【摘要】：目的:目前對(duì)腔靜脈濾器使用能有效減少致死性肺栓塞的發(fā)生國(guó)內(nèi)外已有共識(shí),但有報(bào)道及我們臨床中發(fā)現(xiàn)濾器置入存在一些并發(fā)癥如腔靜脈濾器血栓形成,濾器的移位、傾斜、阻塞等,本研究通過(guò)建立濾器植入后的腔靜脈體外物理模型,采用粒子圖像測(cè)速技術(shù)(particle image velocimetry,PIV)進(jìn)行檢測(cè),觀察植入的濾器對(duì)腔靜脈流場(chǎng)的影響,并通過(guò)動(dòng)物實(shí)驗(yàn)進(jìn)行觀察濾器植入后下腔靜脈的病理性變化及濾器表面覆蓋組織情況。方法:1.回顧性分析2008年6月至2014年6月期間成功回收的164例可回收下腔靜脈濾器(OPTEASE),觀察取出的可回收下腔靜脈濾器粘附血栓大小、部位等特點(diǎn),并分析濾器繼發(fā)血栓形成與濾器傾斜度、鉤端貼壁、濾器置入后腔靜脈擴(kuò)張率、留置時(shí)間、抗凝的相關(guān)性。2.選取2010年1月~2013年1月行OPTEASE植入后100例患者的影像學(xué)資料,分別測(cè)量濾器植入后濾器體部固定段、錐形部中點(diǎn)及鄰近段正常下腔靜脈直徑,根據(jù)這些數(shù)據(jù)按照1:1的比例,制作濾器植入后腔靜脈的體外物理管狀模型。3.循環(huán)液采用黏度與人體血液相似的35%的甘油水溶液,采用PIV測(cè)試技術(shù),對(duì)制作的物理模型進(jìn)行流場(chǎng)測(cè)試,觀察該模型的濾器植入段局部流場(chǎng)中流體流速變化以及渦量的分布等。4.選用健康成年Beagle犬共20只,4只為對(duì)照組,余16只為濾器植入組。麻醉后通過(guò)股靜脈為入路進(jìn)行操作,濾器組將可回收下腔靜脈濾器(OPTEASE)植入下腔靜脈腎下段1cm處。術(shù)后2周、4周、8周、12周后分4批行彩超檢查、雙源CT掃描及重建,后處死動(dòng)物,第批4只,取出包括濾器植入段的下腔靜脈及鄰近的正常下腔靜脈1cm,通過(guò)肉眼觀察、光學(xué)顯微鏡以及掃描電鏡檢查,對(duì)濾器支柱的內(nèi)膜覆蓋情況進(jìn)行觀察并分析,比較術(shù)后2周、4周、8周、12周的濾器表面覆蓋的新生內(nèi)膜情況。結(jié)果:1.本組臨床病例濾器相關(guān)性血栓形成率為31.1%,當(dāng)濾器最大傾斜度≥15°、鉤端貼壁、濾器置入后腔靜脈擴(kuò)張率≥50%、濾器留置時(shí)間2周,其濾器相關(guān)性血栓形成率分別為70.3%、79.6%、64.7%和86.2%,與對(duì)照組相比,濾器血栓形成的差異均有明顯統(tǒng)計(jì)學(xué)意義(p0.001)。而血栓平均長(zhǎng)度分別為8.6±1.7mm、5.3±1.4mm、10.1±2.2mm和3.6±0.9mm,濾器最大傾斜度≥15°和濾器置入后腔靜脈擴(kuò)張率≥50%與濾器置留時(shí)間2周相比血栓長(zhǎng)度差異有統(tǒng)計(jì)學(xué)意義(p0.05)。2.成功制成濾器植入后的腔靜脈體外物理模型,濾器植入前下腔靜脈血流為層流為主,濾器植入后濾器段下腔靜脈明顯擴(kuò)張,血流減慢,濾器傾斜角0°、5°、10°時(shí)濾器內(nèi)仍有層流為主,軸流未見(jiàn)偏離,血流對(duì)血管壁的剪切力低;濾器傾斜角15°、鉤端貼壁時(shí)濾器內(nèi)層流消失,軸流偏離,血流對(duì)血管壁的剪切力明顯增高,濾器偏向側(cè)形成血流郁滯區(qū)及渦流。3.濾器組16只實(shí)驗(yàn)犬均成功植入下腔靜脈濾器,術(shù)后彩色多普勒檢查發(fā)現(xiàn)術(shù)前下腔靜脈腎下段血管平均直徑為13.47?0.38mm,濾器植入后2、4、8、12周下腔靜脈明顯擴(kuò)張,平均直徑為17.81?0.47mm、17.70?0.46mm、17.65?0.40mm及17.39?0.56mm。濾器植入前、后比較下腔靜脈直徑有明顯差異(p㩳0.001);術(shù)前下腔靜脈平均血流速度為45.6?1.69cm/s,術(shù)后濾器內(nèi)軸流平均流速2、4、8、12周分別為23.3?2.01cm/s、23.4?1.8cm/s、25.5?2.3cm/s及25.4?3.4cm/s,濾器植入前、后比較下腔靜脈內(nèi)血流速度有明顯差異(p㩳0.001);而維持血流速度的壓力梯度術(shù)前為0.844?0.078mmhg,術(shù)后2、4、8、12周分別為0.186?0.036mmhg、0.190?0.035mmhg、0.197?0.034mmhg及0.212?0.058mmhg,濾器植入前、后比較下腔靜脈內(nèi)血流壓力梯度有明顯差異(p㩳0.001),對(duì)照組術(shù)前、術(shù)后無(wú)變化。4.濾器組術(shù)后雙源ct掃描及多維重建檢查發(fā)現(xiàn)ctv顯示濾器植入段下腔靜脈擴(kuò)張,濾器處腰椎靜脈叢側(cè)支血管開(kāi)放,2周時(shí)4例濾器全部支撐桿均局限在ivc管腔內(nèi);4周時(shí)1例濾器支撐桿大部分穿出ivc壁;8周時(shí)2例濾器支撐桿大部分穿出ivc壁,2例濾器支撐桿完全在ivc管腔以外,在濾器支撐柱突出管腔處,靜脈壁增厚,其中有1例下腔靜脈內(nèi)發(fā)現(xiàn)有條狀血栓形成;12周時(shí)4例濾器支撐桿W4完全在ivc管腔以外,靜脈壁呈偏心性增厚,下腔靜脈內(nèi)均可發(fā)現(xiàn)條狀血栓形成。ct仿真內(nèi)窺鏡成像(ctve)發(fā)現(xiàn)濾器支撐柱固定處內(nèi)腔面凹陷,鄰近支撐柱兩側(cè)血管內(nèi)膜明顯增厚,形成嵴突起,濾器植入處下腔靜脈內(nèi)腔面凹凸不平,并見(jiàn)有條狀血栓漂浮,而鄰近正常血管內(nèi)腔內(nèi)光滑,對(duì)照組術(shù)前、術(shù)后無(wú)變化。5.大體及鏡下觀察發(fā)現(xiàn)術(shù)后2、4、8、12周下腔靜脈外膜完整,濾器組均未見(jiàn)穿破下腔靜脈突入周?chē)M織臟器,術(shù)后2周濾器支撐柱大部分陷入血管壁內(nèi),濾器表面覆蓋半透明的薄層組織,濾器與血管壁分離容易;術(shù)后4、8、12周濾器支撐柱已經(jīng)完全嵌入在增生的內(nèi)膜下,濾器表面覆蓋組織增厚,厚度不均,濾器鉤端與血管壁粘連,術(shù)后4周剝離濾器困難,并撕裂少許內(nèi)膜組織,術(shù)后8周濾器附著少許血栓,剝離濾器極困難,撕裂較多內(nèi)膜組織,術(shù)后12周濾器附著血栓增多,濾器的支撐柱及鉤端全部陷入血管壁內(nèi),增生的內(nèi)膜覆蓋較厚,腔靜脈內(nèi)腔面粗糙不平,濾器不能剝離腔靜脈,強(qiáng)行剝離則撕斷腔靜脈。