【作者】 张喜成；

【导师】 李晓强；

【作者基本信息】 苏州大学 ， 胸心血管外科学（专业学位）， 2014， 博士

【摘要】 目的：髂静脉(iliac vein,IV)狭窄或闭塞性病变，支架植入是其首选的治疗方案，但目前在血管支架植入过程中，支架近端如何定位还存在不同意见。由于髂静脉病变多位于髂腔静脉（髂静脉-下腔静脉）连接部位，支架植入后容易被挤向远端，导致远期再狭窄或闭塞，故目前较多学者主张血管支架的近端部分或全部进入下腔静脉(inferiorvena cava,IVC)以保证完全覆盖髂静脉病变段、降低后期再狭窄几率。但进入下腔静脉的网状支架会部分或全部的覆盖对侧的髂静脉开口，本实验的目的是探讨支架植入覆盖对侧髂静脉开口，分别通过粒子图像测速技术（particle image velocimetry，PIV）、动物实验来观察局部流场的变化，以及对侧髂静脉开口的通畅性和病理改变。方法：1.选取2008年5月～2013年11月行髂静脉DSA造影或CT静脉成像的100例患者的影像学资料，分别测量双侧髂总静脉、下腔静脉分叉部位的平均直径，以及男性、女性的双侧髂静脉与下腔静脉的成角，根据这些数据按照1.2:1的比例，分别制作男性组和女性组髂腔静脉连接部的体外物理管状模型。2.循环液采用黏度与人体血液相似的35%的甘油水溶液，采用PIV测试技术，对制作的物理管状模型进行髂腔静脉连接部的流场测试，观察该管状模型在支架植入前后局部流场中流体流速变化以及涡量的分布等。3.选用健康成年Beagle犬共12只，麻醉后通过右侧颈静脉为入路，将自膨式裸支架植入左侧髂总静脉，血管支架的近端完全覆盖右侧髂静脉开口并进入下腔静脉。分别于术后4周、8周、12周分别行彩色多普勒检查血流情况，4周、8周、12周分3组处死动物，取出包括血管支架在内的双侧髂静脉、下腔静脉，通过肉眼观察、光学显微镜以及扫描电镜检查，对血管支架的内膜覆盖情况进行观察并分析，比较术后4周、8周、12周的覆盖对侧髂静脉开口部位支架表面的新生内膜情况。结果：1.成功制成髂腔静脉连接部的体外物理模型，支架植入前双侧髂静脉血流汇入下腔静脉后主流动方向基本位于中轴线，其中女性组略右偏。植入左侧髂静脉支架后，双侧髂静脉流体汇合的主流动方向明显右侧偏移，双侧髂静脉的流速无明显降低，也未见到髂腔静脉连接部有明显的涡流产生。2.12只实验犬均成功植入血管支架，术后彩色多普勒检查双侧髂静脉均通畅，无髂静脉支架或对侧髂静脉血栓形成。髂静脉支架标本显示血管支架在左髂静脉段明显内膜增生并完全覆盖支架，在覆盖右侧髂静脉开口的裸支架部分可以见到边缘有明显的新生内膜，并向支架中央爬行，其中以支架下缘的内膜增生最明显，并覆盖部分右髂静脉的开口。增生的内膜以胶原纤维和平滑肌细胞为主。术后4周、8周和12周的右髂静脉开口部裸支架的新生内膜面积分别为（9.33±1.54）%、（10.65±1.01）%和（10.92±1.30）%，组间相比差异均无统计学意义（P＞0.05）；电镜下观察覆盖右髂静脉开口部中央的支架网丝也有胶原纤维沉积，术后4周、8周中间支架网丝表面的胶原纤维覆盖率分别为（63.58±12.39）%、（97.13±2.71）%，二者相比有显著性差异（P＜0.001），12周内膜覆盖成分主要为内皮细胞，覆盖率为（99.63±0.60）%，与8周组相比无统计学差异（P＞0.05）。结论：髂静脉支架植入后覆盖对侧的髂静脉开口，通过PIV测试发现髂腔静脉连接部位在支架植入前后的流场流速无明显影响，未见明显涡流，表明裸支架植入后完全覆盖对侧髂静脉开口对另侧髂静脉的血液回流影响较小。植入髂静脉支架的动物实验表明，覆盖右侧的髂静脉开口部位，彩超提示对血液回流无明显影响，右髂静脉开口部位支架会有一定程度的内膜增生，增生的内膜覆盖了部分开口部的支架网丝，中间的支架网丝表面也有胶原纤维沉积、内皮细胞覆盖，并随时间延长更加明显。更多还原

