Abstract 102: A Novel Swine Model of Infrarenal Abdominal Aortic Aneurysm

Abstract

Introduction: A reproducible large animal model for abdominal aortic aneurysms (AAAs) does not exist. This study sought to develop a large animal AAA model in swine using β-aminopropionitrile (BAPN), a lysyl oxidase inhibitor, an enzyme responsible for collagen cross-linking. We hypothesized that elastase/collagenase perfusion and balloon dilatation in combination with BAPN administration would result in AAA formation. Methods: Uncastrated Yorkshire male swine were fed BAPN (0.12g/kg) daily for one week prior to surgery and continued throughout the experiment. After anesthesia, the aorta was exposed from the renal arteries to the aortic bifurcation. The infrarenal aorta was cannulated via the caudal mesenteric artery and an aortic angioplasty was performed to dilate the aorta to 200% of its original diameter. Next, a 30 mL solution consisting of 500 units of elastase and 8,000 units of Type I collagenase was perfused into the infrarenal aorta for 10 minutes. This solution was also then topically applied for 10 minutes. The abdomen was irrigated and closed. Antibiotics and analgesic medications were administered. Results: BAPN-fed swine sacrificed at 28 days (n=5) had a 101% increase in infrarenal aorta diameter compared with day 0 (p=0.008). Swine (n=4) sacrificed at 7 and 14 days showed an increase of 114 and 75%, respectively. Histologically on day 28, collagen decreased by 20% and smooth muscle cell expression decreased by 40% (p=0.0001) in the aortic wall compared with control suprarenal aorta. Infrarenal aortas also showed a strong predilection for M1-polarized macrophages (MCP-1 positive staining, p=0.0165) compared with M2 macrophages (Arg-1 positive staining). MMP2 activity by zymography (p=0.0127) and IL-18 by array was also significantly increased (p=0.0202) on day 28 in the infrarenal AAA. Conclusions: Compared with previous large animal AAA models, this model using conventional techniques including balloon dilatation, elastase/collagenase perfusion, in addition to oral BAPN led to robust AAA with similar molecular and histologic changes to those seen in human AAA. This novel swine AAA model may serve as a much-needed link that will allow for the progression of studies from rodents to humans.