What is the central question of this study? How does hypoxic pulmonary vasoconstriction and the response to supplemental oxygen change over time at high altitude? What is the main finding and its importance? Lowlanders and partially de-acclimatized Sherpa both demonstrated pulmonary vascular responsiveness to supplemental oxygen that was maintained for 12days' exposure to progressively increasing altitude. An additional 2 weeks' acclimatization at 5050m altitude rendered the pulmonary vasculature minimally responsive to oxygen similar to the fully acclimatized non-ascent Sherpa. Additional hypoxic exposure at that time point did not augment hypoxic pulmonary vasoconstriction. Prolonged alveolar hypoxia leads to pulmonary vascular remodelling. We examined the time course at altitude, over which hypoxic pulmonary vasoconstriction goes from being acutely reversible to potentially irreversible. Study subjects were lowlanders (n=20) and two Sherpa groups. All Sherpa were born and raised at altitude. One group (ascent Sherpa, n=11) left altitude and after de-acclimatization in Kathmandu for ∼7days re-ascended with the lowlanders over 8-10days to 5050m. The second Sherpa group (non-ascent Sherpa, n=12) remained continuously at altitude. Pulmonary artery systolic pressure (PASP) and pulmonary vascular resistance (PVR) were measured while breathing ambient air and following supplemental oxygen. During ascent PASP and PVR increased in lowlanders and ascent Sherpa; however, with supplemental oxygen, lowlanders had significantly greater decrease in PASP (P=0.02) and PVR (P=0.02). After ∼14days at 5050m, PASP decreased with supplemental oxygen (mean decrease: 3.9mmHg, 95% CI 2.1-5.7mmHg, P<0.001); however, PVR was unchanged (P=0.49). In conclusion, PASP and PVR increased with gradual ascent to altitude and decreased via oxygen supplementation in both lowlanders and ascent Sherpa. Following ∼14days at 5050m altitude, there was no change in PVR to hypoxia or O2 supplementation in lowlanders or either Sherpa group. These data show that both duration of exposure and residential altitude influence the pulmonary vascular responses to hypoxia.
Read full abstract