【作者】 田彦龙；

【导师】 毛颖； 宋冬雷；

【作者基本信息】 复旦大学 ， 外科学， 2009， 博士

【摘要】 第一章实验性犬颈总动脉侧壁动脉瘤模型的建立目的建立一种稳定的宽颈囊状侧壁动脉瘤模型,为颅内专用带膜支架临床试验前期的动物试验做准备。方法运用显微外科端侧吻合技术将犬的颈外静脉(EJV)囊吻合到犬颈总动脉(CCA)侧壁,建立宽颈囊状侧壁动脉瘤模型,DSA检查模型动脉瘤的情况,并进一步开展带膜支架试验。结果20只杂种家犬术后全部健康存活,建立犬颈总动脉侧壁宽颈动脉瘤模型40个,手术成功率100%(40/40)。所有模型动脉瘤均经DSA检查证实,并进行了带膜支架试验。结论以颈总动脉作为动脉瘤模型的载瘤动脉,采用显微外科技术将一侧颈外静脉囊与双侧颈总动脉端侧吻合建立犬颈部囊状侧壁动脉瘤模型,无论从实验动物的选择、模型的建立技术、手术成功率等方面考虑,都是令人满意的,是进行相关的血管内治疗材料特别是带膜支架的试验研究的适用模型。第二章颅内专用带膜支架治疗实验性犬颈总动脉瘤目的探讨国产颅内专用球囊扩张式Willis带膜支架系统治疗犬颈总动脉瘤模型的有效性、安全性,为进一步临床试验提供依据。方法10条健康杂种犬应用显微外科技术成功建立囊状侧壁动脉瘤模型20个,其中12个动脉瘤模型用ePTFE(Expanded polytetrafluoroethylene)Willis带膜支架覆盖瘤颈进行治疗,6个动脉瘤模型用裸支架覆盖瘤颈治疗作为对照,2个不予介入处理作为空白对照。采用血管内介入技术在实验犬颈总动脉内跨越动脉瘤颈植入12枚带膜支架和6枚裸支架,术后带膜支架组、裸支架组及空白对照组均给予抗血小板聚集治疗。支架置入术后1、3、6个月分别进行随访,不同随访时间结束后,进行组织病理学检查。结果带膜支架植入后即刻造影,接受治疗的动脉瘤不再显影,直至6个月的随访中动脉瘤腔未见显影,载瘤动脉无明显狭窄。2枚动脉瘤出现局部ePTFE膜凹陷,表现为局部的血管扩张样改变。裸支架植入后即刻,接受治疗的动脉瘤仍然显影,直至6个月的随访中动脉瘤及载瘤动脉均畅通,瘤内部分血栓形成。未予介入处理的空白对照组,在随访中动脉瘤腔及载瘤动脉均显影良好。组织学观察表明,光镜下所有带膜支架治疗的动脉瘤腔内均见血栓及纤维组织填充,支架表面被新生的内膜所覆盖;扫描电镜发现带膜支架置入后1个月内皮化已经开始,3个月时基本完成内皮化。结论带膜支架可使动脉瘤腔与正常血循环隔绝,并能保持载瘤动脉通畅,是一种简单、安全、有效的治疗囊状动脉瘤的方法。带膜支架具有较好的机械支撑力、较好的顺应性、理化稳定性、及生物相容性,可能具有较好的临床应用前景。但部分动脉瘤颈部ePTFE膜凹陷,表现为局部的血管扩张样改变,在形态上有一定缺陷,在制作工艺上有待改进。第三章自制内皮化肝素化聚氨酯带膜支架治疗犬颈总动脉瘤模型目的建立自制内皮化肝素化聚氨酯带膜支架的制作方法,并在实验性犬颈总动脉瘤模型上初步检验其治疗动脉瘤的可行性及其效果。方法1.建立实验性犬颈总动脉瘤模型,同时取犬颈外静脉分离培养出血管内皮细胞,并进行体外鉴定。2.建立肝素化聚氨酯带膜支架。3.将血管内皮细胞贴附于肝素化聚氨酯带膜支架内表面,形成内皮化肝素化聚氨酯带膜支架。4.将内皮化肝素化聚氨酯带膜支架压握于球囊导管之上,采用神经介入技术将支架植入模型动脉瘤的瘤颈处,以未经内皮化肝素化改性的普通聚氨酯带膜支架作为对照。5.术后1、3、6个月采用CTA或DSA随访影像学结果,并行组织病理学观察,评价内皮化肝素化聚氨酯带膜支架的治疗效果。结果成功建立内皮化肝素化聚氨酯带膜支架,对4枚模型动脉瘤植入内皮化肝素化聚氨酯带膜支架进行治疗,2枚模型动脉瘤植入未经内皮化肝素化改性的聚氨酯带膜支架作为对照。随访证实治疗组动脉瘤完全消除,无内漏,无再通,内皮细胞覆盖完整,无明显血管狭窄,而2枚对照动脉瘤,1月及3月随访时即发现载瘤动脉闭塞。结论犬血管内皮细胞可牢固贴附于肝素化的聚氨酯带膜支架表面,形成具有一定抗血流冲刷能力的内皮化肝素化聚氨酯带膜支架,对实验犬颈总动脉瘤模型治疗效果可靠,在保留载瘤动脉的通畅性方面明显优于未经内皮化肝素化改性的聚氨酯带膜支架。第四章颅内专用带膜支架在复杂性脑动脉瘤治疗中的应用目的评价颅内专用Willis带膜支架系统对于颅内复杂性动脉瘤的治疗效果。方法于2006年10月至2007年9月间共采用国产颅内专用血管内带膜支架(Willis颅内带膜支架系统,Microport公司,中国上海)治疗7例颅内复杂性动脉瘤,其中颈内动脉海绵窦段复杂动脉瘤3例,颈内动脉眼动脉段复杂动脉瘤l例,颈内动脉后交通段复杂性复发动脉瘤1例,椎动脉小脑后下动脉下段动脉瘤2例。男性6例,女性1例;年龄37～56岁,平均47.29岁。本组动脉瘤均难以用可脱性弹簧圈行动脉瘤囊内栓塞治愈,也难以直接开颅手术夹闭,为难治性复杂性颅内动脉瘤。术后采用抗血小板聚集治疗、临床随访及脑血管造影随访。结果所有7例患者共释放9枚带膜支架,其中8枚成功释放于载瘤动脉。6例患者达到消除动脉瘤并保持载瘤动脉通畅目的,临床效果满意;1例椎动脉瘤患者,植入2枚带膜支架后仍有少量内漏;1例颈动脉瘤患者在带膜支架输送过程中发生支架脱落事件,第二枚支架植入成功。1例术中发生颅内远端血管破裂出血,经开颅手术清除血肿治愈。无其他手术相关并发症。7例患者术后5～12个月全部获得脑血管造影随访,显示动脉瘤无再通,载瘤动脉通畅、无狭窄。结论颅内专用带膜支架对于部分颅内复杂性动脉瘤是有效的治疗工具,但在制作工艺和材料研制方面仍有待发展和进步,从而使颅内专用带膜支架真正适用于脑血管系统。第五章颅内专用带膜支架在颈内动脉海绵窦瘘治疗中的应用目的评价Willis颅内专用带膜支架系统对于颈内动脉海绵窦瘘的治疗效果方法于2006年11月至2007年6月间共采用国产血管内带膜支架(Willis颅内专用带膜支架系统,Microport公司,中国上海)治疗7例颈内动脉海绵窦瘘,男性5例,女性2例,年龄33～68岁,平均47.29岁。其中6例为车祸外伤导致的外伤性颈动脉海绵窦瘘,表现为突眼、球结膜充血水肿、眼球运动障碍和颅内杂音;1例无外伤史,头痛进行性加重1年,表现为头痛和颅内杂音。将支架植入颈内动脉瘘口处封闭瘘口,术后采用抗血小板聚集治疗、临床随访及脑血管造影随访。结果7例患者带膜支架全部成功释放于颈内动脉内瘘口处,其中4例达到瘘口完全消除并保持颈内动脉通畅,临床效果满意;1例自发性CCF少量内漏,临床症状有改善;两例支架释放后回撤球囊时发生支架移位,瘘口重新开放,改用可脱性球囊栓塞治疗。无其它手术相关并发症。4例患者术后4～8个月获得脑血管造影随访,显示瘘口未再通,颈内动脉通畅;其余患者未获影像学随访,临床随访症状明显改善。结论带膜支架对于部分颈内动脉海绵窦瘘是有效的血管内治疗工具,但在制作工艺和材料研制方面仍有待发展和进步,增加其稳定性,从而使带膜支架真正适用于更多脑血管系统病变的治疗。更多还原

