| Efficient myocyte gene delivery with complete cardiac surgical isolation in situ. | |
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MedLine Citation:
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PMID: 16256790 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Previously, we used cardiopulmonary bypass with incomplete cardiac isolation and antegrade administration of vector for global cardiac gene delivery. Here we present a translatable cardiac surgical procedure that allows for complete surgical isolation of the heart in situ with retrograde (through the coronary venous circulation) administration of both vector and endothelial permeabilizing agents to increase myocyte transduction efficiency. METHODS: In 6 adult dogs the heart was completely isolated with tourniquets placed around both vena cavae and cannulas and all pulmonary veins. On cardiopulmonary bypass, the aorta and pulmonary artery were crossclamped, and the heart was isolated. Crystalloid cardioplegia at 4 degrees C containing 10(13) particles of adenovirus encoding LacZ and 15 microg of vascular endothelial growth factor was infused retrograde into the coronary sinus and recirculated for a total of 30 minutes. The dogs were then weaned from cardiopulmonary bypass and allowed to recover. With a catheter, 3 control dogs underwent retrograde infusion of the same cocktail without cardiac isolation or cardiopulmonary bypass. RESULTS: Beta-galactosidase activities in the cardiopulmonary bypass group were several orders of magnitude higher in both the right and left ventricles when compared with those in the control group (P < .05). X-gal staining from the cardiopulmonary bypass group showed unequivocal evidence of myocyte gene expression globally in a significant proportion of cardiac myocytes. No myocyte gene expression was observed in the control group. CONCLUSION: A novel cardiac surgical technique has been developed. This approach with cardiac isolation and retrograde delivery of vector through the coronary sinus results in efficient myocyte transduction in an adult large animal in vivo. |
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Authors:
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Charles R Bridges; Kapil Gopal; David E Holt; Charles Yarnall; Steven Cole; Rochelle B Anderson; Xiaoqing Yin; Anthony Nelson; Benjamin W Kozyak; Zhonglin Wang; James Lesniewski; Leonard T Su; Danielle M Thesier; Hari Sundar; Hansell H Stedman |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: The Journal of thoracic and cardiovascular surgery Volume: 130 ISSN: 1097-685X ISO Abbreviation: J. Thorac. Cardiovasc. Surg. Publication Date: 2005 Nov |
Date Detail:
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Created Date: 2005-10-31 Completed Date: 2005-12-29 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0376343 Medline TA: J Thorac Cardiovasc Surg Country: United States |
Other Details:
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Languages: eng Pagination: 1364 Citation Subset: AIM; IM |
Affiliation:
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Department of Surgery of the University of Pennsylvania Health System, Philadelphia, Pa 19104, USA. cbridges@pahosp.com |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cardiac Surgical Procedures / methods* Dogs Gene Therapy / methods* Myocytes, Cardiac* |
| Grant Support | |
ID/Acronym/Agency:
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1-R21-EB003223-01/EB/NIBIB NIH HHS; T32DK07748-07/DK/NIDDK NIH HHS |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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