【Abstract】 Objective：Stent implantation is the primary treatment of iliac venous stenosis orocclusive lesions. Opinions regarding the accurate positioning of proximal end of the stentsignificantly vary. A majority of iliac venous lesions are located at the iliocava junction(thejunction of iliac vein and inferior vena cava), which are likely to be squeezed toward thedistal end after stent implantation, leading to distal end re-stenosis or occlusion. Therefore,scholars proposed that partial or entire proximal end of vascular stents should be placedinto the inferior vena cava to guarantee complete covering the iliac venous lesions.However, the mesh stent within the inferior vena cava partially or completely covers theopening of the contralateral iliac vein. The purpose of this experiment is to discuss theimpact of iliac venous stent implantation upon the contralateral iliac vein detected byparticle image velocimetry (PIV) and animal experiments.Methods: Imaging data from100patients undergoing iliac venous angiography or CTvenography between May2008and November2013were collected in this study. A varietyof parameters including the diameter of bilateral common iliac veins, mean diameter ofinferior vena cava and the angle between bilateral iliac veins and inferior vena cava weremeasured in both genders. Based on these data, the iliocava junction models were in vitroconstructed at a male to female ratio of1.2:1. The working fluid consists of glycerine andwater mixed to35%similar to human blood. PIV was adopted to perform velocity fieldtest in the iliocava junction of physical models and observe the changes in topical velocityfield before and after stent implantation. Twelve healthy adult Beagle canines were subjectto self-expandable bare stent implantation into the left common iliac vein via the rightjugular route under anesthesia. Proximal end of the vascular stent completely covered theopening of the right iliac vein and entered into the inferior vena cava. Color Doppler examination was conducted to monitor the blood flow at postoperative4,8and12weeks.Animals were sacrificed at postoperative4-,8-and12-weeks. Iliac vein and inferior venacava including vascular stents were collected. Light and scanning electron microscopywere performed to observe and analyze the growth of neointima onto the stents, andstatistically compare the covering of the new neointima on the stent surface located at theopening of contralateral iliac vein.Results: Physical models of the iliocava junction were successfully established invitro. Prior to stent implantation, bilateral iliac venous blood flows converged at theinferior vena cava and the main blood flow was located at the middle axes. Female patientshad a slight leaning towards the right side. After stent implantation into the left iliac vein,the direction of the main convergence flow of bilateral iliac venous fluid was significantshifted to the right side. Neither significant reduction in the velocity of bilateral iliacvenous flow nor obvious eddy current was observed. Stents were successfully implantedinto12animals. Postoperative color Doppler examination revealed that the blood flow inbilateral iliac veins was open and smooth. No iliac venous stent-induced thrombosis orcontralateral iliac venous thrombosis formed. Iliac venous stent samples showed thatsignificant intimal hyperplasia was noted in the left iliac vein, which completely coveredthe stent. New neointima formed adjacent to the edge of bare stent located at the openingof right iliac vein and grew towards the stent center, especially the intimal hyperplasiasurrounding the inferior edge of the stent which partially covered the opening of the rightiliac vein. hyperplastic neointima was mainly composed of collagen fiber and smoothmuscle cells. At postoperative4,8and12weeks, the area of new neointima on the barestent located at the opening of the right iliac vein were （9.33±1.54）%,（10.65±1.01）%and （10.92±1.30）%with no statistical significance among three groups (P>0.05).Electron microscopy revealed that new neointima was notably seen the central stent at theopening of right iliac vein. The covering rates of neointima on the stent struts were（63.58±12.39）%,（97.13±2.71）%and （99.63±0.60）%at postoperative4,8and12weeks,there is a statistical significance between4and8weeks groups(P<0.001).Scaningelecton analysis showed the saface of endomembrane were composed of endothelialcells,but there is no statistical significance between8and12weeks groups.Conclusions: After iliac venous stent implantation, new neointima covered theopening of contralateral iliac vein. PIV revealed moderate changes in the velocity fields of the iliocava junction before and after stent implantation, suggesting that complete coverageof bare stent on the opening of contralateral iliac vein seldom affects its blood flow afterstent implantation. Experimental outcomes indicated that a certain degree of intimalhyperplasia occurred in the stent at the opening of right iliac vein and partially covered theopening of bare stent. Obvious coverage of hyperplastic neointima were seen on the stentmesh in the middle of the the opening of contralateral iliac vein. But these experimentaloutcomes indicated that there are no significant effects upon the blood backflow after thestent covering the the contralateral iliac vein.更多还原