A. Z. Fashandi1, M. D. Salmon1, R. B. Hawkins1, M. Spinosa1, G. Lu1, G. Su1, G. Ailawadi1, G. R. Upchurch1 1University Of Virginia,Department Of Surgery,Charlottesville, VA, USA
Introduction: Given the relative unknown biologic antecedents that occur prior to aortic aneurysm rupture in humans, the purpose of this study was to establish a reproducible murine model of aortic aneurysm (AA) rupture.
Methods: Seven-week-old apolipoprotein E deficient (ApoE-/-) mice were fed a high fat diet for 4 weeks and subcutaneous osmotic infusion pumps containing Angiotensin II (ATII) were then implanted. ATII was delivered continuously for 4 weeks at either 1000ng/kg/min (n=25) or 2000ng/kg/min (n=29). A third group of mice (n=14) was given ATII at 2000ng/kg/min and 0.2% β-aminopropionitrile (BAPN) dissolved in the drinking water. Surviving mice were euthanized 28 days after osmotic infusion pump placement and aortic diameters were measured. All animals that died prior to 28 days underwent autopsy to determine cause of death. Survival was analyzed by Kaplan-Meier while rates of aortic rupture and aneurysm formation were analyzed with Chi-squared or Fisher’s exact test, where appropriate. Statistical analysis was performed with GraphPad Prism 7.0 and significance was set at a of 0.05.
Results: Survival was significantly different among the three groups with 80% survival at 28 days in the 1000ng/kg/min group, 52% in the 2000ng/kg/min group, and only 14% survival in the ATII/ BAPN group (p=0.0001; Figure 1). Unadjusted comparisons between each group were also significantly different (p<0.05). Rupture rates were statistically different among groups (8% vs 38% vs 79%, p<0.0001) and were again different on unadjusted comparison between groups (p<0.03). Incidence of abdominal AA formation were 48%, 55% and 93% in the three experimental groups and there were statistically significant differences between the ATII/ BAPN group and both the 1000ng/kg/min ATII and the 2000ng/kg/min ATII groups (p=0.006 and p=0.0165, respectively). Finally, rates of ascending thoracic AA formation were 12%, 52% and 79% in the three experimental groups with statistically significant differences between the 1000ng/kg/min ATII group and both the 2000ng/kg/min ATII and the ATII/ BAPN groups (p=0.0033 and p<0.0001, respectively).
Conclusion: In this study, a reproducible model of aortic rupture was developed with a high incidence of both abdominal and thoracic aortic aneurysm formation. This model should enable further studies to expand on research in aortic aneurysms and the pathogenesis of aortic rupture, as well as targeted strategies to prevent human aortic aneurysm rupture.
