Department of Biomedical Engineering, Health Sciences Center, T15-090, Stony Brook University, Stony Brook, NY, 11794-8151, USA.
Biomech Model Mechanobiol. 2013 Nov;12(6):1127-41. doi: 10.1007/s10237-013-0469-0. Epub 2013 Jan 29.
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.
血液再循环装置，如心室辅助设备和人工心脏瓣膜，存在血栓栓塞并发症的负担，需要进行复杂且终身的抗凝治疗，同时伴有出血风险。此类装置中存在的病理血流模式会导致血小板慢性激活，优化其血栓形成性能需要开发血流诱导的血小板激活模型。然而，现有的模型基于经验相关性，使用已建立的恒定剪切应力幂律范式，作为一定暴露时间内机械血小板激活的因素。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，例如加载速率依赖性和血小板对高应力条件的敏感性，这些现象是装置中动态血流条件的特征。通过开发一类新的现象学应力诱导血小板激活模型，可以解决这些局限性，该模型将血小板激活率指定为整个应力历史的函数，从而得出一个可以直接积分以计算累积激活水平的微分方程。在恒定剪切应力条件下，所提出的模型回归为幂律模型，并且能够描述对在血液再循环装置中发现的各种高度动态的应力条件的实验结果。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。该新模型提供了一种可靠且强大的数学工具，可以将其纳入计算流体动力学研究中，以优化设计，从而提高血液再循环装置的血栓形成性能。
