Document Detail


Ischemia-reperfusion increases transfection efficiency of intracoronary adenovirus type 5 in pig heart in situ.
MedLine Citation:
PMID:  22816318     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Efficiency of intracoronary (IC) adenoviral vector transfection is impaired by the vascular endothelium. Ischemia and substances that increase vascular permeability (sodium nitroprusside, nitroglycerin) may augment adenoviral vector transfection efficiency (TE). We tested whether TE of adenoviral vector following IC infusion is improved by nitrates or by ischemia. Fluoroscopically guided angioplasty balloon catheters occluded the coronary artery in Yorkshire pigs and delivered adenoviral type 5 vector encoding the luciferase gene (Ad5Luc, 10(11) viral particles). TE (luciferase activity) was minimal and was not augmented by IC co-administration of 50 μg/min sodium nitroprusside to nonischemic myocardium. Two (but not one) 3-min episodes of occlusion tended to increase luciferase activity (p=0.06), and luciferase activity was further increased by IC co-administration of nitroglycerin (p<0.001). After 75 min of coronary artery occlusion, luciferase activity was greater than with shorter periods of ischemia, and was significantly greater in the ischemia-reperfused zone compared to the border zone 3 and 14 days after infusion; there was no transfection in nonischemic myocardium. IC delivery of Ad5Luc into post-ischemic myocardium caused no local inflammation or hemodynamic instability. We conclude that the uptake of IC Ad5 to ischemic reperfused myocardium validates use of IC Ad5 delivery protocols in future human gene therapy trials in patients following myocardial ischemia.
Authors:
Weiwei Shi; L Susan Schmarkey; Rong Jiang; C Collin Bone; Marah E Condit; Dirck L Dillehay; Robert L Engler; Gabor M Rubanyi; Jakob Vinten-Johansen
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-07-20
Journal Detail:
Title:  Human gene therapy methods     Volume:  23     ISSN:  1946-6544     ISO Abbreviation:  Hum Gene Ther Methods     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-08-08     Completed Date:  2013-01-08     Revised Date:  2014-05-14    
Medline Journal Info:
Nlm Unique ID:  101573202     Medline TA:  Hum Gene Ther Methods     Country:  United States    
Other Details:
Languages:  eng     Pagination:  204-12     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adenoviridae / genetics,  metabolism*
Analysis of Variance
Animals
Balloon Occlusion
Cardiac Catheterization
Coronary Vessels / metabolism
DNA Primers / genetics
Genetic Therapy / methods*
Genetic Vectors / genetics,  metabolism*
Ischemia / metabolism*
Luciferases / genetics,  metabolism
Myocardium / metabolism*
Nitroglycerin
Nitroprusside
Polymerase Chain Reaction
Sus scrofa
Transfection / methods*,  standards
Chemical
Reg. No./Substance:
0/DNA Primers; 169D1260KM/Nitroprusside; EC 1.13.12.-/Luciferases; G59M7S0WS3/Nitroglycerin
Comments/Corrections

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