Proarrhythmic changes in human cardiomyocytes during hypothermia by milrinone and isoprenaline, but not levosimendan: an experimental in vitro study.


Journal

Scandinavian journal of trauma, resuscitation and emergency medicine
ISSN: 1757-7241
Titre abrégé: Scand J Trauma Resusc Emerg Med
Pays: England
ID NLM: 101477511

Informations de publication

Date de publication:
25 Oct 2023
Historique:
received: 25 08 2023
accepted: 15 10 2023
medline: 27 10 2023
pubmed: 26 10 2023
entrez: 26 10 2023
Statut: epublish

Résumé

Accidental hypothermia, recognized by core temperature below 35 °C, is a lethal condition with a mortality rate up to 25%. Hypothermia-induced cardiac dysfunction causing increased total peripheral resistance and reduced cardiac output contributes to the high mortality rate in this patient group. Recent studies, in vivo and in vitro, have suggested levosimendan, milrinone and isoprenaline as inotropic treatment strategies in this patient group. However, these drugs may pose increased risk of ventricular arrhythmias during hypothermia. Our aim was therefore to describe the effects of levosimendan, milrinone and isoprenaline on the action potential in human cardiomyocytes during hypothermia. Using an experimental in vitro-design, levosimendan, milrinone and isoprenaline were incubated with iCell Milrinone and isoprenaline both significantly increases action potential triangulation during hypothermia, and thereby the risk of ventricular arrhythmias. Levosimendan, however, does not increase triangulation and the contractile properties also remain preserved during hypothermia down to 26 °C. Levosimendan remains a promising candidate drug for inotropic treatment of hypothermic patients as it possesses ability to treat hypothermia-induced cardiac dysfunction and no increased risk of ventricular arrhythmias is detected. Milrinone and isoprenaline, on the other hand, appears more dangerous in the hypothermic setting.

Sections du résumé

BACKGROUND BACKGROUND
Accidental hypothermia, recognized by core temperature below 35 °C, is a lethal condition with a mortality rate up to 25%. Hypothermia-induced cardiac dysfunction causing increased total peripheral resistance and reduced cardiac output contributes to the high mortality rate in this patient group. Recent studies, in vivo and in vitro, have suggested levosimendan, milrinone and isoprenaline as inotropic treatment strategies in this patient group. However, these drugs may pose increased risk of ventricular arrhythmias during hypothermia. Our aim was therefore to describe the effects of levosimendan, milrinone and isoprenaline on the action potential in human cardiomyocytes during hypothermia.
METHODS METHODS
Using an experimental in vitro-design, levosimendan, milrinone and isoprenaline were incubated with iCell
RESULTS RESULTS
Milrinone and isoprenaline both significantly increases action potential triangulation during hypothermia, and thereby the risk of ventricular arrhythmias. Levosimendan, however, does not increase triangulation and the contractile properties also remain preserved during hypothermia down to 26 °C.
CONCLUSIONS CONCLUSIONS
Levosimendan remains a promising candidate drug for inotropic treatment of hypothermic patients as it possesses ability to treat hypothermia-induced cardiac dysfunction and no increased risk of ventricular arrhythmias is detected. Milrinone and isoprenaline, on the other hand, appears more dangerous in the hypothermic setting.

Identifiants

pubmed: 37880801
doi: 10.1186/s13049-023-01134-5
pii: 10.1186/s13049-023-01134-5
pmc: PMC10601188
doi:

Substances chimiques

Simendan 349552KRHK
Milrinone JU9YAX04C7
Cardiotonic Agents 0
Isoproterenol L628TT009W
Hydrazones 0
Pyridazines 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

61

Subventions

Organisme : Helse Nord RHF
ID : HNF1337-17

Informations de copyright

© 2023. Norwegian Air Ambulance Foundation.

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Auteurs

Anders Lund Selli (AL)

Experimental and Clinical Pharmacology, Department of Medical Biology, Faculty of Health Sciences, UiT - The Arctic University of Norway, Postboks 6050, 9037, Langnes, Tromsø, Norway.

Mohammadreza Ghasemi (M)

Clyde Biosciences, Newhouse, Scotland.

Taylor Watters (T)

Clyde Biosciences, Newhouse, Scotland.

Francis Burton (F)

Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, Scotland.
Clyde Biosciences, Newhouse, Scotland.

Godfrey Smith (G)

Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, Scotland.
Clyde Biosciences, Newhouse, Scotland.

Erik Sveberg Dietrichs (ES)

Experimental and Clinical Pharmacology, Department of Medical Biology, Faculty of Health Sciences, UiT - The Arctic University of Norway, Postboks 6050, 9037, Langnes, Tromsø, Norway. erik.sveberg.dietrichs@uit.no.
Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway. erik.sveberg.dietrichs@uit.no.
Institute of Oral Biology, University of Oslo, Oslo, Norway. erik.sveberg.dietrichs@uit.no.

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