Monocrotaline-Induced PAH Model | Rat Pulmonary Hypertension

Monocrotaline (MCT)-Induced PAH Rat Model

The monocrotaline-induced PAH rat model is a well-established preclinical model of pulmonary vascular injury, pulmonary hypertension, and right ventricular pressure overload.

Following a single MCT administration, rats develop increased pulmonary arterial pressure, vascular remodeling, right ventricular hypertrophy, and functional cardiopulmonary impairment within approximately 3–4 weeks.

IPS Therapeutique uses this model to evaluate PAH-directed therapies, including vasodilators, anti-remodeling agents, anti-inflammatory compounds, and disease-modifying candidates.

MCT-Induced PAH - Methodology

Model design

Species: rat
Induction: single monocrotaline administration
Disease development: approximately 28 days
Treatment design: preventive or therapeutic
Optional comparison with standard-of-care reference compounds

Disease features

Pulmonary vascular injury
Increased pulmonary arterial pressure
Right ventricular pressure overload
Right ventricular hypertrophy
Pulmonary vascular remodeling

Design considerations

Robust and widely used PAH model
Useful for early efficacy screening
Less occlusive vascular remodeling than SuHx PAH
Best interpreted using integrated hemodynamic, echocardiographic, and histological endpoints

MCT-Induced PAH - Readouts & Application

Hemodynamic readouts

Pulmonary arterial pressure
Systemic arterial pressure
Pulse pressure
Pulmonary vascular resistance, or PVR
Heart rate
Oxygen saturation, or SpO₂

Right-heart and echocardiographic readouts

Right ventricular hypertrophy
Right ventricular structure and function
Stroke volume
Cardiac output
PAAT and pulmonary flow parameters

Histological readouts

Pulmonary vascular remodeling
Medial wall thickening
Muscularization of small pulmonary arteries
Right ventricular remodeling
Fulton index, when applicable

Drug development applications

PAH efficacy testing
Dose-response studies
Vasodilator evaluation
Anti-remodeling therapy assessment
Mechanism-of-action support
Candidate selection before more severe PAH models

Interpretation note

The MCT model is a practical and reproducible PAH model, but it should not be treated as a full reproduction of advanced human PAH. Its strongest value is in well-controlled efficacy screening with integrated cardiovascular, pulmonary, and histological endpoints.