Decreased [3H]ouabain binding sites in skeletal muscle of rats with chronic heart failure

1997 ◽  
Vol 83 (1) ◽  
pp. 323-323 ◽  
Author(s):  
Joel G. Pickar ◽  
John P. Mattson ◽  
Steve Lloyd ◽  
Timothy I. Musch
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Body Weight ◽  
Chronic Heart Failure ◽  
Exercise Capacity ◽  
Binding Sites ◽  
Weight Ratio ◽  
Left Ventricular ◽  
Body Weight Ratio ◽  
Ouabain Binding

Pickar, Joel G., John P. Mattson, Steve Lloyd, and Timothy I. Musch. Decreased [3H]ouabain binding sites in skeletal muscle of rats with chronic heart failure. J. Appl. Physiol. 83(1): 323–329, 1997.—Abnormalities intrinsic to skeletal muscle are thought to contribute to decrements in exercise capacity found in individuals with chronic heart failure (CHF). Na+-K+-adenosinetriphosphatase (the Na+ pump) is essential for maintaining muscle excitability and contractility. Therefore, we investigated the possibility that the number and affinity of Na+ pumps in locomotor muscles of rats with CHF are decreased. Myocardial infarction (MI) was induced in 8 rats, and a sham operation was performed in 12 rats. The degree of CHF was assessed ∼180 days after surgery. Soleus and plantaris muscles were harvested, and Na+pumps were quantified by using a [3H]ouabain binding assay. At the time of muscle harvest, MI and sham-operated rats were similar in age (458 ± 54 vs. 447 ± 34 days old, respectively). Compared with their sham-operated counterparts, MI rats had a significant amount of heart failure, right ventricular-to-body weight ratio was greater (48%), and the presence of pulmonary congestion was suggested by an elevated lung-to-body weight ratio (29%). Left ventricular end-diastolic pressure was significantly increased in the MI rats (11 ± 1 mmHg) compared with the sham-operated controls (1 ± 1 mmHg). In addition, mean arterial blood pressure was lower in the MI rats compared with their control counterparts. [3H]ouabain binding sites were reduced 18% in soleus muscle (136 ± 12 vs. 175 ± 13 pmol/g wet wt, MI vs. sham, respectively) and 22% in plantaris muscle (119 ± 12 vs. 147 ± 8 pmol/g wet wt, MI vs. sham, respectively). The affinity of these [3H]ouabain binding sites was similar for the two groups. The relationship between the reduction in Na+ pump number and the reduced exercise capacity in individuals with CHF remains to be determined.

scholarly journals Progressive chronic heart failure slows the recovery of microvascular O2 pressures after contractions in the rat spinotrapezius muscle

2010 ◽  
Vol 299 (6) ◽  
pp. H1755-H1761 ◽  
Author(s):  
Steven W. Copp ◽  
Daniel M. Hirai ◽  
Leonardo F. Ferreira ◽  
David C. Poole ◽  
Timothy I. Musch
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Body Weight ◽  
Chronic Heart Failure ◽  
Diastolic Pressure ◽  
Fiber Type ◽  
Weight Ratio ◽  
Left Ventricular ◽  
Type I ◽  
Body Weight Ratio

Chronic heart failure (CHF) induces muscle fiber-type specific alterations in skeletal muscle O2 delivery and utilization during metabolic transitions. As a result, the recovery of microvascular Po2 (PmvO2) is prolonged in slow-twitch skeletal muscle but not fast-twitch skeletal muscle in rats with CHF. We tested the hypothesis that CHF slows PmvO2 recovery in rat skeletal muscle of a mixed fiber-type analogous to human locomotory muscles and that the degree of slowing correlates with central indexes of heart failure. Healthy control [ n = 6, left ventricular end-diastolic pressure (LVEDP): 10 ± 1 mmHg], moderate CHF ( n = 6, LVEDP: 18 ± 2 mmHg), and severe CHF ( n = 4, LVEDP: 34 ± 2 mmHg) female Sprague-Dawley rats had their right spinotrapezius muscles (41% type I, 7% type IIa, and 52% type IIb and d/x) exposed, and PmvO2 was measured via phosphorescence quenching during 180 s of recovery from 180 s of electrically induced twitch contractions (1 Hz, 4–6 V). CHF progressively slowed the mean response time (MRT; the time to reach 63% of the overall dynamic response) of PmvO2 recovery (MRToff; control: 60.2 ± 6.9, moderate CHF: 72.8 ± 6.6, and severe CHF: 109.8 ± 6.6 s, P < 0.05 for all). MRToff correlated positively with central hemodynamic (LVEDP: r = 0.76, P < 0.01) and morphological (right ventricle-to-body weight ratio: r = 0.74, P < 0.01; and lung weight-to-body weight ratio: r = 0.79, P < 0.01) indexes of heart failure. The present investigation suggests that slowed PmvO2 kinetics during recovery in CHF constitutes a mechanistic link between impaired circulatory and metabolic recovery after contractions in CHF.

