Abstract 12050: Ketone Ester Supplementation Reduces Cardiac Inflammation and Enhances Cardiac Energetics in Acute Myocardial Infarction

• Published in: Circulation (New York, N.Y.) Vol. 146; no. Suppl_1; p. A12050
• Main Authors: Yurista, Salva, Welsh, Aidan, Jiang, William, Eder, Robert, Chen, Shi, Foster, Anna, Coll-Font, Jaume, Rosenzweig, Anthony, Nguyen, Christopher T
• Format: Journal Article
• Language: English
• Published: Lippincott Williams & Wilkins 08-11-2022
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circ.146.suppl_1.12050

IntroductionMyocardial infarction (MI) is a major risk factor for the development of heart failure with reduce ejection fraction (HFrEF). While previous studies have focused on HFrEF, the role of ketone bodies in MI is unclear. HypothesisK etone may exert some cardioprotective effects following MI. MethodsMale Yorkshire pigs underwent percutaneous balloon occlusion of the LAD for 80 minutes followed by 72 hours reperfusion period. Oral ketone ester (BHB-butanediol monoester, KE, 550 mg/kg) or vehicle was administered during reperfusion and continued during the follow-up period. Simultaneous blood sampling from coronary sinus and artery was obtained to quantify the extraction fraction of major cardiac substrates. Scar size was measured by LGE CMR and molecular markers were assessed in the LV. The study was approved by the IACUC at the Massachusetts General Hospital. ResultsKE induced ketosis within 30 min after ingestion. KE increased β-hydroxybutyrate (βOHB) extraction in healthy swine without affecting glucose and fatty acid (FA) consumption. Despite similar infarct size in both MI and MI-KE groups, cardiac expression of proinflammatory cytokines TNF-⍺, IL-1, IL-6, and cardiac injury TTNI3 alongside with plasma hs-cTnI were reduced by KE. The untreated MI hearts consumed less FA with no changes in glucose uptake, whereas hearts from KE-treated animals consumed more βOHB and FA. KE increased cardiac expression of genes involved in ketone utilization MCT1 and SCOT after MI (p<0.05 for all), indicating that cardiac uptake and utilization of βOHB as fuel were augmented. Together these metabolic changes were associated with an increase in cardiac ATP production. RNA-seq analysis identified differentially expressed genes related to mitochondrial energy metabolism. ConclusionsOral KE induced ketosis and enhanced cardiac βOHB extraction in both healthy and infarcted hearts. Although infarct size was unchanged 72h after MI, acute oral supplementation with KE supressed cardiac inflammation and injury, altered cardiac substrate uptake and enhanced cardiac energetics following acute MI. Evaluating the potential chronic benefits of these changes on long-term remodeling after MI will be an exciting direction for future studies.