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Exercise training alters skeletal muscle mitochondrial morphometry in heart failure patients
Abstract
Previous research has demonstrated that exercise intolerance in heart failure patients is associated with significant alterations in skeletal muscle ultrastructure and oxidative metabolism that may be more consequential than cardiac output.
To examine the effect of exercise training on skeletal muscle mitochondrial size in chronic heart failure patients.
Six heart failure patients participated in 16-weeks of supervised upper and lower extremity exercise training. At the conclusion of training, percutaneous needle biopsies of the vastus lateralis were taken and electron microscopy was used to assess mitochondrial sizes.
The exercise programme resulted in a significant increase in peak maximal oxygen consumption ( P< 0.05) and anaerobic threshold (P < 0.04). Knee extension muscle force increased following training ( P< 0.02). After exercise training, the average size of the mitochondria increased by 23.4% (0.036 to 0.046 mu(2), P< 0.015) and the average shape was unaltered.
Exercise training with heart failure patients alters skeletal muscle morphology by increasing mitochondrial size, with no change in shape. This may enhance oxidative metabolism resulting in an increased exercise tolerance.
... Also (cryo)-electron microscopy (EM) analysis of fixed specimens has been widely applied to analyze mitochondrial (ultra )structure (e.g. [41,[166][167][168]). As a consequence, morphometric analyses have been historically important to quantify mitochondrial properties using EM images [169]. ...
Mitochondria play a key role in signal transduction, redox homeostasis and cell survival, which extends far beyond their classical functioning in ATP production and energy metabolism. In living cells, mitochondrial content ("mitochondrial mass") depends on the cell-controlled balance between mitochondrial biogenesis and degradation. These processes are intricately linked to changes in net mitochondrial morphology and spatiotemporal positioning ("mitochondrial dynamics"), which are governed by mitochondrial fusion, fission and motility. It is becoming increasingly clear that mitochondrial mass and dynamics, as well as its ultrastructure and volume, are mechanistically linked to mitochondrial function and the cell. This means that proper quantification of mitochondrial morphology and content is of prime importance in understanding mitochondrial and cellular physiology in health and disease. This review first presents how cellular mitochondrial content is regulated at the level of mitochondrial biogenesis, degradation and dynamics. Next we discuss how mitochondrial dynamics and content can be analyzed with a special emphasis on quantitative live-cell microscopy strategies.
... Increase in mitochondrial volume density positively correlates with changes in VO 2 peak and anaerobic threshold exercise [112] or changes in type I fiber percentage, and negatively with muscle venous lactate for a given workload [113]. As exercise training in heart failure patients increases mitochondrial size [114], it is likely that it will also increase muscle oxidative capacity in skeletal muscle, resulting in increased exercise tolerance. In older human skeletal muscle, exercise enhances mitochondrial activity, which is likely related to the concomitant increase in mitochondrial biogenesis [115]. ...
As endurance training improves symptoms and quality of life and decreases mortality rate and hospitalization, it is increasingly recognized as a beneficial practice for heart failure (HF) patients. However, the mechanisms involved in the beneficial effects of exercise training are far from being understood and need further evaluation. Independent of hemodynamics effects, exercise training participates in tissue remodeling. While heart failure induces a generalized metabolic myopathy, adaptation to endurance training mainly improves energetic aspects of muscle function. In the present review, after presenting the main characteristics of cardiac and skeletal muscle energy metabolism and the effects of exercise training, we will discuss the evidence for the beneficial effects of endurance training on cardiac and skeletal muscle oxidative metabolism and intracellular energy transfer in HF.
These beneficial effects of exercise training seen in heart failure patients are also relevant to other chronic diseases (chronic obstructive pulmonary disease, diabetes, and obesity) and even for highly sedentary or elderly individuals [Booth F.W., Chakravathy M.V., Spangenburg E.E. Exercise and gene expression: physiological regulation of the human genome through physical activity. J Physiol (Lond) 2002;543:399–411][1]. Physical rehabilitation is thus a major health issue for populations in industrialized countries.
