The investigation of novel technology and technique in the treatment of vascular disease

Cardiovascular disease takes more human life than any other disease process. The vascular specialist fights a daily battle to limit the progression of atherosclerosis and replenish the circulation when it is compromised. Increasingly reliant on technological advances, the specialty is responsible for the evaluation of new devices and techniques through scientific method. This thesis represents a body of work which addresses several advances within the realm of vascular disease.In the first experimental portion a large animal model was established to evaluate a novel, nitinol, anastomotic device, the U-clip. Arteriovenous fistulae were created to compare the local cellular response around it and the conventional suture material. A distinct advantage was observed for the new technology with less intimal hyperplasia, necrosis and proliferating cells at earlier time points. The second experimental portion saw a focus on carotid artery stenting (CAS), a percutaneous method of revascularisation which utilises nitinol for both the carotid stent and the cerebral protection device (CPD). In a comprehensive histological and biomarker analysis the debris collected in the distal-filter CPD was found to contain more calcified tissue and fewer foam cells in symptomatic patients compared to asymptomatic ones. It also demonstrated a greater proportion of inflammatory cytokines, macrophage specific proteins and matrix metelloproteinase (MMP)-9, a gelatinase known to incite histological features of plaque vulnerability. In a second study a new technique to perform CAS guided by extra-vascular ultrasound was compared with standard CAS (fluoroscopy/angiography). This demonstrated significantly less contrast use and fewer direct cerebral injections whilst maintaining equivalent safety and efficacy. A corrosion-resistance analysis of nitinol stents used throughout the human body was performed to compare five stents used in clinical practice. It found a degree of difference in the corrosion-resistance properties of those five devices and demonstrated that corrosion in isolation may lead to stent fracture. Finally, the evolution of clinical practice in the treatment of critical lower limb ischaemia was evaluated in a single-centre experience. A shifting paradigm toward an endovascular-first strategy resulted in fewer major amputations and considerably less reliance on hospital inpatient resources compared to the open-surgery-first approach of a bygone era