Skeletal muscle ouabain binding sites are reduced in rats with chronic heart failure

2002 ◽  
Vol 92 (6) ◽  
pp. 2326-2334 ◽  
Author(s):  
Timothy I. Musch ◽  
Swen Wolfram ◽  
K. Sue Hageman ◽  
Joel G. Pickar
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Chronic Heart Failure ◽  
Oxygen Uptake ◽  
Binding Sites ◽  
Ouabain Binding ◽  
High Affinity ◽  
Lv Dysfunction ◽  
Run Time ◽  
Fast Twitch

Intrinsic skeletal muscle abnormalities decrease muscular endurance in chronic heart failure (CHF). In CHF patients, the number of skeletal muscle Na+-K+ pumps that have a high affinity for ouabain (i.e., the concentration of [3H]ouabain binding sites) is reduced, and this reduction is correlated with peak oxygen uptake. The present investigation determined whether the concentration of skeletal muscle [3H]ouabain binding sites found during CHF is related to 1) severity of the disease state, 2) muscle fiber type composition, and/or 3) endurance capacity. Four muscles were chosen that represented slow-twitch oxidative (SO), fast-twitch oxidative glycolytic (FOG), fast-twitch glycolytic (FG), and mixed fiber types. Measurements were obtained 8–10 wk postsurgery in 23 myocardial infarcted (MI) and 18 sham-operated control (sham) rats. Eighteen rats had moderate left ventricular (LV) dysfunction [LV end-diastolic pressure (LVEDP) < 20 mmHg], and five had severe LV dysfunction (LVEDP > 20 mmHg). Rats with severe LV dysfunction had significant pulmonary congestion and were likely in a chronic state of compensated congestive failure as indicated by an approximately twofold increase in both lung and right ventricle weight. Run time to fatigue and maximal oxygen uptake (V˙o 2 max) were significantly reduced (↓39 and ↓28%, respectively) in the rats with severe LV dysfunction and correlated with the magnitude of LV dysfunction as indicated by LVEDP (run time: r = 0.60, n = 21, P < 0.01 and V˙o 2 max: r = 0.93, n = 13, P < 0.01). In addition, run time to fatigue was significantly correlated withV˙o 2 max ( r = 0.87, n = 15, P < 0.01). The concentration of [3H]ouabain binding sites (Bmax) was significantly reduced (21–28%) in the three muscles comprised primarily of oxidative fibers [soleus: 259 ± 14 vs. 188 ± 17; plantaris: 295 ± 17 vs. 229 ± 18; red portion of gastrocnemius: 326 ± 17 vs. 260 ± 14 pmol/g wet tissue wt]. In addition, Bmax was significantly correlated withV˙o 2 max (soleus: r = 0.54, n = 15, P < 0.05; plantaris: r = 0.59, n = 15, P < 0.05; red portion of gastrocnemius: r = 0.65, n = 15, P < 0.01). These results suggest that downregulation of Na+-K+ pumps that possess a high affinity for ouabain in oxidative skeletal muscle may play an important role in the exercise intolerance that attends severe LV dysfunction in CHF.

Lansoprazole alleviates pressure overload-induced cardiac hypertrophy and heart failure in mice by blocking the activation of β-catenin

2019 ◽  
Vol 116 (1) ◽  
pp. 101-113 ◽  
Author(s):  
Hairuo Lin ◽  
Yang Li ◽  
Hailin Zhu ◽  
Qiancheng Wang ◽  
Zhenhuan Chen ◽  
...  
Keyword(s):  
Heart Failure ◽  
Body Weight ◽  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Weight Ratio ◽  
Left Ventricular ◽  
Neonatal Rat ◽  
Cardiac Remodelling ◽  
Heart Weight ◽  
Body Weight Ratio

