Document Detail


Erythropoietin receptor expression in adult rat cardiomyocytes is associated with an acute cardioprotective effect for recombinant erythropoietin during ischemia-reperfusion injury.
MedLine Citation:
PMID:  15059965     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Erythropoietin (EPO), the principal hematopoietic cytokine that regulates mammalian erythropoiesis, exhibits diverse cellular effects in non-hematopoietic tissues. The physiologic functions of EPO are mediated by its specific cell-surface receptor EPOR. In this study, we demonstrate EPOR expression in adult rat cardiac myocytes and examine the direct effects of EPO on the heart to investigate whether recombinant EPO may exert an acute cardioprotective effect during ischemia-reperfusion injury. To determine whether EPO is cardioprotective, isolated rat hearts were perfused for 10 min in the Langendorff-mode with Krebs-Henseleit buffer in the absence or presence of brief recombinant EPO treatment while left-ventricular-developed pressure (LVDP) was measured continuously to assess contractile function. The hearts were then subjected to 20 min of normothermic global ischemia followed by 25 min of reperfusion. The post-ischemic recovery of LVDP in the untreated control hearts was 26 +/- 5% of their baseline LVDP, whereas hearts pretreated with EPO exhibited significantly improved post-ischemic recovery to 57 +/- 7%. We used 31P nuclear magnetic resonance (NMR) spectroscopy to determine whether modulation of intracellular pH and/or high-energy phosphate levels during ischemia contributed to EPO-mediated cardioprotection. These experiments revealed that the rapid cardioprotective effect of EPO during ischemia-reperfusion injury was associated with preservation of ATP levels in the ischemic myocardium.
Authors:
Gary L Wright; Paul Hanlon; Khalid Amin; Charles Steenbergen; Elizabeth Murphy; Murat O Arcasoy
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.     Date:  2004-04-01
Journal Detail:
Title:  FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  18     ISSN:  1530-6860     ISO Abbreviation:  FASEB J.     Publication Date:  2004 Jun 
Date Detail:
Created Date:  2004-06-02     Completed Date:  2004-11-02     Revised Date:  2012-02-15    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1031-3     Citation Subset:  IM    
Affiliation:
Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / metabolism
Animals
Buffers
Cardiotonic Agents / pharmacology*
Erythropoietin / pharmacology*
Heart / drug effects,  physiopathology
Hemodynamics / drug effects
Hydrogen-Ion Concentration
Magnetic Resonance Spectroscopy
Male
Myocardial Contraction / drug effects
Myocardium / cytology,  metabolism
Myocytes, Cardiac / drug effects,  metabolism
Perfusion
Phosphocreatine / metabolism
RNA, Messenger / genetics,  metabolism
Rats
Rats, Sprague-Dawley
Receptors, Erythropoietin / genetics*,  metabolism*
Recombinant Proteins / pharmacology
Reperfusion Injury / physiopathology,  prevention & control*
Time Factors
Grant Support
ID/Acronym/Agency:
R01-HL-39752/HL/NHLBI NIH HHS; R21-DK-65065/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Buffers; 0/Cardiotonic Agents; 0/RNA, Messenger; 0/Receptors, Erythropoietin; 0/Recombinant Proteins; 11096-26-7/Erythropoietin; 56-65-5/Adenosine Triphosphate; 67-07-2/Phosphocreatine

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


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