INTRAVENOUS NITROGLYCERIN INFUSION INHIBITS CYCLIC BLOOD-FLOW RESPONSES CAUSED BY PERIODIC PLATELET THROMBUS FORMATION IN STENOSED CANINE CORONARY-ARTERIES

Background. Nitroglycerin and other clinically relevant organic nitrate derivatives have been shown to inhibit platelet aggregation in vitro. This antithrombotic effect of nitrates is potentiated by reduced thiol. To determine the potential relevance of this mechanism of action in vivo, we examined the effect of intravenous nitroglycerin infusion on periodic platelet thrombus formation in a canine model of coronary artery stenosis. Methods and Results. We used a canine model of coronary artery stenosis associated with cyclic reductions in coronary blood flow that have been shown to depend on periodic platelet thrombus formation. We quantified the frequency of cycles per 40-minute observation period and monitored the effect of a continuous infusion of intravenous nitroglycerin on the cycle frequency. The administration of 10-15-mu-g/kg/min nitroglycerin reduced cyclic platelet thrombus formation significantly and did so without a significant change in coronary artery blood flow. Pretreatment with the reduced thiol, N-acetylcysteine (100 mg/kg during 30 minutes), led to inhibition of cyclic platelet thrombus formation by intravenous nitroglycerin at doses that alone had no such effect (5-mu-g/kg/min). Conclusion. These data suggest that one mechanism by which intravenous nitroglycerin improves ischemia in acute coronary artery disease syndromes may be by inhibition of platelet thrombus formation and may highlight the potential importance of reduced thiol in this mechanism.