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<p>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&#xa0;kg, 5&#xa0;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 (SvO<sub>2</sub>). Intravenous 3-OHB infusion and a matching control solution were administered for 120&#xa0;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&#xa0;L/min (95%CI 0.4–1.3&#xa0;L/min) compared with control infusion. SvO<sub>2</sub> (<i>P</i> = 0.026) and heart rate (<i>P</i> &lt; 0.001) increased. Stroke volume (<i>P</i> = 0.6) was not altered. LV&#xa0;contractile function as determined by LV&#xa0;end-systolic elastance improved during 3-OHB infusion compared with control infusion (<i>P</i> = 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.</p> Graphical abstract <p></p>

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

  • 期刊论文

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  • 发表日期：

    2025年4月12日

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  • Oskar Kjærgaard Hørsdal,
  • Alexander Møller Larsen,
  • Kasper Lykke Wethelund,
  • Frederik Flyvholm Dalsgaard,
  • Jacob Marthinsen Seefeldt,
  • Ole Kristian Lerche Helgestad,
  • Niels Moeslund,
  • Jacob Eifer Møller,
  • Hanne Berg Ravn,
  • Roni Ranghøj Nielsen,
  • Henrik Wiggers,
  • Kristoffer Berg-Hansen,
  • Nigopan Gopalasingam

摘要

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.

Graphical abstract