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Published ahead of print on December 18, 2002, doi:10.1164/rccm.200206-519OC

Am. J. Respir. Crit. Care Med., Volume 167, Number 6, March 2003, 873-879

A more recent version of this article appeared on March 15, 2003
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Submitted on June 10, 2002
Accepted on December 13, 2002

Mitochondrial electron transport chain function is enhanced in inspiratory muscles of COPD patients

Florence Ribera1, Benoit N'Guessan1, Joffrey Zoll1, Dominique Fortin2, Bernard Serrurier3, Bertrand Mettauer4, Xavier Bigard3, Renee Ventura-Clapier2, and Eliane Lampert5*

1 Physiologie, Faculte de Medecine, Strasbourg, France; Service EFR et exercices, Hopitaux Universitaires, Strasbourg, France, 2 U-446 INSERM, Faculte de Pharmacie, Chatenay, France, 3 unite de Bioenergetique, CRSSA, La Tronche, France, 4 Physiologie, Faculte de Medecine, Strasbourg, France, 5 Service EFR et exercices, Hopitaux Universitaires, Strasbourg, France; Physiologie, Faculte de Medecine, Strasbourg, France

* To whom correspondence should be addressed. E-mail: Eliane.Lampert{at}physio-ulp.u-strasbg.fr.

In COPD, 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 to 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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