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

*Corresponding author for this work

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

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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    Akhter, S. A., D'Souza, K. M., Malhotra, R., Staron, M. L., Valeroso, T. B., Fedson, S. E., Anderson, A. S., Raman, J., & Jeevanandam, V. (2010). Reversal of impaired myocardial β-adrenergic receptor signaling by continuous-flow left ventricular assist device support. Journal of Heart and Lung Transplantation, 29(6), 603-609. https://doi.org/10.1016/j.healun.2010.01.010