXA-PNP patients (207.3±47.7mm3 vs. 153.0±47.1mm3 in controls, p = 0.001 was found as significant morphological correlate of the sensory neuronopathy. In contrast, peripheral nerves only exhibited minor morphological alterations qualitatively. Quantitatively, sciatic nerve caliber (27.3±6.7mm2 vs. 27.4±7.4mm2, p = 0.80 and nT2 signal were not significantly changed in patients (1.32±0.22 vs. 1.22±0.26, p = 0.16. AD, RD, and MD showed a non-significant decrease in patients, while FA was unchanged.OXA-PNP manifests with morphological and functional correlates that can be detected in vivo by MRN. We report hypertrophy of the DRG that stands in contrast to experimental and postmortem studies. DRG volume should be further investigated as a biomarker in other sensory peripheral neuropathies and ganglionopathies.

  20. Incidence, degree, and development of graft hypertrophy 24 months after matrix-induced autologous chondrocyte implantation: association with clinical outcomes.

    Science.gov (United States)

    Ebert, Jay R; Smith, Anne; Fallon, Michael; Butler, Rodney; Nairn, Robert; Breidahl, William; Wood, David J

    2015-09-01

    Graft hypertrophy is a common occurrence after periosteal, collagen-covered and matrix-induced autologous chondrocyte implantation (MACI). The purpose of this study was to investigate the incidence, development, and degree of graft hypertrophy at 24 months after MACI. The hypothesis was that graft hypertrophy would not be associated with clinical outcome at 24 months. Case series, Level of evidence, 4. This study was undertaken in 180 consecutive patients (113 male, 67 female) after MACI in the knee. All patients were assessed clinically using the Knee injury and Osteoarthritis Outcome Score (KOOS) and underwent magnetic resonance imaging (MRI) at 3, 12, and 24 months after surgery. The incidence of hypertrophy relevant to anatomic graft site was investigated, as was the progressive change in hypertrophic studies postoperatively. The degree of tissue overgrowth in hypertrophic cases was investigated, as was its association with patient clinical outcome at 24 months after surgery. Of the 180 patients, 50 demonstrated a hypertrophic graft at 1 or more postoperative time points. This included 9 grafts (5.0%) at 3 months and 32 grafts (18.7%) at 12 months. At 24 months, 47 grafts (26.1%)-43 (32.1%) tibiofemoral and 4 (8.7%) patellofemoral-were hypertrophic. Patients with hypertrophic grafts at 24 months (n = 47) were younger (P = .051), they had a lower body mass index (BMI; P = .069), and significantly fewer of them had patellofemoral grafts (P = .007) compared with patients who had grafts with full (100%) tissue infill (n = 61). There were no significant differences in any of the KOOS subscales between patients with graft hypertrophy or full (100%) tissue infill at 24 months after surgery, while the severity of graft hypertrophy was not associated with KOOS subscales at 24 months. Hypertrophic grafts after MACI were common and continued to develop through to 24 months after surgery. Hypertrophic growth was associated with being younger and having a lower BMI, was

  1. Cardiac ACE2/angiotensin 1-7/Mas receptor axis is activated in thyroid hormone-induced cardiac hypertrophy.

    Science.gov (United States)

    Diniz, Gabriela P; Senger, Nathalia; Carneiro-Ramos, Marcela S; Santos, Robson A S; Barreto-Chaves, Maria Luiza M

    2016-08-01

    Thyroid hormone (TH) promotes marked effects on the cardiovascular system, including the development of cardiac hypertrophy. Some studies have demonstrated that the renin-angiotensin system (RAS) is a key mediator of the cardiac growth in response to elevated TH levels. Although some of the main RAS components are changed in cardiac tissue on hyperthyroid state, the potential modulation of the counter regulatory components of the RAS, such as angiotensin-converting enzyme type 2 (ACE2), angiotensin 1-7 (Ang 1-7) levels and Mas receptor induced by hyperthyroidism is unknown. The aim of this study was to investigate the effect of hyperthyroidism on cardiac Ang 1-7, ACE2 and Mas receptor levels. Hyperthyroidism was induced in Wistar rats by daily intraperitoneal injections of T4 for 14 days. Although plasma Ang 1-7 levels were unchanged by hyperthyroidism, cardiac Ang 1-7 levels were increased in TH-induced cardiac hypertrophy. ACE2 enzymatic activity was significantly increased in hearts from hyperthyroid animals, which may be contributing to the higher Ang 1-7 levels observed in the T4 group. Furthermore, elevated cardiac levels of Ang 1-7 levels were accompanied by increased Mas receptor protein levels. The counter-regulatory components of the RAS are activated in hyperthyroidism and may be contributing to modulate the cardiac hypertrophy in response to TH. © The Author(s), 2015.

  2. Never in mitosis gene A related kinase-6 attenuates pressure overload-induced activation of the protein kinase B pathway and cardiac hypertrophy.

    Directory of Open Access Journals (Sweden)

    Zhouyan Bian

    Full Text Available Cardiac hypertrophy appears to be a specialized form of cellular growth that involves the proliferation control and cell cycle regulation. NIMA (never in mitosis, gene A-related kinase-6 (Nek6 is a cell cycle regulatory gene that could induce centriole duplication, and control cell proliferation and survival. However, the exact effect of Nek6 on cardiac hypertrophy has not yet been reported. In the present study, the loss- and gain-of-function experiments were performed in Nek6 gene-deficient (Nek6-/- mice and Nek6 overexpressing H9c2 cells to clarify whether Nek6 which promotes the cell cycle also mediates cardiac hypertrophy. Cardiac hypertrophy was induced by transthoracic aorta constriction (TAC and then evaluated by echocardiography, pathological and molecular analyses in vivo. We got novel findings that the absence of Nek6 promoted cardiac hypertrophy, fibrosis and cardiac dysfunction, which were accompanied by a significant activation of the protein kinase B (Akt signaling in an experimental model of TAC. Consistent with this, the overexpression of Nek6 prevented hypertrophy in H9c2 cells induced by angiotonin II and inhibited Akt signaling in vitro. In conclusion, our results demonstrate that the cell cycle regulatory gene Nek6 is also a critical signaling molecule that helps prevent cardiac hypertrophy and inhibits the Akt signaling pathway.

