scholarly journals Systemic oxidative stress is associated with lower aerobic capacity and impaired skeletal muscle energy metabolism in heart failure patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Takashi Yokota ◽  
Shintaro Kinugawa ◽  
Kagami Hirabayashi ◽  
Mayumi Yamato ◽  
Shingo Takada ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Skeletal Muscle ◽  
Energy Metabolism ◽  
Aerobic Capacity ◽  
Plantar Flexion ◽  
Exercise Intolerance ◽  
Whole Body ◽  
Resonance Spectroscopy ◽  
Systemic Oxidative Stress

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.

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

2011 ◽  
Vol 300 (5) ◽  
pp. R1142-R1147 ◽  
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.

scholarly journals Resveratrol improves exercise performance and skeletal muscle oxidative capacity in heart failure

2017 ◽  
Vol 312 (4) ◽  
pp. H842-H853 ◽  
Author(s):  
Miranda M. Sung ◽  
Nikole J. Byrne ◽  
Ian M. Robertson ◽  
Ty T. Kim ◽  
Victor Samokhvalov ◽  
...  
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Exercise Performance ◽  
Glucose Utilization ◽  
Exercise Intolerance ◽  
Whole Body ◽  
Microbiota Composition ◽  
Resveratrol Treatment ◽  
Gut Microbiota Composition ◽  
Improve Fatigue

We investigated whether treatment of mice with established pressure overload-induced heart failure (HF) with the naturally occurring polyphenol resveratrol could improve functional symptoms of clinical HF such as fatigue and exercise intolerance. C57Bl/6N mice were subjected to either sham or transverse aortic constriction surgery to induce HF. Three weeks postsurgery, a cohort of mice with established HF (%ejection fraction <45) was administered resveratrol (~450 mg·kg−1·day−1) or vehicle for 2 wk. Although the percent ejection fraction was similar between both groups of HF mice, those mice treated with resveratrol had increased total physical activity levels and exercise capacity. Resveratrol treatment was associated with altered gut microbiota composition, increased skeletal muscle insulin sensitivity, a switch toward greater whole body glucose utilization, and increased basal metabolic rates. Although muscle mass and strength were not different between groups, mice with HF had significant declines in basal and ADP-stimulated O2 consumption in isolated skeletal muscle fibers compared with sham mice, which was completely normalized by resveratrol treatment. Overall, resveratrol treatment of mice with established HF enhances exercise performance, which is associated with alterations in whole body and skeletal muscle energy metabolism. Thus, our preclinical data suggest that resveratrol supplementation may effectively improve fatigue and exercise intolerance in HF patients. NEW & NOTEWORTHY Resveratrol treatment of mice with heart failure leads to enhanced exercise performance that is associated with altered gut microbiota composition, increased whole body glucose utilization, and enhanced skeletal muscle metabolism and function. Together, these preclinical data suggest that resveratrol supplementation may effectively improve fatigue and exercise intolerance in heart failure via these mechanisms. Listen to this article's corresponding podcast at https://ajpheart.podbean.com/e/resveratrol-and-exercise-capacity-in-heart-failure/ .

scholarly journals Exercise training in chronic heart failure: improving skeletal muscle O2transport and utilization

2015 ◽  
Vol 309 (9) ◽  
pp. H1419-H1439 ◽  
Author(s):  
Daniel M. Hirai ◽  
Timothy I. Musch ◽  
David C. Poole
Keyword(s):  
Quality Of Life ◽  
Heart Failure ◽  
Skeletal Muscle ◽  
Chronic Heart Failure ◽  
Exercise Training ◽  
Physical Capacity ◽  
Exercise Intolerance ◽  
Whole Body ◽  
Functional Components

Chronic heart failure (CHF) impairs critical structural and functional components of the O2transport pathway resulting in exercise intolerance and, consequently, reduced quality of life. In contrast, exercise training is capable of combating many of the CHF-induced impairments and enhancing the matching between skeletal muscle O2delivery and utilization ( Q̇mO2and V̇mO2, respectively). The Q̇mO2/ V̇mO2ratio determines the microvascular O2partial pressure (PmvO2), which represents the ultimate force driving blood-myocyte O2flux (see Fig. 1). Improvements in perfusive and diffusive O2conductances are essential to support faster rates of oxidative phosphorylation (reflected as faster V̇mO2kinetics during transitions in metabolic demand) and reduce the reliance on anaerobic glycolysis and utilization of finite energy sources (thus lowering the magnitude of the O2deficit) in trained CHF muscle. These adaptations contribute to attenuated muscle metabolic perturbations (e.g., changes in [PCr], [Cr], [ADP], and pH) and improved physical capacity (i.e., elevated critical power and maximal V̇mO2). Preservation of such plasticity in response to exercise training is crucial considering the dominant role of skeletal muscle dysfunction in the pathophysiology and increased morbidity/mortality of the CHF patient. This brief review focuses on the mechanistic bases for improved Q̇mO2/ V̇mO2matching (and enhanced PmvO2) with exercise training in CHF with both preserved and reduced ejection fraction (HFpEF and HFrEF, respectively). Specifically, O2convection within the skeletal muscle microcirculation, O2diffusion from the red blood cell to the mitochondria, and muscle metabolic control are particularly susceptive to exercise training adaptations in CHF. Alternatives to traditional whole body endurance exercise training programs such as small muscle mass and inspiratory muscle training, pharmacological treatment (e.g., sildenafil and pentoxifylline), and dietary nitrate supplementation are also presented in light of their therapeutic potential. Adaptations within the skeletal muscle O2transport and utilization system underlie improvements in physical capacity and quality of life in CHF and thus take center stage in the therapeutic management of these patients.

