title: Delayed anesthetic preconditioning protects against myocardial infarction via activation of nuclear factor-κB and upregulation of autophagy.
abstract: OBJECTIVE
  Delayed volatile anesthetic preconditioning (APC) can protect against myocardial ischemia/reperfusion (I/R) injury; the delayed phase is called the second window of protection (SWOP), but the underlying mechanism is unclear. Nuclear factor-κB (NF-κB) is involved in the myocardial protection conferred by APC in the acute phase; autophagy has been reported to confer apoptosis inhibition and infarction reduction. We hypothesized that APC initiates delayed cardioprotection against I/R injury via the activation of NF-kB and upregulation of autophagy, thus attenuating the inflammatory response and apoptosis
  
  
  METHODS
  After a rat I/R model was set up, left ventricular samples were obtained before I/R to assess NF-κB-DNA binding activity and microtubule-associated protein 1 light chain 3 (LC3) and cathepsin B protein expression, and to examine autophagosomes with a transmission electron microscope. Infarct size and the expressions of tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and caspase-3 were measured at the end of 2-h reperfusion.
  
  
  RESULTS
  The infarct size was significantly reduced in the SWOP group (30 ± 3 %) when compared with that in the I/R group (47 ± 7 %, P < 0.05), and this finding was associated with increased NF-κB-DNA binding activity and autophagosomes. In addition, the expressions of LC3-II and cathepsin B were also up-regulated, and the expressions of TNF-α, IL-1β, and caspase-3 were attenuated in the SWOP group when compared with the findings in the I/R group. However, this protection was abolished by the administration of parthenolide (PTN) before sevoflurane inhalation, which resulted in an infarct size that was significantly increased (47 ± 5 %, P < 0.05 PTN + SWOP vs. SWOP group).
  
  
  CONCLUSIONS
  Delayed APC protected the rat heart from I/R injury. The underlying mechanisms may include NF-κB activation, upregulation of autophagy, and the attenuation of TNF-α, IL-1β, and caspase-3 expressions.
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou 215004, People's Republic of China.
authors.forename: Shigang
authors.initials: S
authors.lastname: Qiao
authors.forename: Hong
authors.initials: H
authors.lastname: Xie
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.forename: Xuemei
authors.initials: X
authors.lastname: Wu
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.forename: Chunfeng
authors.initials: C
authors.lastname: Liu
mesh_terms: D000704:Analysis of Variance; D000769:Anesthesia, Inhalation; D018685:Anesthetics, Inhalation / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D007249:Inflammation / Q000517:prevention & control; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology; D046529:Microscopy, Electron, Transmission; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D009206:Myocardium / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism*; D010588:Phagosomes / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D018685:Anesthetics, Inhalation; D015415:Biomarkers; D008738:Methyl Ethers; D016328:NF-kappa B; D000077149:Sevoflurane