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Ischemia-Reperfusion Increases Transfection Efficiency of Intracoronary Adenovirus type 5 in Pig Heart In Situ.
MedLine Citation:
PMID:  22746169     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Efficiency of intracoronary (IC) adenoviral vector (Ad) transfection is impaired by the vascular endothelium. Ischemia and substances that increase vascular permeability [sodium nitroprusside (SNP), nitroglycerin (NTG)] may augment Ad transfection efficiency (TE). We tested whether TE of Ad following intracoronary (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 (Ad5Luc, 1011vp) encoding the luciferase gene. TE (luciferase activity, LA) was minimal and was not augmented by IC co-administration of 50 µg/min SNP to non-ischemic myocardium. Two (but not one) 3-minute episodes of occlusion tended to increase LA (p=0.06), and LA was further increased by IC co-administration of NTG (p<0.001). After 75 minutes of coronary artery occlusion, LA 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 non-ischemic 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; Laura 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     Date:  2012-6-29
Journal Detail:
Title:  Human gene therapy. Part B. Methods     Volume:  -     ISSN:  1946-6544     ISO Abbreviation:  Hum Gene Ther Methods     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-7-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101573202     Medline TA:  Hum Gene Ther Methods     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Emory University Hospital Midtown, Surgery, 550 Peachtree St, CTRL, Atlanta, Georgia, United States, 30308, 4046861813; wshi6@emory.edu.
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