Thrombolytic Effects of a Novel Modified Tissue Plasminogen Activator, E6010, on Coronary Thrombosis in the Pig.
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- Adachi Hideyuki
- Eisai Tsukuba Research Laboratories
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- Nagaoka Naoko
- Eisai Tsukuba Research Laboratories
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- Nomoto Ken-ichi
- Eisai Tsukuba Research Laboratories
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- Yuzuriha Teruaki
- Eisai Tsukuba Research Laboratories
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- Shoji Tadao
- Eisai Tsukuba Research Laboratories
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説明
-This study was conducted to compare the thrombolytic effect of a novel modified tissue plasminogen activator, E6010, with that of recombinant human tissue plasminogen activator (t-PA), administered by single intravenous bolus injection in pigs with occlusive coronary thrombosis. Thrombosis was induced by electrical stimulation of the intimal surface of the left circumflex coronary artery. Coronary blood flow velocity and hemodynamic parameters were observed for 1 hr after complete cessation of coronary flow. Ten minutes after heparin injection (300 U/kg), E6010, t-PA or placebo was intravenously administered as a bolus. E6010 at 0.2 and 0.4 mg/kg caused recanalization of the occluded coronary artery in 1 of 6 and 5 of 5 pigs, respectively. The time to recanalization after 0.4 mg/kg of E6010 was 22 ± 11 min (mean ± S.E.M.). t-PA (0.4 mg/kg) caused recanalization in only 1 of 5 pigs. Recanalization did not occur in any of the 6 animals administered placebo. Plasma clearance of E6010 was smaller than that of t-PA (4.9 ± 0.3 vs. 9.4 ± 3.8 ml/min/kg). There were no significant differences in plasma levels of fibrinogen, α2-plasmin inhibitor and plasminogen among the placebo, E6010 and t-PA groups. These results suggest that the slower clearance of E6010 from plasma contributes to the effective thrombolytic action of E6010 following single intravenous bolus injection.
収録刊行物
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- Jpn.J.Pharmacol.
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Jpn.J.Pharmacol. 58 (3), 309-319, 1992
公益社団法人 日本薬理学会
