Document Detail


Reperfusion injury in humans: a review of clinical trials on reperfusion injury inhibitory strategies.
MedLine Citation:
PMID:  17306241     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The principal therapy in patients with myocardial infarction to limit infarct size is myocardial reperfusion by mechanical or pharmacological intervention. Reperfusion has been proposed to cause myocardial injury beyond that caused by the preceding ischaemia, termed "reperfusion injury" (RI). While the precise mechanism of RI is still incompletely understood, a large number of clinical studies have been performed over the past decade targeting some of the postulated mechanisms of RI. These clinical studies were based on experimental data demonstrating significant myocardial salvage. Nevertheless, clinical benefits were absent or very limited. The purpose of this review is to provide an overview of the various strategies that inhibit RI and to discuss potential mechanisms that may contribute to the discrepancy between the promising pre-clinical data and the rather disappointing results obtained from prospective clinical trials. There are numerous differences between the experimental models and clinical studies, including the fact that experimental studies typically use abrupt occlusion and reperfusion protocols in animals with previously healthy myocardium that apparently do not predict the therapeutic efficacy of novel cardioprotective agents in a clinical setting with pre-existing progressive coronary disease, intermittent coronary occlusion, and relatively late reperfusion. However, discrepancies also exist between experimental studies. Future experimental studies of reperfusion injury should use models that mimic the clinical situation more closely. Furthermore, future large clinical trials should only be performed in cases where the drug under investigation proved to reduce RI in a series of well-designed (possibly multicenter) experimental studies and in clinical trials with predefined subgroups.
Authors:
Maurits T Dirksen; Gerrit J Laarman; Maarten L Simoons; Dirk J G M Duncker
Publication Detail:
Type:  Journal Article; Review     Date:  2007-01-23
Journal Detail:
Title:  Cardiovascular research     Volume:  74     ISSN:  0008-6363     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  2007 Jun 
Date Detail:
Created Date:  2007-05-14     Completed Date:  2007-09-17     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  343-55     Citation Subset:  IM    
Affiliation:
Amsterdam Department of Interventional Cardiology, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Adenosine / therapeutic use
Antioxidants / therapeutic use
Calcium Channel Blockers / therapeutic use
Clinical Trials as Topic
Coronary Disease / drug therapy
Forecasting
Humans
Ischemic Preconditioning, Myocardial / methods
Myocardial Ischemia / drug therapy*
Myocardial Reperfusion Injury / prevention & control*
Sodium-Hydrogen Antiporter / antagonists & inhibitors
Treatment Outcome
Chemical
Reg. No./Substance:
0/Antioxidants; 0/Calcium Channel Blockers; 0/Sodium-Hydrogen Antiporter; 58-61-7/Adenosine

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


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