Combined thrombolysis by joint action of the tissue plasminogen activator and A urokinase—fibrinogen conjugate upon sequential double bolus introduction in dogs with venous thrombosis model

Abstract

One method to increase the efficacy ofthrombolytic therapy consists in using a combination of plasminogen activators [1, 2]. This approach may reduce the frequency of complications after thrombolysis, allow a decrease in the total dose of the drugs introduced, accelerate the drug action compared to the case of monotherapy, and lower the costs of the course of therapy [1-5] . In order to develop this approach, we have previously synthesized and studied in vivo the preparations of different plasminogen activators producing mutually complementary effects [6, 7] and possessing significantly differing pharmacokinetic profiles [8]. Experiments on the model of venous thrombosis in dogs revealed the phenomenon of fast response for the combined administration of the recombinant tissue plasrninogen activator (TPA) and a fibrinogen-modified urokinasefibrinogen ( U K Fbg) conjugate, although these results were achieved using a rather prolonged and complicated bolusinfusion-bolus administration schedule [9]. Recent experiments in vitro also justified expediency of the further investigation of the thrombolytic