Experimental Study Of Biodegradable Magnesium Alloys Covered Stent For A Lateral Aneurysm Model Of Common Carotid Artery In Rabbits

Chapter one IntroductionAneurismal subarachnoid haemorrhage (SAH) is one of the most frequent cerebral vascular diseases, which second only to the brain infarction and hypertensive cerebral haemorrhage, with incidence rate about 8-16 per 100,000 per year. Mortality and morbidity rate after aneurysm rupture could achieve more than 40% and 33% respectively. Cerebral aneurysm rupture is a threat to patient like a time bomb at any time.The course of the intracranial ICA traverses a relatively compact region of skull bone base with complex nerval and vascular surroundings. These anatomical features make neurosurgery at this region run a higher risk. Recently, endovascular treatment (EVT) with micro-invasive technical method has made a rapid advance and broken this restricted zone of neurosurgery, thus becoming the first option for cerebral vascular lesions in the region. However, endovascular treatment of aneurysm, beginning in 1990’s, commonly used coil embolism technique which exist the following deficiency:the operation behaviour occurred in the aneurysm sac which may increase procedural hemorrhage or rehemorrhage rate; coils in the sac may cause mass effect after operation; low rate of complete occlusion; high rate of the recurrence or recanalization rate; extreme expensive; et al. The recurrence rate is even higher in some complicated intracranial aneurysms such as large or giant, wide-necked, pseudoaneurysms, et al. Provided that the complicated intracranial aneurysms can not be cured effectively, a lot of patients are to be faced the risk of death and disability. The deficiency of material and technology also brings negative effect to both doctors and patients either in mind or in practice.Recently, with the development of science and the concept of Medical treatment, a more reliable endovascular reconstructive technique is to transfer the target lesion from the aneurysm sac to the diseased parent artery for achieving anatomical heals. Endovascular reconstructive technique includes single/multiple bare stent placement, low porosity stent placement and covered stent placement. The former two stents do not suit to for acute aneurysmal subarachnoid haemorrhage. This new kind of intracranial balloon-expandable Willis covered stent developed by our team is just a product with obtaining approval of CFDA base on this theory, which could achieve immediate isolate of the aneurysm sac, reconstruction of the parent artery, restoration normal hemodynamics in the diseased area and prompt the thrombosis in aneurysm sac. However, these metal stent may delay endothelialization and lead to restenosis when placed in the vessel for a long time. The first step of the study was to construct degradable covered stent basing on biodegradable magnesium alloys. Through a series animal experiment study, we tried to explore the feasibility, reliability and endothelialization mechanism of biodegradable covered stent for canine carotid aneurysmal model, as well as provided a new approach for cerebral aneurysms.Consequently, we begin this study and expect to accomplish the following targets:① building the lateral aneurysm model of common carotid artery in rabbits;② an primary angiographic and histopathological study of biodegradable magnesium alloys covered stent for a lateral aneurysm model of common carotid artery in rabbits;③ Comparative DSA study of biodegradable magnesium alloys covered stent and Willis covered stent for a lateral aneurysm model in common carotid artery of rabbits.Chapter two Building the lateral aneurysm model of common carotid artery in rabbitsPurpose:To evaluate the successful rate of building the lateral aneurysm model of common carotid artery and the parent artery patency rate in rabbits.Methods:40 New Zealand rabbits were randomly classified two groups (20) after breeding for one week. To first group, a lateral aneurysm model of common carotid artery was established with discontinue extroversion suture, which was applied for anastomosis of venous pouch with common carotid artery with 6-0 microsuture line.To second group, one month after the left common carotid artery was ligated, a lateral aneurysm model was established with the same mathod.The digital subtraction angiography (DSA) angiography was performed to evaluate the lateral aneurysm model during 72 hours after building the lateral aneurysm model.Results:The lateral aneurysm models in common carotid artery were successfully made in all 40 rabbits. These DSA angiograms showed lateral aneurysm models in all 20 rabbits of second group with common carotid artery patency and in 17 rabbits of first group. In first group, there were the occlusion of the lateral aneurysm model in 2 rabbits, and common carotid artery in 1 rabbit, and the mild to moderate stenosis of common carotid artery in 4 rabbits. In second group, the mild stenosis of common carotid artery in 2 rabbits.Conclusions:The improvement of the lateral aneurysm model of common carotid artery in rabbits was a useful approach for enhancement of the model successful rate and patency rate of the common carotid artery.Chapter three An angiographic and histopathological study of biodegradable magnesium alloys covered stent for a lateral aneurysm model of common carotid artery in rabbitsPurpose:To evaluate the feasibility of biodegradable magnesium alloys covered stent for a rabbit lateral aneurysm model in the common carotid artery (CCA),and to follow-up the biodegradable behaviour and endothelial progress during 12 months, by building the lateral aneurysm model of common carotid artery in rabbits.Methods:Biodegradable magnesium alloys covered stent was performed within 72 hour after forming a lateral aneurysm model. Digital subtraction angiography (DSA) was performed to evaluate the aneurysm model and common carotid artery of rabbits prior to the procedure,3,6 and 12 months after stent implantation. The degradation behaviour is invastagated with molybdenum target photograph and light microscope, and the endothelial progress with electron microscope.Results:A lateral aneurysm model of common carotid artery in 20 New Zealand rabbits was successfully implanted with biodegradable magnesium alloys covered stent. DSA angiography before stent placement demonstrated lateral aneurysm models in all 20 rabbits with common carotid artery patency. DSA after biodegradable magnesium alloys covered stent placement displayed disappearance of the aneurysms and patency of the common carotid artery in all 20 rabbits during follow-ups. The degradation of the biodegradable magnesium alloys covered stent was investigated with molybdenum target and electron microscope during follow-ups. The degradation significantly occurred in 3-6 months, and only a small amount of stent skeleton was observed in 12 months. The endothelial progress began in 1 month after stent placement and had completed in 6 months.Conclusions:Biodegradable magnesium alloys covered stent was a feasible approach for the treatment of a right common carotid artery lateral aneurysm in rabbits.The degradation of the biodegradable magnesium alloys covered stent gradually degraded during follow-ups.Chapter four Comparative DSA study of biodegradable magnesium alloys covered stent and Willis covered stent fora lateral aneurysm model of common carotid artery in rabbits.Objective:Willis covered stent has been widely deployed in a variety of vascular lesions of carotid artery. Compared with Willis covered stent, to evaluate the feasibility of biodegradable magnesium alloys covered stent for a lateral aneurysm model in common carotid artery of rabbits.Methods:After 20 New Zealand rabbits were fed for one week to form a lateral aneurysm model. Biodegradable magnesium alloys covered stent and Willis covered stent were successfully performed within 72 hour after forming a lateral aneurysm model. Comparative DSA angiography was performed prior to the procedure,3,6 and 12 months after stent placement, including the occlusion of aneurysm, leakage, vascular spasm, vascular injury, thrombosis and vascular occlusion, et al.Results:Biodegradable magnesium alloys covered stents and Willis covered stents were implanted respectively in 10 aneurysms, the technical success rate of stenting placement was 100%. Complete exclusion was achieved in 20 aneurysms of all 20 rabbits immediately after these stents, and common carotid artery of rabbits remain patency, and vascular spasm was observed respectively in 3 rabbits and 1 rabbit. The 3 months and 12 months follow-ups exhibited complete occlusion in all aneurysms and patency of the CCA of all rabbits.Conclusions:Biodegradable covered magnesium alloys stent was a feasible approach for the treatment of a lateral aneurysm model in common carotid artery of rabbits.