FOCAL CEREBRAL-ISCHEMIA IN RATS - EFFECT OF HEMODILUTION WITH ALPHA-ALPHA-CROSS-LINKED HEMOGLOBIN ON BRAIN INJURY AND EDEMA

The effect of hemodilution, with alpha-alpha cross-linked hemoglobin (DCLHb), on brain injury and edema was assessed after temporary middle cerebral artery occlusion in rats. Injury was analyzed with 2,3,5-triphenyltetrazolium chloride (TTC) stain and edema by microgravimety. Part A: DCLHb was given to maintain one of the following hematocrits (Hct) and normotension: 1) 45/Hct, 2) 30/Hct, 3) 16/Hct, or 4) 9/Hct. Brain injury (% of ischemic hemisphere, mean +/- SD) was less in the 30/Hct group (31 +/- 4) versus the 45/Hct group (42 +/- 5); and in the 16/Hct (20 +/- 3) and 9/Hct (19 +/- 4) groups versus the 45/Hct and 30/Hct groups. Edema was less in the hemodiluted groups versus the 45/Hct group. Part B: DCLHb was given to maintain one of the following hematocrits and hyper (HTN) - or normotension (Norm): 1) 45/Norm, 2) 30/Norm, 3) 30/HTN, 4) 16/Norm, or 5) 16/HTN. In hematocrit matched groups hypertension decreased brain injury (30/HTN - 24 +/- 2 < 30/Norm - 34 +/- 4; and 16/HTN - 17 +/- 3 < 16/Norm - 24 +/- 4). Edema was not effected by hypertension. These results suggest that hemodilution with DCLHb decreases focal ischemic injury, and is most effective when given in a manner that induces hypertension.