a Department of Physiology and Cell Biology , The Ohio State University Wexner Medical Center , Columbus, OH, USA.
b Dorothy M. Davis Heart and Lung Research Institute , The Ohio State University Wexner Medical Center , Columbus, OH, USA.
Expert Opin Drug Discov. 2019 Apr;14(4):355-363. doi: 10.1080/17460441.2019.1582636. Epub 2019 Mar 12.
When investigating drugs that treat heart diseases, it is critical when choosing an animal model for the said model to produce data that is translatable to the human patient population, while keeping in mind the principles of reduction, refinement, and replacement of the animal model in the research. Areas covered: In this review, the authors focus on mammalian models developed to study the impact of drug treatments on human heart failure. Furthermore, the authors address human patient variability and animal model invariability as well as the considerations that need to be made regarding choice of species. Finally, the authors discuss some of the most common models for the two most prominent human heart failure etiologies; increased load on the heart and myocardial ischemia. Expert opinion: In the authors' opinion, the data generated by drug studies is often heavily impacted by the choice of species and the physiologically relevant conditions under which the data are collected. Approaches that use multiple models and are not restricted to small rodents but involve some verification on larger mammals or on human myocardium, are needed to advance drug discovery for the very large patient population that suffers from heart failure.
在研究治疗心脏病的药物时，选择动物模型至关重要，所选模型应能产生可转化为人类患者群体的数据，同时牢记研究中动物模型的减少、优化和替代原则。
在这篇综述中，作者重点介绍了为研究药物治疗对人类心力衰竭的影响而开发的哺乳动物模型。此外，作者还讨论了人类患者的变异性和动物模型的不变性，以及在选择物种时需要考虑的因素。最后，作者讨论了两种最常见的人类心力衰竭病因的常见模型；心脏负荷增加和心肌缺血。
作者认为，药物研究产生的数据往往受到物种选择和数据收集的生理相关条件的严重影响。需要采用多种模型的方法，而不仅仅局限于小型啮齿动物，还需要在较大的哺乳动物或人类心肌上进行一些验证，以推进针对患有心力衰竭的庞大患者群体的药物发现。
