In vitro analysis of synergistic effects of fibrinolytic agents and prostacyclin analogues.
We investigated the in vitro thrombolytic effects of streptokinase, urokinase, alteplase and saruplase, alone or in combination, with the prostacyclin analogues, iloprost and taprostene. Human platelet-rich plasma was stimulated with collagen (1 microgram/ml) to generate thrombi containing platelets and fibrin. Following treatment with fibrinolytic agents, lysis was allowed to proceed for 30 min and was then terminated with aprotinin (2,000 CIU/ml). To evaluate the combinatory effects of fibrinolytic agents and prostacyclin analogues, we used concentrations of fibrinolytic agents which reduced thrombi weight by less than 50%. Neither iloprost nor taprostene alone demonstrated any thrombolytic effects. Furthermore, the thrombolytic efficacies of streptokinase, alteplase and saruplase were not enhanced by prostacyclin analogues. The thrombolytic activities of alteplase and urokinase, however, were additive. Similarly, the combination of urokinase with saruplase had an additive thrombolytic effect in our in vitro model. The effects of alteplase and saruplase were synergistic at a molar ratio of 1:4.7.
Spiecker
M
M
II. Medical Clinic, Johannes Gutenberg-Universität, Mainz, Germany. mwspiecker@bics.bwh.harvard.edu
Heinke
B
B
Meyer
J
J
Darius
H
H
D000328:Adult; D004357:Drug Synergism; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006801:Humans; D016285:Iloprost / Q000494:pharmacology*; D008297:Male; D011465:Prostaglandins, Synthetic / Q000494:pharmacology; D013300:Streptokinase / Q000494:pharmacology; D010959:Tissue Plasminogen Activator / Q000494:pharmacology; D014568:Urokinase-Type Plasminogen Activator / Q000494:pharmacology
D005343:Fibrinolytic Agents; D011465:Prostaglandins, Synthetic; C039188:taprostene; D011464:Epoprostenol; D013300:Streptokinase; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; D016285:Iloprost