Effects of the novel thromboxane antagonist Bay U 3405 : on experimental coronary artery disease

Bay U 3405 is a novel thromboxane receptor blocker. The present investigations describe its effects on experimental canine and porcine cardiac damage. In anesthetized dogs, a coronary artery was occluded for 6 hours and reperfused for 30 minutes. Bay U 3405 was administered intravenously 15 minutes after occlusion (1 mg/kg) followed by infusion of 10 mg/kg/hr from 30 minutes after ligature. In a second study, the effects of Bay U 3405 on endoperoxide analogue U-46619-induced coronary constriction were studied in anesthetized, open-chest pigs. Bay U 3405 reduced myocardial infarct expansion by 65% (p less than 0.01) assessed with biochemical staining. Hemodynamics and collateral blood flow were unaffected. However, reperfusion arrhythmias were suppressed. In porcine experiments, 1 mg/kg Bay U 3405, given intravenously or intraduodenally, antagonized U-46619-induced coronary vasoconstriction over 5 hours. The studies demonstrate anti-ischemic and antivasoconstrictor properties of Bay U 3405 probably due to binding to platelet and smooth muscle thromboxane receptors. This may have clinical relevance in angina pectoris and myocardial infarction.