而術(shù)后8、12周濾器表面增生的內(nèi)膜較術(shù)后2、4周肉眼觀察明顯增厚。術(shù)后2周鏡下發(fā)現(xiàn)濾器植入處見(jiàn)內(nèi)皮細(xì)胞變扁,內(nèi)彈力層變薄,血管壁內(nèi)見(jiàn)裂隙形成,濾器支撐柱接觸處內(nèi)皮細(xì)胞損傷,內(nèi)膜下膠原纖維暴露。術(shù)后8、12周濾器表面內(nèi)膜層纖維組織明顯增生,局灶膠原化,增生的內(nèi)膜成分主要為平滑肌細(xì)胞、膠原纖維和少量的巨噬細(xì)胞所組成。濾器抽取后的空洞周?chē)梢?jiàn)大量膠原纖維增生,排列紊亂,血管壁間見(jiàn)大量裂隙形成,引起血管壁結(jié)構(gòu)損傷。對(duì)照組術(shù)前、術(shù)后無(wú)變化。6.掃描電子顯微鏡觀察術(shù)后2周濾器表面見(jiàn)條索狀、粗細(xì)不等的膠原纖維相互交織,并見(jiàn)少許內(nèi)細(xì)胞覆蓋。術(shù)后4周濾器表面膠原纖維增粗、聚集,部分為膠原纖維覆蓋。術(shù)后8周濾器表面膠原纖維明顯增粗、增厚,并有血小板粘附,大部分為膠原纖維覆蓋。術(shù)后12周濾器表面被增生內(nèi)膜基本覆蓋,膠原纖維增生、堆積,并有血小板及紅細(xì)胞沉積形成血栓。術(shù)后2、4、8、12周的濾器血栓捕獲區(qū)表面的新生內(nèi)膜覆蓋率分別是(14.34?8.85)%、(29.52?12.38)%、(62.63?12.94)%、和(68.88?10.74)%。術(shù)后2周、術(shù)后4周與術(shù)后8、12周組間差異有統(tǒng)計(jì)學(xué)意義(p0.001);術(shù)后8周與12周組間差異無(wú)統(tǒng)計(jì)學(xué)意義(p0.05);術(shù)后2、4、8、12周濾器側(cè)支撐柱表面的內(nèi)膜覆蓋率分別是(42.57?8.20)%、(93.58?5.46)%、100%、和100%,術(shù)后2周與術(shù)后4、8、12周組間差異有統(tǒng)計(jì)學(xué)意義(P0.001),術(shù)后4周、8周、12周組間差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。結(jié)論:1.濾器植入后使腔靜脈局部擴(kuò)張,血流減慢,通過(guò)PIV測(cè)試發(fā)現(xiàn)濾器傾斜角大于15°時(shí),濾器內(nèi)層流消失,軸流偏離,濾器偏向側(cè)形成湍流及渦流,血流對(duì)血管壁的剪切力增強(qiáng)。表明濾器植入后對(duì)腔靜脈血流有阻擋作用,隨著傾斜角的增大,濾器對(duì)腔靜脈的流速、流態(tài)、軸流偏離及血管壁的切應(yīng)力產(chǎn)生影響,是繼發(fā)腔靜脈血栓,引起腔靜脈阻塞的危險(xiǎn)因素。2.植入腔靜脈濾器的動(dòng)物實(shí)驗(yàn)影像檢查提示濾器植入后腔靜脈擴(kuò)張,血流減慢,并見(jiàn)腰椎側(cè)支血管開(kāi)放,表明濾器對(duì)腔血流有阻攔作用。大體及鏡下發(fā)現(xiàn)濾器植入后血管壁內(nèi)膠原組織增生,產(chǎn)生叢多裂隙改變,引起血管壁損傷及重塑,濾器植入時(shí)間的延長(zhǎng),濾器表面膠原纖維交織、增厚,并激發(fā)血小板、紅細(xì)胞貼附,繼發(fā)血栓形成,此型濾器植入后8周出現(xiàn)濾器表面內(nèi)膜增生明顯,側(cè)支撐柱及鉤端完全包埋于增生的內(nèi)膜下,并易繼發(fā)血栓形成,取出濾器極困難,并撕裂內(nèi)膜組織。
[Abstract]:Objective: at present, the use of the vena cava filter can effectively reduce the occurrence of fatal pulmonary embolism at home and abroad. However, it is reported that some complications such as thrombus formation of the vena cava filter, the displacement of the filter, the tilt and obstruction are found in the filter, and the external physical model of the vena cava after the filter is established in this study. Particle image velocimetry (PIV) was used to detect the effect of the implanted filter on the flow field of the vena cava, and the pathological changes of the inferior vena cava and the surface of the filter were observed through animal experiments. 1. retrospective analysis of the period from June 2008 to June 2014. 