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

Increasing iron bioavailability attenuates hypoxic pulmonary vasoconstriction in both lowlanders and Sherpa at high altitude. In contrast, the pulmonary vasculature of Andeans suffering with chronic mountain sickness is resistant to iron administration. While pulmonary vascular remodeling and hypertension are characteristic features of chronic mountain sickness, the impact of iron administration in healthy Andeans has not been investigated. If the interplay between iron status and pulmonary vascular tone in healthy Andeans remains intact, this could provide valuable clinical insight into the role of iron regulation at high altitude.

Is the pulmonary vasculature in healthy Andeans responsive to iron infusion?

In a double-blinded, block-randomized design, 24 healthy high-altitude Andeans and 22 partially acclimatized lowlanders at 4300 m (Cerro de Pasco, Peru), received an i.v. infusion of either iron [iron (III)-hydroxide sucrose; 200mg] or saline. Markers of iron status were collected at baseline and 4 hours after infusion. Echocardiography was performed during room-air breathing (PIO2=∼96 mmHg) and during exaggerated hypoxia (PIO2=∼73 mmHg), at baseline, and at 2 and 4 hours following the infusion.

Iron infusion reduced pulmonary artery systolic pressure (PASP) by ∼2.5 mmHg in room air (main effect P<0.001), and by ∼7 mmHg during exaggerated hypoxia (main effect P<0.001) in both lowlanders and healthy Andean highlanders. There was no change in PASP following the infusion of saline. Iron metrics were comparable between groups, except for serum ferritin, which was 1.8-fold higher at baseline in the Andeans when compared to lowlanders [95% confidence interval (CI) 74-121 ng/ml vs. 37-70 ng/ml, respectively; P=0.003].

The pulmonary vasculature of healthy Andeans and lowlanders remains sensitive to iron infusion and this response seems to differ from the pathological characteristics of chronic mountain sickness.