Comparison of Ventilatory, Blood Oxygenation and Acid-Base Acclimatization Between Males and Females with Ascent to and Residence at 3500m over 10-days

With ascent to high altitude (HA), increased ventilation protects oxygenation but reduces the pressure of arterial (Pa)CO 2 (i.e., hypocapnia), resulting in respiratory alkalosis. Subsequent renal compensation is mediated through reductions in [HCO 3 - ]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 in ventilatory and renal acclimatization have not been characterized. We compared ventilatory, blood oxygenation and acid-base responses with rapid ascent to and residence at 3500m over 10-days between males and females. We recruited 38 lowland participants (18M; 20F) before and after rapid ascent to and residence at 3500m in La Paz, Bolivia, performing radial arterial blood draws (Abbott i-STAT) to assess blood oxygenation and acid-base variables before (1100m), and following ascent to 3500m both early HA (E-HA; days 2/3) and late HA (L-HA; days 9/10). Females had lower PaCO 2 and [HCO 3 - ]a at 1100m (P=0.0280, P=0.0119), confirmed with a larger archived dataset from our group (n=123; 71M, 52F; p<0.0001), suggesting higher basal ventilation and bicarbonate excretion in females at baseline, before ascent to HA. With E-HA, all participants had higher V· A , and lower PaO 2 and SaO 2 (p<0.0001), with subsequent increases in V· A , [Hb] and CaO 2 L-HA (P=0.0056; P=0.0003; P=0.0013). Although females had higher V· A and PaO 2 than males E-HA (p<0.0001; P=0.0143), males had higher [Hb] and CaO 2 at 1100m (p<0.0001), 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 PaCO 2 and [HCO 3 - ]a, and higher pHa than 1100m (p<0.0001; P=0.0004, p<0.0001), suggesting respiratory alkalosis and partial renal compensation. L-HA, PaCO 2 and [HCO 3 - ]a were further reduced (P=0.0062; P=0.0202), with pHa only partly-compensated (P=0.4306). E-HA, PaCO 2 , [HCO 3 - ]a and pHa were significantly higher in males (p<0.0001; p<0.0001; P=0.0457), suggesting more complete renal compensation in females. However, these acid-base sex differences were not apparent L-HA (P>0.5341). Upon rapid ascent to and residence at 3500m, we demonstrated more rapid and larger magnitude ventilatory and renal responses in females. This is the first clear demonstration of differential ventilatory, oxygenation and acid-base compensation between sexes at baseline and with ascent to HA. Natural Science and Engineering Research Council of Canada, HBI RHISE and University of Calgary Transdisciplinary Connector Grants. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.