Catheter-mediated subselective intracoronary gene delivery to the rabbit heart: introduction of a novel method
✍ Scribed by Cyrus J. Parsa; Robyn C. Reed; G. Brant Walton; Laura S. Pascal; Richard B. Thompson; Jason A. Petrofski; Sitaram M. Emani; Francisco Folgar; Ryan U. Riel; Christopher V. Nicchitta; Walter J. Koch
- Book ID
- 102338549
- Publisher
- John Wiley and Sons
- Year
- 2005
- Tongue
- English
- Weight
- 342 KB
- Volume
- 7
- Category
- Article
- ISSN
- 1099-498X
- DOI
- 10.1002/jgm.704
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✦ Synopsis
Abstract
Background
Recent studies suggest that gene therapy using replication‐deficient adenoviruses will benefit treatment of cardiovascular diseases including heart failure. A persistent hurdle is the effective and reproducible delivery of a transgene to the myocardium with minimal iatrogenic morbidity. In this study, we sought to design a relatively non‐invasive percutaneous gene delivery system that would maximize cardiac transgene expression and minimize mortality after intracoronary adenovirus injection.
Methods
Adult rabbits received a left circumflex coronary artery (LCx) infusion of 5 × 10^11^ total viral particles of an adenovirus containing the marker transgene β‐galactosidase (Adeno‐βGal) via either a continuous infusion method utilizing an oxygenated, normothermic, physiologic pH Krebs solution driven by a Langendorff apparatus (n = 12) or a timed bolus and set concentration at a constant infusion rate to the LCx (n = 12). Six rabbits underwent global transgene delivery via an invasive method involving intraventricular delivery and aortic root cross‐clamping. The efficacy of transgene expression via these three distinct delivery methods was determined in the left ventricle at 5 days by histological staining and colorimetric quantification assay.
Results
While the open‐chest, aortic cross‐clamping method provides the highest level of gene expression throughout the heart, the morbidity of this procedure is clinically prohibitive. Percutaneous LCx delivery of Adeno‐βGal using the Langendorff apparatus was associated with the lowest morbidity and mortality while still supporting significant myocardial gene expression.
Conclusions
Percutaneous delivery of an adenovirus solution using a continuous infusion of oxygenated Krebs solution via a Langendorff apparatus appears to be a gene delivery modality offering the best compromise of gene expression and clinical utility to maximize any potential therapeutic outcome. Copyright © 2005 John Wiley & Sons, Ltd.