Abstract

BACKGROUND:

In reperfused acute myocardial infarction (RAMI), cardioprotective treatments may enhance myocardial salvage and hence reduce the area of necrosis. Based on studies showing that plasmid-mediated vascular endothelial growth factor (pVEGF) gene transfer reduces infarct size by combining angio-arteriogenic and cardiomyogenic effects and that erythropoietin (EPO) exerts anti-apoptotic actions in animal models of AMI, we aimed to assess if their association would reduce infarct size to a larger extent than any of them individually in a large mammalian model of RAMI.

METHODS:

Adult sheep subjected to 90-minute coronary artery occlusion received upon reperfusion intramyocardial pVEGF 3.8mg plus intravenous EPO 1000IU/kg (n=8), pVEGF (n=8), EPO (n=8) or placebo (n=8).

RESULTS:

Fifteen days after treatment, infarct size was smaller in the 3 treatment groups (pVEGF+EPO: 8±1%; pVEGF: 16±5%; EPO: 13±4%) compared to placebo (25±7%, p<0.001). However, in the EPO+VEGF group infarct size was significantly smaller than in the groups receiving EPO or VEGF individually (p<0.05). DNA fragmentation, a hallmark of late apoptosis, was significantly lower in sheep receiving EPO. The combined treatment, while not affecting global left ventricular performance, improved regional peri-infarct function and prevented over-time expansion of the post-infarct perfusion defect.

CONCLUSIONS:

Combined pVEGF and EPO treatment might be clinically useful to enhance the benefits of early revascularization in patients with acute myocardial infarction.

Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.