Cited by 1,062Cardiac Ischemia and ReperfusionOrgan Transplantation Techniques and OutcomesCell death mechanisms and regulation

Preconditioning the myocardium: from cellular physiology to clinical cardiology

YELLON, DEREK M., DOWNEY, JAMES M.·2003·Physiological Reviews

Abstract

Yellon, Derek M., and James M. Downey. Preconditioning the Myocardium: From Cellular Physiology to Clinical Cardiology. Physiol Rev 83: 1113-1151, 2003; 10.1152/physrev.00009.2003.—The phenomenon of ischemic preconditioning, in which a period of sublethal ischemia can profoundly protect the cell from infarction during a subsequent ischemic insult, has been responsible for an enormous amount of research over the last 15 years. Ischemic preconditioning is associated with two forms of protection: a classical form lasting ∼2 h after the preconditioning ischemia followed a day later by a second window of protection lasting ∼3 days. Both types of preconditioning share similarities in that the preconditioning ischemia provokes the release of several autacoids that trigger protection by occupying cell surface receptors. Receptor occupancy activates complex signaling cascades which during the lethal ischemia converge on one or more end-effectors to mediate the protection. The end-effectors so far have eluded identification, although a number have been proposed. A range of different pharmacological agents that activate the signaling cascades at the various levels can mimic ischemic preconditioning leading to the hope that specific therapeutic agents can be designed to exploit the profound protection seen with ischemic preconditioning. This review examines, in detail, the complex mechanisms associated with both forms of preconditioning as well as discusses the possibility to exploit this phenomenon in the clinical setting. As our understanding of the mechanisms associated with preconditioning are unravelled, we believe we can look forward to the development of new therapeutic agents with novel mechanisms of action that can supplement current treatment options for patients threatened with acute myocardial infarction.

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Crossref · 10.1152/physrev.00009.2003

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Authors
YELLON, D. M., & DOWNEY, J. M.
Affiliations
University College Hospital (GB)
Venue
Physiological Reviews
Published
2003-10
Volume
83
Issue
4
Pages
1113-1151
ISSN
  • 0031-9333 (ISSN-L)
  • 1522-1210
OpenAlex
W2047876380
Cited by
1,062
References
424
Citations by year
2026: 9 · 2025: 12 · 2024: 18 · 2023: 17 · 2022: 19 · 2021: 28 · 2020: 23 · 2019: 25 · 2018: 30 · 2017: 30 · 2016: 51 · 2015: 41 · 2014: 41 · 2013: 64 · 2012: 73
FWCI
8.24
Type
journal article
Language
en
Open access
closed
Locations
  • Physiological Reviews (publishedVersion)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
  • Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Keywords
ischemic preconditioning, myocardial infarction, cardioprotection, autacoids, second window of protection, pharmacological preconditioning
MeSH terms
Animals, Humans, Myocardium, Myocardial Ischemia, Ischemic Preconditioning, Myocardial, Myocytes, Cardiac

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