title: Role of nuclear factor-κB in volatile anaesthetic preconditioning with sevoflurane during myocardial ischaemia/reperfusion.
abstract: OBJECTIVE
  Anaesthetic preconditioning (APC) protects against myocardial ischaemia/reperfusion injury. Nuclear factor-kappaB (NF-kappaB) has been implicated in APC-induced myocardial protection in vitro. Our study tested the hypothesis that in-vivo APC with sevoflurane is triggered by NF-kappaB through downregulation of inflammatory mediators and upregulation of antiapoptosis factors to prevent myocardial injury during ischaemia/reperfusion.
  
  
  METHODS
  In this in-vivo study, rats were anaesthetized and maintained with sodium pentobarbital throughout the experiment. Rats were exposed to 30 min of 2.5% sevoflurane followed by 15 min washout (APC group) or no inhalation anaesthetics (ischaemia/reperfusion group) before ischaemia/reperfusion. In the sevoflurane group, rats were exposed to 30 min sevoflurane followed by a 165 min washout period. The NF-kappaB inhibitor parthenolide (PTN) was used before or after exposure to sevoflurane (PTN+APC group and APC+PTN group). Left ventricular samples were obtained to measure infarct size, pro-inflammation and apoptosis. A P value less than 0.05 was considered significant.
  
  
  RESULTS
  APC reduced infarct size (34 +/- 6%) compared with ischaemia/reperfusion (53 +/- 6%, P<0.05). PTN administered before or after APC abolished the cardioprotection (53 +/- 5 and 52 +/- 7%, respectively, P < 0.05). APC decreased the myocardium apoptosis compared with the ischaemia/reperfusion only group (6 +/- 1 vs.19 +/- 3%, P < 0.05); PTN administered before or after sevoflurane preconditioning abolished this effect. APC induced upregulation of NF-kappaB p50/p65 before ischaemia (51 +/- 4/26 +/- 3% vs. 15 +/- 1/11 +/- 1% in the control group, P < 0.05). After reperfusion, NF-kappaB was upregulated in the ischaemia/reperfusion and APC groups, but it was lower in the APC group than in the ischaemia/reperfusion group. PTN administered before and after APC inhibited the expressions. Before ischaemia, Bcl-2 was increased in the APC and sevoflurane groups (94 +/- 3 and 102 +/- 4%, respectively) compared with the control group (68 +/- 2%, P < 0.05). After reperfusion, intercellular adhesion molecule-1, tumour necrosis factor-alpha and caspase-3 expressions were significantly increased in the ischaemia/reperfusion group (92 +/- 5, 115 +/- 4 and 65 +/- 2% compared with the control group, P < 0.05); these increases were blunted in the APC group.
  
  
  CONCLUSIONS
  APC with sevoflurane produced myocardial protection against ischaemia/reperfusion in vivo. NF-kappaB acted not only as a trigger but also as a mediator that played an important role in APC through upregulation of NF-kappaB and the antiapoptosis protein Bcl-2 during the preconditioning period and then through downregulation of the inflammatory proteins intercellular adhesion molecule-1 and tumour necrosis factor-alpha during reperfusion, ultimately decreasing caspase-3 expression and apoptosis.
authors.affiliation: Department of Anaesthesiology, the Second Affiliated Hospital of Soochow University, and Institute of Neuroscience, Soochow University, Suzhou, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.forename: Hong
authors.initials: H
authors.lastname: Xie
authors.forename: Xia
authors.initials: X
authors.lastname: Liu
authors.forename: Qin
authors.initials: Q
authors.lastname: Qin
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: D018685:Anesthetics, Inhalation; D000818:Animals; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D008738:Methyl Ethers / Q000008:administration & dosage*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control*; D016328:NF-kappa B / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D016328:NF-kappa B; D000077149:Sevoflurane