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

Acute pulmonary hypertension occurring after cardiopulmonary bypass can be a cause of post-operative morbidity and mortality. The purpose of this study was to investigate whether bosentan, a non-peptidic mixed endothelin antagonist affected the pulmonary hypertension induced by experimental cardiopulmonary bypass.Pigs were anesthetized and instrumented to determine hemodynamic measurements. Pigs were randomized to receive either 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 for a 120-min period.In the control group, cardiopulmonary bypass induced a dramatic pulmonary hypertension (+78 +/- 13%, P < 0.005) and accompanied an increase of pulmonary vascular resistance (+228 +/- 50%, P < 0.005), whereas, in the treated group, bosentan completely prevented these deleterious effects of cardiopulmonary bypass with only a moderate decrease of systemic vascular resistance (-19 +/- 14.6%, P < 0.05).The present findings support the hypothesis that endogenous endothelin is a mediator of acute pulmonary hypertension occurring after cardiopulmonary bypass. Bosentan, a mixed endothelin antagonist completely prevented pulmonary hypertension after cardiopulmonary bypass and may, therefore, have therapeutic applications in the management of patients following cardiac surgery.