Hypervolemic-hemodilution during cerebral ischemia in rats: effect of diaspirin cross-linked hemoglobin (DCLHb) on neurologic outcome and infarct volume.

In a rat model of middle cerebral artery occlusion (MCAo) and reperfusion (120 min), previous studies have demonstrated that hemodilution with molecular hemoglobin decreases ischemic brain injury. However, long-term recovery data on the therapeutic efficacy of molecular hemoglobin for cerebral ischemia are lacking. Accordingly, we assessed the effect of hemodilution, with alpha-alpha diaspirin cross-linked hemoglobin (DCLHb, 10 g/dl) on neurologic outcome and infarct volume after 120 min of MCAo and 72 h of reperfusion. Ischemia was achieved by passing a 0.26-mm suture, via the external carotid artery, to internally occlude the middle cerebral artery. Immediately after MCAo, the rats were randomized to one of the following groups: Control-hematocrit not manipulated (44%); 30/Hct-hematocrit maintained at 30% with DCLHb; or 16/Hct-hematocrit maintained at 16% with DCLHb. After 120 min of MCAo, the suture was removed and the rats allowed to recover. Daily neurologic examinations were performed, and after 72 h, the brains were analyzed for infarct volume with TTC stain. Infarct volume (mm3) was less in the 30/Hct group (67 +/- 10; mean +/- SD) than in the Control group (141 +/- 17); and less in the 16/Hct group (40 +/- 12) than the other two groups (p < 0.05). Neurologic outcome was improved in both hemodilution groups versus the Control group (p < 0.05). These data are consistent with previous studies, performed in a model of short-term reperfusion, which indicate a dose-dependent decrease in ischemic injury by DCLHb.