Determinants of Peak Oxygen Uptake in Patients with Chronic Obstructive Pulmonary Disease: Looking Beyond the Lungs

Abstract

Peak oxygen uptake (V̇O2peak), a primary determinant of prognosis, mortality, and quality of life, is diminished in patients with chronic obstructive pulmonary disease (COPD). Of importance, even after lung function is restored, by lung transplant, V̇O2peak remains markedly attenuated, emphasizing the critical importance of peripheral dysfunction in this pathology. However, the peripheral determinants of V̇O2peak in patients with COPD remain poorly understood. Therefore, the purpose of this investigation was to assess the peripheral determinants of V̇O2peak in patients with COPD, to better understand disease‐related peripheral adaptations. Oxygen transport and utilization at peak single‐leg knee‐extensor exercise were assessed from arterial and femoral venous oxygenation measurements and leg blood flow (by thermodilution) in 8 patients with COPD (FEV1 = 0.9 ± SE 0.1 L, 30% of predicted) and 8 well‐matched control subjects. This exercise modality was utilized to minimize cardiopulmonary exercise limitations. Muscle convective O2 delivery (0.44 ± 0.06 vs. 0.69 ± 0.07 l/min, p<0.05) and muscle diffusive O2 conductance (6.6 ± 0.8 vs. 10.4 ± 0.9 ml/min/mmHg, p<0.05) were both ~1/3 lower in COPD patients than control subjects, resulting in a significantly attenuated leg V̇O2peak in the patients (0.27 ± 0.04 vs. 0.42 ± 0.05 l/min, p<0.05). Thus, in an exercise paradigm that minimizes cardiopulmonary limitations, the convective and diffusive components of oxygen transport within skeletal muscle, key determinants of V̇O2peak, are markedly diminished in patients with COPD. These findings emphasize the importance of peripheral factors, beyond the lungs, that limit exercise capacity, exacerbate inactivity, and increase the risk for cardiovascular disease in patients with COPD.Support or Funding InformationSupported by National Heart, Lung, and Blood Institute Grant HL‐091830This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.