Proarrhythmic changes in human cardiomyocytes during hypothermia by milrinone and isoprenaline, but not levosimendan: an experimental in vitro study
Permanent link
https://hdl.handle.net/10037/31748Date
2023-10-25Type
Journal articleTidsskriftartikkel
Peer reviewed
Author
Selli, Anders Lund; Ghasemi, Mohammadreza; Watters, Taylor; Burton, Francis; Smith, Godfrey L; Dietrichs, Erik SvebergAbstract
Methods Using an experimental in vitro-design, levosimendan, milrinone and isoprenaline were incubated with iCell2 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. Oneway repeated measures ANOVA was performed to evaluate diferences from baseline recordings and one-way ANOVA was performed to evaluate diferences between drugs, untreated control and between drug concentrations at the specifc temperatures.
Results Milrinone and isoprenaline both signifcantly 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.