Piktel Joseph S, Wilson Lance D
Department of Emergency Medicine, Emergency Care Research Institute and Heart and Vascular Research Center, MetroHealth Campus of Case Western Reserve University, Cleveland, OH, United States.
Front Cardiovasc Med. 2019 Sep 10;6:135. doi: 10.3389/fcvm.2019.00135. eCollection 2019.
We discuss large animal translational models of arrhythmia susceptibility and sudden cardiac death, focusing on important considerations when interpreting the data derived before applying them to human trials. The utility of large animal models of arrhythmia and the pros and cons of specific translational large animals used will be discussed, including the necessary tradeoffs between models designed to derive mechanisms vs. those to test therapies. Recent technical advancements which can be applied to large animal models of arrhythmias to better elucidate mechanistic insights will be introduced. Finally, some specific examples of past successes and challenges in translating the results of large animal models of arrhythmias to clinical trials and practice will be examined, and common themes regarding the success and failure of translating studies to therapy in man will be discussed.
我们讨论心律失常易感性和心源性猝死的大型动物转化模型，重点关注在将从这些模型获得的数据应用于人体试验之前进行解读时的重要考量因素。将讨论心律失常大型动物模型的实用性以及所使用的特定转化大型动物的优缺点，包括旨在推导机制的模型与用于测试疗法的模型之间必要的权衡。将介绍可应用于心律失常大型动物模型以更好地阐明机制见解的最新技术进展。最后，将审视过去在将心律失常大型动物模型的结果转化为临床试验和临床实践方面取得的成功及面临的挑战的一些具体实例，并讨论关于将研究转化为人类治疗方法成败的共同主题。
