Sevoflurane post-conditioning reduces rat myocardial ischemia reperfusion injury through an increase in NOS and a decrease in phopshorylated NHE1 levels
Authors: Jianfang Cao
Chen Wang
Ying Sun
Haorong Wu
Hong Xie
Shigang Qiao
Ming Ying
Qin Shao
Jiang Zhu
Journal: International Journal of Molecular Medicine (2015)
Discipline: CLINICAL MEDICINE
Keywords: sevoflurane post-conditioning; myocardial ischemia/reperfusion injury; protective effects; molecular mechanisms; rat hearts
Affiliations: Department of Anesthesiology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China.

Abstract:  The protective effects of sevoflurane post-conditioning against myocardial ischemia/reperfusion (I/R) injury (MIRI) have been previously reported. However, the mechanisms responsible for these protective effects remain elusive. In this study, in order to investigate the molecular mechanisms responsible for the protective effects of sevoflurane post-conditioning on isolated rat hearts subjected to MIRI, Sprague-Dawley rat hearts were randomly divided into the following 6 groups: i) the sham-operated control; ii) 2.5% sevoflurane; iii) ischemia/reperfusion (I/R); iv) 2.5% sevoflurane post-conditioning plus I/R; v) 2.5% sevoflurane post-conditioning + NG-nitro-L-arginine methyl ester (L-NAME) plus I/R; and vi) L-NAME plus I/R. The infarct size was measured using 2,3,5-triphenyl tetrazolium chloride (TTC) staining. Additionally, the myocardial nitric oxide (NO), NO synthase (NOS) and nicotinamide adenine dinucleotide (NAD+) levels were determined. Autophagosomes and apoptosomes in the myocardium were detected by transmission electron microscopy. The levels of Bcl-2, cleaved caspase-3, Beclin-1, microtubule-associated protein light chain 3 (LC3)‑I/II, Na+/H+ exchanger 1 (NHE1) and phosphorylated NHE1 protein were measured by western blot analysis. NHE1 mRNA levels were measured by reverse transcription-quantitative polymerase chain reaction. Compared with the I/R group, 15 min of exposure to 2.5% sevoflurane during early reperfusion significantly decreased the myocardial infarct size, the autophagic vacuole numbers, the NHE1 mRNA and protein expression of cleaved caspase-3, Beclin-1 and LC3-I/II. Post-conditioning with 2.5% sevoflurane also increased the NO and NOS levels and Bcl-2 protein expression (p&lt;0.05 or p&lt;0.01). Notably, the cardioprotective effects of sevoflurane were partly abolished by the NOS inhibitor, L-NAME. The findings of the present study suggest that sevoflurane post-conditioning protects the myocardium against I/R injury and reduces the myocardial infarct size. The underlying protective mechanisms are associated with the inhibition of mitochondrial permeability transition pore opening, and with the attenuation of cardiomyoctye apoptosis and excessive autophagy. These effects are mediated through an increase in NOS and a decrease in phopshorylated NHE1 levels. 

Retracted: No

PubPeer comments:
 Figure 2A. * Blue boxes. Sometimes two hearts can beat as one, but here two whole rows of hearts appear to look very similar, albeit shown at a different aspect ratio. ![file] , 
 Correction, 4 January 2021: https: www.spandidos-publications.com 10.3892 ijmm.2021.4843  *Following the publication of the above article, an interested reader drew to the authors attention that the data shown for the I R and L-NAME experiments in Fig. 2A appeared to be strikingly similar. After having re-examined their raw data, the authors realized that the data panel of the L-NAME group was inadvertently loaded incorrectly, resulting in a duplication of the I R data in the Figure.* *The revised version of Fig. 2, containing the correct data for the L-NAME group in Fig. 2A, is shown below. The authors are grateful to the Editor of International Journal of Molecular Medicine for granting them the opportunity to publish this Corrigendum, and stress that this error did not significantly affect either the results or the conclusions of the paper. All the authors agree with the publication of this Corrigendum, and apologize to the readership for any inconvenience caused.* I thank the authors and the journal for correcting this duplication. ![file] , 
 The authors thank this interested reader for pointing out this error, and the editors of the International Journal of Molecular Medicine for giving us the opportunity to publish the Corrigendum. ,