A Novel In Vivo Rabbit Model of Abdominal Aortic Aneurysm Induced by Periarterial Incubation of Papain

Purpose: The objective of this study was to determine the possibility of creating a novel animal model of abdominal aortic aneurysm (AAA) in rabbits by the periarterial application of papain. Materials and Methods: Twelve New Zealand white rabbits were randomized into two groups: (1) the papain group, which received 2 mg of papain (n = 8) and (2) the control group, which received physiologic saline solution (n = 4). A 1-cm aortic segment proximal to the bifurcation was isolated, and its adventitia was incubated with papain for 20 minutes. The rabbits underwent intravenous digital subtraction angiography (IVDSA) 5 and 21 days after the operation. The animals were then humanely killed for histomorphometric and immunohistochemical studies. Results: All animals in the papain group developed AAA, with an average aneurysm diameter of 4.0 +/- 0.6 and 4.1 +/- 0.4 mm on days 5 and 21, respectively. No aneurysms were seen in the control group. On day 5, the papain-incubated aortas exhibited thinned and disorganized aortic walls, with decreased smooth muscle cells (SMCs) and fragmented and almost nonexistent elastic lamella. Media thickening, intimal hyperplasia, and smooth muscle cell regeneration were obvious on day 21. Immunostaining of matrix metalloproteinase (MMP)-9 and RAM11 showed strong expression in the papain group. On the contrary, the control group did not present histologic alterations and showed almost no expression of MMP-9 and RAM11. Conclusions: A novel in vivo rabbit model of AAA can be induced through periarterial application of papain for 20 minutes. This model is similar to an elastase-induced aneurysm model and could be useful to clarify AAA pathogenesis and endovascular treatment intervention.