Effect of a Synthetic Factor Xa Inhibitor, YM-60828, on Blood Vessel Patency in Combination with a Thrombolytic Agent and on Blood Loss from the Operation Site in a Rat Model of Arterial Thrombosis

Tomihisa Kawasaki; Kazuo Sato; Fukushi Hirayama; Hiroyuki Koshio; Yuta Taniuchi; Yuzo Matsumoto

doi:10.1055/s-0037-1615078

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1998; 79(04): 859-864
DOI: 10.1055/s-0037-1615078

Rapid Communication

Schattauer GmbH

Effect of a Synthetic Factor Xa Inhibitor, YM-60828, on Blood Vessel Patency in Combination with a Thrombolytic Agent and on Blood Loss from the Operation Site in a Rat Model of Arterial Thrombosis

Authors

Tomihisa Kawasaki

¹From the Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Tsukuba, Ibaraki, Japan
Kazuo Sato

¹From the Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Tsukuba, Ibaraki, Japan
Fukushi Hirayama

¹From the Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Tsukuba, Ibaraki, Japan
Hiroyuki Koshio

¹From the Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Tsukuba, Ibaraki, Japan
Yuta Taniuchi

¹From the Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Tsukuba, Ibaraki, Japan
Yuzo Matsumoto

¹From the Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Tsukuba, Ibaraki, Japan

Abstract

Summary

We examined the adjunctive effect of a novel factor Xa inhibitor, YM-60828, on vessel patency and blood loss from the operation site after successful thrombolysis with a modified tissue-type plasminogen activator (moPA) in an electrically-induced carotid artery thrombosis model in rats. Five minutes after the induction of occlusive thrombus, a test drug (YM-60828, argatroban, heparin or saline) was administered by i.v. bolus injection followed by continuous infusion. Thrombolysis was induced with moPA by i.v. bolus injection at a dose of 650,000 IU/ kg. YM-60828 at 1 mg/kg i.v. followed by 3 mg/kg/h significantly prevented reocclusion, increased the duration of patency, and improved vessel patency after successful thrombolysis without any significant increase in blood loss from the operation site. Argatroban at 1 mg/kg i.v. followed by 3 mg/kg/h and heparin at 300 U/kg i.v. followed by 150 U/kg/h also significantly improved these parameters, but were accompanied by a significant increase in blood loss. These results suggest that the factor Xa inhibitor YM-60828 may be a potent and useful adjunctive agent with a lower risk of bleeding complications than argatroban and heparin in thrombolytic therapy.

Full Text

References

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