Document Detail


Cardiac preconditioning for ischaemia: lost in translation.
MedLine Citation:
PMID:  20075380     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Coronary heart disease (CHD) is the leading cause of death worldwide. The development of novel treatment strategies for protecting the myocardium against the detrimental effects of acute ischaemia-reperfusion injury, termed cardioprotection, and for improving clinical outcomes in patients with CHD requires the use of appropriate animal disease models. The concept of cardioprotection was first conceived in the late 1960s and has evolved to include the endogenous cardioprotective phenomenon of ischaemic conditioning, a concept in which the heart can be protected from an episode of acute lethal ischaemia-reperfusion injury by applying brief non-lethal episodes of ischaemia and reperfusion either to the heart itself or to an organ or tissue that is remote from the heart. The brief conditioning episodes of ischaemia and reperfusion can be applied prior to the index ischaemic episode (ischaemic preconditioning), after the onset of the index ischaemic episode (ischaemic perconditioning), or at the onset of reperfusion (ischaemic postconditioning). Elucidation of the signal transduction pathways underlying ischaemic conditioning has identified a variety of pharmacological agents that are capable of reproducing its cardioprotective actions. Despite a wealth of preclinical, experimental animal data demonstrating clear cardioprotective benefits with these treatment strategies, their translation into clinical therapy has been hugely disappointing. This review explores the potential reasons behind this failure; it will focus primarily on the inadequacy of the experimental animal disease models that are currently being used to investigate novel cardioprotective strategies, which on the whole are not adequately representative of the clinical scenario, and finally, we will discuss potential solutions to remedy this problem.
Authors:
Andrew J Ludman; Derek M Yellon; Derek J Hausenloy
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Disease models & mechanisms     Volume:  3     ISSN:  1754-8411     ISO Abbreviation:  Dis Model Mech     Publication Date:    2010 Jan-Feb
Date Detail:
Created Date:  2010-01-15     Completed Date:  2010-03-10     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  101483332     Medline TA:  Dis Model Mech     Country:  England    
Other Details:
Languages:  eng     Pagination:  35-8     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Clinical Trials as Topic
Comorbidity
Disease Models, Animal
Humans
Ischemic Preconditioning, Myocardial*
Myocardial Reperfusion Injury / pathology
Translational Medical Research*
Grant Support
ID/Acronym/Agency:
RG/08/015/26411//British Heart Foundation; //British Heart Foundation; //Department of Health

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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