Development of an experimental model of acute myocardial infarction and the effects of a thromboxane synthetase inhibitor (OKY-046).
An experimental model of acute myocardial infarction is presented. Intracoronary thrombus was precipitated by a mock ruptured atheromatous plaque, which is a cholesterol-collagen mixture, protruding into the stenosed left anterior descending coronary artery. Twenty-five dogs, divided into two groups, were studied: a control group of 15 dogs and a treated group of 10 dogs. Intracoronary thrombus was precipitated by the mock atheromatous plaque in 13 of 15 control animals. Myocardial infarction was induced in 10 and sudden death in two. Coronary blood flow decreased gradually or cyclically to end in myocardial infarction. The model was utilized to investigate the effects of a thromboxane synthetase inhibitor, OKY-046, on 10 additional animals. OKY-046 could significantly decrease the incidence of occlusive thrombus formation and myocardial infarction when administered intravenously during coronary blood flow reduction (3 of 10 in the treated group vs 12 of 15 in the control group, p less than 0.02). Thromboxane B2 was significantly elevated in the coronary venous blood during reduction of the coronary blood flow, while thromboxane B2 was reduced and 6-ketoprostaglandin F1 alpha increased during OKY-046 administration. The reduction in thromboxane A2 production associated with increased prostacyclin appeared to be the major mechanism of the interruption of the thrombus formation by OKY-046.
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000179:Acrylates / Q000627:therapeutic use*; D000818:Animals; D003328:Coronary Thrombosis / Q000517:prevention & control; D004285:Dogs; D011464:Epoprostenol / Q000378:metabolism; D005260:Female; D008297:Male; D008689:Methacrylates / Q000627:therapeutic use*; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000209:etiology; D013928:Thromboxane A2 / Q000378:metabolism; D013929:Thromboxane B2 / Q000378:metabolism; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D000179:Acrylates; D008689:Methacrylates; D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D013930:Thromboxane-A Synthase; C034364:ozagrel