Synergy of in vitro thrombolytic action of combinations of recombinant staphylokinase and single-chain urokinase-type plasminogen activator.
Kinetics of lysis of human plasma clots immersed in plasma were studied in vitro at 37 degrees C under the influence of recombinant staphylokinase, single-chain urokinase-type plasminogen activator (scu-PA), and their simultaneous and consecutive combinations. Staphylokinase and scu-PA caused concentration- and time-dependent lysis of the clots; 32 nM staphylokinase and 75 nM scu-PA separately caused 50% lysis in 4 h. At these equally effective concentrations staphylokinase in 4 h induced a significantly lesser exhaustion of the plasma plasminogen, alpha(2)-antiplasmin, and fibrinogen than scu-PA. Combinations of staphylokinase (<30 nM) and scu-PA (<75 nM) rendered synergic thrombolytic action on the clots. The synergy of thrombolytic action was more pronounced on the simultaneous addition of the two agents than on their consecutive addition, scu-PA 30 min after staphylokinase. In 4 h after the addition, staphylokinase (25 nM) or scu-PA (15 nM) induced 24% and 2% lysis, respectively, whereas the simultaneous and consecutive combination of the same concentrations of these agents induced 58% and 50% lysis, respectively. The simultaneous combination of 15 nM staphylokinase and 15 nM scu-PA resulted in maximal 3.8-fold increase in the thrombolytic effect as compared to the expected total effect of the individual agents. Synergic combinations of the two agents caused lesser exhaustion of plasma plasminogen, alpha(2)-antiplasmin, and fibrinogen as compared with the expected total effect of these agents used separately. Thus, simultaneous and consecutive combinations of staphylokinase and scu-PA in a relatively narrow range of their concentrations possessed synergistic fibrin-selective thrombolytic action on the plasma clot in vitro.
Aisina
R B
RB
Faculty of Chemistry, Lomonosov Moscow State University, Moscow, 119992, Russia. arb@enzyme.chem.msu.ru
Moukhametova
L I
LI
Varfolomeyev
S D
SD
D001777:Blood Coagulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004357:Drug Synergism; D005340:Fibrinogen / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008666:Metalloendopeptidases / Q000737:chemistry / Q000494:pharmacology*; D010958:Plasminogen / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology*; D010959:Tissue Plasminogen Activator / Q000737:chemistry / Q000494:pharmacology*; D014568:Urokinase-Type Plasminogen Activator / Q000737:chemistry / Q000494:pharmacology*; D000979:alpha-2-Antiplasmin / Q000378:metabolism
D004338:Drug Combinations; D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; D000979:alpha-2-Antiplasmin; D005340:Fibrinogen; D010958:Plasminogen; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; D008666:Metalloendopeptidases; C022653:auR protein, Staphylococcus aureus