Modeling heart failure in animal models for novel drug discovery and development.

INTRODUCTION: 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.