Fu Xuebin, Segiser Adrian, Carrel Thierry P, Tevaearai Stahel Hendrik T, Most Henriette
Department of Cardiac and Vascular Surgery, Inselspital University Hospital , Berne , Switzerland.
Front Cardiovasc Med. 2016 Oct 19;3:34. doi: 10.3389/fcvm.2016.00034. eCollection 2016.
Unloading of the failing left ventricle in order to achieve myocardial reverse remodeling and improvement of contractile function has been developed as a strategy with the increasing frequency of implantation of left ventricular assist devices in clinical practice. But, reverse remodeling remains an elusive target, with high variability and exact mechanisms still largely unclear. The small animal model of heterotopic heart transplantation (hHTX) in rodents has been widely implemented to study the effects of complete and partial unloading on cardiac failing and non-failing tissue to better understand the structural and molecular changes that underlie myocardial recovery. We herein review the current knowledge on the effects of volume unloading the left ventricle different methods of hHTX in rats, differentiating between changes that contribute to functional recovery and adverse effects observed in unloaded myocardium. We focus on methodological aspects of heterotopic transplantation, which increase the correlation between the animal model and the setting of the failing unloaded human heart. Last, but not least, we describe the late use of sophisticated techniques to acquire data, such as small animal MRI and catheterization, as well as ways to assess unloaded hearts under "reloaded" conditions. While giving regard to certain limitations, heterotopic rat heart transplantation certainly represents the crucial model to mimic unloading-induced changes in the heart and as such the intricacies and challenges deserve highest consideration. Careful translational research will further improve our knowledge of the reverse remodeling process and how to potentiate its effect in order to achieve recovery of contractile function in more patients.
随着临床实践中左心室辅助装置植入频率的增加，为实现心肌逆向重构和改善收缩功能而对衰竭的左心室进行卸载已成为一种策略。但是，逆向重构仍然是一个难以捉摸的目标，其变异性很大，确切机制仍不清楚。啮齿动物异位心脏移植（hHTX）的小动物模型已被广泛用于研究完全和部分卸载对心脏衰竭和非衰竭组织的影响，以更好地理解心肌恢复的结构和分子变化。我们在此回顾了目前关于大鼠左心室容量卸载的影响以及不同hHTX方法的知识，区分了有助于功能恢复的变化和在卸载心肌中观察到的不良反应。我们关注异位移植的方法学方面，这增加了动物模型与衰竭卸载的人类心脏情况之间的相关性。最后但同样重要的是，我们描述了后期使用复杂技术获取数据的情况，如小动物MRI和导管插入术以及在“再负荷”条件下评估卸载心脏的方法。尽管存在某些局限性，但异位大鼠心脏移植无疑是模拟心脏卸载诱导变化的关键模型，因此其复杂性和挑战值得高度关注。仔细的转化研究将进一步提高我们对逆向重构过程的认识以及如何增强其效果，以便在更多患者中实现收缩功能的恢复。
