Daytime Ventilatory and Blood Acid-Base Responses During Ascent to 3500 m Are Larger and More Rapid in Females Than Males.
5 affiliations
- 1Department of Biology, Faculty of Science and Technology Mount Royal University Calgary Alberta Canada.
- 2Department of Emergency Medicine, Cumming School of Medicine University of Calgary Calgary Alberta Canada.
- 3Mineral Springs Hospital Banff Alberta Canada.
- 4High Altitude Pulmonary and Pathology Institute (HAPPI-IPPA) La Paz Bolivia.
- 5Department of Physiology and Pharmacology, Cumming School of Medicine University of Calgary Calgary Alberta Canada.
Abstract
With ascent to high altitude (HA), increased ventilation reduces the pressure of PaCO₂ (i.e., hypocapnia), resulting in respiratory alkalosis. A subsequent renal compensation is mediated through reductions in [HCO₃ ⁻]a, partly-correcting pHa. High inter-individual variability exists in ventilation, blood oxygenation, and acid-base responses with ascent to HA, but potential sex differences have not been well-characterized. We recruited 38 lowland participants (20 M; 18 F) before and after rapid ascent to and residence at 3500 m over 10 days in La Paz, Bolivia. We performed radial arterial blood draws to assess blood oxygenation and acid-base variables before (1100 m), and following ascent to 3500 m both early HA (E-HA; D2/3) and late HA (L-HA; D9/10). With E-HA, all participants had higher calculated V̇ A, and lower PaO₂ and SaO₂ (p < 0.0001), with subsequent increases in V˙ A, [Hb] and CaO₂ L-HA (p = 0.0056; p = 0.0003; p = 0.0013). Although females had higher V˙ A and PaO₂ than males E-HA (p < 0.0001; p = 0.0143), males had higher [Hb] and CaO₂ at 1100 m, at both E-HA (p = 0.0008; p = 0.0085) and L-HA (p = 0.0007; p = 0.0045). E-HA, all participants had lower PaCO₂ and [HCO₃ ⁻]a, and higher pHa than 1100 m (p < 0.0001; p = 0.0004, p < 0.0001), suggesting respiratory alkalosis and partial renal compensation. L-HA, PaCO₂ and [HCO₃ ⁻]a were further reduced (p = 0.0062; p = 0.0202), with pHa only partly-compensated (p = 0.4306). E-HA, PaCO₂, [HCO₃ ⁻]a and pHa were significantly lower in females (p < 0.0001; p < 0.0001; p = 0.0457), suggesting more complete renal compensation. However, these sex-differences were not apparent at L-HA (p > 0.5341). This is the first clear demonstration of differential ventilatory, oxygenation and acid-base compensation between sexes with rapid ascent to HA.
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BibTeX
@article{bushfield2026daytime,
title = {{Daytime Ventilatory and Blood Acid-Base Responses During Ascent to 3500 m Are Larger and More Rapid in Females Than Males.}},
author = {Nicole V Bushfield and Benjamin W L MacKenzie and Nicole A Johnson and Rodion Isakovich and Jamie L Keess and Nicholas D J Strzalkowski and Gustavo Zubieta-Calleja and Richard J A Wilson and Trevor A Day},
journal = {Comprehensive physiology},
year = {2026},
month = oct,
doi = {10.1002/cph4.70279},
url = {https://europepmc.org/article/MED/42926907},
note = {CC BY},
}
RIS
TY - JOUR
TI - Daytime Ventilatory and Blood Acid-Base Responses During Ascent to 3500 m Are Larger and More Rapid in Females Than Males.
AU - Nicole V Bushfield
AU - Benjamin W L MacKenzie
AU - Nicole A Johnson
AU - Rodion Isakovich
AU - Jamie L Keess
AU - Nicholas D J Strzalkowski
AU - Gustavo Zubieta-Calleja
AU - Richard J A Wilson
AU - Trevor A Day
PY - 2026
DA - 2026/10/24
JO - Comprehensive physiology
DO - 10.1002/cph4.70279
UR - https://europepmc.org/article/MED/42926907
AB - With ascent to high altitude (HA), increased ventilation reduces the pressure of PaCO₂ (i.e., hypocapnia), resulting in respiratory alkalosis. A subsequent renal compensation is mediated through reductions in [HCO₃ ⁻]a, partly-correcting pHa. High inter-individual variability exists in ventilation, blood oxygenation, and acid-base responses with ascent to HA, but potential sex differences have not been well-characterized. We recruited 38 lowland participants (20 M; 18 F) before and after rapid ascent to and residence at 3500 m over 10 days in La Paz, Bolivia. We performed radial arterial blood draws to assess blood oxygenation and acid-base variables before (1100 m), and following ascent to 3500 m both early HA (E-HA; D2/3) and late HA (L-HA; D9/10). With E-HA, all participants had higher calculated V̇ A, and lower PaO₂ and SaO₂ (p < 0.0001), with subsequent increases in V˙ A, [Hb] and CaO₂ L-HA (p = 0.0056; p = 0.0003; p = 0.0013). Although females had higher V˙ A and PaO₂ than males E-HA (p < 0.0001; p = 0.0143), males had higher [Hb] and CaO₂ at 1100 m, at both E-HA (p = 0.0008; p = 0.0085) and L-HA (p = 0.0007; p = 0.0045). E-HA, all participants had lower PaCO₂ and [HCO₃ ⁻]a, and higher pHa than 1100 m (p < 0.0001; p = 0.0004, p < 0.0001), suggesting respiratory alkalosis and partial renal compensation. L-HA, PaCO₂ and [HCO₃ ⁻]a were further reduced (p = 0.0062; p = 0.0202), with pHa only partly-compensated (p = 0.4306). E-HA, PaCO₂, [HCO₃ ⁻]a and pHa were significantly lower in females (p < 0.0001; p < 0.0001; p = 0.0457), suggesting more complete renal compensation. However, these sex-differences were not apparent at L-HA (p > 0.5341). This is the first clear demonstration of differential ventilatory, oxygenation and acid-base compensation between sexes with rapid ascent to HA.
SN - 2040-4603
ER -