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

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

Scand J Trauma Resusc Emerg Med

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

Published: October 2023

AI Article Synopsis

  • Accidental hypothermia is a serious condition marked by a core temperature below 35°C, with a mortality rate of up to 25%, primarily due to cardiac dysfunction.
  • Recent research has looked at drugs like levosimendan, milrinone, and isoprenaline as potential treatments during hypothermia, but concerns about their safety regarding ventricular arrhythmias have arisen.
  • The study found that while milrinone and isoprenaline increased the risk of arrhythmias during hypothermia, levosimendan did not, making it a safer and more effective option for treating cardiac issues in hypothermic patients.

Article Abstract

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: Using an experimental in vitro-design, levosimendan, milrinone and isoprenaline were incubated with iCell hiPSC-derived cardiomyocytes and cellular action potential waveforms and contraction were recorded from monolayers of cultured cells. Experiments were conducted at temperatures from 37 °C down to 26 °C. One-way repeated measures ANOVA was performed to evaluate differences from baseline recordings and one-way ANOVA was performed to evaluate differences between drugs, untreated control and between drug concentrations at the specific temperatures.

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: 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10601188PMC
http://dx.doi.org/10.1186/s13049-023-01134-5DOI Listing

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