Abstract Aims Proton pump inhibitors (PPIs) are widely used in patients receiving percutaneous coronary intervention to prevent gastric bleeding, but whether PPIs are beneficial for the heart is controversial. Here, we investigated the effects of lansoprazole on cardiac hypertrophy and heart failure, as well as the underlying mechanisms. Methods and results Adult male C57 mice were subjected to transverse aortic constriction (TAC) or sham surgery and then were treated with lansoprazole or vehicle for 5 weeks. In addition, cultured neonatal rat ventricular cardiomyocytes and fibroblasts were exposed to angiotensin II in the presence or absence of lansoprazole. At 5 weeks after TAC, the heart weight/body weight ratio was lower in lansoprazole-treated mice than in untreated mice, as was the lung weight/body weight ratio, while left ventricular (LV) fractional shortening and the maximum and minimum rates of change of the LV pressure were higher in lansoprazole-treated mice, along with less cardiac fibrosis. In cultured cardiomyocytes, lansoprazole inhibited angiotensin II-induced protein synthesis and hypertrophy, as well as inhibiting proliferation of fibroblasts. Lansoprazole decreased myocardial levels of phosphorylated Akt, phosphorylated glycogen synthase kinase 3β, and active β-catenin in TAC mice and in angiotensin II-stimulated cardiomyocytes. After overexpression of active β-catenin or knockdown of H+/K+-ATPase α-subunit, lansoprazole still significantly attenuated myocyte hypertrophy. Conclusion Lansoprazole inhibits cardiac remodelling by suppressing activation of the Akt/GSK3β/β-catenin pathway independent of H+/K+-ATPase inhibition, and these findings may provide a novel insight into the pharmacological effects of PPIs with regard to alleviation of cardiac remodelling.

scholarly journals Adiponectin Deficiency, Diastolic Dysfunction, and Diastolic Heart Failure

Endocrinology ◽  
2010 ◽  
Vol 151 (1) ◽  
pp. 322-331 ◽  
Author(s):  
Flora Sam ◽  
Toni-Ann S. Duhaney ◽  
Kaori Sato ◽  
Richard M. Wilson ◽  
Koji Ohashi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Body Weight ◽  
Diastolic Dysfunction ◽  
Diastolic Heart Failure ◽  
Weight Ratio ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Body Weight Ratio ◽  
Ventricular Ejection Fraction ◽  
Ventricular Filling

Abstract Aldosterone infusion results in left ventricular hypertrophy (LVH) and hypertension and may involve profibrotic and proinflammatory mechanisms. In turn, hypertension is the major cause of diastolic heart failure (HF). Adiponectin, an adipose-derived plasma protein, exerts antiinflammatory and anti-hypertrophic effects and is implicated in the development of hypertension and systolic HF. We thus tested the hypothesis that hypoadiponectinemia in aldosterone-induced hypertension exacerbated cardiac remodeling and diastolic HF. Wild-type (WT) or adiponectin-deficient (APNKO) mice underwent saline or aldosterone infusion and uninephrectomy and were fed 1% salt water for 4 wk. Blood pressure was increased in aldosterone-infused WT (132 ± 2 vs. 109 ± 3 mm Hg; P &lt; 0.01) and further augmented in APNKO mice (140 ± 3 mm Hg; P &lt; 0.05 vs. aldosterone-infused WT). LVH was increased in aldosterone-infused WT vs. WT mice (LV/body weight ratio, 4.8 ± 0.2 vs. 4.1 ± 0.2 mg/g) and further increased in aldosterone-infused APNKO mice (LV/body weight ratio, 6.0 ± 0.4 mg/g). Left ventricular ejection fraction was not decreased in either aldosterone-infused WT or APNKO hearts. Pulmonary congestion however was worse in APNKO mice (P &lt; 0.01). The ratio of early ventricular filling over late ventricular filling (E/A) and the ratio of mitral peak velocity of early filling to early diastolic mitral annular velocity (E/e’), measures of diastolic function, were increased in aldosterone-infused WT hearts and further increased in APNKO hearts (P &lt; 0.05 for both). Renal function and cardiac fibrosis were no different between both aldosterone-infused groups. Aldosterone increased matrix metalloproteinase-2 expression in WT hearts (P &lt; 0.05 vs. WT and P &lt; 0.01 vs. APNKO). Myocardial atrial natriuretic peptide, interferon-γ, and TNF-α expression were increased in aldosterone-infused WT hearts. Expression of these proteins was further increased in aldosterone-infused APNKO hearts. Therefore, hypoadiponectinemia in hypertension-induced diastolic HF exacerbates LVH, diastolic dysfunction, and diastolic HF. Whether or not adiponectin replacement prevents the progression to diastolic HF will warrant further study.

