Background: In chronic obstructive pulmonary disease (COPD), leg muscle blood flow may be compromised during dynamic exercise due to the competing influence of respiratory muscle work for available ...cardiac output. This study examined the flow demand limits of skeletal muscle flow in varying muscle mass recruitment. It employed one leg knee extension (1L-KE) and two-leg knee extension (2L-KE) to examine the mass-specific work rates at which peripheral circulatory function may become compromised due to elevated respiratory demands. Methods: Three male COPD patients (70 ± 5 yr; FEV1 /FVC = 42 ± 11%) and two aged-controls (74 ± 1 yr; FEV1/FVC = 76 ± 5%) completed three sets of 7-minute steady state 1L-KE and 2L-KE at 20, 40 and 65% (SS20%; SS40%; SS65%) of previously determined ergometer-specific peak power, separated by rest periods of 15 min. Leg muscle blood flow (BF) was determined using pulsed Doppler sonography of the femoral artery during incremental exercise loads and post-exercise. ECG, blood pressure, ventilatory parameters and VO2 were obtained continuously, and dye dilution cardiac output was measured at rest and during exercise. Results: Preliminary data showed that, for each exercise intensity, the required VO2 is similar in both groups. However, the workloads in COPD are between 60% and 82% of the control group workloads. During 1L-KE and 2L-KE, BF is consistently higher in COPD compared to controls. For 1L-KE, the increase in BF from rest (mean ± SD in ml/min; COPD vs controls) are SS20%: 763 ± 244 vs 105 ± 34; SS40%: 1157 ± 597 vs 310 ± 97; SS65%: 1493 ± 348 vs 424 ± 45. BF relative to workload is at least 3-fold higher in COPD compared to controls for all exercise intensities. Conclusions: These data suggest that mean muscle blood flow may not be compromised during knee-extensor exercise in COPD patients, and ongoing data will clarify whether this is a compensatory response to altered peripheral muscle metabolic function.
Patients with mitochondrial myopathies characteristically exhibit pronounced exercise intolerance, often associated with lactic acidosis, tachycardia and muscle weakness. These clinical features are ...attributable to impaired electron transport chain function in skeletal muscle. The usual etiology is a primary defect in mitochondrial DNA (mtDNA), where the severity of impairment is presumably linked to the ratio of mutant to wild-type mtDNA. This dissertation presents novel therapeutic approaches to these genetic defects, aimed at attenuating mitochondrial dysfunction and ameliorating the clinical condition by employing exercise training alone or in conjunction with pharmacological therapy. Dichloroacetate (DCA) was administered to augment mitochondrial capacity by activating pyruvate dehydrogenase, thereby decreasing lactic acidosis. Endurance and resistance training paradigms were employed to induce mitochondrial and satellite cell proliferation respectively. The goals were to augment respiratory chain function, increase levels of wild type mtDNA, and reverse effects of chronic inactivity. The effects of these treatments on functional and mitochondrial capacity were defined by changes in: (1) work capacity, oxygen utilization, and circulatory responses during maximal exercise; (2) heart rate and blood lactate during submaximal exercise; (3) recovery kinetics of phosphate-containing metabolites measured using phosphorus magnetic resonance spectroscopy ( 31P MRS); (4) scores on a quality of life questionnaire. The cellular correlates for these indices were defined by changes in: (1) mitochondrial volume, (2) respiratory chain enzyme activity, and (3) levels of mutant/wild-type mtDNA. Although DCA administration alone lowered blood lactate, endurance training was more effective in improving exercise capacity, heart rate and blood lactate, 31P MRS recovery kinetics, and quality of life. Increased mitochondrial volume and respiratory chain function were closely linked to these improvements and occurred despite increases in mutant/wild-type mtDNA, suggesting that absolute numbers of wild-type mtDNA, rather than the ratio alone, is functionally important. The variability of the training effect and long-term consequences of increased mutant/wild-type mtDNA raises concern about endurance training as a general treatment option. In contrast, resistance training led to remarkable decreases in mutant/wild-type mtDNA in a preliminary study in a patient with mitochondrial myopathy. This suggests that “gene shifting” may hold promise for improving muscle function and quality of life in many patients with mitochondrial myopathies.
Patients with mitochondrial myopathies characteristically exhibit pronounced exercise intolerance, often associated with lactic acidosis, tachycardia and muscle weakness. These clinical features are ...attributable to impaired electron transport chain function in skeletal muscle. The usual etiology is a primary defect in mitochondrial DNA (mtDNA), where the severity of impairment is presumably linked to the ratio of mutant to wild-type mtDNA. This dissertation presents novel therapeutic approaches to these genetic defects, aimed at attenuating mitochondrial dysfunction and ameliorating the clinical condition by employing exercise training alone or in conjunction with pharmacological therapy. Dichloroacetate (DCA) was administered to augment mitochondrial capacity by activating pyruvate dehydrogenase, thereby decreasing lactic acidosis. Endurance and resistance training paradigms were employed to induce mitochondrial and satellite cell proliferation respectively. The goals were to augment respiratory chain function, increase levels of wild type mtDNA, and reverse effects of chronic inactivity. The effects of these treatments on functional and mitochondrial capacity were defined by changes in: (1) work capacity, oxygen utilization, and circulatory responses during maximal exercise; (2) heart rate and blood lactate during submaximal exercise; (3) recovery kinetics of phosphate-containing metabolites measured using phosphorus magnetic resonance spectroscopy ( 31P MRS); (4) scores on a quality of life questionnaire. The cellular correlates for these indices were defined by changes in: (1) mitochondrial volume, (2) respiratory chain enzyme activity, and (3) levels of mutant/wild-type mtDNA. Although DCA administration alone lowered blood lactate, endurance training was more effective in improving exercise capacity, heart rate and blood lactate, 31P MRS recovery kinetics, and quality of life. Increased mitochondrial volume and respiratory chain function were closely linked
Exercise intolerance is a common presenting symptom. The physiology of exercise intolerance in illustrative neurologic diseases is reviewed. Roles for exercise testing are identified, particularly in ...the evaluation of metabolic myopathies. The potential benefits of low intensity aerobic exercise training are described.
PDF