Background: Previous studies have suggested living high-training low (HiLo) is effective in 4-6 weeks. We know little bout the acclimatization time of mitochondria and activities of enzyme complexes during the process of HiLo. Objective: Using rat models under simulated HiLo condition, to observe the dynamic changes in mitochondrial respiration and activities of enzyme complexes during the process of HiLo under hypoxia, so as to investigate the acclimatization time of mitochondria and enzyme complexes of respiratory chain needed during HiLo. Design: Grouping and controlled animal trial. Setting: Exercise Physiology Laboratory of Physical Education Institute of Liaoning Normal University. Materials: Forty healthy adult SD rats, either male or female, were provided by the Animal Experimental Center of Dalian Medical University. The animal procedure was accorded with the animal ethics. The hypoxia partial pressure machine (HTS) was from Hypoxico Company of America, and Oxygen partial pressure monitor was TOXIBLAEPGM-36 from America. Methods: After 1 week of adaptive feeding, the rats were randomly divided into normoxic control group, HiLo 1, 2, 3, and 4 weeks groups with 8 rats in each group. HiLo groups lived at 2 500 m (O 2 content was around 15.4%) and swam at 1300 m (O 2 content was around 19.4%), 1 hour once for 4 weeks. Main Outcome Measures: The activities of enzyme complexes I-IV in the respiratory chain of mitochondria were measured using UV-spectrophotometer, and the method of Bradford was used to quantify protein of mitochondria. Results: The activities of enzyme complexes I IV of respiratory chain reduced significantly compared with control group in the first week (P < 0.05-0.01); the activities of enzyme complexes III recovered completely in the second week, which was not significantly different from the control group (P > 0.05). The activities of enzyme complexes I -IV recovered completely in third week compared with the control group (P > 0.05). There was no significant difference in protein quantity of mitochondria between HiLo 1 and 2 weeks groups and control group (P > 0.05), but significant differences were found between HiLo 3 and 4 weeks groups and control group (P < 0.05) Conclusion: The acclimatization of the activities of enzyme complexes I -IV in the respiratory chain will complete in three weeks in rats during the process of HiLo.
Fat deposition in health and illnessDefining obesityCauses of obesityMetabolic adaptations to weight gain and the development of insulin resistanceMetabolic complicationsIdentification and screening for metabolic complicationsLong-term risksManagement of obesity and its co-morbiditiesSelection of pediatric candidates for pharmacotherapyTiming of pharmacologic interventionMedication selection and therapeutic objectivesDuration of pharmacologic treatmentPrevention of complicationsPrevention of childhood obesityReferences
Purpose: The purpose of this study was to investigate the effect of non-instrumental resistance training on exercise capacity of patients with chronic heart disease. Methods: Nineteen elderly male patients (66.2±5.7 years) participated in the study. All had experienced coronary artery bypass surgery, coronary artery intervention, or aortic valve replacement [left ventricular ejection fraction (EF): 54.0±15.8 %]. Patients were divided into two groups. T group (N=9) performed combined aerobic and non-instrumental resistance training; and C group (N=10) performed only aerobic exercise. Resistance training involved 10 to 15 repetitions (maximum)(RM) of squats, push ups, calf raises and trunk curls. Each exercise included 3 sets of 10 repetitions repeated 3 times a week. Aerobic exercise was prescribed at the intensity of the aerobic threshold (AT) level 3 times a week. There was no significant base line for either T group or C group. Results: After three months of exercise, peak torque, peak V̇O2, and peak watts were significantly greater in T group, compared to those of C group. However, there was no significant correlation (r=.49) between the improvement of peak V̇O2 and peak torque. Conclusion: It was concluded that combined aerobic and non-instrumental resistance training is more effective than aerobic exercise alone for exercise capacity of patients with chronic heart disease. Home-based non-instrumental resistance training is usually highly significant from the perspective of the exercise capacity of patients with chronic heart disease.
Chronic heart failure (CHF) impairs critical structural and functional components of the O2 transport 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 skeletal muscle O2 delivery-utilization matching (QmO2 and VmO2, respectively). The QmO2/VmO2 ratio determines the microvascular O2 partial pressure (PmvO2) which represents the ultimate force driving blood-myocyte O2 flux (Figure 1). Improvements in perfusive and diffusive O2 conductances are essential to support faster rates of oxidative phosphorylation (reflected as faster VmO2 kinetics during metabolic transitions) and reduce the reliance on anaerobic glycolysis and utilization of finite energy sources (thus lowering the magnitude of the O2 deficit) in trained CHF muscle. These adaptations contribute to attenuated muscle metabolic perturbations and improved physical capacity (i.e., elevated critical power and maximal VmO2). This brief review focuses on the mechanistic bases for improved QmO2/VmO2 matching (and enhanced PmvO2) with exercise training in CHF with both preserved and reduced ejection fraction (HFpEF and HFrEF, respectively). Specifically, O2 convection within the muscle microcirculation, O2 diffusion 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 are also presented in light of their therapeutic potential. Adaptations within the skeletal muscle O2 transport 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.
Copyright © 2015, American Journal of Physiology - Heart and Circulatory Physiology.
