title: Focal cerebral ischemia in rats: effect of hemodilution with alpha-alpha 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 alpha-alpha 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.
authors.affiliation: Department of Anesthesiology, Loma Linda University, CA 92354.
authors.forename: D J
authors.initials: DJ
authors.lastname: Cole
authors.forename: R M
authors.initials: RM
authors.lastname: Schell
authors.forename: R J
authors.initials: RJ
authors.lastname: Przybelski
authors.forename: J C
authors.initials: JC
authors.lastname: Drummond
authors.forename: K
authors.initials: K
authors.lastname: Bradley
mesh_terms: D000818:Animals; D001241:Aspirin / Q000031:analogs & derivatives* / Q000494:pharmacology; D001921:Brain / Q000098:blood supply; D002545:Brain Ischemia / Q000188:drug therapy*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006438:Hemodilution; D006454:Hemoglobins / Q000737:chemistry / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR
chemical_list: D003432:Cross-Linking Reagents; D006454:Hemoglobins; C021630:bis(3,5-dibromosalicyl)fumarate; D001241:Aspirin