ALTERED SKELETAL-MUSCLE METABOLIC RESPONSE TO EXERCISE IN CHRONIC HEART-FAILURE - RELATION TO SKELETAL-MUSCLE AEROBIC ENZYME-ACTIVITY

Article

关键词: LEFT-VENTRICULAR DYSFUNCTION;    NUCLEAR MAGNETIC-RESONANCE;    HIGH-ENERGY PHOSPHATES;    BLOOD-FLOW;    SUBMAXIMAL EXERCISE;    ANAEROBIC THRESHOLD;    QUADRICEPS FEMORIS;    BIOPSY SAMPLES;    LACTATE;    ABNORMALITIES;   

DOI  :  10.1161/01.CIR.84.4.1597

来源: SCIE

【 摘 要 】

Background. Exertional fatigue, which frequently limits exercise in patients with chronic heart failure, is associated with early anaerobic metabolism in skeletal muscle. The present study was designed to examine the skeletal muscle metabolic response to exercise in this disorder and determine the relation of reduced muscle blood flow and skeletal muscle biochemistry and histology to the early onset of anaerobic metabolism in patients. Methods and Results. We evaluated leg blood flow, blood lactate, and skeletal muscle metabolic responses (by vastus lateralis biopsies) during upright bicycle exercise in 11 patients with chronic heart failure (ejection fraction 21 +/- 8%) and nine normal subjects. In patients compared to normal subjects, peak exercise oxygen consumption was decreased (13.0 +/- 3.3 ml/kg/min versus 30.2 +/- 8.6 ml/kg/min, p < 0.01), whereas peak respiratory exchange ratio and femoral venous oxygen content were not different (both p > 0.25), indicating comparable exercise end points. At rest in patients versus normals, there was a reduction in the activity of hexokinase (p = 0.08), citrate sythetase (p < 0.02), succinate dehydrogenase (p = 0.0007), and 3-hydroxyacyl CoA dehydrogenase (p = 0.04). In patients, leg blood flow was decreased at rest, submaximal, and maximal exercise when compared to normal subjects (all p < 0.05), and blood lactate accumulation was accelerated. In patients, during submaximal exercise blood lactate levels were not closely related to leg blood flow but were inversely related to rest citrate synthetase activity in skeletal muscle (r = -0.74, p < 0.05). At peak exercise there were no intergroup differences in skeletal muscle glycolytic intermediates, adenosine nucleotides, or glycogen, whereas in patients compared to normal subjects less lactate accumulation and phosphocreatine depletion were noted (both p < 0.05), suggesting that factors other than the magnitude of phosphocreatine depletion or lactate accumulation may influence skeletal muscle fatigue in this disorder. Conclusions. The results of the present study suggest that in patients with chronic heart failure reduced aerobic activity in skeletal muscle plays an important role in mediating the early onset of anaerobic metabolism during exercise. Our findings are consistent with the concept that reduced aerobic enzyme activity in skeletal muscle is, in part, responsible for determining exercise tolerance and possibly the response to chronic interventions in patients with chronic heart failure.

【 授权许可】

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