Table 1.

Summary of experimental models of hypoxia in pulmonary hypertension

Model	Species	Methodology	Histopathology	Strengths	Weaknesses
Chronic hypoxia219–222	Rats, mice, Guinea pig, pig, sheep	Chronic exposure to hypoxia	Pulmonary vasoconstriction, muscularization of non-muscular arterioles, increased media thickness and matrix deposition	• Widely used • Simple	• Variable response to hypoxia
SU5416+Hypoxia223–225	Rats, mice	VEGFR-2 blockade coupled with chronic hypoxia	Development of PH with complex plexiform-like lesions	• Mimics human PAH	• Skill-specific • May not adequately model Group 3 PH • More costly
Fawn-hooded rats226, 227	Rats	Rat strain with deficient serotonin uptake into platelets	Rats have immature development of lungs, reduced number of alveoli, and development of PH	• May be useful to study specific pathways in PH	• Mimics limited features of PH • Cost
Broiler chicken228–233	Chicken	Pulmonary diffusion limitation leading to hypoxemia, possibly inherent mitochondrial dysfunction,	Right ventricular hypertrophy, perivascular leakage, vascular medial hypertrophy, perivascular inflammatory infiltration	• May be useful to study specific pathways in PH	• Mimics limited features of PH • Cost
Bleomycin234–236	Rats, mice, rabbits	Administration of bleomycin, commonly intratracheally	Bleomycin leads to pulmonary fibrosis development with increased lung inflammation and muscularization	• Useful to study PH in ILD • Simple • Relatively inexpensive	• Mimics only limited features of human PH
Term and preterm237–243	Mice, rats, rabbits, sheep, baboons	Varies depending on model but commonly preterm animals with mechanical ventilation. Hyperoxia and inflammation by bacterial LPS also used.	Alveolar simplification (rarefication) and loss of surfactant	• Useful to study PH in BPD	• Variability in lung and vascular injury dependent on species, age of animal, and mechanisms of injury • Heterogeneity of lung pathologies in human BPD is not accurately recapitulated in animals

SU5416 = Sugen 5416. VEGFR-2 = vascular endothelial growth factor receptor 2. PH = pulmonary hypertension. PAH = pulmonary arterial hypertension. ILD = interstitial lung disease. LPS = lipopolysaccharide. BPD = bronchopulmonary dysplasia. Adapted from Nogueira-Ferreira, et al. Cardiol and Cardiovasc Med²⁴⁴.