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Author Notes:

Address correspondence to: Dr. Weiwei Shi, Cardiothoracic Research Laboratory, Carlyle Fraser Heart Center, Emory University, 550 Peachtree Street NE, Atlanta, GA 30308-2225. E-mail:wshi6@emory.edu

The authors are grateful for the continued support of the Carlyle Fraser Heart Center of Emory University Hospital Midtown.

Author Disclosure Statement: Robert L. Engler is a consultant and stockholder for Cardium Therapeutics. Garbor M. Rubanyl is an employee and stockholder of Cardium Therapeutics. No other competing financial interests exist.

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Research Funding:

These studies were supported by a small business innovative research (SBIR) grant from the National Institutes of Health (National Heart, Lung and Blood Institute), and Cardium Therapeutics, Inc.

Ischemia-Reperfusion Increases Transfection Efficiency of Intracoronary Adenovirus Type 5 in Pig Heart In Situ

Tools:

Journal Title:

Human Gene Therapy Methods

Volume:

Volume 23, Number 3

Publisher:

, Pages 204-212

Type of Work:

Article | Post-print: After Peer Review

Abstract:

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, 1011 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.

Copyright information:

© 2012, Mary Ann Liebert, Inc.

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