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Ann Thorac Surg 1999;68:377-382
© 1999 The Society of Thoracic Surgeons

Original Articles

An essential role for NF-{kappa}B in the cardioadaptive response to ischemia

Elizabeth N. Morgan, MDa, Edward M. Boyle, Jr, MDa, Wang Yun, MDa, Jeanette M. Griscavage-Ennis, PhDa, Angela L. Farr, BAa, Timothy G. Canty, Jr, MDa, Timothy H. Pohlman, MDa, Edward D. Verrier, MDa

a Division of Cardiothoracic Surgery, Department of Surgery, University of Washington School of Medicine, Seattle, Washington, USA

Address reprint requests to Dr Verrier, Division of Cardiothoracic Surgery, University of Washington, 1959 Pacific Ave NE, Box 356310, Seattle, WA 98195
e-mail: edver{at}u.washington.edu

Presented at the Thirty-fifth Annual Meeting of The Society of Thoracic Surgeons, San Antonio, TX, Jan 25–27, 1999.

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-{kappa}B 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-{kappa}B inhibitor, followed by I/R (IPProDTC + I/R). Infarct size, indices of regional contractility, and NF-{kappa}B 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-{kappa}B activation with IP that was blocked by ProDTC. I/R and IPProDTC + I/R groups showed NF-{kappa}B activation with I/R that was absent in preconditioned animals.

Conclusions. The cytoprotective effects induced by IP require activation of NF-{kappa}B.




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