Sevoflurane post-conditioning protects isolated rat hearts against ischemia-reperfusion injury via activation of the ERK1/2 pathway

Aim： To investigate the role of extracellular signal-regulated kinases （ERKs） in sevoflurane post-conditioning induced cardioprotection in vitro. Methods： Isolated rat hearts were subjected to 30 min ischemia followed by 120 min reperfusion （I/R）. Sevoflurane post-conditioning was carried out by administration of O2-enriched gas mixture with 3% sevoflurane f, SEVO） for 15 rain from the onset of reperfusion. Cardiac functions, myocardial infarct size, myocardial ATP and NAD＋ contents, mitochondrial ultrastructure, and anti-apototic and anti- oncosis protein levels were measured. Results： Sevoflurane post-conditioning significantly improved the heart function, decreased infarct size and mitochondria damage, and increased myocardial ATP and NAD＋ content in the I/R hearts. Furthermore, sevoflurane post-conditioning significantly increased the levels of p-ERK and p-pTOS6K, decreased the levels of porimin, caspase-8, cleaved caspese-3, and cytosolic cytochrome c in the I/R hearts. Co-administration of the ERK1/2 inhibitor PD98059 （20 μmol/L） abolished the sevoflurane-induced protective effects against myocardial I/R. Conclusion： Sevoflurane post-conditioning protects isolated rat hearts against myocardial I/R injury and inhibits cell oncosis and apoptosis via activation of the ERK1/2 pathway.