Neurohormonal excitation and dyspnea are the hallmarks of heart failure (HF) and have long been associated with poor prognosis in HF patients. Sympathetic nerve activity (SNA) and ventilatory equivalent of carbon dioxide (VE/VO(2)) are elevated in moderate HF patients, and increased even further in severe HF patients. The increase in SNA in HF patients is present regardless of age, gender, and etiology of systolic dysfunction. Neurohormonal activation is the major mediator of the peripheral vasoconstriction characteristic of HF patients. In addition, reduction in peripheral blood flow increases muscle inflammation, oxidative stress and protein degradation, which is the essence of the skeletal myopathy and exercise intolerance in HF. Here we discuss the beneficial effects of exercise training on resting SNA in patients with systolic HF and its central and peripheral mechanisms of control. Further, we discuss the exercise-mediated improvement in peripheral vasoconstriction in patients with HF. We will also focus on the effects of exercise training on ventilatory responses. Finally, we review the effects of exercise training on features of the skeletal myopathy in HF. In summary, exercise training plays an important role in HF, working synergistically with pharmacological therapies to ameliorate these abnormalities in clinical practice.
Copyright © 2014, American Journal of Physiology - Heart and Circulatory Physiology.
Mitochondrial morphology has been associated with numerous pathologies including cancer, diabetes, obesity and heart disease. However, the connection is poorly understood—in part due to the difficulty of characterizing the morphology. This impedes the use of morphology as a tool for disease detection/monitoring. Here, we use the Brownian motion of isolated mitochondria to characterize their size and shape in a high throughput fashion. By using treadmill exercise training, mitochondria from heart and gastrocnemius of Balb/c mice were modulated in size and used to investigate the protocol. Consistent with previous reports, the heart mitochondria of untrained mice increased 5% in diameter immediately after a single bout of moderate exercise (1.091 ± 0.004 μm) as compared to completely sedentary controls (1.040 ± 0.022 μm). In addition, no change was observed in the size of gastrocnemius mitochondria (1.025 ± 0.018 μm), which was also in agreement with previous studies. The method was also successfully applied to smaller Saccharomyces cerevisiae mitochondria.
FUNDAMENTO: O termo insuficiência cardíaca (IC) refere-se à falha do coração em bombear sangue para suprir as necessidades do organismo. A função pulmonar e os músculos respiratórios podem estar afetados e os sintomas típicos apresentados pelos pacientes são desconforto aos mínimos esforços. OBJETIVO: Verificar a função pulmonar e a força dos músculos respiratórios em pacientes com IC em classes funcionais II e III, segundo a New York Heart Association (NYHA). MÉTODOS: O estudo foi descritivo e observacional, sendo incluídos 12 indivíduos com IC em classes II e III que estavam em acompanhamento ambulatorial. A função pulmonar (volume expiratório forçado no primeiro segundo VEF1 e capacidade vital forçada CVF) foi avaliada por meio da microespirometria e a força muscular respiratória (pressão expiratória máxima PEmáx e pressão inspiratória máxima PImáx), por meio de manovacuometria (marca Globalmed®). RESULTADOS: Houve diferença entre as classes II e III em relação à função pulmonar (VEF1: II = 91,17 ± 19,87 e III = 68,17 ± 21,78; CVF: II = 68,17 ± 21,78 e III = 73,67 ± 22,94) e à força muscular respiratória (PImáx: II = 71,67 ± 40,70 e III = 53,33 ± 29,27; PEmáx: II = 98,83 ± 34,56 e III = 58,33 ± 15,06). A classe II apresentou valores maiores que a III, em todos os parâmetros avaliados, com diferença estatisticamente significativa na PEmáx. CONCLUSÃO: A função pulmonar e a força muscular respiratória estão prejudicadas na IC, onde os indivíduos da classe III apresentam valores menores que a II, principalmente na PEmáx.
The purpose of this study was to measure the effects of a 12 month, progressive resistance training intervention on muscle morphology and strength gains in postmenopausal women. Skeletal muscle biopsies were obtained from the vastus lateralis of five (N=5) independent community dwelling women, (mean age: 75.6 ± 4.28 yrs; mean height: 163 ± 5.34 cm; mean weight: 72 ± 17.5 kg) before, six months and 12 months after progressive resistance training. Muscle strength (1-RM) was measured at the same time points. After six months of training morphological analysis revealed evidence of increased proteolysis and tissue repair, and rudimentary fiber development. The percent of Z bands with mild Z band disruption increased from 43.9% at baseline to 66.7% after six months of training (p < 0.01). Mitochondrial volume also increased (% of mitochondria = 0.86% at baseline, 1.19% at six months and 1.04% at 12 months, p<0.05) and there was a shift to larger sized mitochondria. The training did not result in statistically significant increases in muscle leg strength (p<0.18). It appears that mild Z band disruption acts as a precursor for increased protein synthesis and stimulates an increase in mitochondrial mass. Therefore, while a progressive resistance training program in this population did not increase muscle strength, it did demonstrate clinical applications that lend support to the importance of resistance training in older adults.
