Signal transduction in the cardioprotective effect of volatile anesthetics

挥发性麻醉药心脏保护作用中的信号转导

• 批准号: 16592032
• 负责人: MIYAMAE Masami
• 金额: $ 2.18万
• 依托单位: Osaka Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16592032/
• 关键词: sevoflurane; preconditioning; heart; ischemia-reperfusion; alcohol; mitochondrial K_<ATP> channel; protein kinase C; guinea pig; ischemia; Mitochondrial K_<ATP> channel; p38 MAP kinase; SB203580

1. Is p38 MAPK involved in the cardioprotective effect of sevoflurane?Isolated perfused guinea pig hearts underwent 30 min global ischemia and 120 min reperfusion. APC was elicited with 10 min of sevoflurane administration (1 MAC ; 2%) with a 10 min washout period prior to ischemia (SEV, n=10 ; control vehicle (CTL), n=10). SB203580 (2μM), a p38 MAPK inhibitor, was administered for 20 min, starting 10 min before sevoflurane (SEV+SB, n=10) or vehicle (CTL+SB, n=10) administration. A high dose SB group was also studied (10μM ; SEV+SB-H group, n=6). To inhibit p38 MAPK during sustained ischemia, SB203580 was administered for 30 min until the onset of ischemia with no washout in an additional group (SEV+SB-L group, n=6). Contractile recovery was monitored by left ventricular developed (LVDP) and end-diastolic (LVEDP) pressure. Infarct size was determined by triphenyltetrazolium chloride stain.After ischemia/reperfusion, SEV, SEV+SB, SEV+SB-H and SEV+SB-L hearts had higher LVDP and lower LV … More EDP compared to CTL. Infarct size was significantly reduced in SEV compared to CTL (19±2% versus 39±2%, p<0.05). SB administration failed to abolish this cardioprotective effect of sevoflurane in SEV+SB, SEV+SB-H and SEV+SB-L.p38 MAPK activation is not required as a trigger or mediator for sevoflurane-induced cardiac preconditioning.2. Is there any interaction between ethanol induced and sevoflurane induced preconditioning?The protocol of ischemia-reperfusion was same as above. Controls (CTL, n=10) were neither ethanol nor sevoflurane-treated. Ethanol-treated group (EtOH, n=10) received 2.5% ethanol in their drinking water for 6 weeks. The protocol of anesthetic preconditioning was also same as above in hearts from ethanol-treated (EtOH+SEVO, n=10) or non-ethanol-treated (SEVO, n=10) animals. To investigate the involvement of protein kinase C (PKC) and mitochondrial K_<ATP> channels, each inhibitor, chelerythrine (CHE, 10μM) and 5-hydroxydecanoate (5-HD, 200μM) respectively, were administered for 20 min, starting 10 min before sevoflurane (EtOH+SEVO+CHE, EtOH+SEVO+5-HD, n=10 each) or vehicle (CTL+CHE, CTL+5-HD, n=10 each) administration. After ischemia-reperfusion, EtOH, SEVO and EtOH+SEVO had higher LVDP and lower LVEDP compared to CTL. Infarct size was significantly reduced in EtOH and SEVO compared to CTL (27±2%, 23±2% vs 45±4%, respectively, p<0.05). Administration of sevoflurane to EtOH led to further reduction of infarct size to 15±2% in EtOH+SEVO. CHE and 5-HD administration abolished this cardioprotective effect of both sevoflurane and ethanol. Sevoflurane enhances cardiac preconditioning induced by low regular ethanol consumption. Activation of PKC activation and mitochondrial K_<ATP> channels are necessary in mediating this cardiac preconditioning. Less

1。p38 MAPK是否参与了七氟硫烷？孤立的灌注豚鼠心脏的心脏保护作用，经历了30分钟的全球缺血和120分钟的再灌注。在缺血前10分钟的冲洗周期（SEV，n = 10;控制车辆（CTL），n = 10）之前，用10分钟的Sevoflurane给药（1 Mac; 2％）对APC进行了。 SB203580（2μM）是P38 MAPK抑制剂，在Sevoflurane（Sev+SB，N = 10）或媒介物（CTL+SB，N = 10）给药前10分钟开始施用20分钟。还研究了一个高剂量SB组（10μM； SEV+SB-H组，n = 6）。为了抑制持续缺血期间的p38 MAPK，将SB203580施用30分钟，直到缺血发作，而另外一组没有冲洗（SEV+SB-L组，n = 6）。通过左心室开发（LVDP）和末期舒张（LVEDP）压力监测收缩的回收。梗塞大小是通过三苯基二唑烷染色来确定的。与CTL相比，局部缺血/再灌注后，SEV，SEV+SB，SEV+SB，SEV+SB-H和SB-L心脏具有更高的LVDP和较低的EDP…更多的EDP。与CTL相比，SEV的梗塞大小显着降低（19±2％对39±2％，p <0.05）。 SB给药未能废除Sevoflurane在SEV+SB中，SEV+SB-H和SEV+SB-L.P38 MAPK激活中的这种心脏保护作用，作为Sevoflurane诱导心脏诱导的触发器或介体的触发器或中介。乙醇诱导的和七氟乙烷引起的预处理之间是否存在任何相互作用？缺血 - 重新灌注的方案与上述相同。对照（CTL，n = 10）既不是乙醇，也不是经七氟乙烷处理的。经乙醇处理的组（ETOH，n = 10）在其饮用水中接受2.5％的乙醇6周。麻醉预处理的方案与乙醇处理的心脏（eTOH+sevo，n = 10）或非乙醇治疗（Sevo，n = 10）动物中的心脏相同。研究蛋白激酶C（PKC）和线粒体K_ <ATP>通道的参与，每个抑制剂，螯合剂（CHE，10μm）和5-羟基苯二甲酸酯（5-HD，200μm）分别为20分钟，在Sevoflurane（sevofoharane+Sevo+Sevo+Sevo+Sevo+Sevo+Sevo+Sevo+Sevo+Sevo+Sevo+Sevo+Sevo+Sevo+Sevo+Sevo+Sevo+Sevo+Sevo+Sevo+Sevo+Sevo+Sevo+Sevo+Sevo+Sevo+Sevo+Sevo。每个）或车辆（CTL+CHE，CTL+5-HD，n = 10）。与CTL相比，在缺血 - 再灌注后，EtOH，Sevo和EtOH+Sevo具有更高的LVDP和LVEDP。与CTL相比，ETOH和SEVO的梗塞大小显着降低（分别为27±2％，23±2％和45±4％，P <0.05）。在EtOH+sevo中，将Sevoflurane施用到ETOH上，导致梗塞大小进一步降低至15±2％。 CHE和5-HD管理消除了Sevoflurane和乙醇的这种心脏保护作用。 Sevoflurane增强了低常规乙醇消耗引起的心脏预处理。 PKC激活和线粒体K_ <ATP>通道的激活对于介导这种心脏预处理是必要的。较少的