YM866, A NOVEL MODIFIED TISSUE-TYPE PLASMINOGEN-ACTIVATOR, AFFECTS LEFT-VENTRICULAR FUNCTION AND MYOCARDIAL INFARCT DEVELOPMENT IN DOGS WITH CORONARY-ARTERY THROMBI

YM866 is a novel modified tissue-type plasminogen activator (t-PA). It s effects on left ventricular function and myocardial infarct developm ent in dogs with copper coil-induced coronary artery thrombosis were c ompared with those of a native t-PA, alteplase. YM866 (bolus injection ) and alteplase (bolus plus infusion) were administered 15 min after c oronary artery occlusion. YM866 and alteplase produced reperfusion in all animals, with a median time to reperfusion of 10 min. In contrast, no reperfusion occurred in the vehicle control group. Left ventricula r ejection fraction (LVEF) significantly decreased 15 min after corona ry occlusion. YM866 and alteplase improved LVEF 3 hr and 4 hr after ad ministration, respectively, while LVEF did not improve in the vehicle control group. Only slight myocardial infarct areas were observed in b oth YM866- and alteplase-administered groups, while the area in the ve hicle control group accounted for 18.2% of left ventricular myocardial area. In conclusion, although both YM866 and alteplase reperfused occ luded coronary arteries, inhibited myocardial infarct development and improved LVEF in dogs with coronary artery thrombi, only a single bolu s injection of YM866 was necessary to achieve these improvements. Ther efore, YM866 shows promise as an improved clinical agent in treating a cute myocardial infarction.