title: Synergistic fibrinolysis: The combined effects of tissue plasminogen activator and recombinant staphylokinase in vitro.
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.
  
  
  CONCLUSIONS
  The results show that combined thrombolysis may be more effective and safer than thrombolysis with each activator alone.
authors.affiliation: Chemical Enzymology Department, Chemistry Faculty, The M.V. Lomonosov Moscow State University, 119992 Moscow, Leninskie gori 1/3, Russian Federation. Electronic address: aisina2004@mail.ru.
authors.forename: Roza
authors.initials: R
authors.lastname: Aisina
authors.affiliation: Chemical Enzymology Department, Chemistry Faculty, The M.V. Lomonosov Moscow State University, 119992 Moscow, Leninskie gori 1/3, Russian Federation.
authors.forename: Liliya
authors.initials: L
authors.lastname: Mukhametova
authors.affiliation: Chemical Enzymology Department, Chemistry Faculty, The M.V. Lomonosov Moscow State University, 119992 Moscow, Leninskie gori 1/3, Russian Federation.
authors.forename: Sergei
authors.initials: S
authors.lastname: Varfolomeyev
mesh_terms: D005340:Fibrinogen / Q000737:chemistry* / Q000378:metabolism; D005342:Fibrinolysis; D006801:Humans; D010958:Plasminogen / Q000737:chemistry* / Q000378:metabolism; D013300:Streptokinase / Q000737:chemistry*; D010959:Tissue Plasminogen Activator / Q000737:chemistry*
chemical_list: D005340:Fibrinogen; D010958:Plasminogen; D013300:Streptokinase; D010959:Tissue Plasminogen Activator
keywords: Combination; Fibrinogenolysis; Fibrinolysis; Staphylokinase; Synergy; Tissue plasminogen activator