Impaired Skeletal Muscle Oxygenation and Exercise Tolerance in Pulmonary Hypertension

Background Limb muscle dysfunction is documented in pulmonary arterial hypertension (PAH), but little is known regarding muscle oxygen (O-2) supply and its possible effects on exercise tolerance in PAH. Methods Ten patients with PAH and 10 matched controls underwent progressive maximal cardiopulmonary exercise test, voluntary and nonvolitional dominant quadriceps muscle strength measures, and nondominant quadriceps biopsy to assess maximal oxygen uptake, muscle function, and lower limb fiber type and capillarity, respectively. Both groups then performed normoxic and hyperoxic submaximal intensity exercise protocol at the same absolute workload during which muscle O-2 supply was assessed by measuring changes in myoglobin-deoxyhemoglobin level ([Mb-HHb]) and tissue oxygenation index in the dominant quadriceps using near-infrared spectroscopy. Changes in cardiac output, estimated systemic O-2 delivery, and systemic O-2 saturation were also assessed noninvasively throughout both submaximal exercises. Results Patients with PAH displayed lower maximal oxygen uptake (P < 0.01), skeletal muscle strength (P < 0.05), and capillarity (P = 0.01). Throughout the normoxic submaximal exercise protocol, [Mb-HHb] (P < 0.01) was higher whereas changes in tissue oxygenation index (P < 0.01) and systemic O-2 saturation (P = 0.01) were lower in patients with PAH compared with those in controls. Conversely, changes in cardiac output and estimated systemic O-2 delivery were similar between groups. Muscle oxygenation remained unchanged with O-2 supplementation. Among variables known to influence tissue oxygenation, only quadriceps capillarity density correlated with [Mb-HHb] (r = -0.66, P < 0.01), which in turn correlated with maximal oxygen uptake (r = -0.64, P < 0.01), 6-min walked distance (r = -0.74, P = 0.01), and both voluntary (r = -0.46, P = 0.04) and nonvolitional (r = -0.50, P = 0.02) quadriceps strength. Conclusions Capillary rarefaction within the skeletal muscle influences exercise tolerance and quadriceps strength at least partly through impaired muscle oxygen supply in PAH.