An essential role for NF-kappaB in the cardioadaptive response to ischemia.
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.
Morgan
E N
EN
Department of Surgery, University of Washington School of Medicine, Seattle 98195, USA.
Boyle
E M
EM
Yun
W
W
Griscavage-Ennis
J M
JM
Farr
A L
AL
Canty
T G
TG
Pohlman
T H
TH
Verrier
E D
ED
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
D016328:NF-kappa B