title: Role of O2-hemoglobin affinity on cerebrovascular response to carbon monoxide hypoxia.
abstract: Our previous studies showed that, in contrast to hypoxic and anemic hypoxia, CO hypoxia increased cerebral O2 delivery and decreased cerebral fractional O2 extraction. These changes were correlated with the accompanying decrease in P50 (PO2 at 50% saturation of non-CO bound sites on hemoglobin). To assess directly the role of P50 in the cerebrovascular response to CO, we first performed isovolemic exchange transfusions on unanesthetized newborn lambs, replacing their high-O2-affinity hemoglobin with low-affinity adult sheep donor blood. Exchange transfusion resulted in an average increase in P50 of 10 Torr and in a uniform decrease of regional cerebral blood flow and cerebral O2 delivery of 14%. Thus shifts in P50 can produce cerebrovascular changes during normoxia, implying that the mechanism regulating cerebral blood flow does not have a discrete threshold to an hypoxic stimulus. Induction of CO hypoxia (20-40% carboxyhemoglobin) after the exchange transfusion returned P50 to the control level, and with it restored both cerebral O2 delivery and fractional O2 extraction to the pretransfusion values. We conclude that the fall in P50, rather than a direct tissue effect of CO, is responsible for the relative cerebral overperfusion during CO hypoxia. The importance of the position of oxyhemoglobin dissociation curve as a determinant of cerebral blood flow supports the presence of a highly sensitive, tissue O2-dependent mechanism regulating the cerebral circulation.
mesh_terms: D000818:Animals; D001794:Blood Pressure; D002249:Carbon Monoxide Poisoning / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D005260:Female; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D008863:Microspheres; D009928:Organ Specificity; D010100:Oxygen / Q000097:blood*; D010108:Oxyhemoglobins / Q000378:metabolism*; D012039:Regional Blood Flow; D012756:Sheep
chemical_list: D010108:Oxyhemoglobins; D010100:Oxygen