Effect of OKY-1581, a thromboxane synthetase inhibitor, on coronary thrombosis in the conscious dog

Abstract

OKY-1581, a new thromboxane synthetase inhibitor, was studied in a conscious canine model of coronary thrombosis. After thoracotomy with placement of a left circumflex coronary artery flow probe and implantation of an electrode into the circumflex artery, animals were assigned randomly to the following groups: 0.9% NaCl vehicle control or OKY-1581 1 mg/kg every 4 h intravenously for 24 h. During the drug treatment period, a 50 [mu]A anodal current was passed through the circumflex electrode, and venous blood was obtained for platelet aggregation studies. As compared to control animals, the OKY-1581 treated animals developed a greater mean coronary flow at the end of the treatment period, smaller thrombi by wet weight, smaller infarcts, and fewer ventricular arrhythmias. Ex vivo platelet aggregation studies revealed significant inhibition of aggregation to standard aggregating agents for the drug treated group only. OKY-1581 is an effective antitbrombotic agent which maintains coronary flow after a thrombogenic stimulus, presumably via blockade of the synthesis of thromboxane by blood platelets.