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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

Masaru Hashimoto
1   Laboratory of Physiology, Faculty of Nutrition, Kobe Gakuin University and Kobe Gakuin University High Technology Research Centre, Kobe, Japan
,
Tsutomu Yamashita
1   Laboratory of Physiology, Faculty of Nutrition, Kobe Gakuin University and Kobe Gakuin University High Technology Research Centre, Kobe, Japan
,
Kazuhiro Oiwa
2   Communications Research Laboratory, Kansai Advanced Research Centre, Kobe, Japan
,
Sadahiro Watanabe
3   Division of Basic Medical Science, Kobe City College of Nursing, Kobe, Japan
,
John C. Giddings
4   Department of Haematology, University of Wales College of Medicine, Cardiff, UK
,
Junichiro Yamamoto
1   Laboratory of Physiology, Faculty of Nutrition, Kobe Gakuin University and Kobe Gakuin University High Technology Research Centre, Kobe, Japan
› Author Affiliations
Further Information

Publication History

Received 09 March 2001

Accepted after revision 11 September 2001

Publication Date:
13 December 2017 (online)

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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
 

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