scholarly journals Exercise training restores the myogenic response in skeletal muscle resistance arteries and corrects peripheral edema in rats with heart failure

2019 ◽  
Vol 317 (1) ◽  
pp. H87-H96 ◽  
Author(s):  
Suliana M. Paula ◽  
Gisele K. Couto ◽  
Milene T. Fontes ◽  
Soraia K. Costa ◽  
Carlos E. Negrão ◽  
...  
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Exercise Training ◽  
Exercise Intolerance ◽  
Calcium Handling ◽  
Moderate Intensity ◽  
Myogenic Response ◽  
Resistance Arteries ◽  
Peripheral Edema ◽  
First Time

Impairment of the myogenic response can affect capillary hydrostatic pressure and contribute to peripheral edema and exercise intolerance, which are markers of heart failure (HF). The aim of this study was to assess the effects of exercise training (ET) on myogenic response in skeletal muscle resistance arteries and peripheral edema in HF rats, focusing on the potential signaling pathways involved in these adjustments. Male Wistar rats were submitted to either coronary artery occlusion or a sham-operated surgery. After 4 wk, an exercise test was performed, and the rats were divided into the following groups: untrained normal control (UNC) and untrained HF (UHF) and exercise- trained (on treadmill, 50–60% of maximal capacity) NC (TNC) and exercise-trained HF (THF). Caudal tibial artery (CTA) myogenic response was impaired in UHF compared with UNC, and ET restored this response in THF to NC levels and increased it in TNC. Rho kinase (ROCK) inhibitor abolished CTA myogenic response in the untrained and blunted it in exercise-trained groups. CTA-stored calcium (Ca2+) mobilization was higher in exercise-trained rats compared with untrained rats. The paw volume was higher in UHF rats, and ET decreased this response compared with UNC. Myogenic constriction was positively correlated with maximal running distance and negatively correlated with paw volume. The results demonstrate, for the first time, that HF impairs the myogenic response in skeletal muscle arteries, which contributes to peripheral edema in this syndrome. ET restores the myogenic response in skeletal muscle arteries improving Ca2+ sensitization and handling. Additionally, this paradigm also improves peripheral edema and exercise intolerance. NEW & NOTEWORTHY The novel and main finding of the present study is that moderate intensity exercise training restores the impaired myogenic response of skeletal muscle resistance arteries, exercise intolerance and peripheral edema in rats with heart failure. These results also show for the first time to our knowledge that exercise training improving calcium sensitization through the ROCK pathway and enhancing intracellular calcium handling could contribute to restoration of flow autoregulation to skeletal muscle 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.

scholarly journals Impaired training-induced angiogenesis process with loss of pericyte-endothelium interactions is associated with an abnormal capillary remodelling in the skeletal muscle of COPD patients

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Léo Blervaque ◽  
Emilie Passerieux ◽  
Pascal Pomiès ◽  
Matthias Catteau ◽  
Nelly Héraud ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Exercise Training ◽  
Exercise Intolerance ◽  
Moderate Intensity ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Link Type ◽  
Copd Patients ◽  
Response To Exercise

Abstract Chronic obstructive pulmonary disease (COPD) is associated with exercise intolerance and limits the functional gains in response to exercise training in patients compared to sedentary healthy subjects (SHS). The blunted skeletal muscle angiogenesis previously observed in COPD patients has been linked to these limited functional improvements, but its underlying mechanisms, as well as the potential role of oxidative stress, remain poorly understood. Therefore, we compared ultrastructural indexes of angiogenic process and capillary remodelling by transmission electron microscopy in 9 COPD patients and 7 SHS after 6 weeks of individualized moderate-intensity endurance training. We also assessed oxidative stress by plasma-free and esterified isoprostane (F2-IsoP) levels in both groups. We observed a capillary basement membrane thickening in COPD patients only (p = 0.008) and abnormal variations of endothelial nucleus density in response to exercise training in these patients when compared to SHS (p = 0.042). COPD patients had significantly fewer occurrences of pericyte/endothelium interdigitations, a morphologic marker of capillary maturation, than SHS (p = 0.014), and significantly higher levels of F2-IsoP (p = 0.048). Last, the changes in pericyte/endothelium interdigitations and F2-IsoP levels in response to exercise training were negatively correlated (r = − 0.62, p = 0.025). This study is the first to show abnormal capillary remodelling and to reveal impairments during the whole process of angiogenesis (capillary creation and maturation) in COPD patients. Trial registration NCT01183039 & NCT01183052, both registered 7 August 2010 (retrospectively registered).

