Sevoflurane postconditioning protects against myocardial ischemia/reperfusion injury by restoring autophagic flux via an NO-dependent mechanism
Authors: An Wang
Jia Qiu
Ying Sun
Chen Wang
Jian-Zhong An
Bo Sun
Hui-Ling Zhang
Shi-Gang Qiao
Lei Hong
Journal: Acta Pharmacologica Sinica (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: NG-nitro-L-arginine methyl ester; autophagy; chloroquine; myocardial reperfusion injury; nitric oxide
Affiliations: Department of Pharmacology and Laboratory of Cerebrovascular and Cardiovascular Pharmacology, College of Pharmaceutical Science, Soochow University, Suzhou, 215123, China., Institute of Clinical Medicine Research, the Affiliated Suzhou Hospital of Nanjing Medical University; Suzhou Science and Technology Town Hospital, Suzhou, 215153, China., Department of Anesthesiology and Perioperative Medicine, the Affiliated Suzhou Hospital of Nanjing Medical University; Suzhou Science and Technology Town Hospital, Suzhou, 215153, China., Department of Anesthesiology, the Second Affiliated Hospital of Soochow University, Suzhou, 215004, China., Institute of Clinical Medicine Research, the Affiliated Suzhou Hospital of Nanjing Medical University; Suzhou Science and Technology Town Hospital, Suzhou, 215153, China. ., Department of Anesthesiology and Perioperative Medicine, the Affiliated Suzhou Hospital of Nanjing Medical University; Suzhou Science and Technology Town Hospital, Suzhou, 215153, China. ., Department of Pharmacology and Laboratory of Cerebrovascular and Cardiovascular Pharmacology, College of Pharmaceutical Science, Soochow University, Suzhou, 215123, China. .

Abstract:  Volatile anesthetics improve postischemic cardiac function and reduce infarction even when administered for only a brief time at the onset of reperfusion. A recent study showed that sevoflurane postconditioning (SPC) attenuated myocardial reperfusion injury, but the underlying mechanisms remain unclear. In this study, we examined the effects of sevoflurane on nitric oxide (NO) release and autophagic flux during the myocardial ischemia/reperfusion (I/R) injury in rats in vivo and ex vivo. Male rats were subjected to 30 min ischemia and 2 h reperfusion in the presence or absence of sevoflurane (1.0 minimum alveolar concentration) during the first 15 min of reperfusion. We found that SPC significantly improved hemodynamic performance after reperfusion, alleviated postischemic myocardial infarction, reduced nicotinamide adenine dinucleotide content loss, and cytochrome c release in heart tissues. Furthermore, SPC significantly increased the phosphorylation of endothelial nitric oxide synthase (NOS) and neuronal nitric oxide synthase, and elevated myocardial NOS activity and NO production. All these effects were abolished by treatment with an NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg, i.v.). We also observed myocardial I/R-induced accumulation of autophagosomes in heart tissues, as evidenced by increased ratios of microtubule-associated protein 1 light chain 3 II/I, up-regulation of Beclin 1 and P62, and reduced lysosome-associated membrane protein-2 expression. SPC significantly attenuated I/R-impaired autophagic flux, which were blocked by L-NAME. Moreover, pretreatment with the autophagic flux blocker chloroquine (10 mg/kg, i.p.) increased autophagosome accumulation in SPC-treated heart following I/R and blocked SPC-induced cardioprotection. The same results were also observed in a rat model of myocardial I/R injury ex vivo, suggesting that SPC protects rat hearts against myocardial reperfusion injury by restoring I/R-impaired autophagic flux via an NO-dependent mechanism. 

Retracted: No

PubPeer comments:
 Retracted [12 February 2021] . --------------------------------------- The Editor and Publisher of Neuropsychiatric Disease and Treatment wish to retract the published article. The journal was notified by the Editor of *Metabolic Brain Disease* of a submission they received from another author group which had significant overlap with the paper published in *Neuropsychiatric Disease and Treatment*. The authors of the *Neuropsychiatric Disease and Treatment* paper could not be contacted for an explanation. The Editor has determined the findings are no longer valid and has requested for the paper to be retracted. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as u201cRetractedu201d. ,