Abstract
Could the fibrinolytic activity of autogenous vein grafts be enhanced by the luminal application of a plasminogen activator such as urokinase? To understand the effects of pharmacologic concentrations of urokinase-type plasminogen activator on endothelial fibrinolytic activity, the authors exposed the luminal surface of paired fresh human saphenous veins to urokinase 500 U/mL or control solutions. To measure the fibrinolytic activity of intact endothelium, a new assay system was devised in which vein pieces were suspended in solution and the supernatant was assayed for plasmin activity by use of a chromogenic substrate. Net fibrinolytic activity (including the effects of plasma inhibitors) was estimated by performing the assay in plasma, while total fibrinolytic activity was estimated by using a plasma-free assay with purified plasminogen as the substrate.
When veins were briefly exposed to urokinase, their net and total fibrinolytic activities were very significantly increased (P < 0.0001) compared with controls. High versus low molecular weight urokinase showed equivalent effects. These results suggest that the exposure of intact endothelium to exogenous urokinase can significantly enhance the subsequent endothelial-dependent fibrinolytic activity of vein grafts, at least temporarily.
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