Involvement of apoptosis in the cardioprotective effect of volatile anesthetics

1. Akt（抗凋亡激酶）是否参与七氟烷的心脏保护作用？已有研究表明，异氟烷诱导的心肌预适应依赖于磷脂酰肌醇-3-激酶（PI 3 K）/Akt信号通路，而PI 3 K/Akt信号通路在再灌注损伤补救激酶级联反应中起重要作用。目前尚不清楚这种信号级联是否参与七氟烷诱导的预处理。豚鼠离体心脏缺血30 min再灌注120 min。七氟烷诱导的预处理是通过在缺血前给予10分钟七氟烷（1 MAC; 2%）和10分钟洗脱（SEVO）引起的。通过蛋白质印迹评估Akt的磷酸化。缺血再灌注后，SEVO组左室舒张末期压较CTL组低，左室舒张末期压较CTL组高。与CTL相比，SEVO中的肿瘤大小显著减小。Akt磷酸化在缺血和再灌注后10分钟没有增加，这与发现相反。 ...更多信息 先前在异氟烷诱导的预处理中证实的结果。其他再灌注损伤补救激酶如丝裂原活化蛋白激酶/细胞外信号调节激酶（MEK）和细胞外信号调节激酶（ERK）在七氟烷诱导的预处理中可能更重要.乙醇和七氟烷诱导的预处理之间是否存在相互作用？我们研究了七氟醚是否增强乙醇预处理以及蛋白激酶C（PKC）和线粒体KATP通道的抑制是否减弱了这种增强的心脏保护作用。离体灌注豚鼠心脏进行30分钟的全脑缺血和120分钟的再灌注（对照：CTL）。乙醇组（EtOH）饮用含2.5%乙醇的饮用水6周。通过在乙醇（EtOH+SEVO）或非乙醇（SEVO）心脏中暴露于七氟烷（1 MAC; 2%）10分钟引发麻醉预处理。白屈菜红碱（CHE）和5-羟基癸酸（5-HD）预处理可分别抑制PKC和线粒体KATP通道。缺血再灌注后，与CTL相比，EtOH、七氟醚（SEVO）和EtOH+SEVO组的LVDP较高，LVEDP较低。与CTL相比，EtOH和SEVO心脏中的冠状动脉尺寸减小。七氟烷进一步减少EtOH心脏的梗死面积。CHE和5-HD在SEVO和EtOH心脏保护的心脏中均消除了心脏保护作用。在EtOH心脏中，iNOS表达减少，eNOS表达增加。七氟烷增强由常规EtOH消耗诱导的心脏预适应。这一作用部分是通过调节PKC和线粒体K_<ATP>通道，并可能通过改变NOS表达来介导的。少

1. Is Akt, antiapoptotic kinase, involved in the cardioprotective effect of sevoflurane ?It has been reported that isoflurane-induced myocardial preconditioning is dependent on phosphatidylinositol-3-kinase (PI3K)/Akt signaling which plays a central role of reperfusion injury salvage kinase cascade. It remains unclear whether this signaling cascade is involved in sevoflurane-induced preconditioning. Isolated perfused guinea pig hearts underwent 30 min global ischemia and 120 min reperfusion (CTL). Sevoflurane-induced preconditioning was elicited by administration of 10 min of sevoflurane (1 MAC; 2%) with 10 min washout before ischemia (SEVO). Phosphorylation of Akt was assessed by western blot. After ischemia-reperfusion, SEVO had higher left ventricular developed and lower end-diastolic pressure versus CTL. Infarct size was significantly reduced in SEVO compared to CTL. Akt phosphorylation was not increased during ischemia and 10 min after reperfusion, which is in contrast to the find … More ings previously demonstrated in isoflurane-induced preconditioning. Other reperfusion injury salvage kinases such as mitogen-activated protein kinase/extracellular signal-regulated kinases (MEK) and extra-cellular signal-regulated kinase (ERK) may be more important in sevoflurane-induced preconditioning.2. Is there any interaction between ethanol-and sevoflurane-induced preconditioning ?We investigated whether sevoflurane enhances ethanol preconditioning and whether inhibition of protein kinase C (PKC) and mitochondrial KATP channels attenuated this enhanced cardioprotection. Isolated perfused guinea pig hearts underwent 30 min global ischemia and 120 min reperfusion (Control: CTL). The ethanol group (EtOH) received 2.5% ethanol in their drinking water for 6 weeks. Anesthetic preconditioning was elicited by 10 min exposure to sevoflurane (1 MAC; 2%) in ethanol (EtOH+SEVO) or non-ethanol (SEVO) hearts. PKC and mitochondrial KATP channels were inhibited with chelerythrine (CHE) and 5-hydroxydecanoate (5-HD) pretreatment, respectively. After ischemia-reperfusion, EtOH, sevoflurane (SEVO), and EtOH+SEVO groups had higher LVDP and lower LVEDP compared with CTL. Infarct size was reduced in EtOH and SEVO hearts compared with CTL. Sevoflurane further reduced infarct size in EtOH hearts. CHE and 5-HD abolished cardioprotection in both SEVO and EtOH cardioprotected hearts. iNOS expression was reduced and eNOS expression was increased in EtOH hearts. Sevoflurane enhances cardiac preconditioning induced by regular EtOH consumption. This effect is mediated in part by modulation of PKC and mitochondrial K_<ATP> channels, and possibly by altered modulation of NOS expression. Less