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 (FEV(1)) 66+/-15% predicted) and 19 control subjects (age 67+/-9 yrs, FEV(1) 95+/-18% pred). State 3 and 4 mitochondrial oxygen consumption (V'(O(2),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 micromol 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'(O(2),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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Skeletal muscle dysfunction (SMD) is frequent in patients with chronic obstructive pulmonary disease (COPD). Mitochondrial abnormalities appear to play a role in the pathogenesis of SMD. The mitochondrion permeability transition pore (MPTP) facilitates the leakage of mitochondrial matrix constituents, such as cytochrome c (cyto-c), and triggers apoptosis, known to occur in skeletal muscle of patients with COPD. Our objective was to study MPTP kinetics and cyto-c release in skeletal muscle mitochondria of patients with COPD. Mitochondria were isolated from the vastus lateralis (VL), external intercostalis (EI), and latissimus dorsi (LD) in 11 patients with COPD (66 +/- 9 yr; FEV(1) 66 +/- 13%) and 15 smokers with normal lung function (64 +/- 6 yr; FEV(1) 95 +/- 11%) who required thoracic surgery for a localized lung neoplasm. MPTP kinetics were determined spectrophotometrically (time to reach V'max, V'max and mitochondrial swelling) and cyto-c release by enzyme-linked immunosorbent assay. MPTP kinetics and cyto-c release were abnormal in patients with COPD in the three muscles studied. In addition, V'max of VL mitochondria was significantly related (P < 0.01) to BMI (r = -0.75 COPD, -0.67 control) and aerobic capacity (r = -0.70 COPD, -0.60 control) for the COPD group. MPTP kinetics and cyto-c release are abnormal in skeletal and respiratory muscles of patients with moderate COPD, suggesting a systemic mechanism(s) occurring early during the course of the disease.

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