ADJUVANT EFFECT OF ARGATROBAN ON STAPHYLOKINASE INDUCED THROMBOLYSIS OF PLATELET RICH THROMBI IN RAT MESENTERIC VENULES IN VIVO

Effective, therapeutic thrombolysis should not only promote dissolution of fibrin but should also regulate continued thrombin-induced fibrin formation and the accumulation of platelets on the thrombotic lesion. The aim of the present study was to assess the use of a synthetic, low molecular weight t...

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Bibliographic Details
Published in:Thrombosis research 1997-04, Vol.86 (2), p.115-126
Main Authors: Kawano, Makiko, Watanabe, Sadahiro, Sasaki, Yasuto, Giddings, John C, Yamamoto, Junichiro
Format: Article
Language:English
Subjects:
Animals
Antithrombins - administration & dosage
argatroban
Biological and medical sciences
Blood Platelets - drug effects
Blood Platelets - ultrastructure
Blood. Blood coagulation. Reticuloendothelial system
Disease Models, Animal
Dose-Response Relationship, Drug
Drug Synergism
Fibrinolysis - drug effects
Fibrinolytic Agents - administration & dosage
Image Processing, Computer-Assisted
Male
Medical sciences
Metalloendopeptidases - administration & dosage
Microscopy, Electron
Pharmacology. Drug treatments
Pipecolic Acids - administration & dosage
Rats
Rats, Wistar
Recombinant Proteins - administration & dosage
staphylokinase
thrombolysis
thrombosis
Thrombosis - drug therapy
Thrombosis - pathology
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Summary:Effective, therapeutic thrombolysis should not only promote dissolution of fibrin but should also regulate continued thrombin-induced fibrin formation and the accumulation of platelets on the thrombotic lesion. The aim of the present study was to assess the use of a synthetic, low molecular weight thrombin inhibitor, argatroban in association with a well defined thrombolytic agent in a reproducible animal model of thrombolysis in vivo. Thrombi were formed in rat mesenteric venules with a helium neon (He-Ne) laser in the presence of Evans blue and were stabilised for 10 minutes. Thrombi formed in this manner were shown by transmission electron microscopy to be composed mainly of platelets. Thrombolysis was induced with recombinant staphylokinase in the presence and absence of argatroban and the process was monitored using computerised image analysis. Co-infusion of argatroban at a dose of 2.0mg/kg/h with staphylokinase significantly enhanced the rate of thrombolysis. The results suggested that administration of the thrombin inhibitor together with the fibrinolytic agent moderated platelet-dependent mechanisms and led to a more rapid restoration of blood vessel patency. © 1997 Elsevier Science Ltd
ISSN:0049-3848
1879-2472
DOI:10.1016/S0049-3848(97)00055-8