Reversal of impaired myocardial β-adrenergic receptor signaling by continuous-flow left ventricular assist device support

Shahab A. Akhter, Karen M. D'Souza, Ricky Malhotra, Michelle L. Staron, Tracy B. Valeroso, Savitri E. Fedson, Allen S. Anderson, Jai Raman, Valluvan Jeevanandam

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Background: Myocardial β-adrenergic receptor (β-AR) signaling is severely impaired in chronic heart failure (HF). This study was conducted to determine if left ventricular (LV) β-AR signaling could be restored after continuous-flow LV assist device (LVAD) support. Methods: Twelve patients received LVADs as a bridge to transplant. Paired LV biopsy specimens were obtained at the time of LVAD implant (HF group) and transplant (LVAD group). The mean duration of LVAD support was 152 ± 34 days. Myocardial β-AR signaling was assessed by measuring adenylyl cyclase (AC) activity, total β-AR density (Bmax), and G protein-coupled receptor kinase-2 (GRK2) expression and activity. LV specimens from 8 non-failing hearts (NF) were used as controls. Results: Basal and isoproterenol-stimulated AC activity was significantly lower in HF vs NF, indicative of β-AR uncoupling. Continuous-flow LVAD support restored basal and isoproterenol-stimulated AC activity to levels similar to NF. Bmax was decreased in HF vs NF and increased to nearly normal in the LVAD group. GRK2 expression was increased 2.6-fold in HF vs NF and was similar to NF after LVAD support. GRK2 activity was 3.2-fold greater in HF vs NF and decreased to NF levels in the LVAD group. Conclusions: Myocardial β-AR signaling can be restored to nearly normal after continuous-flow LVAD support. This is similar to previous data for volume-displacement pulsatile LVADs. Decreased GRK2 activity is an important mechanism and indicates that normalization of the neurohormonal milieu associated with HF is similar between continuous-flow and pulsatile LVADs. This may have important implications for myocardial recovery.

Original languageEnglish (US)
Pages (from-to)603-609
Number of pages7
JournalJournal of Heart and Lung Transplantation
Volume29
Issue number6
DOIs
StatePublished - Jun 2010
Externally publishedYes

Keywords

  • left ventricular assist device
  • molecular biology
  • myocardial recovery
  • signal transduction
  • β-adrenergic receptor signaling

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine
  • Transplantation

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