Summary
We have investigated the effects of diffusive and convective transport on fibrinolysis.
Using a constant pressure drop (ΔP/L) from 0 to 3.7 mmHg/cm-clot to drive fluid permeation,
various regimes of lytic agents were delivered into fine and coarse fibrin gels (3
mg/ml) and whole blood clots. Using plasmin (1 μM) delivered into pure fibrin or urokinase
(1 μM) delivered into glu-plasminogen (2.2 μM)-laden fibrin, the velocity at which
a lysis front moved across fibrin was greatly enhanced by increasing ΔP/L. Lysis of
fine and coarse fibrin clots by 1 μM plasmin at ΔP/L of 3.67 and 1.835 mmHg/cm-clot,
respectively, led to a 12-fold and 16-fold enhancement of the lysis front velocity
compared to lysis without pressure-driven permeation. For uPA-me-diated lysis of coarse
fibrin at ΔP/L = 3.67 mmHg/cm-clot, the velocity of the lysis front was 25-fold faster
than the lysis front velocity measured in the absence of permeation. Similar permeation-enhanced
phenomenon was seen for the lysis of whole blood clots. Without permeation, the placement
of a lytic agent adjacent to a clot boundary led to a reaction front that moved at
a velocity dependent on the concentration of plasmin or uPA used. Overall, these studies
suggest that transport phenomena within the clot can play a major role in determining
the time needed for reperfusion during fibrinolysis.