164 cases of the recovery of the inferior vena cava filter (OPTEASE) were recovered, and the size and location of the recoverable inferior vena cava filter were observed. The secondary thrombus formation and the gradient of the filter, the Leptospira wall, the dilation rate of the vena cava after the filter, the retention time, and the correlation of anticoagulant.2. were selected to select OP in January 2010 ~2013. The imaging data of 100 patients after TEASE implantation were measured. The diameter of the normal inferior vena cava in the midpoint and adjacent segment of the filter was measured respectively. According to the ratio of 1:1, the external physical tubular model of the vena cava after the filter implanted into the vena cava was used as the 35% Gump of the human blood similar to the human blood. In the oil and water solution, the PIV test technique was used to test the flow field of the physical model. 20 healthy adult Beagle dogs were selected to observe the flow velocity changes in the local flow field and the distribution of the vorticity in the local flow field of the filter. 4 of the control groups were used as the control group and the other 16 were implanted into the filter. The femoral vein was used as the approach after anesthesia. The filter group was implanted the inferior vena cava filter (OPTEASE) into the inferior vena cava subrenal segment 1cm. 2 weeks, 4 weeks, 8 weeks, and 12 weeks after the operation, color Doppler ultrasound was divided into 4 batches, double source CT scan and reconstruction, and then the animals were killed, 4 were taken out of the inferior vena cava including the filter implant segment and the adjacent normal inferior vena cava 1cm. The optical microscope was observed by the naked eye. Optical microscope was used for optical microscopy. And scanning electron microscopy (SEM) examination and analysis of the intima coverage of the filter support, compared with the 2 weeks, 4 weeks, 8 weeks and 12 weeks of the neointima on the filter surface. Results: 1. the incidence of thrombus formation was 31.1% in the 1. clinical cases, the maximum slope of the filter was more than 15 degrees, the Leptospira was adhered to the wall, and the dilatation rate of the vena cava after the filter was placed. 50% and 2 weeks, the filter related thrombus formation rate was 70.3%, 79.6%, 64.7% and 86.2%, respectively. Compared with the control group, the difference in the formation of the filter was statistically significant (p0.001). The average length of the thrombus was 8.6 + 1.7mm, 5.3 + 1.4mm, 10.1 + 2.2mm and 3.6 + 0.9mm, the maximum gradient of the filter was more than 15 degrees and the filter was placed. The dilation rate of the posterior vena cava was more than 50% and the length of the filter was 2 weeks. The difference in the length of the thrombus was statistically significant (P0.05).2. was successfully made into the external physical model of the vena cava after the filter implantation. The blood flow of the inferior vena cava was mainly laminar flow before the filter implantation. The lower cavity vein, the blood flow slowed down, the tilt angle of the filter was 0, 5 degrees, after the filter implantation. There is still