ArticleeLife2021
β-hydroxybutyrate accumulates in the rat heart during low-flow ischaemia with implications for functional recovery.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- Redox coupling of lactate and β-hydroxybutyrate: An inter-organ circuit linking metabolic flexibility, mitochondrial adaptation, and disease.Redox biology · 2026Review
- Differential transcriptomic and metabolomic landscape between human hearts donated after cardiac vs brain death.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2026Article
- Brain-derived ketone bodies can replace glucose to power neural function.bioRxiv : the preprint server for biology · 2026Article
- Regulatory mechanisms and interactions of mitophagy and ketone body metabolism in cardiac metabolism.Frontiers in cardiovascular medicine · 2026Review
- Emerging therapy strategies for energy metabolism in acute myocardial infarction.Journal of translational medicine · 2025Review
- The regulatory role of exercise in heart failure and myocardial energy metabolism: A review.Biomolecules & biomedicine · 2025Review
- β-Hydroxybutyrate Facilitates Homeostasis of Hypoxic Endothelial Cells After Myocardial Infarction via Histone Lysine β-Hydroxybutyrylation of CPT1A.JACC. Basic to translational science · 2025Article
- CD8Journal of inflammation research · 2025Article
- Beta-adrenergic agonism protects mitochondrial metabolism in the pancreatectomised rat heart.Scientific reports · 2024Article
- Empagliflozin improves mitochondrial dysfunction in diabetic cardiomyopathy by modulating ketone body metabolism and oxidative stress.Redox biology · 2024Article
- Glucagon and exenatide improve contractile recovery following ischaemia/reperfusion in the isolated perfused rat heart.Physiological reports · 2023Article
- Ischemia promotes acyl-CoAs dephosphorylation and propionyl-CoA accumulation.Metabolomics : Official journal of the Metabolomic Society · 2023Article
- Emerging Roles of SIRT3 in Cardiac Metabolism.Frontiers in cardiovascular medicine · 2022Review
- Article
- Ketone Body Metabolism in the Ischemic Heart.Frontiers in cardiovascular medicine · 2021Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Extrahepatic tissues which oxidise ketone bodies also have the capacity to accumulate them under particular conditions. We hypothesised that acetyl-coenzyme A (acetyl-CoA) accumulation and altered redox status during low-flow ischaemia would support ketone body production in the heart. Combining a Langendorff heart model of low-flow ischaemia/reperfusion with liquid chromatography coupled tandem mass spectrometry (LC-MS/MS), we show that β-hydroxybutyrate (β-OHB) accumulated in the ischaemic heart to 23.9 nmol/gww and was secreted into the coronary effluent. Sodium oxamate, a lactate dehydrogenase (LDH) inhibitor, increased ischaemic β-OHB levels 5.3-fold and slowed contractile recovery. Inhibition of β-hydroxy-β-methylglutaryl (HMG)-CoA synthase (HMGCS2) with hymeglusin lowered ischaemic β-OHB accumulation by 40%, despite increased flux through succinyl-CoA-3-oxaloacid CoA transferase (SCOT), resulting in greater contractile recovery. Hymeglusin also protected cardiac mitochondrial respiratory capacity during ischaemia/reperfusion. In conclusion, net ketone generation occurs in the heart under conditions of low-flow ischaemia. The process is driven by flux through both HMGCS2 and SCOT, and impacts on cardiac functional recovery from ischaemia/reperfusion.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.