  3. Curcumin attenuates cardiomyocyte hypertrophy induced by high glucose and insulin via the PPARγ/Akt/NO signaling pathway.

    Science.gov (United States)

    Chen, Rongchun; Peng, Xiaofeng; Du, Weimin; Wu, Yang; Huang, Bo; Xue, Lai; Wu, Qin; Qiu, Hongmei; Jiang, Qingsong

    2015-05-01

    To investigate the potential effect of curcumin on cardiomyocyte hypertrophy and a possible mechanism involving the PPARγ/Akt/NO signaling pathway in diabetes. The cardiomyocyte hypertrophy induced by high glucose (25.5mmol/L) and insulin (0.1μmol/L) (HGI) and the antihypertrophic effect of curcumin were evaluated in primary culture by measuring the cell surface area, protein content and atrial natriuretic factor (ANF) mRNA expression. The mRNA and protein expressions were assayed by reverse transcription PCR and Western blotting, whereas the NO concentration and endothelial NO synthase (eNOS) activity were determined using nitrate reduction and ELISA methods, respectively. The cardiomyocyte hypertrophy induced by HGI was characterized by increasing ANF mRNA expression, total protein content, and cell surface area, with downregulated mRNA and protein expressions of both PPARγ and Akt, which paralleled the declining eNOS mRNA expression, eNOS content, and NO concentration. The effects of HGI were inhibited by curcumin (1, 3, 10μmol/L) in a concentration-dependent manner. GW9662 (10μmol/L), a selective PPARγ antagonist, could abolish the effects of curcumin. LY294002 (20μmol/L), an Akt blocker, and N(G)-nitro-l-arginine-methyl ester (100μmol/L), a NOS inhibitor, could also diminish the effects of curcumin. The results suggested that curcumin supplementation can improve HGI-induced cardiomyocytes hypertrophy in vitro through the activation of PPARγ/Akt/NO signaling pathway. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. Prevention of angiotensin II-induced hypertension, cardiovascular hypertrophy and oxidative stress by acetylsalicylic acid in rats.

    Science.gov (United States)

    Wu, Rong; Laplante, Marc-André; De Champlain, Jacques

    2004-04-01

    Angiotensin II (Ang II)-induced oxidative stress has been suspected to play an important part in the pathogenesis of many cardiovascular diseases. Our previous study demonstrated that acetylsalicylic acid (ASA) possesses potent antioxidative properties. To evaluate the pathogenetic role of oxidative stress in Ang II-induced hypertension and cardiovascular hypertrophy. Chronic infusion of Ang II (200 ng/kg per min for 12 days) increased the aortic and cardiac tissue production of superoxide anion (O2) (lucigenin-enhanced chemiluminescence method) by 77 and 35%, respectively. These effects were associated with progressive increases in systolic blood pressure (from 135 to 194 mmHg) and heart/body weight ratio (from 2.25 to 2.69). Chronic treatment with oral ASA alone (100 mg/kg per day for 12 days) significantly reduced aortic and cardiac production of O2 (by 31 and 33%, respectively), without alteration in blood pressure and heart/body weight ratio in control normotensive animals. However, concurrent treatment with ASA in Ang II-infused rats completely prevented the Ang II-induced production of O2, in addition to hypertension and cardiac hypertrophy. Similar protective effects were observed in cultured aortic smooth muscle cells, in which increases in O2 production and [H]leucine incorporation (221 and 38%, respectively) induced by Ang II (10 mol/l) were totally prevented by concurrent incubation with ASA (10 mol/l). Losartan, but not PD 123319, also blocked the Ang II-induced oxidative and hypertrophic effects in those cells. Other anti-inflammatory drugs, such as salicylic acid, indomethacin and ibuprofen, did not show similar anti-Ang II and antioxidative effects in vivo. Oxidative stress plays a major part in chronic Ang II-induced hypertension and cardiovascular hypertrophy. Chronic concurrent treatment with ASA was found to prevent those Ang II-induced effects on the cardiovascular system, presumably through its antioxidative properties.

  5. Ventricular fibrillation induced by coagulating mode bipolar electrocautery during pacemaker implantation in Myotonic Dystrophy type 1 patient

    OpenAIRE

    Russo, Vincenzo; Rago, Anna; Di Meo, Federica; CIOPPA, NADIA DELLA; PAPA, ANDREA ANTONIO; Russo, Maria Giovanna; Nigro, Gerardo

    2014-01-01

    The occurrence of ventricular fibrillation, induced by bipolar electrocautery during elective dual chamber pacemaker implantation, is reported in a patient affected by Myotonic Distrophy type 1 with normal left ventricular ejection fraction

  6. Ventricular fibrillation induced by coagulating mode bipolar electrocautery during pacemaker implantation in Myotonic Dystrophy type 1 patient.

    Science.gov (United States)

    Russo, Vincenzo; Rago, Anna; DI Meo, Federica; Cioppa, Nadia Della; Papa, Andrea Antonio; Russo, Maria Giovanna; Nigro, Gerardo

    2014-12-01

    The occurrence of ventricular fibrillation, induced by bipolar electrocautery during elective dual chamber pacemaker implantation, is reported in a patient affected by Myotonic Distrophy type 1 with normal left ventricular ejection fraction.

