Introduction: Abdominal aortic aneurysms (AAA) are responsible for over 150,000 deaths worldwide annually. Attempts at producing a reliable large-animal model of AAA have proven challenging. We sought to create a reproducible swine model of AAA using enzymatic degradation of the aortic wall. Methods: A total of 9 male Yorkshire swine received periadventitial injections of type 1 collagenase (23.5 mg) and porcine pancreatic elastase (500 mg) into a 4 cm segment of infrarenal aorta. Aortic diameter growth was monitored at POD 7 and 14 using ultrasound. The animals were euthanized on POD 21, and the suprarenal (control) and infrarenal (treated) aorta was harvested for analysis, after gross measurement of aortic diameter under physiologic blood pressure. Sections of control and treated aorta were used to obtain tensile strength using a tensiometer. Additional segments of the aorta were collected for histopathological analysis (H&E, elastin, alpha smooth muscle actin). PCR of matrix metalloproteinases (MMP9) was conducted. Groups were compared with paired t-tests, or ANOVA for repeated measures, where appropriate. Results: Average percent growth of aortic diameter at POD 21 for treated segments was 27% +/- 16.5% versus 4.5% +/- 4% for control tissue. The average difference in aortic growth by subject, was 26.7% [14.6%-38.8%]; (p<0.001). Aortic medial thickness was decreased in treated tissue; 235 um +/- 208 um versus 645 um +/- 191 um (p<0.0001). Quantity of both medial elastin fibers, and vascular smooth muscles cells was decreased in treated tissue; 1.8% +/- 3.16%, compared to 9.9% +/- 6.85% (p<0.0001), and 24% +/- 6.8% versus 37.4% +/- 6.9%, respectively. Tensile strength was also decreased in treated tissue; 16.7 MPa +/- 7 MPa versus 29.5 MPa +/- 10.7 MPa (p=0.0002). A 12-fold increase in expression of MMP9 mRNA was also demonstrated in aneurysmal tissue (p=0.002) Conclusion: A reproducible, large-animal model of AAA, with anatomical, histopathological, and biomechanical properties that are clinically translatable, can be achieved with extraluminal enzymatic degradation.
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