Thrombolytic activity of a novel modified tissue-type plasminogen activator, YM866, in a canine model of coronary artery thrombosis.
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| Abstract |
The thrombolytic activity of a novel modified t-PA, YM866, was compared with that of a recombinant t-PA in a canine model of copper coil-induced coronary thrombosis. The coronary thrombus was allowed to age for 1, 3 or 6 hr before either drug was administered. YM866 was administered by i.v. bolus injection, while t-PA was given by the same method, as well as by 60-min i.v. infusion. YM866 showed thrombolytic activity 2 to 4 times as potent as that of t-PA when administered by bolus injection, the difference in thrombolytic effect being obvious in the 3- and 6-hr-old thrombi. Coronary reperfusion was achieved more rapidly with YM866 than with i.v. infusion of t-PA. In animals injected with doses of more than 0.1 mg/kg of YM866, no acute reocclusion occurred. Depletion of plasma fibrinogen to 70% of baseline levels was observed in animals given 0.2 mg/kg YM866, 0.4 mg/kg t-PA by bolus, and 0.6 mg/kg t-PA via infusion. The residual plasma YM866 and t-PA antigen 30 min after bolus injection was 25% and 3% of the peak levels, respectively. YM866, administered by i.v. bolus injection, was thus confirmed to exert a thrombolytic effect superior to that of bolus injection and infusion of t-PA, without systemic fibrinolytic activation. These results suggest the potential clinical applicability of YM866 as a thrombolytic agent that can be administered by i.v. bolus injection for acute myocardial infarction.
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| Authors | T Kawasaki, M Katoh, S Kaku, H Gushima, T Takenaka, Y Yui, C Kawai |
| Journal | Japanese journal of pharmacology (Jpn J Pharmacol) Vol. 63 Issue 1 Pg. 9-16 (Sep 1993) ISSN: 0021-5198 [Print] Japan |
| PMID | 8271535 (Publication Type: Journal Article) |
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