  7. Vagus nerve stimulation reverses ventricular electrophysiological changes induced by hypersympathetic nerve activity.

    Science.gov (United States)

    Huang, Jie; Qian, Jin; Yao, Wei; Wang, Neng; Zhang, Zhenjian; Cao, Chuanbin; Song, Bo; Zhang, Zhuo

    2015-03-01

    What is the central question of this study? Previous studies have shown that hypersympathetic nerve activity results in ventricular electrophysiological changes and facilitates the occurrence of ventricular arrhythmias. Vagus nerve stimulation has shown therapeutic potential for myocardial infarction-induced ventricular arrhythmias. However, the actions of vagus nerve stimulation on hypersympathetic nerve activity-induced ventricular electrophysiological changes are still unknown. What is the main finding and its importance? We show that vagus nerve stimulation is able to reverse hypersympathetic nerve activity-induced ventricular electrophysiological changes and suppress the occurrence of ventricular fibrillation. These findings further suggest that vagus nerve stimulation may be an effective treatment option for ventricular arrhythmias, especially in patients with myocardial infarction or heart failure. Vagus nerve stimulation (VNS) has shown therapeutic potential for myocardial infarction-induced ventricular arrhythmias. This study aimed to investigate the effects of VNS on ventricular electrophysiological changes induced by hypersympathetic nerve activity. Seventeen open-chest dogs were subjected to left stellate ganglion stimulation (LSGS) for 4 h to simulate hypersympathetic tone. All animals were randomly assigned to the VNS group (n = 9) or the control group (n = 8). In the VNS group, VNS was performed at the voltage causing a 10% decrease in heart rate for hours 3-4 during 4 h of LSGS. During the first 2 h of LSGS, the ventricular effective refractory period (ERP) and action potential duration (APD) were both progressively and significantly decreased; the spatial dispersion of ERP, maximal slope of the restitution curve and pacing cycle length of APD alternans were all increased. With LSGS + VNS during the next 2 h, there was a significant return of all the altered electrophysiological parameters towards baseline levels. In the eight control

  8. Effects of pressure- or volume-overload hypertrophy on passive stiffness in isolated adult cardiac muscle cells

    Science.gov (United States)

    Kato, S.; Koide, M.; Cooper, G. 4th; Zile, M. R.

    1996-01-01

    It has been hypothesized that the changes in myocardial stiffness induced by chronic hemodynamic overloading are dependent on changes in the passive stiffness of the cardiac muscle cell (cardiocyte). However, no previous studies have examined the passive constitutive properties of cardiocytes isolated from animals with myocardial hypertrophy. Accordingly, changes in relative passive stiffness of cardiocytes isolated from animals with chronic pressure- or volume-overload hypertrophy were determined by examining the effects of anisosmotic stress on cardiocyte size. Anisosmotic stress was produced by altering superfusate osmolarity. Hypertrophied cardiocytes were enzymatically isolated from 16 adult cats with right ventricular (RV) pressure-overload hypertrophy induced by pulmonary artery banding (PAB) and from 6 adult cats with RV volume-overload hypertrophy induced by creating an atrial septal defect (ASD). Left ventricular (LV) cardiocytes from each cat served as nonhypertrophied, normally loaded, same-animal controls. Superfusate osmolarity was decreased from 305 +/- 3 to 135 +/- 5 mosM and increased to 645 +/- 4 mosM. During anisosmotic stress, there were no significant differences between hypertrophied RV and normal LV cardiocytes in pressure overload PAB cats with respect to percent change in cardiocyte area (47 +/- 2% in RV vs. 48 +/- 2% in LV), diameter (46 +/- 3% in RV vs. 48 +/- 2% in LV), or length (2.4 +/- 0.2% in RV vs. 2.0 +/- 0.3% in LV), or sarcomere length (1.5 +/- 0.1% in RV vs. 1.3 +/- 0.3% in LV). Likewise, there were no significant differences in cardiocyte strain between hypertrophied RV and normal LV cardiocytes from ASD cats. In conclusion, chronic pressure-overload hypertrophy and chronic volume-overload hypertrophy did not alter the cardiocyte response to anisosmotic stress. Thus chronic overload hypertrophy did not alter relative passive cardiocyte stiffness.

  9. Phosphatidic acid enhances mTOR signaling and resistance exercise induced hypertrophy.

    Science.gov (United States)

    Joy, Jordan M; Gundermann, David M; Lowery, Ryan P; Jäger, Ralf; McCleary, Sean A; Purpura, Martin; Roberts, Michael D; Wilson, Stephanie Mc; Hornberger, Troy A; Wilson, Jacob M

    2014-01-01

    The lipid messenger phosphatidic acid (PA) plays a critical role in the stimulation of mTOR signaling. However, the mechanism by which PA stimulates mTOR is currently unknown. Therefore, the purpose of this study was to compare the effects of various PA precursors and phospholipids on their ability to stimulate mTOR signaling and its ability to augment resistance training-induced changes in body composition and performance. In phase one, C2C12 myoblasts cells were stimulated with different phospholipids and phospholipid precursors derived from soy and egg sources. The ratio of phosphorylated p70 (P-p70-389) to total p70 was then used as readout for mTOR signaling. In phase two, resistance trained subjects (n = 28, 21 ± 3 years, 77 ± 4 kg, 176 ± 9 cm) consumed either 750 mg PA daily or placebo and each took part in an 8 week periodized resistance training program. In phase one, soy-phosphatidylserine, soy-Lyso-PA, egg-PA, and soy-PA stimulated mTOR signaling, and the effects of soy-PA (+636%) were significantly greater than egg-PA (+221%). In phase two, PA significantly increased lean body mass (+2.4 kg), cross sectional area (+1.0 cm), and leg press strength (+51.9 kg) over placebo. PA significantly activates mTOR and significantly improved responses in skeletal muscle hypertrophy, lean body mass, and maximal strength to resistance exercise.

  10. Differential requirement for satellite cells during overload-induced muscle hypertrophy in growing versus mature mice.

