论文标题:症状性头颈部动脉狭窄老年患者的临床干预与相关实验研究
Clinical Intervention and Related Experimental Research on Elderly Patients with Symptomatic Stenosis of Head and Neck Arteries
论文作者
论文导师 周定标,论文学位 博士后,论文专业 神经外科学
论文单位 中国人民解放军军医进修学院,点击次数 144,论文页数 117页File Size9984K
2007-12-01论文网 http://www.lw23.com/lunwen_3528557/
Carotid Artery;; Vertebral Artery;; Basilar Artery;; Stenosis;; Elderly Patient;; Stenting;; Medical Treatment;; Atherosclerosis;; Animal Model;; Mini-pig;; Hemodynamic;; Elongation and Tortuosity;; Numerical Simulation
背景各种原因(尤其是动脉粥样硬化)引起的颈动脉和椎基底动脉系统的狭窄和闭塞与缺血性脑卒中的发生密切相关,其临床干预主要包括内科治疗、外科手术和血管内介入治疗等。近年来,动脉狭窄的支架成形术已被越来越多地用于头颈部动脉狭窄的治疗,但目前尚缺乏老年患者的专题研究。同时,也需要建立适合于介入研究的理想头颈部动脉粥样硬化性狭窄动物模型以进行相关研究。在临床实践中,我们还发现了许多患者有严重的动脉迂曲,但是,颈部动脉的迂曲是否与脑缺血和缺血性脑卒中有相关性一直存在争议。 目的(1)探讨症状性头颈部动脉狭窄老年患者的支架成形术或/和内科治疗的可行性、安全性及短期疗效。(2)探讨建立适合神经介入研究的、稳定可靠的动脉粥样硬化性颈动脉狭窄动物模型。(3)建立颈部动脉伸长扭曲的血流动力学理论分析模型,总结伸长扭曲动脉中血液流动的血流动力学变化规律,探讨动脉伸长扭曲和脑缺血的关系。 方法(1)选择近5年我院诊治的经血管造影证实有颈动脉或椎-基底动脉狭窄(狭窄≥50%)且有相关临床症状的老年患者(年龄≥60岁),均行内科治疗,部分还行狭窄动脉支架成形术。分颈动脉组和椎-基底动脉组,分析两组患者的临床、影像学、治疗和随访资料。(2)以15头小型猪为对象,随机取3头猪作为预实验或意外死亡的备用动物;另外12头动物随机分为高脂饲养组和普通饲养组,分别予高脂配方饲料和普通饲料饲养。选取每头猪的一侧颈动脉进行球囊扩张致内、中膜损伤。该12头猪的24条颈动脉被分为4个亚组,即高脂饲养加动脉损伤组(HF&I),高脂饲养动脉未损伤组(HF&NI),普通饲养加动脉损伤组(N&I)和普通饲养动脉未损伤组(N&NI)。运用体外超声、数字减影血管造影(DSA)和血管内超声(IVUS)进行颈动脉狭窄形成的监测与评价,最后制作标本并行病理检查。(3)以颈内动脉的生理解剖参数为原型,建立了动脉扭曲的几何模型;给出血液流动的边界条件以及计算条件,对扭曲动脉的血液流动进行了有限元数值模拟,测量在流量一定情况下不同角度的压降,分析验证数值模拟与实验模拟的结果。测量15例动脉扭曲组患者和15例对照组被检查者的颈内动脉和椎动脉的血流动力学参数,用血管造影机计算扭曲动脉的直径和长度。比较数值模拟、模拟试验和临床实测结果,分析不同角度动脉扭曲的伸长长度、压降的变化,解释动脉扭曲引起血流动力学改变的可能内在规律。 结果(1)124例颈动脉狭窄患者入选,其中男107例;年龄60-89岁,平均69.8岁。随访1-57月(平均27.3月),102例(82.3%)临床症状改善或消失;住院和随访期间总卒中发生率为4.8%(6/124),无卒中相关性死亡。此124例患者中83例(66.9%)共93例次接受颈动脉支架成形术,技术成功率为100%,动脉狭窄率由(88.3±10.4)%降至(10.3±6.7)%,t=23.4,P=0.000。术中和术后30天内2例(2.4%,2/83)发生手术相关性卒中,手术相关性死亡率为0。平均随访28.3月,73例(88.0%)患者临床症状缓解或消失,2例(2.4%,2/83)发生同侧颈内动脉供血区域脑卒中;56例复查颈部血管超声,3例(3.6%,3/83)显示支架内再狭窄(狭窄≥50%)。117例椎-基底动脉狭窄患者入选,其中男100例;年龄60-87岁,平均68.1岁;随访1-55月,平均28.4月。94例(80.3%)患者的临床症状改善或消失;住院及随访期间总卒中发生率为5.1%(6/117),卒中相关死亡率为1.7%(2/117)。此117例患者中70例(59.8%)共78例次行椎-基底动脉狭窄支架成形术,技术成功率为98.7%(77/78),动脉狭窄率由术前(81.7±14.3)%降至(8.3±4.2)%,t=21.3,P=0.000。术中和术后30天内4例(5.7%,4/70)发生手术相关性卒中,其中2例死亡(2.9%,2/70);68例支架成形术患者平均随访27.7月,60例(85.7%)症状改善或消失,1例(1.4%,1/70)发生后循环卒中。34例复查颈部血管超声,10例(29.4%,9/34)发现支架内再狭窄。(2)动物实验中DSA显示:16周时HF&I组平均狭窄率为(33.32±12.84)%,HF&NI组为(6.07±4.92)%;N&I组平均狭窄率为(3.65±6.83)%,N&NI组为0%。病理检查证实:16周时高脂饲养组动物球囊损伤后的颈动脉有明显动脉粥样硬化斑块形成。(3)数值模拟的结果显示在不同的扭曲情况下,压降和流场等流体动力学指标有着很大的变化。随着动脉扭曲角度的减小,血流的压降增大;在血管扭曲约20°与30°之间时,血流压降变化明显,在约30°扭曲时,血管压降最大。模拟实验结果显示了相同的变化曲线,二者吻合性较好。临床实测结果显示出相同的变化趋势,在动脉扭曲角度小于30°后压降明显增加。 结论(1)症状性头颈部动脉狭窄老年患者的支架成形术或(和)内科药物治疗的短期疗效良好,狭窄的支架成形术方法可行,相对安全。(2)采用高脂饲养和颈动脉球囊损伤的方法,16周可以初步建立小型猪颈动脉粥样硬化性狭窄模型。(3)建立了颈部动脉扭曲的数学理论模型和动脉扭曲的体外模拟系统,二者经临床验证,具有可用性。动脉扭曲可以造成血压下降,扭曲角度小于30°后血压下降明显。在一定情况下,严重的动脉扭曲可能是脑缺血发作相关因素之一。
Background Stenosis and occlusion of carotid and veretebrobasilar arteries, arising from variable factors especially atherosclerosis, is significantly related with ischemic stroke, and is mainly managed by medical treatment, surgery and endovascular intervention. In recent years, there is an increasing tendency to choose endovascular stenting in managing artery stenosis. However, there is lack of related reports about its effect on elderly peoples. There is also a need to establish an optimal animal model with head and neck arteries atherosclerotic stenosis suitable for interventional neuroradiology research to do related researches. In our clinical practices, we also found a clue that some ischemic stroke patients had seriously tortuous elongated internal carotid artery or vertebral artery. But there is a controversy whether tortuous elongated artery contributes to cerebral ischemia. Purpose (1) To evaluate the feasibility, safety and efficacy of stent-assisted angioplasty and/or medical treatment for elderly patients with symptomatic atherosclerotic occlusive disease of the head and neck