The ketone body 3-hydroxybutyrate increases cardiac output and cardiac contractility in a porcine model of cardiogenic shock: a randomized, blinded, crossover trial

Anderson JL, Baim DS, Fein SA, Goldstein RA, LeJemtel TH, Likoff MJ (1987) Efficacy and safety of sustained (48 hour) intravenous infusions of milrinone in patients with severe congestive heart failure: a multicenter study. J Am Coll Cardiol 9:711–722. https://doi.org/10.1016/S0735-1097(87)80223-1

Article  CAS  PubMed  Google Scholar 

Annoni F, Su F, Peluso L, Lisi I, Caruso E, Pischiutta F, Gouvea Bogossian E, Garcia B, Njimi H, Vincent J-L, Gaspard N, Ferlini L, Creteur J, Zanier ER, Taccone FS (2024) Infusion of sodium DL-3-ß-hydroxybutyrate decreases cerebral injury biomarkers after resuscitation in experimental cardiac arrest. Crit Care 28:314. https://doi.org/10.1186/s13054-024-05106-8

Article  PubMed  PubMed Central  Google Scholar 

Antonopoulos AS, Goliopoulou A, Vogiatzi G, Tousoulis D (2018) Myocardial oxygen consumption. Coronary artery disease. Elsevier, Amsterdam, pp 127–136

Chapter  Google Scholar 

Berg-Hansen K, Gopalasingam N, Christensen KH, Ladefoged B, Andersen MJ, Poulsen SH, Borlaug BA, Nielsen R, Møller N, Wiggers H (2024) Cardiovascular Effects of Oral Ketone Ester Treatment in Patients With Heart Failure With Reduced Ejection Fraction: A Randomized, Controlled, Double-Blind Trial. Circulation. https://doi.org/10.1161/CIRCULATIONAHA.123.067971

Berg-Hansen K, Christensen KH, Gopalasingam N, Nielsen R, Eiskjær H, Møller N, Birkelund T, Christensen S, Wiggers H (2023) Beneficial effects of ketone ester in patients with cardiogenic shock: a randomized, controlled, double-blind trial. JACC Heart Fail 11:1337–1347. https://doi.org/10.1016/j.jchf.2023.05.029

Article  CAS  PubMed  Google Scholar 

Brand MD, Nicholls DG (2011) Assessing mitochondrial dysfunction in cells. Biochemical Journal 435:297–312. https://doi.org/10.1042/BJ20110162

Article  CAS  PubMed  Google Scholar 

Byrne NJ, Soni S, Takahara S, Ferdaoussi M, Al Batran R, Darwesh AM, Levasseur JL, Beker D, Vos DY, Schmidt MA, Alam AS, Maayah ZH, Schertzer JD, Seubert JM, Ussher JR, Dyck JRB (2020) Chronically Elevating Circulating Ketones Can Reduce Cardiac Inflammation and Blunt the Development of Heart Failure. Circ Heart Fail 13. https://doi.org/10.1161/CIRCHEARTFAILURE.119.006573

Chirinos JA, Rietzschel ER, Shiva-Kumar P, De Buyzere ML, Zamani P, Claessens T, Geraci S, Konda P, De Bacquer D, Akers SR, Gillebert TC, Segers P (2014) Effective Arterial Elastance Is Insensitive to Pulsatile Arterial Load. Hypertension 64:1022–1031. https://doi.org/10.1161/HYPERTENSIONAHA.114.03696

Article  CAS  PubMed  Google Scholar 

Chu Y, Hua Y, He L, He J, Chen Y, Yang J, Mahmoud I, Zeng F, Zeng X, Benavides GA, Darley-Usmar VM, Young ME, Ballinger SW, Prabhu SD, Zhang C, Xie M (2024) β-hydroxybutyrate administered at reperfusion reduces infarct size and preserves cardiac function by improving mitochondrial function through autophagy in male mice. J Mol Cell Cardiol 186:31–44. https://doi.org/10.1016/j.yjmcc.2023.11.001

