Chacko, S, Mamas, MA, El-Omar, M, Simon, D, Haseeb, S, Fath-ordoubadi, F, Clarke, B, Neyses, L and Dunn, WB (2021) Perturbations in cardiac metabolism in a human model of acute myocardial ischaemia. Metabolomics, 17 (9). ISSN 1573-3882

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Introduction Acute myocardial ischaemia and the transition from reversible to irreversible myocardial injury are associated with abnormal metabolic patterns. Advances in metabolomics have extended our capabilities to define these metabolic perturbations on a metabolome-wide scale. Objectives This study was designed to identify cardiac metabolic changes in serum during the first 5 min following early myocardial ischaemia in humans, applying an untargeted metabolomics approach. Methods Peripheral venous samples were collected from 46 patients in a discovery study (DS) and a validation study (VS) (25 for DS, 21 for VS). Coronary sinus venous samples were collected from 7 patients (4 for DS, 3 for VS). Acute myocardial ischaemia was induced by transient coronary occlusion during percutaneous coronary intervention (PCI). Plasma samples were collected at baseline (prior to PCI) and at 1 and 5 min post-coronary occlusion. Samples were analyzed by Ultra Performance Liquid Chromatography-Mass Spectrometry in an untargeted metabolomics approach. Results The study observed changes in the circulating levels of metabolites at 1 and 5 min following transient coronary ischaemia. Both DS and VS identified 54 and 55 metabolites as significant (P < 0.05) when compared to baseline levels, respectively. Fatty acid beta-oxidation and anaerobic respiration, lysoglycerophospholipids, arachidonic acid, docosahexaenoic acid, tryptophan metabolism and sphingosine-1-phosphate were identified as mechanistically important. Conclusion Using an untargeted metabolomics approach, the study identified important cardiac metabolic changes in peripheral and coronary sinus plasma, in a human model of controlled acute myocardial ischaemia. Distinct classes of metabolites were shown to be involved in the rapid cardiac response to ischemia and provide insights into diagnostic and interventional targets.

Item Type: Article
Additional Information: Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit
Uncontrolled Keywords: Acute myocardial ischemia; Coronary sinus serum; Metabolomics; Metabolism; PCI
Subjects: R Medicine > R Medicine (General)
R Medicine > RD Surgery
Divisions: Faculty of Medicine and Health Sciences > School of Medicine
Depositing User: Symplectic
Date Deposited: 09 Sep 2021 09:51
Last Modified: 19 Nov 2021 11:50

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