title: Cerebral pressure-flow and metabolic responses to sustained hypoxia: effect of CO2.
abstract: 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 (PaO2) = 40 Torr, arterial PCO2 (PaCO2) = 27 Torr] and 2) eucapnic (EH; n = 9; PaCO2 = 40 Torr, PaCO2 = 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 (Qcp), were elevated significantly (P < 0.05) throughout hypoxia in all sheep; cerebral blood flow was greater in EH sheep (P < 0.05). Qcp 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 Qcp and increased Picp-Psag gradients during HH likely compensate the increased intracranial volume in AMS, and 3) CO2 supplementation at constant PaO2 did not reduce AMS, Picp, or brain tissue edema.
authors.affiliation: Hermann Rahn Laboratory of Environmental Physiology, Department of Physiology, School of Medicine and Biomedical Sciences, University of Buffalo, New York 14214.
authors.forename: S P
authors.initials: SP
authors.lastname: Yang
authors.forename: G W
authors.initials: GW
authors.lastname: Bergö
authors.forename: E
authors.initials: E
authors.lastname: Krasney
authors.forename: J A
authors.initials: JA
authors.lastname: Krasney
mesh_terms: D000532:Altitude Sickness / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D001784:Blood Gas Analysis; D001834:Body Water / Q000502:physiology; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology*; D001929:Brain Edema / Q000378:metabolism / Q000503:physiopathology; D002245:Carbon Dioxide / Q000494:pharmacology*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D004326:Drinking / Q000502:physiology; D004435:Eating / Q000502:physiology; D005260:Female; D006400:Hematocrit; D006454:Hemoglobins / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D016857:Hypocapnia / Q000503:physiopathology; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D007427:Intracranial Pressure / Q000502:physiology; D012756:Sheep
chemical_list: D006454:Hemoglobins; D002245:Carbon Dioxide