Myocardial Atrophy and Chronic Mechanical Unloading of the Failing Human Heart
Myocardial Atrophy and Chronic Mechanical Unloading of the Failing Human Heart
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DOI：
10.1016/j.jacc.2014.05.073
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发表时间：
2014-10-14
影响因子：
24
通讯作者：
Drakos, Stavros G.
中科院分区：
文献类型：
--
作者：
Diakos, Nikolaos A.;Selzman, Craig H.;Drakos, Stavros G.
背景：在异位移植的动物模型中，正常的、非肥厚的心脏机械卸载会导致萎缩。主要基于这些动物数据，慢性左心室辅助装置(LVAD)诱导的卸载将导致萎缩的概念主导了临床心力衰竭领域，抗萎缩药物已被用于提高一些LVAD患者的心脏恢复潜力。目的探讨连续流左心反搏机械卸载是否会导致心肌萎缩。方法前瞻性检测44例左冠状动脉左前降支患者和18例未移植的正常供者的心肌组织、血流动力学和超声心动图资料。结果心肌细胞横截面积从1,238+/81 mU m(2)减小到1,011+/-68 mm(2)(p=0.001)。但不超过正常供心(682+/-56MU(2))。电子显微镜超微结构评估、心肌细胞糖原含量以及超声心动图对心肌质量和左心功能的评估也没有提示心肌萎缩。与这些发现一致的是，T管形态、细胞质穿透和距离兰尼定受体的距离并不表明在左冠状动脉前降支过程中正在进行的萎缩性重塑。分子分析显示，泛素蛋白酶体系统的前萎缩性基因和蛋白没有上调。结论结构、超微结构、微结构、代谢、分子和临床功能数据表明，长时间的连续流LVAD卸载不会导致肥厚退化到萎缩和退行性变的程度。这些发现可能有助于设计未来的研究，将LVAD卸载和药物治疗结合起来，作为恢复衰竭心脏的桥梁。(C)2014年，由美国心脏病学会基金会提供。
BACKGROUND In animal models of heterotopic transplantation, mechanical unloading of the normal, nonhypertrophic heart results in atrophy. Primarily on the basis of these animal data, the notion that chronic left ventricular assist device (LVAD)-induced unloading will result in atrophy has dominated the clinical heart failure field, and anti-atrophic drugs have been used to enhance the cardiac recovery potential observed in some LVAD patients. However, whether unloading-induced atrophy in experimental normal heart models applies to failing and hypertrophic myocardium in heart failure patients unloaded by continuous-flow LVADs has not been studied.OBJECTIVES The study examined whether mechanical unloading by continuous-flow LVAD leads to myocardial atrophy.METHODS We prospectively examined myocardial tissue and hemodynamic and echocardiographic data from 44 LVAD patients and 18 untransplanted normal donors.RESULTS Cardiomyocyte size (cross-sectional area) decreased after LVAD unloading from 1,238 +/- 81 mu m(2) to 1,011 +/- 68 mm(2) (p = 0.001), but not beyond that of normal donor hearts (682 +/- 56 mu m(2)). Electron microscopy ultrastructural evaluation, cardiomyocyte glycogen content, and echocardiographic assessment of myocardial mass and left ventricular function also did not suggest myocardial atrophy. Consistent with these findings, t-tubule morphology, cytoplasmic penetration, and distance from the ryanodine receptor were not indicative of ongoing atrophic remodeling during LVAD unloading. Molecular analysis revealed no up-regulation of proatrophic genes and proteins of the ubiquitin proteasome system.CONCLUSIONS Structural, ultrastructural, microstructural, metabolic, molecular, and clinical functional data indicated that prolonged continuous-flow LVAD unloading does not induce hypertrophy regression to the point of atrophy and degeneration. These findings may be useful in designing future investigations that combine LVAD unloading and pharmaceutical therapies as a bridge to recovery of the failing heart. (C) 2014 by the American College of Cardiology Foundation.