    Science.gov (United States)

    Murach, Kevin A; White, Sarah H; Wen, Yuan; Ho, Angel; Dupont-Versteegden, Esther E; McCarthy, John J; Peterson, Charlotte A

    2017-07-10

    Pax7+ satellite cells are required for skeletal muscle fiber growth during post-natal development in mice. Satellite cell-mediated myonuclear accretion also appears to persist into early adulthood. Given the important role of satellite cells during muscle development, we hypothesized that the necessity of satellite cells for adaptation to an imposed hypertrophic stimulus depends on maturational age. Pax7(CreER)-R26R(DTA) mice were treated for 5 days with vehicle (satellite cell-replete, SC+) or tamoxifen (satellite cell-depleted, SC-) at 2 months (young) and 4 months (mature) of age. Following a 2-week washout, mice were subjected to sham surgery or 10 day synergist ablation overload of the plantaris (n = 6-9 per group). The surgical approach minimized regeneration, de novo fiber formation, and fiber splitting while promoting muscle fiber growth. Satellite cell density (Pax7+ cells/fiber), embryonic myosin heavy chain expression (eMyHC), and muscle fiber cross sectional area (CSA) were evaluated via immunohistochemistry. Myonuclei (myonuclei/100 mm) were counted on isolated single muscle fibers. Tamoxifen treatment depleted satellite cells by ≥90% and prevented myonuclear accretion with overload in young and mature mice (p Satellite cells did not recover in SC- mice after overload. Average muscle fiber CSA increased ~20% in young SC+ (p = 0.07), mature SC+ (p satellite cells for overload-induced hypertrophy is dependent on maturational age, and global responses to overload differ in young versus mature mice.

  11. Volumetric and functional assessment of the left atrium in young competitive athletes without left ventricular hypertrophy: the MAGYAR-Sport Study.

    Science.gov (United States)

    Nemes, Attila; Domsik, Péter; Kalapos, Anita; Orosz, Andrea; Oszlánczi, Mónika; Török, László; Balogh, László; Márton, János; Forster, Tamás; Lengyel, Csaba

    2017-06-01

    Left atrial (LA) remodeling may be regarded as a physiologic adaptation to exercise conditioning. Three-dimensional speckle tracking echocardiography (3DSTE) is a new promising tool for volumetric and functional characterization of the LA. The present study was undertaken to assess adaptive changes in LA volumes and functional properties respecting cardiac cycle in young competitive athletes without left ventricular hypertrophy (LVH) by detailed 3DSTE assessment. The study group consisted of 20 young elite basketball and handball players (mean age: 28.1±10.1 years, 8 men) without LVH, their results were compared to 23 age- and gender-matched non-sportive healthy controls (mean age: 31.7±8.5 years, 11 men. All subjects had undergone standard transthoracic two-dimensional Doppler echocardiographic study with 3DSTE. Increased systolic maximum (66.5±13.6 mL vs. 38.5±8.6 mL, P<0.0001) and diastolic minimum (36.7±8.1 mL vs. 17.5±5.8 mL, P<0.0001) and preatrial contraction (46.2±10.1 mL vs. 26.2±7.8 mL, P<0.0001) LA volumes could be demonstrated in athletes. Total (29.7±9.0 mL vs. 20.7±5.0 mL, P=0.0002) and passive LA stroke volumes (19.8±8.7 mL vs. 12.4±4.6 mL, P=0.0009) were increased, while total (44.2±9.1 mL vs. 54.2±9.4 mL, P=0.001) and active LA emptying fractions (20.6±11.8% vs. 31.9±8.7%, P=0.0008) proved to be decreased in athletes as compared to controls. Active LA stroke volume (9.9±5.8 mL vs. 8.3±3.3 mL, P=0.29) and passive LA emptying fraction (29.1±10.6 mL vs. 32.6±11.2 mL, P=0.31) did not differ between the groups. Only circumferential global (21.1±7.7% vs. 27.6±9.9%, P=0.02) and mean segmental (26.1±7.1% vs. 35.7±12.0%, P=0.003) peak LA strains proved to be significantly reduced in athletes as compared to controls. 3DSTE-derived increased cyclic LA volumes and specific alterations in LA functional properties could be demonstrated in young competing athletes which is most likely a physiologic consequence of a global cardiac

  12. Adenosine induced ventricular arrhythmias in the emergency room

    NARCIS (Netherlands)

    Tan, H. L.; Spekhorst, H. H.; Peters, R. J.; Wilde, A. A.

    2001-01-01

    While adenosine effectively terminates most supraventricular tachycardias (SVT), rare case reports have demonstrated its proarrhythmic potential, including induction of ventricular tachycardia (VT). The aim of this study was to define the proarrhythmic effects of adenosine in a large, unselected

  13. Abnormal Left Ventricular Mechanics of Ventricular Ectopic Beats: Insights into Origin and Coupling Interval in Premature Ventricular Contraction-Induced Cardiomyopathy

    Science.gov (United States)

    Potfay, Jonathan; Kaszala, Karoly; Tan, Alex Y.; Sima, Adam P.; Gorcsan, John; Ellenbogen, Kenneth A.; Huizar, Jose F.

    2015-01-01

    Background Left ventricular (LV) dyssynchrony caused by premature ventricular contractions (PVCs) has been proposed as a mechanism of PVC-induced cardiomyopathy (CM). We sought to understand the impact of different PVC locations and coupling intervals (prematurity) on LV regional mechanics and global function of the PVC beat itself. Methods and Results Using our premature pacing algorithm, pentageminal PVCs at coupling intervals of 200–375ms were delivered from the epicardial right ventricular (RV) apex, RV outflow tract (RVOT), and LV free wall, as well as premature atrial contractions (PACs) from the left atrial (LA) appendage at a coupling interval of 200ms in seven healthy canines. LV short axis echocardiographic images, LV stroke volume (SV) and dP/dtmax were obtained during all ectopic beats and VP. LV dyssynchrony was assessed by dispersion of QRS-to-peak strain (earliest – last QRS-to-peak strain) between 6 different LV segments during each of the aforementioned beats (GE, EchoPac). LV dyssynchrony was greater during long- rather than short-coupled PVCs and PVCs at 375ms compared with rapid VP at 400ms (P<0.0001), whereas, no difference was found between PVC locations. Longer PVC coupling intervals were associated with greater SV and dP/dtmax despite more pronounced dyssynchrony (P<0.001). Conclusions PVCs with longer coupling intervals demonstrate more pronounced LV dyssynchrony, whereas PVC location has minimal impact. LV dyssynchrony cannot be attributed to prematurity or abnormal ventricular activation alone, but rather to a combination of both. This study suggests that late-coupled PVCs may cause a more severe cardiomyopathy if dyssynchrony is the leading mechanism responsible for PVC-induced CM. PMID:26297787

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

    Science.gov (United States)

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

    2014-01-01

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

  15. G protein-coupled receptor kinase 2 promotes cardiac hypertrophy

    Science.gov (United States)

    Tscheschner, Henrike; Gao, Erhe; Schumacher, Sarah M.; Yuan, Ancai; Backs, Johannes; Most, Patrick; Wieland, Thomas; Koch, Walter J.; Katus, Hugo A.; Raake, Philip W.

