NITROGLYCERIN INHIBITS EXPERIMENTAL THROMBOSIS AND REOCCLUSION AFTER THROMBOLYSIS

Nitroglycerin inhibits platelet aggregation in vitro, but its effect o n thrombosis and platelet function in vivo is controversial. This stud y assessed the effect of nitroglycerin on primary thrombus formation i n response to vessel walt injury and secondary thrombus formation, or rethrombosis, after lysis of an existing thrombus. In the first protoc ol the right carotid artery was instrumented with a flow probe, stenos is, an anodal electrode, and a proximal infusion line. A 300 mu A anod al current was used to induce endothelial injury and subsequent thromb otic occlusion of the vessel. Anisoylated plasminogen streptokinase ac tivator complex (APSAC; 0.05 U/kg intraarterially) was injected proxim al to the thrombus 30 minutes after occlusion. After APSAC, nitroglyce rin (1 mu g/kg/min intraarterially, n = 7) or vehicle (n = 6) was infu sed proximal to the thrombus for 3 hours. Reocclusion occurred in two of seven nitroglycerin-treated dogs and six of six vehicle-treated dog s (p < 0.05). In the second protocol both carotid arteries were instru mented as described previously. Anodal current (300 mu A, 180 minutes) was applied to the right carotid (n = 12) artery to determine control times to occlusion. The left carotid artery served as the test vessel , receiving either nitroglycerin (1 mu g/kg/min intraarterially, n = 6 ) or trimethaphan (0.05 mg/kg/hr intraarterially, n = 6). Trimethaphan was used to produce controlled hypotension to match the approximately 10% decrease in mean arterial blood pressure that was observed during nitroglycerin infusion. Control arteries and those treated with trime thaphan formed occlusive thrombi in all instances. Nitroglycerin infus ion resulted in a lower incidence of occlusion (1 of 6; p < 0.05 vs co ntrol value) and inhibited ex vivo platelet aggregation to adenosine d iphosphate and arachidonic acid (p < 0.05). Local infusion of nitrogly cerin reduced the formation of primary thrombi, independent of the hyp otensive effect of the drug, and exerted systemic effects on platelet aggregation. Furthermore, platelet inhibition with nitroglycerin reduc ed the incidence of secondary thrombus formation (rethrombosis) after thrombolysis. The results suggest that a potential benefit of nitrogly cerin therapy may be derived from its ability to inhibit thrombotic ev ents in patients with unstable angina or myocardial infarction.