Document Detail


Positive effect of darbepoetin on peri-infarction remodeling in a porcine model of myocardial ischemia-reperfusion.
MedLine Citation:
PMID:  17597149     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Erythropoietin (Epo) has anti-apoptotic and pro-angiogenic effects in rodent models of myocardial infarction (MI). We tested the hypothesis that a long-acting Epo derivative (darbepoetin) has a beneficial effect on infarct size and peri-infarct remodeling in a clinically relevant large animal model of ischemia-reperfusion. A human acute MI scenario was simulated in 16 domestic pigs by inflating an angioplasty balloon in the proximal left circumflex (LCx) artery for 60 min. The animals were randomized to darbepoetin 30 microg/kg i.v. or placebo (saline) at the time of reperfusion. Treatment with darbepoetin did not lead to a reduction in the infarct size at 2 weeks as assessed by histology (30.3+/-1.8% of the volume at risk for placebo vs. 33.2+/-2.5% for darbepoetin). However, significant effects were seen in the peri-infarct region. Histological evaluation revealed decreased interstitial fibrosis (6.8+/-0.7% of myocardial sections area vs. 9.6+/-0.7%, p=0.02) and increased average capillary area (106+/-3% of the non-infarcted myocardium vs. 89+/-4%, p=0.003) in the treatment arm in the absence of significant cardiac hypertrophy. This resulted in preserved regional wall motion as assessed by tissue Doppler-derived radial strain (subepicardial radial strain 90.1+/-21.2% for darbepoetin vs. 20.3+/-10.1% for placebo, p<0.05). However, this did not translate to improved wall thickening (126.5+/-6.0% of diastolic thickness for darbepoetin vs. 119.8+/-5.4% for placebo, p=NS). Beneficial effects of darbepoetin to peri-infarct remodeling were observed in a clinically relevant model of ischemia-reperfusion. Although the infarct size was not reduced, there was a limited decrease in interstitial fibrosis, increased capillary area and regional functional improvement in darbepoetin-treated animals.
Authors:
Catalin Toma; Dustin P Letts; Masaki Tanabe; John Gorcsan; Peter J Counihan
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-05-24
Journal Detail:
Title:  Journal of molecular and cellular cardiology     Volume:  43     ISSN:  0022-2828     ISO Abbreviation:  J. Mol. Cell. Cardiol.     Publication Date:  2007 Aug 
Date Detail:
Created Date:  2007-07-23     Completed Date:  2007-09-19     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  0262322     Medline TA:  J Mol Cell Cardiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  130-6     Citation Subset:  IM    
Affiliation:
Cardiovascular Institute, University of Pittsburgh Medical Center, Scaife Hall S559, 200 Lothrop Street, Pittsburgh, PA 15213, USA. tomac@upmc.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Capillaries / drug effects,  physiopathology
Disease Models, Animal
Echocardiography
Erythropoietin / analogs & derivatives*,  pharmacology
Male
Myocardial Infarction / physiopathology*
Myocardial Reperfusion Injury / physiopathology*
Receptors, Erythropoietin / metabolism
Swine
Ventricular Remodeling / drug effects*
Chemical
Reg. No./Substance:
0/Receptors, Erythropoietin; 11096-26-7/Erythropoietin; 15UQ94PT4P/darbepoetin alfa

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


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