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

Sitaram M. Emani, Ashish S. Shah, David C. White, Donald D. Glower, Walter J. Koch

Research output: Contribution to journalArticle

Abstract

Background. Increased right ventricular (RV) afterload results in RV hypertrophy and dysfunction, as well as increased levels of intracellular β-adrenergic receptor kinase (βARK1). We hypothesize that gene transfer of a βARK1 inhibitor (βARKct) 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 βARKct peptide (n = 14), β-galactosidase (n = 10), or an empty adenovirus (n = 19). After banding, hemodynamic instability and maximal rate of increase in right ventricular pressure (RV dP/dtmax) were documented. For 7 days after banding, animals were monitored for mortality, activity, and appetite. Results. When compared with controls, animals receiving the βARKct 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/dtmax (NS), and increased hemodynamic stability at the time of banding (78% vs 41%, p = 0.03). Conclusions. Selective RV expression of βARKct improves survival and morbidity after PA banding. This represents a novel therapeutic modality for clinical situations involving increased RV afterload.

Original languageEnglish (US)
Pages (from-to)1657-1661
Number of pages5
JournalAnnals of Thoracic Surgery
Volume72
Issue number5
DOIs
StatePublished - 2001
Externally publishedYes

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Genetic Therapy
Adrenergic Receptors
Pulmonary Artery
Phosphotransferases
Adenoviridae
Hemodynamics
Galactosidases
Right Ventricular Dysfunction
Morbidity
Right Ventricular Hypertrophy
Lethargy
Mortality
Appetite
Ventricular Pressure
Transgenes
Genes
Coronary Vessels
Rabbits
Peptides
Injections

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

Cite this

Right ventricular gene therapy with a β-adrenergic receptor kinase inhibitor improves survival after pulmonary artery banding. / Emani, Sitaram M.; Shah, Ashish S.; White, David C.; Glower, Donald D.; Koch, Walter J.

In: Annals of Thoracic Surgery, Vol. 72, No. 5, 2001, p. 1657-1661.

Research output: Contribution to journalArticle

Emani, Sitaram M. ; Shah, Ashish S. ; White, David C. ; Glower, Donald D. ; Koch, Walter J. / Right ventricular gene therapy with a β-adrenergic receptor kinase inhibitor improves survival after pulmonary artery banding. In: Annals of Thoracic Surgery. 2001 ; Vol. 72, No. 5. pp. 1657-1661.
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abstract = "Background. Increased right ventricular (RV) afterload results in RV hypertrophy and dysfunction, as well as increased levels of intracellular β-adrenergic receptor kinase (βARK1). We hypothesize that gene transfer of a βARK1 inhibitor (βARKct) 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 βARKct peptide (n = 14), β-galactosidase (n = 10), or an empty adenovirus (n = 19). After banding, hemodynamic instability and maximal rate of increase in right ventricular pressure (RV dP/dtmax) were documented. For 7 days after banding, animals were monitored for mortality, activity, and appetite. Results. When compared with controls, animals receiving the βARKct 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/dtmax (NS), and increased hemodynamic stability at the time of banding (78{\%} vs 41{\%}, p = 0.03). Conclusions. Selective RV expression of βARKct improves survival and morbidity after PA banding. This represents a novel therapeutic modality for clinical situations involving increased RV afterload.",
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AU - Koch, Walter J.

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