NITRIC-OXIDE SYNTHASE INHIBITION REDUCES CAUDATE INJURY FOLLOWING TRANSIENT FOCAL ISCHEMIA IN CATS

Background and Purpose We tested the hypothesis that inhibiting nitric oxide production either before or during transient focal ischemia aff ects early postischemic brain injury. Methods Halothane-anesthetized c ats underwent 1 hour of left middle cerebral artery occlusion plus 3 h ours 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 reperfus ion (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 (2 00 mg/kg per hour) for the remainder of reperfusion (n = 10). Results Microsphere-determined blood flow to ipsilateral caudate nucleus and i nferior temporal cortex decreased to the same extent during ischemia a nd 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 le ss (P<.05) compared with that in cats pretreated with saline (72 +/- 5 %) or cats treated with L-NAME plus L-arginine (68 +/- 5%). Ipsilatera l cerebral hemispheric injury volume was similar among the four groups (23 +/- 5%, 13 +/- 3%, 18 +/- 5%, and 29 +/- 5% of hemisphere in grou ps treated with L-NAME before ischemia and during ischemia, the saline -treated group, and the group treated with L-NAME plus L-arginine, res pectively). 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 f avorable redistribution of blood flow during ischemia and reperfusion. Because L-NAME was efficacious when administered at reperfusion, nitr ic oxide generated during reperfusion appears to contribute to caudate injury.