The Usefulness of Systemic Administration of Recombinant Human Tissue-Type Plasminogen Activator in Femoral Arterial Thrombolysis of Rabbits

Abstract

The thrombolytic effect of locally or systemically administered recombinant human tissue-type plasminogen activator (rt-PA) was investigated in comparison with the effect of tissue culture urokinase (TCUK), using a model of femoral artery thrombosis in rabbits. An ¹²⁵1-labeled fibrinogen thrombus was formed in the femoral artery following injury of the intima by diluted sulfuric acid, and thrombolytic activity was evaluated one hour after the end of infusion of the agents. Local infusion of rt-PA (500-10, 000 IU/kg) and TCUK (10, 000 IU/kg) induced a marked thrombolysis. When rt-PA and TCUK were injected systemically in a high dose (200, 000 IU/kg), rt-PA but not TCUK had a significant thrombolytic activity. In these cases, rt-PA was not accompanied by systemic activation of the fibrinolytic system, as evaluated by unaltered levels of α₂-antiplasmin in the plasma, while TCUK led to a substantial decrease in the α₂-antiplasmin level. These results suggest that systemically administered rt-PA but not TCUK induce a significant thrombolysis without systemic activation of the fibrinolytic system in cases of peripheral artery thrombosis.