Objective: To review the benefits of exercise intervention in older persons and the role of exercise in the prevention and treatment of chronic disease.Methods: Qualitative assessment of the literature focusing on randomized controlled trials.Results: Participation in regular physical activity, including aerobic exercise and strength training, can improve health, functional ability, and quality of life in older persons. Higher levels of aerobic activity are associated with increased physical fitness, decreased total mortality, and improvements in cardiovascular risk profile. Resistance training combats myopathy and osteopenia and increases muscle endurance and function. Additional benefits from exercise include improved bone health and improved postural stability. Starting an exercise program in later life can significantly modify risk factors for morbidity and mortality even if a person has been sedentary in prior years.Conclusion: Physical activity should be encouraged in healthy seniors and should be considered a primary or adjunctive therapy in the treatment of chronic diseases associated with aging. Physicians can play a major role in communicating the benefits of exercise and encouraging physical activity in their patients.
Heart failure represents a major source of morbidity and mortality in industrialized nations. As the leading hospital discharge diagnosis in the United States in patients over the age of 65, it is also associated with substantial economic costs. While the acute symptoms of volume overload frequently precipitate inpatient admission, it is the symptoms of chronic heart failure, including fatigue, exercise intolerance and exertional dyspnea, that impact quality of life. Over the last two decades, research into the enzymatic, histologic and neurohumoral alterations seen with heart failure have revealed that hemodynamic derangements do not necessarily correlate with symptoms. This "hemodynamic paradox" is explained by alterations in the skeletal musculature that occur in response to hemodynamic derangements. Importantly, gender specific effects appear to modify both disease pathophysiology and response to therapy. The following review will discuss our current understanding of the systemic effects of heart failure before examining how exercise training and cardiac resynchronization therapy may impact disease course.
Morphometric measurements of mitochondria in human skeletal muscles provide useful information relating to tissue oxidative energy production, nutrition, exercise, and aging. Morphometric data such as area, perimeter, long axis, and short axis can be obtained by delineating individual mitochondria in electron micrographs. However, manual counting and delineating of individual mitochondria is a formidable task. The purpose of this study was to develop a fully automated computer algorithm for quantifying mitochondrial morphometry in electron micrographs. The algorithm locates mitochondria with a two-dimensional matched filter and then traces the borders of individual mitochondria. The delineation is accomplished by edge detection along radial lines launched outwards from the center of each mitochondrion. Shape descriptors applied to delineated mitochondria are used to reject likely false-positive selections. The results show that the fully automated algorithm detects mitochondria with a false-positive rate of 2% and a false-negative rate of 36%. The errors are easily and rapidly corrected by user intervention using a second semiautomated delineation algorithm. Morphometric measurements collected with the automated algorithm are equivalent to those obtained manually by human experts. The algorithm significantly improves the speed of image analysis and it also provides copious quantities of high-quality mitochondrial morphometric data.
To determine the efficacy of exercise training and its effects on outcomes in patients with heart failure.
MEDLINE, Medscape, and the Cochrane Controlled Trials Registry were searched for trials of exercise training in heart failure patients. Data relating to training protocol, exercise capacity, and outcome measures were extracted and reviewed.
A total of 81 studies were identified: 30 randomized controlled trials, five nonrandomized controlled trials, nine randomized crossover trials, and 37 longitudinal cohort studies. Exercise training was performed in 2387 patients. The average increment in peak oxygen consumption was 17% in 57 studies that measured oxygen consumption directly, 17% in 40 studies of aerobic training, 9% in three studies that only used strength training, 15% in 13 studies of combined aerobic and strength training, and 16% in the one study on inspiratory training. There were no reports of deaths that were directly related to exercise during more than 60,000 patient-hours of exercise training. During the training and follow-up periods of the randomized controlled trials, there were 56 combined (deaths or adverse events) events in the exercise groups and 75 combined events in the control groups (odds ratio [OR] = 0.98; 95% confidence interval [CI]: 0.61 to 1.32; P = 0.60). During this same period, 26 exercising and 41 nonexercising subjects died (OR = 0.71; 95% CI: 0.37 to 1.02; P = 0.06).
Exercise training is safe and effective in patients with heart failure. The risk of adverse events may be reduced, but further studies are required to determine whether there is any mortality benefit.
Patients with chronic heart failure have diminished exercise capacity as a major aspect of their clinical syndrome, regardless of the cause of their left ventricular contractile dysfunction. The mechanisms for the reduction in exercise capacity are multifactorial and include central cardiac, peripheral vascular, respiratory, and skeletal muscle maladaptations that accompany the pathophysiology of heart failure. Increased sympathetic nervous system activity and elevations in circulating neurohormones and cytokines also influence the cardiovascular and metabolic responses to exercise in these patients. Despite the improvements in clinical outcomes with beta-blockers and resynchronization therapy in heart failure patients, their exercise capacity remains substantially reduced when compared with normal age-matched patients. Exercise training has the potential to reverse or improve most of the abnormal physiologic responses to exercise in these patients, and it may serve as adjunctive therapy to standard medical care of these patients. In addition, a body of evidence is being accumulated that suggests that exercise training itself has important secondary prevention benefit in these patients. This review identifies the potential mechanisms whereby exercise training may improve exercise capacity in patients with chronic heart failure and presents the current information regarding clinical outcomes of this therapy.
In this manuscript we discuss the pathogenesis of type 2 diabetes in children, emphasizing the central importance of obesity, insulin resistance, dyslipidemia, hypertension and endothelial dysfunction. We then review critically the benefits of diet, exercise and pharmacotherapy in preventing type 2 diabetes and vascular complications in high risk children and young adults.
Heart failure (HF) is the inability of the heart to pump enough blood to supply the necessities of the body. Pulmonary function and respiratory muscles can be affected and typical symptoms presented by the patients include discomfort at a minimal exertion.
To verify pulmonary function and respiratory muscle strength in patients with class II and III HF as defined by the New York Heart Association (NYHA).
The study was descriptive and observational, and comprised 12 class II and III HF patients in follow-up at the out-patient. Pulmonary function assessments [Forced Expiratory Volume in the first second (FEV1) and Forced Vital Capacity (FVC)] were performed using microspirometry and respiratory muscle strength [Maximal Expiratory Pressure (MEPmax) and Maximal Inspiratory Pressure (MIPmax)] were evaluated using a pressure transducer (Globalmed).
Differences were found between the functional classes II and III in relation to pulmonary function: FEV1 (II: 91.17 +/- 19.87; III: 68.17 +/- 21.78); FVC (II: 68.17 +/- 21.78; III: 73.67 +/- 22.94); and respiratory muscle strength: MIPmax (II: 71.67 +/- 40.70; III: 53.33 +/- 29.27) and MEPmax (II: 98.83 +/- 34.56; III: 58.33 +/- 15.06). The class II were higher for all study parameters, only MEPmax revealed a statistically significant difference.
The pulmonary function and respiratory muscle strength are impaired in heart failure patients class III patients, particularly in relation to MEPmax.
The pathophysiology of chronic heart failure (CHF) is typically conceptualized in terms of cardiac dysfunction. However, alterations in peripheral blood flow and intrinsic skeletal muscle properties are also now recognized as mechanisms for exercise intolerance that can be modified by therapeutic exercise. This overview focuses on blood delivery, oxygen extraction and utilization that result from heart failure. Related features of inflammation, changes in skeletal muscle signaling pathways, and vulnerability to skeletal muscle atrophy are discussed. Specific focus is given to the ways in which perfusion and skeletal muscle properties affect exercise intolerance and how peripheral improvements following exercise training increase aerobic capacity. We also identify gaps in the literature that may constitute priorities for further investigation.
The capacity to perform physical activity largely depends on physical fitness. Muscle fiber-type distribution (Muscle(FTD)) is associated with physical fitness and may influence the capacity to perform physical activity. The purpose of this study was to determine whether habitual physical activity in daily life (PA(DL)) and Muscle(FTD) are related. Thirty-eight healthy non-athletes (31 women, 7 men) were recruited. PA(DL) was measured twice for 14 days using a tri-axial accelerometer for movement registration (Tracmor). From Tracmor output, the proportion of time subjects were physically active at low, moderate, and high intensities was determined (%Low, %Moderate, and %High, respectively). A total activity index (PA(index)) and sub-scores on work, leisure-time and sports were obtained using the Baecke questionnaire. Muscle(FTD) was determined using immuno-fluorescence against respective myosin heavy chain isoforms. No relationship was observed between PA(DL) and Muscle(FTD). %Low, %Moderate, and %High, as well as PA(index) and its sub-scores, were not related to Muscle(FTD) either. The time spent on sports was associated with the proportion of type I and II(X) fibers (P=0.06 and P<0.01, respectively). In conclusion, Muscle(FTD) probably cannot explain why some people are more prone to engaging in physical activities than others.
Activity-related energy expenditure is the most variable component of total energy expenditure and thus an important determinant of energy balance.Objective:To determine whether body composition is related to physical activity in both men and women.
A total of 134 healthy participants were recruited (80 women, 54 men; aged 21+/-2 years; body mass index, 22.0+/-2.4). Physical activity was measured for a period of 2 weeks using a triaxial accelerometer for movement registration (Tracmor). Percentage body fat (%BF) was determined by underwater weighing and deuterium dilution according to Siri's three-compartment model.
