%0 Journal Article %A Laurence Dewachter %A Benoit Rondelet %A Celine Dewachter %A Francois Kerbaul %A Xin Kang %A Pierre Fesler %A Serge Brimioulle %A Robert Naeije %T Prolonged overcirculation-induced pulmonary arterial hypertension, as a cause of right ventricular failure %D 2011 %J European Respiratory Journal %P 3432 %V 38 %N Suppl 55 %X Three-month chronic systemic-to-pulmonary shunting in piglets has been reported as an early pulmonary arterial hypertension (PAH) model with preserved right ventricular (RV) function. We hypothesized that prolonged shunting would induce severe PAH and RV failure. Fourteen piglets were randomized to a sham operation or the anastomosis of the left innominate artery to pulmonary arterial trunk. Six months later, animals underwent hemodynamic evaluation followed by tissue sampling for pathobiological assessment. Prolonged shunting resulted in increased pulmonary vascular resistance and pulmonary arteriolar medial thickness, while cardiac output was decreased. The ratio of end-systolic to arterial elastances (Ees/Ea) decreased from 1.4±0.1 to 0.7±0.1, suggesting a RV failure. At RV tissue level, pro-apoptotic Bax/Bcl2 ratio and caspase-3 activation were upregulated, with an inverse correlation between RV Ees/Ea and pro-apoptotic Bax/Bcl-2 ratio.In the failing RV, IL-1α, IL-1β and TNF-α expressions were locally increased, along with increased circulating levels of TNF-α. RV capillary densities were similar between the 2 groups, while gene expressions of VEGF and angiopoietin-2 were decreased in the failing RV tissue. Prolonged left-to-right shunting in piglets does not further aggravate PAH, but is a cause of RV failure, which appears related to an activation of apoptosis, hypertrophy and inflammation. %U