    2017-01-01

    The increase in protein activity and upregulation of G-protein coupled receptor kinase 2 (GRK2) is a hallmark of cardiac stress and heart failure. Inhibition of GRK2 improved cardiac function and survival and diminished cardiac remodeling in various animal heart failure models. The aim of the present study was to investigate the effects of GRK2 on cardiac hypertrophy and dissect potential molecular mechanisms. In mice we observed increased GRK2 mRNA and protein levels following transverse aortic constriction (TAC). Conditional GRK2 knockout mice showed attenuated hypertrophic response with preserved ventricular geometry 6 weeks after TAC operation compared to wild-type animals. In isolated neonatal rat ventricular cardiac myocytes stimulation with angiotensin II and phenylephrine enhanced GRK2 expression leading to enhanced signaling via protein kinase B (PKB or Akt), consecutively inhibiting glycogen synthase kinase 3 beta (GSK3β), such promoting nuclear accumulation and activation of nuclear factor of activated T-cells (NFAT). Cardiac myocyte hypertrophy induced by in vitro GRK2 overexpression increased the cytosolic interaction of GRK2 and phosphoinositide 3-kinase γ (PI3Kγ). Moreover, inhibition of PI3Kγ as well as GRK2 knock down prevented Akt activation resulting in halted NFAT activity and reduced cardiac myocyte hypertrophy. Our data show that enhanced GRK2 expression triggers cardiac hypertrophy by GRK2-PI3Kγ mediated Akt phosphorylation and subsequent inactivation of GSK3β, resulting in enhanced NFAT activity. PMID:28759639

  16. Attenuation of microRNA-16 derepresses the cyclins D1, D2 and E1 to provoke cardiomyocyte hypertrophy

    Science.gov (United States)

    Huang, Shuai; Zou, Xiao; Zhu, Jie-Ning; Fu, Yong-Heng; Lin, Qiu-Xiong; Liang, Ye-You; Deng, Chun-Yu; Kuang, Su-Juan; Zhang, Meng-Zhen; Liao, Yu-Lin; Zheng, Xi-Long; Yu, Xi-Yong; Shan, Zhi-Xin

    2015-01-01

    Cyclins/retinoblastoma protein (pRb) pathway participates in cardiomyocyte hypertrophy. MicroRNAs (miRNAs), the endogenous small non-coding RNAs, were recognized to play significant roles in cardiac hypertrophy. But, it remains unknown whether cyclin/Rb pathway is modulated by miRNAs during cardiac hypertrophy. This study investigates the potential role of microRNA-16 (miR-16) in modulating cyclin/Rb pathway during cardiomyocyte hypertrophy. An animal model of hypertrophy was established in a rat with abdominal aortic constriction (AAC), and in a mouse with transverse aortic constriction (TAC) and in a mouse with subcutaneous injection of phenylephrine (PE) respectively. In addition, a cell model of hypertrophy was also achieved based on PE-promoted neonatal rat ventricular cardiomyocyte and based on Ang-II-induced neonatal mouse ventricular cardiomyocyte respectively. We demonstrated that miR-16 expression was markedly decreased in hypertrophic myocardium and hypertrophic cardiomyocytes in rats and mice. Overexpression of miR-16 suppressed rat cardiac hypertrophy and hypertrophic phenotype of cultured cardiomyocytes, and inhibition of miR-16 induced a hypertrophic phenotype in cardiomyocytes. Expressions of cyclins D1, D2 and E1, and the phosphorylated pRb were increased in hypertrophic myocardium and hypertrophic cardiomyocytes, but could be reversed by enforced expression of miR-16. Cyclins D1, D2 and E1, not pRb, were further validated to be modulated post-transcriptionally by miR-16. In addition, the signal transducer and activator of transcription-3 and c-Myc were activated during myocardial hypertrophy, and inhibitions of them prevented miR-16 attenuation. Therefore, attenuation of miR-16 provoke cardiomyocyte hypertrophy via derepressing the cyclins D1, D2 and E1, and activating cyclin/Rb pathway, revealing that miR-16 might be a target to manage cardiac hypertrophy. PMID:25583328

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

    Directory of Open Access Journals (Sweden)

    Cléber do Lago Mazzaro

    2008-04-01

    Full Text Available FUNDAMENTO: A hipertrofia ventricular esquerda (HVE é um importante e independente fator de risco cardiovascular. Inexistem, no Brasil, estudos desenhados para testar a eficácia do eletrocardiograma (ECG no diagnóstico desse grave processo patológico. OBJETIVO: Avaliar um novo escore eletrocardiográfico para diagnóstico de HVE pelo ECG: soma da maior amplitude da onda S com a maior da onda R no plano horizontal, multiplicando-se o resultado pela duração do QRS [(S+R X QRS] e comparando-o com os critérios eletrocardiográficos clássicos. MÉTODOS: Foram analisados os ecocardiogramas e ECG de 1.204 pacientes hipertensos em tratamento ambulatorial. Avaliou-se o índice de massa do ventrículo esquerdo (IMVE pelo ecocardiograma, firmando-se o diagnóstico de HVE quando > 96 g/m² para mulheres e > 116 g/m² para homens. No ECG analisaram-se quatro critérios clássicos de HVE, além do novo escore a ser testado. RESULTADOS: Todos os índices estudados tiveram correlação estatisticamente significativa com a massa calculada do ventrículo esquerdo (VE. Porém, o novo escore foi o que apresentou maior correlação (r = 0,564. Os outros critérios apresentaram as seguintes correlações: Romhilt-Estes (r = 0,464; Sokolow-Lyon (r = 0,419; Cornell voltagem (r = 0,377; Cornell duração (r = 0,444. Para avaliação da acurácia do índice testado, utilizou-se o ponto de corte de 2,80 mm.s. Com esse valor foram obtidas as seguintes cifras para sensibilidade e especificidade: 35,2% e 88,7%, respectivamente. CONCLUSÃO: Todos os critérios eletrocardiográficos para avaliação da massa do VE apresentaram baixa sensibilidade. O novo escore foi o que apresentou melhor correlação com o IMVE em relação aos outros avaliados.BACKGROUND: The left ventricular hypertrophy (LVH is an important and independent cardiovascular risk factor. There is a scarcity of studies in Brazil designed to test the efficacy of the electrocardiogram (ECG in the diagnosis

