TY - JOUR
T1 - The ketone body 3-hydroxybutyrate increases cardiac output and cardiac contractility in a porcine model of cardiogenic shock
T2 - a randomized, blinded, crossover trial
AU - Hørsdal, Oskar Kjærgaard
AU - Larsen, Alexander Møller
AU - Wethelund, Kasper Lykke
AU - Dalsgaard, Frederik Flyvholm
AU - Seefeldt, Jacob Marthinsen
AU - Helgestad, Ole Kristian Lerche
AU - Moeslund, Niels
AU - Møller, Jacob Eifer
AU - Ravn, Hanne Berg
AU - Nielsen, Roni Ranghøj
AU - Wiggers, Henrik
AU - Berg-Hansen, Kristoffer
AU - Gopalasingam, Nigopan
PY - 2025/6
Y1 - 2025/6
N2 - Cardiogenic shock (CS) is characterized by reduced cardiac output (CO), reduced end-organ perfusion, and high mortality. Medical therapies have failed to improve survival. The ketone body 3-hydroxybutyrate (3-OHB) enhances cardiac function in heart failure and CS. We aimed to elucidate the cardiovascular and cardiometabolic effects of 3-OHB treatment during CS. In a randomized, assessor-blinded crossover design, we studied 16 female pigs (60 kg, 5 months of age). CS was induced by left main coronary artery microsphere injections. Predefined criteria for CS were a 30% reduction in CO or mixed venous saturation (SvO2). Intravenous 3-OHB infusion and a matching control solution were administered for 120 min in random order. Hemodynamic measurements were obtained by pulmonary artery catheterization and a left ventricular (LV) pressure-volume catheter. Myocardial mitochondrial function was assessed using high resolution respirometry. During CS, infusion with 3-OHB increased CO by 0.9 L/min (95%CI 0.4-1.3 L/min) compared with control infusion. SvO2 (P = 0.026) and heart rate (P < 0.001) increased. Stroke volume (P = 0.6) was not altered. LV contractile function as determined by LV end-systolic elastance improved during 3-OHB infusion compared with control infusion (P = 0.004). Systemic and pulmonary vascular resistance decreased, and diuresis increased. LV mitochondrial function was higher after 3-OHB infusion compared with control. We conclude that 3-OHB infusion enhances cardiac function by increasing contractility and reducing vascular resistance, while also preserving myocardial mitochondrial respiratory function in a large animal model of ischemic CS. These novel findings support the therapeutic potential of exogenous ketone supplementation in CS management.
AB - Cardiogenic shock (CS) is characterized by reduced cardiac output (CO), reduced end-organ perfusion, and high mortality. Medical therapies have failed to improve survival. The ketone body 3-hydroxybutyrate (3-OHB) enhances cardiac function in heart failure and CS. We aimed to elucidate the cardiovascular and cardiometabolic effects of 3-OHB treatment during CS. In a randomized, assessor-blinded crossover design, we studied 16 female pigs (60 kg, 5 months of age). CS was induced by left main coronary artery microsphere injections. Predefined criteria for CS were a 30% reduction in CO or mixed venous saturation (SvO2). Intravenous 3-OHB infusion and a matching control solution were administered for 120 min in random order. Hemodynamic measurements were obtained by pulmonary artery catheterization and a left ventricular (LV) pressure-volume catheter. Myocardial mitochondrial function was assessed using high resolution respirometry. During CS, infusion with 3-OHB increased CO by 0.9 L/min (95%CI 0.4-1.3 L/min) compared with control infusion. SvO2 (P = 0.026) and heart rate (P < 0.001) increased. Stroke volume (P = 0.6) was not altered. LV contractile function as determined by LV end-systolic elastance improved during 3-OHB infusion compared with control infusion (P = 0.004). Systemic and pulmonary vascular resistance decreased, and diuresis increased. LV mitochondrial function was higher after 3-OHB infusion compared with control. We conclude that 3-OHB infusion enhances cardiac function by increasing contractility and reducing vascular resistance, while also preserving myocardial mitochondrial respiratory function in a large animal model of ischemic CS. These novel findings support the therapeutic potential of exogenous ketone supplementation in CS management.
KW - 3-Hydroxy butyrate
KW - Cardiac output
KW - Cardiogenic shock
KW - Cardiometabolic
KW - Hemodynamics
KW - Mitochondrial function
UR - https://www.scopus.com/pages/publications/105002473642
U2 - 10.1007/s00395-025-01103-2
DO - 10.1007/s00395-025-01103-2
M3 - Journal article
C2 - 40220139
SN - 0300-8428
VL - 120
SP - 579
EP - 596
JO - Basic Research in Cardiology
JF - Basic Research in Cardiology
IS - 3
M1 - 100504
ER -