1 Department of Psychiatry, Radiology, Public Health, Nursing and Medicine, School of Nursing, University of Santiago de Compostela, Santiago de Compostela, Spain.
2 Health Research Institute of Santiago de Compostela (IDIS), Galician Health System, Clinical University Hospital, Santiago de Compostela, Spain.
Biol Res Nurs. 2019 Oct;21(5):466-472. doi: 10.1177/1099800419861694. Epub 2019 Jul 4.
Levosimendan is a myocardial Ca sensitizer and opener of ATP-dependent potassium channels with inotropic, vasodilating, and cardioprotective properties. It was originally developed for the treatment of acute decompensated heart failure, but its complex mechanism of action means that it could also play a role in organ protection in response to infection. Using an in vitro approach, we explored whether levosimendan administration influenced cell responses to lipopolysaccharide (LPS). Primary human umbilical vein endothelial cells were stimulated with 1 µg/ml LPS from (). Cells were treated with levosimendan at 0, 0.1, 1, or 10 µM 3 hr later. Samples were taken 24 hr after treatment to measure cell necrosis, apoptosis, pro-inflammatory mediators (interleukin 6 [IL-6] and toll-like receptor 4 [TLR4]), and oxidative stress (total reactive oxygen species/reactive nitrogen species [ROS/RNS]). Levosimendan at 1 and 10 µM protected against LPS-induced endothelial cell death and reduced TLR4 expression ( < .05). All doses reduced levels of IL-6 and ROS/RNS ( < .05). Findings suggest that levosimendan may exert protective effects against endothelial cell death in this model via attenuation of inflammation and oxidative stress pathways. Future studies might explore the potential beneficial role of levosimendan in modulating molecular mechanisms triggered by infections.
左西孟旦是一种心肌 Ca 增敏剂和 ATP 依赖性钾通道开放剂，具有正性肌力、血管扩张和心脏保护作用。它最初是为治疗急性失代偿性心力衰竭而开发的，但它复杂的作用机制意味着它也可能在针对感染的器官保护中发挥作用。我们采用体外方法，探讨了左西孟旦给药是否影响细胞对脂多糖（LPS）的反应。用 1 µg/ml LPS 刺激原代人脐静脉内皮细胞（）。3 小时后，用 0、0.1、1 或 10 µM 的左西孟旦处理细胞。治疗 24 小时后取样，测量细胞坏死、凋亡、促炎介质（白细胞介素 6 [IL-6]和 Toll 样受体 4 [TLR4]）和氧化应激（总活性氧/活性氮 [ROS/RNS]）。1 和 10 µM 的左西孟旦可预防 LPS 诱导的内皮细胞死亡，并降低 TLR4 表达（<0.05）。所有剂量均降低了 IL-6 和 ROS/RNS 的水平（<0.05）。这些发现表明，左西孟旦可能通过抑制炎症和氧化应激途径，在该模型中发挥内皮细胞死亡的保护作用。未来的研究可能会探索左西孟旦在调节感染触发的分子机制方面的潜在有益作用。
