title: Right ventricular gene therapy with a beta-adrenergic receptor kinase inhibitor improves survival after pulmonary artery banding.
abstract: 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.
authors.affiliation: Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Emani
authors.forename: A S
authors.initials: AS
authors.lastname: Shah
authors.forename: D C
authors.initials: DC
authors.lastname: White
authors.forename: D D
authors.initials: DD
authors.lastname: Glower
authors.forename: W J
authors.initials: WJ
authors.lastname: Koch
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000627:therapeutic use*; D015316:Genetic Therapy / Q000379:methods*; D006352:Heart Ventricles; D010455:Peptides; D011651:Pulmonary Artery; D011817:Rabbits; D011994:Recombinant Proteins; D015996:Survival Rate; D019076:Transgenes; D018497:Ventricular Dysfunction, Right / Q000401:mortality / Q000473:pathology / Q000628:therapy*
chemical_list: D002352:Carrier Proteins; D010455:Peptides; D011994:Recombinant Proteins; C445259:beta-adrenergic receptor kinase inhibitory peptide