Document Detail


Transthoracic direct current shock facilitates intramyocardial transfection of naked plasmid DNA infused via coronary vessels in canines.
MedLine Citation:
PMID:  16511524     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Catheter-mediated, percutaneous, transluminal delivery of naked plasmid DNA (pDNA) into myocardium may offer a valuable strategy to heart diseases. Here, we examined whether clinically available transthoracic direct current (DC) shock improves intracoronary naked DNA transfection into myocardium. Plasmid vector encoding the GL3 luciferase was infused retrogradely into the coronary veins of beagle dogs, whereas another pDNA solution was infused into the left coronary artery. During and after these procedures, the coronary venous sinus was occluded by balloon, and transthoracic DC shock of 200 J was applied immediately after the infusions. Without DC shock, no remarkable increase in luciferase activity was demonstrated in any part of the left ventricular myocardium. In the presence of DC pulsation, significant luciferase expression was detected in the regions that were supplied by left anterior descending coronary artery (LAD), whereas the gene expression in the right coronary artery (RCA) regions was much less drastic. X-gal (5-bromo-4-chloro-3-indolyl-beta-D-galactoside) staining of cardiac cross-sections also revealed regional expression of beta-galactosidase. Immunohistochemical examinations of heart cryosections revealed that cardiomyocytes in LAD regions successfully expressed transgene product. The present system may enable a new strategy for myocardial gene therapy, without any special device or technique other than cardiac catheterization and DC cardioversion that are generally performed in ordinary hospitals.
Authors:
Y Iida; Y Oda; S Nakamori; S Tsunoda; T Kishida; S Gojo; M Shin-Ya; H Asada; J Imanishi; T Yoshikawa; H Matsubara; O Mazda
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Gene therapy     Volume:  13     ISSN:  0969-7128     ISO Abbreviation:  Gene Ther.     Publication Date:  2006 Jun 
Date Detail:
Created Date:  2006-05-18     Completed Date:  2006-09-18     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9421525     Medline TA:  Gene Ther     Country:  England    
Other Details:
Languages:  eng     Pagination:  906-16     Citation Subset:  IM    
Affiliation:
Department of Molecular Cardiology and Vascular Regenerative Medicine, Kyoto Prefectural University of Medicine, Kamikyo, Kyoto 602-8566, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Coronary Vessels
DNA / administration & dosage*
Dogs
Electric Stimulation
Electrocardiography
Electromyography
Female
Gene Expression
Gene Therapy / methods*
Heart Catheterization
Heart Diseases / therapy*
Immunohistochemistry / methods
Luciferases / analysis,  genetics
Myocardium / metabolism*
Transfection / methods*
Chemical
Reg. No./Substance:
9007-49-2/DNA; EC 1.13.12.-/Luciferases

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