title: Differential inhibition with antifibrinolytic agents of staphylokinase and streptokinase induced clot lysis.
abstract: The inhibitory effects of antifibrinolytic amino acids on clot lysis induced with recombinant staphylokinase (SakSTAR) or with streptokinase (SK) were evaluated in a human plasma milieu in vitro and in a hamster pulmonary embolism model in vivo. Addition of tranexamic acid to a system composed of 60 microliters 125I-fibrin-labeled plasma clots submerged in 0.5 ml human plasma, caused dose-dependent inhibition of lysis; complete lysis in 120 min required 30 nM SakSTAR or 100 nM SK and was reduced to 50% with 0.015 mM or with 0.07 mM tranexamic acid, respectively. Aprotinin also produced dose-dependent inhibition; lysis with SakSTAR or with SK was reduced to 50% of the control value with 8 KIU/ml or with 10 KIU/ml aprotinin, respectively. Thus, in human plasma in vitro the antifibrinolytic potency of tranexamic acid was 5-fold higher towards SakSTAR than towards SK, whereas that of aprotinin was comparable towards both agents. In hamsters with pulmonary embolism given 0.063 mg/kg SakSTAR or 0.20 mg/kg SK over 30 min, the antifibrinolytic potency of tranexamic acid, administered as a single bolus injection or as a bolus injection followed by continuous infusion, was 8- to 10-fold higher towards SakSTAR than toward SK (50% reduction of clot lysis with SakSTAR at 12.5 mg/kg, as compared to 100-150 mg/kg with SK). In contrast, aprotinin was equipotent towards SakSTAR and SK (50% reduction of clot lysis with 2,000 to 2,700 KIU/kg).(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000818:Animals; D000931:Antidotes; D000933:Antifibrinolytic Agents / Q000494:pharmacology*; D007611:Aprotinin / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006224:Cricetinae; D005342:Fibrinolysis / Q000187:drug effects*; D005343:Fibrinolytic Agents / Q000494:pharmacology* / Q000633:toxicity; D006470:Hemorrhage / Q000139:chemically induced / Q000517:prevention & control; D006801:Humans; D008647:Mesocricetus; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D011655:Pulmonary Embolism / Q000097:blood / Q000188:drug therapy; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013300:Streptokinase / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D015912:Thrombolytic Therapy; D014148:Tranexamic Acid / Q000494:pharmacology
chemical_list: D000931:Antidotes; D000933:Antifibrinolytic Agents; D001426:Bacterial Proteins; D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; D014148:Tranexamic Acid; D007611:Aprotinin; D013300:Streptokinase; D008666:Metalloendopeptidases; C022653:auR protein, Staphylococcus aureus