. 2022 Jan 6;118(15):3016–3051. doi: 10.1093/cvr/cvab370

Table 3.

Examples of animal models with reduced contractile function and animal-free alternatives

Species	Experimental animal model and pathological features	Applications	Limitations animal model	Animal-free alternatives	Limitations animal-free alternatives
Mouse, rat, pig, dog	Ischaemia–reperfusion Regions of infarction, no reflow, haemorrhage, stunning, contractile function^29–31	Assessment of cardiac contractile function, aryhthmias and long-term inflammation and LV remodelling Study sequential events Study systemic effects of insults (toxic compounds, inflammation) and therapies	Healthy young animals are commonly used, with minimal coronary collaterals Relatively large infarcts, induced by artery ligation or balloon inflation	Mimicking ischaemia–reperfusion in primary CMs, hiPSC-CMs, EHT, cardiac organoids^32,33	Simulated ischaemia differs from true ischaemia (altered buffer instead of blood) Lack of tissue architecture, other cell types, and comorbidities CMs have an immature phenotype Only early stage effects of ischaemia can be mimicked
Mouse, rat, pig, dog, sheep, non-human primate	Myocardial infarction by reperfused acute myocardial infarction, surgical occlusion of coronary arteries, coronary microembolization Fibrosis, systolic dysfunction^34–39			Mimicking acute and chronic ischaemia in cell-based models^32,33
Mouse, pig	Spontaneous myocardial infarction in genetic mouse models, large animals on special diets. Spontaneous plaque rupture with thrombotic occlusion, MI^40,41		High heterogeneity and unpredictability	None
Mouse, Pig	Cancer chemotherapy cardiotoxicity. CM death, vascular injury, contractile dysfunction^42–44		Some commonly used models do not recapitulate the dosing regime used in humans, and typically use healthy (not tumour-bearing) animals	Primary CMs⁴² hiPSC-CMs, EHT Cardiac organoids³³	Lack tissue architecture and non-myocytes Immature CMs No tumour present
Mouse	Viral myocarditis Myocardial inflammation, autoimmune reaction^45,46		Non-physiological methods of administration (e.g. intravenous)	hiPSC-CM, EHT^47,48	Can only assess direct effects since no inflammatory cells are present

Abbreviations: MI, myocardial infarction; CM, cardiomyocyte; LV, left ventricle; hiPSC-CMs, human induced pluripotent stem cell-derived cardiomyocytes; EHT, engineered heart tissue.