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Stroke, Vol 25, 877-885, Copyright © 1994 by American Heart Association

ARTICLES

Nitric oxide synthase inhibition reduces caudate injury following transient focal ischemia in cats

T Nishikawa, JR Kirsch, RC Koehler, M Miyabe and RJ Traystman
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, Md 21287-4963.

BACKGROUND AND PURPOSE: We tested the hypothesis that inhibiting nitric oxide production either before or during transient focal ischemia affects early postischemic brain injury. METHODS: Halothane- anesthetized cats underwent 1 hour of left middle cerebral artery occlusion plus 3 hours of reperfusion. Pretreatment groups received either intravenous N omega-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg, n = 10) or an equal volume of diluent (10 mL saline, n = 10) over 30 minutes before ischemia. Posttreatment groups received intravenous L-NAME (10 mg/kg) over 30 minutes from 45 minutes of ischemia to 15 minutes of reperfusion (n = 10) or intravenous L-NAME (10 mg/kg) plus L-arginine (200 mg/kg) over the same period followed by continuous L-arginine infusion (200 mg/kg per hour) for the remainder of reperfusion (n = 10). RESULTS: Microsphere-determined blood flow to ipsilateral caudate nucleus and inferior temporal cortex decreased to the same extent during ischemia and recovered to the same extent during reperfusion in the four groups. Triphenyltetrazolium-determined injury volume of ipsilateral caudate nucleus in cats treated with L-NAME before or during ischemia (42 +/- 7% and 42 +/- 3% of caudate nucleus, respectively; mean +/- SE) was less (P < .05) compared with that in cats pretreated with saline (72 +/- 5%) or cats treated with L-NAME plus L-arginine (68 +/- 5%). Ipsilateral cerebral hemispheric injury volume was similar among the four groups (23 +/- 5%, 13 +/- 3%, 18 +/- 5%, and 29 +/- 5% of hemisphere in groups treated with L-NAME before ischemia and during ischemia, the saline-treated group, and the group treated with L-NAME plus L-arginine, respectively). CONCLUSIONS: Inhibition of nitric oxide synthase decreases caudate injury volume from transient focal cerebral ischemia in cats. The beneficial effect is reversed by L-arginine and is not caused by favorable redistribution of blood flow during ischemia and reperfusion. Because L-NAME was efficacious when administered at reperfusion, nitric oxide generated during reperfusion appears to contribute to caudate injury.

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