Document Detail

Profound cardioprotection with chloramphenicol succinate in the swine model of myocardial ischemia-reperfusion injury.
MedLine Citation:
PMID:  20837911     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Emerging evidence suggests that "adaptive" induction of autophagy (the cellular process responsible for the degradation and recycling of proteins and organelles) may confer a cardioprotective phenotype and represent a novel strategy to limit ischemia-reperfusion injury. Our aim was to test this paradigm in a clinically relevant, large animal model of acute myocardial infarction.
METHODS AND RESULTS: Anesthetized pigs underwent 45 minutes of coronary artery occlusion and 3 hours of reperfusion. In the first component of the study, pigs received chloramphenicol succinate (CAPS) (an agent that purportedly upregulates autophagy; 20 mg/kg) or saline at 10 minutes before ischemia. Infarct size was delineated by tetrazolium staining and expressed as a % of the at-risk myocardium. In separate animals, myocardial samples were harvested at baseline and 10 minutes following CAPS treatment and assayed (by immunoblotting) for 2 proteins involved in autophagosome formation: Beclin-1 and microtubule-associated protein light chain 3-II. To investigate whether the efficacy of CAPS was maintained with "delayed" treatment, additional pigs received CAPS (20 mg/kg) at 30 minutes after occlusion. Expression of Beclin-1 and microtubule-associated protein light chain 3-II, as well as infarct size, were assessed at end-reperfusion. CAPS was cardioprotective: infarct size was 25±5 and 41±4%, respectively, in the CAPS-pretreated and CAPS-delayed treatment groups versus 56±5% in saline controls (P<0.01 and P<0.05 versus control). Moreover, administration of CAPS was associated with increased expression of both proteins.
CONCLUSIONS: Our results demonstrate attenuation of ischemia-reperfusion injury with CAPS and are consistent with the concept that induction of autophagy may provide a novel strategy to confer cardioprotection.
Javier A Sala-Mercado; Joseph Wider; Vishnu Vardhan Reddy Undyala; Salik Jahania; Wonsuk Yoo; Robert M Mentzer; Roberta A Gottlieb; Karin Przyklenk
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Circulation     Volume:  122     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-09-14     Completed Date:  2010-10-01     Revised Date:  2013-12-17    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  S179-84     Citation Subset:  AIM; IM    
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MeSH Terms
Anti-Bacterial Agents / pharmacology
Apoptosis Regulatory Proteins / metabolism
Autophagy / drug effects
Cardiotonic Agents / pharmacology*
Chloramphenicol / analogs & derivatives*,  pharmacology
Disease Management
Gene Expression Regulation / drug effects
Microtubule-Associated Proteins / biosynthesis
Myocardial Infarction / metabolism,  pathology,  prevention & control*
Myocardial Reperfusion Injury / metabolism,  pathology,  prevention & control*
Myocardium / metabolism*,  pathology
Grant Support
Reg. No./Substance:
0/Anti-Bacterial Agents; 0/Apoptosis Regulatory Proteins; 0/Cardiotonic Agents; 0/Microtubule-Associated Proteins; 66974FR9Q1/Chloramphenicol; ZCX619U9A1/chloramphenicol succinate

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

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