Growth hormone reverses age-related cardiac myofilament dysfunction in rats

2001 ◽  
Vol 281 (2) ◽  
pp. H915-H922 ◽  
Author(s):  
Thomas Wannenburg ◽  
Amir S. Khan ◽  
David C. Sane ◽  
Mark C. Willingham ◽  
Tony Faucette ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Cardiac Contractility ◽  
Left Ventricular ◽  
Force Generation ◽  
Brown Norway ◽  
Isolated Hearts ◽  
Gh Replacement ◽  
Age Related ◽  
Cardiac Myofilament ◽  
Lv Volume

We tested the hypotheses that aging is associated with a reduction in overall cardiac contractility and myofilament force generation that could be reversed with growth hormone (GH) replacement. Three groups of male Brown-Norway rats were studied: young (YSAL: 8 mo old, n = 13), old (OSAL: 28 mo old, n = 13), and old GH-treated (OGH: 28 mo old, n = 12; 300 μg bovine GH, twice a day for 30 days). The left ventricular (LV) pressure-volume relation was derived in isolated hearts, after which isolated trabecular muscles from these hearts were permeabilized and maximal myofilament force generation (Fmax) was measured. LV developed pressures at a LV volume of 0.3 ml were significantly depressed with age: 84 ± 6 vs. 71 ± 6 mmHg (YSAL vs. OSAL, respectively, P= 0.001) and not restored by GH (69 ± 4 mmHg). Fmaxwas reduced in the aged hearts: 47.5 ± 3.12 vs. 35.9 ± 3.03 mN/mm2 (YSAL vs. OSAL, respectively, P = 0.014) but was restored with GH replacement to 46.7 ± 3.12 mN/mm2 (OSALvs. OGH, P = 0.021). Our results suggest that cellular myofilament contractility is reduced with aging and restored with GH replacement.

Abstract 33: Prostaglandin E2 Reduces Cardiac Contractility via EP3 Receptor

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Xiaosong Gu ◽  
Jiang Xu ◽  
Xiao-Ping Yang ◽  
Edward Peterson ◽  
Pamela Harding
Keyword(s):  
Prostaglandin E2 ◽  
Cardiac Contractility ◽  
Peak Height ◽  
Left Ventricular ◽  
Reduced Ejection Fraction ◽  
Langendorff Preparation ◽  
Cell Contractility ◽  
Isolated Hearts ◽  
Developed Pressure ◽  
Ep3 Receptor

Prostaglandin E2 (PGE2) EP receptors EP3 and EP4 are present in the heart and signal via decreased and increased cAMP production, respectively. Previously we reported that cardiomyocyte-specific EP4 KO mice develop a phenotype of dilated cardiomyopathy with reduced ejection fraction. We thus hypothesized that PGE2 decreases contractility via EP3. To test this hypothesis, the effects of PGE2 and the EP1/EP3 agonist sulprostone (sulp) were examined in the mouse langendorff preparation and in adult mouse cardiomyocytes (AVM) using the IonOptix cell contractility system. Isolated hearts of 18-20 wk old male C57Bl/6 mice were mounted and equilibrated for 10 min, then perfused with PGE2 (10 -6 mol/l) or sulp (10 -6 mol/l) for 30 min. Values at the end of equilibration were set to 100%. Compared to vehicle, PGE2 decreased +dp/dt (77.8±3% vs 96.7±3%, p<0.01) and left ventricular developed pressure, LVDP (77.2±2% vs 96.8±3%, p<0.001). Sulp decreased +dp/dt (75.9±2% vs 96.7±3%, p<0.001), -dp/dt (72.2±1% vs 85.7±1%, p<0.01) and LVDP (70.9±1% vs 96.8±3%, p<0.001). The effects of both PGE2 and sulp were reversed by the EP3 antagonist, L789,106 (10 -6 mol/l). Myocyte contractility was evaluated on the IonOptix system with pacing at 1Hz. Treatment with PGE2 (10 -9 M) for 10 min reduced contractility as measured by peak height (3.69 ± 0.48% for vehicle vs 2.00 ± 0.22% for PGE2, p < 0.05 ), departure velocity (-171.9 ± 22.9 um/sec for vehicle vs -106.3± 12.5 um/sec for PGE2, p < 0.05) and return velocity (87.7 ± 16.3 um/sec for vehicle vs 36.7 ± 6.6 um/sec for PGE2, p < 0.05) with similar effects noted for sulp. Sulp reduced change in peak height (4.79 ± 1.15% for vehicle vs 1.81 ± 0.37% for sulp, p < 0.05), departure velocity (-169.1 ± 35.8 um/sec for vehicle vs -59.4 ± 10.3 um/sec for sulp, p < 0.05) and return velocity (86.5 ± 23.8 um/sec for vehicle vs 16.9 ± 14.7 um/sec for sulp, p < 0.05). We then examined the acute effects of PGE2 and sulp on expression of phosphorylated phospholamban (PLN) and SERCA using Western blot. Treatment of AVM for 15min with either PGE2 or sulp decreased expression of phosphorylated PLN corrected to total PLN, by 67% and 43%. SERCA2a expression was unaffected. In conclusion, PGE2 and sulp reduce contractility via the EP3 receptor through effects on PLN.

