title: Insensitivity of cerebral oxygen transport to oxygen affinity of hemoglobin-based oxygen carriers.
abstract: The cerebrovascular effects of exchange transfusion of various cell-free hemoglobins that possess different oxygen affinities are reviewed. Reducing hematocrit by transfusion of a non-oxygen-carrying solution dilates pial arterioles on the brain surface and increases cerebral blood flow to maintain a constant bulk oxygen transport to the brain. In contrast, transfusion of hemoglobins with P50 of 4-34 Torr causes constriction of pial arterioles that offsets the decrease in blood viscosity to maintain cerebral blood flow and oxygen transport. The autoregulatory constriction is dependent on synthesis of 20-HETE from arachidonic acid. This oxygen-dependent reaction is apparently enhanced by facilitated oxygen diffusion from the red cell to the endothelium arising from increased plasma oxygen solubility in the presence of low or high-affinity hemoglobin. Exchange transfusion of recombinant hemoglobin polymers with P50 of 3 and 18 Torr reduces infarct volume from experimental stroke. Cell-free hemoglobins do not require a P50 as high as red blood cell hemoglobin to facilitate oxygen delivery.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University, Baltimore, Maryland 21287, USA. rkoehler@jhmi.edu
authors.forename: Raymond C
authors.initials: RC
authors.lastname: Koehler
authors.forename: Clara
authors.initials: C
authors.lastname: Fronticelli
authors.forename: Enrico
authors.initials: E
authors.lastname: Bucci
mesh_terms: D001160:Arterioles / Q000502:physiology; D016913:Blood Component Transfusion / Q000379:methods; D001783:Blood Flow Velocity; D001921:Brain / Q000378:metabolism*; D002474:Cell-Free System / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000502:physiology*; D004337:Drug Carriers / Q000378:metabolism*; D006454:Hemoglobins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D010100:Oxygen / Q000097:blood*; D010108:Oxyhemoglobins / Q000008:administration & dosage / Q000378:metabolism* / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000378:metabolism; D012996:Solutions; D014661:Vasoconstriction
chemical_list: D004337:Drug Carriers; D006454:Hemoglobins; D006893:Hydroxyeicosatetraenoic Acids; D010108:Oxyhemoglobins; D011994:Recombinant Proteins; D012996:Solutions; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D010100:Oxygen