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

Abstract

Right ventricular dysfunction is a poorly understood but persistent clinical problem. This study was undertaken to evaluate ventricular performance and beta-adrenergic receptor signaling in a tricuspid regurgitation model of right ventricular overload. Seventeen dogs were chronically instrumented with epicardial dimension transducers. By means of the shell-subtraction model, right ventricular pressure-volume relationships were evaluated in normal and right ventricular overload states. Right ventricular chamber performance was quantified by the stroke work at an end-diastolic volume relationship. Right ventricular volume overload caused a 28% +/- 11% and 31% +/- 9% decline in chamber performance acutely and at 1 week, respectively, whereas end-diastolic volume increased from 45 +/- 21 to 60 +/- 30 mL (P =. 019). beta-Adrenergic receptor signaling in myocardial samples was assessed, examining adenylyl cyclase and G-protein-coupled receptor kinase activity. Stimulated adenylyl cyclase activity significantly decreased, and G-protein-coupled receptor kinase activity significantly increased in both left and right ventricular samples caused by increased levels of beta-adrenergic receptor kinase 1. No change in beta-adrenergic receptor density was seen at 1 week. Early right ventricular overload is associated with impaired right ventricular chamber contractility, dilation, and, importantly, a biventricular alteration of beta-adrenergic receptor signaling.