ENDOGENOUS AND EXOGENOUS NITRIC-OXIDE PROTECT AGAINST INTRACORONARY THROMBOSIS AND REOCCLUSION AFTER THROMBOLYSIS

Background Nitric oxide (NO), an endothelium-derived relaxing factor, plays an important role in regulating platelet activation. We evaluated the effect of NO in a canine model of intracoronary thrombosis, thrombolysis, and reocclusion. Methods and Results Before thrombosis was induced, 34 anesthetized dogs were treated with a continuous intracoronary infusion of saline (n=8); N-G-nitro-L-arginine (L-NNA, n=8), an inhibitor of NO synthetase; L-arginine (n=7), the precursor for NO; or sodium nitroprusside (SNP, n=11), an NO donor. Ten minutes after the infusion was begun, an electric current of 150 mu A was applied to the endothelium of coronary arteries to induce thrombosis. Occlusive thrombi developed in all dogs in the saline group (38+/-4 minutes) and the L-NNA group (30+/-6 minutes), in 6 of 7 dogs in the L-arginine group (81+/-18 minutes), and in 6 of 11 dogs in the SNP group (102+/-21 minutes) (P<.01). The time to thrombus was prolonged by L-arginine (P<.05) and SNP (P<.01). After 3 hours of thrombus formation in coronary arteries, tissue plasminogen activator and heparin were administered intravenously. Thrombi were lysed in 4 (of 8) dogs in the saline group (71+/-8 minutes), in 4 (of 8) dogs in the L-NNA group (72+/-8 minutes), in 4 (of 6) dogs in the L-arginine group (50+/-14 minutes), and in 4 (of 6) dogs in the SNP group (49+/-11 minutes) (P>.05). After thrombolysis, coronary artery reocclusion developed in all reperfused dogs in the saline group (30+/-8 minutes) and in the L-NNA group (48+/-12 minutes), in 3 (of 4) reperfused dogs in the L-arginine group (123+/-26 minutes), and in 3 (of 4) reperfused dogs in the SNP group (128+/-19 minutes) (P<.01). The ex vivo platelet aggregation induced by collagen was inhibited after in vivo treatment with L-arginine or SNP. Conclusions Increasing NO production or giving an NO donor may inhibit platelet aggregation and delay intracoronary thrombus formation and reocclusion after thrombolysis.