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The influence of hemoconcentration on hypoxic pulmonary vasoconstriction in acute, prolonged, and lifelong hypoxemia

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posted on 21.10.2021, 13:11 authored by Mike Stembridge, Ryan L Hoiland, Alexandra M. Williams, Connor A Howe, Joseph DonnellyJoseph Donnelly, Tony DawkinsTony Dawkins, Aimee DraneAimee Drane, Michael M. Tymko, Christopher Gasho, James Anholm, Lydia L. Simpson, Jonathan P. Moore, Damian M. Bailey, David B. MacLeod, Philip N. Ainslie
Hemoconcentration can influence hypoxic pulmonary vasoconstriction (HPV) via increased frictional force and vasoactive signaling from erythrocytes, but whether the balance of these mechanism is modified by the duration of hypoxia remains to be determined. We performed three sequential studies: 1) at sea level, in normoxia and isocapnic hypoxia with and without isovolumic hemodilution (n = 10, aged 29 ± 7 yr); 2) at altitude (6 ± 2 days acclimatization at 5,050 m), before and during hypervolumic hemodilution (n = 11, aged 27 ± 5 yr) with room air and additional hypoxia [fraction of inspired oxygen (FIO2)= 0.15]; and 3) at altitude (4,340 m) in Andean high-altitude natives with excessive erythrocytosis (EE; n = 6, aged 39 ± 17 yr), before and during isovolumic hemodilution with room air and hyperoxia (end-tidal Po2 = 100 mmHg). At sea level, hemodilution mildly increased pulmonary artery systolic pressure (PASP; +1.6 ± 1.5 mmHg, P = 0.01) and pulmonary vascular resistance (PVR; +0.7 ± 0.8 wu, P = 0.04). In contrast, after acclimation to 5,050 m, hemodilution did not significantly alter PASP (22.7 ± 5.2 vs. 24.5 ± 5.2 mmHg, P = 0.14) or PVR (2.2 ± 0.9 vs. 2.3 ± 1.2 wu, P = 0.77), although both remained sensitive to additional acute hypoxia. In Andeans with EE at 4,340 m, hemodilution lowered PVR in room air (2.9 ± 0.9 vs. 2.3 ± 0.8 wu, P = 0.03), but PASP remained unchanged (31.3 ± 6.7 vs. 30.9 ± 6.9 mmHg, P = 0.80) due to an increase in cardiac output. Collectively, our series of studies reveal that HPV is modified by the duration of exposure and the prevailing hematocrit level. In application, these findings emphasize the importance of accounting for hematocrit and duration of exposure when interpreting the pulmonary vascular responses to hypoxemia.


This work was supported by the National Science and Engineering Research Council, Canada (to P.N.A.) and The Physiological Society, UK (to M.S.)


Published in

American Journal of Physiology-Heart and Circulatory Physiology


American Physiological Society


VoR (Version of Record)


Stembridge, M., Hoiland, R.L., Williams, A.M., Howe, C.A., Donnelly, J., Dawkins, T.G., Drane, A., Tymko, M.M., Gasho, C., Anholm, J., Simpson, L.L. et al (2021) 'The influence of hemoconcentration on hypoxic pulmonary vasoconstriction in acute, prolonged and life-long hypoxemia', American Journal of Physiology-Heart and Circulatory Physiology. https://doi.org/10.1152/ajpheart.00357.2021

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Cardiff Met Affiliation

  • Cardiff School of Sport and Health Sciences

Cardiff Met Authors

Mike Stembridge Tony Dawkins Aimee Drane

Cardiff Met Research Centre/Group

  • Cardiovascular Physiology

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© The Authors