A reproducible swine model of proximal descending thoracic aortic aneurysm created with intra-adventitial application of elastase

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Abstract

Objective Animal models are required to explore the mechanisms of and therapy for proximal descending thoracic aortic aneurysm (TAA). This study aimed to establish a reproducible swine model of proximal descending TAA that can further explain the occurrence and progression of proximal descending TAA. Methods Eighteen Chinese Wuzhishan miniature pigs (30.32 ± 1.34 kg) were randomized into the elastase group (n = 12) and the control group (n = 6). The elastase group received intra-adventitial injections of elastase (5 mL, 20 mg/mL), and the control group received injections of physiologic saline solution. A 4-cm descending thoracic aortic segment proximal to the left subclavian artery was isolated. The distance between the left subclavian artery and the injection starting point of the descending thoracic aorta was 0.5 cm. Elastic protease was circumferentially injected intra-adventitially into the isolated segment of the aortic wall in the elastase group by a handmade bent syringe. The length of the elastic protease injection was 2 cm. An average of 12 injection points were distributed in this 2-cm aortic segment. Each injection point used about 0.4 mL of elastic protease. The distance between two injection points was about 1.5 cm. All animals underwent digital subtraction angiography preoperatively and 3 weeks after operation. Three weeks after TAA induction, aortas were harvested for biochemical and histologic measurements. Results All animals in the elastase group developed TAAs. No aneurysms were observed in the control group. The distance between the left subclavian artery and the TAA was 8.00 ± 4.19 mm. Preoperative and postoperative aortic diameters of the elastase group were 15.42 ± 0.43 mm and 24.53 ± 1.41 mm, respectively (P <.0001). Preoperative and postoperative aortic diameters of the control group were 15.31 ± 0.33 mm and 15.57 ± 0.40 mm, respectively (P =.5211). The changes of aortic structure and composition included reduction of smooth muscle cells and degradation of elastic fibers. Levels of matrix metalloproteinases 2 and 9 were increased in TAA tissue. Conclusions This study established a reproducible large animal model of proximal descending TAA. This model has the same biochemical characteristics as human aneurysms in the aspects of aortic expansion, aortic middle-level degeneration, and changes in the levels of matrix metalloproteinases and provides a platform for further study. Clinical Relevance Proximal descending thoracic aortic aneurysm (TAA) remains clinically difficult to manage. Studies in a clinically relevant swine model are important for a deep understanding of the mechanism of proximal descending TAA and to refine the interventional equipment to better treat this disease. This study revealed a reproducible model to facilitate research on the mechanisms and treatment of TAA.

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Tian, Y., Zhang, W., Sun, J., Zhai, H., Yu, Y., Qi, X., … Zhong, H. (2018). A reproducible swine model of proximal descending thoracic aortic aneurysm created with intra-adventitial application of elastase. Journal of Vascular Surgery, 67(1), 300-308.e2. https://doi.org/10.1016/j.jvs.2016.12.120

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