Sympathetic hyperactivity differentially affects skeletal muscle mass in developing heart failure: role of exercise training

2009 ◽  
Vol 106 (5) ◽  
pp. 1631-1640 ◽  
Author(s):  
Aline V. N. Bacurau ◽  
Maíra A. Jardim ◽  
Julio C. B. Ferreira ◽  
Luiz R. G. Bechara ◽  
Carlos R. Bueno ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Skeletal Muscle ◽  
Exercise Training ◽  
Exercise Tolerance ◽  
Muscular Atrophy ◽  
Exercise Intolerance ◽  
Muscle Morphology ◽  
Sympathetic Hyperactivity ◽  
Capillary Rarefaction

Sympathetic hyperactivity (SH) is a hallmark of heart failure (HF), and several lines of evidence suggest that SH contributes to HF-induced skeletal myopathy. However, little is known about the influence of SH on skeletal muscle morphology and metabolism in a setting of developing HF, taking into consideration muscles with different fiber compositions. The contribution of SH on exercise tolerance and skeletal muscle morphology and biochemistry was investigated in 3- and 7-mo-old mice lacking both α2A- and α2C-adrenergic receptor subtypes (α2A/α2CARKO mice) that present SH with evidence of HF by 7 mo. To verify whether exercise training (ET) would prevent skeletal muscle myopathy in advanced-stage HF, α2A/α2CARKO mice were exercised from 5 to 7 mo of age. At 3 mo, α2A/α2CARKO mice showed no signs of HF and preserved exercise tolerance and muscular norepinephrine with no changes in soleus morphology. In contrast, plantaris muscle of α2A/α2CARKO mice displayed hypertrophy and fiber type shift (IIA → IIX) paralleled by capillary rarefaction, increased hexokinase activity, and oxidative stress. At 7 mo, α2A/α2CARKO mice displayed exercise intolerance and increased muscular norepinephrine, muscular atrophy, capillary rarefaction, and increased oxidative stress. ET reestablished α2A/α2CARKO mouse exercise tolerance to 7-mo-old wild-type levels and prevented muscular atrophy and capillary rarefaction associated with reduced oxidative stress. Collectively, these data provide direct evidence that SH is a major factor contributing to skeletal muscle morphological changes in a setting of developing HF. ET prevented skeletal muscle myopathy in α2A/α2CARKO mice, which highlights its importance as a therapeutic tool for HF.

scholarly journals Influence of N-Acetylcysteine on Oxidative Stress in Slow-Twitch Soleus Muscle of Heart Failure Rats

2015 ◽  
Vol 35 (1) ◽  
pp. 148-159 ◽  
Author(s):  
Paula F. Martinez ◽  
Camila Bonomo ◽  
Daniele M. Guizoni ◽  
Silvio A. Oliveira Junior ◽  
Ricardo L. Damatto ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Skeletal Muscle ◽  
Nadph Oxidase ◽  
Soleus Muscle ◽  
Oxidase Activity ◽  
Left Ventricular ◽  
Exercise Intolerance ◽  
Contributing Factors ◽  
Nadph Oxidase Activity

Background: Chronic heart failure is characterized by decreased exercise capacity with early exacerbation of fatigue and dyspnea. Intrinsic skeletal muscle abnormalities can play a role in exercise intolerance. Causal or contributing factors responsible for muscle alterations have not been completely defined. This study evaluated skeletal muscle oxidative stress and NADPH oxidase activity in rats with myocardial infarction (MI) induced heart failure. Methods and Results: Four months after MI, rats were assigned to Sham, MI-C (without treatment), and MI-NAC (treated with N-acetylcysteine) groups. Two months later, echocardiogram showed left ventricular dysfunction in MI-C; NAC attenuated diastolic dysfunction. In soleus muscle, glutathione peroxidase and superoxide dismutase activity was decreased in MI-C and unchanged by NAC. 3-nitrotyrosine was similar in MI-C and Sham, and lower in MI-NAC than MI-C. Total reactive oxygen species (ROS) production was assessed by HPLC analysis of dihydroethidium (DHE) oxidation fluorescent products. The 2-hydroxyethidium (EOH)/DHE ratio did not differ between Sham and MI-C and was higher in MI-NAC. The ethidium/DHE ratio was higher in MI-C than Sham and unchanged by NAC. NADPH oxidase activity was similar in Sham and MI-C and lower in MI-NAC. Gene expression of p47phox was lower in MI-C than Sham. NAC decreased NOX4 and p22phox expression. Conclusions: We corroborate the case that oxidative stress is increased in skeletal muscle of heart failure rats and show for the first time that oxidative stress is not related to increased NADPH oxidase activity.

