THROMBOLYSIS OF CANINE FEMORAL-ARTERY THROMBUS BY A NOVEL MODIFIED TISSUE-TYPE PLASMINOGEN-ACTIVATOR (E6010)

The thrombolytic activity of a novel modified tissue-type plasminogen activator (t-PA) (E6010) was examined in a canine model with copper co il-induced femoral artery thrombus. This model, in which thrombolytic activity can be easily and directly quantified by determining changes in thrombus weight, should be useful for comparing the activities of v arious thrombolytic agents. Using this model, the present study showed that the thrombolytic activity of bolus intravenous injection of E601 0 was identical to that of continuous intravenous infusion of recombin ant t-PA at the same dose. This thrombolytic activity can be explained by changes in blood concentrations of the administered thrombolytic a gents. On the other hand, administration of the thrombolytic agents do se-dependently caused significant changes in the levels of hemostatic and fibrinolytic factors. These changes were not so marked with admini stration of E6010, and therefore we concluded that E6010 is unlikely t o cause bleeding complications after administration.