Abstract 16687: Abnormal Peripheral Muscle Oxygenation During Submaximal Exercise Contributes to Exercise Intolerance in Pulmonary Arterial Hypertension

Abstract

Introduction: Pulmonary arterial hypertension (PAH) is a vascular remodeling disease leading to right ventricular failure. Despite the most modern therapies, most patients display persistent and significant exercise intolerance. Many observations suggest that exercise limitation in PAH is not simply due to pulmonary hemodynamic impairment, but that other determinants intrinsic to the skeletal muscle are involved. Hypothesis: We hypothesized that O2 delivery to skeletal muscles during exercise is impaired in PAH independently of cardiac output. Methods and Results: Ten PAH patients performed a submaximal exercise at 70% of their peak workload (mean workload = 58 (15) W). Ten healthy controls performed the same exercise at the same workload as the PAH patients with whom they were paired. The increase in muscle deoxyhemoglobin concentration [HHb] (near-infrared spectroscopy, ISS) of the dominant quadriceps was significantly higher in PAH patients compared to healthy controls (29.6 (3.7) vs 9.7 (2.5) %; p<0.01) at the end of the submaximal exercise. This was not related to differences in cardiac output increases during exercise (+4.0 (0.7) vs +3.2 (0.4) L/min; p=0.29) (Nexfin BMEYE) or hemoglobin level (138.4 (2.4) vs 138.1 (3.7) g/L; p=0.94) for PAH patients and controls, respectively. Conversely, exercise-induced arterial O2 desaturation was more pronounced for PAH patients (-5.5 (1.8) vs -0.2 (0.6) %; p=0.03). Adding O2 supplementation did not significantly modified end-exercise muscle [HHb] (p=0.53), cardiac output increases (p=0.72) and arterial O2 desaturation (p=0.18). Quadriceps muscle biopsy confirmed that PAH patients had lower capillarity density compared to healthy controls (202 (27) vs 304 (23) #cap/mm2; p=0.01) that correlated with end-exercise muscle [HHb] (R2=0.37; p<0.01). Finally, muscle [HHb] during submaximal exercise correlated with VO2 max (R2=0.65; p<0.01) and 6 minutes walk test distance (R2=0.54; p=0.01). Conclusions: Our results demonstrate that PAH patients exhibit a lower skeletal muscle capillarity density that contributes to inadequate muscle O2 supply during exercise and exercise intolerance.