【Abstract】 CHAPTER ONE THE CREATING OF LATERAL WIDE-NECK ANEURYSMS OF COMMON CAROTID ARTERY IN CANINE MODELSOBJECTIVE:Animal aneurysm models are required for the study of the treatments to intracranial aneurysms in humans with covered stents and so that experimental treatments can be tested prior to clinical trials.We are going to develope a canine model that consistently produces stable saccular wide-neck aneurysms similar in morphological features and hemodynamics to human intracranial aneurysms.METHODS:In 20 mongrel dogs,a harvested segment of the external jugular vein(EJV) was anastomosed to a common carotid artery(CCA) arteriotomy site to create a lateral wide-neck aneurysm.The end-to-side anastomosis was repeated on the contralateral side in each animal to form a second lateral wide-neck aneurysm.RESULTS:All animals survived the surgery uneventfully,and all 40 lateral wide-neck aneurysms were confirmed in 20 dogs by digital subtraction angiography (DSA) 2 to 4 weeks after surgery.There were some contrast material stagnation in the aneurysms cavity,but no spontaneous occlusion was found,nor obvious stenosis of the parent artery also.CONCLUSION:Lateral wide-neck aneurysms of sufficient size for endovascular access can be created in a reproducible fashion in mongrel dogs.This model is useful for studying complex endovascular procedures in aneurysms that mimic the human condition and for testing new devices and techniques. CHAPTER TWO EXPERIMENTAL STUDY OF COMMON CAROTID ARTERY ANEURYSMS TREATED WITH HOMEMADE COVERED STENTS DESIGNED FOR INTRACRANIAL VASCULATURE IN VIVO OF CANINE MODELSOBJECTIVE:To assess the effectiveness and biocompatibility of the covered stents in the treatment of experimental saccular aneurysms in canine models and to observe the occlusion of aneurysm with preservation of the parent vessel.METHODS:Ten healthy mongrel dogs were included in our study.20 experimental lateral wide-neck saccular aneurysms were created successfully using a microsurgical technique to produce end-to-side anastomosis from venous pouches of unilateral external jugular vein to the bilateral common arteries at a right angle.12 of 20 experimental aneurysms were treated with ePTFE covered stents,another 6 were treated with bare stents,and the other 2 were untreated to serve as bare controls. Altogether there were twelve ePTFE covered stents were implanted endovascularly in the common carotid arteries covering the orifice of the aneurysms.Control angiograpy was performed immediately after the procedure and 1,3,and 6 months, anticoagulant and antiplatelet therapy was performed.At each ending point,the aneurysm and its parent artery was removed,and fixed with paraformaldehyde(PFA) solution or 2%glutaraldehyde phosphate buffer for light microscopy or scanning electron microscopy.RESULTS:Pre-stenting angiography of the common carotid arteries showed lateral wide-neck saccular aneurysms and it’s complex blood flow.The aneurysms were no longer visible and the parent arteries kept patent while control angiography was performed post stenting,the follow up angiography also showed the same result. All controlled aneurysms and their parent arteries kept patent within 6mon follow-up period.Histopathological analysis by light microscopy disclosed that all treated aneurysms were filled with thrombus,as well as with fibrotic reactive scar tissue. Stent wires were found to be embeded the vessel wall and encased by an extension of the tunica intima vasorum;Scanning electron microscopy indicated that the endothelialization began at 1 month,endothelialization began from stent woven wire mesh and extended to struts,and endothelium became mature at 3 months. CONCLUSION:The covered stent can exclude the aneurysms from circulation and promote thrombosis by changing hemodynamics