  18. Low-load bench press and push-up induce similar muscle hypertrophy and strength gain

    National Research Council Canada - National Science Library

    Naoki Kikuchi; Koichi Nakazato

    2017-01-01

    ...) bench press on muscle hypertrophy and strength gain in men. Methods: Eighteen male participants (age, 20.2 ± 0.73 years, range: 19−22 years, height: 169.8 ± 4.4 cm, weight: 64.5 ± 4.7 kg...

  19. Exercise-induced changes in left ventricular global longitudinal strain in asymptomatic severe aortic stenosis.

    Science.gov (United States)

    Lech, Agnieszka K; Dobrowolski, Piotr P; Klisiewicz, Anna; Hoffman, Piotr

    2017-01-01

    The management of patients with asymptomatic severe aortic stenosis (ASAS) is still under discussion. Therefore, it is advisable to search for the parameters of early damage to left ventricular (LV) function. The aim of the study was to assess exercise-induced changes in LV global longitudinal strain (GLS) in ASAS. The ASAS group consisted of 50 patients (26 women and 24 men, aged 38.4 ± 18.1 years) meeting the echocardiographic criteria of severe aortic stenosis (AVA 4 m/s, mean aortic gradient > 40 mm Hg), with normal LV ejection fraction (LVEF ≥ 55%) and sinus rhythm on electrocardiogram, and without significant concomitant valvular heart diseases. The control group consisted of 21 people matched for age and sex. Echocardiographic examinations and echocardiographic stress tests with the assessment of GLS using the speckle tracking imaging were performed. The ASAS group was characterised by statistically significantly higher LV mass index (LVMI) and higher LVEF. GLS values at rest in both groups were within normal limits but were significantly higher in the control group (-18.9 ± 2.4% vs. -20.7 ± 1.7%, p = 0.006). An increase in GLS at peak exercise in both groups was observed, lower in the ASAS group (the difference was not statistically significant: -0.8 ± 3.0% vs. -2.2 ± 3.1%, p = 0.086). Changes in GLS during exercise (ΔGLS) did not correlate with the parameters of the severity of aortic stenosis. In the multivariate model, LVMI proved to be a factor associated with GLS at rest and during exercise. In patients with ASAS, GLS is a non-invasive marker of an early stage of LV myocardial damage associated with myocardial hypertrophy. An increase in GLS during exercise in the ASAS group, smaller than in the control group, indicates a preserved functional reserve of the LV myocardium but smaller than in healthy individuals. The assessment of the clinical usefulness of exercise-induced changes in GLS requires further research.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-09-01

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

  1. Cytoskeletal mechanics in pressure-overload cardiac hypertrophy

    Science.gov (United States)

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

    1997-01-01

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

  2. Towards a re-definition of 'cardiac hypertrophy' through a rational characterization of left ventricular phenotypes: a position paper of the Working Group 'Myocardial Function' of the ESC.

    Science.gov (United States)

    Knöll, Ralph; Iaccarino, Guido; Tarone, Guido; Hilfiker-Kleiner, Denise; Bauersachs, Johann; Leite-Moreira, Adelino F; Sugden, Peter H; Balligand, Jean-Luc

    2011-08-01

    Many primary or secondary diseases of the myocardium are accompanied with complex remodelling of the cardiac tissue that results in increased heart mass, often identified as cardiac 'hypertrophy'. Although there have been numerous attempts at defining such 'hypertrophy', the present paper delineates the reasons as to why current definitions of cardiac hypertrophy remain unsatisfying. Based on a brief review of the underlying pathophysiology and tissue and cellular events driving myocardial remodelling with or without changes in heart dimensions, as well as current techniques to detect such changes, we propose to restrict the use of the currently popular term 'hypertrophy' to cardiac myocytes that may or may not accompany the more complex tissue rearrangements leading to changes in shape or size of the ventricles, more broadly referred to as 'remodelling'. We also discuss the great potential of genetically modified (mouse) models as tools to define the molecular pathways leading to the different forms of left ventricle remodelling. Finally, we present an algorithm for the stepwise assessment of myocardial phenotypes applicable to animal models using well-established imaging techniques and propose a list of parameters most suited for a critical evaluation of such pathophysiological phenomena in mouse models. We believe that this effort is the first step towards a much auspicated unification of the terminology between the experimental and the clinical cardiologists.

  3. Interleukin-6-induced reciprocal expression of SERCA and natriuretic peptides mRNA in cultured rat ventricular myocytes.

    Science.gov (United States)

    Tanaka, T; Kanda, T; Takahashi, T; Saegusa, S; Moriya, J; Kurabayashi, M

    2004-01-01

    We investigated the effect of interleukin-6 (IL-6) expression on sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA), atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) mRNA levels in cultured rat neonatal ventricular myocytes. IL-6 plays a key role in regulating cardiac hypertrophy and the development of heart failure, and SERCA, ANP and BNP are all cardiac hormones with regulatory properties. Compared with baseline measurements, treatment with 50 U/ml IL-6 significantly decreased SERCA gene expression, but significantly increased ANP and BNP gene expression in the cardiac myocytes. These results suggest that the clinical overproduction of IL-6 in response to infection, autoimmune disease and cancer might be responsible for cardiac hypertrophy. Cardiac hypertrophy may result from the imbalance of both natriuretic peptides and SERCA transcription levels, caused by elevated IL-6 expression.

