The Establishment Of Fusiform Aneurysm In A Rabbit Model And Its Process Of Repair

Part one A unique creation of a fusiform aneurysm in a rabbit model using a topical application of porcine pancreatic elastaseObjective: Intracranial aneurysm is a cerebrovascular disease with significant risk,while the detailed pathological mechanisms of formation have not been elucidated. The purpose of this study was to introduce a novel, simple and effective technique for creating a reliable fusiform aneurysm in a rabbit model created by use of topical porcine elastase.METHODS:A total of 60 New Zealand White rabbits were divided into 2 separate groups of heparinized and non-heparinized(n=30 per group). This was to determine if there was a need for systemic heparinization during the study. The two groups were then divided into five subgroups(n=6 per group) respectively: groups A-E and groups a-e. Porcine pancreatic elastase, at a concentration of 0, 0.5, 1, 2.5 and 5 U/μL, was incubated topically to the right common carotid artery(RCCA) to define the optimal concentration. The rabbits underwent angiography, HE stain,EVG stain,histomorphometry and immunohistochemistry at three weeks post application to evaluate the effect and formation of the fusiform aneurysm.RESULTS:At the follow up evaluation of all specimens, we demonstrated that the optimal concentration of elastase in this model was 5 U/μL according to the balance between aneurysm size and incidence of fusiform aneurysm. On further evaluation, we also demonstrated that the dosage of 5 U/μL increased the intraluminal carotid diameter from 2.50±0.32 to 3.11±0.55(p<0.01). There was also an association between the elastic lamina and the smooth muscle cell’s lamina which were markedly attenuated and the intimal endothelial lamina became thin or absent. The study also demonstrated that the heparin was indispensable, the group that received heparin showed no evidence of thrombus formation however, in the non-heparin groups, the incidence of thrombosis was 0%, 16.7%, 33.3%, 66.7% and 100%. CONCLUSION:We have demonstrated the development of a new modified technique to the elastase aneurysm model. Although there have been previous elastase models described, we find our model easier to perform and highly reproducible.Part two The process of aneurysm repair in a rabbit model using by porcine pancreatic elastaseObjective: This study tried to survey the remodeling process and its effect of aneurysm which it is created by use of topical porcine elastase in a rabbit.METHODS:Forty-five adult New Zealand white rabbits were subjected to nine groups(n=5 per group),they are respectively sham surgery group, immediately after surgery group,1 day after surgery group,3 days after surgery group,7 days after surgery group,14 days after surgery group,1 month after surgery group,2 months after surgery group, 3 months after surgery group. Immediately after rabbit euthanasia at immediately, 1 day, 3 days, 7 days, 14 days, 1 month, 2 months, 3 months after surgery, the arteries were perfused. The vascular were dissected, stained with HE, Masson and EVG for smooth muscle cells and internal elastic lamina respectively. Sections were then stained with mouse monoclonal antibodies(anti-e NOS, anti-i NOS, and anti-CD31 for endothelial cells, anti-NK-κB and anti-TNF-α for proinflammatory factor) for immunohistochemistry analysis. And anti-α-SMA for α-smooth muscle actin, anti-MMP-9 for extracellular matrix-degrading enzymes carried out immunofluorescence analysis.RESULTS:It could keep the character of fusiform aneurysm during the first month after surgery that the elastic fibers,the collagen fibers,the smooth muscle cells and the endothelial cells,However,these characters disappeared after the first month. The expression of e NOS decreased while the expression of i NOS increased. The smooth muscle cells were obviously multiplicative and secreted MMP and TNF-α and NF-κB.CONCLUSION:The model could keep the character of fusiform aneurysm during the one month after surgery. The fuction of the endothelial cells in the vessel after surgery have become different from the regular endothelial cells and so are the smooth muscle cells. The extracellular matrix may be the key factor in the process of the aneurysm’s repair.