YM866 is a novel modified
tissue-type plasminogen activator (t-PA). Its effects on left ventricular function and
myocardial infarct development in dogs with
copper coil-induced coronary artery
thrombosis were compared with those of a native t-PA,
alteplase.
YM866 (bolus injection) and
alteplase (bolus plus infusion) were administered 15 min after coronary 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 ventricular ejection fraction (LVEF) significantly decreased 15 min after
coronary occlusion.
YM866 and
alteplase improved LVEF 3 hr and 4 hr after administration, respectively, while LVEF did not improve in the vehicle control group. Only slight
myocardial infarct areas were observed in both YM866- and
alteplase-administered groups, while the area in the vehicle control group accounted for 18.2% of left ventricular myocardial area. In conclusion, although both
YM866 and
alteplase reperfused occluded coronary arteries, inhibited
myocardial infarct development and improved LVEF in dogs with coronary artery thrombi, only a single bolus injection of
YM866 was necessary to achieve these improvements. Therefore,
YM866 shows promise as an improved clinical agent in treating acute
myocardial infarction.