Alterations in brain hexokinase activity associated with heart failure in rats

1993 ◽  
Vol 265 (4) ◽  
pp. R923-R928 ◽  
Author(s):  
K. P. Patel ◽  
P. L. Zhang ◽  
T. L. Krukoff
Keyword(s):  
Heart Failure ◽  
Coronary Occlusion ◽  
Diastolic Pressure ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Right Atrial ◽  
Metabolic Enzyme ◽  
Control Group ◽  
Hexokinase Activity ◽  
The Brain

This study examined the activity of discrete regions of the brain as assessed with histological localization and photodensitometric quantification of the metabolic enzyme hexokinase in a group of rats with coronary occlusion (HF) and in sham-operated control rats. Three weeks after surgery, the mean left ventricular end diastolic pressure and right atrial pressure were elevated, and left ventricular peak systolic pressure was decreased in the HF group compared with the sham group; these findings are also observed during heart failure. In addition, histological data indicated that there was a 37.6 +/- 2.8% outer and 40.8 +/- 3.1% inner infarct of the myocardium in the group of rats with HF (n = 6). Rats in the control group had no observable damage to the myocardium (n = 6). Accompanying these symptoms of heart failure were significant increases in hexokinase activity in the parvocellular (pPVN, 16.3%) and magnocellular (mPVN, 17.6%) divisions of the paraventricular nucleus of the hypothalamus, and in the locus ceruleus (LC, 17.1%). No changes in hexokinase activity were observed in the median preoptic area, supraoptic nucleus (SON), subfornical organ, or posterior hypothalamus. These results reinforce the idea that heart failure (with coronary occlusion) is associated with changes in specific areas in the brain and that metabolic alterations in the pPVN, mPVN, and LC are likely related to alterations in vasopressin production, blood volume regulation, and sympathoexcitation observed in the heart failure state.

scholarly journals Elevated Swelling-Activated Chloride Current Densities in Hypertrophied Ventricular Myocytes in a Rabbit Heart Failure Model

2019 ◽  
Vol 22 (2) ◽  
pp. E107-E111
Author(s):  
Hongwei Shi ◽  
Zhenming Jiang ◽  
Teng Wang ◽  
Yongting Chen ◽  
Feng Cao
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Protein Expression ◽  
Diastolic Pressure ◽  
Rabbit Model ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Control Group ◽  
Sham Operation ◽  
Failure Group

Background: The status of the swelling-activated chloride channel (ICl, swell) during heart failure remains unclear. This study aimed to investigate whether the ICl, swell activity is altered during heart failure and to determine how the ICl, swell influences atrial arrhythmias of the failing heart. Methods: We established a heart failure rabbit model and analyzed the hemodynamic indicators 8 weeks after myocardial infarction, which include left ventricular systolic pressure (LVSP) and left ventricular end-diastolic pressure (LVDEP). Five untreated rabbits and 5 receiving a sham operation served as the control group. Left auricular appendage tissues were obtained and CLCN3 mRNA/CLCN3 protein expression levels were examined by using reverse transcription–polymerase chain reaction and Western blot, respectively. Results: Compared to the control group, the heart failure group showed a significantly decreased LVSP (14.2 ± 0.27 versus 16.9 ± 0.86 kPa, P <.05)and elevated LVDEP (2.49 ± 0.30 versus 0.15 ± 0.03 kPa, P <.05), indicating that myocardial infarction leads to progressive heart failure of rabbits in the heart failure group. CLCN3 mRNA and CLCN3 protein expression were both significantly elevated in the heart failure group compared to the control group (P <.05). Conclusion: In sum, we propose that the dynamic nature of ICl, swell upregulation may contribute to the elevated expression of CLCN3 mRNA and CLCN3 protein, resulting in myocardial cell remodeling induced by heart failure. However, further study is needed to investigate the potential functions of ICl, swell, especially the relation between ICl, swell augmentation and arrhythmia after heart failure.

