α-α diaspirin crosslinked hemoglobin, nitric oxide, and cerebral ischemic injury in rats

Abstract

Prior studies indicate that α-α diaspirin crosslinked hemoglobin (DCLHb®) decreases cerebral ischemia. One mechanism whereby DCLHb may ameliorate cerebral ischemia is by binding nitric oxide (NO), which has been implicated as neurotoxic. We assessed the effect of L-NAME (NO synthase inhibitor) and L-arginine (NO substrate) on ischemic brain injury after DCLHb infusion. Rats were randomized to one of the following groups: Control-no hematocrit manipulation; DCLHb-hematocrit decreased to 16% with 10% DCLHb; DCLHb/L-NAME-hematocrit decreased to 16% with DCLHb, and L-NAME given; DCLHb/L-arg-hematocrit decreased to 16% with DCLHb, and L-arginine given. After 90-min of middle cerebral artery occlusion and 4-hr of reperfusion, infarct volume was determined with TTC stain. Infarct volume (mm3, 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 DCLHb/L-arg group than the DCLHb and DCLHb/L-NAME groups (p < 0.05); but was 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 injury.