Clinical & Experimental Cardiology
Open Access

Abstract

Activation of Hypoxia-Inducible Factor by Di-Methyl Oxalyl Glycine (DMOG) Increases Neovascularization within Ischaemic Myocardium in a Porcine Coronary Artery Occlusion Model

D J S Kelly, A C Morton, N D Arnold, J Mecinovic, C Schofield, H Lupton, K Al-Lamee, D C Crossman, J Gunn and A Gershlick

Introduction: Chronic total coronary artery occlusion (CTO) in man remains a significant challenge for percutaneous coronary intervention (PCI) and a common reason for coronary artery bypass surgery, as often the CTO cannot be crossed. This study investigated whether a potential angiogenic treatment, the prolyl-4-hydroxylase inhibitor, di-methyl oxalyl glycine (DMOG), would increase collateral vessel formation and myocardial perfusion without opening the CTO in a porcine model of coronary CTO.
Methods: We assessed the effect of DMOG upon tube formation of HUVEC in a matrigel assay in vitro. DMOG was loaded onto a polymer-coated coronary stent. Copper-coated stents were used to produce a coronary CTO in 20 pigs. DMOG-loaded or control stents were implanted in an alternating, blinded manner at day 28, proximal to the CTO. Angiographic and physiological flow data were collected at day 56, when the animals were sacrificed and the collateral vessels counted.
Results: DMOG increased tubule formation in vitro by 77% compared with control (p<0.0001). DMOG was successfully loaded onto the polymer coated stent, as evidenced by the same assay. A CTO was present at angiography in all animals 28 days. At 56 days there was a trend towards a greater increase in angiographic collateral vessel area around the CTO in the DMOG group compared with controls +84.5% vs. +16.5%, respectively, p=0.057). Histology revealed a significant increase in the number of collateral vessels around the site of occlusion in the DMOG group vs control (29.9?2.6 vs 18.4?3.1, respectively; p=0.01). There was no difference between the groups in terms of collateral flow index at day 56.
Conclusion: DMOG, delivered on a polymer-coated stent, proximal to an occluded porcine coronary artery, increased the number of collateral vessels seen at the site of vessel occlusion but not to a level sufficient to increase measures of functional flow.