Endothelin receptor blockade prevents the rise in pulmonary vascular resistance after cardiopulmonary bypass in lambs with increased pulmonary blood flow

Background: Children,vith increased pulmonary blood flow may experience mor bidity as the result of increased pulmonary vascular resistance after opera tions in which cardiopulmonary bypass is used. Plasma levels of endothelin- 1, a potent vasoactive substance implicated in pulmonary hypertension, are increased after cardiopulmonary bypass. Objectives: In a lamb model of incr eased pulmonary blood flow after in utero placement of an aortopulmonary sh unt, we characterized the changes in pulmonary vascular resistance induced by hypothermic cardiopulmonary bypass and investigated the role of endothel in-l and endothelin-a receptor activation in postbypass pulmonary hypertens ion. Methods: Tn eleven 1-month-old lambs, the shunt was closed, and vascul ar pressures and blood flows were monitored. An infusion of a selective end othelin-A receptor blocker (PD 156707; 1.0 mg/kg/h) or drug vehicle (saline solution) was then begun 30 minutes before cardiopulmonary bypass and cont inued for 4 hours after bypass. The hemodynamic variables were monitored, a nd plasma endothelin-1 concentrations were determined before, during, and f or 6 hours after cardiopulmonary bypass. Results: After 90 minutes of hypot hermic cardiopulmonary bypass, both pulmonary arterial pressure and pulmona ry vascular resistance increased significantly in saline-treated lambs duri ng the 6-hour study period (P <.05), In lambs pretreated with PD 156707, pu lmonary arterial pressure and pulmonary vascular resistance decreased (P <. 05) After bypass, plasma endothelin-1 concentrations increased in all lambs : there was a positive correlation between postbypass pulmonary vascular re sistance and plasma endothelin-1 concentrations (P <.05), Conclusions: This study suggests that endothelin-A receptor-induced pulmonary vasoconstricti on mediates, in part, the rise in pulmonary vascular resistance after cardi opulmonary bypass. Endothelin-A receptor antagonists may decrease morbidity in children at risk for postbypass pulmonary hypertension. This potential therapy warrants further investigation.