Abstract
Cell-free hemoglobin based oxygen carriers (HBOC) wet the endothelial surfaces and deliver oxygen directly to tissues, bypassing plasma. Simulations show that carriers with oxygen affinity higher than blood would best deliver oxygen to tissues, although good delivery is produced within a large range of affinities. We tested this hypothesis using a solution of either a high oxygen affinity polymer (ZL-HbBv, P50 = 4mmHg) or of sebacoyl crosslinked hemoglobin, DECA, with P50 = 30mmHg. The polymer does not extravasate and does not produce a pressor response in infused animals. ZLHbBv decreased the volume of cerebral infarct by 40% in mice, while in the cat the lower affinity DECA failed to reduce the infarct volume. At reduced plasma viscosity ZL-HbBv produced a cerebral vasoconstriction due to excessive oxygen delivery, while at high plasma viscosity it produced a compensating vasodilation. In rabbit jejunum membranes, superfused under hypoxic conditions, the presence of the DECA allowed metabolites transport across the mucosa. Equivalent suspensions of red cells failed to allow transport. It is suggested that non-extravasating HBOC with high oxygen affinity can still deliver oxygen to ischemic tissues. Under nonischemic conditions with reduced blood viscosity cerebral vasoconstriction appears to occur in response to hyperoxygenation of tissues.
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