laminar flow in the filter at 10 degrees, the axial flow is not deviated, the shear force of blood flow to the blood vessel wall is low, the tilt angle of the filter is 15 degrees, the inner flow of the filter is disappeared, the axial flow deviates, the shear force of the blood flow to the blood vessel wall is obviously increased, and the blood flow stagnation area and the.3. filter group of the filter are successfully implanted into the inferior vena cava. The filter, postoperative color Doppler examination revealed that the mean diameter of the inferior vena cava was 13.47? 0.38mm before operation, and the vena cava dilated obviously at 2,4,8,12 weeks after the filter implantation. The average diameter was 17.81? 0.47mm, 17.70? 0.46mm, 17.65? 0.40mm and 17.39? 0.56mm. filters were implanted before, and the inferior vena cava diameter was significantly different (P? 0.001); before operation, the inferior vena cava was significantly different (P? 0.001). The mean velocity of blood flow in the vena cava was 45.6? 1.69cm/s. The average axial flow velocity in the postoperative filter was 23.3? 2.01cm/s, 23.4? 1.8cm/s, 25.5? 2.3cm/s and 25.4? 3.4cm/s. The velocity of the blood flow in the inferior vena cava was significantly different (P? 0.001) before the filter was implanted (P? 0.001), and the pressure gradient of the blood flow velocity was 0.844? 0.078mmhg, and postoperative 2,4 The 8,12 weeks were 0.186? 0.036mmhg, 0.190? 0.035mmhg, 0.197? 0.034mmhg and 0.212? 0.058mmhg. The pressure gradient in the inferior vena cava was significantly different (P? 0.001) before the filter was implanted (P? 0.001). Before operation, the double source CT scan and multidimensional reconstruction of the.4. filter group found CTV display filter implantation in the inferior vena cava after the operation. On the filter, the collateral vessels of the lumbar plexus were open. At 2 weeks, all the support rods of the 4 filters were confined to the IVC cavity. At 4 weeks, 1 of the filter support rods were mostly through the IVC wall; 2 cases of filter support rods were mostly through the IVC wall at 8 weeks, 2 of the filter support rods were completely outside the IVC cavity, and the vein wall thickened at the filter support column. The vein wall thickened, among them the wall thickened. Among them, the venous wall thickened. Among them, the venous wall thickened. Among them, venous wall thickened. Among them, venous wall thickened. Among them, venous wall thickened. Among them, venous wall thickened. Among them, venous wall thickened. Among them vein walls thickened. Among them, venous walls thickened. 