Focal Cerebral Ischemia in Rats: Effect of Hemodilution with α-α Cross-Linked Hemoglobin on CBF

Abstract

Hemodilution has had limited success as a treatment of cerebral ischemia. When using a nonoxygen binding fluid, the therapeutic efficacy of hemodilution-induced increases in CBF are offset by concomitant decreases in oxygen content. The effect of hemodilution, with diaspirin α-α cross-linked hemoglobin (DCLHb), on CBF during middle cerebral artery occlusion was assessed. Rats were hemodiluted to one of the following hematocrits (Hct): (a) 44/Hct, (b) 37/Hct, (c) 30/Hct, (d) 23/Hct, (e) 16/Hct, or (f) 9/Hct. After 10 min of ischemia, CBF was determined with ¹⁴C-iodoantipyrine. Coronal brain sections were evaluated for areas with a CBF of 0–10 and 11–20 ml 100 g⁻¹ min⁻¹. In addition, oxygen delivery was calculated. In the center of the ischemic zone, both areas of low CBF were less in the 30/Hct, 23/Hct, and 16/Hct groups compared with the 44/Hct and 37/Hct groups; and both areas were less in the 9/Hct group compared with the other five groups ( p < 0.05). For the hemisphere contralateral to occlusion, there was a direct correlation between hematocrit and oxygen delivery. However, for the hemisphere ipsilateral to occlusion, oxygen delivery increased as hematocrit decreased (44/Hct, 8.6 ± 0.3 vs. 9/Hct, 13.6 ± 0.4 [mean ± SD, ml 100 g⁻¹ min⁻¹]). The results of this study support a hypothesis that hemodilution with DCLHb decreases the extent of focal cerebral ischemia.