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

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Author
Willie, Christopher
Patrician, Alexander
Hoiland, Ryan
Williams, Alexandra
Gasho, Chris
Subedi, Prajan
Anholm, James
Drane, Aimee L.
Tymko, Michael
Nowak-Flück, Daniela
Plato, Sawyer
McBride, Emily
Varoli, Giovanfrancesco
Binsted, Gord
Eller, Lindsay
Reimer, Raylene
MacLeod, David
Stembridge, Mike
Ainslie, Philip
Date
2020
Acceptance date
2020-12-16
Type
Article
Publisher
Wiley
ISSN
0022-3751
1469-7793 (electronic)
Embargoed until
2100-01-01
Metadata
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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 hepcidin 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 (PIO2=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.
Journal/conference proceeding
Journal of Physiology;
URI
http://hdl.handle.net/10369/11252
Description
Article accepted for publication in Journal of Physiology
Rights
http://www.rioxx.net/licenses/under-embargo-all-rights-reserved
Sponsorship
Cardiff Metropolitan University (Grant ID: Cardiff Metropolian (Internal))
Canada Research Chairs (Chaires de recherche du Canada): Philip N Ainslie, -; Gouvernement du Canada | Natural Sciences andEngineering Research Council of Canada (Conseil de Recherches enSciences Naturelles et en Génie du Canada): Alexander Patrician, Ryan LHoiland, Michael M Tymko
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  • Sport Research Groups [1083]

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