Stanford B型主动脉夹层腔内隔绝术后再发破裂的生物力学机制研究

Endovascular stent-graft repair was introduced as an important alternative to conventional open surgery for the treatment of descending aortic dissections. But studies reported various complications caused by stent-grafts, among which, stent graft-induced new entry is not a rare complication and with high mortality. 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 endograft and the local hymodynamic effects response for the onset of new entry. .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 of new entry, 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 event; Third, according to above mechanical analyses, modify the configuration of the stent-graft and use it on the animal model of Stanford type B 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-induced new entry, 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.

主动脉夹层腔内隔绝术后，部分病例可在腔内移植物远、近端再发破裂，导致患者猝死，其发生发展的生物力学机制亟需研究。我们前期研究表明：腔内移植物与主动脉管壁的不匹配和再发破裂密切相关。据此我们提出：是否可以通过研究这种形态学上的不匹配导致再发破裂的生物力学机制，建立腔内移植物机械力学-血液动力学-管壁应力学的再发破裂风险模型，从而为腔内移植物的改进与应用提供理论依据？拟开展以下研究：①通过分析临床资料，深入筛选再发破裂相关危险因素，为生物力学分析提供关键靶点；②通过计算机血液动力学、移植物与管壁相互作用的机械力学分析，研究管壁的应力分布，阐明再发破裂的力学条件；③将力学影响，以不同构型的腔内移植物，应用于夹层动物模型，进行生物力学分析，建立再发破裂风险模型，并验证改进的腔内移植物的生物力学效能。本研究将有助于阐明再发破裂的生物力学机制，为提高主动脉夹层腔内治疗水平提供实验依据和新的研究思路。

主动脉夹层可导致分支动脉缺血或主动脉破裂等，是累及主动脉最严重的疾病之一。对于降主动脉夹层，从1998年开始正式使用腔内移植物行腔内隔绝术，它以其微创性和良好的早期临床结果得以广泛开展。然而，随着腔内隔绝术的广泛应用，由腔内移植物导致的并发症也愈发受到重视。其中，发生于腔内移植物边缘的内膜再发破裂，是威胁生命的主要并发症，据报道其死亡率高达26.3%。但是，对于再发破裂这一严重的并发症，其发生机制不清楚，无法确定该如何预防其发生。.我们从移植物机械力学-血液动力学-主动脉管壁应力学三个方面深入探讨主动脉夹层腔内隔绝术后再发破裂的机理，并试图对再发破裂进行预防调控。.通过临床研究发现了近端oversize rate、锚定部位和治疗时期与腔内移植物近端再发破裂密切相关；远端不匹配率与腔内移植物远端再发破裂密切相关。.通过体外力学模拟分析发现：真腔狭窄导致远近端管壁的压应力分布存在明显差异，狭窄局部的壁切应力明显增大，显著增大了近端和远端发生再发破裂的风险；不同构型的腔内移植物置于主动脉夹层管壁中，产生的管壁应力分布模式差异显著，而细丝多冠（丝径0.2mm，12冠）的支架构型其管壁应力明显小于其他构型的支架；腔内移植物远端采用适当口径的限制性裸支架，明显减少局部的管壁应力，通过临床研究证实能够明显降低远端再发破裂的发生率。.通过基于动物实验的管壁分析证实了：主动脉管壁以巨噬细胞浸润为代表的炎症水平与管壁材料强度负相关；采用不同的支架构型作用于同一口径同一部位的主动脉管壁，产生的管壁炎症水平不一，细丝多冠的支架构型能够明显减轻管壁炎症浸润，改善管壁材料学强度。.筛选出的细丝多冠等支架构型已申请相关专利，制成初步样品，具备转化潜力。目前限制性裸支架技术已经获得了业内普遍推广，成为治疗降主动脉真腔明显狭窄的主动脉夹层的重要治疗选择，有效地促进了主动脉真腔重构、降低了再发破裂的发生率。