Recent studies show the importance of platelet activation and thrombosis in ischemic heart disease. Pharmacological strategies are being evolved to decrease platelet aggregation in patients with coronary disease with the aim of reducing the incidence of myocardial infarction. An alternate approach is to supplement the diet with omega-3 fatty acids which have been shown in epidimiological studies to lower the incidence of ischemic heart disease. The goal of this study is to determine the mechanisms by which omega-3 fatty acids delay the development of coronary occlusion in an in vivo model of coronary thrombosis that more closely mimics the clinical situation. 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 current to the arterial lumen. After stopping the current, thrombus spontaneously extends to occlude the artery. Platelet aggregation will be assessed by changes in plasma serotonin levels drawn via coronary sinus catheters. In vivo vascular reactivity (vasomotion) will be measured by microcrystals sewn to the arterial wall. Serotonin will be assayed by a sensitive radioenzymatic method. Correlative measurements of myocardial functions will be made using Doppler flow probes, length segment crystals (left ventricular contractility), Millar catheters (blood pressure), and epicardial ECGs. Dogs will be pretreated with fish oil for 12 weeks and its effect on time for thrombotic occlusion, in vivo and in vitro platelet aggregation, vascular reactivity, platelet and vessel wall thromboxane, and prostacyclin synthesis will be determined. Selected agents will be used to determine the site and the mechanism of action of omega- 3 fatty acids. The thrust of these experiments is to determine how fish oil feeding may alter the spontaneous extension of a preexisting thrombus leading to coronary occlusion, not to investigate the initial events associated with thrombogenesis. Preliminary studies show the feasibility of accomplishing these experiments in an in vivo model that can quantitatively assess platelet aggregation, thrombus formation, and vascular reactivity.