scholarly journals Pioglitazone improves whole-body aerobic capacity and skeletal muscle energy metabolism in patients with metabolic syndrome

2017 ◽  
Vol 8 (4) ◽  
pp. 535-541 ◽  
Author(s):  
Takashi Yokota ◽  
Shintaro Kinugawa ◽  
Kagami Hirabayashi ◽  
Tadashi Suga ◽  
Shingo Takada ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Metabolic Syndrome ◽  
Energy Metabolism ◽  
Aerobic Capacity ◽  
Whole Body ◽  
Muscle Energy ◽  
Muscle Energy Metabolism

scholarly journals Mitochondrial reactive oxygen species generation in blood cells is associated with disease severity and exercise intolerance in heart failure patients

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ryosuke Shirakawa ◽  
Takashi Yokota ◽  
Takayuki Nakajima ◽  
Shingo Takada ◽  
Miwako Yamane ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Functional Class ◽  
Exercise Intolerance ◽  
Ros Generation ◽  
Oxygen Species ◽  
Mitochondrial Reactive Oxygen Species ◽  
Class Iii ◽  
Nyha Functional Class ◽  
Systemic Oxidative Stress

Abstract Systemic oxidative stress plays a key role in the development of chronic heart failure (CHF). We tested the hypothesis that mitochondrial reactive oxygen species (ROS) generation in circulating peripheral blood mononuclear cells (PBMCs) contributes to CHF progression. A total of 31 patients who had a history of hospital admission due to worsening HF were enrolled and grouped as having either mild CHF defined as New York Heart Association (NYHA) functional class I-II or moderate-to-severe CHF defined as NYHA functional class III. ROS levels in PBMC mitochondria were significantly increased in CHF patients with NYHA functional class III compared to those with NYHA functional class I-II, accompanied by impaired mitochondrial respiratory capacity in PBMCs. ROS generation in PBMC mitochondria was positively correlated with urinary 8-hydroxydeoxyguanosine, a systemic oxidative stress marker, in CHF patients. Importantly, mitochondrial ROS generation in PBMCs was directly correlated with plasma levels of B-type natriuretic peptide, a biomarker for severity of HF, and inversely correlated with peak oxygen uptake, a parameter of exercise capacity, in CHF patients. The study showed that ROS generation in PBMC mitochondria was higher in patients with advanced CHF, and it was associated with disease severity and exercise intolerance in CHF patients.

scholarly journals Impact of age on exercise-induced ATP supply during supramaximal plantar flexion in humans

2015 ◽  
Vol 309 (4) ◽  
pp. R378-R388 ◽  
Author(s):  
Gwenael Layec ◽  
Joel D. Trinity ◽  
Corey R. Hart ◽  
Seong-Eun Kim ◽  
H. Jonathan Groot ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Plantar Flexion ◽  
Atp Synthesis ◽  
The Elderly ◽  
Exercise Intolerance ◽  
Resonance Spectroscopy ◽  
Metabolic Demand ◽  
Age Related ◽  
Exercise Induced ◽  
The Impact

Currently, the physiological factors responsible for exercise intolerance and bioenergetic alterations with age are poorly understood due, at least in art, to the confounding effect of reduced physical activity in the elderly. Thus, in 40 healthy young (22 ± 2 yr) and old (74 ± 8 yr) activity-matched subjects, we assessed the impact of age on: 1) the relative contribution of the three major pathways of ATP synthesis (oxidative ATP synthesis, glycolysis, and the creatine kinase reaction) and 2) the ATP cost of contraction during high-intensity exercise. Specifically, during supramaximal plantar flexion (120% of maximal aerobic power), to stress the functional limits of the skeletal muscle energy systems, we used 31P-labeled magnetic resonance spectroscopy to assess metabolism. Although glycolytic activation was delayed in the old, ATP synthesis from the main energy pathways was not significantly different between groups. Similarly, the inferred peak rate of mitochondrial ATP synthesis was not significantly different between the young (25 ± 8 mM/min) and old (24 ± 6 mM/min). In contrast, the ATP cost of contraction was significantly elevated in the old compared with the young (5.1 ± 2.0 and 3.7 ± 1.7 mM·min−1·W−1, respectively; P < 0.05). Overall, these findings suggest that, when young and old subjects are activity matched, there is no evidence of age-related mitochondrial and glycolytic dysfunction. However, this study does confirm an abnormal elevation in exercise-induced skeletal muscle metabolic demand in the old that may contribute to the decline in exercise capacity with advancing age.

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