arteries. (2) To establish a stable and reliable animal model with carotid artery atherosclerotic stenosis suitable for interventional neuroradiology research. (3) To establish a theoretical model of hemodynamic analysis for the elongation and tortuosity of internal carotid artery and vertebral artery, to summarize the rules of hemodynamic in this kind of arteries, and to explore the relationship between tortuous elongated arteries and cerebral ischemia. Methods (1) Two groups of patients demonstrated by cerebral angiography were identified from our cerebrovascular disease registry in recent 5 years(between January 2003 and October 2007), one group of elderly patients (≥60 years) with symptomatic carotid artery stenosis (≥50%) (CA group) and the other group of elderly patients (≥60 years) with symptomatic vertebrobasilar stenosis (≥50%) (VBA group). All of the patients were treated with medical therapy, some of them treated with additional artery stenting. Clinical, imaging, intervention and follow-up data of the patients of the two groups were collected and analyzed. (2) Fifteen Guangxi BA-MA Mini-Pigs were chosen, three of which were randomly selected as preliminary experiment animals or spare animals. The other 12 pigs were randomly assigned into high fat/cholesterol feeding group (HG) and normal feeding group (NG) which were fed on atherogenic diet and ordinary diet respectively. When the hyperlipemia status of the HG pigs was confirmed, unilateral carotid artery of the HG pigs and NG pigs were injuried by endovascular balloon dilation. And all the twenty-four porcine carotid arteries were further assigned into four subgroups, high fat/cholesterol feeding and injury group (HF&I), high fat/cholesterol feeding and non-injury group (HF&NI), normal feeding and injury group (N&I), normal feeding and non-injury group (N&NI). Duplex ultrasound, digital subtraction angiography (DSA) and intravascular ultrasound (IVUS) exams were used to evaluate atherosclerotic plaques and stenosis of those carotid arteries. Histological exam of those arteries specimens were also carried out. (3) A geometric model of a tortuous elongated artery was constructed according to the normal physiological and anatomical parameters of internal carotid artery. The boundary conditions and calculation conditions of blood flow were proposed. The numerical simulation of the blood flow in the tortuous elongated artery was carried out with finite element method. Pressure drop was measured at different angle of the elongated artery while flow rate was fixed. The results of numerical simulation and experiment simulation were analyzed and validated. Hemodynamic parameters of internal carotid artery and vertebral artery were measured in 15 cases of normal control group and in 15 cases with the elongation and tortuosity of internal carotid artery and vertebral artery. The diameter and length of the above artery were measured and calculated by the computer of DSA machine. Datas of numerical simulation and experimental simulation were compared with clinical datas. The variance of hemodynamic parameters such as elongated length and pressure drop was analyzed. The fundamental regularity of variations in hemodynamic parameters caused by the tortuous elongated artery was interpreted. Results (1) One hundred and twenty-four elderly patients (107 males and 17 females) were included with a mean age of 69.8 years (60-89 years) in the CA group. A stroke rate of 4.8% and no stroke-related death were found in this group during hospitalization and follow-up (1-57 months, mean 27.3 months), with symptoms resolved or improved clinically in 82.3% of the patients. Nighty-three stents were placed in 83 patients of the CA group with a technical success rate of 100%. The mean degree of stenosis was significantly reduced from (88.3±10.4)% before stenting