Wohlschlaeger J, Kawaguchi N, Levkau B, Schmid C, Scheld H H, Baba H A
Institut für Pathologie, Universität Essen-Duisburg, Hufelandstrasse 55, 45122 Essen, Deutschland.
Verh Dtsch Ges Pathol. 2004;88:113-21.
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, LVAD support sporadically results in improved cardiac function, and heart transplantation is not necessary even after removal of LVAD in a subset of patients ("bridge to recovery"). Additionally, LVAD appears to be an optional treatment alternative to heart transplantation in patients with contraindication for organ replacement ("destination therapy"). The underlying process has descriptively been termed "reverse remodeling". The molecular basis remains incompletely understood at present, however, some mechanisms have been identified in the past. Alterations of several molecular pathways are involved in the development of chronic heart failure. Some of the pathways appear to be reversible and have been shown to be regulated by LVAD treatment. LVAD lead to lowered cardiac pressure and volume overload followed by decreased ventricular wall tension, reduction of cardiomyocyte hypertrophy, improved coronary perfusion and a decrease of chronic ischemia in the myocardium. Improved coronary flow and myocardial perfusion as well as decreased ventricular wall tension may serve as a possible explanation for changes of the molecular systems involved in the development of chronic cardiac insuffiency. This review focuses on the roles of apoptosis, heme-oxygenase-1 (HO-1), Metallothionein (MT) and the transcription factor NFkkappaB in chronic heart failure after mechanical circulatory support.
左心室辅助装置(LVAD)用于“桥接”终末期心力衰竭患者,直至能够进行供体心脏移植(“桥接至移植”)。然而,LVAD支持偶尔会使心脏功能得到改善,并且在一部分患者中,即使移除LVAD后也无需进行心脏移植(“桥接至恢复”)。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”)。这种潜在过程在描述上被称为“逆向重塑”。目前其分子基础仍未完全明确,不过,过去已经确定了一些机制。几种分子途径的改变参与了慢性心力衰竭的发展。其中一些途径似乎是可逆的,并且已被证明受LVAD治疗的调节。LVAD可降低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心肌慢性缺血。冠状动脉血流和心肌灌注的改善以及心室壁张力的降低,可能是参与慢性心力衰竭发展的分子系统发生变化的一个可能解释。本综述重点关注细胞凋亡、血红素加氧酶-1(HO-1)、金属硫蛋白(MT)和转录因子NFκB在机械循环支持后慢性心力衰竭中的作用。