title: NO and CO binding profiles of hemoglobin vesicles as artificial oxygen carriers.
abstract: Hemoglobin vesicles (HbVs) are artificial oxygen carriers encapsulating purified and concentrated Hb solution in phospholipid vesicles (liposomes). We examined in-vitro reaction profiles of a formulation of HbV with NO and CO in anaerobic and aerobic conditions using stopped-flow spectrophotometry and a NO electrode. Reaction rate constants of NO to deoxygenated and oxygenated HbV were considerably smaller than those of cell-free Hb because of the intracellular NO-diffusion barrier. The reaction of CO with deoxygenated HbV was slightly slower than that of cell-free Hb solely because of the co-encapsulated allosteric effector, pyridoxal 5'-phosphate. The NO depletion in an aerobic condition in the presence of empty vesicles was monitored using a NO electrode, showing that the hydrophobic bilayer membrane of HbV, which might have higher gas solubility, does not markedly facilitate the O(2) and NO reaction, and that the intracellular Hb is the major component of NO depletion. In conclusion, HbV shows retarded gas reactions, providing some useful information to explain the absence of vasoconstriction and hypertension when they are intravenously injected.
authors.affiliation: Research Institute for Science and Engineering, Waseda University, Tokyo 169-8555, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Sakai
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sato
authors.forename: Peter
authors.initials: P
authors.lastname: Sobolewski
authors.forename: Shinji
authors.initials: S
authors.lastname: Takeoka
authors.forename: John A
authors.initials: JA
authors.lastname: Frangos
authors.forename: Koichi
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Marcos
authors.initials: M
authors.lastname: Intaglietta
authors.forename: Eishun
authors.initials: E
authors.lastname: Tsuchida
mesh_terms: D000693:Anaerobiosis; D001802:Blood Substitutes / Q000378:metabolism*; D002248:Carbon Monoxide / Q000097:blood*; D004337:Drug Carriers; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008051:Lipid Bilayers; D009569:Nitric Oxide / Q000097:blood*; D010100:Oxygen / Q000097:blood*; D010108:Oxyhemoglobins / Q000378:metabolism; D011732:Pyridoxal Phosphate / Q000378:metabolism; D012995:Solubility; D012996:Solutions; D013053:Spectrophotometry
chemical_list: D001802:Blood Substitutes; D004337:Drug Carriers; D006454:Hemoglobins; D008051:Lipid Bilayers; D010108:Oxyhemoglobins; D012996:Solutions; D009569:Nitric Oxide; D011732:Pyridoxal Phosphate; D002248:Carbon Monoxide; D010100:Oxygen