Effects of ketone body 3-hydroxybutyrate on cardiac and mitochondrial function during donation after circulatory death heart transplantation
© 2024. The Author(s)..
Normothermic regional perfusion (NRP) allows assessment of therapeutic interventions prior to donation after circulatory death transplantation. Sodium-3-hydroxybutyrate (3-OHB) increases cardiac output in heart failure patients and diminishes ischemia-reperfusion injury, presumably by improving mitochondrial metabolism. We investigated effects of 3-OHB on cardiac and mitochondrial function in transplanted hearts and in cardiac organoids. Donor pigs (n = 14) underwent circulatory death followed by NRP. Following static cold storage, hearts were transplanted into recipient pigs. 3-OHB or Ringer's acetate infusions were initiated during NRP and after transplantation. We evaluated hemodynamics and mitochondrial function. 3-OHB mediated effects on contractility, relaxation, calcium, and conduction were tested in cardiac organoids from human pluripotent stem cells. Following NRP, 3-OHB increased cardiac output (P < 0.0001) by increasing stroke volume (P = 0.006), dP/dt (P = 0.02) and reducing arterial elastance (P = 0.02). Following transplantation, infusion of 3-OHB maintained mitochondrial respiration (P = 0.009) but caused inotropy-resistant vasoplegia that prevented weaning. In cardiac organoids, 3-OHB increased contraction amplitude (P = 0.002) and shortened contraction duration (P = 0.013) without affecting calcium handling or conduction velocity. 3-OHB had beneficial cardiac effects and may have a potential to secure cardiac function during heart transplantation. Further studies are needed to optimize administration practice in donors and recipients and to validate the effect on mitochondrial function.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
Scientific reports - 14(2024), 1 vom: 08. Jan., Seite 757 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Seefeldt, Jacob Marthinsen [VerfasserIn] |
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| Links: |
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| Themen: |
3-Hydroxybutyric Acid |
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| Anmerkungen: |
Date Completed 10.01.2024 Date Revised 11.01.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41598-024-51387-y |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM366825135 |
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| 520 | |a Normothermic regional perfusion (NRP) allows assessment of therapeutic interventions prior to donation after circulatory death transplantation. Sodium-3-hydroxybutyrate (3-OHB) increases cardiac output in heart failure patients and diminishes ischemia-reperfusion injury, presumably by improving mitochondrial metabolism. We investigated effects of 3-OHB on cardiac and mitochondrial function in transplanted hearts and in cardiac organoids. Donor pigs (n = 14) underwent circulatory death followed by NRP. Following static cold storage, hearts were transplanted into recipient pigs. 3-OHB or Ringer's acetate infusions were initiated during NRP and after transplantation. We evaluated hemodynamics and mitochondrial function. 3-OHB mediated effects on contractility, relaxation, calcium, and conduction were tested in cardiac organoids from human pluripotent stem cells. Following NRP, 3-OHB increased cardiac output (P < 0.0001) by increasing stroke volume (P = 0.006), dP/dt (P = 0.02) and reducing arterial elastance (P = 0.02). Following transplantation, infusion of 3-OHB maintained mitochondrial respiration (P = 0.009) but caused inotropy-resistant vasoplegia that prevented weaning. In cardiac organoids, 3-OHB increased contraction amplitude (P = 0.002) and shortened contraction duration (P = 0.013) without affecting calcium handling or conduction velocity. 3-OHB had beneficial cardiac effects and may have a potential to secure cardiac function during heart transplantation. Further studies are needed to optimize administration practice in donors and recipients and to validate the effect on mitochondrial function | ||
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| 650 | 7 | |a Calcium |2 NLM | |
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| 700 | 1 | |a Berg, Katrine |e verfasserin |4 aut | |
| 700 | 1 | |a Jespersen, Nichlas Riise |e verfasserin |4 aut | |
| 700 | 1 | |a Lassen, Thomas Ravn |e verfasserin |4 aut | |
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| 700 | 1 | |a Ryhammer, Pia |e verfasserin |4 aut | |
| 700 | 1 | |a Pedersen, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Ilkjaer, Lars Bo |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Michiel A |e verfasserin |4 aut | |
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| 700 | 1 | |a Bøtker, Hans Erik |e verfasserin |4 aut | |
| 700 | 1 | |a Caspi, Oren |e verfasserin |4 aut | |
| 700 | 1 | |a Eiskjær, Hans |e verfasserin |4 aut | |
| 700 | 1 | |a Moeslund, Niels |e verfasserin |4 aut | |
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