Sevoflurane Pre-conditioning Ameliorates Diabetic Myocardial Ischemia/Reperfusion Injury Via Differential Regulation of p38 and ERK

Abstract

Diabetes mellitus (DM) significantly increases myocardial ischemia/reperfusion (MI/R) injury. During DM, cardioprotection induced by conventional pre-conditioning (PreCon) is decreased due to impaired AMP-activated protein kinase (AMPK) signaling. The current study investigated whether PreCon with inhaled anesthetic sevoflurane (SF-PreCon) remains cardioprotective during DM, and identified the involved mechanisms. Normal diet (ND) and high-fat diet (HFD)-induced DM mice were randomized into control and SF-PreCon (3 cycles of 15-minute period exposures to 2% sevoflurane) groups before MI/R. SF-PreCon markedly reduced MI/R injury in DM mice, as evidenced by improved cardiac function (increased LVEF and ±Dp/dt), decreased infarct size, and decreased apoptosis. To determine the relevant role of AMPK, the effect of SF-PreCon was determined in cardiac-specific AMPKα2 dominant negative expressing mice (AMPK-DN). SF-PreCon decreased MI/R injury in AMPK-DN mice. To explore the molecular mechanisms responsible for SF-PreCon mediated cardioprotection in DM mice, cell survival molecules were screened. Interestingly, in ND mice, SF-PreCon significantly reduced MI/Rinduced activation of p38, a pro-death MAPK, without altering ERK and JNK. In DM and AMPK-DN mice, the inhibitory effect of SF-PreCon upon p38 activation was significantly blunted. However, SF-PreCon significantly increased phosphorylation of ERK1/2, a pro-survival MAPK in DM and AMPK-DN mice. We demonstrate that SF-PreCon protects the heart via AMPK-dependent inhibition of pro-death MAPK in ND mice. However, SF-PreCon exerts cardioprotective action via AMPK-independent activation of a pro-survival MAPK member in DM mice. SF-PreCon may be beneficial compared to conventional PreCon in diabetes or clinical scenarios in which AMPK signaling is impaired.

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.…”

Volatile anesthetic preconditioning modulates oxidative stress and nitric oxide in patients undergoing coronary artery bypass grafting

“…[ 27 ] Sevoflurane preconditioning mitigates the ischemia-reperfusion injury and improves the cardiac function. [ 28 29 30 ] Erturk et al . observed that sevoflurane provides better protection from ischemic reperfusion injury in thoracic surgical patients after one lung ventilation compared to propofol by lower rise in malondialdehyde and ischemia modified albumin levels during the perioperative period.…”

Autologous transplantation of adipose-derived stromal cells combined with sevoflurane ameliorates acute lung injury induced by cecal ligation and puncture in rats

“…In our study, rats with ALI downregulates α-, β-and γ-ENaC expressions and ADSCs could reverse the ALI-induced reduction of three ENaC subunits levels. Sevoflurane has been shown to reduce mortality via non-anesthetic properties in clinical patients 48 , and has been widely accepted to reduce the levels of inflammatory mediators (IL-1β, TNFα, and IL-6) 49 . Although ADSC treatment was more effective than sevoflurane in the current research, previous studies showed that sevoflurane had cytoprotective effects in ARDS and ALI 50 .…”