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


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.

DOI: 10.1016/j.healun.2010.01.010

Cite this paper

@article{Akhter2010ReversalOI, title={Reversal of impaired myocardial beta-adrenergic receptor signaling by continuous-flow left ventricular assist device support.}, author={Shahab A. Akhter and Karen D'Souza and Ricky Malhotra and Michelle L Staron and Tracy B Valeroso and Savitri E. Fedson and Allen S. Anderson and Jaishankar Raman and Valluvan Jeevanandam}, journal={The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation}, year={2010}, volume={29 6}, pages={603-9} }