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

J Heart Lung Transplant. 2010 Jun;29(6):603-9. doi: 10.1016/j.healun.2010.01.010. Epub 2010 Mar 4.


Background: Myocardial beta-adrenergic receptor (beta-AR) signaling is severely impaired in chronic heart failure (HF). This study was conducted to determine if left ventricular (LV) beta-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 beta-AR signaling was assessed by measuring adenylyl cyclase (AC) activity, total beta-AR density (B(max)), 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 beta-AR uncoupling. Continuous-flow LVAD support restored basal and isoproterenol-stimulated AC activity to levels similar to NF. B(max) 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 beta-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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Chronic Disease
  • Down-Regulation
  • Female
  • G-Protein-Coupled Receptor Kinase 2 / metabolism
  • Heart Failure / metabolism*
  • Heart Failure / physiopathology
  • Heart Failure / therapy*
  • Heart-Assist Devices*
  • Humans
  • Lymphocytes / enzymology
  • Male
  • Middle Aged
  • Myocardium / enzymology
  • Myocardium / metabolism*
  • Receptors, Adrenergic, beta / metabolism*
  • Recovery of Function
  • Signal Transduction*
  • Time Factors


  • Receptors, Adrenergic, beta
  • GRK2 protein, human
  • G-Protein-Coupled Receptor Kinase 2