Objective: Abrupt increases in right ventricular afterload occur after cardiac transplantation and pulmonary artery banding, which can result in right ventricular hypertrophy and dilatation. Right ventricular dysfunction is also accompanied by β-adrenergic receptor desensitization. We sought to determine whether selective right ventricular expression of a transgene encoding a β-adrenergic receptor kinase inhibitor can improve right ventricular remodeling early after pulmonary artery banding. Methods: Rabbits underwent pulmonary artery banding 3 days after percutaneous right coronary artery injection of empty adenovirus (n = 19), a control adenovirus containing the β-galactosidase transgene (n = 10), or an adenovirus containing the β-adrenergic receptor kinase inhibitor transgene (n = 14). Sham-operated animals (n = 7) underwent instrumentation without deployment of the pulmonary artery band. Right ventricular function was assessed in each rabbit before and 7 days after pulmonary artery banding. Right ventricular mass and dimensions (surface area and volume) were obtained, and biochemical analysis was performed to confirm transgene expression and to characterize β-adrenergic receptor signaling. Results: Right ventricular mass was increased in animals treated with adenovirus containing the β-adrenergic receptor kinase inhibitor transgene, adenovirus containing the β-galactosidase transgene, and empty adenovirus after banding when compared with results in sham-operated animals. However, right ventricular volume and surface area, as measures of dilatation, were significantly lower in pulmonary artery banded rabbits pretreated with adenovirus containing the β-adrenergic receptor kinase inhibitor transgene when compared with those treated with empty adenovirus or adenovirus containing the β-galactosidase transgene. Right ventricular contractility and defective β-adrenergic receptor signaling were significantly enhanced in rabbits expressing the β-adrenergic receptor kinase inhibitor after pulmonary artery banding. Conclusions: Right ventricular preconditioning with the β-adrenergic receptor kinase inhibitor transgene can attenuate the early right ventricular dilatation and dysfunction associated with pulmonary artery banding. Thus β-adrenergic receptor kinase inhibition might represent a novel target for limiting ventricular remodeling after increased right ventricular afterload.
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine