098 Régression of overcirculation-induced expérimental pulmonary arterial vasculopathy after surgical treatment

Abstract

Chronic thromboembolic pulmonary hypertension is due to partial obstruction of the pulmonary arterial bed. The disease can be cured by pulmonary thromboendarterectomy (PTE). Persistent pulmonary hypertension, the main postoperative complication, could be due to the development of a vasculopathy in the nonobstructed territory subjected to an overcirculation. The aim of this study is to analyze in piglets whether this induced vasculopathy could be reversed after suppression of the overcirculation. Pulmonary overcirculation was induced by a 5 weeks aorto-pulmonary shunt (n = 10), and reversibility of the vasculopathy was analyzed 5 weeks after closure of the shunt (n = 10). Thèse groups were compared to sham animais (n = 10). We studied hemo-dynamics, pulmonary artery vasoreactivity, morphometry, and quantified endothelin-1 (ET-1), ETA, ETB, eNOS and iNOS by Western blot and RT-PCR, and angiopoietin-1 and its receptor Tie2 by Western blot. Overcirculation resulted in an increase of the média thic-kness in the distal pulmonary arteries (55.6% + 1.2 vs 35.9% ± 0.8; p < 0.0001), a decrease of endothelium-dependant relaxation (51.9% ± 5.42 vs 66.8% + 6.6; p < 0.0001) and an over-expression of ET-1 (p < 0.01) and angiopoietin-1 (p = 0.049). After closure of the shunt, the média thickness decreased significantly (40.9% +1%) and the endothelium-dependant relaxation retumed to normal values (67.6% + 5.4). The level of expression of ET-1 and angiopoietin-1 also returned to normal values. In contrast, ETB increased significantly 5 weeks after closure of the shunt. Overcirculation vasculopathy induced by an aorto-pulmonary shunt regressed 5 weeks after closure of the shunt. Endothelin-1 and angiopoietin-1 may hâve a major rôle in the development of this vasculopathy. Hence, they may be important therapeutic targets to prevent the persistance of pulmonary hypertension after PTE.