Masanori Suzuki, Toshiyuki Funatsu, Hideyuki Tanaka and Shinji Usuda
Applied Pharmacology Laboratories, Yamanouchi Pharmaceutical Co.,Ltd, 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan
Abstract: 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.
Keywords: Modified tissue-type plasminogen activator, Left ventricular ejection fraction (LVEF), Myocardial infarction, Coronary artery thrombosis, Thrombolysis