Global Research Expedition on Altitude-related Chronic Health 2018 Iron Infusion at High Altitude Reduces Hypoxic Pulmonary Vasoconstriction Equally in Both Lowlanders and Healthy Andean Highlanders

Abstract

Increasing iron bioavailability attenuates hypoxic pulmonary vasoconstriction in both lowlanders and Sherpas at high altitude. In contrast, the pulmonary vasculature of Andean individuals with chronic mountain sickness (CMS) is resistant to iron administration. Although pulmonary vascular remodeling and hypertension are characteristic features of CMS, the effect of iron administration in healthy Andean individuals, to our knowledge, has not been investigated. If theinterplay between iron status and pulmonary vascular tone in healthy Andean individuals remains intact, this could provide valuable clinical insight into the role of iron regulation at high altitude. Is the pulmonary vasculature in healthy Andean individuals responsive to iron infusion? In a double-blinded, block-randomized design, 24 healthy high-altitude Andean individuals and 22 partially acclimatized lowlanders at 4,300m (Cerro de Pasco, Peru) received an IV infusion of either 200mg of iron (III)-hydroxide sucrose or saline. Markers of iron status were collected at baseline and 4h after infusion. Echocardiography was performed in participants during room air breathing (partial pressure of inspired oxygen [Pio2] of approximately 96mmHg) and during exaggerated hypoxia (Pio2 of approximately 73mmHg) at baseline and at 2 and 4h after the infusion. Iron infusion reduced pulmonary artery systolic pressure (PASP) by approximately 2.5mmHg in room air (main effect, P< .001) and by approximately 7mmHg during exaggerated hypoxia (main effect, P< .001) in both lowlanders and healthy Andean highlanders. There was no change in PASP after the infusion of saline. Iron metrics were comparable between groups, except for serum ferritin, which was 1.8-fold higher at baseline in the Andean individuals than in the lowlanders (95%CI, 74-121ng/mL vs37-70ng/mL, respectively; P= .003). The pulmonary vasculature of healthy Andean individuals and lowlanders remains sensitive to iron infusion, and this response seems to differ from the pathologic characteristics of CMS.