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

• Published in: Thrombosis research Vol. 86; no. 2; pp. 115 - 126
• Main Authors: Kawano, Makiko, Watanabe, Sadahiro, Sasaki, Yasuto, Giddings, John C, Yamamoto, Junichiro
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Ltd 15.04.1997; Elsevier Science
• 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; thrombolysis; thrombosis; staphylokinase; argatroban; Drug combination; Intravenous administration; Serine endopeptidases; Rat; Enzyme; Thrombus; Mesenteric vein; Rodentia; Argatroban; Enzyme inhibitor; Thrombin; Anticoagulant; Biological activity; Peptidases; Vertebrata; Mammalia; Animal; Lysis; Hydrolases; Recombinant protein; Fibrinolytic
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/S0049-3848(97)00055-8

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