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Postconditioning Signalling in the Heart: Mechanisms and Translatability.
MedLine Citation:
PMID:  25303373     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The protective effect of ischaemic postconditioning (short cycles of reperfusion and reocclusion of a previously occluded vessel) was identified over a decade ago commanding intense interest as an approach for modifying reperfusion injury which contributes to infarct size in acute myocardial infarction. Elucidation of the major mechanisms of postconditioning has identified potential pharmacological targets for limitation of reperfusion injury. These include ligands for membrane-associated receptors, activators of phosphokinase survival signalling pathways and inhibitors of the mitochondrial permeability transition pore. In experimental models, numerous agents that target these mechanisms have shown promise as postconditioning mimetics. Nevertheless, clinical studies of ischaemic postconditioning and pharmacological postconditioning mimetics have been equivocal. The majority of experimental research is conducted in animal models which do not fully portray the complexity of risk factors and comorbidities with which patients present and which we now know modify the signalling pathways recruited in postconditioning. Cohort size and power, patient selection and deficiencies in clinical infarct size estimation may all represent major obstacles to assessing the therapeutic efficacy of postconditioning. Furthermore, chronic treatment of these patients with drugs like ACE inhibitors, statins, nitrates etc. may modify signalling, inhibiting the protective effect of postconditioning mimetics, or conversely, induce a maximally protected state wherein no further benefit can be demonstrated. Arguably, successful translation of postconditioning can not occur until all of these issues are addressed i.e. experimental investigation requires more complex models that better reflect the clinical setting, while clinical investigation requires bigger trials with appropriate patient selection and standardisation of clinical infarct size measurements.
Authors:
Justin S Bice; Gary F Baxter
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-10-10
Journal Detail:
Title:  British journal of pharmacology     Volume:  -     ISSN:  1476-5381     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2014 Oct 
Date Detail:
Created Date:  2014-10-10     Completed Date:  -     Revised Date:  2014-10-11    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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This article is protected by copyright. All rights reserved.
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