The Effect of Gypenosides on Cardiac Function and Expression of Cytoskeletal Genes of Myocardium in Diabetic Cardiomyopathy Rats

2009 ◽  
Vol 37 (06) ◽  
pp. 1059-1068 ◽  
Author(s):  
Min Ge ◽  
Shanfeng Ma ◽  
Liang Tao ◽  
Sudong Guan
Keyword(s):  
Cardiac Function ◽  
Diabetic Cardiomyopathy ◽  
Diastolic Pressure ◽  
Pure Water ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Control Group ◽  
Sprague Dawley ◽  
Gene Expressions ◽  
Ventricular Systolic Pressure

The relationship between changes of cardiac function and the gene expressions of two major myocardial skeleton proteins, titin and nebulin, and the effect of gypenosides on these gene expressions in diabetic cardiomyopathy rat were explored in the present study. Forty Sprague-Dawley rats were randomly divided into three groups: control group, diabetic cardiomyopathy group and gypenosides-treated diabetic cardiomyopathy group. The diabetic cardiomyopathy was induced in rats by injecting streptozotocin (STZ, 55 mg/kg) intraperitoneally. Seven weeks after the rats suffered from diabetes, the rats were treated with gypenosides 100 mg/kg per day orally for six weeks in gypenosides-treated group. In the meanwhile, the pure water was given to diabetic cardiomyopathy and the control groups. Subsequently, the cardiac functions, including left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), ± dP/dtmax and t–dP/dmaxt, as well as the mRNA content and proteins of titin and nebulin in myocardium were determined. The results indicated that (1) the diabetic cardiomyopathy rats had decreased LVSP and ± dP/dtmax, increased LVEDP, and prolonged t–dP/dtmax than normal rats; (2) LVSP and ± dP/dtmax in diabetic cardiomyopathy rats treated with gypenosides were significantly higher and LVEDP and t–dP/dtmax were significantly lower than those without giving gypenosides; (3) the mRNA contents and proteins of titin and nebulin in diabetic cardiomyopathy rats were remarkably lower than those in the control rats and gypenosides had no effect on mRNA and protein expression levels of titin and nebulin in diabetic cardiomyopathy rats. We conclude that (1) the cardiac function as well as the mRNA expressions of titin and nebulin decreased in diabetic cardiomyopathy rats; (2) gypenosides secure cardiac muscles and their function from diabetic impairment and these beneficial effects of gypenosides are not by changing the expressions of titin and nebulin.

Congestive Heart Failure in Copper-Deficient Mice

2003 ◽  
Vol 228 (7) ◽  
pp. 811-817 ◽  
Author(s):  
Laila Elsherif ◽  
Raymond V. Ortines ◽  
Jack T. Saari ◽  
Y. James Kang
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Left Ventricle ◽  
Diastolic Pressure ◽  
Systolic Pressure ◽  
Pressure Rise ◽  
Experimental Models ◽  
Left Ventricular ◽  
Mouse Heart ◽  
Total Period

Copper Deficiency (CuD) leads to hypertrophic cardiomyopathy in various experimental models. The morphological, electrophysiological, and molecular aspects of this hypertrophy have been under investigation for a long time. However the transition from compensated hypertrophy to decompensated heart failure has not been investigated in the study of CuD. We set out to investigate the contractile and hemodynamic parameters of the CuD mouse heart and to determine whether heart failure follows hypertrophy in the CuD heart. Dams of FVB mice were fed CuD or copper-adequate (CuA) diet starting from the third day post delivery and the weanling pups were fed the same diet for a total period of 5 weeks (pre- and postweanling). At week 4, the functional parameters of the heart were analyzed using a surgical technique for catheterizing the left ventricle. A significant decrease in left ventricle systolic pressure was observed with no significant change in heart rate, and more importantly contractility as measured by the maximal rate of left ventricular pressure rise (+dP/dt) and decline (−dP/dt) were significantly depressed in the CuD mice. However, left ventricle end diastolic pressure was elevated, and relaxation was impaired in the CuD animals; the duration of relaxation was prolonged. In addition to significant changes in the basal level of cardiac function, CuD hearts had a blunted response to the stimulation of the β-adrenergic agonist isoproterenol. Furthermore, morphological analysis revealed increased collagen accumulation in the CuD hearts along with lipid deposition. This study shows that CuD leads to systolic and diastolic dysfunction in association with histopathological changes, which are indices commonly used to diagnose congestive heart failure.

