scholarly journals Muscle oxygen transport and utilization in heart failure: implications for exercise (in)tolerance

2012 ◽  
Vol 302 (5) ◽  
pp. H1050-H1063 ◽  
Author(s):  
David C. Poole ◽  
Daniel M. Hirai ◽  
Steven W. Copp ◽  
Timothy I. Musch
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Cardiac Output ◽  
Uptake Kinetics ◽  
Exercise Intolerance ◽  
Transport Pathway ◽  
Muscle Oxygen ◽  
Patient Morbidity ◽  
Oxidative Function ◽  
Factor Α

The defining characteristic of chronic heart failure (CHF) is an exercise intolerance that is inextricably linked to structural and functional aberrations in the O2 transport pathway. CHF reduces muscle O2 supply while simultaneously increasing O2 demands. CHF severity varies from moderate to severe and is assessed commonly in terms of the maximum O2 uptake, which relates closely to patient morbidity and mortality in CHF and forms the basis for Weber and colleagues' ( 167 ) classifications of heart failure, speed of the O2 uptake kinetics following exercise onset and during recovery, and the capacity to perform submaximal exercise. As the heart fails, cardiovascular regulation shifts from controlling cardiac output as a means for supplying the oxidative energetic needs of exercising skeletal muscle and other organs to preventing catastrophic swings in blood pressure. This shift is mediated by a complex array of events that include altered reflex and humoral control of the circulation, required to prevent the skeletal muscle “sleeping giant” from outstripping the pathologically limited cardiac output and secondarily impacts lung (and respiratory muscle), vascular, and locomotory muscle function. Recently, interest has also focused on the dysregulation of inflammatory mediators including tumor necrosis factor-α and interleukin-1β as well as reactive oxygen species as mediators of systemic and muscle dysfunction. This brief review focuses on skeletal muscle to address the mechanistic bases for the reduced maximum O2 uptake, slowed O2 uptake kinetics, and exercise intolerance in CHF. Experimental evidence in humans and animal models of CHF unveils the microvascular cause(s) and consequences of the O2 supply (decreased)/O2 demand (increased) imbalance emblematic of CHF. Therapeutic strategies to improve muscle microvascular and oxidative function (e.g., exercise training and anti-inflammatory, antioxidant strategies, in particular) and hence patient exercise tolerance and quality of life are presented within their appropriate context of the O2 transport pathway.

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.

scholarly journals Exercise limitations in heart failure with reduced and preserved ejection fraction

2018 ◽  
Vol 124 (1) ◽  
pp. 208-224 ◽  
Author(s):  
David C. Poole ◽  
Russell S. Richardson ◽  
Mark J. Haykowsky ◽  
Daniel M. Hirai ◽  
Timothy I. Musch
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Ejection Fraction ◽  
Clinical Intervention ◽  
Exercise Intolerance ◽  
Transport Pathway ◽  
Phosphorescence Quenching ◽  
Reduced Ejection Fraction ◽  
Emerging Therapies ◽  
Underlying Mechanisms

The hallmark symptom of chronic heart failure (HF) is severe exercise intolerance. Impaired perfusive and diffusive O2 transport are two of the major determinants of reduced physical capacity and lowered maximal O2 uptake in patients with HF. It has now become evident that this syndrome manifests at least two different phenotypic variations: heart failure with preserved or reduced ejection fraction (HFpEF and HFrEF, respectively). Unlike HFrEF, however, there is currently limited understanding of HFpEF pathophysiology, leading to a lack of effective pharmacological treatments for this subpopulation. This brief review focuses on the disturbances within the O2 transport pathway resulting in limited exercise capacity in both HFpEF and HFrEF. Evidence from human and animal research reveals HF-induced impairments in both perfusive and diffusive O2 conductances identifying potential targets for clinical intervention. Specifically, utilization of different experimental approaches in humans (e.g., small vs. large muscle mass exercise) and animals (e.g., intravital microscopy and phosphorescence quenching) has provided important clues to elucidating these pathophysiological mechanisms. Adaptations within the skeletal muscle O2 delivery-utilization system following established and emerging therapies (e.g., exercise training and inorganic nitrate supplementation, respectively) are discussed. Resolution of the underlying mechanisms of skeletal muscle dysfunction and exercise intolerance is essential for the development and refinement of the most effective treatments for patients with 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.

Metabolic Myopathy in Heart Failure

Physiology ◽  
2002 ◽  
Vol 17 (5) ◽  
pp. 191-196 ◽  
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.

