血流作用下血管外损伤血小板聚集的数学模型
A Mathematical Model of Platelet Aggregation in an Extravascular Injury Under Flow
摘要：
我们提出了血管外损伤中血流介导的主要止血的第一个数学模型，该模型可以跟踪从初始沉积到闭塞的过程。该模型由描述血小板聚集（粘附和凝聚）、可溶性激动剂依赖性血小板活化和通过损伤的血液流动的常微分方程（ODE）系统组成。血小板聚集体的形成增加了流经损伤的阻力，这是使用斯托克斯-布林克曼方程建模的。来自模拟实验（微流体流动）和偏微分方程模型的数据告知了在血小板粘附、凝聚和活化的ODE模型描述中使用的参数值。该模型预测在一定范围的流动和血小板活化条件下的损伤闭塞。模拟测试剪切和激活率的影响，导致延迟闭塞和聚集体的异质性。这些结果验证了我们的假设，即流动介导的稀释激活化学ADP阻碍聚集体的发展。这种新的建模框架可以扩展到包括更多的血小板活化机制以及凝血的生化反应的添加，从而产生计算效率高的高通量筛选工具。
英文摘要：
We present the first mathematical model of flow-mediated primary hemostasis in an extravascular injury, which can track the process from initial deposition to occlusion. The model consists of a system of ordinary differential equations (ODE) that describe platelet aggregation (adhesion and cohesion), soluble-agonist-dependent platelet activation, and the flow of blood through the injury. The formation of platelet aggregates increases resistance to flow through the injury, which is modeled using the Stokes-Brinkman equations. Data from analogous experimental (microfluidic flow) and partial differential equation models informed parameter values used in the ODE model description of platelet adhesion, cohesion, and activation. This model predicts injury occlusion under a range of flow and platelet activation conditions. Simulations testing the effects of shear and activation rates resulted in delayed occlusion and aggregate heterogeneity. These results validate our hypothesis that flow-mediated dilution of activating chemical ADP hinders aggregate development. This novel modeling framework can be extended to include more mechanisms of platelet activation as well as the addition of the biochemical reactions of coagulation, resulting in a computationally efficient high throughput screening tool.
机构、总结、中文摘要均由AI分析而来，可能存在错误，请以论文正文为准。
