Document Detail

Acute myocardial rescue with endogenous endothelial progenitor cell therapy.
MedLine Citation:
PMID:  20719564     Owner:  NLM     Status:  MEDLINE    
PURPOSE: Post-myocardial infarction heart failure is a major health concern with limited therapy. Molecular revascularisation utilising granulocyte-macrophage colony stimulating factor (GMCSF) mediated endothelial progenitor cell (EPC) upregulation and stromal cell derived factor-1α (SDF) mediated myocardial EPC chemokinesis, may prevent myocardial loss and adverse remodelling. Vasculogenesis, viability, and haemodynamic improvements following therapy were investigated.
PROCEDURES: Lewis rats (n=91) underwent LAD ligation and received either intramyocardial SDF and subcutaneous GMCSF or saline injections at the time of infarction. Molecular and haemodynamic assessments were performed at pre-determined time points following ligation.
FINDINGS: SDF/GMCSF therapy upregulated EPC density as shown by flow cytometry (0.12±0.02% vs. 0.06±0.01% circulating lymphocytes, p=0.005), 48hours following infarction. A marked increase in perfusion was evident eight weeks after therapy, utilising confocal angiography (5.02±1.7×10(-2)μm(3)blood/μm(3)myocardial tissue vs. 2.03±0.710(-2)μm(3)blood/μm(3)myocardial tissue, p=0.00004). Planimetric analysis demonstrated preservation of wall thickness (0.98±0.09mm vs. 0.67±0.06mm, p=0.003) and ventricular diameter (7.81±0.99mm vs. 9.41±1.1mm, p=0.03). Improved haemodynamic function was evidenced by echocardiography and PV analysis (ejection fraction: 56.4±18.1% vs. 25.3±15.6%, p=0.001; pre-load adjusted maximal power: 6.6±2.6mW/μl(2) vs. 2.7±1.4mW/μl(2), p=0.01).
CONCLUSION: Neovasculogenic therapy with GMCSF-mediated EPC upregulation and SDF-mediated EPC chemokinesis maybe an effective therapy for infarct modulation and preservation of myocardial function following acute myocardial infarction.
Pavan Atluri; Corinna M Panlilio; George P Liao; William Hiesinger; David Andrew Harris; Ryan C McCormick; Jeffrey E Cohen; Tao Jin; Wei Feng; Rebecca D Levit; Nianguo Dong; Y Joseph Woo
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-08-16
Journal Detail:
Title:  Heart, lung & circulation     Volume:  19     ISSN:  1444-2892     ISO Abbreviation:  Heart Lung Circ     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-18     Completed Date:  2011-03-18     Revised Date:  2013-05-28    
Medline Journal Info:
Nlm Unique ID:  100963739     Medline TA:  Heart Lung Circ     Country:  Australia    
Other Details:
Languages:  eng     Pagination:  644-54     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Australasian Society of Cardiac and Thoracic Surgeons and the Cardiac Society of Australia and New Zealand. Published by Elsevier B.V. All rights reserved.
Division of Cardiovascular Surgery, Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, United States.
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MeSH Terms
Chemokine CXCL12 / pharmacology,  therapeutic use*
Endothelial Cells / drug effects*
Flow Cytometry
Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology,  therapeutic use*
Heart / drug effects*
Heart Ventricles / anatomy & histology
Hematopoietic Stem Cells / physiology
Hemodynamics / drug effects*
Models, Animal
Myocardial Infarction / drug therapy*
Myocardium / pathology
Neovascularization, Physiologic / drug effects*
Rats, Inbred Lew
Ventricular Function, Left / drug effects*
Grant Support
1 F32 HL79769-01/HL/NHLBI NIH HHS; HL072812/HL/NHLBI NIH HHS; K08 HL072812-01A1/HL/NHLBI NIH HHS; R01 HL089315/HL/NHLBI NIH HHS; R01 HL089315-02/HL/NHLBI NIH HHS
Reg. No./Substance:
0/Chemokine CXCL12; 83869-56-1/Granulocyte-Macrophage Colony-Stimulating Factor

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

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