A pulmonary hypertension model induced by continuous pulmonary air embolization.

Abstract

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 &#xb1; 1 at baseline to 35 &#xb1; 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 PaO(2) 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.