within the aneurysm with patency of the parent artery.In this study,it was proved that the ePTFE covered stent may have a good prospect in clinical application with a good mechanical strength,compliance,physicochemical stability,and biocompatibility. It’s an expedient,safe,and effective tool to treat some aneurysms.CHAPTER THREE EXPERIMENTAL STUDY OF COMMON CAROTID ARTERY LATERAL ANEURYSMS TREATED WITH SELF-MADE ENDOTHELIALIZED HEPARINIZED POLYURETHANE COVERED STENTS IN VIVO OF CANINE MODELSOBJECTIVE:To establish the method of making an endothelialized heparinized PUR covered stent and check the feasibility and effect of treatment in vivo for canine carotid artery lateral aneurysm models.METHODS:1.Establish the experimental CCA aneurysms in canine models, meanwhile dissect the external jugular vein from the canine models.Endothelial cells were isolated and cultured from the canine external jugular vein and identified in vitro. 2.Establish the heparinized PUR covered stent.3.The vascular endothelial cells were adhered to the internal surface of the stent covered with heparinized polyurethane,and an endothelialized heparinized PUR covered stent was established.4.The covered stent was compressed on a balloon catheter,and deployed to the aneurismal orifice site in CCA of the canine model with neurovascular interventional technique.5.After deployment the follow up was performed via CTA or DSA in 1,3,and 6 months,and the histopathological assay was also carried out. RESULTS:The endothelialized heparinized PUR covered stent was established successfully.Four experimental CCA aneurysms were treated with the endothelialized heparinized PUR covered stents.It was confirmed that all aneurysms were cured,without endoleak or recanalization.The EC(Endothelial Cell) developed good over the whole internal surface of the covered stents.No obviously stenosis was found,otherwise,the parent arteries of controlled aneurysms treated with an ordinary PUR covered stent,had been found occluded spontaneously at 1 and 3 months.CONCLUSION:Canine vascular endothelial cells can adhere to the surface of the stent covered with heparinized polyurethane to form an endothelialized heparinized polyurethane covered stent with the capability of anti-washout to the blood flow.From this study,we can see that the treatment effect to the experimental CCA lateral aneurysms in canine models was good.CHAPTER FOUR CLINICAL STUDY OF INTRACRANIAL COMPLICATED ANEURYSMS TREATED WITH WILLIS COVERED STENT DESIGNED FOR INTRACRANIAL VASCULATUREOBJECTIVE:The study was to evaluate the endovascular treatment efficacy of a home-made Willis covered stent specially designed for the intracranial vasculature in the management of complicated intracranial aneurysms of the cranial internal carotid artery(CICA) and vertebral artery(VA).METHODS:From October 2006 to September 2007,Willis intracranial covered stents were used to treat complicated intracranial aneurysms in seven patients aged from 37 to 56 years.Three complicated aneurysms at cavernous segment of the internal carotid artery(ICA-Cav);one at ophthalmic segment of the internal carotid artery(ICA-Oph);one recurrent complicated aneurysm at posterior communicating segment of the internal carotid artery(ICA-Pcom);and two at subdural segment of the vertebral artery(VA-Sub).All these aneurysms cannot be treated