Experimental Study on Prevention of Intracoronary Thrombus Formation and Myocardial Infarction by a Thromboxane Synthetase Inhibitor (OKY-046)

Effects of a thromboxane synthetase inhibitor was studied in an experimental model of acute myocardial infarction. Intracoronary thrombus was precipitated by a mock atheromatous plaque in 13 of 15 control dogs.Myocardial infarction was induced in 10 of them and sudden death in 2.There were 2 types of reduction of the coronary blood flow due to thrombus formation: a gradual decrease associated with the delayed appearance of abnormalities in myocardial contraction and the electrocardiogram in 7 of the 12 dogs with myocardial infarction or sudden death (Type A) and repetition of the alteration of reduction and sudden increase in coronary blood flow in the remaining (Type B). In either type, coronary blood flow decreased to induce myocardial infarction in 212±41 minutes.Thromboxane B2 and 6-keto-prostaglandin F1α were significantly elevated in the coronary venous blood during the reduction of the coronary blood flow.The model was utilized to investigate the effects of a selective thromboxane synthetase inhibitor, OKY-046, on an additional 10 dogs. OKY-046 could significantly interrupt the occurrence of myocardial infarction when administered intravenously during Type A or B reduction of the coronary blood flow (3/10 vs. 12/15, p<0.02). A significant reduction in thromboxane A2 appeared to be the major mechanism of the interruption of the thombus formation and completion of myocardial infarction.