  4. Exercise-Induced Ventricular Fibrillation: Seven Years Follow-Up

    Directory of Open Access Journals (Sweden)

    Gökmen Gemici

    2011-11-01

    Full Text Available We present a 7-year follow-up of a 55-year-old male who experienced ventricular fibrillation during the recovery period of exercise testing and refused implantation of an ICD. Normal left ventricular systolic function was found on echocardiographic examination, and coronary angiography revealed only a side branch disease with a vessel diameter of less than 2 millimeters. The patient was discharged on metoprolol and ASA in addition to his previous treatment with lisinopril and simvastatin. Outpatient cardiac evaluation by repeated 24-hour ECG monitorizations (Holter revealed normal findings. On follow up visits every six months for the past seven years, the patient was found to be asymptomatic.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    Left ventricular hypertrophy [LVH, high left ventricular mass (LVM)] is traditionally classified as concentric or eccentric based on left ventricular relative wall thickness. We evaluated left ventricular systolic function in a new four-group LVH classification based on left ventricular dilatatio...

  6. Myocardial fibrosis in patients with symptomatic obstructive hypertrophic cardiomyopathy: correlation with echocardiographic measurements, sarcomeric genotypes, and pro-left ventricular hypertrophy polymorphisms involving the renin-angiotensin-aldosterone system.

    Science.gov (United States)

    Blauwet, Lori A; Ackerman, Michael J; Edwards, William D; Riehle, Darren L; Ommen, Steve R

    2009-01-01

    Hypertrophic cardiomyopathy (HCM) is a heterogeneous disorder of the cardiac sarcomere, resulting in myocyte hypertrophy and disarray, interstitial fibrosis, and cardiac dysfunction. Our aim was to determine whether the amount of fibrosis in HCM correlates with echocardiographic measures of diastolic dysfunction, presence of HCM-susceptibility mutations, or polymorphisms in the renin-angiotensin-aldosterone system (RAAS). Surgical specimens from patients with obstructive HCM undergoing septal myectomy at the Mayo Clinic (2001-2004) were examined and compared with autopsy-derived tissues from age- and sex-matched normal controls. Digital image analysis was used to quantitate the fibrosis in representative microscopic sections. Genotyping was performed for myofilament-HCM using polymerase chain reaction, high-performance liquid chromatography, and direct DNA sequencing. RAAS polymorphism status was similarly established. The study included 59 HCM cases and 44 controls. Patients with HCM exhibited more fibrosis (mean 17%, range 3-45%) than controls (mean 8%, range 3-17%) (P or =1 C-encoding allele in CYP11B2-encoded aldosterone synthase. Patients with HCM undergoing septal myectomy had significantly more myocardial interstitial fibrosis than controls. The amount of fibrosis in HCM patients correlated with degree of septal hypertrophy and left ventricular systolic and diastolic function. Notably, neither mutations in cardiac myofilament proteins or polymorphisms in RAAS exhibited strong associations with severity of myocardial fibrosis.

  7. Muscle hypertrophy induced by the Ski protein: cyto-architecture and ultrastructure.

    Science.gov (United States)

    Bruusgaard, J C; Brack, A S; Hughes, S M; Gundersen, K

    2005-10-01

    Transgenic mice overexpressing the c-ski proto-oncogene driven by the MSV promoter undergo muscle hypertrophy, most notably fast fibres of the lower limb. This hypertrophy is not accompanied by a correspondingly large increase in force, and individual skinned muscle fibres exhibit a 30% reduction in force per cross-sectional area. In this respect, the MSV ski model is different from most other hypertrophy models and we here aim at describing the mechanisms for the reduced specific force. Cyoarchitecture and ultrastructure of muscle fibres from the fast extensor digitorum longus muscle of 2-3 months old MSV ski mice was studied. In addition to electron microscopy, we used in vivo intracellular injections of myonuclear dye to investigate nuclear number. The number of nuclei did not increase in proportion to size, and consequently nuclear domains were increased compared with wild type. The fraction of the cytoplasm occupied by contractile material was reduced by 18%. In addition we observed poor intracellular alignment of Z-discs. Such staggering has been reported to reduce force in desmin deficient mice, but the amount and distribution of desmin in the MSV ski mice seemed normal. The mitochondria of MSV ski mice showed irregularly spaced cristae that were frequently disrupted. The reduction in specific force observed in MSV ski mice could be explained by a reduced fraction of contractile material and reduced transversal mechanical coupling. The ultrastructural abnormalities could be related to an increase in nuclear domains.

  8. Left ventricular failure produces profound lung remodeling and pulmonary hypertension in mice: heart failure causes severe lung disease.

    Science.gov (United States)

    Chen, Yingjie; Guo, Haipeng; Xu, Dachun; Xu, Xin; Wang, Huan; Hu, Xinli; Lu, Zhongbing; Kwak, Dongmin; Xu, Yawei; Gunther, Roland; Huo, Yuqing; Weir, E Kenneth

    2012-06-01

    Chronic left ventricular failure causes pulmonary congestion with increased lung weight and type 2 pulmonary hypertension. Understanding the molecular mechanisms for type 2 pulmonary hypertension and the development of novel treatments for this condition requires a robust experimental animal model and a good understanding of the nature of the resultant pulmonary remodeling. Here we demonstrate that chronic transverse aortic constriction causes massive pulmonary fibrosis and remodeling, as well as type 2 pulmonary hypertension, in mice. Thus, aortic constriction-induced left ventricular dysfunction and increased left ventricular end-diastolic pressure are associated with a ≤5.3-fold increase in lung wet weight and dry weight, pulmonary hypertension, and right ventricular hypertrophy. Interestingly, the aortic constriction-induced increase in lung weight was not associated with pulmonary edema but resulted from profound pulmonary remodeling with a dramatic increase in the percentage of fully muscularized lung vessels, marked vascular and lung fibrosis, myofibroblast proliferation, and leukocyte infiltration. The aortic constriction-induced left ventricular dysfunction was also associated with right ventricular hypertrophy, increased right ventricular end-diastolic pressure, and right atrial hypertrophy. The massive lung fibrosis, leukocyte infiltration, and pulmonary hypertension in mice after transverse aortic constriction clearly indicate that congestive heart failure also causes severe lung disease. The lung fibrosis and leukocyte infiltration may be important mechanisms in the poor clinical outcome in patients with end-stage heart failure. Thus, the effective treatment of left ventricular failure may require additional efforts to reduce lung fibrosis and the inflammatory response.