to (10.3±6.7)% after stenting, t=23.4, P=0.000. Two (2.4%) perioperative procedure-related strokes occurred and none led to death. During follow-up (mean 28.3 months), symptoms were resolved or improved clinically in 88.0% of the patients who received endovascular therapy and two (2.4%) experienced ipsilateral carotid territory stroke. Ultrasound exam of 56 patients demonstrated three (3.6%) in-stent restenosis (≥50%). One hundred and seventeen elderly patients (100 males and 17 females) with vertebrobasilar stenosis were included in the VBA group with a mean age of 68.1 years (60-87 years). A stroke rate of 5.1% and stroke-related mortality rate of 1.7% were found during hospitalization and follow-up (1-55 months, mean 28.4 months), with symptoms resolved or improved clinically in 80.3% of the patients. Seventy-eight balloon-expandable stents were placed in 70 of the 117 patients with a technical success rate of 98.7%. The mean degree of stenosis was significantly reduced from (81.7±14.3)% before stenting to (8.3±4.2)% after stenting, t=21.3, P=0.000. Four (5.7%) perioperative procedure-related strokes occurred, of which two led to death. During follow-up (mean 27.7 months), symptoms were resolved or improved clinically in 85.7% of the patients who received endovascular therapy and only one (1.4%) patient experienced a posterior circulation stroke, while ultrasound exams of 34 patients demonstrated 10 (29.4%, 9/34) in-stent restenosis (≥50%). (2) In the animal study, the average stenosis rate of those carotid arteries were calculated according to the DSA exam results after those pigs were fed for 16 weeks, which were as following: HF&I (33.32±12.84)%, HF&NI (6.07±4.92)%, N&I (3.65±6.83)%, N&NI 0%. Pathological exam demonstrated obvious atherosclerotic plaques in those balloon-injured carotid arteries of high fat/cholesterol feeding animals. (3) Numerical simulation results indicated the hydrodynamic parameters such as pressure drop and flow field changed at different angle of tortuous artery. Pressure drop of blood flow and elongated length of artery was increased with diminution of the angle of tortuous artery. The pressure drop of blood flow changed significantly when the angle of tortuous artery is between 20°and 30°. And it changed to the largest when the angle of tortuous artery approximates to 30°. Experimental simulation results showed the same trends as numerical simulation. Clinical measurement datas disclosed the same trend in the same curve as numerical simulation and experimental simulation. Pressure drop of blood pressure increased obviously when the angle of tortuous elongated artery was less than 30°. Conclusions (1) Appropriate management including endovascular stenting and/or medical treatment may improve short-term outcome of elderly patients with symptomatic atherosclerotic occlusive disease of the carotid and vertebrobasilar arteries; meanwhile, stent-assisted angioplasty is technically feasible and relatively safe. (2) A feasible Mini-pig model with carotid artery atherosclerotic stenosis can be established by the means of high fat/cholesterol feeding and balloon injury of porcine carotid arteries in 16 weeks. (3) A mathematical theoretical model and a set of experimental simulation equipment for the elongation and tortuosity of internal carotid artery and vertebral artery were established. Their usability was validated by comparing with clinical measurement results. The elongation and tortuosity of internal carotid artery and vertebral artery results in decrease of blood pressure. When the angle of tortuous elongated artery is less than 30°, decrease of blood pressure is obvious. Kinking of internal carotid artery and vertebral artery may be one of related factors leading to cerebral ischemia in certain conditions.
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