Clinical Intervention And Related Experimental Research On Elderly Patients With Symptomatic Stenosis Of Head And Neck Arteries

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.