Department of Surgery, Section of Cardiac and Thoracic Surgery, University of Chicago Medical Center, Chicago, Illinois 60637, USA.
J Heart Lung Transplant. 2010 Jun;29(6):603-9. doi: 10.1016/j.healun.2010.01.010. Epub 2010 Mar 4.
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.
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.
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.
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.
心肌β肾上腺素能受体（β-AR）信号在慢性心力衰竭（HF）中严重受损。本研究旨在确定连续血流左心室辅助装置（LVAD）支持后，左心室（LV）β-AR 信号是否可以恢复。
12 名患者接受 LVAD 作为移植的桥接。在 LVAD 植入时（HF 组）和移植时（LVAD 组）获得配对的 LV 活检标本。LVAD 支持的平均时间为 152±34 天。通过测量腺苷酸环化酶（AC）活性、总β-AR 密度（B（max））、G 蛋白偶联受体激酶-2（GRK2）表达和活性来评估心肌β-AR 信号。8 个非衰竭心脏（NF）的 LV 标本用作对照。
HF 与 NF 相比，基础和异丙肾上腺素刺激的 AC 活性显着降低，表明β-AR 解偶联。连续血流 LVAD 支持将基础和异丙肾上腺素刺激的 AC 活性恢复到类似于 NF 的水平。B（max）在 HF 中低于 NF，在 LVAD 组中增加到接近正常。HF 与 NF 相比，GRK2 表达增加了 2.6 倍，在 LVAD 支持后与 NF 相似。HF 与 NF 相比，GRK2 活性增加了 3.2 倍，在 LVAD 组中降低到 NF 水平。
连续血流 LVAD 支持后，心肌β-AR 信号可恢复至接近正常水平。这与以前关于容积置换搏动性 LVAD 的数据相似。GRK2 活性降低是一个重要机制，并表明与 HF 相关的神经激素环境的正常化在连续流动和搏动性 LVAD 之间相似。这可能对心肌恢复具有重要意义。
