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CLINICAL STUDY

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

Bertrand Mettauer, MD, PhD^*, Joffrey Zoll, BS^*, Hervé Sanchez, BS^*, Eliane Lampert, MD^*, Florence Ribera, BS^*, Vladimir Veksler, MD, PhD, Xavier Bigard, MD, PhD, Philippe Mateo, PhD, Eric Epailly, MD^*, Jean Lonsdorfer, MD^* and Renée Ventura-Clapier, PhD

^* Département de Physiologie, Faculté de Médecine, Université Louis Pasteur, Strasbourg, France
Cardiologie Cellulaire et Moléculaire U-446 INSERM, Faculté de Pharmacie, Université Paris-Sud, Châtenay-Malabry, France
Unité de Bioénergétique, CRSSA, La-Tronche Cedex, France

Manuscript received December 7, 2000; revised manuscript received May 21, 2001, accepted June 11, 2001.

Reprint requests and correspondence: Dr. Bertrand Mettauer, Département de Physiologie, Faculté de Médecine, 11, rue Humann, 67000 Strasbourg, France
Bertrand.Mettauer{at}physio-ulp.u-Strasbg.fr

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 (V_max) respiration rates and to assess mitochondrial regulation by ADP. All patients received angiotensin-converting enzyme (ACE) inhibitors.

RESULTS

The pVO₂ differed 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 (V_max, 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 pVO₂ and muscle oxidative capacity observed in controls was displaced toward lower pVO₂ values.

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.

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme   ACR = acceptor control ratio   ACT = active normal controls   ADP = adenosine diphosphate   CHF = chronic heart failure   CK = creatine kinase   CS = citrate synthase   HR = heart rate   LDH = lactate dehydrogenase   MHC = myosin heavy chain   NO = nitric oxide   RER = respiratory exchange ratio   SED = true sedentary controls   VADP = ADP-stimulated tissue oxygen uptake   VCO2 = carbon dioxide produced   Vmax = maximal tissue oxygen uptake   VO2max = predicted normal maximal oxygen uptake   VO2 = oxygen uptake   VT = ventilatory threshold

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