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Abnormal mitochondrial function in locomotor and respiratory muscles of COPD patients

¹ Servicio de Neumología, ² Unidad de Medicina y Cirugía Experimental, and ³ Servicio de Cirugía de Tórax, Hospital General Universitario Gregorio Marañón, Madrid, ⁴ Servicio de Cirugía de Tórax and ⁵ Servicio de Neumología, Fundación Jiménez Díaz, Madrid, ⁶ CIBER Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, ⁷ Servicio Neumología, Hospital Universitario Son Dureta, Palma, and ⁸ Fundación Caubet-Cimera, Bunyola, Mallorca, Spain.

CORRESPONDENCE: L. Puente-Maestu, Servicio de Neumología, Hospital General Universitario Gregorio Marañón, c/ Doctor Ezquerdo 46, 28007 Madrid, Spain. Fax: 34 915868018. E-mail: lpuente{at}separ.es and lpuente.hgugm{at}salud.madrid.org

Keywords: Chronic obstructive pulmonary disease pathophysiology, muscle disorders, oxidative stress, quadriceps muscle, reactive oxygen species, respiratory muscles

Received: July 22, 2008
Accepted December 5, 2008

Several cellular and molecular alterations have been described in skeletal and respiratory muscles of patients with chronic obstructive pulmonary disease (COPD), but information on potential abnormalities of mitochondrial function is scarce. The aim of the present study was to investigate mitochondrial function in the vastus lateralis (VL) and external intercostalis (EI) of COPD patients.

Biopsies from VL and EI were obtained during surgery for lung cancer in 13 patients with mild to moderate COPD (age 68±6 yrs, forced expiratory volume in one second (FEV₁) 66±15% predicted) and 19 control subjects (age 67±9 yrs, FEV₁ 95±18% pred). State 3 and 4 mitochondrial oxygen consumption (V'_O2,m), ATP synthesis, citrate synthase, cytochrome oxidase (COX) and complex I–III activities, as well as reactive oxygen species (ROS) production, were determined.

In COPD patients, in both muscles, COX activity (VL: COPD 3.0±0.8 versus control 2.0±0.8; EI: 3.7±1.6 versus 2.4±0.9 µmol·min^–1·mg^–1) and ROS production (VL: 1,643±290 versus 1,285±468; EI: 1,033±210 versus 848±288 arbitrary units) were increased, whereas state 3 V'_O2,m was reduced (VL: 2.9±0.3 versus 3.6±0.4; EI: 3.6±0.3 versus 4.1±0.4 mmol·min^–1·kg^–1).

Skeletal muscle mitochondria of patients with chronic obstructive pulmonary disease show electron transport chain blockade and excessive production of reactive oxygen species. The concurrent involvement of both vastus lateralis and external intercostalis suggests a systemic (rather than a local) mechanism(s) already occurring in relatively early stages (Global Initiative for Chronic Obstructive Lung Disease stage II) of the disease.

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