ALPHA-ALPHA DIASPIRIN CROSS-LINKED HEMOGLOBIN, NITRIC-OXIDE, AND CEREBRAL ISCHEMIC-INJURY IN RATS

Prior studies indicate that alpha-alpha diaspirin crosslinked hemoglob in (DCLHb(TM)) decreases cerebral ischemia. One mechanism whereby DCLH b may ameliorate cerebral ischemia is by binding nitric oxide (NO), wh ich has been implicated as neurotoxic. We assessed the effect of L-NAM E (NO synthase inhibitor) and L-arginine (NO substrate) on ischemic br ain injury after DCLHb infusion. Rats were randomized to one of the fo llowing groups: Control-no hematocrit manipulation; DCLHb-hematocrit d ecreased to 16% with 10% DCLHb; DCLHb/L-NAME-hematocrit decreased to 1 6% with DCLHb, and L-NAME given; DCLHb/L-arg-hematocrit decreased to 1 6% with DCLHb, and L-arginine given. After 90-min of middle cerebral a rtery occlusion and 4-hr of reperfusion, infarct volume was determined with TTC stain. Infarct volume (mm(3), mean+/-SD) was greater in the Control group (142+/-16) than the DCLHb (43+/-12), DCLHb/L-NAME (45+/- 14), and DCLHb/L-arg (71+/-18) groups (p <0.05); was greater in the DC LHb/L-arg group than the DCLHb and DCLHb/L-NAME groups (p<0.05); but w as not different between the DCLHb and DCLHb/L-NAME groups. These data indicate that DCLHb decreases ischemic brain injury, and that binding NO may be one mechanism by which DCLHb decreases ischemic brain injur y.