Effects of acute hypoxia on cerebrovascular responses to carbon dioxide

New Findings What is the central question of this study? In acute hypoxia, the reduction in arterial CO2 tension due to the hypoxic ventilatory response (respiratory chemoreflex) stimulates cerebral vasoconstriction, which opposes the degree of hypoxic cerebral vasodilatation. The aim was to examine this interaction further. Specifically, we questioned whether arterial CO2 tension-mediated effects on cerebrovascular regulation are attenuated during acute hypoxia. What is the main finding and its importance? Cerebrovascular CO2 reactivity and CO2-mediated effects on dynamic cerebral autoregulation were attenuated during acute hypoxia. These findings suggest that blunted cerebrovascular responses to CO2 may limit the degree of CO2-mediated vasoconstriction to help maintain adequate cerebral blood flow for cerebral O2 homeostasis during acute hypoxia. In normoxic conditions, a reduction in arterial carbon dioxide tension causes cerebral vasoconstriction, thereby reducing cerebral blood flow and modifying dynamic cerebral autoregulation (dCA). It is unclear to what extent these effects are altered by acute hypoxia and the associated hypoxic ventilatory response (respiratory chemoreflex). This study tested the hypothesis that acute hypoxia attenuates arterial CO2 tension-mediated regulation of cerebral blood flow to help maintain cerebral O2 homeostasis. Eight subjects performed three randomly assigned respiratory interventions following a resting baseline period, as follows: (1) normoxia (21% O2); (2) hypoxia (12% O2); and (3) hypoxia with wilful restraint of the respiratory chemoreflex. During each intervention, 0, 2.0, 3.5 or 5.0% CO2 was sequentially added (8 min stages) to inspired gas mixtures to assess changes in steady-state cerebrovascular CO2 reactivity and dCA. During normoxia, the addition of CO2 increased internal carotid artery blood flow and middle cerebral artery mean blood velocity (MCAVmean), while reducing dCA (change in phase=-0.73 +/- 0.22rad, P=0.005). During acute hypoxia, internal carotid artery blood flow and MCAVmean remained unchanged, but cerebrovascular CO2 reactivity (internal carotid artery, P=0.003; MCAVmean, P=0.031) and CO2-mediated effects on dCA (P=0.008) were attenuated. The effects of hypoxia were not further altered when the respiratory chemoreflex was restrained. These findings support the hypothesis that arterial CO2 tension-mediated effects on the cerebral vasculature are reduced during acute hypoxia. These effects could limit the degree of hypocapnic vasoconstriction and may help to regulate cerebral blood flow and cerebral O2 homeostasis during acute periods of hypoxia.