Reduced mitochondrial density in the vastus lateralis muscle of COPD patients with low fat free mass

Muscle wasting affecting a subgroup of patients with COPD, is a predictor of health related quality of life and survival. These patients have a further reduction in exercise capacity and evidence of decreased limb muscle oxidative capacity. We hypothesise that a further decrease in mitochondrial density occurs in patients with muscle wasting and may contribute to a lower oxidative capacity of the muscle. Mitochondrial ultrastructure was analysed using transmission electron microscopy in the vastus lateralis of seventeen COPD patients, ten with low fat free mass index (FFMI) (COPD L ) (FEV 1 33±4.3 %pred, FFMI 15±0.2 Kg.m -2 ), seven with preserved FFMI (COPD N ) (FEV 1 47±7.3 %pred, FFMI 19±0.6 Kg.m -2 ) and compared with nine age and gender-matched healthy sedentary subjects (C) (FEV 1 96±4.0 %pred, FFMI 20±0.9 Kg.m -2 ). Mitochondrial density was reduced in COPD L in comparison to COPD N (1.82±0.25 % and 2.72±0.34 % respectively, p L showed a reduction in mitochondrial least diameter (0.15±0.0µm and 0.13±0.00 µm respectively, p Mitochondrial density correlated with parameters of lung function, muscle function, exercise capacity and exacerbation frequency. Only exacerbations frequency remained independently related to mitochondrial density in a multiple regression analysis. We conclude that peripheral muscle of COPD L patients have a reduced mitochondrial density that is likely to contribute to a decreased oxidative capacity of the muscle. Supported by Chief Scientist Office (CSO) Scotland 06/S1103/5 and The British Lung Foundation (Trevor Clay, Tc07/09). SG was supported by an ERS long term research fellowship.