Thrombolytic effect of single-chain pro-urokinase in a rabbit jugular vein thrombosis model.
The thrombolytic effect of single-chain pro-urokinase (SCPU) was examined in the rabbit using a jugular vein thrombosis model. Infusion of a low dose (120,000 IU/kg) of either urokinase (UK) or SCPU did not produce any significant thrombolysis. However, UK administration at such a low dose caused 20% degradation of circulating fibrinogen. A high dose (480,000 IU/kg) caused significant thrombolysis. The degree of fibrinogenolysis was about 20% in SCPU, but about 80% in UK. The thrombolytic efficiency of SCPU was thus about 3 times larger than that of UK. Analysis of fibrinolytic parameters such as plasminogen, alpha 2-plasmin inhibitor, etc. suggested that UK caused systemic activation of the fibrinolytic system, but SCPU, locally limited activation on the fibrin surface (fibrinolysis). These results indicate that SCPU represents a highly efficient thrombolytic agent without producing fibrinogenolysis.
D000818:Animals; D004195:Disease Models, Animal; D005342:Fibrinolysis / Q000187:drug effects*; D007263:Infusions, Parenteral; D007601:Jugular Veins; D007700:Kinetics; D010960:Plasminogen Activators / Q000008:administration & dosage / Q000627:therapeutic use*; D011817:Rabbits; D013927:Thrombosis / Q000188:drug therapy*; D013997:Time Factors; D014568:Urokinase-Type Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use*
D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator