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Eur J Cardiothorac Surg 1999;15:346-352
© 1999 Elsevier Science NL

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

^a Laboratoire de Chirurgie Experimentale, Faculte de Medecine de Nancy, Nancy, France
^b Pharma Division, Preclinical Research, F. Hoffmann-la Roche Ltd, CH-4002 Basel, Switzerland

Received 8 June 1998; received in revised form 21 December 1998; accepted 8 January 1999.

Corresponding author. Service de Chirurgie Cardiaque et de Transplantation Cardiothoracique, C.H.U. de Brabois, Rue du Morvan, 54511 Vandoeuvre les Nancy, France. Tel.: +33-383-153-034; fax: +33-383-440-844; e-mail: jp.carteaux@chu-nancy.fr

Background: 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. Methods: 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. Results: 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). Conclusions: 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.

Key Words: Acute pulmonary arterial hypertension • Cardiopulmonary bypass • Endothelin • Bosentan • Pig

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