Department of Emergency Medicine National Taiwan University Hospital Taipei Taiwan.
Department of Emergency Medicine College of Medicine National Taiwan University Taipei Taiwan.
J Am Heart Assoc. 2020 Jun 16;9(12):e016139. doi: 10.1161/JAHA.120.016139. Epub 2020 Jun 1.
Background This study investigated whether levosimendan, an inotropic calcium sensitizer, when combined with moderate therapeutic hypothermia, may exert synergistic benefits on post-cardiac arrest myocardial dysfunction and improve outcomes. Methods and Results After 9.5-minute asphyxia-induced cardiac arrest and resuscitation, 48 rats were randomized equally into 4 groups following return of spontaneous circulation (ROSC), including normothermia, hypothermia, normothermia-levosimendan, and hypothermia-levosimendan groups. For the normothermia group, the target temperature was 37°C while for the hypothermia group, the target temperature was 32°C, both of which were to be maintained for 4 hours after ROSC. Levosimendan was administered after ROSC with a loading dose of 10 μg/kg and then infused at 0.1 μg/kg per min for 4 hours. In the hypothermia-levosimendan group, left ventricular systolic function and cardiac output increased significantly, whereas the heart rate and systemic vascular resistance decreased significantly compared with the normothermia group. Also, the concentrations of interleukin 1β at 4 hours post-ROSC and the production of NO between 1 hour and 4 hours post-ROSC were reduced significantly in the hypothermia-levosimendan group compared with the normothermia group. The 72-hour post-ROSC survival and neurological recovery were also significantly better in the hypothermia-levosimendan group compared with the normothermia group (survival, 100% versus 50%, χ test, =0.006). Conclusions Compared with normothermia, only combined moderate therapeutic hypothermia and levosimendan treatment could consistently improve post-cardiac arrest myocardial dysfunction and decrease the release of pro-inflammatory molecules, thereby improving survival and neurological outcomes. These findings suggest synergistic benefits between moderate therapeutic hypothermia and levosimendan.
本研究旨在探讨左西孟旦（一种正性肌力钙增敏剂）与亚低温联合应用对心脏骤停后心肌功能障碍的协同作用，并改善复苏后结局。
在 9.5 分钟窒息诱导的心脏骤停和复苏后，48 只大鼠随机分为 4 组，包括常温组、低温组、常温左西孟旦组和低温左西孟旦组，在自主循环恢复（ROSC）后，常温组目标温度为 37°C，低温组目标温度为 32°C，两组均在 ROSC 后 4 小时内维持。ROSC 后给予左西孟旦负荷量 10μg/kg，然后以 0.1μg/kg/min 的速度输注 4 小时。与常温组相比，低温左西孟旦组左心室收缩功能和心输出量明显增加，而心率和全身血管阻力明显降低。此外，低温左西孟旦组 ROSC 后 4 小时的白细胞介素 1β浓度和 ROSC 后 1 至 4 小时的 NO 生成量均明显低于常温组。低温左西孟旦组的 72 小时 ROSC 后存活率和神经功能恢复也明显优于常温组（存活率，100%比 50%，χ检验，=0.006）。
与常温相比，只有联合应用亚低温和左西孟旦治疗才能持续改善心脏骤停后心肌功能障碍，减少促炎分子的释放，从而提高存活率和神经功能结局。这些发现提示亚低温和左西孟旦之间存在协同作用。
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