Faculty Opinions recommendation of Fatigability, exercise intolerance, and abnormal skeletal muscle energetics in heart failure.

AbstractOxidative stress plays a role in the progression of chronic heart failure (CHF). We investigated whether systemic oxidative stress is linked to exercise intolerance and skeletal muscle abnormalities in patients with CHF. We recruited 30 males: 17 CHF patients, 13 healthy controls. All participants underwent blood testing, cardiopulmonary exercise testing, and magnetic resonance spectroscopy (MRS). The serum thiobarbituric acid reactive substances (TBARS; lipid peroxides) were significantly higher (5.1 ± 1.1 vs. 3.4 ± 0.7 μmol/L, p < 0.01) and the serum activities of superoxide dismutase (SOD), an antioxidant, were significantly lower (9.2 ± 7.1 vs. 29.4 ± 9.7 units/L, p < 0.01) in the CHF cohort versus the controls. The oxygen uptake (VO2) at both peak exercise and anaerobic threshold was significantly depressed in the CHF patients; the parameters of aerobic capacity were inversely correlated with serum TBARS and positively correlated with serum SOD activity. The phosphocreatine loss during plantar-flexion exercise and intramyocellular lipid content in the participants' leg muscle measured by 31phosphorus- and 1proton-MRS, respectively, were significantly elevated in the CHF patients, indicating abnormal intramuscular energy metabolism. Notably, the skeletal muscle abnormalities were related to the enhanced systemic oxidative stress. Our analyses revealed that systemic oxidative stress is related to lowered whole-body aerobic capacity and skeletal muscle dysfunction in CHF patients.

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Soothing the sleeping giant: improving skeletal muscle oxygen kinetics and exercise intolerance in HFpEF

Journal of Applied Physiology ◽

10.1152/japplphysiol.01127.2014 ◽

2015 ◽

Vol 119 (6) ◽

pp. 734-738 ◽

Cited By ~ 14

Author(s):

Satyam Sarma ◽

Benjamin D. Levine

Keyword(s):

Heart Failure ◽

Skeletal Muscle ◽

Oxygen Consumption ◽

Functional Capacity ◽

Oxidative Capacity ◽

Exercise Intolerance ◽

Aerobic Performance ◽

Muscle Oxygen ◽

Oxygen Kinetics ◽

Patients With Heart Failure

Patients with heart failure with preserved ejection fraction (HFpEF) have similar degrees of exercise intolerance and dyspnea as patients with heart failure with reduced EF (HFrEF). The underlying pathophysiology leading to impaired exertional ability in the HFpEF syndrome is not completely understood, and a growing body of evidence suggests “peripheral,” i.e., noncardiac, factors may play an important role. Changes in skeletal muscle function (decreased muscle mass, capillary density, mitochondrial volume, and phosphorylative capacity) are common findings in HFrEF. While cardiac failure and decreased cardiac reserve account for a large proportion of the decline in oxygen consumption in HFrEF, impaired oxygen diffusion and decreased skeletal muscle oxidative capacity can also hinder aerobic performance, functional capacity and oxygen consumption (V̇o2) kinetics. The impact of skeletal muscle dysfunction and abnormal oxidative capacity may be even more pronounced in HFpEF, a disease predominantly affecting the elderly and women, two demographic groups with a high prevalence of sarcopenia. In this review, we 1) describe the basic concepts of skeletal muscle oxygen kinetics and 2) evaluate evidence suggesting limitations in aerobic performance and functional capacity in HFpEF subjects may, in part, be due to alterations in skeletal muscle oxygen delivery and utilization. Improving oxygen kinetics with specific training regimens may improve exercise efficiency and reduce the tremendous burden imposed by skeletal muscle upon the cardiovascular system.

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Evidence that a higher ATP cost of muscular contraction contributes to the lower mechanical efficiency associated with COPD: preliminary findings

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00835.2010 ◽

2011 ◽

Vol 300 (5) ◽

pp. R1142-R1147 ◽

Cited By ~ 27

Author(s):

Gwenael Layec ◽

Luke J. Haseler ◽

Jan Hoff ◽

Russell S. Richardson

Keyword(s):

Skeletal Muscle ◽

Muscle Contraction ◽

Energy Cost ◽

Plantar Flexion ◽

Mechanical Efficiency ◽

Exercise Intolerance ◽

Chronic Obstructive ◽

Small Subset ◽

Resonance Spectroscopy ◽

Muscle Energetics

Impaired metabolism in peripheral skeletal muscles potentially contributes to exercise intolerance in chronic obstructive pulmonary disease (COPD). We used 31P-magnetic resonance spectroscopy (31P-MRS) to examine the energy cost and skeletal muscle energetics in six patients with COPD during dynamic plantar flexion exercise compared with six well-matched healthy control subjects. Patients with COPD displayed a higher energy cost of muscle contraction compared with the controls (control: 6.1 ± 3.1% of rest·min−1·W−1, COPD: 13.6 ± 8.3% of rest·min−1·W−1, P = 0.01). Although, the initial phosphocreatine resynthesis rate was also significantly attenuated in patients with COPD compared with controls (control: 74 ± 17% of rest/min, COPD: 52 ± 13% of rest/min, P = 0.04), when scaled to power output, oxidative ATP synthesis was similar between groups (6.5 ± 2.3% of rest·min−1·W−1 in control and 7.8 ± 3.9% of rest·min−1·W−1 in COPD, P = 0.52). Therefore, our results reveal, for the first time that in a small subset of patients with COPD a higher ATP cost of muscle contraction may substantially contribute to the lower mechanical efficiency previously reported in this population. In addition, it appears that some patients with COPD have preserved mitochondrial function and normal energy supply in lower limb skeletal muscle.

