冠脉分叉部位专用血管支架药物涂层的缓释规律及优化研究

Coronary bifurcation stenting has a much higher rate of restenosis than the stenting of nonbifurcation coronary arteries. The applicant believes that there is a fundamental difference in hemodynamic characteristics between coronary bifurcations and other nonbifurcation coronary arteries, which is the main reason for the high restenosis rate of coronary bifurcation stenting. This kind of difference in hemodynamic characteristics may result in significant disparity in drug release pattern of a drug-eluting stent. The proposed research project is aimed to investigate the hemodynamic characteristics and the resulted drug release pattern in coronary bifurcations with drug-eluting stents implanted, so as to provide a theoretical basis for the optimization of drug coating design of drug-eluting stents dedicated to coronary bifurcation stenting strategies. To do so, the following computational and experimental research works have been designed:.(1) Human coronary artery bifurcation model with virtual realilty drug-eluting stents implanted will be re-constructed from MRI images Then, the hemodynamic characteristics and drug release pattern in the model (drug release rate, concentration distribution of the drug in the vessel lumen etc) will be investigated numerically. An in vitro model of coronary bifurcation stenting will be set up to study the adhesion distribution of platelets and monocytes; (2) Based on the results of work (1), the configuration and drug coating strategy of stents for coronary bifurcation stenting will be optimized, enabling the drug-eluting stents release drug according to the local hemodynamic characteristics in order to minimize the restenosis and the acute thrombosis in the bifurcation; (3) The aformentined optimal drug coating of the drug-eluting stent will be validated using an in vitro phantom experiment.

冠脉分叉部位支架介入治疗的再狭窄率远高于其它部位。申请人认为，冠脉分叉处与其它部位的血流动力学特性有着根本区别，这是导致其再狭窄率高的重要原因。这种血流动力学特性的差异会导致药物涂层支架在冠脉分叉处的缓释规律不同于冠脉其它部位。本项目旨在研究支架植入后冠脉分叉处的血流动力学特性及其药物涂层支架的缓释规律，为专用于冠脉分叉处的支架药物涂层优化提供理论依据。本项目将用计算机数值模拟和体外实验的方法开展以下工作：（1）建立基于医学影像的人体冠脉分叉模型、研究药物涂层支架植入后血管分叉部位的血流动力学特性及其药物缓释规律（药物释放速度、药物随时间和空间的分布等）。建立体外实验模型，研究支架植入后血小板和单核细胞粘附的规律；（2）基于研究内容（1），对支架的构型和药物涂层进行优化设计，以使药物能根据当地血流动力学特性按需有规律地进行释放；（3）用体外实验来验证支架构型和药物涂层优化设计的效果。

本项目针对冠脉分叉部位支架介入治疗的再狭窄问题，通过计算机数值模拟和体外实验的方法，研究了支架植入后冠脉分叉处的血流动力学特性及药物涂层支架的缓释规律。具体开展了如下4个方面的研究工作：1）建立了人体冠脉分叉模型，研究了支架植入后血管分叉部位的血流动力学特性，发现血管分叉处靠外侧壁面，血流非常紊乱，而支架的植入更加剧了这种紊乱程度。2）研究了分叉血管血流特征对药物传输的影响，发现血管分叉部位，血流发生紊乱，在分叉处外侧壁面处形成漩涡区，从而导致此处的药物集聚量增多。3）通过体外实验，研究了流动特征、血管管径变化对血小板活化和粘附的影响，发现旋动流能够通过影响血小板在血管内壁的黏附从而抑制急性血栓形成。4）基于数值计算分析结果，提出了一种具有非均匀释放率的药物洗脱支架。项目在基本按计划完成研究任务的同时又有所延伸，关注了血液非牛顿特性对药物洗脱支架中药物传输的影响、药物洗脱支架+金属裸支架（DES+BMS）介入治疗中的药物传输问题等。此外，项目组成员还开展了广泛的学术交流活动。