We tested a hypothesis that
liposome-encapsulated hemoglobin (LEH) with high
oxygen (O2 ) affinity (h-LEH, P50 O2 = 10 mm Hg) may work better than LEH with low O2 affinity (l-LEH, P50 O2 = 40 mm Hg) in
cerebral ischemia and
reperfusion injury using positron emission tomography (PET) in primates undergoing middle cerebral artery (MCA) occlusion and reperfusion. Cerebral blood flow (CBF), O2 extract fraction (OEF), and cerebral metabolic rate of O2 (CMRO2 ) were successively determined by PET before
ischemia, at 2 h of
ischemia, immediately after reperfusion, and 3 h after reperfusion. Five minutes after MCA occlusion, 10 mL/kg of h-LEH (n = 6) was intravenously infused and compared with the results from previous data of monkeys treated with l-LEH (n = 6), empty
liposome (n = 4), or saline (n = 8) as control. After the series of PET studies, the integrated area of
cerebral infarction was determined histologically in 12 coronal brain slices. There was no significant difference in CBF, OEF, or CMRO2 up to 2 h of
ischemia. A high CBF with a low OEF tended to be suppressed after reperfusion in LEH-treated monkeys. Three hours after reperfusion, the area of mild CMRO2 reduction (down to -30%) decreased (P < 0.05) and the area of mild CMRO2 increase (up to 30%) expanded in LEH-treated monkeys (P < 0.05) regardless of O2 affinity with no difference in the area of moderate-to-severe reduction (<-30%) or increase (<+30%) in CMRO2 compared to animals treated with empty
liposome or saline. Distribution of CMRO2 reduction and histological damages showed that LEH mainly protected the cerebral cortex rather than basal ganglia where neuronal dendritic processes were severely lost. There was little difference between the animals treated with l-LEH or h-LEH both
at 10 mL/kg or between treatment with empty
liposome or saline. In conclusion, LEH was effective regardless of O2 affinity in preserving CMRO2 and in reducing the area of histological damage in the cerebral cortex, but not in basal ganglia, shortly after occlusion/reperfusion of MCA in monkey.