Cardioprotective and functional effects of levosimendan and milrinone in mice with cecal ligation and puncture-induced sepsis
Cardioprotective and functional effects of levosimendan and milrinone in mice with cecal ligation and puncture-induced sepsis
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DOI：
10.1007/s00210-018-1527-z
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发表时间：
2018-09-01
影响因子：
3.6
通讯作者：
Hattori, Yuichi
中科院分区：
文献类型：
--
作者：
Yamashita, Shigeyuki;Suzuki, Tokiko;Hattori, Yuichi
左西孟旦和米力农可以用来代替多巴酚丁胺，以增加脓毒症患者的心输出量，由于心功能受损，心输出量低。在盲肠结扎穿孔（CLP）诱导的脓毒症小鼠模型中，研究了两种正性肌力药物对心脏炎症和左心室（LV）性能的影响。CLP小鼠表现出显著的心脏炎症，如心肌组织中促炎细胞因子和中性粒细胞浸润的高度增加所示。当连续给药时，左西孟旦预防了心脏炎症，但米力农加重了心脏炎症，但它们显著降低了血浆心肌肌钙蛋白I和心脏型脂肪酸结合蛋白（心脏损伤的临床标志物）的升高。心脏功能的超声心动图评估表明，左西孟旦，通过静脉推注，左心室性能受损的CLP小鼠，而米力农产生的变力反应同样在假手术和CLP小鼠。左西孟旦对CLP后左心室功能的影响较小，也发现在自发跳动的Langendorff灌注心脏。在从对照组和CLP小鼠分离的心室肌细胞中，左西孟旦而不是米力农引起L型钙电流的大幅增加。这项研究表明，左西孟旦和米力农具有心脏保护特性，但对脓毒症中的心脏炎症/功能障碍具有不同的优点和缺点。
Levosimendan and milrinone may be used in place of dobutamine to increase cardiac output in septic patients with a low cardiac output due to impaired cardiac function. The effects of the two inotropic agents on cardiac inflammation and left ventricular (LV) performance were examined in mice with cecal ligation and puncture (CLP)-induced sepsis. CLP mice displayed significant cardiac inflammation, as indicated by highly increased pro-inflammatory cytokines and neutrophil infiltration in myocardial tissues. When continuously given, levosimendan prevented but milrinone exaggerated cardiac inflammation, but they significantly reduced the elevations in plasma cardiac troponin-I and heart-type fatty acid-binding protein, clinical markers of cardiac injury. Echocardiographic assessment of cardiac function showed that the effect of levosimendan, given by an intravenous bolus injection, on LV performance was impaired in CLP mice, whereas milrinone produced inotropic responses equally in sham-operated and CLP mice. A lesser effect of levosimendan on LV performance after CLP was also found in spontaneously beating Langendorff-perfused hearts. In ventricular myocytes isolated from control and CLP mice, levosimendan, but not milrinone, caused a large increase in the L-type calcium current. This study represents that levosimendan and milrinone have cardioprotective properties but provide different advantages and drawbacks to cardiac inflammation/dysfunction in sepsis.