Incomplete recovery of myocyte contractile function despite improvement of myocardial architecture with left ventricular assist device support.
Incomplete recovery of myocyte contractile function despite improvement of myocardial architecture with left ventricular assist device support.
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DOI：
10.1161/circheartfailure.111.961326
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发表时间：
2011-07
期刊：
影响因子：
--
通讯作者：
Buttrick PM
中科院分区：
文献类型：
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作者：
Ambardekar AV;Walker JS;Walker LA;Cleveland JC Jr;Lowes BD;Buttrick PM
使用左心室辅助装置 (LVAD) 减轻衰竭心脏的负荷可以改善射血分数 (EF) 和左心室 (LV) 大小；然而，通过 LVAD 移植术恢复的情况很少见。我们假设 LVAD 前后肌细胞收缩力和肌节水平的生物化学评估可以解释器官水平的变化。配对的左心室组织样本是从 8 名非缺血性心肌病患者在 LVAD 植入时（LVAD 前）和移植前（LVAD 后）冷冻而来。将它们与 8 个未衰竭的心脏进行比较。纯化分离的带皮肌细胞，将其连接至力传感器，并评估尺寸、最大钙饱和力（Fmax）、钙敏感性和肌丝协同性。测量了肌节收缩蛋白的相对亚型丰度和磷酸化水平。在 LVAD 支持下，无负荷 EF 改善（10.0±1.0 至 25.6±11.0%，p=0.007），左室尺寸减小（LVIDd 7.6±1.2 至 4.9±1.4cm，p<0.001），肌细胞尺寸减小（横截面积 1247±346 至 638±254μm2， p=0.001）。 LVAD 后 Fmax 有所改善（3.6±0.9 至 7.3±1.8mN/mm2，p<0.001），但仍低于未失败的患者（7.3±1.8 与 17.6±1.8mN/mm2，p<0.001）。注意到 LVAD 后肌钙蛋白 I (TnI) 磷酸化增加，但 TnI 的蛋白激酶 C 磷酸化减少。 LVAD 后未观察到其他肌节蛋白的生化变化。 LVAD 使 LV 和肌细胞大小显着改善，但 EF 和肌细胞收缩力仅部分恢复。 LVAD 支持仅与 TnI 的生化变化相关。这表明替代机制可能会导致 LVAD 后的收缩变化，并且可能需要额外的干预措施来改变肌节的生化重塑，以进一步增强肌丝和器官水平的恢复。
Unloading a failing heart with a left ventricular assist device (LVAD) can improve ejection fraction (EF) and left ventricular (LV) size; however, recovery with LVAD explantation is rare. We hypothesized that evaluation of myocyte contractility and biochemistry at the sarcomere level before and after LVAD may explain organ level changes. Paired LV tissue samples were frozen from 8 patients with nonischemic cardiomyopathy at LVAD implantation (Before LVAD) and prior to transplant (After LVAD). These were compared to 8 nonfailing hearts. Isolated skinned myocytes were purified, attached to a force transducer, and dimensions, maximal calcium saturated force (Fmax), calcium sensitivity, and myofilament cooperativity were assessed. Relative isoform abundance and phosphorylation levels of sarcomeric contractile proteins were measured. With LVAD support, the unloaded EF improved (10.0±1.0 to 25.6±11.0%, p=0.007), LV size decreased (LVIDd 7.6±1.2 to 4.9±1.4cm, p<0.001), and myocyte dimensions decreased (cross-sectional area 1247±346 to 638±254μm2, p=0.001). Fmax improved after LVAD (3.6±0.9 to 7.3±1.8mN/mm2, p<0.001), but was still lower than nonfailing (7.3±1.8 vs. 17.6±1.8mN/mm2, p<0.001). An increase in troponin I (TnI) phosphorylation after LVAD was noted, but protein kinase C phosphorylation of TnI decreased. Biochemical changes of other sarcomeric proteins were not observed after LVAD. There is significant improvement in LV and myocyte size with LVAD, but there is only partial recovery of EF and myocyte contractility. LVAD support was only associated with biochemical changes in TnI. This suggests that alternate mechanisms might contribute to contractile changes after LVAD and that additional interventions may be needed to alter biochemical remodeling of the sarcomere to further enhance myofilament and organ level recovery.