Wohlschlaeger Jeremias, Schmitz Klaus J, Schmid Christof, Schmid Kurt W, Keul Petra, Takeda Atsushi, Weis Serge, Levkau Bodo, Baba Hideo A
Institut für Pathologie, Universitätsklinik Essen, Universität Duisburg-Essen, Hufelandstrasse 55, D-45147 Essen, Germany.
Cardiovasc Res. 2005 Dec 1;68(3):376-86. doi: 10.1016/j.cardiores.2005.06.030. Epub 2005 Jul 18.
Left ventricular assist devices (LVAD) are used to "bridge" patients with end-stage heart failure until transplantation of a donor heart can be performed ("bridge to transplantation"). However, in a subset of patients, support by LVAD sporadically results in improved cardiac function, with heart transplantation no longer necessary even after removal of the LVAD ("bridge to recovery"). Also, LVAD appears to be an optional treatment alternative to heart transplantation in patients with contraindications for organ replacement ("destination therapy"). The processes resulting in these effects have descriptively been termed "reverse remodeling". Although the molecular mechanisms are incompletely understood at present, there are several aspects of the reverse remodeling process that have been identified in the past. Alterations of many molecular pathways are involved in the development of chronic heart failure. Some of these appear to be reversible and have been shown to be regulated by LVAD treatment. LVAD lead to lowered cardiac pressure and volume overload in the myocardium followed by decreased ventricular wall tension, reduced cardiomyocyte hypertrophy, improved coronary perfusion and decreased chronic ischemia. Improved coronary flow and myocardial perfusion as well as decreased ventricular wall tension may possibly alter the molecular systems involved in the development of chronic cardiac insufficiency. Aside from describing the morphological changes, this review focuses on the roles of signal transduction, transcriptional regulation, apoptosis, stress proteins, matrix remodeling, and neurohormonal signaling in the failing human heart before and after mechanical circulatory support.
左心室辅助装置（LVAD）用于“过渡”终末期心力衰竭患者，直至能够进行供体心脏移植（“过渡到移植”）。然而，在一部分患者中，LVAD支持偶尔会导致心脏功能改善，即使在移除LVAD后也不再需要心脏移植（“过渡到康复”）。此外，对于有器官置换禁忌证的患者，LVAD似乎是心脏移植的一种可选治疗替代方案（“目标治疗”）。导致这些效应的过程在描述上被称为“逆向重构”。尽管目前对分子机制的理解还不完全，但过去已经确定了逆向重构过程的几个方面。许多分子途径的改变参与了慢性心力衰竭的发展。其中一些似乎是可逆的，并且已被证明受LVAD治疗调控。LVAD可降低心肌的心脏压力和容量超负荷，随后降低心室壁张力、减少心肌细胞肥大、改善冠状动脉灌注并减轻慢性缺血。改善的冠状动脉血流和心肌灌注以及降低的心室壁张力可能会改变参与慢性心脏功能不全发展的分子系统。除了描述形态学变化外，本综述重点关注机械循环支持前后，信号转导、转录调控、细胞凋亡、应激蛋白、基质重塑和神经激素信号在衰竭人类心脏中的作用。
