Document Detail


Cytokine combination therapy with long-acting erythropoietin and granulocyte colony stimulating factor improves cardiac function but is not superior than monotherapy in a mouse model of acute myocardial infarction.
MedLine Citation:
PMID:  20670846     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
BACKGROUND: Erythropoietin (EPO) and granulocyte colony stimulating factor (GCSF) are potential novel therapies after myocardial infarction (MI). We first established the optimal and clinically applicable dosages of these drugs in mobilizing hematopoietic stem cells (HSC), and then tested the efficacy of monotherapy and combination therapy post-MI.
METHODS AND RESULTS: Optimal doses were established in enhanced green fluorescent protein (eGFP) + chimeric mice (n = 30). Next, mice underwent MI and randomized into 4 groups (n = 18/group): 1) GCSF; 2) EPO; 3) EPO+GCSF; and 4) control. Left ventricular (LV) function was analyzed pre-MI, at 4 hours and at 28 days post-MI. Histological assessment of infarct size, blood vessels, apoptotic cardiomyocytes, and engraftment of eGFP+ mobilized cells were analyzed at day 28. LV function in the control group continued to deteriorate, whereas all treatments showed stabilization. The treatment groups resulted in less scarring, increased numbers of mobilized cells to the infarct border zone (BZ), and a reduction in the number of apoptotic cardiomyocytes. Both EPO groups had significantly more capillaries and arterioles at the BZ.
CONCLUSION: We have established the optimal doses for EPO and GCSF in mobilizing HSC from the bone marrow and demonstrated that therapy with these agents, either as monotherapy or combination therapy, led to improvement of cardiac function post-MI. Combination therapy does not seem to have additive benefit over monotherapy in this model.
Authors:
Yerem Yeghiazarians; Muhammad Khan; Franca S Angeli; Yan Zhang; Sarah Jahn; Megha Prasad; Rachel Mirsky; Henry Shih; Petros Minasi; Andrew Boyle; William Grossman
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-05-04
Journal Detail:
Title:  Journal of cardiac failure     Volume:  16     ISSN:  1532-8414     ISO Abbreviation:  J. Card. Fail.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-07-30     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9442138     Medline TA:  J Card Fail     Country:  United States    
Other Details:
Languages:  eng     Pagination:  669-78     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2010 Elsevier Inc. All rights reserved.
Affiliation:
Division of Cardiology, Department of Medicine, University of California, San Francisco, San Francisco, California 94143-0103, USA. yeghiaza@medicine.ucsf.edu
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