Influence of iron manipulation on hypoxic pulmonary vasoconstriction and pulmonary reactivity during ascent and acclimatization to 5050 m

Autor: David B. MacLeod, Giovanfrancesco Varoli, Alexandra M. Williams, Christopher Gasho, Philip N. Ainslie, Mike Stembridge, Daniela Nowak-Flück, Alexander Patrician, Lindsay K. Eller, Michael M. Tymko, Gordon Binsted, Prajan Subedi, Ryan L. Hoiland, Emily McBride, Raylene A. Reimer, Christopher K. Willie, Sawyer Plato, James D. Anholm, Aimee L. Drane
Rok vydání: 2021
Předmět:
Zdroj: The Journal of Physiology. 599:1685-1708
ISSN: 1469-7793
0022-3751
DOI: 10.1113/jp281114
Popis: Key points Iron acts as a cofactor in the stabilization of the hypoxic-inducible factor family, and likely plays an influential role in the modulation of hypoxic pulmonary vasoconstriction. It is uncertain whether iron regulation is altered in lowlanders during either 1) ascent to high altitude, or 2) following partial acclimatization, when compared to high-altitude adapted Sherpa. During ascent to 5050 m, the rise in pulmonary artery systolic pressure (PASP) was blunted in Sherpa, compared to lowlanders; however, upon arrival to 5050 m PASP levels were comparable in both groups, but the reduction in iron bioavailability was more prevalent in lowlanders, compared to Sherpa. Following partial acclimatization to 5050 m, there were differential influences of iron status manipulation (via iron infusion or chelation) at rest and during exercise between lowlanders and Sherpa on the pulmonary vasculature. Abstract To examine the adaptational role of iron bioavailability on the pulmonary vascular responses to acute and chronic hypobaric hypoxia, the hematological and cardiopulmonary profile of lowlanders and Sherpa were determined during: 1) a nine-day ascent to 5050m (20 lowlanders; 12 Sherpa), and 2) following partial acclimatization (11±4 days) to 5050m (18 lowlanders; 20 Sherpa), where both groups received either an i.v. infusion of iron (iron (iii)-hydroxide sucrose) or an iron chelator (desferrioxamine). During ascent, there were reductions in iron status in both lowlanders and Sherpa; however, Sherpa appeared to demonstrate a more efficient capacity to mobilize stored iron, compared to lowlanders, when expressed as a Δhepcidin per unit change in either body iron or the soluble transferrin receptor index, between 3400-5050m (p = 0.016 and p = 0.029 respectively). The rise in pulmonary artery systolic pressure (PASP) was blunted in Sherpa, compared to lowlanders during ascent; however, PASP was comparable in both groups upon arrival to 5050m. Following partial acclimatization, despite Sherpa demonstrating a blunted hypoxic ventilatory response and greater resting hypoxemia, they had similar hypoxic pulmonary vasoconstriction when compared to lowlanders at rest. Iron-infusion attenuated PASP in both groups at rest (p = 0.005), while chelation did not exaggerate PASP in either group at rest or during exaggerated hypoxemia (PI O2 = 67 mmHg). During exercise at 25% peak wattage, PASP was only consistently elevated in Sherpa, which persisted following both iron infusion or chelation. These findings provide new evidence on the complex interplay of iron regulation on pulmonary vascular regulation during acclimatization and adaptation to high altitude. This article is protected by copyright. All rights reserved.
Databáze: OpenAIRE
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