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