Dj. Cole et al., ALPHA-ALPHA DIASPIRIN CROSS-LINKED HEMOGLOBIN, NITRIC-OXIDE, AND CEREBRAL ISCHEMIC-INJURY IN RATS, Artificial cells, blood substitutes, and immobilization biotechnology, 25(1-2), 1997, pp. 141-152
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.