Key Laboratory of Biomechanics and Mechanobiology (Beihang University), Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, 100083, China.
Key Laboratory of Biomechanics and Mechanobiology (Beihang University), Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, 100083, China.
Comput Biol Med. 2023 Sep;164:107379. doi: 10.1016/j.compbiomed.2023.107379. Epub 2023 Aug 14.
To develop a mathematical model for predicting shear-induced von Willebrand factor (vWF) function modification which can be used to guide ventricular assist devices (VADs) design, and evaluate the damage of high molecular weight multimers (HMWM)-vWF in VAD patients for reducing clinical complications.
Mathematical models were constructed based on three morphological variations (globular vWF, unfolded vWF and degraded vWF) of vWF under shear stress conditions, in which parameters were obtained from previous studies or fitted by experimental data. Different clinical support modes (pediatric vs. adult mode), different VAD operating states (pulsation vs. constant mode) and different clinical VADs (HeartMate II, HeartWare and CentriMag) were utilized to analyze shear-induced damage of HMWM-vWF based on our vWF model. The accuracy and feasibility of the models were evaluated using various experimental and clinical cases, and the biomechanical mechanisms of HMWM-vWF degradation induced by VADs were further explained.
The mathematical model developed in this study predicted VAD-induced HMWM-vWF degradation with high accuracy (correlation with experimental data r > 0.99). The numerical results showed that VAD in the pediatric mode resulted in more HMWM-vWF degradation per unit time and per unit flow rate than in the adult mode. However, the total degradation of HMWM-vWF is less in the pediatric mode than in the adult mode because the pediatric mode has fewer times of blood circulation than the adult mode in the same amount of time. The ratio of HMWM-vWF degradation was lower in the pulsation mode than in the constant mode. This is due to the increased flushing of VADs in the pulsation mode, which avoids prolonged stagnation of blood in high shear regions. This study also found that the design feature, rotor size and volume of the VADs, and the superimposed regions of high shear stress and long residence time inside VADs affect the degradation of HMWM-vWF. The axial flow VADs (HeartMate II) showed higher degradation of HMWM-vWF compared to centrifugal VADs (HeartWare and CentriMag). Compared to fully magnetically suspended VADs (CentriMag), hydrodynamic suspended VADs (HeartWare) produced extremely high degradation of HWMW-vWF in its narrow hydrodynamic clearance. Finally, the study used a mathematical model of HMWM-vWF degradation to interpret the clinical statistics from a biomechanical perspective and found that minimizing the rotating speed of VADs within reasonable limits helps to reduce HWMW-vWF degradation. All predicted conclusions are supported by the experimental and clinical data.
This study provides a validated mathematical model to assess the shear-induced degradation of HMWM-vWF, which can help to evaluate the damage of HMWM-vWF in patients implanted with VADs for reducing clinical complications, and to guide the optimization of VADs for improving hemocompatibility.
开发一种预测剪切诱导的血管性血友病因子（vWF）功能改变的数学模型，可用于指导心室辅助装置（VAD）的设计，并评估 VAD 患者中高分子量多聚体（HMWM）-vWF 的损伤，以减少临床并发症。
根据 vWF 在剪切应力条件下的三种形态变化（球形 vWF、展开的 vWF 和降解的 vWF）构建数学模型，其中参数来自先前的研究或通过实验数据拟合。利用不同的临床支持模式（儿科模式与成人模式）、不同的 VAD 工作状态（搏动模式与持续模式）和不同的临床 VAD（HeartMate II、HeartWare 和 CentriMag），基于我们的 vWF 模型分析剪切诱导的 HMWM-vWF 损伤。使用各种实验和临床病例评估模型的准确性和可行性，并进一步解释 VAD 引起的 HMWM-vWF 降解的生物力学机制。
本研究开发的数学模型能够高度准确地预测 VAD 诱导的 HMWM-vWF 降解（与实验数据的相关性 r>0.99）。数值结果表明，儿科模式下单位时间和单位流量内的 HMWM-vWF 降解比成人模式多。然而，由于儿科模式在相同时间内的血液循环次数比成人模式少，因此儿科模式中的 HMWM-vWF 总降解量较少。搏动模式下的 HMWM-vWF 降解率比持续模式低。这是由于搏动模式下 VAD 的冲洗增加，避免了血液在高剪切区域的长时间停滞。本研究还发现，VAD 的设计特征、转子大小和体积，以及 VAD 内高剪切应力和长驻留时间的叠加区域，都会影响 HMWM-vWF 的降解。轴流 VAD（HeartMate II）比离心 VAD（HeartWare 和 CentriMag）显示出更高的 HMWM-vWF 降解。与完全磁悬浮 VAD（CentriMag）相比，液力悬浮 VAD（HeartWare）在其狭窄的液力间隙中产生了极高的 HWMW-vWF 降解。最后，该研究使用 HMWM-vWF 降解的数学模型从生物力学角度解释临床统计数据，发现合理限制 VAD 的转速有助于减少 HWMW-vWF 降解。所有预测的结论都得到了实验和临床数据的支持。
本研究提供了一种经过验证的数学模型来评估 HMWM-vWF 的剪切诱导降解，这有助于评估 VAD 植入患者中 HMWM-vWF 的损伤，以减少临床并发症，并指导 VAD 的优化以提高血液相容性。