Influence of age and run training on cardiac Na+/Ca2+ exchange

2003 ◽  
Vol 95 (5) ◽  
pp. 1994-2003 ◽  
Author(s):  
Lisa C. Mace ◽  
Bradley M. Palmer ◽  
David A. Brown ◽  
Korinne N. Jew ◽  
Joshua M. Lynch ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Action Potential ◽  
Left Ventricular ◽  
Brown Norway ◽  
Resting Membrane Potential ◽  
Whole Cell Patch Clamp ◽  
Age Related ◽  
Intracellular Ca ◽  
Whole Heart ◽  
Exchange Activity

Effects of age and training on myocardial Na+/Ca2+ exchange were examined in young sedentary (YS; 14-15 mo), aged sedentary (AS; 27-31 mo), and aged trained (AT; 8- to 11-wk treadmill run training) male Fischer Brown Norway rats. Whole heart performance and isolated cardiocyte Na+/Ca2+ exchange characteristics were measured. At the whole heart level, a small but significant slowing of late isovolumic left ventricular (LV) relaxation, which may be indicative of altered Na+/Ca2+ exchange activity, was seen in hearts from AS rats. This subtle impairment in relaxation was not observed in hearts from AT rats. At the single-cardiocyte level, late action potential duration was prolonged, resting membrane potential was more positive, and overshoot potential was greater in cardiocytes from AS rats than from YS rats ( P < 0.05). Training did not influence any of these age-related action potential characteristics. In electrically paced cardiocytes, neither shortening nor intracellular Ca2+ concentration ([Ca2+]i) dynamics was influenced by age or training. Similarly, neither age nor training influenced the rate of [Ca2+]i clearance via forward (Nain+ /Caout2+) Na+/Ca2+ exchange after caffeine-induced Ca2+ release from the sarcoplasmic reticulum or cardiac Na+/Ca2+ exchanger protein (NCX1) expression. However, when whole cell patch-clamp techniques combined with fluorescence microscopy were used to evaluate the ability of Na+/Ca2+ exchange to alter cytosolic [Ca2+] ([Ca2+]c) under conditions where membrane potential ( Vm) and internal and external [Na+] and [Ca2+] could be controlled, we observed age-associated increases in forward Na+/Ca2+ exchange-mediated [Ca2+]c clearance ( P < 0.05) that were not influenced by training. The age-related increase in forward Na+/Ca2+ exchange activity provides a hypothetical explanation for the late action potential prolongation observed in this study.

Inhaled nitric oxide prevents left ventricular impairment during endotoxemia

1998 ◽  
Vol 85 (6) ◽  
pp. 2018-2024 ◽  
Author(s):  
Satoshi Ishihara ◽  
John A. Ward ◽  
Osamu Tasaki ◽  
Basil A. Pruitt ◽  
Cleon W. Goodwin ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Left Ventricle ◽  
Cardiac Contractility ◽  
Ringer Solution ◽  
Left Ventricular ◽  
Control Group ◽  
Baseline Levels ◽  
Lv Volume

