Metabolomic Profile of Human Myocardial Ischemia by Nuclear Magnetic Resonance Spectroscopy of Peripheral Blood Serum: A Translational Study Based on Transient Coronary Occlusion Models

Abstract

The aim of this study was to investigate the metabolomic profile of acute myocardial ischemia (MIS) using nuclear magnetic resonance spectroscopy of peripheral blood serum of swine and patients undergoing angioplasty balloon-induced transient coronary occlusion. Biochemical detection of MIS is a major challenge. The validation of novel biosignatures is of utmost importance. High-resolution nuclear magnetic resonance spectroscopy was used to profile 32 blood serum metabolites obtained (before and after controlled ischemia) from swine (n = 9) and patients (n = 20) undergoing transitory MIS in the setting of planned coronary angioplasty. Additionally, blood serum of control patients (n = 10) was sequentially profiled. Preliminary clinical validation of the developed metabolomic biosignature was undertaken in patients with spontaneous acute chest pain (n = 30). Striking differences were detected in the blood profiles of swine and patients immediately after MIS. MIS induced early increases (10 min) of circulating glucose, lactate, glutamine, glycine, glycerol, phenylalanine, tyrosine, and phosphoethanolamine; decreases in choline-containing compounds and triacylglycerols; and a change in the pattern of total, esterified, and nonesterified fatty acids. Creatine increased 2 h after ischemia. Using multivariate analyses, a biosignature was developed that accurately detected patients with MIS both in the setting of angioplasty-related MIS (area under the curve 0.94) and in patients with acute chest pain (negative predictive value 95%). This study reports, to the authors' knowledge, the first metabolic biosignature of acute MIS developed under highly controlled coronary flow restriction. Metabolic profiling of blood plasma appears to be a promising approach for the early detection of MIS in patients.