Acute pulmonary hypertension after cardiopulmonary bypass in pig: the roleof endogenous endothelin

Background: Acute pulmonary hypertension occurring after cardiopulmonary by pass can be a cause of post-operative morbidity and mortality. The purpose of this study was to investigate whether bosentan, a non-peptidic mixed end othelin antagonist affected the pulmonary hypertension induced by experimen tal cardiopulmonary bypass. Methods: Pigs were anesthetized and instrumente d to determine hemodynamic measurements. Pigs were randomized to receive ei ther 3 mg/kg bolus + 7 mg/kg per h bosentan (n = 8) or saline (n = 7). All pigs underwent 90 min of cardiopulmonary bypass and were further observed f or a 120-min period. Results: In the control group, cardiopulmonary bypass induced a dramatic pulmonary hypertension (+78 +/- 13%, P < 0.005) and acco mpanied an increase of pulmonary vascular resistance (+228 +/- 50%, P < 0.0 05), whereas, in the treated group, bosentan completely prevented these del eterious effects of cardiopulmonary bypass with only a moderate decrease of systemic vascular resistance (-19 +/- 14.68, P < 0.05). Conclusions: The p resent findings supper? the hypothesis that endogenous endothelin is a medi ator of acute pulmonary hypertension occurring after cardiopulmonary bypass . Bosentan, a mixed endothelin antagonist completely prevented pulmonary hy pertension after cardiopulmonary bypass and may, therefore, have therapeuti c applications in the management of patients following cardiac surgery. (C) 1999 Elsevier Science B.V. All rights reserved.