Right ventricular gene therapy with a beta-adrenergic receptor kinase inhibitor improves survival after pulmonary artery banding.

Published

Journal Article

BACKGROUND: Increased right ventricular (RV) afterload results in RV hypertrophy and dysfunction, as well as increased levels of intracellular beta-adrenergic receptor kinase (betaARK1). We hypothesize that gene transfer of a betaARK1 inhibitor (betaARKct) may improve RV performance, morbidity, and mortality early after pulmonary artery (PA) banding. METHODS: Rabbits underwent PA banding 3 days after right coronary artery injection of an adenovirus containing the gene encoding the betaARKct peptide (n = 14), beta-galactosidase (n = 10), or an empty adenovirus (n = 19). After banding, hemodynamic instability and maximal rate of increase in right ventricular pressure (RV dP/dt(max)) were documented. For 7 days after banding, animals were monitored for mortality, activity, and appetite. RESULTS: When compared with controls, animals receiving the betaARKct transgene showed improvement in survival at 7 days (92.8% +/- 7% vs 48.3% +/- 9%, p = 0.01), less lethargy, a trend toward greater RV dP/dt(max) (NS), and increased hemodynamic stability at the time of banding (78% vs 41%, p = 0.03). CONCLUSIONS: Selective RV expression of betaARKct improves survival and morbidity after PA banding. This represents a novel therapeutic modality for clinical situations involving increased RV afterload.

Full Text

Duke Authors

Cited Authors

  • Emani, SM; Shah, AS; White, DC; Glower, DD; Koch, WJ

Published Date

  • November 2001

Published In

Volume / Issue

  • 72 / 5

Start / End Page

  • 1657 - 1661

PubMed ID

  • 11722061

Pubmed Central ID

  • 11722061

International Standard Serial Number (ISSN)

  • 0003-4975

Digital Object Identifier (DOI)

  • 10.1016/s0003-4975(01)03130-7

Language

  • eng

Conference Location

  • Netherlands