bis(3-5-dibromosalicyl)fumarate and Brain-Ischemia

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.. 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.. 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.. 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.

Topics: Albumins; Animals; Aspirin; Brain Edema; Brain Injuries; Brain Ischemia; Cross-Linking Reagents; Hemodilution; Hemoglobins; Male; Rats; Rats, Inbred SHR

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.

Topics: Animals; Aspirin; Brain; Brain Ischemia; Cerebrovascular Circulation; Cross-Linking Reagents; Disease Models, Animal; Dose-Response Relationship, Drug; Hemodilution; Hemoglobins; Male; Rats; Rats, Inbred SHR