Minimally Invasive Porcine Model for Chronic Thromboembolic Pulmonary Hypertension.

Area of Science:

• Cardiovascular Research
• Pulmonary Hypertension Research
• Animal Modeling

Background:

• Chronic thromboembolic pulmonary hypertension (CTEPH) involves complex pathophysiology and often requires invasive animal models.
• Current research methods conflict with animal welfare principles, necessitating refined experimental approaches.

Purpose of the Study:

• To develop a fully minimally invasive porcine model for chronic thromboembolic pulmonary hypertension (CTEPH).
• To adhere to the 3Rs principles (Replacement, Reduction, Refinement) in experimental animal research.

Main Methods:

• A minimally invasive technique was employed in five female large white pigs.
• An intravascular plug was inserted into the left pulmonary artery, followed by weekly embolization of the right lower lobe artery.
• Magnetic resonance imaging (MRI), plasma molecular analysis, and macroscopic/microscopic examinations were conducted.

Main Results:

• The minimally invasive procedure was successful, with no residual perfusion observed.
• Significant increases in mean pulmonary artery pressure (mPAP) and total pulmonary resistance (TPR) were recorded.
• Hemodynamic, morphological, and molecular changes consistent with CTEPH were observed, including elevated endothelin-1 and reduced nitric oxide metabolites.

Conclusions:

• This study successfully established a refined, fully minimally invasive porcine model for CTEPH.
• The model demonstrates key hemodynamic, morphological, and molecular features of CTEPH.
• This approach enhances experimental animal welfare while maintaining research validity.