Recent studies demonstrate the importance of thrombosis in coronary occlusion and myocardial infarction. However, the mechanism underlying thrombosis and resulting coronary occlusion remain unresolved. The majority of studies on thrombus formation have been conducted in in vitro systems. The primary goal of this study is to determine the role of platelet aggregation and vasoconstriction in coronary artery occlusion in an in vivo model of spontaneous coronary thrombosis. Serotonin release during platelet aggregation will be used as an in vivo index of platelet aggregation. A partial coronary thrombus will be formed in dogs by application of D/C current to the arterial lumen. After the current is stopped, thrombus spontaneously extends to occlude the artery. Platelet aggregation will be assessed by changes in plasma serotonin levels drawn via coronary sinus catheter. Serotonin will be assayed by a sensitive radioenzymatic method. In vivo vascular reactivity (vasomotion) will be measured by microcrystals sewn to the arterial wall. Correlative measurements of myocardial function will be made using Doppler flow probes, length segment crystals (left ventricular contractility), Millar catheters (blood pressure), and epicardial ECGs. Selected agents (aspirin, LY53857, dazoxiben, aminophylline, PGE1, SQ29548, heparin, diltiazem) will be used singly or in combination to inhibit specific mechanisms that lead to platelet aggregation and vasoconstriction. Infusion studies with epinephrine, serotonin or histamine will assess the alteration in local vascular response to autocoids that may be present during thrombus formation. The thrust of these experiments is to better understand the role of platelets and vascular reactivity in occlusive coronary thrombosis, not to the initial events associated the thrombogenesis. Preliminary studies in this laboratory have demonstrated the feasibility of these experiments in an in vivo model that can quantitatively assess platelet aggregation, thrombus formation, and vascular reactivity simultaneously with dynamic measurements of coronary of blood flow and myocardial function.
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