Abstract
The fibrin agarose plate assay is widely used in the detection of thrombolysis efficacy. However, a rigorous mathematical model for analyzing data or comparing activities of different thrombolytics has been absent. This study investigated the relationship between thrombolysis radius, R, and diffusion time, t, of molecular medicines in an agarose hydrogel system by deriving a model based on Fick’s law and experimental verification by the fibrin agarose plate assay method. The theoretical results showed that a plot of log(R) versus log(t) has a linear curve with the slope of 1/2 and this was verified by experimental results using urokinase as a modeling agent. Moreover, it was found that \(\frac{R} {{\sqrt t }}\) is constant for a specific thrombolytic and can be used as a parameter for evaluating activities of different thrombolytics. The theoretical model has potential for improving the understanding of mechanisms involved in molecular medicine diffusion and offers benefits for thrombolytic therapy.
Highlights
It was found that is constant for a specific thrombolytic and can be used as a parameter for t evaluating activities of different thrombolytics
The theoretical model has potential for improving the understanding of mechanisms involved in molecular medicine diffusion and offers benefits for thrombolytic therapy
Thrombolytic therapy has been a major treatment of thrombosis to date, using thrombolytics such as streptokinase (SK) [6], urokinase (UK) [7] or its mutant [8] and tissue type plasminogen activator (t-PA) [3,7] to dissolve thrombi
Summary
Thrombosis, such as acute myocardial infarction [1], pulmonary embolism [2], ischemic stroke [3] and peripheral arterial occlusions [4], is a severe clinical condition in which thrombus forms in a critical blood vessel [5]. The fibrin agarose plate assay (FAPA) has been widely used to determine the fibrinolytic activity of thrombolytics, due to its good reproducibility, specificity, low cost and high sensitivity [9]. The general procedure of FAPA is to inject thrombolytic agents such as SK, UK or t-PA, into a fibrin agarose plate. The thrombolytics directly catalyze the conversion of plasminogen into plasmin that, in turn, degrades fibrin and subsequently leads to the appearance of fibrinolytic discs in the agarose gel plate. Establishing a mathematical computing model is of critical importance
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