Taprostene, a stable prostacyclin analogue, enhances the thrombolytic efficacy of Saruplase (cas 99149-95-8) (recombinant single-chain urokinase-type plasminogen activator) in rabbits with pulmonary embolized thrombi

Add time:07/18/2019    Source:sciencedirect.com

Cooperative effects of the prostacyclin analogue taprostene and the thrombolytic agent Saruplase (cas 99149-95-8) (r-scu-PA) were studied in anesthetized rabbits with pulmonary thromboembolism. Thrombolysis was evaluated as decrease of the total weight and of the incorporated 125J-fibrin-radioactivity of the embolized thrombi. Saruplase (10.0-–46.4 μg/kg·min, i.v.) produced dose-dependent lytic effects. Taprostene, infused in dose (0.1 μg/kg·min, i.v.) that inhibited ADP-induced decrease of circulating platelets by 56%, reduced the total thrombus weight (p < 0.05 vs control) and in combination it further augmented the saruplase (21.5 μg/kg·min)-induced thrombolysis (p < 0.05 vs saruplase alone). Taprostene did not increase the spontaneous lysis rate of the incorporated 125J-fibrin (7.3 ± 1.4% vs 8.1 ± 1.4%), but further enhanced the fibrinolytic effect of saruplase (37.2 ± 5.6% saruplase vs 53.6 ± 2.3% saruplase + taprostene; p < 0.05). This overadditive synergism is tentatively ascribed to the platelet inhibition by the prostacyclin analogue that may facilitate the action of the thrombolytic agent. Taprostene lowered mean arterial blood pressure by 22% in anesthetized rabbits; it did not significantly modify the slight decrease of the plasma fibrinogen level (20–30%) by 21.5 μg/kg·min saruplase. The results show that the prostacyclin analogue taprostene reduces the total thrombus weight and enhances the efficacy of the thrombolytic agent saruplase in pulmonary thromboembolism in rabbits.

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