A pulmonary hypertension model induced by continuous pulmonary air embolization

Background: Our goal was to create a clinically relevant large animal model of pulmonary hypertension to serve as a platform allowing preclinical risk/benefit assessment of innovative therapies including artificial lung prototypes. Methods: Small amounts of filtered air were continuously infused into the pulmonary circulation of sheep (n = 4) for 8 wk. Hemodynamics and blood gases were measured daily. After termination of air embolization, the sheep were observed for 1 additional wk to assess the constancy of the pulmonary artery pressure changes. At the end of wk 9, all sheep were sacrificed and necropsy was performed. Results: All animals survived the study and developed pulmonary hypertension by wk 5. Mean pulmonary artery pressures were elevated from 14 ± 1 at baseline to 35 ± 1 mmHg at wk 8 (P < 0.01) and remained unchanged throughout wk 9. A similar increase in pulmonary vascular resistance was observed. Systemic arterial pressure and PaO₂ dropped slightly compared with baselines but remained in safe ranges. Histologic evidence of severe pulmonary arterial remodeling and significant right ventricle hypertrophy was observed. Conclusions: We conclude that our 8-wk model of continuous air embolization produces reliable, chronic pulmonary hypertension in sheep with sustained hemodynamic changes, significant pulmonary vascular remodeling, and right ventricle hypertrophy.