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

• DOI: 10.1007/s00395-025-01103-2
• Publication Date: 2025-04-12T09:52:32Z
• Authors: Oskar Kjærgaard H...; Alexander Møller ...; Kasper Lykke Weth...; Frederik Flyvholm...; Jacob Marthinsen ...; Ole Kristian Lerc...; Niels Moeslund; Jacob Eifer Møller; Hanne Berg Ravn; Roni Ranghøj Nielsen; Henrik Wiggers; Kristoffer Berg-H...; Nigopan Gopalasingam
• Keywords: Contractility; Crossover study; Double blinded

Cardiogenic shock (CS) is characterized by reduced cardiac output (CO), end-organ perfusion, and high mortality. Medical therapies have failed to improve survival. The ketone body 3-hydroxybutyrate (3-OHB) enhances function in heart failure CS. We aimed elucidate the cardiovascular cardiometabolic effects of 3-OHB treatment during In a randomized, assessor-blinded crossover design, we studied 16 female pigs (60 kg, 5 months age). CS was induced left main coronary artery microsphere injections. Predefined criteria for were 30% reduction CO or mixed venous saturation (SvO2). Intravenous infusion matching control solution administered 120 min random order. Hemodynamic measurements obtained pulmonary catheterization ventricular (LV) pressure-volume catheter. Myocardial mitochondrial assessed using resolution respirometry. During CS, with increased 0.9 L/min (95%CI 0.4-1.3 L/min) compared infusion. SvO2 (P = 0.026) rate < 0.001) increased. Stroke volume 0.6) not altered. LV contractile as determined end-systolic elastance improved 0.004). Systemic vascular resistance decreased, diuresis higher after control. conclude that increasing contractility reducing resistance, while also preserving myocardial respiratory large animal model ischemic These novel findings support therapeutic potential exogenous supplementation management.