调控腔内移植物近端构型预防逆行撕裂A型夹层的生物力学研究

Endovascular stent-graft repair was introduced as an important alternative to conventional open surgery for the treatment of descending aortic dissections. As the rapid development of the endovascular treatment of aortic dissection, stent-graft has been planted into ascending aorta and aortic arch. But the development of stent-graft cannot match the great progress of the endovascular procedure. Recently, some studies reported various complications caused by stent-grafts, among which, retrograde type A dissection (RTAD) is not a rare complication and with high mortality. Despite of its importance, investigation on how to prevent RTAD has been least carried out. .As an alien objective, the stent-graft is much stiffer than the host arterial tissues. Moreover, when it is deployed, it can induce high mechanical stress concentrations over the contact region, which mediate the aortic wall injury. Our previous study indicate that different configuration of the stent can change the wall stress distribution. Therefore, the hypothesis of this study is that: the high stress concentration in the curved aortic segment induced by the stent-graft can be diminished by manipulating the stent configuration. And the biologic reaction of the contacting aortic wall is also ameliorated accordingly..This study will be conducted in three aspects: First, retrospectively analyze the clinical data of RTAD to sieve out the risk factors on aortic morphology and stent-graft configuration.Thus to determine the targets and make strategy for following mechanical test. Second, accurately calculate and depict the stress concentration over the contact region induced by different stent configuration, using photoelastic study. Combined with ex-vivo mechanical analyses of stent-graft, the modified stent configuration can be recognized. It should have enough circumferencial strength but generating minimal and adqulis wall stress. Third, use the modified stent-graft on the animal model, test and analyze the biomechanical effects on the aorta as a whole, as well as on the local artery tissue of different contact regions. Then, integrating these results into a “stent configuration — wall stress — aortic biological reaction” effect model, which will help to find out the histologic evidence of the mechanical effects, and to identify the best proximal configuration of stent-graft for respective aortic dissection..This study will provide important in-sight on the mechanism of aortic injury induced by different wall stress distribution. And it will be essential for optimizing the configuration of proximal part of the stent-graft to preferably match the aortic dissection morphology. As biomechanical rationales of endovascular treatment of aortic dissection, the outcomes of this study may have great clinical potential.

主动脉夹层腔内治疗后，腔内移植物近端逆行撕裂A型夹层（RTAD）是影响治疗预后的主要并发症之一，如何预防亟需研究。腔内移植物近端对主动脉管壁的损伤是RTAD的直接原因。我们前期研究表明：管壁应力大小及分布与管壁损伤的血管重构密切相关，而改变腔内移植物构型可影响管壁应力；据此提出：是否可建立腔内移植物构型-管壁应力-管壁生物学反应的效应关系模型，通过调控腔内移植物构型来减轻管壁损伤？拟开展以下研究：①分析RTAD临床风险，筛选夹层形态学和腔内移植物关键构型参数，进行分层量化和合理组合，形成差异构型腔内移植物测试方案；②通过光弹性实验和体外力学测试，研究差异构型腔内移植物产生的管壁应力分布，筛选优化构型；③将优化构型腔内移植物应用于动物模型，建立管壁应力-管壁生物学反应关系模型，验证其生物力学效能。本研究有助于阐明腔内移植物近端构型的生物力学效应，为提高主动脉夹层腔内治疗的安全性提供实验依据。

主动脉夹层这一危重疾病在中国有发病率逐年上升的趋势。其腔内治疗已成为主要治疗方式之一；目前临床上的热点问题是如何进一步提高腔内治疗远期的安全性和有效性。由于主动脉夹层管壁的薄弱性仍无有效方法去调控强化，要实现更好的远期安全性和有效性，目前的解决方案就是减轻腔内移植物对主动脉夹层管壁的损伤，从而预防近端再发夹层（RTAD）等临床并发症。本研究通过深入研究，取得以下主要研究发现：.2.1 通过回顾性临床研究，筛选发现支架移植物近端放大率（oversize）与RTAD发生密切相关：oversize率越大，RTAD风险越高（术前oversize率122.7±4.9% vs 109.9±3.4%, p＜0.05）；.2.2本研究采用光弹实验、计算机有限元分析、体外力学测试相结合的方法，筛选发现支架移植物构型和支架的力学作用之间的对应关系：丝径对径向压强的影响最大；螺距对径向压强的影响基本可以忽略；波头数对径向压强都会有影响，影响有限；波头数增加，径向压强减小；波头数减少，径向压强增大；波幅值对径向压强有影响，影响也有限，但强于波头数对压强的影响。波幅增大，径向压强减小；波幅减小，径向压强增大。.2.3通过大动物夹层模型的腔内隔绝术模拟治疗并观察管壁的炎症反应等，发现：越大的支架移植物作用力（如较大的放大率）植入实验动物体内后，主动脉管壁局部炎症因子（hsCRP、IL-1、IL-6、TNF-α）有差异，放大率越大的主动脉标本炎症因子升高的程度越高。.2.4 通过对以上结果的综合分析，最终筛选得到能够实现既达到良好隔绝，又不增加RTAD风险的目标的支架移植物近端构型：波头数分别为大弯侧4波头+小弯侧8波头，波幅为10mm。.本项目根据主动脉夹层近端锚定区的基本形态学特征，改变腔内移植物支架骨架构型的若干关键参数（支架丝粗细、支架口径、冠数、波幅等），分析其在主动脉不同部位（升主动脉-主动脉弓-降主动脉起始段）产生的管壁应力，并在动物模型上观察不同管壁应力引起的管壁生物学反应，最终建立起腔内移植物支架构型关键参数产生的管壁应力和管壁生物学反应的效应关系模型。