Early effects of right ventricular volume overload on ventricular performance and beta-adrenergic signaling

Objective: Right ventricular dysfunction is a poorly understood but persist ent clinical problem. This study was undertaken to evaluate ventricular per formance and beta-adrenergic receptor signaling in a tricuspid regurgitatio n model of right ventricular overload. Methods: Seventeen dogs were chronically instrumented with epicardial dimen sion transducers. By means of the shell-subtraction model, right ventricula r pressure-volume relationships were evaluated in normal and right ventricu lar overload states. Right ventricular chamber performance was quantified b y the stroke work at an end-diastolic volume relationship, Results: Right ventricular volume overload caused a 28% +/- 11% and 31% +/- 9% decline in chamber performance acutely and at 1 week, respectively, whe reas end-diastolic volume increased from 45 +/- 21 to 60 +/- 30 mt (P =.019 ). beta-Adrenergic receptor signaling in myocardial samples was assessed, e xamining adenylyl cyclase and G-protein-coupled receptor kinase activity, S timulated adenylyl cyclase activity significantly decreased, and G-protein- coupled receptor kinase activity significantly increased in both left and r ight ventricular samples caused by increased levels of beta-adrenergic rece ptor kinase 1, No change in beta-adrenergic receptor density was seen at 1 week. Conclusions: Early right ventricular overload is associated with impaired r ight ventricular chamber contractility, dilation, and, importantly, a biven tricular alteration of beta-adrenergic receptor signaling.