scholarly journals Ginsenoside Re Improves Isoproterenol-Induced Myocardial Fibrosis and Heart Failure in Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Quan-wei Wang ◽  
Xiao-feng Yu ◽  
Hua-li Xu ◽  
Xue-zhong Zhao ◽  
Da-yuan Sui
Keyword(s):  
Heart Failure ◽  
Myocardial Fibrosis ◽  
Group Treatment ◽  
Transforming Growth Factor ◽  
Diastolic Pressure ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Heart Weight ◽  
Hydroxyproline Content ◽  
Ginsenoside Re

Objective. Panax ginseng is used widely for treatment of cardiovascular disorders in China. Ginsenoside Re is the main chemical component of P. ginseng. We aimed to investigate the protective effect of ginsenoside Re on isoproterenol-induced myocardial fibrosis and heart failure in rats. Methods. A model of myocardial fibrosis and heart failure was established by once-daily subcutaneous injection of isoproterenol (5 mg/kg/day) to rats for 7 days. Simultaneously, rats were orally administrated ginsenoside Re (5 or 20 mg/kg) or vehicle daily for 4 weeks. Results. Isoproterenol enhanced the heart weight, myocardial fibrosis, and hydroxyproline content in rat hearts. Ginsenoside Re inhibited (at least in part) the isoproterenol-induced increase in heart weight, myocardial fibrosis, and hydroxyproline content. Compared with the isoproterenol group, treatment with ginsenoside Re ameliorated changes in left ventricular systolic pressure, left ventricular end diastolic pressure, and the positive and negative maximal values of the first derivative of left ventricular pressure. Ginsenoside Re administration also resulted in decreased expression of transforming growth factor (TGF)-β1 in serum and decreased expression of Smad3 and collagen I in heart tissue. Conclusion. Ginsenoside Re can improve isoproterenol-induced myocardial fibrosis and heart failure by regulation of the TGF-β1/Smad3 pathway.

Factors involved in delaying the rise in peripheral resistance in developing heart failure

1994 ◽  
Vol 267 (1) ◽  
pp. H211-H216 ◽  
Author(s):  
K. Kiuchi ◽  
R. P. Shannon ◽  
N. Sato ◽  
M. Bigaud ◽  
C. Lajoie ◽  
...  
Keyword(s):  
Heart Failure ◽  
Diastolic Pressure ◽  
Peripheral Resistance ◽  
Left Ventricular ◽  
Right Atrial ◽  
Plasma Norepinephrine ◽  
Peripheral Vascular ◽  
Vascular Control ◽  
Developing Heart

The development of heart failure (HF) on peripheral vascular control was studied in 10 conscious dogs with measurements of cardiac output (CO) and left ventricular (LV), arterial, and right atrial pressures. At 3 wk after pacing-induced HF, CO was not decreased from 2.5 +/- 0.2 l/min, whereas LV dP/dt fell (from 2,858 +/- 71 to 1,409 +/- 69 mmHg/s) and LV end-diastolic pressure increased (from 4.8 +/- 0.4 to 27.3 +/- 1.1 mmHg) (P < 0.05). At 4–7 wk after pacing, CO was significantly decreased (to 1.6 +/- 0.1 l/min; P < 0.05), but total peripheral resistance (TPR) did not rise, despite increases in plasma norepinephrine and renin activity (P < 0.05). In the presence of ganglionic blockade, TPR was still not increased in HF. In vitro studies in isolated femoral artery segments demonstrated reduced intrinsic tone (0.028 +/- 0.007 g/mg; P < 0.05) as compared with vessels from sham-operated controls (0.124 +/- 0.023 g/mg), whereas the intracellular calcium level was not altered in HF. Thus, during the development of HF, severe contractile dysfunction precedes the fall in CO, which, in turn, precedes the rise in TPR. The delayed rise in TPR appears to involve a reduction in intrinsic peripheral vascular tone, despite neurohumoral activation.

scholarly journals Novel Neuromodulation Approach to Improve Left Ventricular Contractility in Heart Failure

2020 ◽  
Vol 13 (11) ◽  
Author(s):  
Vivek Y. Reddy ◽  
Jan Petrů ◽  
Filip Málek ◽  
Lee Stylos ◽  
Steve Goedeke ◽  
...  
Keyword(s):  
Heart Failure ◽  
Pulmonary Artery ◽  
Diastolic Pressure ◽  
Acute Decompensated Heart Failure ◽  
Systolic Pressure ◽  
Decompensated Heart Failure ◽  
Left Ventricular ◽  
Ventricular Contractility ◽  
Right Pulmonary Artery ◽  
The Right

Background: Morbidity and mortality outcomes for patients admitted for acute decompensated heart failure are poor and have not significantly changed in decades. Current therapies are focused on symptom relief by addressing signs and symptoms of congestion. The objective of this study was to test a novel neuromodulation therapy of stimulation of epicardial cardiac nerves passing along the posterior surface of the right pulmonary artery. Methods: Fifteen subjects admitted for defibrillator implantation and ejection fraction ≤35% on standard heart failure medications were enrolled. Through femoral arterial access, high fidelity pressure catheters were placed in the left ventricle and aortic root. After electro anatomic rendering of the pulmonary artery and branches, either a circular or basket electrophysiology catheter was placed in the right pulmonary artery to allow electrical intravascular stimulation at 20 Hz, 4 ms pulse width, and ≤20 mA. Changes in maximum positive dP/dt (dP/dt Max ) indicated changes in ventricular contractility. Results: Of 15 enrolled subjects, 5 were not studied due to equipment failure or abnormal pulmonary arterial anatomy. In the remaining subjects, dP/dt Max increased significantly by 22.6%. There was also a significant increase in maximum negative dP/dt (dP/dt Min ), mean arterial pressure, systolic pressure, diastolic pressure, and left ventricular systolic pressure. There was no significant change in heart rate or left ventricular diastolic pressure. Conclusions: In this first-in-human study, we demonstrated that in humans with stable heart failure, left ventricular contractility could be accentuated without an increase in heart rate or left ventricular filling pressures. This benign increase in contractility may benefit patients admitted for acute decompensated heart failure.

Vascular β-adrenergic receptor system is dysfunctional after myocardial infarction

2001 ◽  
Vol 280 (3) ◽  
pp. H1129-H1135 ◽  
Author(s):  
Mohamed A. Gaballa ◽  
Andrea Eckhart ◽  
Walter J. Koch ◽  
Steven Goldman
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Carotid Artery ◽  
Membrane Protein ◽  
Adrenergic Receptor ◽  
Vascular Reactivity ◽  
Diastolic Pressure ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Receptor System

We identified abnormalities in the vascular β-adrenergic receptor (β-AR) signaling pathway in heart failure after myocardial infarction (MI). To examine these abnormalities, we measured β-AR-mediated hemodynamics, vascular reactivity, and the vascular β-AR molecular signaling components in rats with heart failure after MI. Six weeks after MI, these rats had an increased left ventricular (LV) end-diastolic pressure, decreased LV systolic pressure, and decreased rate of LV pressure change (dP/d t). LV dP/d t responses to isoproterenol were shifted downward, although the responses for systemic vascular resistance were shifted upward in heart failure rats ( P < 0.05). Isoproterenol- and IBMX-induced vasorelaxations were blunted in heart failure rats ( P< 0.05) with no change in the forskolin-mediated vasorelaxation. These changes were associated with the following alterations in β-AR signaling ( P < 0.05): decreases in β-AR density (aorta: 58.7 ± 6.0 vs. 35.7 ± 1.9 fmol/mg membrane protein; carotid: 29.6 ± 5.6 vs. 18.0 ± 3.9 fmol/mg membrane protein, n = 5), increases in G protein-coupled receptor kinase activity levels (relative phosphorimage counts of 191 ± 39 vs. 259 ± 26 in the aorta and 115 ± 30 vs. 202 ± 7 in the carotid artery, n = 5), and decreases in cGMP and cAMP in the carotid artery (0.85 ± 0.10 vs. 0.31 ± 0.06 pmol/mg protein and 2.3 ± 0.3 vs. 1.2 ± 0.1 pmol/mg protein, n = 5) with no change in Gαs or Gαi in the aorta. Thus in heart failure there are abnormalities in the vascular β-AR system that are similar to those seen in the myocardium. This suggests a common neurohormonal mechanism and raises the possibility that treatment in heart failure focused on the myocardium may also affect the vasculature.

scholarly journals Involvement of Sirtuins and Klotho in Cardioprotective Effects of Exercise Training Against Waterpipe Tobacco Smoking-Induced Heart Dysfunction

2021 ◽  
Vol 12 ◽  
Author(s):  
Samaneh Sadat Alavi ◽  
Siyavash Joukar ◽  
Farzaneh Rostamzadeh ◽  
Hamid Najafipour ◽  
Fatemeh Darvishzadeh-mahani ◽  
...  
Keyword(s):  
Exercise Training ◽  
Tobacco Smoking ◽  
Diastolic Pressure ◽  
Heart Function ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Smoke Inhalation ◽  
Control Group ◽  
Heart Dysfunction ◽  
Waterpipe Tobacco Smoking

Despite its negative effect on the cardiovascular system, waterpipe smoking (WPS) is currently popular worldwide, especially among youth. This study investigated the effects of moderate endurance exercise on heart function of rats exposed to WPS and its possible mechanism. The animals were randomly divided into four groups: control group (CTL), the exercise group (Ex) which trained for 8 weeks, the waterpipe tobacco smoking group (S) exposed to smoke inhalation (30 min per day, 5 days each week, for 8 weeks), and the group that did exercise training and received waterpipe tobacco smoke inhalation together (Ex + S). One day after the last session of Ex and WPS, cardiac pressures and functional indices were recorded and calculated. The levels of SIRT1, SIRT3, Klotho, Bax, and Bcl-2 in the serum and heart, the expression of phosphorylated GSK3β of heart tissue, and cardiac histopathological changes were assessed. WPS reduced systolic pressure, +dP/dt max, -dP/dt max, and heart contractility indices (P &lt; 0.001 vs. CTL) and increased cardiac tissue lesions (P &lt; 0.05 vs. CTL) and end diastolic pressure and Tau index (P &lt; 0.001 vs. CTL) of the left ventricle. Exercise training normalized the left ventricular end diastolic pressure, +dP/dt max, and contractility index. Also, exercise improved the levels of SIRT1, SIRT3, Klotho, and Bcl-2 and reduced Bax level in the heart. The findings showed that WPS causes left ventricular dysfunction. Moderate exercise prevented WPS-induced heart dysfunction partly through its anti-apoptotic features and activation of the sirtuins and Klotho pathways.

Abstract 12325: Compensatory Increase of Left Atrial External Work to Left Ventricular Dysfunction During Afterload Increase: Insights Into the Mechanism of Decompensation in Heart Failure With Preserved Ejection Fraction

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Katsuji Inoue ◽  
Toshihiko Asanuma ◽  
Kasumi Masuda ◽  
Daisuke Sakurai ◽  
Masamichi Oka ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Diastolic Pressure ◽  
Systolic Pressure ◽  
Strain Curve ◽  
Left Ventricular ◽  
Preserved Ejection Fraction ◽  
External Work ◽  
Reservoir Function ◽  
Left Pulmonary Vein

Introduction: Afterload mismatch is considered as a cause of acute decompensation in patients with heart failure with preserved ejection fraction (HFPEF). However, behaviors of left atrium (LA) and ventricle (LV) to afterload increase have not been fully elucidated. We investigated how LA and LV acted to acute increase in afterload using speckle tracking echocardiography. Methods: Serial echocardiographic and hemodynamic data were acquired in 10 dogs during banding of the descending aorta (AoB). LA pressure was measured by a micromanometer via left pulmonary vein. As shown in Figure, peak negative strain during LA contraction and strain change during LA relaxation (early reservoir strain) and that during systole (late reservoir strain) were generated by simultaneous acquisition of LA longitudinal strain and volume. Pressure-strain curve showed 2 loops (A-loop, V-loop) and areas in A-loop and V-loop were computed as the work during active contraction and relaxation (A-work) and that during passive filling and emptying (V-work), respectively. Results: AoB increased LV systolic pressure by about 60 mmHg, mean LA pressure (3.8±1.3 vs. 7.1±2.0 mmHg) and LV end-diastolic pressure (4.5±1.7 vs. 10.7±4.0 mmHg, all p < 0.01). LV global circumferential strain decreased (-18.8±3.5 vs. -13.2±3.5%, p < 0.01) but LV stroke volume was maintained (8.4±2.3 vs. 9.6±3.6 ml). LA peak negative strain (-2.9±2.3 vs. -9.8±4.0%, p < 0.01) and early reservoir strain (3.4±1.1 vs. 7.8±2.6%, p < 0.01) increased substantially by AoB, but late reservoir function did not change (9.3±3.5 vs. 6.1±2.0%). A-work significantly increased (3.2±2.0 to 19.2±15.1 mmHg %, p < 0.01), while V-work did not change (13.3±7.1 vs. 13.6±8.0 mmHg %). Conclusions: During aortic banding, LA contraction, early reservoir function and thereby external work during the phase increased as a compensation to LV dysfunction. The failure of this mechanism may lead to decompensation in HFPEF.

GH-releasing peptides improve cardiac dysfunction and cachexia and suppress stress-related hormones and cardiomyocyte apoptosis in rats with heart failure

2005 ◽  
Vol 289 (4) ◽  
pp. H1643-H1651 ◽  
Author(s):  
Xiang-Bin Xu ◽  
Jin-Jiang Pang ◽  
Ji-Min Cao ◽  
Chao Ni ◽  
Rong-Kun Xu ◽  
...  
Keyword(s):  
Heart Failure ◽  
Diastolic Pressure ◽  
Systolic Pressure ◽  
Pressure Overload ◽  
Chronic Administration ◽  
Posterior Wall ◽  
Left Ventricular ◽  
Cardiomyocyte Apoptosis ◽  
Lv Function ◽  
Cardiac Cachexia

Growth hormone (GH)-releasing peptides (GHRP), a class of synthetic peptidyl GH secretagogues, have been reported to exert a cardioprotective effect on cardiac ischemia. However, whether GHRP have a beneficial effect on chronic heart failure (CHF) is unclear, and the present work aims to clarify this issue. At 9 wk after pressure-overload CHF was created by abdominal aortic banding in rats, one of four variants of GHRP (GHRP-1, -2, and -6 and hexarelin, 100 μg/kg) or saline was injected subcutaneously twice a day for 3 wk. Echocardiography and cardiac catheterization were performed to monitor cardiac function and obtain blood samples for hormone assay. GHRP treatment significantly improved left ventricular (LV) function and remodeling in CHF rats, as indicated by increased LV ejection fraction, LV end-systolic pressure, and diastolic posterior wall thickness and decreased LV end-diastolic pressure and LV end-diastolic dimension. GHRP also significantly alleviated development of cardiac cachexia, as shown by increases in body weight and tibial length in CHF rats. Plasma CA, renin, ANG II, aldosterone, endothelin-1, and atrial natriuretic peptide were significantly elevated in CHF rats but were significantly decreased in GHRP-treated CHF rats. GHRP suppressed cardiomyocyte apoptosis and increased cardiac GH secretagogue receptor mRNA expression in CHF rats. GHRP also decreased myocardial creatine kinase release in hypophysectomized rats subjected to acute myocardial ischemia. We conclude that chronic administration of GHRP alleviates LV dysfunction, pathological remodeling, and cardiac cachexia in CHF rats, at least in part by suppressing stress-induced neurohormonal activations and cardiomyocyte apoptosis.

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