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

Abstract

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 O 2 -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 antioncosis 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.

WITHDRAWN: Sevoflurane post-conditioning protects primary rat cortical neurons against oxygen–glucose deprivation/resuscitation via down-regulation in mitochondrial apoptosis axis of Bid, Bim, Puma–Bax and Bak mediated by Erk1/2

“…Interestingly, sevoflurane exposure alone increased phosphorylation of Erk1/2 slightly, but PD98059 treatment alone could significantly attenuate the increase of phosphorylation of Erk1/2 induced by OGD/R. It has been found that, sevoflurane post-conditioning inhibits myocardial cell death via activation of Erk1/2 pathway [11,25]. Our study indicated that, sevoflurane post-conditioning could protect primary rat cortical neurons against OGD/R mediated by activation of Erk1/2.…”

Long non-coding NEAT1 weakens the protective role of sevoflurane on myocardial ischemia/reperfusion injury by mediating the microRNA-140/RhoA axis

“…Excessive apoptosis is associated with myocardial ischemia, I/R injury as well as postischemia cardiac remodeling [18], while infarct size is an independent indicator effective in predicting mortality after infarction [19]. In the current work, we observed that Sev worked as a cardio-protector against injury induced by myocardial I/R by reducing LVEF, LVFS, myocardial infarct size and apoptosis rate, indicating the bene cial role of Sev on I/R injury [20,21]. Moreover, Sev was found to diminish NEAT1, which was enhanced in mice with myocardial I/R, by microarray analysis.…”

Deferoxamine-activated hypoxia-inducible factor-1 restores cardioprotective effects of sevoflurane postconditioning in diabetic rats

“…Sevoflurane, a commonly used inhalation anaesthetic agent in clinical practice, is considered the cornerstone of this drug class because of its favourable characteristics, including smooth induction of anaesthesia, rapid post-operative recovery and minimal impact on hemodynamics. Several studies have demonstrated that SpostC can protect healthy myocardium from I/R injury, [6][7][8][9]28 but the underlying mechanism remains unclear. Interestingly, our previous studies found that the protective effects of SpostC on isolated myocardial mitochondria can be attributed to the upregulation of HIF-1a.…”