Seki Yoshimoto, Jesmin Subrina, Shimojo Nobutake, Islam Md Majedul, Rahman Md Arifur, Khatun Tanzila, Sakuramoto Hideaki, Oki Masami, Sonobe Aiko, Kamiyama Junko, Hagiya Keiichi, Kawano Satoru, Mizutani Taro
Department of Emergency and Critical Care Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Department of Emergency and Critical Care Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Life Sci. 2014 Nov 24;118(2):357-63. doi: 10.1016/j.lfs.2014.04.005. Epub 2014 Apr 13.
Landiolol hydrochloride, an ultra-short-acting highly cardio-selective β-1 blocker, has become useful for various medical problems. Recent studies have demonstrated that co-treatment with landiolol protects against acute lung injury and cardiac dysfunction in rats of lipopolysaccharide (LPS)-induced systemic inflammation, and was also associated with a significant reduction in serum levels of the inflammation mediator HMGB-1 and histological lung damage. Endothelin (ET)-1, a potent vasoconstrictor, has been implicated in pathogenesis of sepsis and sepsis-induced multiple organ dysfunction syndrome. Here, we investigated whether landiolol hydrochloride can play important roles in ameliorating LPS-induced alterations in cardiac ET system of septic rats.
Eight-week-old male Wistar rats were administered LPS only for 3 h and the rest were treated with LPS as well as with landiolol non-stop for 3 h.
At 3 h after LPS (only) administration, circulatory tumor necrosis factor (TNF)-α level, blood lactate concentration and percentage of fractional shortening of heart were significantly increased. In addition, LPS induced a significant expression of various components of cardiac ET-1 system compared to control. Finally, treatment of LPS-administered rats with landiolol for 3 h normalized LPS-induced blood lactate levels and cardiac functional compensatory events, without altering levels of plasma TNF-α and ET-1. Most strikingly, landiolol treatment significantly normalized various components of cardiac ET-1 signaling system in septic rat.
Taken together, these data led us to conclude that landiolol may be cardio-protective in septic rats by normalizing the expression of cardiac vasoactive peptide such as ET, without altering the circulatory levels of inflammatory cytokines.
盐酸兰地洛尔是一种超短效、高度心脏选择性β-1受体阻滞剂，已被用于多种医疗问题。最近的研究表明，与兰地洛尔联合治疗可保护脂多糖（LPS）诱导的全身炎症大鼠免受急性肺损伤和心脏功能障碍，并且还与炎症介质高迁移率族蛋白B1（HMGB-1）血清水平的显著降低以及肺部组织学损伤有关。内皮素（ET）-1是一种强效血管收缩剂，与脓毒症及脓毒症诱导的多器官功能障碍综合征的发病机制有关。在此，我们研究了盐酸兰地洛尔是否能在改善脓毒症大鼠心脏ET系统的LPS诱导改变中发挥重要作用。
8周龄雄性Wistar大鼠仅给予LPS 3小时，其余大鼠给予LPS并同时持续给予兰地洛尔3小时。
在仅给予LPS后3小时，循环肿瘤坏死因子（TNF）-α水平、血乳酸浓度和心脏缩短分数百分比显著升高。此外，与对照组相比，LPS诱导了心脏ET-1系统各种成分的显著表达。最后，用兰地洛尔治疗给予LPS的大鼠3小时可使LPS诱导的血乳酸水平和心脏功能代偿事件恢复正常，而不会改变血浆TNF-α和ET-1水平。最显著的是，兰地洛尔治疗使脓毒症大鼠心脏ET-1信号系统的各种成分显著恢复正常。
综上所述，这些数据使我们得出结论，兰地洛尔可能通过使诸如ET等心脏血管活性肽的表达恢复正常而对脓毒症大鼠具有心脏保护作用，而不会改变循环炎症细胞因子水平。
