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.