Cerebral pressure-flow and metabolic responses to sustained hypoxia: Effect of CO₂

This study was designed to determine the role of CO₂ in the cerebral hemodynamic, metabolic, and fluid shift responses in a conscious sheep model of acute mountain sickness (AMS). Ewes were instrumented chronically with left ventricular, aortic, inferior vena cava, sagittal sinus, and epidural catheters and exposed to 96 h of hypoxia in an environmental chamber in two groups: 1) hypocapnic [HH; n = 12; arterial PO₂ (Pa(O₂) = 40 Torr, arterial Pco₂ (Pa(CO₂) = 27 Torr] and 2) eucapnic (EH; n = 9; Pa(O₂) = 40 Torr, Pa(CO₂) = 37 Torr). AMS, estimated from food and water intakes and behavior, occurred in 9 of 12 HH and 9 of 9 EH sheep. Intracranial pressure (Picp) and the pressure gradient between Picp and sagittal sinus (Psag) increased in AMS sheep only. Total and regional cerebral blood flows, except in the choroid plexus (Q̇cp), were elevated significantly (P < 0.05) throughout hypoxia in all sheep; cerebral blood flow was greater in EH sheep (P < 0.05). Q̇cp decreased in HH (P < 0.05) but remained unchanged in EH sheep. Cerebral O₂ and glucose uptakes were not altered in either group. Brain edema, reflected by elevated wet-to-dry tissue weight ratios (P < 0.0001), occurred only in AMS sheep. We conclude 1) AMS is associated with cerebral edema and normal brain aerobic metabolism, 2) decreased Q̇cp and increased Picp-Psag gradients during HH likely compensate the increased intracranial volume in AMS, and 3) CO₂ supplementation at constant Pa(O₂) did not reduce AMS, Picp, or brain tissue edema.