INNER CLOT DIFFUSION AND PERMEATION DURING FIBRINOLYSIS
INNER CLOT DIFFUSION AND PERMEATION DURING FIBRINOLYSIS
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DOI：
10.1016/s0006-3495(93)81314-6
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发表时间：
1993-12-01
影响因子：
3.4
通讯作者：
ANAND, S
中科院分区：
文献类型：
--
作者：
DIAMOND, SL;ANAND, S
采用多组分对流扩散方程，考虑均相反应和非均相吸附反应，建立了纤维蛋白溶解模型。纤维蛋白酶是溶解性固定相，纤溶酶原、组织纤溶酶原激活物（tPA）、尿激酶（uPA）和纤溶酶是可溶性移动的物质。该模型是基于纤维蛋白纤维和原纤维结构的精确分子描述，不包含可调参数和一个从实验中估计的唯象参数。该模型可以预测裂解前沿移动通过纤维蛋白凝块（细或粗纤维）的各种密度下使用uPA和tPA不同的管理制度。我们预测，压力驱动的渗透是主要的运输方式，允许在临床情况下的动力学显着的溶栓。在没有渗透的情况下，凝块溶解将受到严重的扩散限制，并且将需要数百分钟。在渗透条件下，tPA对纤维蛋白的吸附是一个非平衡过程，倾向于用tPA前负荷凝块。设计最佳溶栓药物的蛋白质工程努力可能会受到溶栓过程中发生的渗透过程的影响。
A model of fibrinolysis was developed using multicomponent convection-diffusion equations with homogeneous reaction and heterogeneous adsorption and reaction. Fibrin is the dissolving stationary phase and plasminogen, tissue plasminogen activator (tPA), urokinase (uPA), and plasmin are the soluble mobile species. The model is based on an accurate molecular description of the fibrin fiber and protofibril structure and contains no adjustable parameters and one phenomenological parameter estimated from experiment. The model can predict lysis fronts moving across fibrin clots (fine or coarse fibers) of various densities under different administration regimes using uPA and tPA. We predict that pressure-driven permeation is the major mode of transport that allows for kinetically significant thrombolysis during clinical situations. Without permeation, clot lysis would be severely diffusion limited and would require hundreds of minutes. Adsorption of tPA to fibrin under conditions of permeation was a nonequilibrium process that tended to front load clots with tPA. Protein engineering efforts to design optimal thrombolytics will likely be affected by the permeation processes that occur during thrombolysis.