Sustained thrombolysis with DNA-recombinant tissue type plasminogen activator in rabbits.
Tissue type plasminogen activator (t-PA) is an effective thrombolytic agent in experimental animals. The duration of the thrombolytic effect of infused t-PA is unknown. We compared the duration of the thrombolytic effect of t-PA with streptokinase by measuring the lysis of 125I-fibrin-labeled thrombi in rabbit jugular veins at different times after a bolus injection of the fibrinolytic agents. The pharmacodynamics of both thrombolytic agents were determined in rabbits using a sensitive ex vivo fibrinolytic assay. Streptokinase and t-PA were given as a bolus dose of 15,000 U/kg. There was no detectable circulating fibrinolytic activity 30 minutes after the bolus dose of t-PA and 120 minutes after the bolus dose of streptokinase. The t-PA injection produced 34% thrombolysis at 30 minutes, 90% thrombolysis at 120 minutes, and 96% thrombolysis at 240 minutes. The streptokinase injection produced 17% thrombolysis at 30 minutes, 34% at 120 minutes, and 34% at 240 minutes. These observations indicate that the thrombolytic effect of t-PA is sustained beyond its time of clearance from the circulation whereas the thrombolytic effect of streptokinase closely parallels its activity in the circulation.
D000818:Animals; D004274:DNA, Recombinant; D005342:Fibrinolysis / Q000187:drug effects*; D007457:Iodine Radioisotopes; D007601:Jugular Veins; D007700:Kinetics; D010960:Plasminogen Activators / Q000096:biosynthesis / Q000494:pharmacology*; D011817:Rabbits; D013300:Streptokinase / Q000494:pharmacology; D013997:Time Factors
D004274:DNA, Recombinant; D007457:Iodine Radioisotopes; D013300:Streptokinase; D010960:Plasminogen Activators