A pulmonary hypertension model induced by continuous pulmonary air embolization

Area of Science:

• Cardiovascular Research
• Pulmonary Medicine
• Animal Modeling

Background:

• Developing clinically relevant animal models is crucial for assessing novel therapies.
• Pulmonary hypertension (PH) requires robust preclinical models for risk/benefit analysis.
• Artificial lung prototypes necessitate a suitable platform for evaluation.

Purpose of the Study:

• To establish a large animal model of chronic pulmonary hypertension.
• To create a platform for preclinical evaluation of innovative therapies for PH.
• To assess the risk and benefits of new treatments, including artificial lungs.

Main Methods:

• Continuous infusion of small amounts of filtered air into the pulmonary circulation of sheep (n=4) over 8 weeks.
• Daily monitoring of hemodynamics and blood gases.
• Post-embolization observation for 1 week and necropsy at 9 weeks.

Main Results:

• All sheep survived and developed pulmonary hypertension by week 5.
• Mean pulmonary artery pressure increased significantly (14±1 to 35±1 mmHg) and remained elevated.
• Histological analysis revealed pulmonary arterial remodeling and right ventricle hypertrophy.

Conclusions:

• Continuous air embolization reliably induces chronic pulmonary hypertension in sheep.
• The model demonstrates sustained hemodynamic changes, pulmonary vascular remodeling, and right ventricle hypertrophy.
• This sheep model serves as a valuable platform for preclinical assessment of pulmonary hypertension therapies.