2010kellydjmdCorrected..pdf (42.55 MB)
A Pre-clinical Evaluation of Growth Factor-eluting Stents for the Treatment of Chronic Total Coronary Artery Occlusion
thesisposted on 2010-10-19, 08:47 authored by Damian John Kelly
Objectives: Chronic total coronary artery occlusion (CTO) remains a significant challenge for percutaneous coronary intervention. Using a novel endovascular porcine model of coronary occlusion we investigated a strategy of promoting antegrade collateral vessels without crossing the occlusion. The prolyl-4-hydroxylase inhibitor, dimethyl oxalyl glycine (DMOG) was used to up-regulate a pro-angiogenic transcription factor, hypoxia inducible factor-1α. Method: DMOG was loaded onto a polymer-coated coronary stent. We developed a novel, entirely endovascular, method of inducing a coronary occlusion. Copper-coated stents were delivered percutaneously to produce CTO lesions in 20 Yorkshire white pigs. DMOG stents were implanted at day 28 and angiographic and physiological data collected on distal coronary and collateral flow. At day 56 the animals were sacrificed and histological analysis performed. Results: A complete total coronary occlusion was present in all animals at day 28 following implantation of a copper stent. At 56 days there was a greater percentage increase in angiographic collateral area in the DMOG group compared with the control (polymer-only stent) group (84.5±34.5% versus 16.5±5.9%, p=0.057). There was no difference between the groups in a surrogate measure of collateral flow at day 56. Histology revealed a significant increase in collateral vessels around the site of occlusion in the DMOG group compared with controls (29.9±2.6 versus 18.4±3.1, p=0.01). Conclusions: DMOG increased the number of collateral vessels at the site of vessel occlusion but not in the distal vessel. The angiogenic effect of DMOG appeared to be restricted to ischaemic tissue. Implantation of a copper stent provides a reliable entirely endovascular method of producing a CTO, with marked antegrade collateral formation present at 28 days. Proximal placement of stents delivering angiogenic compounds such as DMOG may provide a clinical management option in resistant CTO lesion.
Supervisor(s)Gershlick, Anthony H.; Gunn, Julian
Date of award2010-10-01
Awarding institutionUniversity of Leicester