We evaluated the effect of long-term inhalation of nitric oxide (NO) on cardiac contractility after endotoxemia by using the end-systolic elastance of the left ventricle (LV) as a load-independent contractility index. Chronic instrumentation in 12 pigs included implantation of two pairs of endocardial dimension transducers to measure LV volume and a micromanometer to measure LV pressure. One week later, the animals were divided into a control group ( n = 6) or a NO group ( n = 6). All animals received intravenous Escherichia coliendotoxin (10 μg ⋅ kg−1 ⋅ h−1) and equivalent lactated Ringer solution. NO inhalation (20 parts/million) was begun 30 min after the initiation of endotoxemia and was continued for 24 h. In both groups, tachycardia, pulmonary hypertension, and systemic hyperdynamic changes were noted. The end-systolic elastance in the control group was significantly decreased beyond 7 h. NO inhalation maintained the end-systolic elastance at baseline levels and prevented its impairment. These findings indicate that NO exerts a protective effect on LV contractility in this model of endotoxemia.

Impaired distensibility of the left ventricle after stiffening of the right ventricle

2001 ◽  
Vol 91 (1) ◽  
pp. 435-440 ◽  
Author(s):  
Masanori Shirakabe ◽  
Seiji Yamaguchi ◽  
Yoshiaki Tamada ◽  
Gajendra Baniya ◽  
Akio Fukui ◽  
...  
Keyword(s):  
Diastolic Pressure ◽  
Left Ventricular ◽  
Coronary Artery Ligation ◽  
Free Wall ◽  
Artery Ligation ◽  
Isolated Hearts ◽  
Regional Area ◽  
Myocardial Stretch ◽  
Lv Volume ◽  
The Right

Acute and chronic alterations of right ventricular (RV) wall properties can change left ventricular (LV) performance. We investigated whether and how stiffening of the RV free wall alters LV diastolic distensibility. We used cross-circulated isolated hearts, in which the LV and RV were independently controllable. Stiffness of the RV free wall was altered by intramuscular injections of glutaraldehyde into the RV free wall after right coronary artery ligation. We measured circumferential and longitudinal regional lengths in the septum and LV free wall. During data acquisition, RV volume was held constant. After the RV free wall was stiffened by glutaraldehyde, the LV diastolic pressure-volume relation shifted upward and became steeper. Importantly, stiffening of the RV free wall increased the diastolic regional area in the septum and LV free wall under constant LV volume. The augmented regional dimensions may result in enhanced regional tension under constant LV volume and may be related to the observed increase in LV diastolic intracavitary pressure. The impaired LV diastolic distensibility by stiffening of the RV free wall may be at least partly explained by myocardial stretch, probably due to LV deformation.

Nitric oxide modulates cardiac contractility and oxygen consumption without changing contractile efficiency

1998 ◽  
Vol 275 (1) ◽  
pp. H41-H49 ◽  
Author(s):  
Naoyuki Suto ◽  
Atsushi Mikuniya ◽  
Tomoyuki Okubo ◽  
Hiroyuki Hanada ◽  
Nobuyo Shinozaki ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Oxygen Consumption ◽  
Cardiac Contractility ◽  
Systolic Pressure ◽  
Oxygen Metabolism ◽  
Left Ventricular ◽  
Before And After ◽  
Lv Volume ◽  
Synthase Inhibitor

Nitric oxide (NO) affects myocardial contractility and myocardial oxygen consumption (MV˙o 2) in vitro. In α-chloralose-anesthetized dogs instrumented for the measurements of left ventricular (LV) pressure, LV volume using a conductance catheter, coronary blood flow, and coronary venous oxygen saturation (S[Formula: see text]) using a fiber-optic catheter, LV end-systolic pressure-volume relationships (ESPVR) and the relationship between MV˙o 2 and LV pressure-volume area (PVA) were analyzed before and after intravenous infusions of the NO synthase inhibitor N G-monomethyl-l-arginine acetate (l-NMMA; 5 mg/kg, 8 dogs) and the NO substrate l-arginine (600 mg/kg, 7 dogs). l-NMMA increased the slope of the ESPVR ( E max) ( P < 0.05) without changing contractile efficiency indicated by the inverse of the slope of the MV˙o 2-PVA line.l-NMMA also increased unloaded MV˙o 2, indicated by the y-axis intercept of the MV˙o 2-PVA line ( P < 0.05). In contrast,l-arginine decreased E max( P < 0.05) while decreasing MV˙o 2( P < 0.05), and without changing contractile efficiency. The basal oxygen metabolism was not affected byl-NMMA andl-arginine. These data imply that endogenous NO spares MV˙o 2 by reducing oxygen use in excitation-contraction coupling and attenuates cardiac contractility without changing contractile efficiency.

