Sustained Hypoxic Pulmonary Hypertension and Systemic Vascular Dysfunction in High‐Altitude Dwellers Prone to Re‐Entry High Altitude Pulmonary Edema, Improvement by Anti‐Oxidants

Abstract

Re‐entry high altitude pulmonary edema (HAPE) is a live‐threatening problem that occurs on return from low altitude in otherwise healthy high‐altitude dwellers. The underlying mechanism is poorly understood. Circumstantial data suggest that pulmonary vascular dysfunction facilitating hypoxic pulmonary vasoconstriction plays a role. There is increasing evidence that at in high altitude dwellers, pulmonary vascular dysfunction is often associated with alterations of the systemic circulation related to altered redox regulation. We speculated that re‐entry HAPE prone subjects display sustained pulmonary and systemic vascular dysfunction related to increased oxidative stress.We therefore measured systolic pulmonary artery pressure (PAP, echocardiography), flow mediated dilation of the brachial artery and carotid intima‐media thickness (IMT) in re‐entry HAPE prone subjects and controls living at 3600 m. The main new findings were 2‐fold: 1) PAP was significantly higher in re‐entry‐HAPE prone than control subjects (38±2 vs. 24±1 mm Hg, p<0.001, X±SE) and this pulmonary vascular dysfunction was associated with systemic vascular alterations, as evidenced by increased IMT (485±21 vs. 404±10µm, p=0.002) and decreased FMD (5.1±0.6 vs. 9.7±0.8%, p<0.001). 2) Vit. C administration normalized FMD (Vit C 3 g i.v., 9.2±1.3% p=NS vs. controls) and decreased PAP (Vit C 1g/d for 30 d, 31 ± 1 vs. 38±2 mm Hg, p=0.04) in re‐entry HAPE prone subjects. Here we show for the first time that re‐entry HAPE prone high‐altitude dwellers display generalized vascular dysfunction that is related to altered redox‐regulation.