Plasminogen acceleration of urokinase thrombolysis.
PURPOSE: A relative deficiency of plasminogen within the thrombus may be the rate limiting factor in clot lysis. METHODS: To investigate this hypothesis, we used an in vitro perfusion system and expanded polytetrafluoroethylene graft segments filled with radiolabeled human thrombus. Three groups of five perfusions were compared: (1) urokinase infusion (333 IU/min) into clots laced with buffer, (2) urokinase infusion (333 IU/min) into clots laced with plasminogen (44 CU), and (3) control, D5W infusion into clots laced with buffer. Two end points were measured over time: the amount of lysed thrombus and the flow through the graft. RESULTS: Urokinase infusion resulted in augmented flow through the graft when compared with control (p < 0.05). Lacing with plasminogen resulted in more rapid restoration of flow when compared with urokinase infusion alone (p < 0.05). Similarly, the rate of clot dissolution was significantly greater in plasminogen-laced thrombi (p < 0.05) when compared with the control and urokinase groups. Embolization of particles of thrombus was uniformly observed in the urokinase group, resulting in a temporary decrease in flow through the thrombosed graft. This event characteristically occurred after 60 minutes of infusion but was never seen in the urokinase/plasminogen treatment group. CONCLUSIONS: These results suggest that plasminogen supplementation of urokinase thrombolysis may result in significant clinical benefits with respect to the rate of clot lysis and the uniformity of clot dissolution with a lower likelihood of secondary embolization.
Stroughton, J; Ouriel, K; Shortell, CK; Cho, JS; Marder, VJ
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