scholarly journals Long-term growth hormone (GH) replacement of adult GH deficiency (GHD) benefits the heart

2019 ◽  
Vol 181 (1) ◽  
pp. 79-91 ◽  
Author(s):  
A Ziagaki ◽  
D Blaschke ◽  
W Haverkamp ◽  
U Plöckinger
Keyword(s):  
Heart Failure ◽  
Growth Hormone ◽  
Gh Deficiency ◽  
Interventricular Septum ◽  
Standard Deviation Score ◽  
Left Ventricular ◽  
Amino Terminal ◽  
Gh Replacement

Objective Growth hormone (GH) deficiency is related to increased cardiovascular mortality. We studied clinical status, concentration of amino-terminal-pro B-type natriuretic-peptide (NT-proBNP) and echocardiographic parameters during long-term GH replacement (GH-R). Methods Fifty-one patients (29 females), 45.9 ± 11.3 years (mean ± s.d.), median follow-up 36.2 months, echocardiography and laboratory determinations initially and at 12-months intervals. Results At the last follow-up (last observation carried forward) (LFU (LOCF)) insulin-like growth-factor-1 standard deviation score (IGF-1 SDS) was ±1 in 92% of the patients. The median NT-proBNP declined significantly and stabilized (−40.5%) at LFU (LOCF) due to patients with a basal NT-proBNP >125 ng/L (indicative of heart failure). The basal NT-proBNP and the final IGF-1 SDS were significant predictors of the NT-proBNP at LFU (LOCF). Initially left ventricular enddiastolic diameter (LVEDD), left ventricular posterior wall diameter (LVPWD) and ejection fraction (EF) were normal, while interventricular septum diameter (IVSD) and left ventricular mass index (LVMi) were slightly increased. LVPWD and IVSD had significantly declined by year three. The LVMi was moderately to severely abnormal in 37.3 and 52.0% of patients initially and at LFU (LOCF). At LFU (LOCF) LVMi and IGF-1 were significantly correlated in the 14 male patients of this subgroup. Conclusion Long-term GH-R of GHD positively affected ISVD and LVPWD. In a subgroup of patients with severe GHD, LVMi increased concomitantly to the decline in NT-proBNP and this was positively correlated to the final IGF-1 concentration. Whether this observation indicates a positive development in a structurally altered heart muscle (reversal of adverse remodelling) or poses a future risk for heart failure needs further follow-up.

scholarly journals Hemodynamic and electromechanical effects of paraquat in rat heart

2020 ◽  
Author(s):  
Chih-Chuan Lin ◽  
Kuang-Hung Hsu ◽  
Gwo-Jyh Chang
Keyword(s):  
Ventricular Myocytes ◽  
Cardiac Contractility ◽  
Left Ventricular ◽  
Qtc Interval ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Isolated Hearts ◽  
Dose Dependent

AbstractParaquat (PQ) is a highly lethal herbicide. Ingestion of large quantities of PQ usually results in cardiovascular collapse and eventually death. However, the mechanism of acute PQ poisoning induced cardiotoxicity is poorly understood. Therefore, the purpose of the present study was to aim to investigate the mechanisms of PQ induced cardiotoxicity by examining the effects of PQ on hemodynamics in vivo, as well as in vitro on isolated hearts and ventricular myocytes in rats. Intravenous administration of PQ (100 or 180 mg/kg) in anesthetized rats induced dose-dependent decreases in heart rate, blood pressure, and cardiac contractility (left ventricular [LV] dP/dtmax). Furthermore, it prolonged the rate-corrected QT (QTc) interval. In Langendorff-perfused isolated hearts, PQ (33 or 60 μM) decreased LV pressure and contractility (LV dP/dtmax in isolated ventricular myocytes), PQ (10–60 μM) decreased the amplitude of Ca2+ transients and cell shortening in a concentration-dependent manner. Patch-clamp experiments demonstrated that PQ decreased the amplitude and availability of the transient outward K+ channel (Ito) and altered its gating kinetics. These results suggest that PQ-induced cardiotoxicity results mainly from diminished Ca2+ transients and inhibited K+ channels, which lead to the suppression of LV contractile force and prolongation of the QTc interval.

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