Enhancement of Endogenous Plasminogen Activator-induced Thrombolysis by Argatroban and APC and Its Control by TAFI, Measured in An Arterial Thrombolysis Model In Vivo Using Rat Mesenteric Arterioles

Masaru Hashimoto; Tsutomu Yamashita; Kazuhiro Oiwa; Sadahiro Watanabe; John C. Giddings; Junichiro Yamamoto

doi:10.1055/s-0037-1612952

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2002; 87(01): 110-113
DOI: 10.1055/s-0037-1612952

Review Article

Schattauer GmbH

Enhancement of Endogenous Plasminogen Activator-induced Thrombolysis by Argatroban and APC and Its Control by TAFI, Measured in An Arterial Thrombolysis Model In Vivo Using Rat Mesenteric Arterioles

Authors

Masaru Hashimoto

¹Laboratory of Physiology, Faculty of Nutrition, Kobe Gakuin University and Kobe Gakuin University High Technology Research Centre, Kobe, Japan
Tsutomu Yamashita

¹Laboratory of Physiology, Faculty of Nutrition, Kobe Gakuin University and Kobe Gakuin University High Technology Research Centre, Kobe, Japan
Kazuhiro Oiwa

²Communications Research Laboratory, Kansai Advanced Research Centre, Kobe, Japan
Sadahiro Watanabe

³Division of Basic Medical Science, Kobe City College of Nursing, Kobe, Japan
John C. Giddings

⁴Department of Haematology, University of Wales College of Medicine, Cardiff, UK
Junichiro Yamamoto

¹Laboratory of Physiology, Faculty of Nutrition, Kobe Gakuin University and Kobe Gakuin University High Technology Research Centre, Kobe, Japan

Abstract

Summary

Recent in vitro studies have demonstrated that thrombin inhibits fibrinolysis through thrombin-activatable fibrinolysis inhibitor (TAFI, plasma procarboxypeptidase B). We have recently shown that endogenous fibrinolysis in vivo is enhanced by activated protein C (APC) and the selective thrombin inhibitor, argatroban. The aim of the present study was to examine the role of TAFI in these fibrinolytic mechanisms in vivo using purified porcine pancreatic carboxypeptidase B (PPCPB) and a specific TAFIa inhibitor, potato tuber carboxypeptidase B inhibitor (PTCI) in a newly established arterial thrombolysis model. Non-occlusive, mural, platelet-rich thrombi were formed by helium-neon laser irradiation in rat mesenteric arterioles and thrombus size was measured by computerised image analysis. We confirmed that endogenous thrombolysis was enhanced by argatroban (2.0 mg/4 ml/kg/h) or APC (1.62 mg/2.31 ml/kg). PTCI (5.0 mg/2 ml/kg) also accelerated endogenous thrombolysis. PPCPB (3.5 mg/2 ml/kg) inhibited thrombolysis in the absence and presence of argatroban or APC. PTCI tended to further promote APC-induced thrombolysis but the differences did not reach statistical significance. The present findings were in keeping with the results of earlier studies and demonstrated that arterial, platelet-rich thrombi in vivo are degraded by naturally generated plasminogen activators. TAFI may play a significant role in the control of these mechanisms.

Keywords

Endogenous thrombolysis - fibrinolysis - thrombin - TAFI

Full Text

References

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