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

Background. Increased right ventricular (RV) afterload results in RV hypert rophy and dysfunction, as well as increased levels of intracellular beta -a drenergic receptor kinase (beta ARK1). We hypothesize that gene transfer of a,beta ARK1 inhibitor (beta ARKct) may improve RV performance, morbidity, and mortality early after pulmonary artery (PA) banding. Methods. Rabbits underwent PA banding 3 days after ri-ht coronary artery in jection of an adenovirus containing the gene encoding the beta ARKct peptid e (n = 14), beta -galactosidase (n = 10), or an empty adenovirus (n = 19). After banding, hemodynamic instability and maximal rate of increase in righ t ventricular pressure (RV dP/dt(max)) were documented. For 7 days after ba nding, animals were monitored for mortality, activity, and appetite. Results. When compared with controls, animals receiving the beta ARKct tran sgene 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 beta ARKct improves survival and mo rbidity after PA banding. This represents a novel therapeutic modality for clinical situations involving increased RV afterload. (C) 2001 by The Socie ty of Thoracic Surgeons.