1. Synergistic fibrinolysis: The combined effects of tissue plasminogen activator and recombinant staphylokinase in vitro.
- Author
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Aisina R, Mukhametova L, and Varfolomeyev S
- Subjects
- Fibrinogen metabolism, Humans, Plasminogen metabolism, Fibrinogen chemistry, Fibrinolysis, Plasminogen chemistry, Streptokinase chemistry, Tissue Plasminogen Activator chemistry
- Abstract
Background: Mechanisms of fibrin-specificity of tissue plasminogen activator (tPA) and recombinant staphylokinase (STA) are different, therefore we studied in vitro the possibility of the synergy of their combined thrombolytic action., Methods: Thrombolytic effects of tPA, STA and their combinations were measured by lysis rate of human plasma clot and side effects were evaluated by decreasing in fibrinogen, plasminogen and α2-antiplasmin levels in the surrounding plasma at 37°C in vitro., Results: STA and tPA induced dose- and time-dependent clot lysis: 50% lysis in 2 h was obtained with 30 nM tPA and 75 nM STA, respectively. At these concentrations, tPA produced greater degradation of plasma fibrinogen than STA. According to a mathematical analysis of dose-response curves by the isobole method, combinations of tPA and STA caused a considerable synergistic thrombolytic effect. The simultaneous and sequential combinations of tPA (<4 nM) and STA (<35 nM) induced a significant fibrin-specific synergistic thrombolysis, which was more pronounced in 2 h at simultaneous combinations than at sequential addition of STA after 30 min of tPA action. Simultaneous combination of 2.5 nM tPA and 15 nM STA showed a maximal 3-fold increase in thrombolytic effect compared to the expected total effect of the individual agents. Sequential combinations caused a lower depletion of plasma proteins compared to simultaneous combinations., Conclusions: The simultaneous and sequential combinations of tPA and STA possessed synergistic fibrin-specific thrombolytic action on clot lysis in vitro., General Significance: The results show that combined thrombolysis may be more effective and safer than thrombolysis with each activator alone., (Copyright © 2015 Elsevier B.V. All rights reserved.)
- Published
- 2016
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