Human and bovine hemoglobins are investigated for obtaining oxygen carriers which could be used in health care delivery procedures. Three main difficulties must be overcome: the short intravascular retention time and the high oxygen affinity of hemaglobin, in cell-free conditions and the vascular toxicity present in hemolysates. Bovine hemoglobin will be especially investigated for its hemolysates. Bovine hemoglobin will be especially investigated for its peculiar functional characteristics namely the strong sensitivity of its oxygen affinity to anions and the relative insensitivity to polyphosphates. In bovine hemoglobin there is a methionine in position beta1, which substitutes for the Val-His dipeptide in position beta1-beta2 in human hemoglobin. This may be responsible for the different functional attitudes of human and bovine hemoglobins. Reacting bovine deoxyhemoglobin with fumaryl diaspirin it is possible to obtain an oxygen carrier with P50 near 60 mmHg at pH 7.4. There is an intramolecular crosslink between the beta subunits of this compound, while the same reaction produces a crosslink between the alpha subunits in human hemoglobin. As already noticed for human hemolysates, bovine hemolysates inhibit the relaxation produced by endothelium derived relaxing factor in rings of rabbit aorta. They do not inhibit the beta receptor. Specific goals of the project are 1) To elucidate the peculiar interaction of bovine hemoglobin with mono and polyvalent anions, exploring the possible role of the methionine at beta1 in these phenomena. 2) To elucidate the structure function relationship in hemoglobins whose tetrameric structure has been stabilized by intramolecular crosslinks. 3) To prolong the retention time of hemoglobins by mild polymerization and by modifying their hydrodynamic volume. 4) To clarify the pharmacological origin of the vascular toxicity of hemoglobin solutions.
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