Ketone body 3-hydroxybutyrate elevates cardiac output through peripheral vasorelaxation and enhanced cardiac contractility

• DOI: 10.1007/s00395-023-01008-y
• Publication Date: 2023-09-09T06:01:45Z
• Authors: Casper Homilius; Jacob Marthinsen ...; Julie Sørensen Ax...; Tina Myhre Pedersen; Trine Monberg Sør...; Roni Nielsen; Henrik Wiggers; Jakob Hansen; Vladimir V. Matchkov; Hans Erik Bøtker; Ebbe Boedtkjer
• Keywords: Contractility

The ketone body 3-hydroxybutyrate (3-OHB) increases cardiac output and myocardial perfusion without affecting blood pressure in humans, but the cardiovascular sites of action remain obscure. Here, we test hypothesis rats that 3-OHB acts directly on heart to increase contractility vessels lower systemic vascular resistance. We investigate effects (a) vivo hemodynamics using echocardiography invasive measurements, (b) isolated perfused hearts Langendorff systems, (c) arteries veins isometric myographs. compare Na-3-OHB equimolar NaCl added physiological buffers or injection solutions. At plasma concentrations 2-4 mM vivo, (by 28.3±7.8%), stroke volume 22.4±6.0%), left ventricular ejection fraction 13.3±4.6%), arterial dP/dtmax 31.9±11.2%) lowers resistance 30.6±11.2%) substantially rate pressure. Applied at 3-10 mM, developed by up 26.3±7.4 mmHg coronary 20.2±9.5%. Beginning 1-3 relaxes (EC50=12.4 mM), cerebral, femoral, mesenteric, renal as well brachial, mesenteric 60% pre-contraction within pathophysiological concentration range. Of two enantiomers constitute racemic 3-OHB, D-3-OHB dominates endogenously; tested separately, induce similar vasorelaxation. conclude increased generalized vasorelaxation can explain elevated during administration. These actions strengthen therapeutic rationale for failure management.