Small animal models of heart failure

Abstract

Heart disease is a major cause of death worldwide with increasing prevalence, which urges the development of new therapeutic strategies. Over the last few decades, numerous small animal models have been generated to mimic various pathomechanisms contributing to heart failure (HF). Despite some limitations, these animal models have greatly advanced our understanding of the pathogenesis of the different aetiologies of HF and paved the way to understanding the underlying mechanisms and development of successful treatments. These models utilize surgical techniques, genetic modifications, and pharmacological approaches. The present review discusses the strengths and limitations of commonly used small animal HF models, which continue to provide crucial insight and facilitate the development of new treatment strategies for patients with HF.

Keywords: Animal models; HFpEF; HFrEF; Heart failure; Rodents.

Figure 1

Schematic depicting selected risk factors for the development of heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). Note that some risk factors increase the risk of both HFrEF and HFpEF, and HFpEF may precede the later onset of HFrEF. COPD, chronic obstructive pulmonary disease; LVEF, left ventricular ejection fraction.

Figure 2

Schematic depicting selected stressors to induce heart failure with reduced ejection fraction (HFrEF) in small animal models. Note that these models may also induce heart failure with preserved ejection fraction (HFpEF), which precedes the later onset of HFrEF. Additional animal models with temporary exposure to drugs and temporary genetic gain-of-function or loss-of-function modifications have been developed. DOX, doxorubicin; EtOH, ethanol; Hcy, homocysteine; I/R, ischaemia/reperfusion injury; ISO, isoproterenol; LAD, left anterior descending artery; LV, left ventriclular; MCT, monocrotaline; RV, right ventriclular.