scholarly journals Effects of Active Components of Fuzi and Gancao Compatibility on Bax, Bcl-2, and Caspase-3 in Chronic Heart Failure Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Liqin Wang ◽  
Yu He ◽  
Yuyan Zhang ◽  
Huifen Zhou ◽  
Li Yu ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Caspase 3 ◽  
Weight Ratio ◽  
Left Ventricular ◽  
Protective Effects ◽  
Active Components ◽  
Body Weight Ratio ◽  
Apoptosis Pathways ◽  
Ancient Times

Hypaconitine (HA) and glycyrrhetinic acid (GA) are active components of Fuzi (Aconitum carmichaelii) and Gancao (Glycyrrhiza uralensisFisch); they have been used in compatibility for chronic heart failure (CHF) from ancient times. The purpose of the present research was to explore whether apoptosis pathways were related with the protective effects of HA + GA against CHF rats or not. The rats were progressed with transverse-aortic constriction (TAC) operation for 4 weeks to build the CHF state, and then the Digoxin (1 mg/kg), HA (2.07 mg/kg), GA (25 mg/kg), and HA (2.07 mg/kg) + GA (25 mg/kg) were orally administrated to rats for 1 week. The levels of BNP and cTnI in the plasma were decreased in the HA + GA group, and the heart/body weight ratio (H/B) and left ventricular (LV) parameters of transthoracic echocardiography were also declined; moreover, the expressions of Bax, Bcl-2, and caspase-3 were all improved in the HA + GA group than other groups in the immunohistochemistry and western blot methods. In general, the data suggested that Fuzi and Gancao compatibility could protect the CHF rats from apoptosis, which provided a strong evidence for further searching for mechanisms of them.

scholarly journals Hydrogen sulfide attenuates cardiac dysfunction in a rat model of heart failure: a mechanism through cardiac mitochondrial protection

2010 ◽  
Vol 31 (2) ◽  
pp. 87-98 ◽  
Author(s):  
Xianli Wang ◽  
Qian Wang ◽  
Wei Guo ◽  
Yi Zhun Zhu
Keyword(s):  
Heart Failure ◽  
Body Weight ◽  
Hydrogen Sulfide ◽  
Cytochrome C ◽  
Mrna Expression ◽  
Caspase 3 ◽  
Weight Ratio ◽  
Left Ventricular ◽  
Body Weight Ratio ◽  
Sodium Hydrosulfide

HF (heart failure) after MI (myocardial infarction) is a major cause of morbidity and mortality worldwide. Recent studies have shown that hydrogen sulfide (H2S) has cardioprotective effects. Hence, we aimed to elucidate the potential effects of H2S on HF after MI in rats. The HF model after MI was made by ligating the left anterior descending coronary artery. HF groups and sham-operated groups of rats were treated with vehicle, sodium hydrosulfide (NaHS) or PAG (propagylglycine). Equal volumes of saline, 3.136 mg·kg−1·day−1 NaHS or 37.5 mg·kg−1·day−1 PAG, were intraperitoneally injected into rats for 6 weeks after operation. Survival, lung-to-body weight ratio and left ventricular haemodynamic parameters were measured. The protein and gene expression of Bcl-2, Bax, caspase 3 and cytochrome c were analysed by Western blotting and RT–PCR (reverse transcription–PCR). TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling) and EM (electron microscopy) were used to examine apoptosis of heart tissues. NaHS was found to improve the survival and lower the lung-to-body weight ratio. It increased the LVSP (left ventricular systolic pressure) and the maximum rate of pressure and decreased LVEDP (left ventricular end-diastolic pressure). Furthermore, NaHS promoted Bcl-2 protein and mRNA expression and demoted Bax, caspase 3 protein and mRNA expression in HF rats. We also showed that NaHS decreased the leakage of cytochrome c protein from the mitochondria to the cytoplasm. Histological observation by TUNEL and EM proved that NaHS inhibited cardiac apoptosis in HF hearts and improved mitochondrial derangements, but that PAG aggravated those indices. Hence, H2S has protective effects in HF rats.