The participant characteristics-body mass, height and gender together explained a substantial part of the variation in %BF (R(2)=0.75, SEE=4.0%). Adding physical activity to the model increased the explained variation in %BF with 4% (R(2)=0.79, SEE=3.7%, P<0.001). Taking seasonality into account by adding the number of daylight hours as an independent variable further increased the explained variation with 1% (R(2)=0.80, SEE=3.7%, P<0.05). In analogy, the association was evaluated for both genders separately. In women, %BF and physical activity were significantly associated (P<0.001). In men, %BF was only associated with physical activity when seasonality was taken into account as well (P<0.05). This probably resulted from men participating more in season bound sports, because an association was found without adjusting for seasonality when only men with a consistent year-round participation in sports were considered.
Evidence was found for an association between body composition and physical activity in both genders. A consistent year-round degree of physical activity appears to be a prerequisite to reveal the association. Moreover, Tracmor-assessed physical activity improves the estimate of %BF when a participant's characteristics are taken into account.
Physical exercise training is a powerful tool to maintain or improve mitochondrial density and function (mitochondrial capacity). This study aims to determine whether mitochondrial capacity is also associated with habitual physical activity in daily life (PADL). The capacity of classic markers for mitochondrial density, i.e., the capacity of citrate synthase (CS) and succinate dehydrogenase (SDH), as well the capacity of cytochrome c oxidase (COX) and beta-hydroxyacyl-CoA dehydrogenase (HAD), was determined in homogenized muscle biopsy samples obtained from the vastus lateralis muscle of nonexercising healthy young (age 20+/-2 yr) subjects (31 women, 7 men). PADL was measured during two periods of 14 days using a triaxial accelerometer for movement registration. CS, SDH, and COX were positively associated with PADL [P<0.05, R=0.36, 95% confidence interval (CI): 1.3.10(-4) to 2.2.10(-3); P<0.05, R=0.39, 95% CI: 1.1.10(-5) to 9.9.10(-5); and P<0.05, R=0.33, 95% CI: 7.5.10(-6) to 3.6.10(-4), respectively], and HAD tended to correlate positively with PADL (P=0.06, R=0.31, 95% CI: -2.2.10(-5) to 1.1.10(-3)). The population was subsequently stratified based on the intensity of the activities performed. CS was only associated with PADL in subjects spending more time on high-intensity physical activity, whereas HAD was only associated with PADL in subjects spending less time on low intensity physical activity. We are the first to report that even within the range of normal daily life activities, mitochondrial capacity is positively associated with the level of habitual physical activity in daily life. Thus an active lifestyle may help to maintain or improve mitochondrial capacity.
To determine the effects of a 6-month exercise training program on left ventricular (LV) function and remodeling, 49 consecutive patients (pts) with first Q anterior myocardial infarction (51 +/- 8 years), in I-II NYHA class, were studied 4 to 8 weeks after the acute episode and 6 months later by 2D-ECHO and upright bicycle ergometric test. At entry, pts were randomly allocated to physical training (T = 25pts) or control (C = 24pts). Global endocardial surface area (ESA), LV volumes and EF, extent of abnormal wall motion (%WMA), of regional dilatation (%REG DIL), and the shape distortion (DIST) index were analyzed. After 6 months, a significant increase in work capacity (4,589 +/- 1,417 to 5,379 +/- 1,485 KPM/min, p less than 0.03) and in lactic anaerobic threshold (45 +/- 13 to 63 +/- 15 W, p less than 0.01) was observed only in T. Initial ESA, EDV, EF, %WMA, %REG DIL, and DIST index were similar and they did not change after 6 months in both groups. However, pts with less than 40%EF had greater (p less than 0.0001) EDV and %WMA with marked DIST index at entry and showed further (p less than 0.01) deterioration after 6 months both in C and in T (EDV, ml/m2: 68 +/- 12 to 77 +/- 18 in C, 71 +/- 12 to 74 +/- 18 in T; %REG DIL: 39 +/- 20 to 49 +/- 24 in C, 32 +/- 12 to 35 +/- 23 in T; DIST index: 0.16 +/- 0.07 to 0.21 +/- 0.09 in C, 0.2 +/- 0.07 to 0.22 +/- 0.1 in T). These variables did not change in pts with greater than 40%EF. Thus, from these preliminary data, pts with less than 40%EF at entry are prone to further global and regional LV deterioration. Physical training does not seem to increase this spontaneous deterioration.
To determine the effects of a 6-month exercise training program on left ventricular (LV) function and remodeling, 49 consecutive patients (pts) with first Q anterior myocardial infarction (51 ± 8 years), in I-II NYHA class, were studied 4 to 8 weeks after the acute episode and 6 months later by 2D-ECHO and upright bicycle ergometric test. At entry, pts were randomly allocated to physical training (T = 25pts) or control (C = 24pts). Global endocardial surface area (ESA), LV volumes and EF, extent of abnormal wall motion (%WMA), of regional dilatation (%REG DIL), and the shape distortion (DIST) index were analyzed. After 6 months, a significant increase in work capacity (4,589 ± 1,417 to 5,379 ± 1,485 KPM/min, p 40%EF. Thus, from these preliminary data, pts with <40%EF at entry are prone to further global and regional LV deterioration. Physical training does not seem to increase this spontaneous deterioration.
