Abstract
The conversion of single chain urokinase-type plasminogen activator (scu-PA) to two chain urokinase-type plasminogen activator (tcu-PA) during lysis of normal and tissue-type plasminogen activator (t-PA) pre-treated clots by scu-PA was examined using a combined ELISA assay system which selectively measures either scu-PA or tcu-PA in plasma. At fibrin-specific doses, conversion did not exceed 20% against normal clots. Conversion was found to be dose-dependent and correlated with fibrinolysic efficiency. Against t-PA pre-treated clots the efficacy of lysis by scu-PA, as measured by the length of the lag-phase and maximum rate of lysis, was increased and was accompanied by 30% conversion of scu-PA to tcu-PA. An infusion of tcu-PA equivalent to that generated from scu-PA in the above experiments induced 70% less fibrinolysis and 25% more fibrinogenolysis. These findings indicate that local activation of scu-PA on the fibrin surface induces far more lysis and less non-specific effects than systemic conversion to tcu-PA, and that local activation is well correlated with scu-PA lytic efficiency.
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