A novel mathematical model of activation and sensitization of platelets subjected to dynamic stress histories.
A novel mathematical model of activation and sensitization of platelets subjected to dynamic stress histories.
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DOI：
10.1007/s10237-013-0469-0
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发表时间：
2013-11
影响因子：
3.5
通讯作者：
Bluestein, Danny
中科院分区：
文献类型：
--
作者：
Soares, Joao S.;Sheriff, Jawaad;Bluestein, Danny
关键词：
血液再循环装置，如心室辅助装置和人工心脏瓣膜，具有血栓栓塞并发症的负担，需要复杂的终身抗凝治疗，并具有固有的出血风险。在这些装置中发生的病理性血流模式会长期激活血小板，优化其血栓形成性能需要血流诱导血小板激活模型的发展。然而，现有的模型是基于经验相关性，使用在一定暴露时间内恒定水平的剪切应力作为机械血小板活化因素的成熟幂律范式。这些模型受到其应用范围的限制，并且没有考虑到其他相关现象，例如加载率依赖性和血小板对高应力条件的敏感性，这些现象表征了设备中的动态流动条件。通过开发一类新的现象应力诱导血小板活化模型，解决了这些限制，该模型将血小板活化率指定为整个应激历史的函数，并得出一个微分方程，可以直接积分来计算活化的累积水平。所提出的模型在恒定剪切应力条件下恢复到幂律，并且能够描述在血液循环装置中发现的各种高动态应力条件下的实验结果。该模型在模拟装置流动条件下进行了体外测试，与实验结果吻合良好。这个新模型提供了一个可靠和强大的数学工具，可以纳入计算流体动力学研究，以优化设计，以提高血液再循环装置的血栓形成性能的目标。
Blood recirculating devices, such as ventricular assist devices and prosthetic heart valves, are burdened by thromboembolic complications requiring complex and lifelong anticoagulant therapy with its inherent hemorrhagic risks. Pathologic flow patterns occurring in such devices chronically activate platelets, and the optimization of their thrombogenic performance requires the development of flow-induced platelet activation models. However, existing models are based on empirical correlations using the well-established power law paradigm of constant levels of shear stress during certain exposure times as factors for mechanical platelet activation. These models are limited by their range of application and do not account for other relevant phenomena, such as loading rate dependence and platelet sensitization to high stress conditions, which characterize the dynamic flow conditions in devices. These limitations were addressed by developing a new class of phenomenological stress-induced platelet activation models that specifies the rate of platelet activation as a function of the entire stress history and results in a differential equation that can be directly integrated to calculate the cumulative levels of activation. The proposed model reverts to the power law under constant shear stress conditions and is able to describe experimental results in response to a diverse range of highly dynamic stress conditions found in blood recirculating devices. The model was tested in vitro under emulated device flow conditions and correlates well with experimental results. This new model provides a reliable and robust mathematical tool that can be incorporated into computational fluid dynamic studies in order to optimize design, with the goal of improving the thrombogenic performance of blood recirculating devices.
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