Document Detail


Pharmacological pre- and post- conditioning agents: reperfusion-injury of the heart revisited.
MedLine Citation:
PMID:  18691153     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Ischemic preconditioning (PC) and postconditioning (PostC) are endogenous mechanisms of protection of the ischemic heart. In brief, short cycles of sublethal ischemia separated by brief periods of reperfusion render the heart resistant to infarction from a subsequent lethal episode of prolonged ischemia. Although PC is a powerful form of protection, its clinical application is limited because of ethical and practical reasons. It is of interest that multiple very short periods of ischemia and reperfusion applied at the onset of reperfusion are also capable in limiting the infarct size. In fact, the short ischemic insults in PC have to be applied before the onset of sustained period of ischemia which cannot be precisely anticipated. On the contrary, the very brief insults in postconditioning (PostC) have to be applied immediately after the end of the long ischemia thus making the intervention more easily applicable. Both mechanisms reduce the infarct size by limiting the reperfusion injury. Pharmacological PC and PostC represent ideal alternatives that may substitute the short ischemic insults for pharmaceuticals means. The components of PC share two pathways, one that involves the mitochondrial K(ATP) channels- free radicals and PKC and another one that involves adenosine and PKC. Reperfusion injury salvage kinases (RISK) prevent the mitochondrial permeability transition pores (mPTP) which destroy the mitochondria and cause cell death. PC via PKC and PostC via gradual restoration of pH at reperfusion up-regulate RISK and preserve viable part of the ischemic region of the heart. In order to confer pharmacological protection, novel therapeutic strategies, based on the knowledge of the ligands, of the receptors and of the intracellular signaling pathways have emerged. Adenosine, nicorandil and other agents have been already used as pharmacological mimetics of ischemic PC in multicenter trials. Furthermore, agents that increase RISK or directly prevent mPTP are also under investigation as PostC analogues. We summarize recent studies focused on the pharmacological interventions and on the discovery of novel agents that may reduce the infarct size.
Authors:
Ioanna Andreadou; Efstathios K Iliodromitis; Maria Koufaki; Dimitrios Th Kremastinos
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Mini reviews in medicinal chemistry     Volume:  8     ISSN:  1389-5575     ISO Abbreviation:  Mini Rev Med Chem     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-08-11     Completed Date:  2008-09-19     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101094212     Medline TA:  Mini Rev Med Chem     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  952-9     Citation Subset:  IM    
Affiliation:
Department of Pharmaceutical Chemistry, School of Pharmacy, University of Athens, Panepistimioupolis, Zografou, Athens, Greece. jandread@pharm.uoa.gr
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MeSH Terms
Descriptor/Qualifier:
Animals
Cardiotonic Agents / pharmacology
Chemistry, Pharmaceutical / methods
Coronary Circulation
Drug Design
Heart / physiopathology
Humans
Ischemic Preconditioning, Myocardial / adverse effects,  methods*
Mitochondrial Membrane Transport Proteins / metabolism
Models, Chemical
Myocardial Ischemia / metabolism
Myocardial Reperfusion
Myocardial Reperfusion Injury / drug therapy*,  etiology*,  pathology
Signal Transduction
Chemical
Reg. No./Substance:
0/Cardiotonic Agents; 0/Mitochondrial Membrane Transport Proteins; 0/mitochondrial permeability transition pore

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