Endogenous and exogenous nitric oxide protect against intracoronary thrombosis and reocclusion after thrombolysis
Yao, S.K.; Akhtar, S.; Scott-Burden, T.; Ober, J.C.; Golino, P.; Buja, L.M.; Casscells, W.; Willerson, J.T.
Circulation 92(4): 1005-1010
1995
ISSN/ISBN: 0009-7322 PMID: 7641335 Document Number: 447524
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 lt .01). The time to thrombus was prolonged by L-arginine (P lt .05) and SNP (P lt .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 gt .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 lt .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.