NMR plasma metabolomics study of patients overcoming acute myocardial infarction: in the first 12 h after onset of chest pain with statistical discrimination towards metabolomic biomarkers.

Acute myocardial infarction (AMI) is one of the leading causes of death among adults in older age. Understanding mechanisms how organism responds to ischemia is essential for the ischemic patient's prevention and treatment. Despite the great prevalence and incidence only a small number of studies utilize a metabolomic approach to describe AMI condition. Recent studies have shown the impact of metabolites on epigenetic changes, in these studies plasma metabolites were related to neurological outcome of the patients making metabolomic studies increasingly interesting. The aim of this study was to describe metabolomic response of an organism to ischemic stress through the changes in energetic metabolites and aminoacids in blood plasma in patients overcoming acute myocardial infarction. Blood plasma from patients in the first 12 h after onset of chest pain was collected and compared with volunteers without any history of ischemic diseases via NMR spectroscopy. Lowered plasma levels of pyruvate, alanine, glutamine and neurotransmitter precursors tyrosine and tryptophan were found. Further, we observed increased plasma levels of 3-hydroxybutyrate and acetoacetate in balance with decreased level of lipoproteins fraction, suggesting the ongoing ketonic state of an organism. Discriminatory analysis showed very promising performance where compounds: lipoproteins, alanine, pyruvate, glutamine, tryptophan and 3-hydroxybutyrate were of the highest discriminatory power with feasibility of successful statistical discrimination.

Metabolomic study of altered energy metabolism during global forebrain ischemia and ischemic precoditioning in blood plasma in homocysteine treated rats.

Elevated homocysteine (Hcy) level is a well known risk factor for cardiovascular and neuropsychiatric diseases. In this study, we investigated metabolic changes in blood plasma in Hcy-treated rats. In combination with Hcy injections to induce hyperhomocysteinemia-like state, we used an animal model of global cerebral ischemia to investigate metabolic changes after 24 h reperfusion in rats. We also focused on the endogenous phenomenon known as ischemic tolerance induced by the preischemic treatment. The experiments were carried out on blood plasma samples as they are easily available and metabolically reflect the overall changes in injured organism. We observed significant changes in plasma metabolite levels of: pyruvate, citrate, acetate implicating alterations in energy metabolism, and increase in triacylglycerols, arginine and lysine, in Hcy-treated rats compared with naive animals. Ischemic insult with 24 reperfusion in Hcy-treated rats led to increase in plasma lactate, and decrease in plasma glucose, pyruvate, citrate and acetate. Complementary, an increase in ketone body 3-hydroxybutyrate was observed. The plasma metabolites: alanine, lactate, valine, glucose, leucine, isoleucine, acetate, citrate and 3-hydroxybutyrate were considered to reflect the response induced by ischemic preconditioning in Hcy rats, where the extent of postischemic damage was not as high as in the non-preconditioned rats. Our results provide evidence that nuclear magnetic resonance (NMR) spectra analysis can identify a specific group of metabolites present in plasma with the capability of discriminating between individual groups of animals. Regarding the effect of elevated Hcy level on plasma metabolome, we showed, that acetate, pyruvate and glucose had the excellent discriminatory power between Hcy-treated and naive rats plasma. Concerning ischemic insult in Hcy-treated animals, we also document the ideal discrimination of ischemic from non-ischemic rats by various groups of metabolites, that can be considered as a potential plasma biomarkers.