Piglet model of chronic thromboembolic pulmonary hypertension

Objectives. Chronic thrombo-embolic pulmonary hypertension (CTEPH) is a fatal disease due to a partial obstruction of the pulmonary arterial bed by unresolved and organized clots associated with a vasculopathy in the non-obstructed pulmonary territories leading to an increase of pulmonary vascular resistances. As a consequence, right ventricle (RV) dysfunction develops progressively. So far, no animal model accurately reproduces all the aspects of this disease. The aim of this study was to develop a reliable animal model of CTEPH.Methods. CTEPH was induced in piglet by ligation of the left pulmonary artery (PA) through a midline sternotomy followed by a weekly embolization of the right lower lobe arteries by tissue adhesive under fluoroscopic control for 5 weeks. This CTEPH group (n=5) was compared to Sham operated animals (n=5). Hemodynamics, right ventricle function on echocardiography and lung morphometry were assessed at 5 weeks.Results. Compared to sham, CTEPH animals had increased mean PA pressure (28.5±1.7 mmHg vs. 11.6±1.8 mmHg, p=0.0001) and pulmonary resistances (9.8±2 WU vs. 5.5±1 WU, p=0.05). On echocardiography, they had enlarged right ventricle, increased right ventricle wall thickness (56±5 mm vs. 30±4 mm, p=0.0003), decreased TAPSE (11.3±0.9 mm vs. 14.4±0.4 mm, p=0.01) and a paradoxical septal motion. Morphometric studies demonstrated in the obstructed territories an increase of the number of bronchial arteries per bronchus (8.7±0.9 vs. 2±0.17 p<0.0001) and of distal PA media thickness (60 %±2.8 vs. 29 %±0.9 p<0.0001) consistent with a postobstructive vasculopathy. In the non-obstructed territories, an increase of distal PA media thickness was found (70 %±2.4 vs. 29 %±0.9, p<0.0001). Conclusions. For the first time, we developed a reliable piglet model of CTEPH reproducing all the aspects of this disease : increased mean PA pressure and pulmonary resistances, increased bronchial circulation, pulmonary vasculopathy and RV dysfunction.