ANTITHROMBOTIC EFFECTS OF BMY21190, AN INHIBITOR OF CAMP-PHOSPHODIESTERASE, IN A CANINE MODEL OF CORONARY-ARTERY THROMBOSIS

BMY21190, an inhibitor of cyclic AMP phosphodiesterase, has a coronary vasodilating effect. BMY21190 was evaluated for its ability to modify the development of experimental thrombosis resulting from anodal curr ent injury (100 muA for 6 h) of the intimal surface of the left circum flex coronary artery (LCX) in anesthetized dogs. Two groups of dogs we re studied. One group received BMY21190 (1 mg/kg) and the other group received an equal volume of vehicle infused into the left jugular vein . After a 30 min administration of BMY21190, heart rate and mean coron ary blood flow were increased significantly and mean arterial pressure was decreased. However, the myocardial tension of the left anterior d escending coronary artery (LAD) and LCX areas did not increase signifi cantly after BMY21190 infusion. During LCX stimulation, the first LCX occlusion and hyperemic reaction of the control group both occurred si gnificantly earlier than those of the BMY21190 group. BMY21190 treatme nt reduced the development of the LCX thrombus mass, as compared to th at in the controls. In ex vivo studies, platelet aggregation in respon se to arachidonic acid, ADP or collagen was inhibited by BMY21190. The se results suggest that BMY21190 possesses anti-thrombotic and coronar y vasodilating effects which may be mediated through the inhibition of cyclic AMP phosphodiesterase.