Eleven patients with chronic heart failure secondary to ischaemic heart disease (mean [SEM] age 63·0 [2·3] years; left ventricular ejection fraction 19 [8]%) undertook 8 weeks of home-based bicycle exercise training and 8 weeks of activity restriction (rest) in a physician-blind, random-order, crossover trial. Training increased exercise duration from 14·2 (1·1) min to 16·8 (1·3) min and peak oxygen consumption from 14·3 (1·1) ml.min-1.kg-1 to 16·7 (1·3) ml.min-1.kg-1. Heart rates at submaximum workloads and rate-pressure products were significantly reduced by training, and there was also a significant improvement in patient-rated symptom scores. No adverse events occurred during the training phase. Thus home-based physical training programmes are feasible even in severe chronic heart failure and have a beneficial effect on exercise tolerance, peak oxygen consumption, and symptoms. The commonly held belief that rest is the mainstay of treatment of chronic heart failure should no longer be accepted.
Congestive heart failure is a potentially debilitating disorder that affects a significant number of patients. The age-adjusted death rate has doubled over the past decade. Patients live an average of 4 to 5 years, and nearly all suffer from fatigue and breathlessness, which limits exercise capacity and produces a poor quality of life. Patients have usually been advised to avoid exercise because of concerns that they would experience a further decline in cardiac function. However, it has been demonstrated that exercise capacity is not related to the degree of left ventricular systolic dysfunction. This has led to the suggestion that peripheral changes in skeletal muscle and blood supply may play a major role in determining the exercise capacity of patients with congestive heart failure. Studies have demonstrated abnormalities of skeletal muscle blood flow, metabolism and structure, all of which are consistent with the impaired performance observed in these patients. Although the effects of exercise training have been examined in only a relatively few number of patients, the results have been promising. Exercise training has been found to improve exercise capacity and reduce symptoms. However, to our knowledge no data exist as to the impact of exercise training on left ventricular function, hospital stay or mortality in this population. Even though the early results are promising, they require confirmation of feasibility, clinical benefit and safety in larger, long term randomized trials. It should be determined whether training has a long-term beneficial impact on measures more closely related to daily activities and quality of life. Ultimately, it would be important to determine whether training has an impact on mortality and morbidity.
Muscle fiber fine structure was quantitatively analyzed in 70 longitudinally and 65 transversely sectioned fibers from 10 control subjects without weakness. The average mitochondrial fraction of the fiber volume is close to 4 percent and the mean size of a mitochondrion is about 0.1 mum2. The sarcotubular surface area per unit fiber volume is close to 1.5 mum2/mum3 in transverse sections and 0.65 times this value in longitudinal sections. Only one-third of all fibers contain lipid droplets in the sectioned plane, and for all fibers the droplets account for approximately 0.12 percent of the fiber volume. Variations with the age and sex of the subjects and with different muscles were analyzed and the feasibility of typing human muscle fibers at the ultrastructural level was evaluated.
Twenty-four biopsy specimens from the lower leg muscles of 21 patients with intermittent claudication were studied by electron microscopy. Sixteen of the specimens contained hypertrophic, atrophic, autolytic, or phagocytic fibers, or other forms of macroscopic fiber degeneration. Of the pathological changes in the cell organelles, the most common was simple myofibrillar degeneration, followed by slightly pathological mitochondria and excessive accumulations of glycogen and lipofuscin. Different types of basement membrane alterations and central nuclei were present in 16 of the biopsy specimens. Most of the pathological changes were the same as those previously reported by others to occur in specific diseases of muscle. There was some positive correlation of the degree of pathological changes to the estimated clinical severity of claudication.
We have examined muscle strength, mitochondrial enzyme activity, histochemistry and fibre size in the quadriceps muscle of 9 patients with severe chronic heart failure. A needle biopsy of the quadriceps muscle was taken with patients at rest. Maximum oxygen uptake was measured during treadmill exercise. Mean maximal oxygen consumption was 11.7 ml.kg-1.min-1. Isometric maximum voluntary contraction was reduced to 55% of the predicted value for weight. Eight biopsies were abnormal. Findings included increased acid phosphatase, increased interstitial cellularity, excess intracellular lipid accumulation, atrophy of both type I and II fibres and variation in size with hypertrophy and atrophy of fibers. Muscle fibre capillary density and the activity of mitochondrial enzymes were normal. Changes in skeletal muscle strength may play a role in the limitation of exercise capacity seen in patients with congestive heart failure.
