Endogenous Tissue Plasminogen Activator Enhances Fibrinolysis and Limits Thrombus Formation in a Clinical Model of Thrombosis

OBJECTIVE—Using a clinical model of deep arterial injury, we assessed the ability of exogenous and endogenous tissue plasminogen activator (t-PA) to limit acute in situ thrombus formation. APPROACH AND RESULTS—Ex vivo thrombus formation was assessed in the Badimon chamber at low and high shear rates in 2 double-blind randomized cross-over studies of 20 healthy volunteers during extracorporeal administration of recombinant t-PA (0, 40, 200, and 1000 ng/mL) or during endogenous t-PA release stimulated by intra-arterial bradykinin infusion in the presence or absence of oral enalapril. Recombinant t-PA caused a dose-dependent reduction in thrombus area under low and high shear conditions (P