Annals of biomedical engineering
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Comparative Study
Real-time measurement of lysis of mural platelet deposits by fibrinolytic agents under arterial flow.
An in vitro whole blood reperfusion model was employed to quantify: (a) initial rates of lysis of mural platelet deposits from flowing blood onto fibrin-coated surfaces and (b) plasmin-mediated consumption of plasma plasminogen and fibrinogen, by recombinant tissue-type plasminogen activator (rt-PA) and two t-PA variants, KHRR 296-299 AAAA (K-tPA) and T103N, N117Q, KHRR 296-299 AAAA (TNK-tPA), at wall shear rates of either 500 or 1000 s(-1). K- and TNK-tPA are more fibrin-specific than rt-PA, and are also resistant to inactivation by plasminogen activator inhibitor-1 (PAI-1). At 500 s(-1), no agent showed significant lysis of mural platelet deposits on fibrin, even at concentrations as high as 10 microg/ml of blood. ⋯ On the contrary, rt-PA at 1 microg/ml revealed slight fibrinogenolysis that became extensive at 10 microg/ml. This study demonstrates the potential use of an in vitro model, that mimics the in vivo hemodynamic environment, in evaluating the performance of thrombolytic agents. The data suggest that: (a) adequate flow must accompany fibrinolysis for successful embolization, and (b) the TNK variant may lyse annular thrombi after recanalization, at least as efficiently as rt-PA does, while causing lesser defect of systemic hemostasis.