The beneficial effects of nafazatrom (BAYg6575) on experimental coronary thrombosis

An in vivo model of coronary artery thrombosis in the conscious dog was used to evaluate the potential antithrombotic effect of nafazatrom (BAYg6575). A silver wire electrode was implanted in the left circumflex coronary artery (LCX) and was used at a later time to deliver a 50 uA anodal current for 24 hours to the intimal surface of the vessel. The resulting injury to the endothelium was accompanied by the adhesion, aggregation, and subsequent formation of an occlusive thrombus in the LCX of vehicle-treated dogs. Nafazatrom was given as an intravenous dose of 1 mg/kg for 48 hours, before anodal stimulation of the coronary artery was initiated, and was repeated every 6 hours during anodal stimulation for a total treatment period of 72 hours. As compared to vehicle-treated control dogs, the dogs treated with nafazatrom had smaller thrombi, preservation of coronary blood flow, a lesser degree of ischemic injury in the myocardial region subserved by the LCX, and less frequent premature ventricular complexes during the final 12 hours of the study period. Concomitant ex vivo platelet aggregation studies revealed significant inhibition of platelet aggregation in response to collagen and adenosine diphosphate in drug-treated dogs. The results of these investigations provide evidence that nafazatrom prevents in vivo development of occlusive coronary artery thrombi in response to disruption of the endothelial surface of the vessel.