An essential role for NF-κB 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-κB 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-κB inhibitor, followed by I/R (IPProDTC + I/R). Infarct size, indices of regional contractility, and NF-κB 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 andIPProDTC + I/R groups (p< 0.05). Gel shift analysis showed NF-κB activation with IP that was blocked by ProDTC. I/R and IPProDTC + I/R groups showed NF-κB activation with I/R that was absent in preconditioned animals. Conclusions. The cytoprotective effects induced by IP require activation of NF-κB.