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Cardiovascular Research 2002 55(3):526-533; doi:10.1016/S0008-6363(02)00237-7
© 2002 by European Society of Cardiology
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Copyright © 2002, European Society of Cardiology

Ischemic preconditioning: a plea for rationally targeted clinical trials

Robert A Klonera,b,*, Mark T Speakmana and Karin Przyklenka,b

aHeart Institute, Good Samaritan Hospital, 1225 Wilshire Boulevard, Los Angeles, CA 90017, USA
bDepartment of Medicine, Section of Cardiology, University of Southern California, Los Angeles, CA 90017, USA

* Corresponding author. Tel.: +1-213-977-4050; fax: +1-213-977-4107 rkloner@goodsam.org

Received 31 October 2001; accepted 27 December 2001

KEYWORDS Coronary disease; Preconditioning

The first 150 words of the full text of this article appear below.

The concept of myocardial ischemic ‘preconditioning’ (PC) has been with us since 1986 [1]. A tremendous body of research over the last 15 years has documented this phenomenon in virtually every species tested, with both an early and late phase of PC-induced cardioprotection, manifest ~5–30 min and 12–24 h after the PC trigger, having been identified. A host of additional studies have yielded insight into the cellular mediators and complex second messenger pathways that purportedly contribute to the protection achieved with brief antecedent PC ischemia, with the currently favored paradigm involving initial stimulation of one or more G protein-coupled receptors; subsequent activation of multiple ‘in parallel’ or ‘in series’ kinases (i.e. including, among others, the {varepsilon}-isoform of protein kinase C and one or more isoforms of p38 mitogen activated protein kinase); followed by phosphorylation and activation of a membrane-bound end-effector, possibly the sarcolemmal and/or mitochondrial KATP channel. These mechanistic . . . [Full Text of this Article]


   1. The ‘screening’ models
 
1.1 Isolated human myocardial samples
1.2 Repeated balloon inflations during angioplasty

   2. The ‘prophylaxis’ models
 
2.1 Repeated exercise and the ‘warm-up’ phenomenon
2.2 Coronary artery bypass surgery
2.3 Transplant

   3. The ‘holy grail’: PC-based strategies for the treatment of acute myocardial infarction
 

   4. The underlying problem: preconditioning the aged and diseased heart
 

   5. Summary
 

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