Department of Pediatric Cardiology, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas 77030, USA.
J Heart Lung Transplant. 2010 Jan;29(1):98-104. doi: 10.1016/j.healun.2009.06.030. Epub 2009 Sep 26.
Mechanical support using a left ventricular assist device (LVAD) can lead to functional recovery of the myocardium in patients with end-stage heart failure (HF). Molecular remodeling, cytoskeletal disruption, and apoptosis activation are associated with abnormal gene expression in the failing ventricular myocardium of HF subjects and can normalize in response to medium- and long-term mechanical unloading in adults. However, there is little knowledge of the changes in gene expression after short-term mechanical support in children with HF.
We evaluated left ventricular biopsies from 4 children with HF. The children had implantation of a continuous- or a pulsatile-flow LVAD for 8 to 16 days before undergoing heart transplantation. At the time of LVAD insertion and removal, we performed quantitative real-time polymerase chain reaction (QPCR) to study the expression of 326 genes encoding for structural, transcriptional, and signaling pathways proteins, and immunoblot analysis on dystrophin and apoptotic factors.
Short-term LVAD therapy significantly decreased brain natriuretic peptide (BNP) levels from pre-LVAD (3,584.5 +/- 378.3 pg/ml [95% CI]) to post-LVAD (447.5 +/- 52.7 pg/ml [95% CI]) in 2 patients in whom comparative BNP measurements were available. In addition, short-term LVAD therapy reduced HF and apoptosis markers, whereas it upregulated structural proteins, including dystrophin, as well as pro-hypertrophic and pro-inotropic markers. Furthermore, LVAD therapy normalized expression of genes involved in calcium homeostasis, cell growth, and differentiation.
Our pilot study suggests that even short-term LVAD therapy in children with severe HF can reverse molecular remodeling. This favorable effect should be taken into consideration in eligible children with significant ventricular dysfunction.
使用左心室辅助装置（LVAD）进行机械支持可导致终末期心力衰竭（HF）患者的心肌功能恢复。分子重塑、细胞骨架破坏和细胞凋亡激活与 HF 患者衰竭心室心肌的异常基因表达有关，并可在成人中对中、长期机械卸载作出正常反应。然而，对于 HF 儿童在短期机械支持后的基因表达变化，人们知之甚少。
我们评估了 4 名 HF 儿童的左心室活检。这些儿童在接受心脏移植前接受了连续或搏动流 LVAD 植入 8 至 16 天。在 LVAD 插入和取出时，我们进行了 326 个编码结构、转录和信号通路蛋白的基因的定量实时聚合酶链反应（QPCR）研究，并对肌营养不良蛋白和凋亡因子进行了免疫印迹分析。
短期 LVAD 治疗可显著降低 2 名患者的脑钠肽（BNP）水平，从 LVAD 前（3584.5 +/- 378.3 pg/ml [95% CI]）降至 LVAD 后（447.5 +/- 52.7 pg/ml [95% CI]）。此外，短期 LVAD 治疗可降低 HF 和凋亡标志物，同时上调结构蛋白，包括肌营养不良蛋白，以及促肥厚和促收缩标志物。此外，LVAD 治疗还可使参与钙稳态、细胞生长和分化的基因表达正常化。
我们的初步研究表明，即使是严重 HF 儿童的短期 LVAD 治疗也可以逆转分子重塑。在有明显心室功能障碍的合格儿童中，应考虑这种有利影响。
