Small and large animal models in cardiac contraction research: Advantages and disadvantages

Abstract

The mammalian heart is responsible for not only pumping blood throughout the body but also adjusting this pumping activity quickly depending upon sudden changes in the metabolic demands of the body. For the most part, the human heart is capable of performing its duties without complications; however, throughout many decades of use, at some point this system encounters problems. Research into the heart’s activities during healthy states and during adverse impacts that occur in disease states is necessary in order to strategize novel treatment options to ultimately prolong and improve patients’ lives. Animal models are an important aspect of cardiac research where a variety of cardiac processes and therapeutic targets can be studied. However, there are differences between the heart of a human being and an animal and depending on the specific animal, these differences can become more pronounced and in certain cases limiting. There is no ideal animal model available for cardiac research, the use of each animal model is accompanied with its own set of advantages and disadvantages. In this review, we will discuss these advantages and disadvantages of commonly used laboratory animals including mouse, rat, rabbit, canine, swine, and sheep. Since the goal of cardiac research is to enhance our understanding of human health and disease and help improve clinical outcomes, we will also discuss the role of human cardiac tissue in cardiac research. This review will focus on the cardiac ventricular contractile and relaxation kinetics of humans and animal models in order to illustrate these differences.

Contractility of single cardiomyocytes differentiated from pluripotent stem cells depends on physiological shape and substrate stiffness

“…However, we observed physiological sarcomere lengths around 2 μm and detected no difference in sarcomere length for aspect ratios from 3:1 to 7:1. This may be due to sarcomeric differences of human and murine CMs (8,9).…”

“…Specifically, hPSC-CMs can model myocardial physiology in vitro (7). hPSCCMs may be better in vitro models of contractility than neonatal or mature murine primary CMs, because they can be maintained in culture longer (2) and because the sarcomeric contractile machinery differs between human and murine CMs (8,9). However, hPSC-CMs derived from current differentiation protocols present myofibril alignment resembling that of fetal CMs, limiting their ability to replicate the contractility of primary adult CMs (6).…”

The genetic basis of hypertrophic cardiomyopathy in cats and humans

“…While there are inherent limitations to using mice as models of cardiac structure and function in humans, mouse models of human HCM mutations have nonetheless proven tremendously useful in identifying the most proximal causes of the disease, especially in cases where an abnormal protein directly causes altered muscle function (i.e., a so-called “poison polypeptide”) such as the case with the original R403Q mutation first identified in MYH7 . 82 …”

Afterload-induced diastolic dysfunction contributes to high filling pressures in experimental heart failure with preserved ejection fraction

“…Indeed, we have documented that the diseased myocardium tolerates afterload elevations poorly both in patients with impaired ejection fraction (EF) (19) and in a rat disease model (6). In healthy rats, however, likely owing to particularities in myofilament composition and Ca 2ϩ kinetics (21), only isovolumic afterload significantly impaired relaxation with faint consequences in EDP (6). Most importantly, although it may provide important mechanistic views on myocardial response to sudden afterload, this experimental setup was never applied to the stiff HFpEF myocardium.…”