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

Total myocardial β-adrenergic receptor density (B_max). NF, non-failing controls (n = 8); HF, heart failure group before left ventricular assist device (LVAD) implant (n = 12); LVAD, after LVAD implant (n = 12). *p < 0.05 vs NF; ^#p < 0.01 vs HF and p > 0.05 vs NF. Error bars indicate the standard error of the mean.

Myocardial sarcolemmal membrane adenylyl cyclase activity. ISO, isoproterenol; NF, non-failing controls (n = 8); HF, heart failure group before left ventricular assist device (LVAD) implant (n = 12); LVAD, after LVAD implant (n = 12). *p < 0.01 vs NF, ^#p < 0.05 vs HF and p > 0.05 vs NF. All experiments were performed in triplicate. Error bars indicate the standard error of the mean.

Left ventricular protein expression of G protein-coupled receptor kinase-2 (GRK2) with (top panel) a representative Western blot. NF, non-failing controls (n = 8); HF, heart failure group before left ventricular assist device (LVAD) implant (n = 12); LVAD, after LVAD implant (n = 12). *p < 0.05 vs NF; ^#p < 0.01 vs HF and p > 0.05 vs NF. Error bars indicate the standard error of the mean.

G protein-coupled receptor kinase-2 messenger RNA expression measured by semi-quantitative real-time reverse transcription polymerase chain reaction. NF, non-failing controls (n = 8); HF, heart failure group before left ventricular assist device (LVAD) implant (n = 12); LVAD, after LVAD implant (n = 12). *p < 0.05 vs NF; ^#p < 0.02 vs HF and p > 0.05 vs NF. All experiments were performed in triplicate. Error bars indicate the standard error of the mean.

G protein-coupled receptor kinase-2 activity in left ventricular tissue preparations measured by rhodopsin phosphorylation is shown in the bottom panel. The top panel shows a representative autoradiogram of phospho-incorporation into rhodopsin (Rho) after gel electrophoresis. NF, non-failing controls (n = 8); HF, heart failure group before left ventricular assist device (LVAD) implant (n = 12); LVAD, after LVAD implant (n = 12). *p < 0.05 vs NF; ^#p < 0.01 vs HF and p > 0.05 vs NF. Error bars indicate the standard error of the mean.

Lymphocyte G protein-coupled receptor kinase-2 protein expression in paired blood samples. HF, heart failure group before left ventricular assist device (LVAD) implant (n = 12); LVAD, after LVAD implant (n = 12). *p < 0.04 vs HF. Error bars indicate the standard error of the mean.