Liposome‐Encapsulated Hemoglobin Reduces the Size of Cerebral Infarction in Rats: Effect of Oxygen Affinity

Abstract Liposome‐encapsulated hemoglobin (LEH) with a low oxygen affinity (l‐LEH, P 50 = 45 mm Hg) was found to be protective in the rodent and primate models of ischemic stroke. This study investigated the role of LEH with a high O 2 affinity (h‐LEH, P 50 = 10 mm Hg) in its protective effect on brain ischemia. The extent of cerebral infarction was determined 24 h after photochemically induced thrombosis of the middle cerebral artery from the integrated area of infarction detected by triphenyltetrazolium chloride staining in rats receiving various doses of h‐LEH as well as l‐LEH. Both h‐LEH and l‐LEH significantly reduced the extent of cortical infarction. h‐LEH remained protective at a lower concentration (minimal effective dose [MED]: 0.08 mL/kg) than l‐LEH (MED: 2 mL/kg) in the cortex. h‐LEH reduced the infarction extent in basal ganglia as well (MED: 0.4 mL/kg), whereas l‐LEH provided no significant protection. h‐LEH provided better protection than l‐LEH. The protective effect of both high‐ and low‐affinity LEH may suggest the importance of its small particle size (230 nm) as compared to red blood cells. The superiority of h‐LEH over l‐LEH supports an optimal O 2 delivery to the ischemic penumbra as the mechanism of action in protecting against brain ischemia and reperfusion.