HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Fausto Labruto Jarle Vaage Guro Valen Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Li, G. Articles by Valen, G. Search for Related Content PubMed PubMed Citation Articles by Li, G. Articles by Valen, G. Related Collections Cardiac - physiology Myocardial protection

Eur J Cardiothorac Surg 2004;26:968-973
© 2004 Elsevier Science NL

Myocardial protection by remote preconditioning: the role of nuclear factor kappa-B p105 and inducible nitric oxide synthase

^a Crafoord Laboratory for Experimental Surgery L6.00, Karolinska Hospital, S-17176 Stockholm, Sweden
^b Center of Molecular Medicine, Karolinska Hospital, Stockholm, Sweden
^c Department of Thoracic Surgery, Karolinska Hospital, Stockholm, Sweden

Received 19 April 2004; received in revised form 3 June 2004; accepted 17 June 2004.

^* Corresponding author. Tel.: +46-8-51773560; fax: +46-8-51773557. (E-mail: lampo18{at}yahoo.com).

Objective: Adaptation to ischemia by brief episodes of ischemia and reperfusion (preconditioning) of the heart protects the heart against sustained ischemia, where the transcription factor nuclear factor kappa-B (NFB) appears crucial for the protection. Preconditioning of the heart may even be evoked by brief episodes of ischemia and reperfusion in other organs. The present study investigates a possible role for NFB and inducible nitric oxide synthase (iNOS) in adaption to ischemia by remote, delayed protection. Methods: Mice (wild-types, or with targeted deletions of the NFB p105 or the iNOS gene) were subjected to cycles of occlusion and reperfusion of both hind limbs, and 24h later their hearts were isolated and Langendorff-perfused with induced global ischemia and reperfusion. Infarct size was measured. Skeletal muscles from ischemized limbs as well as hearts were also collected for polymerase chain reaction (PCR) and electromobility shift assay (EMSA). Results: Hind limb preconditioning protected left ventricular function and reduced infarct size during reperfusion in wild-type mice. Nuclear translocation of NFB was detected in both heart and preconditioned skeletal muscle 1–2h after the preconditioning episodes (EMSA); while cardiac mRNA for iNOS gradually increased in a 24-h time course after hind limb preconditioning (real-time PCR). When hind limbs of mice with targeted deletions for the p105 subunit of NFB or the iNOS gene were preconditioned, no beneficial effect was observed in the heart. Conclusions: Delayed cardioprotection induced by hind limb preconditioning involves signaling through NFB and iNOS.

This article has been cited by other articles:

				I. E. Konstantinov and A. N. Redington Linking gene expression, nuclear factor kappa B, remote ischemic preconditioning, and transplantation: A quest for an elusive Holy Grail or a road to an amazing discovery? J. Thorac. Cardiovasc. Surg., February 1, 2006; 131(2): 507 - 509. [Full Text] [PDF]

				I. E. Konstantinov, S. Arab, J. Li, J. G. Coles, C. Boscarino, A. Mori, E. Cukerman, F. Dawood, M. M.H. Cheung, M. Shimizu, et al. The remote ischemic preconditioning stimulus modifies gene expression in mouse myocardium J. Thorac. Cardiovasc. Surg., November 1, 2005; 130(5): 1326 - 1332. [Abstract] [Full Text] [PDF]