Wu J H, Siddiqui K, Diamond S L
Department of Chemical Engineering, State University of New York, Buffalo 14260.
Thromb Haemost. 1994 Jul;72(1):105-12.
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.
我们研究了扩散和对流传输对纤维蛋白溶解的影响。使用从0到3.7 mmHg/cm - 凝块的恒定压降（ΔP/L）来驱动流体渗透，将各种溶解剂输送到细纤维蛋白凝胶和粗纤维蛋白凝胶（3 mg/ml）以及全血凝块中。使用输送到纯纤维蛋白中的纤溶酶（1 μM）或输送到富含谷氨酰胺 - 纤溶酶原（2.2 μM）的纤维蛋白中的尿激酶（1 μM），通过增加ΔP/L，溶解前沿穿过纤维蛋白的速度大大提高。在ΔP/L分别为3.67和1.835 mmHg/cm - 凝块时，1 μM纤溶酶对细纤维蛋白凝块和粗纤维蛋白凝块的溶解作用，与无压力驱动渗透的溶解相比，溶解前沿速度分别提高了12倍和16倍。对于在ΔP/L = 3.67 mmHg/cm - 凝块时uPA介导的粗纤维蛋白溶解，溶解前沿的速度比在无渗透情况下测量的溶解前沿速度快25倍。在全血凝块的溶解中也观察到了类似的渗透增强现象。在无渗透的情况下，将溶解剂放置在凝块边界附近会导致一个反应前沿，其移动速度取决于所用纤溶酶或uPA的浓度。总体而言，这些研究表明凝块内的传输现象在确定纤维蛋白溶解过程中再灌注所需时间方面可能起主要作用。
