Georgia Institute of Technology, GWW School of Mechanical Engineering, Atlanta, Georgia, USA.
Biophys J. 2013 Jul 16;105(2):502-11. doi: 10.1016/j.bpj.2013.05.049.
Thrombus formation over a ruptured atherosclerotic plaque cap can occlude an artery with fatal consequences. We describe a computational model of platelet transport and binding to interpret rate-limiting steps seen in experimental thrombus formation over a collagen-coated stenosis. The model is used to compute shear rates in stenoses with growing boundaries. In the model, moving erythrocytes influence platelet transport based on shear-dependent enhanced diffusivity and a nonuniform platelet distribution. Adhesion is modeled as platelet-platelet binding kinetics. The results indicate that observed thrombus growth rates are limited by platelet transport to the wall for shear rates up to 6000 s(-1). Above 7000 s(-1), the thrombus growth rate is likely limited by binding kinetics (10(-4) m/s). Thrombus growth computed from these rate-limiting steps match the thrombus location and occlusion times for experimental conditions if a lag time for platelet activation is included. Using fitted parameters, the model is then used to predict thrombus size and shape at a higher Reynolds number flow consistent with coronary artery disease.
破裂的动脉粥样硬化斑块上的血栓形成可能会阻塞动脉，导致致命后果。我们描述了一个血小板运输和结合的计算模型，以解释在胶原涂层狭窄处实验性血栓形成中观察到的限速步骤。该模型用于计算具有生长边界的狭窄处的剪切率。在该模型中，运动的红细胞会根据剪切依赖性增强的扩散率和血小板分布的不均匀性影响血小板的运输。黏附被建模为血小板-血小板结合动力学。结果表明，对于剪切速率高达 6000 s(-1)的情况，观察到的血栓生长速率受到血小板向壁面运输的限制。在 7000 s(-1)以上，血栓生长速率可能受结合动力学限制（10(-4) m/s）。如果包括血小板激活的滞后时间，则根据这些限速步骤计算出的血栓生长与实验条件下的血栓位置和阻塞时间相匹配。使用拟合参数，然后使用该模型预测与冠状动脉疾病一致的较高雷诺数流动条件下的血栓大小和形状。
