Potentiation and acceleration effects in combined administration of tissue plasminogen activator and fibrinogen-modified urokinase in dogs with modeled venous thrombosis

Abstract

Combined administration of tissue plasminogen activator and a urokinase-fibrinogen covalent conjugate is studied using modeled venous thrombosis in dogs. In comparison with the effect of the individual preparations the thrombolytic effect was potentiated when intravenous bolus injection of 1 mg tissue plasminogen activator followed by a 2-hour infusion of 4 mg of this preparation was combined with bolus injection of 25,000 IU urokinase-fibrinogen covalent conjugate 15 min after the first bolus. Potentiation and acceleration of thrombolysis were attained with the same scheme when tissue plasminogen activator was administered in a dose of 1 mg for both bolus and infusion and combined with 250,000 IU of fibrinogen-modified urokinase.

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

“…In concluding, we suggest that development of the approach based on the combined thrombolysis using different plasminogen activators [2,6,9,17] is quite promising. A special feature of this approach consists in the use of components having significantly different pharmacokinetic profiles (e.g., of the TPA and urokinase types) to provide for mutually complementary action during the thrombolysis [6,7].…”

“…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 urokinase-fibrinogen (UK-Fbg) conjugate, although these results were achieved using a rather prolonged and complicated bolus-infusion-bolus administration schedule [9]. Recent experiments in vitro also justified expediency of the further investigation of the thrombolytic t Cardiological Research and Production Complex, Ministry of Health and Medical Industries of the Russian Federation, Moscow, Russia.…”

“…The thrombolytic activity of plasminogen activators was studied on the model of venous thrombosis in dogs [9,12]. The experiments were performed on mongrel dogs weighing 12-22 kg (on the average, 18 kg).…”

Thrombolysis strategy: Joint action of plasminogen activators. Thrombolytic compositions (A review)

“…Investigations of the model of venous thrombosis in dogs treated with a TPA in combination with UK-Fbg under the conditions of a bolus-infusion-bolus administration scheme showed an~increase in the magnitude and rate of the thrombolytic effect as compared to the case of separate administration of individual components at the same doses [25]. In designing this combination of two thrombolytic agents, TPA was intended to act as the thrombolysis trigger, while UK-Fbg was planned to serve as an agent capable of supporting the thrombolysis process for a prolonged time [25].…”

“…In designing this combination of two thrombolytic agents, TPA was intended to act as the thrombolysis trigger, while UK-Fbg was planned to serve as an agent capable of supporting the thrombolysis process for a prolonged time [25].…”