Diaspirin Crosslinked Hemoglobin (DCLHb TM): Effect of Hemodilution During Focal Cerebral Ischemia in Rats

Abstract

The efficacy of hemodilution therapy, to ameliorate cerebral ischemia, is limited by an accompanying decrease in oxygen content. We assessed the effect of hemodilution, with diaspirin cross-linked hemoglobin (DCLHb), on cerebral blood flow (CBF) and infarct after middle cerebral artery occlusion (MCAo).

Rats (n = 36) were alloted to a control group in which hematocrit (Hct) was not manipulated, or reduced with DCLHb to 30% (30/DCLHb), 16% (16/DCLHb), or 9% (9/DCLHb). After MCAo, the brain area with a CBF of 0–10 ml· 100g⁻¹· min⁻¹ was determined. This area was decreased in the 30/DCLHb and 16/DCLHb groups vs the Control group; and was less in the 9/DCLHb group vs the other groups.

Different rats (n = 49) were hemodiluted with DCLHb or Albumin (Alb): Control, 30/Alb, 30/DCLHb, 16/DCLHb, or 9/DCLHb. After 3-hr of MCAo and 2-hr of reperfusion, infarct area was determined. Brain infarct was less in the 30/DCLHb and 16/DCLHb groups vs the Control and 30/Alb groups; and was less in the 9/DCLHb group vs the other groups.

The results of this study support the hypothesis that hemodilution with DCLHb decreases cerebral ischemia in a dose-dependent manner, and in terms of brain ischemia is a more proficient hemodiluting fluid than albumin.