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


METHODS
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.


RESULTS
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.


CONCLUSIONS
Early right ventricular overload is associated with impaired right ventricular chamber contractility, dilation, and, importantly, a biventricular alteration of beta-adrenergic receptor signaling.
Department of General and Thoracic Surgery, Duke University Medical Center, Durham, NC 27710, USA.
A S
AS
Shah
B Z
BZ
Atkins
J A
JA
Hata
O
O
Tai
A P
AP
Kypson
R E
RE
Lilly
W J
WJ
Koch
D D
DD
Glower
D000262:Adenylyl Cyclases / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D004285:Dogs; D019204:GTP-Binding Proteins / Q000378:metabolism; D006439:Hemodynamics; D016014:Linear Models; D009206:Myocardium / Q000378:metabolism; D009478:Neuropeptide Y / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D015398:Signal Transduction; D013318:Stroke Volume; D014262:Tricuspid Valve Insufficiency / Q000503:physiopathology; D018497:Ventricular Dysfunction, Right / Q000503:physiopathology*; D017725:Ventricular Pressure
D009478:Neuropeptide Y; D011943:Receptors, Adrenergic, beta; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases