Department of Medicine I, University Hospital Munich, Campus Grosshadern, Ludwig-Maximilians University Munich (LMU), Munich, Germany.
DZHK (German Centre for Cardiovascular Research), Partner Site Munich, Munich Heart Alliance (MHA), Munich, Germany.
Nat Rev Cardiol. 2019 Aug;16(8):457-475. doi: 10.1038/s41569-019-0179-0.
Arrhythmias are common and contribute substantially to cardiovascular morbidity and mortality. The underlying pathophysiology of arrhythmias is complex and remains incompletely understood, which explains why mostly only symptomatic therapy is available. The evaluation of the complex interplay between various cell types in the heart, including cardiomyocytes from the conduction system and the working myocardium, fibroblasts and cardiac immune cells, remains a major challenge in arrhythmia research because it can be investigated only in vivo. Various animal species have been used, and several disease models have been developed to study arrhythmias. Although every species is useful and might be ideal to study a specific hypothesis, we suggest a practical trio of animal models for future use: mice for genetic investigations, mechanistic evaluations or early studies to identify potential drug targets; rabbits for studies on ion channel function, repolarization or re-entrant arrhythmias; and pigs for preclinical translational studies to validate previous findings. In this Review, we provide a comprehensive overview of different models and currently used species for arrhythmia research, discuss their advantages and disadvantages and provide guidance for researchers who are considering performing in vivo studies.
心律失常很常见,会大幅增加心血管发病率和死亡率。心律失常的潜在病理生理学很复杂,目前仍不完全清楚,这也解释了为什么目前主要只能进行对症治疗。评估心脏中各种细胞类型(包括传导系统和工作心肌的心肌细胞、成纤维细胞和心脏免疫细胞)之间的复杂相互作用仍然是心律失常研究中的一个主要挑战,因为只能在体内进行研究。已经使用了多种动物物种,并开发了几种疾病模型来研究心律失常。虽然每种物种都有其用途,并且可能非常适合研究特定的假设,但我们建议未来使用一种实用的动物模型 trio:用于遗传研究、机制评估或早期研究以确定潜在药物靶点的小鼠;用于离子通道功能、复极化或折返性心律失常研究的兔子;以及用于验证先前发现的临床前转化研究的猪。在这篇综述中,我们全面概述了用于心律失常研究的不同模型和当前使用的物种,讨论了它们的优缺点,并为考虑进行体内研究的研究人员提供了指导。
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