via coiling technique in the aneurysmal sac directly,neither can through surgical clipping easily,so be presumed as complicated intractable intracranial aneurysms.Antiplatelet therapy was adopted post stent deployment within six months,clinical and angiography follow up was performed within 12 months.RESULTS:Nine covered stents were used in this study,and eight covered stents were successfully deployed in the parent arteries in all seven cases,obtained total obliteration of the aneurysms with the parent arteries kept patent and favorable clinical outcomes in six cases.There was an endoleak in a vertebral giant fusiform dissecting aneurysm when two covered stent had been deployed.The distal end angiorrhexis lead to a cerebral hematoma in one caes,which was evacuated by a craniotomy and gained a good result.One covered stent slipped away from the balloon,and been captured by a micro guide wire.No other procedure-related complications occurred.Follow up angiograms were performed five to twelve months after covered stent deployment in all seven cases,showed no recanalization of the aneurysms and normal patency of the parent arteries.CONCLUSION:The Willis covered stent system was a useful tool for the endovascular treatment of the complicated intracranial aneurysms.Further research and deployment should be performed to optimize the covered stent technique for the cerebrovascular system(CVS). CHAPTER FIVE CLINICAL STUDY OF CAROTID CAVERNOUS FISTULA TREATED WITH HOMEMADE WILLIS COVERED STENTS DESIGNED FOR INTRACRANIAL VASCULATUREOBJECTIVE:The study was to evaluate the endovascular treatment of carotid cavernous fistula with Home-made Willis Intracranial Covered Stent.METHODS:From November 2006 to June 2007,Home-made Willis Intracranial Covered Stents were used to treat carotid cavernous fistula in seven patients aged from 33 to 68 years.Six of them were traumatic carotid cavernous fistula because of traffic accident,presented with protruding eye,conjunctival congestion,ocular movement disorder and intracranial souffle.The other one was a spontaneous carotid cavernous fistula without traumatic history,presented with progressive encephalalgia and intracranial bruit.RESULTS:The covered stents were successfully deployed at fistula site in the parent arteries in all seven cases,leading to total obliteration of the fistula with the parent arteries kept patent and favorable clinical outcomes in four cases.There was a slight endoleak at the fistula of the spontaneous CCF,and obtained relief of the symptom.The covered stents shifting occurred in two patients,when the balloons withdrawn,and result in reopening of the fistula,and then the fistula and parent arteries had to be occluded with detachable ballons.No other procedure-related complications occurred.Follow up angiograms were performed four to eight months after covered stent deployment in four cases,showed no recanalization of the fistula and normal patency of the parent arteries.No radiology data were obtained in other three patients,and clinical follow up verified that the symptom had been improved.CONCLUSION:The Home-made Willis covered stent system was a useful tool for the endovascular treatment of the carotid cavernous fistula.Further research and deployment should be performed to optimize the covered stent technique for the cerebrovascular system(CVS).更多还原