5. Summary and conclusion

In the process of preclinical drug discovery, due to the complex nature of the dynamic heart, which is not only affected by the proteins and processes in the heart, but also affected by the dynamic changes and interaction of biophysical mechanical forces and currents in the process of beating heart, no animal model is perfect for interpreting every aspect of cardiovascular pathology at one time, thus many of the complex properties thus cannot be captured by a vitro cell model or an in vivo animal alone. Instead, the preclinical pharmacological evaluation of HF often involves in preliminary studies conducted in vitro (including cells and isolated tissues) to identify potential drug targets, new signaling pathways, and regulatory mechanisms, then moving to comprehensive characterization in rodents and large animals (Table 3 ). We summarized the main strengths and weaknesses of these approaches and their applicability to preclinical process in HF research (Figure 2 ). Based on this, we strongly recommend that careful consideration be given to the potential impact of species selection on experimental data during drug research, as well as the physiological conditions for data collection. It is not only limited to small rodent studies, but also should be evaluated by multiple model methods, especially involving the verification of cardiac characteristics in large mammals or humans, so as to promote drug discovery of HF. In addition, we should consider the factors such as complications and side effects while meeting the established research objectives. The therapeutic effect of preclinical HF candidate drugs needs to be supported in a variety of different experimental models. As called for in the scientific statement written by Houser et al., (Houser et al., 2012) a ”one size fits all” approach is not suitable for the selection of experimental models for the study of HF. Instead, animal models should be selected based on the characteristics present in the particular clinical form of HF of interest.