The role of acid‐base balance in cerebrovascular and ventilatory responses to CO2 during 10 h normobaric hypoxia

Hyperventilation-induced alterations in acid-base buffering play a crucial role in resetting the cerebrovascular and ventilatory control during high-altitude acclimatisation. This study examines the relationship between cerebrovascular CO2 reactivity, ventilatory CO2 sensitivity and acid-base balance during a 10 h hypoxic exposure. We assessed resting venous pH and bicarbonate concentrations HCO3 -, middle cerebral artery velocity (MCAv; transcranial Doppler ultrasound) and ventilatory (V̇EV̇₄) responses during hyperoxic rebreathing in 27 healthy individuals (13 females) at 0, 2, 4 and 8 h of 10 h exposures to normobaric normoxia (fraction of inspired O2 (FIO2F{₈{{O₂}}}): 0. 21) and normobaric hypoxia (FIO2F{₈{{O₂}}}: 0. 117, simulated altitude of 5000 m) in a randomised, single-blinded manner. The MCAv- and V̇EV̇₄ -CO2 relationships were analysed using sigmoidal and segmental linear regression fitting, respectively. Compared to normoxia hypoxia progressively increased venous pH and decreased venous HCO3 - throughout the 10 h exposure (P < 0. 001 for both). We observed a progressive decrease in the ventilatory recruitment threshold (VRT) with hypoxia across the day (d = 0. 9, P < 0. 001 vs. normoxia), along with an increased V̇EV̇₄ -CO2 slope by ∼0. 4 l/min/mmHg (d = 0. 3, P = 0. 039). The slope of the MCAv-CO2 response was moderately increased with hypoxia by 0. 5 cm/s/mmHg across all time points (d = 0. 5, P = 0. 006), whereas the midpoint of the MCAv-CO2 response was unchanged (P = 0. 401). Our data support the role of altered blood acid-base buffering in the resetting of the ventilatory CO2 sensitivity to a lower operating point. Because we did not observe a concurrent leftward shift in the MCAv-CO2 response, we attribute this to the lagging compensation of respiratory alkalosis within the cerebrospinal fluid compartment. KEY POINTS: Acid-base balance plays an important role in the control of cerebral blood flow and ventilation, but the compensation of hypoxia-induced respiratory alkalosis in cerebrospinal fluid is slower than that within the arterial compartment. In this study we hypothesized that the rates of resetting between the cerebrovascular and ventilatory responsiveness to CO2 would be different during 10 h exposure to normobaric hypoxia. We found a progressive leftward shift in the ventilatory response to hyperoxic rebreathing, which appears to be linked to changes in blood acid-base balance during early hypoxic exposure. In contrast we did not observe a resetting of cerebrovascular response to CO2 during the 10 h exposure period. Our data demonstrate a dissociation in the rate of resetting between the cerebrovascular and ventilatory responsiveness to CO2 during early hypoxic exposure. We speculate that these differences are due to the slower compensatory metabolic acidosis in the cerebrospinal fluid compared to the arterial/venous compartments.