scholarly journals TNFα is central to the augmented myogenic response of skeletal muscle resistance arteries in heart failure

2011 ◽  
Vol 25 (S1) ◽  
Author(s):  
Jeffrey Thomas Kroetsch ◽  
Anja Meissner ◽  
Abdul Momen ◽  
Mansoor Husain ◽  
Steffen‐Sebastian Bolz
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Myogenic Response ◽  
Resistance Arteries

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 Exercise training delays cardiac dysfunction and prevents calcium handling abnormalities in sympathetic hyperactivity-induced heart failure mice

2008 ◽  
Vol 104 (1) ◽  
pp. 103-109 ◽  
Author(s):  
Alessandra Medeiros ◽  
Natale P. L. Rolim ◽  
Rodrigo S. F. Oliveira ◽  
Kaleizu T. Rosa ◽  
Katt C. Mattos ◽  
...  
Keyword(s):  
Heart Failure ◽  
Exercise Training ◽  
Cardiac Dysfunction ◽  
Ventricular Dysfunction ◽  
Exercise Intolerance ◽  
Calcium Handling ◽  
Plasma Norepinephrine ◽  
Sympathetic Hyperactivity ◽  
Preventive Cardiology ◽  
Significant Difference

Exercise training (ET) is a coadjuvant therapy in preventive cardiology. It delays cardiac dysfunction and exercise intolerance in heart failure (HF); however, the molecular mechanisms underlying its cardioprotection are poorly understood. We tested the hypothesis that ET would prevent Ca2+ handling abnormalities and ventricular dysfunction in sympathetic hyperactivity-induced HF mice. A cohort of male wild-type (WT) and congenic α2A/α2C-adrenoceptor knockout (α2A/α2CARKO) mice with C57BL6/J genetic background (3–5 mo of age) were randomly assigned into untrained and exercise-trained groups. ET consisted of 8-wk swimming session, 60 min, 5 days/wk. Fractional shortening (FS) was assessed by two-dimensional guided M-mode echocardiography. The protein expression of ryanodine receptor (RyR), phospho-Ser2809-RyR, sarcoplasmic reticulum Ca2+ ATPase (SERCA2), Na+/Ca2+ exchanger (NCX), phospholamban (PLN), phospho-Ser16-PLN, and phospho-Thr17-PLN were analyzed by Western blotting. At 3 mo of age, no significant difference in FS and exercise tolerance was observed between WT and α2A/α2CARKO mice. At 5 mo, when cardiac dysfunction is associated with lung edema and increased plasma norepinephrine levels, α2A/α2CARKO mice presented reduced FS paralleled by decreased SERCA2 (26%) and NCX (34%). Conversely, α2A/α2CARKO mice displayed increased phospho-Ser16-PLN (76%) and phospho-Ser2809-RyR (49%). ET in α2A/α2CARKO mice prevented exercise intolerance, ventricular dysfunction, and decreased plasma norepinephrine. ET significantly increased the expression of SERCA2 (58%) and phospho-Ser16-PLN (30%) while it restored the expression of phospho-Ser2809-RyR to WT levels. Collectively, we provide evidence that improved net balance of Ca2+ handling proteins paralleled by a decreased sympathetic activity on ET are, at least in part, compensatory mechanisms against deteriorating ventricular function in HF.

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.

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

2015 ◽  
Vol 119 (6) ◽  
pp. 734-738 ◽  
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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