Table 2.

Animal Models of PH-LHD

Model	Species	Strengths	Limitations
Metabolic Models
Metabolic Syndrome (ZSF1 model) + SU5416/hypoxia	Rat65	Includes metabolic syndrome in phenotype	High Cost Limited molecular tools compared to mice Complicated phenotype
Metabolic Syndrome (ZSF1 model) + Aortic Banding	Rat74	Combined pressure and metabolic injury	High cost Primarily mild PH Complicated phenotype
High fat diet/Obesity	Mouse66 Bovine75	Low cost Metabolic syndrome phenotype	Longer timeline needed Variation in PH-HFpEF phenotype based on mouse strain used
High fat diet + L-NAME (or db/db model) + SU5416/hypoxia	Mouse	Low cost Metabolic syndrome phenotype with added pulmonary vascular disease	Needs to be further studied and validated as a PH-HFpEF phenotype
Mechanical Obstructive/Pressure Overload Models
Aortic Banding	Mouse68 Rat76–78 Feline79	Simple Reproducible Low cost	Does not induce severe PH and RV failure Most synonymous with Aortic stenosis induced-PH, less with non-valvular HFpEF
Transverse Aortic Constriction	Mouse 69, 80	Simple Reproducible	Associated pulmonary fibrosis Most synonymous with Aortic stenosis induced-PH, less with non-valvular HFpEF
Pulmonary vein banding	Porcine70 Bovine81	Represents pulmonary venous hypertension	Higher cost Multiple operators Large animal Not representative of underlying LV disease
Left atrial stenosis	Rat71, 72	Simulates mitral stenosis	Not representative of underlying LV disease Difficult surgical intervention
Ischemic Models
Left coronary artery ligation	Rat73, 82, 84, 100 Mouse85, 86 Porcine83	Primary HFrEF model	Not representative of non-ischemic cardiomyopathy Minimal control of infarct size Low survival