Article  CAS  PubMed  Google Scholar 

Curran J, Burkhoff D, Kloner RA (2019) Beyond Reperfusion: Acute Ventricular Unloading and Cardioprotection During Myocardial Infarction. J Cardiovasc Transl Res 12:95–106. https://doi.org/10.1007/s12265-019-9863-z

Article  PubMed  PubMed Central  Google Scholar 

Doerrier C, Garcia-Souza LF, Krumschnabel G, Wohlfarter Y, Mészáros AT, Gnaiger E (2018) High-Resolution FluoRespirometry and OXPHOS Protocols for Human Cells, Permeabilized Fibers from Small Biopsies of Muscle, and Isolated Mitochondria. pp 31–70

Eichhorn EJ, Konstam MA, Weiland DS, Roberts DJ, Martin TT, Stransky NB, Salem DN (1987) Differential effects of milrinone and dobutamine on right ventricular preload, afterload and systolic performance in congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol 60:1329–1333. https://doi.org/10.1016/0002-9149(87)90616-3

Article  CAS  PubMed  Google Scholar 

Eickelmann C, Lieder HR, Shehada S-E, Thielmann M, Heusch G, Kleinbongard P (2023) Mitochondrial respiration analysis in permeabilized porcine left ventricular and human right atrial specimens with ischemia-reperfusion. American Journal of Physiology-Heart and Circulatory Physiology 325:H125–H135. https://doi.org/10.1152/ajpheart.00172.2023

Article  CAS  PubMed  Google Scholar 

Fincke R, Hochman JS, Lowe AM, Menon V, Slater JN, Webb JG, LeJemtel TH, Cotter G, Investigators SHOCK (2004) Cardiac power is the strongest hemodynamic correlate of mortality in cardiogenic shock: a report from the SHOCK trial registry. J Am Coll Cardiol 44:340–348. https://doi.org/10.1016/j.jacc.2004.03.060

Article  PubMed  Google Scholar 

Francis GS, Sharma B, Hodges M (1982) Comparative hemodynamic effects of dopamine and dobutamine in patients with acute cardiogenic circulatory collapse. Am Heart J 103:995–1000. https://doi.org/10.1016/0002-8703(82)90562-2

Article  CAS  PubMed  Google Scholar 

Frey S, Geffroy G, Desquiret-Dumas V, Gueguen N, Bris C, Belal S, Amati-Bonneau P, Chevrollier A, Barth M, Henrion D, Lenaers G, Bonneau D, Reynier P, Procaccio V (2017) The addition of ketone bodies alleviates mitochondrial dysfunction by restoring complex I assembly in a MELAS cellular model. Biochim Biophys Acta (BBA) Mol Basis Dis 1863:284–291. https://doi.org/10.1016/j.bbadis.2016.10.028

Article  CAS  Google Scholar 

Gambardella J, Jankauskas SS, Kansakar U, Varzideh F, Avvisato R, Prevete N, Sidoli S, Mone P, Wang X, Lombardi A, Santulli G (2023) Ketone bodies rescue mitochondrial dysfunction via epigenetic remodeling. JACC Basic Transl Sci 8:1123–1137. https://doi.org/10.1016/j.jacbts.2023.03.014

Article  PubMed  PubMed Central  Google Scholar 

Genserová L, Duška F, Krajčová A (2024) β-hydroxybutyrate exposure restores mitochondrial function in skeletal muscle satellite cells of critically ill patients. Clin Nutr 43:1250–1260. https://doi.org/10.1016/j.clnu.2024.04.009

Article  CAS  PubMed  Google Scholar 

Gopalasingam N, Christensen KH, Berg Hansen K, Nielsen R, Johannsen M, Gormsen LC, Boedtkjer E, Nørregaard R, Møller N, Wiggers H (2023) Stimulation of the hydroxycarboxylic acid receptor 2 with the ketone body 3-hydroxybutyrate and niacin in patients with chronic heart failure: hemodynamic and metabolic effects. J Am Heart Assoc 12:e029849. https://doi.org/10.1161/JAHA.123.029849

