Decreased infarction by polymeric hemoglobin exchange transfusion during focal cerebral ischemia in the mouse

Reduction of injury during stroke by hemodilution is thought to be limited by the concurrent decrease in O₂ carrying capacity. We determined if transfusion of cell-free, polymeric crosslinked hemoglobin during 2 hr of transient focal cerebral ischemia produced by the suture technique decreases infarct volume in halothane-anesthetized C57B/6 mice. Exchange transfusion with adipyl crosslinked, polymeric bovine hemoglobin at 20 min of ischemia decreased hematocrit from 42±1 to 28±1% with only a small decrease in total hemoglobin concentration (13±0.7 to 11±0.3 g/dL). Mean arterial pressure increased slightly from 80±2 to 88±3 mmHg during ischemia. Infarct volume measured at 22 hr reperfusion (66±8 mm³; SE; n=8) was less than in a non-transfused control group (96±9 mm³; n=8) with the same surgery and anesthesia duration. Perfusion was monitored in superior lateral cortex (ischemic border region) by laser-Doppler flowmetry. In 5 control mice, perfusion decreased to 29±4% of baseline at 15 min ischemia, was maintained at 27±3% at 120 min ischemia, and increased to 103±14% at 30 min reperfusion. In 4 other mice, perfusion decreased to 29±4% at 15 min ischemia, but increased after hemoglobin transfusion to 42±6% at 120 min ischemia and to 86±8% at 30 min reperfusion. Therefore, reducing hematocrit while maintaining hemoglobin concentration improves hemoglobin flux in the ischemic border region and reduces subsequent injury volume in the mouse.