New perspectives in abdominal aortic aneurysm management

A better understanding of the pathophysiology of abdominal aortic aneurysms has recently been established paving the way for potential targeted pharmacotherapy aimed at inhibiting the growth of small aneurysms. In particular the matrix metallopropteinase enzymes have been implicated in the destruction of the aortic wall. To this end the first part of this thesis investigates the potential therapeutic role of doxycycline, a non-specific metalloproteinase inhibitor, in an established model of aneurysmal disease. Subsequently the role of Amlodipine a calcium antagonist and metalloproteinase potentiator is investigated in the same model.;Endovascular AAA repair is a new minimally invasive technique that allows treatment of aortic aneurysms without major abdominal surgery. The feasibility of this technique has been established, however a number of important questions remain unanswered. The second half of this thesis investigates the invasiveness of endovascular repair in comparison to conventional surgery. In particular the impact both procedures have on respiratory, cardiac, renal and metabolic responses is studied in comparative cohorts undergoing both conventional and endovascular AAA repair. Finally the implications of offering a tertiary referral service for AAA treatment is investigated.;The results presented in this thesis demonstrate that doxycycline inhibits MMP activity and thus elastin destruction in a porcine model of aneurysmal disease. In the same model however, Amlodipine potentiates MMP activity and accelerates elastin degradation. There may be a therapeutic role for doxycycline in reducing the growth rate of small aneurysms. The clinical investigations of this thesis show that endovascular AAA repair attenuates the respiratory, cardiovascular, renal and metabolic responses associated with conventional aneurysm surgery. There were however still considerable insults from endoluminal surgery. Endovascular AAA repair may reduce morbidity and mortality rates after elective AAA surgery. The last experimental chapter illustrates that offering endovascular AAA repair as a tertiary centre has considerable clinical and financial implications. Finally a number of problems remain with endovascular AAA surgery which require evaluation by randomised controlled trial before its widespread use.