PDF(Pubmed)
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 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. 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.
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. 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.
摘要：
背景：意外体温过低，由低于35°C的核心温度识别，是一种死亡率高达25%的致命疾病。低温引起的心脏功能障碍导致总外周阻力增加和心输出量减少，导致该患者组的高死亡率。最近的研究,体内和体外，建议左西孟旦，米力农和异丙肾上腺素作为该患者组的正性肌力治疗策略。然而,这些药物可能会增加低温期间室性心律失常的风险.因此，我们的目的是描述左西孟旦的作用，米力农和异丙肾上腺素对低温过程中人心肌细胞动作电位的影响。
方法：使用体外实验设计，左西孟旦,将米力农和异丙肾上腺素与iCell2hiPSC衍生的心肌细胞孵育，并从单层培养的细胞中记录细胞动作电位波形和收缩。在37°C至26°C的温度下进行实验。进行单向重复测量ANOVA以评估与基线记录的差异，并进行单向ANOVA以评估药物之间的差异。未经处理的对照和在特定温度下的药物浓度之间。
结果：米力农和异丙肾上腺素均显著增加低温时的动作电位三角测量，从而增加室性心律失常的风险.左西孟旦,然而,在低体温至26°C的过程中，不会增加三角测量，收缩特性也会保持不变。
结论：左西孟旦仍然是治疗低体温患者的正性肌力治疗的有希望的候选药物，因为它具有治疗低体温引起的心功能不全的能力，并且没有检测到室性心律失常的风险增加。米力农和异丙肾上腺素,另一方面,在低温环境中似乎更危险。
方法：使用体外实验设计，左西孟旦,将米力农和异丙肾上腺素与iCell2hiPSC衍生的心肌细胞孵育，并从单层培养的细胞中记录细胞动作电位波形和收缩。在37°C至26°C的温度下进行实验。进行单向重复测量ANOVA以评估与基线记录的差异，并进行单向ANOVA以评估药物之间的差异。未经处理的对照和在特定温度下的药物浓度之间。
结果：米力农和异丙肾上腺素均显著增加低温时的动作电位三角测量，从而增加室性心律失常的风险.左西孟旦,然而,在低体温至26°C的过程中，不会增加三角测量，收缩特性也会保持不变。
结论：左西孟旦仍然是治疗低体温患者的正性肌力治疗的有希望的候选药物，因为它具有治疗低体温引起的心功能不全的能力，并且没有检测到室性心律失常的风险增加。米力农和异丙肾上腺素,另一方面,在低温环境中似乎更危险。
