Signal transduction in the cardioprotective effect of volatile anesthetics

1. p38 MAPK是否参与七氟烷的心脏保护作用？豚鼠离体心脏缺血30 min，再灌注120 min。在缺血前给予10分钟七氟烷（1 MAC ; 2%）并有10分钟洗脱期（SEV，n=10 ;对照溶剂（CTL），n=10）引发APC。在七氟烷（SEV+SB，n=10）或溶剂（CTL+SB，n = 10）给药前10分钟开始，给予SB 203580（2μM）（一种p38 MAPK抑制剂）20分钟。还研究了高剂量SB组（10μM ; SEV+SB-H组，n=6）。为了在持续缺血期间抑制p38 MAPK，在另一组（SEV+SB-L组，n=6）中施用SB 203580 30分钟直到缺血发作而没有洗脱。通过左室舒张末期压（LVEDP）和左室发展压（LVDP）监测收缩恢复。缺血/再灌注后，SEV、SEV+SB、SEV+SB-H和SEV+SB-L心脏LVDP升高，LV降低 ...更多信息 与CTL相比，EDP。与CTL相比，SEV中的肿瘤大小显著减小（19±2%对39± 2%，p<0.05）。在SEV+SB、SEV+SB-H和SEV+SB-L中，SB给药未能消除七氟醚的这种心脏保护作用。p38 MAPK激活不需要作为七氟醚诱导的心脏预处理的触发或介导。乙醇诱导的预处理和七氟烷诱导的预处理之间是否存在相互作用？缺血再灌注方案同上。对照组（CTL，n=10）既未接受乙醇处理，也未接受七氟烷处理。乙醇治疗组（EtOH，n=10）饮用含2.5%乙醇的饮用水6周。在乙醇处理（EtOH+SEVO，n=10）或非乙醇处理（SEVO，n =10）动物的心脏中，麻醉预处理方案也与上述相同。为了研究蛋白激酶C（PKC）和线粒体K_通道的参与<ATP>，在七氟烷（EtOH+SEVO+CHE，EtOH+SEVO+5-HD，各n=10）或溶剂（CTL+CHE，CTL+5-HD，各n= 10）给药前10 min，分别给予每种抑制剂白屈菜红碱（CHE，10μM）和5-羟基癸酸酯（5-HD，200μM）20 min。缺血再灌注后，EtOH、SEVO和EtOH+SEVO组LVDP高于CTL组，LVEDP低于CTL组。与CTL相比，EtOH和SEVO中的肿瘤大小显著减小（分别为27± 2%、23±2%对45± 4%，p&lt;0.05）。在EtOH+SEVO中，七氟烷与EtOH联合给药导致梗死面积进一步缩小至15±2%。CHE和5-HD给药消除了七氟烷和乙醇的心脏保护作用。七氟醚增强低规律乙醇消耗诱导的心脏预适应。PKC激活和线粒体K通道的激活<ATP>是介导这种心脏预适应的必要条件。少

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