  9. A comparison of Cornell and Sokolow-Lyon electrocardiographic criteria for left ventricular hypertrophy in a military male population in Taiwan: the Cardiorespiratory fitness and HospItalization Events in armed Forces study.

    Science.gov (United States)

    Su, Fang-Ying; Li, Yi-Hwei; Lin, Yen-Po; Lee, Chung-Jen; Wang, Chih-Hung; Meng, Fan-Chun; Yu, Yun-Shun; Lin, Felicia; Wu, Hsien-Tsai; Lin, Gen-Min

    2017-06-01

    The Cornell and Sokolow-Lyon electrocardiography (ECG) criteria have been widely used for diagnosing left ventricular hypertrophy (LVH) in patients with hypertension. However, the correlations of these ECG criteria with LVH were rarely compared in military members who received rigorous training, particularly of the Asian male population. We compared the Cornell voltage and product criteria with the Sokolow-Lyon criteria for the echocardiographic LVH in 539 military male members, ages 18-50 years and free of hypertension in the Cardiorespiratory fitness and HospItalization Events in armed Forces (CHIEF) study in Taiwan. Pearson's correlation coefficient was used to determine the association of each ECG criterion with the index of left ventricular mass (LVM, g)/height (m)2.7. The sensitivities and specificities were estimated using a receiver-operating characteristics (ROC) curve in relation to the echocardiographic LVH which was defined as LVM index ≥49 g/m2.7. The correlations of the Cornell voltage and product criteria (r=0.24 and 0.26 respectively, both P0.1) in the area under the ROC curve analysis. The Cornell ECG criteria for the echocardiographic LVH had better performance than the Sokolow-Lyon criteria in a young military male cohort in Taiwan.

  10. Medicinal effect and its JP2/RyR2-based mechanism of Smilax glabra flavonoids on angiotensin II-induced hypertrophy model of cardiomyocytes.

    Science.gov (United States)

    Cai, Yueqin; Tu, Jue; Pan, Shuizhen; Jiang, Jianping; Shou, Qiyang; Ling, Yun; Chen, Yunxiang; Wang, Dejun; Yang, Weiji; Shan, Letian; Chen, Minli

    2015-07-01

    Rhizome and root of Smilax glabra Roxb (Liliaceae family) is a widely used traditional Chinese medicine (TCM) named Tu-fu-ling (TFL) for cardiac disease therapy. The TFL flavonoids (TFLF) has been extracted and proven to possess the anti-cardiac hypertrophy effect in our previous reports. Such effect could be mediated by the modulation of intracellular Ca(2+) flux in myocardial cells, in which junctophilin-2 (JP2) and ryanodine receptor 2 (RyR2) play an important role. However, its mechanism of the anti-cardiac hypertrophy effect remains unclarified. 2μmol/L Ang II was applied to induce hypertrophy model of rat primary cardiomyocytes. After treatment of TFLF at 0.25, 0.5 and 1.0mg/ml, the cell size was microscopic measured, and the protein and mRNA expressions of JP2 and RyR2 in cardiomyocytes were estimated by immunofluorescence imaging, ELISA and real-time PCR assay. Obvious hypertrophy of cardiomyocytes was induced by Ang II but reversed by TFLF from 0.5 to 1.0mg/ml. The protein and mRNA expressions of JP2 and RyR2 in cardiomyocytes were also inhibited by Ang II but restored by TFLF at its dose range. Such effect of TFLF was exerted at a dose dependent manner, which was even better than that of verapamil. Our findings may evidence the correlation between JP2/RyR2 and myocardiac hypertrophy, and indicate the JP2/RyR2-mediated anti-hypertrophy mechanism of TFLF for the first time. It deserves to be developed as a promising TCM candidate of new drug for myocardial hypertrophy treatment. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. Aerobic interval training reduces inducible ventricular arrhythmias in diabetic mice after myocardial infarction.

    Science.gov (United States)

    Rolim, Natale; Skårdal, Kristine; Høydal, Morten; Sousa, Mirta M L; Malmo, Vegard; Kaurstad, Guri; Ingul, Charlotte B; Hansen, Harald E M; Alves, Marcia N; Thuen, Marte; Haraldseth, Olav; Brum, Patricia C; Slupphaug, Geir; Loennechen, Jan Pål; Stølen, Tomas; Wisløff, Ulrik

    2015-01-01

    Diabetes mellitus (DM) increases the risk of heart failure after myocardial infarction (MI), and aggravates ventricular arrhythmias in heart failure patients. Although exercise training improves cardiac function in heart failure, it is still unclear how it benefits the diabetic heart after MI. To study the effects of aerobic interval training on cardiac function, susceptibility to inducible ventricular arrhythmias and cardiomyocyte calcium handling in DM mice after MI (DM-MI). Male type 2 DM mice (C57BLKS/J Lepr (db) /Lepr (db) ) underwent MI or sham surgery. One group of DM-MI mice was submitted to aerobic interval training running sessions during 6 weeks. Cardiac function and structure were assessed by echocardiography and magnetic resonance imaging, respectively. Ventricular arrhythmias were induced by high-frequency cardiac pacing in vivo. Protein expression was measured by Western blot. DM-MI mice displayed increased susceptibility for inducible ventricular arrhythmias and impaired diastolic function when compared to wild type-MI, which was associated with disruption of cardiomyocyte calcium handling and increased calcium leak from the sarcoplasmic reticulum. High-intensity exercise recovered cardiomyocyte function in vitro, reduced sarcoplasmic reticulum diastolic calcium leak and significantly reduced the incidence of inducible ventricular arrhythmias in vivo in DM-MI mice. Exercise training also normalized the expression profile of key proteins involved in cardiomyocyte calcium handling, suggesting a potential molecular mechanism for the benefits of exercise in DM-MI mice. High-intensity aerobic exercise training recovers cardiomyocyte function and reduces inducible ventricular arrhythmias in infarcted diabetic mice.