Chronic Pulmonary Artery Embolization Models in Large Animals.

Area of Science:

• Cardiovascular Research
• Pulmonary Vascular Disease Modeling
• Preclinical Animal Studies

Background:

• Pulmonary vascular disease (PVD) and pulmonary hypertension (PH) exhibit significant clinical heterogeneity.
• Existing animal models for PH often fail to recapitulate specific disease phenotypes.
• Chronic thromboembolic pulmonary hypertension (CTEPH), a prevalent form of PH, requires a well-established large animal model for preclinical research.

Purpose of the Study:

• To describe a protocol for creating experimental CTEPH models in swine.
• To establish a standardized framework for characterizing PH models, focusing on hemodynamics, right ventricular (RV) function, and PVD histology.
• To facilitate the evaluation of novel diagnostic tools and therapeutic strategies for CTEPH.

Main Methods:

• Utilized recurrent pulmonary embolizations of dextran microspheres in swine.
• Employed non-surgical, fully percutaneous techniques for embolization.
• Administered a minimum of four embolization procedures over a 1-2 month period.

Main Results:

• Achieved mild to moderate PH hemodynamics (mean PA pressure increase of ~20-60%).
• Induced severe pulmonary vascular remodeling with mild right ventricular (RV) remodeling.
• Demonstrated high reproducibility and low mortality (<10%) in the model.

Conclusions:

• The described protocol provides a reproducible, non-surgical method for creating a large animal model of CTEPH in swine.
• This model effectively recapitulates key pathological features of CTEPH, including pulmonary vascular remodeling.
• The standardized framework supports the preclinical evaluation of diagnostic and therapeutic interventions for CTEPH.