Oxidative capacity of skeletal muscle in heart failure patients versus sedentary or active control subjects

OBJECTIVES We investigated the in situ properties of muscle mitochondria us ing the skinned fiber technique in patients with chronic heart failure (CHF ) and sedentary (SED) and more active (ACT) controls to determine: 1) wheth er respiration of muscle tissue in the SED and ACT groups correlates with p eak oxygen consumption (pVo(2)), 2) whether it is altered in CHF, and 3) wh ether this results from deconditioning or CHF-specific myopathy. BACKGROUND Skeletal muscle oxidative capacity is thought to partly determin e the exercise capacity in humans and its decrease to participate in exerci se limitation in CHF. METHODS M. Vastus lateralis biopsies were obtained from 11 SED group member s, 10 ACT group members and 15 patients with CHF at the time of transplanta tion, saponineskinned and placed in an oxygraphic chamber to measure basal and maximal adenosine diphosphate (ADP) -stimulated (V-max) respiration rat es and to assess mitochondrial regulation by ADP. All patients received ang iotensinconverting enzyme (ACE) inhibitors. RESULTS The pVo(2) differed in the order CHF < SED < ACT. Compared with SED , muscle alterations in CHF appeared as decreased citrate synthase, creatin e kinase and lactate dehydrogenase, whereas the myosin heavy chain profile remained unchanged. However, muscle oxidative capacity (V-max, CHF: 3.53 +/ - 0.38; SED: 3.17 +/- 0.48; ACT: 7.47 +/- 0.73, mu mol o(2)(.)min(-1).g(-1) dw, p < 0.001 vs. CHF and SED) and regulation were identical in patients in the CHF and SED groups, differing in the ACT group only. In patients with CHF, the correlation between pVo(2) and muscle oxidative capacity observed in controls was displaced toward lower pVo(2) values. CONCLUSIONS In these patients, the disease-specific muscle metabolic impair ments derive mostly from extramitochondrial mechanisms that disrupt the nor mal symmorphosis relations. The possible roles of ACE inhibitors and level of activity are discussed. (C) 2001 by the American College of Cardiology.