Signal transduction in the cardioprotective effect of volatile anesthetics

1. p38 MAPK是否参与七氟醚的心脏保护作用？离体灌注豚鼠心脏进行30min全脑缺血和120min再灌注。七氟醚给药10分钟（1 MAC, 2%）诱导APC，缺血前10分钟洗脱期（SEV, n=10；对照体（CTL）， n=10）。SB203580 （2μM）是一种p38 MAPK抑制剂，在七氟醚（SEV+SB, n=10）或载体（CTL+SB, n=10）给药前10分钟开始给药20分钟。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，SB203580给药30分钟，直到缺血开始，没有洗清。收缩恢复监测左心室发育（LVDP）和舒张末期（LVEDP）压。用三苯基四唑氯染色法测定梗死面积。缺血/再灌注后，与CTL相比，SEV、SEV+SB、SEV+SB- h和SEV+SB- l心脏LVDP升高，EDP升高。与CTL相比，SEV的梗死面积显著减少（19±2%比39±2%，p<0.05）。在SEV+SB、SEV+SB- h和SEV+SB- l患者中，给药SB未能消除七氟醚的这种心脏保护作用。p38 MAPK活化不需要作为七氟醚诱导的心脏预适应的触发或介质。乙醇诱导的预处理和七氟醚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）既不经乙醇处理，也不经七氟醚处理。乙醇处理组（EtOH, n=10）在其饮用水中添加2.5%乙醇，连续6周。乙醇处理（EtOH+SEVO, n=10）或非乙醇处理（SEVO, n=10）动物心脏的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_<ATP>通道的参与情况，在七氟醚（EtOH+SEVO+CHE, EtOH+SEVO+5-HD，各n=10）或载体（CTL+CHE, CTL+5-HD，各n=10）给药前10分钟，分别给药20 min。缺血再灌注后，与CTL相比，EtOH、SEVO和EtOH+SEVO具有较高的LVDP和较低的LVEDP。与CTL组相比，EtOH组和SEVO组梗死面积显著减小（分别为27±2%、23±2%和45±4%，p<0.05）。在EtOH+SEVO组中，七氟醚可使梗死面积进一步缩小至15±2%。CHE和5-HD均可消除七氟醚和乙醇的这种心脏保护作用。七氟醚增强低常规乙醇消耗量引起的心脏预适应。PKC激活和线粒体K_<ATP>通道的激活是介导这种心脏预适应所必需的。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