1 cases of inferior vena cava were found to form a strip of thrombus; at 12 weeks, 4 cases of filter support rod W4 were entirely outside the IVC cavity, the wall of the vein was eccentric thickening, and a.Ct simulation endoscope imaging (CTVE) found in the inferior vena cava found the inner cavity surface of the filter support column was concave, and the intima intima on both sides of the adjacent support column was thickened obviously. The internal cavity of the inferior vena cava of the filter implants was uneven, and there was a bar like thrombus floating in the inferior vena cava, and the adjacent normal intravascular cavity was smooth. Before operation, no change of.5. in the control group was observed and the external membrane of the vena cava was intact in 2,4,8,12 weeks after operation. The filter group did not penetrate the inferior vena cava into the surrounding tissue, 2 after the operation. The filter's surface covered most of the vascular wall, the filter surface covered with a translucent thin layer of tissue, and the filter was easily separated from the vascular wall. After the operation, the 4,8,12 week filter support column had been completely embedded under the hyperplastic intima. The thickness of the filter surface was thickened, the thickness of the filter was uneven, the hook end of the filter was adhered to the wall of the vessel, and the filter was difficult to be stripped 4 weeks after the operation. Tearing a little intima tissue, a little thrombus was attached to the filter 8 weeks after the operation. The dissection filter was very difficult to tear more intima tissue. The filter attached more thrombosis after 12 weeks. The support column and the hook end of the filter were all trapped inside the vessel wall. The intima of the hyperplasia was thick, the inner cavity of the vena cava was rough, the filter could not peel off the vena cava and forced exfoliation. 2 weeks after the operation, the endothelial cells became flat, the inner elastic layer became thinner, the internal elastic layer became thinner, the inner wall of the vascular wall was formed, the endothelial cells in the contact area of the filter support column were damaged and the intima collagen fibers were exposed. The 8,12 week filter table after the operation was observed at 2 weeks after the operation. The intima fibrous tissue was obviously proliferated and collagenated. The endometrium was composed mainly of smooth muscle cells, collagen fibers and a small number of macrophages. A large number of collagen fibers proliferated around the cavity after the filter extraction. After 2 weeks after the operation, the surface of the filter was observed on the surface of the filter, and the collagenous fibers were interwoven with each other in 2 weeks. The collagen fibers on the surface of the filter were thickened, aggregated and covered with collagen fibers at 4 weeks after the operation. The collagen fibers on the surface of the filter were thickened, thickened and adhered to platelets on the surface of the filter 8 weeks after the operation. Most of these were covered with collagen fibers. 