Cardioprotective actions of a selective thromboxane synthetase inhibitor in acute myocardial ischemia.
OKY-1581, a new thromboxane synthetase inhibitor, at an infusion rate of 1.5 mg/kg/hr inhibited the ischemia-induced increase in circulating thromboxane B2 in cats. Although OKY-1581 failed to restore the S-T segment of the electrocardiogram toward normal values after the onset of ischemia, it prevented the rise in plasma creatine kinase activity usually observed during myocardial ischemia. In addition, OKY-1581 reduced the loss of myocardial creatine kinase activity in the ischemic region of those cats treated with OKY-1581 indicating a significant cardioprotection. No significant effects of OKY-1581 were observed on heart rate, mean arterial blood pressure or the product of the two, the pressure-rate index. Therefore, this agent does not protect by reducing myocardial oxygen demand. The mechanism of the protective action of OKY-1581 in acute myocardial ischemia appears to be either due to prevention of the constrictor and cytolytic actions of thromboxane A2 or to metabolic and cellular actions of OKY-1581 unrelated to thromboxane synthetase inhibition.
D000179:Acrylates / Q000494:pharmacology*; D000818:Animals; D002415:Cats; D003327:Coronary Disease / Q000503:physiopathology*; D003402:Creatine Kinase / Q000097:blood; D004562:Electrocardiography; D006321:Heart / Q000187:drug effects*; D008297:Male; D008689:Methacrylates / Q000494:pharmacology*; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D010101:Oxygen Consumption / Q000187:drug effects; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D000179:Acrylates; D008689:Methacrylates; C031517:2-methyl-3-(4-(3-pyridinylmethyl)phenyl)-2-propenoic acid; D010088:Oxidoreductases; D003402:Creatine Kinase; D013930:Thromboxane-A Synthase