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

Ashish S. Shah, B. Zane Atkins, Jonathan A. Hata, Oliver Tai, Alan P. Kypson, R. Eric Lilly, Walter J. Koch, Donald D. Glower

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: Right ventricular dysfunction is a poorly understood but persistent clinical problem. This study was undertaken to evaluate ventricular performance and β-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). β-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 β-adrenergic receptor kinase 1. No change in β-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 β-adrenergic receptor signaling.

Original languageEnglish (US)
Pages (from-to)342-349
Number of pages8
JournalJournal of Thoracic and Cardiovascular Surgery
Volume120
Issue number2
StatePublished - 2000
Externally publishedYes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

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