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 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 2.0 mg/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.
Kawano
M
M
Laboratory of Physiology, Faculty of Nutrition, Kobe Gakuin University, Japan.
Watanabe
S
S
Sasaki
Y
Y
Giddings
J C
JC
Yamamoto
J
J
D000818:Animals; D000991:Antithrombins / Q000008:administration & dosage*; D001120:Arginine / Q000031:analogs & derivatives; D001792:Blood Platelets / Q000187:drug effects / Q000648:ultrastructure; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005342:Fibrinolysis / Q000187:drug effects; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D007091:Image Processing, Computer-Assisted; D008297:Male; D008666:Metalloendopeptidases / Q000008:administration & dosage*; D008854:Microscopy, Electron; D010875:Pipecolic Acids / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000008:administration & dosage; D013449:Sulfonamides; D013927:Thrombosis / Q000188:drug therapy / Q000473:pathology
D000991:Antithrombins; D005343:Fibrinolytic Agents; D010875:Pipecolic Acids; D011994:Recombinant Proteins; D013449:Sulfonamides; D001120:Arginine; D008666:Metalloendopeptidases; C022653:auR protein, Staphylococcus aureus; C031942:argatroban