Focal cerebral ischemia in rats. Effect of hypervolemic hemodilution with diaspirin cross-linked hemoglobin versus albumin on brain injury and edema.

BACKGROUND

Hemodilution has had limited success as a treatment of cerebral ischemia. When using a non-oxygen-binding fluid, the therapeutic efficacy of hemodilution-induced increases in blood flow are offset by concomitant decreases in oxygen content.

METHODS

The effect of hemodilution, with diaspirin cross-linked hemoglobin (DCLHb), on brain injury and edema was assessed during middle cerebral artery occlusion (180 min) and reperfusion (120 min) in rats (blood volume increased by approximately 30% and n = 10 for each group): (1) 44/B: 8.0 ml of donor blood was given; (2) 30/albumin: hematocrit was decreased to 30% with 10% albumin; (3) 30/DCLHb: hematocrit was decreased to 30% with 10% DCLHb; or (4) 9/DCLHb: hematocrit was decreased to 9% with DCLHb. Infarct size was analyzed with 2,3,5-triphenyltetrazolium chloride, and edema by microgravimetry.

RESULTS

Brain injury (percent of the hemispheric area ipsilateral to ischemia, mean +/- SD) was greater in the 44/B group (44 +/- 4) versus the 30/albumin group (37 +/- 3). In addition, brain injury was greater in the 44/B and 30/albumin groups versus the 30/DCLHb group (27 +/- 4); which was in turn greater than the 9/DLCHb group (18 +/- 3). Specific gravity was greater (less brain water) in all hemodiluted groups versus the 44/B group.

CONCLUSIONS

These results support a hypothesis that hemodilution decreases focal cerebral ischemic injury, and when an oxygen-binding fluid is used, there is a dose-dependent effect of hemodilution on ischemia. In addition, these results suggest that hemodilution, as achieved with DCLHb, was more effective in reducing ischemic brain damage than was the same degree of hemodilution as achieved with albumin.