TY - JOUR

T1 - The influence of hemoconcentration on hypoxic pulmonary vasoconstriction in acute, prolonged and life-long hypoxemia.

AU - Stembridge, Mike

AU - Hoiland, Ryan

AU - Williams, Alexandra

AU - Howe, Connor

AU - Dawkins, Tony

AU - Drane, Aimee

AU - Tymko, Michael M

AU - Gasho, Christopher

AU - Anholm, James

AU - Simpson, Lydia

AU - Bailey, Damian

AU - Moore, Jonathan

AU - MacLeod, David

AU - Ainslie, Phil

PY - 2021/10/1

Y1 - 2021/10/1

N2 - Haemoconcentration can influence hypoxic pulmonary vasoconstriction (HPV) via increased frictional force and vasoactive signalling 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: (i) at sea level, in normoxia and isocapnic hypoxia with and without isovolumic haemodilution (n=10, aged 29±7 years); (ii) at altitude (6±2 days acclimatization at 5050 m), before and during hypervolumic haemodilution (n=11, aged 27±5 years) with room air and additional hypoxia (FiO2 = 0.15), and; (iii) at altitude (4340 m) in Andean high-altitude natives with excessive erythrocytosis (EE; n=6, aged 39±17 years), before and during isovolumic haemodilution with room air and hyperoxia (end-tidal PO2 = 100 mmHg). Results: At sea level, haemodilution 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 5050 m, haemodilution 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 4340 m, haemodilution 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 haematocrit level. In application, these findings emphasize the importance of accounting for haematocrit and duration of exposure when interpreting the pulmonary vascular responses to hypoxemia.

AB - Haemoconcentration can influence hypoxic pulmonary vasoconstriction (HPV) via increased frictional force and vasoactive signalling 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: (i) at sea level, in normoxia and isocapnic hypoxia with and without isovolumic haemodilution (n=10, aged 29±7 years); (ii) at altitude (6±2 days acclimatization at 5050 m), before and during hypervolumic haemodilution (n=11, aged 27±5 years) with room air and additional hypoxia (FiO2 = 0.15), and; (iii) at altitude (4340 m) in Andean high-altitude natives with excessive erythrocytosis (EE; n=6, aged 39±17 years), before and during isovolumic haemodilution with room air and hyperoxia (end-tidal PO2 = 100 mmHg). Results: At sea level, haemodilution 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 5050 m, haemodilution 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 4340 m, haemodilution 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 haematocrit level. In application, these findings emphasize the importance of accounting for haematocrit and duration of exposure when interpreting the pulmonary vascular responses to hypoxemia.

KW - Hypoxic pulmonary vasoconstriction

KW - haemodilution

KW - pulmonary pressure

KW - hypoxia

KW - Viscosity

U2 - 10.1152/ajpheart.00357.2021

DO - 10.1152/ajpheart.00357.2021

M3 - Article

VL - 321

SP - H738-H747

JO - American Journal of Physiology - Heart and Circulatory Physiology

JF - American Journal of Physiology - Heart and Circulatory Physiology

SN - 0363-6135

IS - 4

ER -