Effect of ticlopidine and other antithrombotics on the venous thrombosis induced by endothelial damage of jugular vein in rats.
A venous thrombosis model was produced by vessel wall damage generated by freezing a small segment of the rat jugular vein. The process of thrombus formation was investigated by electron microscopic study. Ultrastructural studies demonstrated that the initiation of thrombus formation could be deendothelialization caused by freezing of vessel. When blood flow was reestablished, platelets adhered to subendothelium within 1 min. Then platelets aggregated on the adhering platelets, and fibrin net was formed. Finally, thrombi composed predominantly of fibrin and red blood cells with platelet aggregates and leukocytes were generated. An anti-platelet agent, ticlopidine, revealed a potent antithrombotic effect in this model. Because ticlopidine decreased the number of platelet aggregates, reduced the size of aggregates, and inhibited platelet degranulation, it is conceivable that platelet aggregation in early phase of thrombus formation plays a crucial role even in venous thrombosis model. A synthetic thrombin inhibitor, argatroban, also showed a potent antithrombotic effect, but a thrombolytic agent, urokinase, was less effective. In conclusion, this model is both platelet- and coagulation-dependent.
Morishita
K
K
Exploratory Research Laboratories 2, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Wada
M
M
Kumada
T
T
Tanaka
T
T
Tomikawa
M
M
Iwamoto
M
M
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives; D004730:Endothelium, Vascular / Q000293:injuries; D005343:Fibrinolytic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D005615:Freezing; D007601:Jugular Veins / Q000293:injuries*; D008297:Male; D008855:Microscopy, Electron, Scanning; D010875:Pipecolic Acids / Q000494:pharmacology / Q000627:therapeutic use; D010973:Platelet Adhesiveness / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D013449:Sulfonamides; D013927:Thrombosis / Q000188:drug therapy* / Q000209:etiology; D013988:Ticlopidine / Q000494:pharmacology / Q000627:therapeutic use*; D014568:Urokinase-Type Plasminogen Activator / Q000494:pharmacology / Q000627:therapeutic use
D005343:Fibrinolytic Agents; D010875:Pipecolic Acids; D010975:Platelet Aggregation Inhibitors; D013449:Sulfonamides; D001120:Arginine; D014568:Urokinase-Type Plasminogen Activator; C031942:argatroban; D013988:Ticlopidine