A characterization and targeting of the infarct border zone in a swine model of myocardial infarction.

Abstract

INTRODUCTION: Novel therapies for myocardial infarction (MI) involving stem cells, gene therapy, biomaterials, or revascularization strategies have shown promise in animal studies and clinical trials, but results have been limited partially due to the injection of therapeutics into ischemic myocardium that cannot support their mechanism of action. Accurate targeting of therapeutics precisely to the infarct border zone (BZ) may be essential for effective repair of the ischemic heart. METHODS: Ischemia-reperfusion MI was induced in Yorkshire swine by inflation of an angioplasty balloon in the left anterior descending coronary artery. Fluorescent microspheres were injected into the BZ under NOGA catheter guidance, and this location was identified grossly then examined by immunohistochemistry and Western analysis. RESULTS: Analysis of the infarct zone two hours post-MI revealed a frankly necrotic region devoid of contractile proteins with marked activation of caspase-3. The NOGA-defined BZ closely approximates the grossly-defined BZ and contains intact myocytes and vasculature. Western analysis detected Akt expression and levels of Ca(2+) handling proteins equivalent to that of viable tissues. CONCLUSIONS: Histological and Western analysis revealed that NOGA mapping precisely identifies grossly and molecularly defined infarct BZ at a location where there are still viable cells and vessels capable of supporting novel therapeutic strategies.