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Metabolic Myopathy in Heart Failure

Physiology ◽

10.1152/nips.01392.2002 ◽

2002 ◽

Vol 17 (5) ◽

pp. 191-196 ◽

Cited By ~ 5

Author(s):

Renée Ventura-Clapier ◽

Elvira De Sousa ◽

Vladimir Veksler

Keyword(s):

Heart Failure ◽

Skeletal Muscle ◽

Exercise Intolerance ◽

Metabolic Myopathy

Heart failure is a syndrome that also affects the periphery. Exercise intolerance and early fatigue seem to be linked in part to intrinsic alterations of skeletal muscle with decreases in both the production of ATP by mitochondria and the transfer of energy through the phosphotransfer kinases.

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Clinical Response to Personalized Exercise Therapy in Heart Failure Patients with Reduced Ejection Fraction Is Accompanied by Skeletal Muscle Histological Alterations

International Journal of Molecular Sciences ◽

10.3390/ijms20215514 ◽

2019 ◽

Vol 20 (21) ◽

pp. 5514 ◽

Cited By ~ 2

Author(s):

Tatiana Lelyavina ◽

Victoria Galenko ◽

Oksana Ivanova ◽

Margarita Komarova ◽

Elena Ignatieva ◽

...

Keyword(s):

Heart Failure ◽

Skeletal Muscle ◽

Ejection Fraction ◽

Clinical Response ◽

Exercise Therapy ◽

Left Ventricular ◽

Exercise Intolerance ◽

Left Ventricular Ejection ◽

Histological Alterations ◽

Before And After

Heart failure (HF) is associated with skeletal muscle wasting and exercise intolerance. This study aimed to evaluate the exercise-induced clinical response and histological alterations. One hundred and forty-four HF patients were enrolled. The individual training program was determined as a workload at or close to the lactate threshold (LT1); clinical data were collected before and after 12 weeks/6 months of training. The muscle biopsies from eight patients were taken before and after 12 weeks of training: histology analysis was used to evaluate muscle morphology. Most of the patients demonstrated a positive response after 12 weeks of the physical rehabilitation program in one or several parameters tested, and 30% of those showed improvement in all four of the following parameters: oxygen uptake (VO2) peak, left ventricular ejection fraction (LVEF), exercise tolerance (ET), and quality of life (QOL); the walking speed at LT1 after six months of training showed a significant rise. Along with clinical response, the histological analysis detected a small but significant decrease in both fiber and endomysium thickness after the exercise training course indicating the stabilization of muscle mechanotransduction system. Together, our data show that the beneficial effect of personalized exercise therapy in HF patients depends, at least in part, on the improvement in skeletal muscle physiological and biochemical performance.

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Skeletal muscle atrophy contributes to exercise intolerance in heart failure

Journal of the American College of Cardiology ◽

10.1016/0735-1097(91)91318-9 ◽

1991 ◽

Vol 17 (2) ◽

pp. A88

Author(s):

Donna M. Mancini ◽

Deborah Nazzaro ◽

Lynne Georgopoulos ◽

Nancy Wagner ◽

James L. Mullen ◽

...

Keyword(s):

Heart Failure ◽

Skeletal Muscle ◽

Muscle Atrophy ◽

Exercise Intolerance ◽

Skeletal Muscle Atrophy

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Effects of ACE inhibition and beta-blockade on skeletal muscle fiber types in dogs with moderate heart failure

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1996.270.1.h115 ◽

1996 ◽

Vol 270 (1) ◽

pp. H115-H120 ◽

Cited By ~ 3

Author(s):

H. N. Sabbah ◽

H. Shimoyama ◽

V. G. Sharov ◽

T. Kono ◽

R. C. Gupta ◽

...

Keyword(s):

Heart Failure ◽

Skeletal Muscle ◽

Exercise Intolerance ◽

Beta Blockade ◽

Muscle Fiber Types ◽

Type I ◽

Fiber Types ◽

Type Ii ◽

Early Therapy ◽

Type I Fibers

The proportion of slow-twitch, fatigue-resistant type 1 skeletal muscle (SM) fibers is often reduced in heart failure (HF), while the proportion of fatigue-sensitive type-II fibers increases. This maladaptation may be partially responsible for the exercise intolerance that characterize HF. In this study, we examined the effects of early monotherapy with the angiotensin-converting enzyme inhibor, enalapril, and the beta-blocker, metoprolol, on SM fiber type composition in 18 dogs with moderate HF produced by intracoronary microembolizations. HF dogs were randomized to 3 mo therapy with enalapril (10 mg twice daily), metoprolol (25 mg twice daily), or no treatment. Triceps muscle biopsies were obtained at baseline, before randomization, and at the end of 30 mo of therapy. Type I and type II SM fibers were differentiated by myofibrillar adenosinetriphosphatase (pH 9.4). In untreated dogs, the proportion of type I fibers was 27 +/- 1% before randomization and decreased to 23 +/- 1% (P < 0.05) at the end of 3 mo of follow up. In dogs treated with enalapril or metoprolol, the proportion of type I fibers was 30 +/- 4 and 28 +/- 2% before randomization and 33 +/- 4 and 33 +/- 1%, respectively, after 3 mo of therapy. In conclusion, in dogs with moderate HF, early therapy with enalapril or metoprolol prevents the progressive decline in the proportion of type I SM fibers.

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