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Mitochondrial Electron Transport Chain Function Is Enhanced in Inspiratory Muscles of Patients with Chronic Obstructive Pulmonary Disease

Service des Explorations Fonctionnelles Respiratoires et de l'Exercice, Hôpitaux Universitaires de Strasbourg, Département de Physiologie, Equipe d'Accueil, Faculté de Médecine, Strasbourg; Faculté de Pharmacie, Cardiologie Cellulaire et Moléculaire U-446 Institut National de la Santé et de la Recherche Médicale, Université Paris-Sud, Châtenay-Malabry; and Unité de Bioénergétique, Centre de Recherche du Service de Santé des Armées, BP 87, La-Tronche Cedex, France

Correspondence and requests for reprints should be addressed to Eliane Lampert, Department of Physiology, Faculty of Medicine, 11 rue Humann, 67,000 Strasbourg, France. E-mail: Eliane.Lampert{at}physio-ulp.u-strasbg.fr

In chronic obstructive pulmonary disease, inspiratory muscles face increased resistive and elastic workloads and therefore increased energy requirements. The adaptive response of these muscles to this higher energy demand includes increased oxidative enzymes and changes in contractile protein expression but the consequences on mitochondrial function and energy metabolism have not been assessed so far. We investigated the in situ properties of the mitochondria of costal diaphragm and external intercostal muscles using the skinned fiber technique in 9 emphysematous and 11 age-matched control patients. Biopsies obtained during thoracic surgery were placed in an oxygraphic chamber to measure maximal oxygen uptake. We observed that the maximal oxidative capacity of diaphragm and external intercostal muscles increased significantly in the emphysematous group compared with the control group (+135 and +37%, respectively). Significant correlations were found between the maximal oxidative capacity and patients' pulmonary indexes of obstruction (diaphragm: r = -0.637, intercostal: r = -0.667, p < 0.005) and hyperinflation (diaphragm: r = 0.639, p < 0.003, intercostal: r = 0.634, p < 0.01). Slow myosin heavy chain isoform increased in the diaphragm of the emphysematous group, with significant relationships between indexes of obstruction and hyperinflation and activities of biochemical mitochondrial markers. Thus, severe emphysema was associated with increased mitochondrial capacity and efficiency in the inspiratory muscles, supporting an endurance training-like effect.

Key Words: diaphragm • intercostal muscle • emphysema

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