12 weeks after the operation, the surface of the filter was basically covered by the hyperplasia intima, collagen fibrils proliferated and accumulated, with platelets and red blood cells deposited to form thrombus. The neointimal coverage on the surface of the filter area on the 2,4,8,12 week after the operation was (14.34? 8.85)%, (29.52? 12.38)%, (62.63? 12.94)%, and (68.88? 10.74)%). There was a significant difference between the 2 weeks after the operation and the 4 weeks after the operation (p0.001), and there was no significant difference between the 8 and 12 weeks after the operation (P0.05), and the intimal coverage on the surface of the lateral support column on the 2,4,8,12 weeks after the operation was (42.57? 8.20)%, (93.58? 5.46), 100%, and 100%, and there was a statistically significant difference between groups after the operation and 4,8,12 weeks after the operation. (P0.001), there was no significant difference between the 4 weeks, 8 weeks and 12 weeks after the operation (P0.05). Conclusion: after the 1. filter was implanted, the vena cava was localized and the blood flow was slowed down. The inner flow of the filter was lost, the axial flow deviated, the flow of the filter was deviated from the filter device, and the shear force of the blood flow to the blood vessel wall increased. After implantation, the vena cava blood flow is obstructed. With the increase of inclination, the flow velocity, flow pattern, axial flow deviation and the shear stress of the vessel wall are influenced by the filter. It is a secondary vena cava thrombus and the risk factor of cava cava obstruction. The animal experimental imaging of the.2. implantation vena cava filter indicates that the filter is implanted into the vena cava after the filter is implanted. Dilation, slow flow of blood flow, and opening of the collateral vessels of the lumbar spine showed that the filter was blocking the blood flow of the cavity. In general and under the microscope, the collagen tissue in the wall of the vessel was proliferated after the filter was implanted, the plexus was changed, the vascular wall was damaged and remolded, the time of the filter implantation was prolonged, the collagen fiber was interwoven, thickened, and platelets were stimulated. Red blood cells were attached and secondary thrombosis was formed. The intimal hyperplasia of the filter surface was obvious at 8 weeks after the filter. The lateral support column and the hook end were completely buried under the intima of the hyperplasia, and the thrombosis was easily secondary. The filter was very difficult to remove the filter and tear the intima tissue.
【學(xué)位授予單位】：蘇州大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2015
【分類(lèi)號(hào)】：R563.5

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