Abstract 2769: Impaired Skeletal Muscle Oxygen Utilization Contributes to Exercise Intolerance in Barth Syndrome

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Carolyn T Spencer ◽  
Randall M Bryant ◽  
Barry Byrne ◽  
Elisabeth Heal ◽  
Renee Margossian ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cardiac Function ◽  
Mitochondrial Dysfunction ◽  
Near Infrared ◽  
Vastus Lateralis ◽  
Barth Syndrome ◽  
Exercise Intolerance ◽  
Peak Exercise ◽  
Indirect Measure ◽  
Muscle Oxygen

Objective s: Barth Syndrome (BTHS) is an X-linked mutation in the TAZ gene characterized by cardiolipin deficiency, mitochondrial dysfunction and cardio-skeletal myopathy. We hypothe- sized that abnormal skeletal muscle oxygen (O 2 ) utilization contributes to exercise intolerance in BTHS. Methods : Boys with BTHS (n=13) and healthy male controls (n=7) performed a graded exercise test on a cycle ergometer with continuous metabolic and EKG monitoring. Near infrared spectroscopy (NIRS), an indirect measure of tissue O 2 saturation and index of skeletal muscle O 2 utilization, was applied to the vastus lateralis during exercise. Cardiac function in BTHS was assessed by echocardiography and serum BNP to examine the relationship between resting cardiac function and exercise capacity in BTHS. Results : Age (16±5 vs 13±3 years; p=0.22), BMI (17±3 vs. 20±5; p=0.14) and BSA (1.0±0.5 vs 1.2±0.6 m 2 ; p=0.3) were not different between BTHS and controls. BTHS had lower peak VO 2 (19±6 vs. 52±6 ml/kg/min, p < 0.001), lower % of predicted peak VO 2 (40±10% vs. 115±12%, p=0.0004), lower peak work rate (58±18 vs. 205±69 watts, p=0.0004), and lower peak O 2 pulse (4.6±1.6 vs. 14±6 ml O 2 /kg/beat, p< 0.00001) than controls. Peak HR in BTHS was lower but remained within normal peak predicted rate (172±14 vs. 197±11 bpm, p=0.001). Vastus lateralis tissue O 2 saturation at peak exercise decreased from baseline in controls as expected (-18±16%, p<0.001) but paradoxically increased from baseline in BTHS (+17±14%, p<0.03, p=0.0005 BTHS vs. controls) indicating impaired muscle O 2 utilization. Absolute (r= - 0.70, p<0.0001) and percent (r= - 0.70, p<0.001) change in NIRS from baseline was negatively associated with peak VO 2 . There was no correlation between peak VO 2 and resting EF (55±7%; r=0.12), SF (30±4%; r= -.26), myocardial performance index (0.4±0.1; r= -.3) or serum BNP (232±381; r=0.1). Conclusion : O 2 consumption during exercise in BTHS is severely reduced and caused, at least in part, by impaired skeletal muscle O 2 utilization. Resting cardiac function is not related to O 2 consumption in BTHS but cardiac dysfunction during exercise in BTHS is not excluded without further studies. Mitochondrial dysfunction likely mediates skeletal muscle O 2 utilization deficits during exercise in BTHS.

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

2019 ◽  
Vol 20 (21) ◽  
pp. 5514 ◽  
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.

scholarly journals Skeletal muscle atrophy contributes to exercise intolerance in heart failure

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

scholarly journals Exercise intolerance in comorbid COPD and heart failure: the role of impaired aerobic function

2019 ◽  
Vol 53 (4) ◽  
pp. 1802386 ◽  
Author(s):  
Alcides Rocha ◽  
Flavio F. Arbex ◽  
Priscila A. Sperandio ◽  
Frederico Mancuso ◽  
Mathieu Marillier ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Output ◽  
Systolic Heart Failure ◽  
Treatment Strategies ◽  
Symptom Burden ◽  
Cardiopulmonary Exercise Test ◽  
Forced Expiratory Volume ◽  
Exercise Intolerance ◽  
Chronic Obstructive ◽  
Aerobic Function

Impaired aerobic function is a potential mechanism of exercise intolerance in patients with combined cardiorespiratory disease. We investigated the pathophysiological and sensory consequences of a low change in oxygen uptake (ΔV′O2)/change in work rate (ΔWR) relationship during incremental exercise in patients with coexisting chronic obstructive pulmonary disease (COPD) and systolic heart failure (HF).After clinical stabilisation, 51 COPD–HF patients performed an incremental cardiopulmonary exercise test to symptom limitation. Cardiac output was non-invasively measured (impedance cardiography) in a subset of patients (n=18).27 patients presented with ΔV′O2/ΔWR below the lower limit of normal. Despite similar forced expiratory volume in 1 s and ejection fraction, the low ΔV′O2/ΔWR group showed higher end-diastolic volume, lower inspiratory capacity and lower transfer factor compared to their counterparts (p<0.05). Peak WR and peakV′O2were ∼15% and ∼30% lower, respectively, in the former group: those findings were associated with greater symptom burden in daily life and at a given exercise intensity (leg discomfort and dyspnoea). The low ΔV′O2/ΔWR group presented with other evidences of impaired aerobic function (sluggishV′O2kinetics, earlier anaerobic threshold) and cardiocirculatory performance (lower oxygen pulse, lower stroke volume and cardiac output) (p<0.05). Despite similar exertional hypoxaemia, they showed worse ventilatory inefficiency and higher operating lung volumes, which led to greater mechanical inspiratory constraints (p<0.05).Impaired aerobic function due to negative cardiopulmonary–muscular interactions is an important determinant of exercise intolerance in patients with COPD–HF. Treatment strategies to improve oxygen delivery to and/or utilisation by the peripheral muscles might prove particularly beneficial to these patients.

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

1996 ◽  
Vol 270 (1) ◽  
pp. H115-H120 ◽  
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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