Abnormal mitochondrial function in locomotor and respiratory muscles of COPD patients

¹ Servicio de Neumología
² Unidad de Medicina y Cirugía Experimental
³ Servicio de Cirugía de Tórax (Hospital General Universitario Gregorio Marañón, Madrid)
⁴ Servicio de Cirugía de Tórax (Fundación Jiménez Díaz, Madrid)
⁵ Servicio Neumologia (Hospital Universitario Son Dureta), Fundación Caubet-Cimera and CIBER Enfermedades Respiratorias (CIBERES), Mallorca, Spain

^* To whom correspondence should be addressed. E-mail: lpuente{at}separ.es.

	Abstract

Several cellular and molecular alterations have been described in skeletal and respiratory muscles of patients with chronic obstructive lung disease (COPD), but information on potential abnormalities of mitochondrial function is scarce.

To study 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 (68±6yrs; FEV₁ 66±15%ref.) and 19 control subjects (67±9yrs; FEV₁ 95±18%ref.). State 3 and 4 mitochondrial oxygen consumption (V'O₂m), ATP synthesis, citrate-synthase (CS), 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 vs control 2.0±0.8; EI: 3.7±1.6 vs 2.4±0.9 µmol·min^-1·mg^-1) and ROS production (VL:1643±290 vs 1285±468; EI:1033±210 vs 848±288 arbitrary units) were increased (p<0.05) whereas state 3 V'O₂m reduced (p<0.05) (VL:2.9±0.3 vs 3.6±0.4, EI:3.6±0.3 vs 4.1±0.4 mmol·min^-1·kg^-1)

Skeletal muscle mitochondria of patients with COPD show electron transport chain blockade and excessive production of ROS. The concurrent involvement of both VL and EI suggests a systemic (rather than a local) mechanism(s) already occurring in relatively early stages (GOLD II) of the disease.