Metabolomic Profiling in Acute ST‐Segment–Elevation Myocardial Infarction Identifies Succinate as an Early Marker of Human Ischemia–Reperfusion Injury
Open accessAbstract
Background: Ischemia–reperfusion injury following ST‐segment–elevation myocardial infarction (STEMI) is a leading determinant of clinical outcome. In experimental models of myocardial ischemia, succinate accumulation leading to mitochondrial dysfunction is a major cause of ischemia–reperfusion injury; however, the potential importance and specificity of myocardial succinate accumulation in human STEMI is unknown. We sought to identify the metabolites released from the heart in patients undergoing primary percutaneous coronary intervention for emergency treatment of STEMI. Methods and Results: Blood samples were obtained from the coronary artery, coronary sinus, and peripheral vein in patients undergoing primary percutaneous coronary intervention for acute STEMI and in control patients undergoing nonemergency coronary angiography or percutaneous coronary intervention for stable angina or non‐STEMI. Plasma metabolites were analyzed by targeted liquid chromatography and mass spectrometry. Metabolite levels for coronary artery, coronary sinus, and peripheral vein were compared to derive cardiac and systemic release ratios. In STEMI patients, cardiac magnetic resonance imaging was performed 2 days and 6 months after primary percutaneous coronary intervention to quantify acute myocardial edema and final infarct size, respectively. In total, 115 patients undergoing acute STEMI and 26 control patients were included. Succinate was the only metabolite significantly increased in coronary sinus blood compared with venous blood in STEMI patients, indicating cardiac release of succinate. STEMI patients had higher succinate concentrations in arterial, coronary sinus, and peripheral venous blood than patients with non‐STEMI or stable angina. Furthermore, cardiac succinate release in STEMI correlated with the extent of acute myocardial injury, quantified by cardiac magnetic resonance imaging. Conclusion: Succinate release by the myocardium correlates with the extent of ischemia.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Aberrant accumulation of fumarate in HLRCC correlates with increased endogenous damage, lower DNA repair efficiency and increased sensitivity to PARP inhibitors.
“In support of this unexpected function of fumarate, it was recently shown that the aberrant accumulation of this metabolite in HLRCC correlates with increased endogenous damage, lower DNA repair efficiency and increased sensitivity to poly-ADP ribose polymerase (PARP) inhibitors178.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [178]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 14 · Cited by 91
- Authors
- Kohlhauer, M., Dawkins, S., Costa, A. S. H., Lee, R., Young, T., Pell, V. R., Choudhury, R. P., Banning, A. P., Kharbanda, R. K., Study, O. A. M. I. (., Saeb‐Parsy, K., Murphy, M. P., Frezza, C., Krieg, T., & Channon, K. M.
- Affiliations
- Inserm (FR)
- John Radcliffe Hospital (GB)
- University of Cambridge (GB)
- NIHR Oxford Biomedical Research Centre (GB)
- Corresponding author
- Krieg, Thomas
- Channon, Keith M.
- ORCID
- Venue
- Journal of the American Heart Association
- Published
- 2018-04-17
- Volume
- 7
- Issue
- 8
- ISSN
- 2047-9980 (ISSN-L)
- PMC
- PMC6015393
- OpenAlex
- W2795910024
- Cited by
- 91
- References
- 14
- Citations by year
- 2026: 7 · 2025: 13 · 2024: 5 · 2023: 13 · 2022: 9 · 2021: 14 · 2020: 9 · 2019: 14 · 2018: 7
- FWCI
- 8.36
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Journal of the American Heart Association (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion, cc-by-nc-nd)
- Apollo
- Funders
- Wellcome Trust (110158/Z/15/Z, 110159/Z/ 15/Z, /Z/15/Z)
- National Institute for Health and Care Research (NF-SI-0514-10166)
- British Heart Foundation (RG/13/1/30181, CH/16/1/32013)
- Academy of Medical Sciences (AMS-SGCL13-Lee)
- European Commission (316738)
- Novo Nordisk Fonden (NNF15SA0018346)
- Medical Research Council (MC_UU_00015/3, MC-U105663142, MC_UU_12022/6)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Acute Myocardial Infarction Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Keywords
- succinic acid, ST-elevation myocardial infarction, ischemia-reperfusion injury, coronary sinus blood, cardiac biomarkers, myocardial edema, infarct size, primary percutaneous coronary intervention, mitochondrial dysfunction
- MeSH terms
- ST Elevation Myocardial Infarction, Adult, Aged, Aged, 80 and over, Female, Follow-Up Studies, Humans, Male, Middle Aged, Myocardium, Prognosis, Retrospective Studies, Time Factors, Biomarkers, Myocardial Reperfusion Injury, Coronary Angiography, Magnetic Resonance Imaging, Cine, Succinic Acid, Percutaneous Coronary Intervention
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
