Liposome-Encapsulated Hemoglobin Reduces the Size of Cerebral Infarction in the Rat

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Abstract
Liposome-encapsulated hemoglobin (LEH; TRM-645) is a novel oxygen (O(2)) carrier with a lower O(2) affinity (P(50)O(2)=40 mm Hg) than red blood cells. In contrast to cell-free hemoglobin, encapsulation prevents hemoglobin extravasation, whereas its subcellular size (230 nm) may improve O(2) delivery and limit the severity of cerebral infarction. The extent of cerebral infarction was determined 24 hours after photochemically induced thrombosis of the middle cerebral artery from the integrated area of infarction detected by triphenyltetrazolium chloride staining in rats receiving no treatment, 10 mL/kg of LEH, homologous blood, empty liposomes, or saline. To develop a dose-response relationship, LEH dose was reduced from 10 mL/kg to 2 mL/kg, 0.4 mL/kg, and 0.08 mL/kg. Infarction extent was significantly suppressed in rats receiving LEH as compared with animals receiving no infusion, saline, empty liposome, or transfusion in the cortex but not in the basal ganglia, where all had similar degrees of damage. The dose-response relationship revealed that as little as 2 mL/kg of LEH was protective, whereas the total blood O(2) content, hemoglobin level, and transfusion and/or infusion of empty liposomes or saline were not effective. Our results suggest that LEH significantly reduces the area of infarction in the cortex but not in basal ganglia after photochemically induced thrombosis of the middle cerebral artery in the rat.

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