Table 2.
Commonly Used Animal Models of Right Ventricular Failure
| Monocrotaline | Hypoxia | Sugen/Hypoxia | PA Banding | |
|---|---|---|---|---|
| Method | Subcutaneous injection of alkaloid monocrotaline (40–60 mg/kg; lower dose results in milder phenotype) | Exposure to FiO2 10% (or 0.5 atmospheric pressure) for 3–5 wk | Subcutaneous injection of VEGFR2 antagonist Su5416 + hypoxia (3 wk) + room air (≥4 wk) | Suture or clip around main PA |
| RVSP, mm Hg | 40–60 | 30–40 | 60–80 | 60–80 |
| Cardiac output | Depressed | Maintained or slightly depressed | Severely depressed | Maintained or depressed (depending on tightness of band and duration of banding) |
| RV histology | Fibrosis, cardiomyocyte hypertrophy, possibly biventricular myocarditis (conflicting data on the latter) | Fibrosis (less than other models), cardiomyocyte hypertrophy | Fibrosis, cardiomyocyte hypertrophy, apoptosis | Fibrosis, cardiomyocyte hypertrophy |
| RV vascular effects | Vascular inflammation, decreased capillary density | Capillary proliferation | No angiogenesis, decreased capillary volume and density | Capillary volume and density maintained or slightly decreased |
| Type of RV remodeling | Maladaptive | Adaptive | Maladaptive | Adaptive or maladaptive (depending on tightness of band and duration of banding) |
| Pulmonary vascular effects | Yes | Yes | Yes | No |
| Systemic effects | Yes | Yes | Yes | No |
| Sex of animal tied to experimental phenotype | Yes (less PH in females) | Yes (less PH in females) | Yes (better RV function in females) | Yes (better RV function in females) |
| What is being modeled? | Inflammatory PAH and RV dysfunction | Chronic hypoxia, high altitude, some aspects of chronic lung disease | Pulmonary vascular endothelial cell injury with uncontrolled proliferation of remaining cells | RV afterload increase without pulmonary vascular injury |
| Modifications of model | Combination with pneumonectomy or aortocaval shunting to result in pulmonary vascular overflow and more pronounced remodeling | Extension of room air exposure associated with progressive pulmonary vascular remodeling and afterload increase |
Definition of abbreviations: PA = pulmonary artery; PAH = pulmonary arterial hypertension; PH = pulmonary hypertension; RV = right ventricle; RVSP = right ventricular systolic pressure; VEGFR2 = vascular endothelial growth factor receptor 2.