腔内移植物与主动脉管壁的相互作用及其对主动脉夹层腔内隔绝术预后的影响

Endovascular stent-graft repair was introduced as an important alternative to conventional open surgery for the treatment of aortic dissections. But studies reported various complications caused by stent-grafts, such as endoleaks, stent graft-induced new entry, which are not rare complications and with high mortalities. Despite of its importance, investigation on this aspect has been least carried out and the underlying mechanisms are still unknown. ..As an alien objective, the endograft is much stiffer than the host arterial tissues. Moreover, when it is deployed, it can induce high mechanical stress concentrations over the contact region. Therefore the hypothesis of this study is the high stress concentration induced by the dismatch between the endograft and the aortic wall, and the local hymodynamic effects response for the onset of complications...This study will be conducted in three aspects: First, retrospectively analyze the clinical data to sieve out the targets for following biomechanical analysis; Second, accurately calculate and depict the stress concentration over the contact region on cases with complications, by computational hemodynamic simulation and the mechanical analyses of the interaction between the endograft and the aortic wall. These analyses will explain the associations between morphological features and the subsequent clinical events; Third, according to above mechanical analyses, modify the configuration of the stent-graft and use it on the animal model of aortic dissection. Then, test and analyze the biomechanical effects on the aorta as a whole, as well as on the local artery tissue of different contact regions. At last, integrating these results into a hazard regression model will help to find out the histologic evidence of the mechanical and hymodynamic effects, and to identify the best stent-graft configuration for respective aortic dissection...This study will provide important in-sight on the mechanism of stent graft-related complications, and it will be essential for optimizing the stent-graft design to preferably match the aortic dissection configuration. As biomechanical rationales of endovascular treatment of aortic dissection, the outcomes of this study may have great clinical potential.

主动脉夹层是指血流撕裂主动脉壁，易发生主动脉破裂致死，病情凶险。血管腔内移植物隔绝裂口实现微创治疗，已成为除传统开放手术之外介入治疗主动脉夹层的重要方法，但内漏、移植物边缘再发夹层等不良预后严重阻碍这一新技术的发展。我们前期研究表明：腔内移植物放置于发生夹层的主动脉特定区域，其差异构型与管壁、血流相互作用产生的生物力学效应与不良预后密切相关，具体机制和调控效应亟待阐明。本项目拟：①分析临床资料，筛选不良预后的危险因素，为力学分析和干预提供关键靶点；②通过计算机模拟不良预后病例的流体-固体力学耦合分析，以及研究相应的管壁组织学和应力应变性质改变，阐明不良预后的生物力学机制；③在动物模型上检验根据力学模拟改进构型的腔内移植物预防不良预后的效能，从而得到并验证不良预后的风险评估模型。本研究有助于阐明腔内隔绝术后不良预后的发生机制，为进一步提高主动脉疾病微创介入治疗水平提供重要的科学依据。

随着腔内治疗技术的进步，应用腔内移植物微创介入治已能处理大部分主动脉夹层，但临床发现的不良预后（内漏、移植物引发再发夹层）严重阻碍了腔内隔绝术这一新技术的发展。本中心从腔内移植物机械力学损伤、血液动力学损伤和主动脉管壁应力三方面来开展研究。从流体-固体施加的力学影响、组织细胞改变和组织材料学强度改变的不同层面探索了导致不良预后的因素。.基于胸主动脉和主动脉夹层形态学数据库，筛选出真腔重度狭窄等腔内修复术不良预后的显著危险因素，建立了最佳风险比例评估模型。针对主动脉夹层管壁与正常主动脉管壁进行了材料学强度测试、病理组织学分析。采用体外移植物力学响应测试对同一直径和高度、不同波数的支架比较发现支架环高度越高，力学性能越弱。采用有限元分析计算不同部位主动脉夹层管壁应力发现移植物释放过程产生的偏差会对应力分布产生很大的影响。对主动脉夹层腔内修复术后发生不良预后的病例进行流固耦合分析发现：限制性裸支架能够明显地消除真腔狭窄段的剪切应力集中现象，使真腔在远期进一步扩张以达到良好形态学重构。在构建的动物疾病模型中应用差异构型的腔内移植物并进行干预发现，不同放大率的移植物其植入实验动物体内后主动脉管壁局部炎症因子存在差异。放大率越大的主动脉标本炎症因子升高的程度越高。并通过动物实验发现使用新型载药主动脉覆膜支架可以有效调控夹层管壁炎症，达到靶向治疗的目的。采用差异构型的腔内移植物、不同的腔内移植物应用方案，植入具有不同管壁条件的主动脉夹层动物模型中，验证根据移植物的生物力学效能，并据此改进腔内移植物的构型，使其能更好地匹配主动脉夹层的形态和管壁的生物学特点，在良好隔绝裂口的同时，又减轻管壁损伤，促进主动脉理想的远期重构。.本项目建立了腔内修复术后不良预后的风险评估模型，并形成了专适于治疗主动脉夹层的腔内移植物，将大大提高主动脉夹层微创介入治疗的水平。