Summary
Experimental data obtained by magnetic resonance imaging and photographing clot dissolution
in vitro have shown that whole blood clots dissolve almost two orders of magnitude
faster when urokinase is introduced into the clot by pressure induced permeation than
when its access is limited to diffusion. In view of these findings, two mathematical
models have been developed that quantitatively link the enzymatic and transport properties
of the fibrinolytic system to the velocity of thrombolysis. Without a pressure gradient
across the thrombus, the plasminogen activator molecules diffuse into the thrombus
through the blood-thrombus boundary plane. The blood-thrombus boundary slowly moves
inwards due to thrombolysis that is spatially restricted to a relatively narrow zone.
The velocity of thrombolysis is primarily limited by the diffusion constants of the
plasminogen activator and plasmin. In contrast, when plasminogen activator is rapidly
distributed along the thrombus by pressure induced bulk flow, lysis occurs at each
segment of the thrombus after a lag period that is due to plasmin activation and sufficient
fibrin degradation. The lag time is determined primarily by the catalytical properties
of the plasminogen activator and plasmin. The mathematical models with the observations
of the clot boundaries during lysis permit the characterization of plasmin action
on the fibrin network.
