Abstract 13267: The Shifted Balance of Arginine Metabolites in Patients With Acute Myocardial Infarction and Its Association With the Composition of the Infarct-Related Culprit Lesion

Abstract

Introduction: We hypothesize that acute phase of myocardial infarction (MI) is associated with suppression of nitric oxide synthase (NOS) and enhanced arginase activity. Moreover, this altered metabolic balance might correlate with the composition of vulnerable culprit lesion in the infarct-related coronary artery (IRA). Methods: Arginine metabolites (μM) including ornithine, citrulline, proline, spermine, spermidine, agmatine, homoarginine, creatine, asymmetric dimethylarginine (ADMA) and monomethyl-L-arginine acetate were measured using liquid chromatography and tandem mass spectrometry in 85 consecutive MI patients upon admission and at 6-month follow-up and were compared with the composition of the IRA culprit lesion assessed with optical coherence tomography (OCT). Results: The concentration of ornithine in acute phase of MI was higher by 44% and homoarginine by 62% whereas level of arginine was lower by 39% and citrulline by 64% (P<0.001 for all), when compared to 6-month stable conditions. Following ischemia, the ratios of citrulline/arginine (0.10 [0.08; 0.14] vs 0.22 [0.18; 0.28]) and citrulline/ornithine (0.09 [0.07; 0.12] vs 0.47 [0.36; 0.55]) were decreased while the indices of ornithine/arginine (1.48 [1.08, 2.39] vs 0.50 [0.41, 0.60]) and homoarginine/arginine (0.17 [0.12; 0.22] vs 0.04 [0.03; 0.05]) were higher as compared with 6-month results (P<0.001 for all). Both, concentrations of arginine metabolites and their ratios were not associated with the mechanism of IRA occlusion, the amount of calcium or lipids and the presence of intramural hematoma. However, in patients with (n=67) versus without (n=18) thin-cap fibroatheroma (TCFA) in OCT the higher median concentrations of ornithine (10.24 [7.86; 12.52] vs 7.82 [4.38; 9.57]), ADMA (0.40 [0.29; 0.49] vs 0.29 [0.23; 0.42]), homoarginine (1.02 [0.81; 1.27] vs 0.74 [0.62; 1.00]) and a higher ornithine/arginine ratio (1.73 [1.29; 2.54] vs 1.18 [1.01; 2.07]) with a lower citrulline/ornithine ratio (0.07 [0.09; 0.11] vs 0.13 [0.09; 0.15]) were found (P<0.05 for all). Conclusions: During acute phase of MI the altered balance of arginine metabolites indicates NOS suppression and enhanced arginase activation and is associated with the presence of TCFA in IRA culprit lesion.