title: An essential role for NF-kappaB in the cardioadaptive response to ischemia.
abstract: BACKGROUND
  Ischemic preconditioning (IP) is the phenomenon whereby brief episodes of ischemia protect the heart against a subsequent ischemic stress. We hypothesize that activation of the transcription factor NF-kappaB mediates IP.
  
  
  METHODS
  Rabbits were randomly allocated to one of three groups: (1) 45 minutes of myocardial ischemia followed by 2 hours of reperfusion (I/R); (2) three cycles of 5-minute ischemia and 5 minutes of reperfusion followed by I/R (IP + I/R); or (3) IP in the presence of ProDTC, a specific NF-kappaB inhibitor, followed by I/R (IPProDTC + I/R). Infarct size, indices of regional contractility, and NF-kappaB activation were determined.
  
  
  RESULTS
  In preconditioned rabbits (IP + I/R), infarct size was reduced 83% compared with both I/R alone and IPProDTC + I/R groups (p < 0.05). Throughout reperfusion, preconditioned myocardium showed enhanced regional contractile function compared with I/R and IPProDTC + I/R groups (p < 0.05). Gel shift analysis showed NF-kappaB activation with IP that was blocked by ProDTC. I/R and IPProDTC + I/R groups showed NF-kappaB activation with I/R that was absent in preconditioned animals.
  
  
  CONCLUSIONS
  The cytoprotective effects induced by IP require activation of NF-kappaB.
authors.affiliation: Department of Surgery, University of Washington School of Medicine, Seattle 98195, USA.
authors.forename: E N
authors.initials: EN
authors.lastname: Morgan
authors.forename: E M
authors.initials: EM
authors.lastname: Boyle
authors.forename: W
authors.initials: W
authors.lastname: Yun
authors.forename: J M
authors.initials: JM
authors.lastname: Griscavage-Ennis
authors.forename: A L
authors.initials: AL
authors.lastname: Farr
authors.forename: T G
authors.initials: TG
authors.lastname: Canty
authors.forename: T H
authors.initials: TH
authors.lastname: Pohlman
authors.forename: E D
authors.initials: ED
authors.lastname: Verrier
mesh_terms: D000818:Animals; D004591:Electrophoresis, Polyacrylamide Gel; D019157:Ischemic Preconditioning, Myocardial; D009200:Myocardial Contraction / Q000502:physiology; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000473:pathology / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000473:pathology; D016328:NF-kappa B / Q000502:physiology*; D011817:Rabbits
chemical_list: D016328:NF-kappa B