title: Restoration of autophagic flux in myocardial tissues is required for cardioprotection of sevoflurane postconditioning in rats.
abstract: OBJECTIVE
  Sevoflurane postconditioning (SpostC) has been shown to protect the heart from ischemia-reperfusion (I/R) injury. In this study, we examined whether SpostC affected autophagic flux in myocardial tissues that contributed to its cardioprotective effects in rats following acute I/R injury.
  
  
  METHODS
  SD rats underwent 30 min of left anterior descending coronary artery ligation followed by 120 min of reperfusion. The rats were subjected to inhalation of 2.4% (v/v) sevoflurane during the first 5 min of reperfusion, and chloroquine (10 mg/kg, ip) was injected 1 h before I/R. Myocardial infarct size was estimated using TTC staining. Autophagosomes in myocardial tissues were detected under TEM. Expression of LC3B-II, beclin-1, p62/SQSTM1, cathepsin B, caspase-3 and cleaved PARP was assessed using Western blot analysis. Plasma cardiac troponin I was measured using ELISA. Cardiomyocyte apoptosis was evaluated with TUNEL staining.
  
  
  RESULTS
  I/R procedure produced severe myocardium infarct and apoptosis accompanied by markedly increased number of autophagosomes, as well as increased levels of LC3B-II, beclin-1 and p62 in myocardial tissues. SpostC significantly reduced infarct size, attenuated myocardial apoptosis, restored intact autophagic flux and improved the lysosomal function in myocardial tissues. Administration of chloroquine that blocked autophagic flux abrogated the cardioprotective effects of SpostC.
  
  
  CONCLUSIONS
  SpostC exerts its cardioprotective effects in rats following I/R injury via restoring autophagic flux in myocardial tissues.
authors.affiliation: 1] State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China [2] Department of Anesthesiology, Fuwai Cardiovascular Hospital, Beijing 100037, China.
authors.forename: Yu-Lin
authors.initials: YL
authors.lastname: Zhang
authors.affiliation: 1] State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China [2] Department of Anesthesiology, Fuwai Cardiovascular Hospital, Beijing 100037, China.
authors.forename: Yun-Tai
authors.initials: YT
authors.lastname: Yao
authors.affiliation: 1] State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China [2] Department of Anesthesiology, Fuwai Cardiovascular Hospital, Beijing 100037, China.
authors.forename: Neng-Xin
authors.initials: NX
authors.lastname: Fang
authors.affiliation: 1] State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China [2] Department of Anesthesiology, Fuwai Cardiovascular Hospital, Beijing 100037, China.
authors.forename: Cheng-Hui
authors.initials: CH
authors.lastname: Zhou
authors.affiliation: 1] State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China [2] Department of Anesthesiology, Fuwai Cardiovascular Hospital, Beijing 100037, China.
authors.forename: Jun-Song
authors.initials: JS
authors.lastname: Gong
authors.affiliation: 1] State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China [2] Department of Anesthesiology, Fuwai Cardiovascular Hospital, Beijing 100037, China.
authors.forename: Li-Huan
authors.initials: LH
authors.lastname: Li
mesh_terms: D018685:Anesthetics, Inhalation / Q000627:therapeutic use*; D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects; D008297:Male; D008738:Methyl Ethers / Q000627:therapeutic use*; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D009206:Myocardium / Q000473:pathology*; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane
chemical_list: D018685:Anesthetics, Inhalation; D002316:Cardiotonic Agents; D008738:Methyl Ethers; D000077149:Sevoflurane