Document Detail


Gene transfer for ischemic heart failure in a preclinical model.
MedLine Citation:
PMID:  21633324     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Various emerging technologies are being developed for patients with heart failure. Well-established preclinical evaluations are necessary to determine their efficacy and safety. Gene therapy using viral vectors is one of the most promising approaches for treating cardiac diseases. Viral delivery of various different genes by changing the carrier gene has immeasurable therapeutic potential. In this video, the full process of an animal model of heart failure creation followed by gene transfer is presented using a swine model. First, myocardial infarction is created by occluding the proximal left anterior descending coronary artery. Heart remodeling results in chronic heart failure. Unique to our model is a fairly large scar which truly reflects patients with severe heart failure who require aggressive therapy for positive outcomes. After myocardial infarct creation and development of scar tissue, an intracoronary injection of virus is demonstrated with simultaneous nitroglycerine infusion. Our injection method provides simple and efficient gene transfer with enhanced gene expression. This combination of a myocardial infarct swine model with intracoronary virus delivery has proven to be a consistent and reproducible methodology, which helps not only to test the effect of individual gene, but also compare the efficacy of many genes as therapeutic candidates.
Authors:
Kiyotake Ishikawa; Dennis Ladage; Lisa Tilemann; Kenneth Fish; Yoshiaki Kawase; Roger J Hajjar
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Video-Audio Media     Date:  2011-05-15
Journal Detail:
Title:  Journal of visualized experiments : JoVE     Volume:  -     ISSN:  1940-087X     ISO Abbreviation:  J Vis Exp     Publication Date:  2011  
Date Detail:
Created Date:  2011-06-02     Completed Date:  2012-04-06     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  101313252     Medline TA:  J Vis Exp     Country:  United States    
Other Details:
Languages:  eng     Pagination:  -     Citation Subset:  IM    
Affiliation:
Cardiovascular Research Center, Mount Sinai School of Medicine.
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MeSH Terms
Descriptor/Qualifier:
Adenoviridae / genetics
Animals
Disease Models, Animal*
Female
Gene Transfer Techniques*
Heart Failure / genetics,  therapy
Myocardial Infarction / genetics,  therapy
Myocardial Ischemia / genetics*,  therapy
Swine
Grant Support
ID/Acronym/Agency:
HL071763/HL/NHLBI NIH HHS; HL080498/HL/NHLBI NIH HHS; HL083156/HL/NHLBI NIH HHS; HL088434/HL/NHLBI NIH HHS; P20HL100396/HL/NHLBI NIH HHS; R01 HL093183/HL/NHLBI NIH HHS
Comments/Corrections

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