Training-induced changes in skeletal muscle Na+-K+ pump number and isoform expression in rats with chronic heart failure

2003 ◽  
Vol 94 (6) ◽  
pp. 2225-2236 ◽  
Author(s):  
Bryan Helwig ◽  
Katherine M. Schreurs ◽  
Joslyn Hansen ◽  
K. Sue Hageman ◽  
Michael G. Zbreski ◽  
...  
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Chronic Heart Failure ◽  
Exercise Training ◽  
Left Ventricular ◽  
Β Subunit ◽  
Severe Left Ventricular Dysfunction ◽  
Subunit Expression ◽  
Run Time ◽  
Isoform Expression

The mechanisms responsible for the decrements in exercise performance in chronic heart failure (CHF) remain poorly understood, but it has been suggested that sarcolemmal alterations could contribute to the early onset of muscular fatigue. Previously, our laboratory demonstrated that the maximal number of ouabain binding sites (Bmax) is reduced in the skeletal muscle of rats with CHF (Musch TI, Wolfram S, Hageman KS, and Pickar JG. J Appl Physiol 92: 2326–2334, 2002). These reductions may coincide with changes in the Na+-K+-ATPase isoform (α and β) expression. In the present study, we tested the hypothesis that reductions in Bmax would coincide with alterations in the α- and β-subunit expression of the sarcolemmal Na+-K+-ATPase of rats with CHF. Moreover, we tested the hypothesis that exercise training would increase Bmax along with producing significant changes in α- and β-subunit expression. Rats underwent a sham operation (sham; n = 10) or a surgically induced myocardial infarction followed by random assignment to either a control (MI; n = 16) or exercise training group (MI-T; n = 16). The MI-T rats performed exercise training (ET) for 6–8 wk. Hemodynamic indexes demonstrated that MI and MI-T rats suffered from severe left ventricular dysfunction and congestive CHF. Maximal oxygen uptake (V˙o 2 max) and endurance capacity (run time to fatigue) were reduced in MI rats compared with sham. Bmax in the soleus and plantaris muscles and the expression of the α2-isoform of the Na+-K+-ATPase in the red portion of the gastrocnemius (gastrocnemiusred) muscle were reduced in MI rats. After ET, V˙o 2 max and run time to fatigue were increased in the MI-T group of rats. This coincided with increases in soleus and plantaris Bmax and the expression of the α2-isoform in the gastrocnemiusred muscle. In addition, the expression of the β2-isoform of the gastrocnemiusred muscle was increased in the MI-T rats compared with their sedentary counterparts. This study demonstrates that CHF-induced alterations in skeletal muscle Na+-K+-ATPase, including Bmax and isoform expression, can be partially reversed by ET.

Reductions of myocardial Na-K-ATPase activity and ouabain binding sites in heart failure: prevention by nadolol

1993 ◽  
Vol 265 (6) ◽  
pp. H2086-H2093 ◽  
Author(s):  
T. H. Fan ◽  
R. P. Frantz ◽  
H. Elam ◽  
S. Sakamoto ◽  
N. Imai ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atpase Activity ◽  
Binding Sites ◽  
Early Stage ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Adrenergic Stimulation ◽  
Ouabain Binding ◽  
Systemic Hemodynamic

To study the changes in myocardial digitalis binding sites in heart failure, we measured myocardial ouabain binding sites, Na-K-adenosinetriphosphatase (ATPase) activity, and ventricular muscle mechanical responses to acetylstrophanthidin in dogs with right-heart failure (RHF) produced by tricuspid avulsion and pulmonary artery constriction. Sham-operated dogs were studied as the control. RHF produced a significant decrease in ouabain binding sites in the right and left ventricular myocardium, which was accompanied by a proportional decrease in Na-K-ATPase activity. However, RHF and sham-operated dogs did not differ in systemic hemodynamic or right ventricular trabeculate muscle isometric contractile responses to acetylstrophanthidin. To determine whether chronic beta-adrenergic stimulation contributed to the development of Na-K-ATPase downregulation, we administered nadolol (40 mg/day) to a separate group of dogs during an early stage of RHF development. Nadolol effectively prevented the reduction of myocardial ouabain binding sites that occurred in RHF. Thus we conclude that myocardial ouabain binding sites and Na-K-ATPase activity are reduced in dogs with experimental heart failure and that these changes probably occur as a result of the attendant heightened sympathetic activity.

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