1H NMR-based metabolomic identification of at-risk areas after myocardial infarction in swine

Abstract

(1)H NMR-based metabolic profiling has been used to investigate areas of the heart after an acute myocardial infarction. Tissue was obtained from control, at-risk (areas that survive within the infarct zone) and necrotic myocardium after 48 min of left anterior descending coronary artery occlusion and 2 h of reperfusion in a swine model. HR-MAS (high resolution magic angle spectroscopy) spectra from intact tissue and tissue extract spectra were obtained for each region and statistical models were built for each type of spectra allowing differentiation between control, at-risk and necrotic heart. At-risk and, especially, necrotic areas have a reduced concentration of NMR visible metabolites as compared to control tissue, total creatine (phosphorilated and unphosphorilated) being the single most important metabolite in the different discriminant models. Creatine concentration decreased from 18.28 +/- 0.84 micromols/g fresh weight in controls to 12.58 +/- 2.89 (P < 0.05) and 9.96 +/- 2.21 (P < 0.01) in at-risk and necrotic areas, respectively. Taurine and myo-inositol were also involved in the discriminant models. HR-MAS spectra also showed an increase in lipid signals at 0.9 and 1.28 ppm as markers of necrotic tissue. These results support the view that the analysis of in vivo (1)H MRS may have value in differentiating normal, at-risk and infarcted myocardium.