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. 2021 Aug 23;17(9):76.
doi: 10.1007/s11306-021-01827-x.

Perturbations in cardiac metabolism in a human model of acute myocardial ischaemia

Sanoj Chacko  1   2   3   4   5 , Mamas A Mamas  6   7 , Magdi El-Omar  6   8 , David Simon  9 , Sohaib Haseeb  10 , Farzin Fath-Ordoubadi  6   8 , Bernard Clarke  6   11 , Ludwig Neyses  6   12 , Warwick B Dunn  11   13
Affiliations

Perturbations in cardiac metabolism in a human model of acute myocardial ischaemia

Sanoj Chacko et al. Metabolomics. .

Abstract

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.

Keywords: Acute myocardial ischemia; Coronary sinus serum; Metabolism; Metabolomics; PCI.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1
Box and whisker plot describing normalized relative intensity values in the concentration of octanoyl carnitine (A) and hexadecanoic acid (B) at three timepoints (0 = baseline, 1 = TP1 and 5 = TP5) for peripheral samples. QC sample data are included (QC). Data for the discovery (left) and validation (right) studies are shown (p < 0.05)
Fig. 2
Fig. 2
Box and whisker plot describing normalized relative intensity values in the concentration of LysoPC(20:4) at three timepoints (0 = baseline, 1 = TP1 and 5 = TP5) for peripheral samples. QC sample data are included (QC). Data for the discovery (left) and validation (right) studies are shown (p < 0.05)
Fig. 3
Fig. 3
Box and whisker plot describing normalized relative intensity values in the concentration of tryptophan at three timepoints (0 = baseline, 1 = TP1 and 5 = TP5) for peripheral samples. QC sample data are included (QC). Data for the discovery (left) and validation (right) studies are shown
Fig. 4
Fig. 4
Box and whisker plot describing normalized relative intensity values in the concentration of arachidonic acid at three timepoints (0 = baseline, 1 = TP1 and 5 = TP5) for peripheral samples. QC sample data are included (QC). Data for the discovery (left) and validation (right) studies are shown (p < 0.05)
See this image and copyright information in PMC

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