Transport phenomena and clot dissolving therapy: an experimental investigation of diffusion-controlled and permeation-enhanced fibrinolysis.
We have investigated the effects of diffusive and convective transport on fibrinolysis. Using a constant pressure drop (delta P/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 microM) delivered into pure fibrin or urokinase (1 microM) delivered into glu-plasminogen (2.2 microM)-laden fibrin, the velocity at which a lysis front moved across fibrin was greatly enhanced by increasing delta P/L. Lysis of fine and coarse fibrin clots by 1 microM plasmin at delta P/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-mediated lysis of coarse fibrin at delta P/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.
Department of Chemical Engineering, State University of New York, Buffalo 14260.
J H
JH
Wu
K
K
Siddiqui
S L
SL
Diamond
D001692:Biological Transport / Q000187:drug effects; D004058:Diffusion; D005337:Fibrin / Q000378:metabolism; D005341:Fibrinolysin / Q000494:pharmacology; D005342:Fibrinolysis / Q000187:drug effects*; D005782:Gels; D006801:Humans; D010539:Permeability; D015912:Thrombolytic Therapy; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D005782:Gels; D005337:Fibrin; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator