Abstract
Heart failure with reduced ejection fraction (HFrEF) is defined by an ejection fraction (EF) below 40%. Many distinct disease processes culminate in HFrEF, among them acute and chronic ischemia, pressure overload, volume overload, cytotoxic medication, and arrhythmia. To study these different etiologies the development of accurate animal models is vital. While small animal models are generally cheaper, allow for larger sample sizes and offer a greater variety of transgenic models, they have important limitations in the context of HFrEF research. Small mammals have much higher heart rates and distinct ion channels. They also have much higher basal metabolic rates and their physiology in many ways does not reflect that of humans. The size of their organs also puts practical constraints on experiments. Therefore, large animal models have been developed to accurately simulate human HFrEF. This review aims to give a short overview of the currently established large animal models of HFrEF. The main animal models discussed are dogs, pigs, and sheep. Furthermore, multiple approaches for modeling the different etiologies of HF are discussed, namely models of acute and chronic ischemia, pressure overload, volume overload as well as cytotoxic, and tachycardic pacing approaches.
Highlights
Heart failure (HF) is a complex clinical entity with multiple different etiologies
This review aims to give a short overview of the currently established large animal models of Heart failure with reduced ejection fraction (HFrEF)
Standard protocols often use weekly injections of microspheres between 40 and 100 μm until a desired ejection fraction (EF) is reached [31]. While this method offers a gradual decline in left ventricular function with a lower mortality rate than acute models of ischemia, it is very labor intensive, and puts more strain on the animals, since multiple interventions are necessary within a short period of time
Summary
Heart failure (HF) is a complex clinical entity with multiple different etiologies. The primary characteristic of HF is reduced contractile force or inadequate filling. Porcine (pig) models have become very popular for cardiovascular research Their physiology, heart size, immune system and anatomy closely resemble that of humans and their coronaries have very little collateral circulation. Used materials include microbeads, collagen, gelatin, coils or autologous platelet aggregates [10,11,12,13,14,15] These models have the advantage of being fairly easy to carry out and of simulating the thrombotic nature of AMI, but they offer less precise control of infarct size than other methods. They do not reflect the typical clinical setting in which AMI patients undergo percutaneous coronary intervention (PCI) and subsequent revascularization. The percutaneous I/R model is especially relevant because it closely models the TABLE 1 | Overview of large animal models of HFrEF
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