Alpha-alpha diaspirin crosslinked hemoglobin, nitric oxide, and cerebral ischemic injury in rats.
Prior studies indicate that alpha-alpha 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.
Cole
D J
DJ
Department of Anesthesiology School of Medicine Loma Linda University, California 92354, USA.
Nary
J C
JC
Drummond
J C
JC
Patel
P M
PM
Jacobsen
W K
WK
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001157:Arterial Occlusive Diseases / Q000188:drug therapy / Q000378:metabolism; D001241:Aspirin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D001784:Blood Gas Analysis; D001786:Blood Glucose; D001802:Blood Substitutes / Q000494:pharmacology*; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D002544:Cerebral Infarction / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D003432:Cross-Linking Reagents / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006400:Hematocrit; D006454:Hemoglobins / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism
D001786:Blood Glucose; D001802:Blood Substitutes; D003432:Cross-Linking Reagents; D004791:Enzyme Inhibitors; D006454:Hemoglobins; D009569:Nitric Oxide; D001120:Arginine; C083478:diaspirin-cross-linked hemoglobin; D001241:Aspirin; D019331:NG-Nitroarginine Methyl Ester