Muscle strength, muscle cross-sectional area, fiber size, fiber type distribution, capillarity, and mitochondrial volume were estimated before and after 6 weeks of heavy-resistance exercise. Isokinetic torque production of the knee extensor muscles increased by a total of 17.6%, mainly during the first half of the training period. The cross-sectional area of the vastus lateralis muscle increased by 8.4%, mainly during the second half of the training period. Morphometrically determined fiber size, fiber type distribution, and capillarity from biopsies of vastus lateralis did not change significantly with training. Likewise, the surface densities of inner and outer mitochondrial membranes as well as the volume density of myofibrils remained unchanged. In contrast, the volume density of mitochondria decreased by 9.6%. However, due to the increase in total muscle volume, the calculated absolute volume of mitochondria remained constant, whereas the absolute volume of myofibrils increased by 10%.
It is concluded that strength training of short duration in previously untrained young male subjects does not change the ultrastructural composition of mitochondria and that the apparent dilution of mitochondria can quantitatively be accounted for by the increase in myofibrillar volume.
Symptoms of congestive heart failure occur most commonly during exercise, but cardiac performance is usually quantitated at rest. The relation between exercise capacity and measurements of cardiac performance at rest is little known. Treadmill exercise was performed in 21 patients with heart failure due to cardiomyopathy. Exercise duration averaged 9.1 +/- 0.7 (standard error of the mean) minutes (normal value 12 or more minutes) and did not correlate with resting ejection fraction of 26.4 +/- 2.7 percent (r = -0.06). Left ventricular diastolic dimension of 6.6 +/0 0.2 cm, mean velocity of circumferential fiber shortening and ratio of preejection period to left ventricular ejection time did not correlate with treadmill time (r = -0.03). Repeat studies after treatment of heart failure also failed to show correlations between changes in exercise capacity and changes in left ventricular performance at rest. Thus, measures of left ventricular performance obtained at rest do not accurately reflect exercise tolerance and symptomatic status of patients with congestive heart failure.
The present study was designed to evaluate the effect of an ambulatory training program on ultrastructural morphology and the oxidative capacity of skeletal muscle and its relation to central and peripheral hemodynamic variables in patients with chronic heart failure.
Clinical evidence supports the hypothesis that exercise intolerance in patients with chronic heart failure is not only a consequence of low cardiac output, but is also a result of alterations in oxidative metabolism of skeletal muscle.
Twenty-two patients were prospectively randomized either to a training group (mean [+/-SD] ejection fraction 26 +/- 9%, n = 12) participating in an ambulatory training program or to a physically inactive control group (ejection fraction 27 +/- 10%, n = 10). At baseline and after 6 months, patients underwent symptom-limited bicycle exercise testing, and central and peripheral hemodynamic variables were measured. Percutaneous needle biopsy samples of the vastus lateralis muscle were obtained at baseline and after 6 months. The ultrastructure of skeletal muscle was analyzed by ultrastructural morphometry.
After 6 months, patients in the training group achieved an increase in oxygen uptake at the ventilatory threshold of 23% (from 0.86 +/- 0.2 to 1.07 +/- 0.2 liters/min, p < 0.01 vs. control group) and at peak exercise of 31% (from 1.49 +/- 0.4 to 1.95 +/- 0.4 liters/min, p < 0.01 vs. control group). There was no significant change in oxygen uptake at the ventilatory threshold and at peak exercise in the control group. The total volume density of mitochondria and volume density of cytochrome c oxidase-positive mitochondria increased significantly by 19% (from 4.7 +/- 1.5 to 5.6 +/- 1.5 vol%, p < 0.05 vs. control group) and by 41% (from 2.2 +/- 1.0 to 3.1 +/- 1.0 vol%, p < 0.05 vs. control group) after 6 months of regular physical exercise. Cardiac output at rest and at submaximal exercise remained unchanged but increased during maximal symptom-limited exercise from 11.9 +/- 4.0 to 14.1 +/- 3.3 liters/min in the training group (p < 0.05 vs. baseline; p = NS vs. control group). Peak leg oxygen consumption increased significantly by 45% (from 510 +/- 172 to 740 +/- 254 ml/min, p < 0.01 vs. control group). Changes in cytochrome c oxidase-positive mitochondria were significantly related to changes in oxygen uptake at the ventilatory threshold (r = 0.82, p < 0.0001) and at peak exercise (r = 0.87, p < 0.0001).
Regular physical training increases maximal exercise tolerance and delays anaerobic metabolism during submaximal exercise in patients with stable chronic heart failure. Improved functional capacity is closely linked to an exercise-induced increase in the oxidative capacity of skeletal muscle.