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

• Published in: Journal of the American College of Cardiology 2001-10, Vol.38 (4), p.947-954
• Main Authors: Mettauer, Bertrand, Zoll, Joffrey, Sanchez, Hervé, Lampert, Eliane, Ribera, Florence, Veksler, Vladimir, Bigard, Xavier, Mateo, Philippe, Epailly, Eric, Lonsdorfer, Jean, Ventura-Clapier, Renée
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Cardiology. Vascular system; Citrate (si)-Synthase - metabolism; Creatine Kinase - metabolism; Exercise - physiology; Female; Heart; Heart Failure - metabolism; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Humans; L-Lactate Dehydrogenase - metabolism; Male; Medical sciences; Middle Aged; Mitochondria, Muscle - metabolism; Muscle, Skeletal - metabolism; Myosin Heavy Chains - metabolism; Oxygen Consumption
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/S0735-1097(01)01460-7

OBJECTIVES We investigated the in situ properties of muscle mitochondria using the skinned fiber technique in patients with chronic heart failure (CHF) and sedentary (SED) and more active (ACT) controls to determine: 1) whether respiration of muscle tissue in the SED and ACT groups correlates with peak oxygen consumption (pVo2), 2) whether it is altered in CHF, and 3) whether this results from deconditioning or CHF-specific myopathy. BACKGROUND Skeletal muscle oxidative capacity is thought to partly determine the exercise capacity in humans and its decrease to participate in exercise limitation in CHF. METHODS M. Vastus lateralis biopsies were obtained from 11 SED group members, 10 ACT group members and 15 patients with CHF at the time of transplantation, saponine-skinned and placed in an oxygraphic chamber to measure basal and maximal adenosine diphosphate (ADP)-stimulated (Vmax) respiration rates and to assess mitochondrial regulation by ADP. All patients received angiotensin-converting enzyme (ACE) inhibitors. RESULTS The pVo2differed in the order CHF < SED < ACT. Compared with SED, muscle alterations in CHF appeared as decreased citrate synthase, creatine kinase and lactate dehydrogenase, whereas the myosin heavy chain profile remained unchanged. However, muscle oxidative capacity (Vmax, CHF: 3.53 ± 0.38; SED: 3.17 ± 0.48; ACT: 7.47 ± 0.73, μmol o2·min−1·g−1dw, 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 pVo2and muscle oxidative capacity observed in controls was displaced toward lower pVo2values. CONCLUSIONS In these patients, the disease-specific muscle metabolic impairments derive mostly from extramitochondrial mechanisms that disrupt the normal symmorphosis relations. The possible roles of ACE inhibitors and level of activity are discussed.