W. Montgomery1, M. Spinosa1, J. Cullen1, M. Salmon1, G. Su1, T. Hassinger1, A. Sharma1, G. Lu1, A. Fashandi1, G. Ailawadi1, G. R. Upchurch1 1University Of Virginia,Surgery,Charlottesville, VA, USA
Introduction:
Flomax® (Tamsulosin) is traditionally prescribed to treat benign prostatic hyperplasia (BPH) in men over the age of 50 years old, the same demographic most susceptible to abdominal aortic aneurysm (AAA) formation. The goal of this study was to investigate the effect of Flomax® on AAA pathogenesis, as it was hypothesized that Flomax® would attenuate AAA growth.
Methods:
AAAs were induced in 8-12 week old C57BL/6 (Wild type: n=9-18/group) using a previously established topical elastase AAA model. Osmotic pumps were implanted in each mouse 5 days prior to surgery to administer either a low dose (0.125 µg/day tamsulosin), high dose (0.250 µg/day tamsulosin), or vehicle treatments both with and without topical elastase application during AAA surgery. Blood pressure in each group was measured preoperatively, and on postoperative days 7 and 14. On postoperative day 14, aortic diameter was measured prior to harvest. Sample aorta were prepared for histology and cytokine analysis. Data was analyzed statistically using Fisher’s exact test or chi-squared test as appropriate with significance set to α<0.05.
Results:
Systolic blood pressure measurements were not significantly different preoperatively, on day 7 or 14 for all groups. Mice treated with both low and high-dose of tamsulosin showed significantly decreased aortic diameter compared to the vehicle-treated control mice (p<0.001). Cytokine analysis demonstrated a significant down-regulation in pro-inflammatory cytokines (TNF-α, IL-1β, IL-7, IL-17, CXCL2, and IFN-γ) in both treatment groups compared with control (p<0.05). Histology exhibited a significant preservation of elastin integrity in both low and high-dose tamsulosin-treated groups (p=0.0041 and p=0.0018, respectively).
Conclusion:
Flomax®, an alpha 1 adrenergic receptor inhibitor, which is used commonly in BPH and affects smooth muscle cell vasorelaxation, attenuates AAA formation in association with increased elastin preservation and decreased pro-inflammatory cytokine production. Further research is required to elucidate the mechanism by which tamsulosin inhibits AAA growth. Flomax® (Tamsulosin) could represent a potential therapeutic medical treatment strategy for AAA disease.
