人工心脏脉动工作模式调控动脉内皮功能及相关血流动力学机制的体外模型研究

连续流人工心脏是治疗终末期心衰的设备。其辅助血泵在恒定转速模式下产生非生理性血流并导致内皮功能失调，而脉动血泵转速可增加动脉血流和血压的脉动性，改善动脉内皮功能。然而，血泵转速的不同脉动工作模式差异调控动脉内皮功能的规律及其机制尚不明确，导致血泵转速工作模式的优化选择缺乏依据。鉴于体外模型能模拟且适于监控细胞微环境信号，本项目利用体外模型研究人工心脏脉动工作模式调控动脉内皮功能及相关的血流动力学机制。首先，通过设计和构建体外模拟循环系统研究人工心脏泵速的不同脉动工作模式与壁面剪应力、血压、牵张应变信号之间的对应关系；其次，搭建能够模拟上述泵速条件下血流动力学信号微环境的微流控内皮细胞培养模型；最后，利用该模型探索上述血流动力学信号的改变差异调控内皮功能的规律及其血流动力学机制。本项目将为连续流人工心脏优化选择泵速工作模式提供科学依据。

Continuous flow artificial hearts have been the devices for the treatment of end-stage heart failure. Its assisted blood pump can generate non-physiologic blood flow and cause endothelial dysfunction due to the constant pump speed. In contrast, the pulsatile pump speed can increase pulsatility of arterial blood flow and pressure, in order to improve arterial endothelial function. However, currently the law and related mechanisms of differentially regulating arterial endothelial function based on the different pulsatile working modes of the pump speed, is still unclear, leading to the lack of basis for the optimal selection of working modes of the pump speed. In view of the fact that the in vitro model can be used to simulate and monitor microenvironmental signals for cells, this project uses in vitro model to study on the arterial endothelial function modulated by pulsatile working modes of the artificial hearts and the related hemodynamic mechanisms. First, an in vitro mock circulatory system is designed and established, to study the corresponding relationship between different pulsatile working modes of the pump speed for the artificial hearts, and the signals of wall shear stress, blood pressure, and strain. Second, a microfluidic endothelial cell culture model is built, which can simulate the microenvironment based on the previously mentioned hemodynamic signals under the conditions of the above pulsatile pump speed. Finally, this microfluidic endothelial cell culture model could be used to explore the law and hemodynamic mechanisms of differentially regulating the endothelial function based on the changes in the above hemodynamic signals. This study could provide the scientific basis for the optimal selection of working modes of the pump speed for the continuous flow artificial hearts.