Article  PubMed  PubMed Central  Google Scholar 

Gopalasingam N, Moeslund N, Christensen KH, Berg-Hansen K, Seefeldt J, Homilius C, Nielsen EN, Dollerup MR, Alstrup Olsen AK, Johannsen M, Boedtkjer E, Møller N, Eiskjær H, Gormsen LC, Nielsen R, Wiggers H (2024) Enantiomer-specific cardiovascular effects of the ketone body 3-hydroxybutyrate. J Am Heart Assoc. https://doi.org/10.1161/JAHA.123.033628

Article  PubMed  PubMed Central  Google Scholar 

Gopalasingam N, Berg-Hansen K, Christensen KH, Ladefoged BT, Poulsen SH, Andersen MJ, Borlaug B, Nielsen R, Møller N, Wiggers H (2024) Randomized crossover trial of 2-week ketone ester treatment in patients with Type 2 diabetes and heart failure with preserved ejection fraction. Circulation. https://doi.org/10.1161/CIRCULATIONAHA.124.069732

Article  PubMed  PubMed Central  Google Scholar 

Han Y, Bedarida T, Ding Y, Somba BK, Lu Q, Wang Q, Song P, Zou M-H (2018) β-Hydroxybutyrate prevents vascular senescence through hnRNP A1-mediated upregulation of Oct4. Mol Cell 71:1064-1078.e5. https://doi.org/10.1016/j.molcel.2018.07.036

Article  CAS  PubMed  PubMed Central  Google Scholar 

Harjola V-P, Lassus J, Sionis A, Køber L, Tarvasmäki T, Spinar J, Parissis J, Banaszewski M, Silva-Cardoso J, Carubelli V, Di Somma S, Tolppanen H, Zeymer U, Thiele H, Nieminen MS, Mebazaa A, CardShock Study Investigators, GREAT network (2015) Clinical picture and risk prediction of short-term mortality in cardiogenic shock. Eur J Heart Fail 17:501–509. https://doi.org/10.1002/ejhf.260

Article  PubMed  Google Scholar 

Hevrøy O, Reikerås O, Grundnes O, Mjøs OD (1988) Cardiovascular effects of positive end-expiratory pressure during acute left ventricular failure in dogs. Clin Physiol 8:287–301. https://doi.org/10.1111/j.1475-097x.1988.tb00271.x

Article  PubMed  Google Scholar 

Homilius C, Seefeldt JM, Axelsen JS, Pedersen TM, Sørensen TM, Nielsen R, Wiggers H, Hansen J, Matchkov VV, Bøtker HE, Boedtkjer E (2023) Ketone body 3-hydroxybutyrate elevates cardiac output through peripheral vasorelaxation and enhanced cardiac contractility. Basic Res Cardiol 118:37. https://doi.org/10.1007/s00395-023-01008-y

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hørsdal OK (2025) Can utilization of the venous-to-arterial carbon dioxide difference improve patient outcomes in cardiogenic shock? A narrative review. Am Heart J Plus Cardiol Res Pract 50:100504. https://doi.org/10.1016/j.ahjo.2025.100504

Article  Google Scholar 

Hørsdal OK, Moeslund N, Berg-Hansen K, Nielsen R, Møller N, Eiskjær H, Wiggers H, Gopalasingam N (2024) Lactate infusion elevates cardiac output through increased heart rate and decreased vascular resistance: a randomised, blinded, crossover trial in a healthy porcine model. J Transl Med 22:285. https://doi.org/10.1186/s12967-024-05064-3

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hørsdal OK, Wethelund KL, Gopalasingam N, Lyhne MD, Ellegaard MS, Møller-Helgestad OK, Ravn HB, Wiggers H, Christensen S, Berg-Hansen K (2024) Cardiovascular effects of increasing positive end-expiratory pressure in a model of left ventricular cardiogenic shock in female pigs. Anesthesiology. https://doi.org/10.1097/ALN.0000000000005201

Article  PubMed  Google Scholar 

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