Daytime Ventilatory and Blood Acid-Base Responses During Ascent to 3500 m Are Larger and More Rapid in Females Than Males

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.