Reversal of impaired myocardial β-adrenergic receptor signaling by continuous-flow left ventricular assist device support
published online 08 March 2010.
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.
aDepartment of Surgery, Section of Cardiac and Thoracic Surgery, University of Chicago Medical Center, Chicago, Illinois
bDepartment of Medicine, Section of Cardiology, University of Chicago Medical Center, Chicago, Illinois
Reprint requests: Shahab A. Akhter, MD, University of Chicago Medical Center, 5841 S Maryland Ave, MC 5040, Chicago, IL 60637. Telephone: 773-702-2500; Fax: 773-702-4187
ABSTRACT