Catheter-mediated subselective intracoronary gene delivery to the rabbit heart: introduction of a novel method.

Published

Journal Article

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 5x10(11) total viral particles of an adenovirus containing the marker transgene beta-galactosidase (Adeno-betaGal) 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-betaGal 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.

Full Text

Duke Authors

Cited Authors

  • Parsa, CJ; Reed, RC; Walton, GB; Pascal, LS; Thompson, RB; Petrofski, JA; Emani, SM; Folgar, F; Riel, RU; Nicchitta, CV; Koch, WJ

Published Date

  • May 2005

Published In

Volume / Issue

  • 7 / 5

Start / End Page

  • 595 - 603

PubMed ID

  • 15651066

Pubmed Central ID

  • 15651066

International Standard Serial Number (ISSN)

  • 1099-498X

Digital Object Identifier (DOI)

  • 10.1002/jgm.704

Language

  • eng

Conference Location

  • England