Published Online
on September 30, 2004

A more recent version of this article appeared on November 1, 2004

This Article Full Text (PDF) All Versions of this Article: 35/11_suppl_1/2676    most recent 01.STR.0000143220.21382.fdv1 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 Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Stein, A. B. Articles by Bolli, R. Search for Related Content PubMed PubMed Citation Articles by Stein, A. B. Articles by Bolli, R. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Cardiomyopathy Hazardous Substances DB NITRIC OXIDE Related Collections Acute coronary syndromes

Submitted on June 16, 2004
Accepted on August 5, 2004

Delayed Adaptation of the Heart to Stress. Late Preconditioning

Adam B. Stein MD; Xian-Liang Tang MD; Yiru Guo MD; Yu-Ting Xuan PhD; Buddhadeb Dawn MD; and Roberto Bolli MD^*

From the Division of Cardiology and the Institute of Molecular Cardiology, University of Louisville, Louisville, Kentucky.

^* To whom correspondence should be addressed. E-mail: rbolli{at}louisville.edu.

Abstract--The early phase of preconditioning (PC) lasts 2 to 3 hours and protects against myocardial infarction, but not against stunning. In contrast, the late phase of PC lasts for 3 to 4 days and protects against both myocardial stunning and infarction, making this phenomenon more clinically relevant. Late PC is a genetic reprogramming of the heart that involves the activation of several stress-responsive genes, which ultimately results in the development of a cardioprotective phenotype. Sublethal ischemic insults release chemical signals (nitric oxide [NO], adenosine, and reactive oxygen species) that trigger a series of signaling events (eg, activation of protein kinase C, Src protein tyrosine kinases, Janus kinases 1/2, and nuclear factor-B) and culminates in increased synthesis of inducible NO synthase, cyclooxygenase-2, heme oxygenase-1, aldose reductase, Mn superoxide dismutase, and probably other cardioprotective proteins. In addition to ischemia, heat stress, exercise, and cytokines can also induce a similar series of events. Perhaps most importantly, many pharmacologic agents (eg, NO donors, adenosine receptor agonists, endotoxin derivatives, or opioid receptor agonists) can mimic the effects of ischemia in inducing the late phase of PC, suggesting that this phenomenon might be exploited therapeutically. The purpose of this review is to summarize the mechanisms that underlie the late phase of ischemic PC.

Key words: ischemic preconditioning • myocardial ischemia • myocardial reperfusion • nitric oxide

This article has been cited by other articles:

				E. Murphy and C. Steenbergen Mechanisms Underlying Acute Protection From Cardiac Ischemia-Reperfusion Injury Physiol Rev, April 1, 2008; 88(2): 581 - 609. [Abstract] [Full Text] [PDF]

				J. Feng, E. Lucchinetti, G. Fischer, M. Zhu, K. Zaugg, M. C. Schaub, and M. Zaugg Cardiac remodelling hinders activation of cyclooxygenase-2, diminishing protection by delayed pharmacological preconditioning: role of HIF1{alpha} and CREB Cardiovasc Res, April 1, 2008; 78(1): 98 - 107. [Abstract] [Full Text] [PDF]

				R. M. Mentzer Jr, M. S. Jahania, and R. D. Lasley Myocardial Protection Card. Surg. Adult, January 1, 2008; 3(2008): 443 - 464. [Full Text]

				T. C. Zhao, G. Cheng, L. X. Zhang, Y. T. Tseng, and J. F. Padbury Inhibition of histone deacetylases triggers pharmacologic preconditioning effects against myocardial ischemic injury Cardiovasc Res, December 1, 2007; 76(3): 473 - 481. [Abstract] [Full Text] [PDF]

				E. M. Southerland, D. M. Milhorn, R. D. Foreman, B. Linderoth, M. J. L. DeJongste, J. A. Armour, V. Subramanian, M. Singh, K. Singh, and J. L. Ardell Preemptive, but not reactive, spinal cord stimulation mitigates transient ischemia-induced myocardial infarction via cardiac adrenergic neurons Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H311 - H317. [Abstract] [Full Text] [PDF]

				R. P. Taylor, M. E. Olsen, and J. W. Starnes Improved postischemic function following acute exercise is not mediated by nitric oxide synthase in the rat heart Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H601 - H607. [Abstract] [Full Text] [PDF]

				M. L. Barreiro Arcos, G. Gorelik, A. Klecha, A. M. Genaro, and G. A. Cremaschi Thyroid hormones increase inducible nitric oxide synthase gene expression downstream from PKC-{zeta} in murine tumor T lymphocytes Am J Physiol Cell Physiol, August 1, 2006; 291(2): C327 - C336. [Abstract] [Full Text] [PDF]

				K. Inagaki, E. Churchill, and D. Mochly-Rosen Epsilon protein kinase C as a potential therapeutic target for the ischemic heart Cardiovasc Res, May 1, 2006; 70(2): 222 - 230. [Abstract] [Full Text] [PDF]