Document Detail

Single high-dose intramyocardial administration of erythropoietin promotes early intracardiac proliferation, proves safety and restores cardiac performance after myocardial infarction in rats.
MedLine Citation:
PMID:  19380336     Owner:  NLM     Status:  MEDLINE    
Various studies demonstrate erythropoietin (EPO) as a cardioprotective growth hormone. Recent findings reveal EPO in addition might induce proliferation cascades inside myocardium. We aimed to evaluate whether a single high-dose intramyocardial EPO administration safely elevates early intracardiac cell proliferation after myocardial infarction (MI). Following permanent MI in rats EPO (3000 U/kg) in MI EPO-treatment group (n=99) or saline in MI control group (n=95) was injected along the infarction border. Intramyocardial EPO injection activated the genes of cyclin D1 and cell division cycle 2 kinase (cdc2) at 24 h after MI (n=6, P<0.05) evaluated by real time-PCR. The number of Ki-67+ intracardiac cells analyzed following immunohistochemistry was significantly enhanced by 45% in the peri-infarction zone at 48 h after EPO treatment (n=6, P<0.001). Capillary density was significantly enhanced by 17% as early as seven days (n=6, P<0.001). After six weeks, left ventricular performance assessed by conductance catheters was restored under baseline and dobutamine induced stress conditions (n=11-14, P<0.05). No thrombus formation was observed in the heart and in distant organs. No deleterious systemic adverse effects were apparent. Single high-dose intramyocardial EPO delivery proved safety and promoted early intracardiac cell proliferation, which might in part have contributed to an attenuated myocardial functional decline.
Ralf Gäbel; Christian Klopsch; Dario Furlani; Can Yerebakan; Wenzhong Li; Murat Ugurlucan; Nan Ma; Gustav Steinhoff
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Publication Detail:
Type:  Journal Article     Date:  2009-04-20
Journal Detail:
Title:  Interactive cardiovascular and thoracic surgery     Volume:  9     ISSN:  1569-9285     ISO Abbreviation:  Interact Cardiovasc Thorac Surg     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-06-23     Completed Date:  2009-08-27     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  101158399     Medline TA:  Interact Cardiovasc Thorac Surg     Country:  England    
Other Details:
Languages:  eng     Pagination:  20-5; discussion 25     Citation Subset:  IM    
Department of Cardiac Surgery, University of Rostock, Germany.
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MeSH Terms
CDC2 Protein Kinase / metabolism
Capillaries / drug effects
Cardiotonic Agents / administration & dosage*
Cell Proliferation / drug effects*
Cyclin D1 / metabolism
Disease Models, Animal
Erythropoietin / administration & dosage*
Injections, Intralesional
Ki-67 Antigen / metabolism
Myocardial Contraction / drug effects*
Myocardial Infarction / drug therapy*,  pathology,  physiopathology
Myocardium / metabolism,  pathology*
Neovascularization, Physiologic / drug effects
Rats, Inbred Lew
Recovery of Function
Time Factors
Ventricular Function, Left / drug effects*
Reg. No./Substance:
0/Cardiotonic Agents; 0/Ccnd1 protein, rat; 0/Ki-67 Antigen; 11096-26-7/Erythropoietin; 136601-57-5/Cyclin D1; EC Protein Kinase

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