@article{APS4513,
author = {Hong Xie and Jing Zhang and Jiang Zhu and Li-xin Liu and Mario Rebecchi and Su-mei Hu and Chen Wang},
title = {Sevoflurane post-conditioning protects isolated rat hearts against ischemia-reperfusion injury via activation of the ERK1/2 pathway},
journal = {Acta Pharmacologica Sinica},
volume = {35},
number = {12},
year = {2016},
keywords = {},
abstract = {Hong XIE1, #, Jing ZHANG2, #, Jiang ZHU1, Li-xin LIU3, Mario REBECCHI3, Su-mei HU1, Chen WANG1, 2, *
1Department of Anesthesiology, The Second Affiliated Hospital of Soochow University, Suzhou 215000, China; 2Institute of Neuroscience, Soochow University, Suzhou 215000, China; 3Department of Anesthesiology, Stony Brook University School of Medicine, Stony Brook, NY 11794, USA
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 (SEVO) for 15 min 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-p70S6K, decreased the levels of porimin, caspase-8, cleaved caspase-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.
Keywords: heart; myocardium; ischemia-reperfusion injury; inhalational anesthetic; sevoflurane; post-conditioning; ERK1/2; PD98059; oncosis; apoptosis
This work is supported by the National Natural Science Foundation of China (Grant No 81372024 to Dr Jiang ZHU), the Technology Bureau of Suzhou, China (Grants No SYS201130, SYSD2012085, and KJXW2011015 to Dr Chen WANG; SYS201125 and SYS201340 to Dr Jiang ZHU). Dr Chen WANG also received support from the Revitalizing the Key Talent’s Subsidy Project in Science and Education (Jiangsu Province, China).
# These two authors contributed equally to this work.
* To whom correspondence should be addressed.
E-mail wangchen1791@163.com
Received 2014-03-09 Accepted 2014-07-29},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/4513}
}