**Abstract**

Studies of not only preclinical cardiovascular research but also those of life science, medical, and pharmacological fields commonly utilize small animal models. However, for the advancement of cardiovascular medicine, researches using large animal models are important step for preclinical validation of therapeutic efficacy and safety by virtue of having models with a body and heart size comparable with that of a human, providing clinically relevant experiments without the concern of over- or under-estimating therapeutic effects and risks. In particular, pigs are considered as a suitable animal model for research in cardiovascular medicine because of the similarities in physiology, metabolism, genomics, and proteomics to those in humans. Another advantage of pigs is the availability of various heart disease models such as myocardial infarction and genetically established cardiomyopathy. The present review updates the contributions of large animal model-based research to the development of cardiovascular medicine, especially focusing on the utility of pig models.

**Keywords:** large animal models, cardiovascular research, translational research, pig models, disease models

### **1. Introduction**

Studies of not only preclinical cardiovascular research but also those of life science, medical, and pharmacological fields commonly utilize small animal models such as rodents. However, the translation of the rodent-based results to clinical trials does not always provide relevant results in humans possibly due to anatomical differences between humans and small animals, or variations in physiological characteristics and mechanisms of the disease development [1–3]. To confirm safety and efficacy in clinical studies, the transition from small-to-large animal studies, which comprise anatomical, biological, and physiological features similar to humans, is anticipated. Therefore, the selection of animal species and preparation of suitable disease models are crucial to obtain clinically relevant results leading to a better translation to human clinical practices [4, 5].

Among traditionally used large animal models in research like non-human primates, horses, bovines, sheep, goats, dogs, cats, and pigs, the pig model is considered to be a desirable experimental model because of its similarity to humans in terms of body and heart size to humans, enabling the researcher to prepare clinically relevant disease models such as a myocardial infarction model [6]. Other advantages of the pig model are its similarities in physiology, metabolism, genomics, and proteomics

to humans [7–10]. Genetically modified pig disease models, such as the genetic cardiomyopathy model, have also been developed [11]. The current review updates the contributions of large animal models for research of cardiovascular medicine, especially focusing on the utility of pig models.
