Determinants of the diminished exercise capacity in patients with chronic obstructive pulmonary disease: looking beyond the lungs.

Peak oxygen uptake ( V ̇ O 2 peak ), a primary determinant of prognosis, mortality and quality of life, is diminished in patients with chronic obstructive pulmonary disease (COPD). Mounting evidence supports an important role of the periphery, particularly skeletal muscle, in the diminished V ̇ O 2 peak with COPD. However, the peripheral determinants of V ̇ O 2 peak have not been comprehensively assessed in this cohort. Thus, the hypothesis was tested that both muscle convective and diffusive oxygen (O2 ) transport, and therefore skeletal muscle peak O2 uptake ( V ̇ M O 2 peak ), are diminished in patients with COPD compared to matched healthy controls, even when ventilatory limitations (i.e. attainment of maximal ventilation) are minimized by using small muscle mass exercise. Muscle O2 transport and utilization were assessed at peak exercise from femoral arterial and venous blood samples and leg blood flow (by thermodilution) in eight patients with severe COPD (forced expiratory volume in 1s (FEV1 ) ± SEM = 0.9 ± 0.1 l, 30% of predicted) and eight controls during single-leg knee-extensor exercise. Both muscle convective O2 delivery (0.44 ± 0.06 vs. 0.69 ± 0.07 l min-1 , P < 0.05) and muscle diffusive O2 conductance (6.6 ± 0.8 vs. 10.4 ± 0.9 ml min-1  mmHg-1 , P < 0.05) were ∼1/3 lower in patients with COPD than controls, resulting in an attenuated V ̇ M O 2 peak in the patients (0.27 ± 0.04 vs. 0.42 ± 0.05 l min-1 , P < 0.05). When cardiopulmonary limitations to exercise are minimized, the convective and diffusive determinants of V ̇ M O 2 peak , at the level of the skeletal muscle, are greatly attenuated in patients with COPD. These findings emphasize the importance of factors, beyond the lungs, that may ultimately influence this population's prognosis, mortality and quality of life.