Introduction: There is a need for large animal models of pulmonary hypertension (PH) that allow application of new therapies in a translational setting.

Aims and objectives: To develop a simple large animal model of PH with right ventricular (RV) failure, mimicking chronic thromboembolic PH (CTEPH). Previous attempts have used short suture segments, microspheres and pharmacological interventions.

Methods: 2-month old pigs were used. Right heart catheterization (RHC) was performed, and  a sheath was advanced into the left or right PA and a pressure transducer was placed at its tip. Long silk sutures were injected into the selected PA, while continuously recording pressures. Embolization was stopped when mean PAP?40 mmHg, or occlusion of the selected branch. The procedure was repeated for 3 weeks,  with a 3-6 weeks follow-up. Echocardiographic and hemodynamic analysis was performed and samples were collected. 

Results: Embolization led to an increase in PA pressure, which was attenuated at re-intervention, but aggravated during follow-up. A significant portion of both right and left lower lobes were obstructed. RHC showed severe PH development (mPAP = 49 +/- 5 mmHg). Significant RV hypertrophy and failure (lower TAPSE and EF) were observed. Adverse remodelling markers (MYH7/MYH6, NPPB and TNFA) were up-regulated, while ATP2A2 was down-regulated. Isolated skinned RV cardiomyocyte analysis showed significantly increased passive stiffness. Vascular remodelling was observed in distal arteries of the right upper lung lobe subjected to high flow/high shear stress. 

Conclusions: We created a model of chronic PH by injecting long sutures into the pulmonary circulation, without the need for additional hits.