Document Detail


Reduction of ischemia/reperfusion injury with bendavia, a mitochondria-targeting cytoprotective Peptide.
MedLine Citation:
PMID:  23130143     Owner:  NLM     Status:  PubMed-not-MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Manifestations of reperfusion injury include myocyte death leading to infarction, contractile dysfunction, and vascular injury characterized by the "no-reflow" phenomenon. Mitochondria-produced reactive oxygen species are believed to be centrally involved in each of these aspects of reperfusion injury, although currently no therapies reduce reperfusion injury by targeting mitochondria specifically.
METHODS AND RESULTS: We investigated the cardioprotective effects of a mitochondria-targeted peptide, Bendavia (Stealth Peptides), across a spectrum of experimental cardiac ischemia/reperfusion models. Postischemic administration of Bendavia reduced infarct size in an in vivo sheep model by 15% (P=0.02) and in an ex vivo guinea pig model by 38% to 42% (P<0.05). In an in vivo rabbit model, the extent of coronary no-reflow was assessed with Thioflavin S staining and was significantly smaller in the Bendavia group for any given ischemic risk area than in the control group (P=0.0085). Myocardial uptake of Bendavia was ≈25% per minute, and uptake remained consistent throughout reperfusion. Postischemic recovery of cardiac hemodynamics was not influenced by Bendavia in any of the models studied. Isolated myocytes exposed to hypoxia/reoxygenation showed improved survival when treated with Bendavia. This protection appeared to be mediated by lowered reactive oxygen species-mediated cell death during reoxygenation, associated with sustainment of mitochondrial membrane potential in Bendavia-treated myocytes.
CONCLUSIONS: Postischemic administration of Bendavia protected against reperfusion injury in several distinct models of injury. These data suggest that Bendavia is a mitochondria-targeted therapy that reduces reperfusion injury by maintaining mitochondrial energetics and suppressing cellular reactive oxygen species levels. (J Am Heart Assoc. 2012;1:e001644 doi: 10.1161/JAHA.112.001644.).
Authors:
Robert A Kloner; Sharon L Hale; Wangde Dai; Robert C Gorman; Takashi Shuto; Kevin J Koomalsingh; Joseph H Gorman; Ruben C Sloan; Chad R Frasier; Corinne A Watson; Phillip A Bostian; Alan P Kypson; David A Brown
Related Documents :
1092443 - Surgery for coronary artery disease and congestive heart failure.
24124583 - Hypercholesterolemic myocardium is vulnerable to ischemia-reperfusion injury and refrac...
3992053 - Infarct-size limitation--real or artifactual. studies with flurbiprofen using a reperfu...
Publication Detail:
Type:  Journal Article     Date:  2012-06-22
Journal Detail:
Title:  Journal of the American Heart Association     Volume:  1     ISSN:  2047-9980     ISO Abbreviation:  J Am Heart Assoc     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-11-06     Completed Date:  2012-11-07     Revised Date:  2013-09-09    
Medline Journal Info:
Nlm Unique ID:  101580524     Medline TA:  J Am Heart Assoc     Country:  England    
Other Details:
Languages:  eng     Pagination:  e001644     Citation Subset:  -    
Affiliation:
Heart Institute of Good Samaritan Hospital, University of Southern California, Los Angeles (R.A.K., S.H., W.D.) ; Keck School of Medicine, Division of Cardiovascular Medicine, University of Southern California, Los Angeles (R.A.K., W.D.).
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Grant Support
ID/Acronym/Agency:
R01 HL063954/HL/NHLBI NIH HHS; R01 HL071137/HL/NHLBI NIH HHS
Comments/Corrections

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


Previous Document:  Risk of idiopathic dilated cardiomyopathy in 29 000 patients with celiac disease.
Next Document:  Delay in presentation after an acute stroke in a multiethnic population in South london: the South l...