Early therapeutic experience with the endothelin antagonist BQ-123 in pulmonary hypertension after congenital heart surgery.

OBJECTIVE: To assess the effect of endothelin type A (ET(A)) receptor antagonism in infants with pulmonary hypertension following corrective surgery for congenital heart disease. DESIGN: Open label, preliminary study. SETTING: Tertiary paediatric cardiothoracic surgical centre. PATIENTS: Three infants (aged 3 weeks, 7 weeks, and 8 months) with postoperative pulmonary hypertension unresponsive to conventional treatment, including inhaled nitric oxide. INTERVENTIONS: Patients received incremental intravenous infusions (0.1 to 0.3 mg/kg/h) of the ET(A) receptor antagonist BQ-123. MAIN OUTCOME MEASURES: The response to BQ-123 administration was determined using continuous invasive monitoring of cardiorespiratory variables. RESULTS: BQ-123 infusion caused a reduction in the ratio of pulmonary to systemic pressures (0.62 (0.01) to 0.52 (0.03), mean (SEM)) with an accompanying decrease in right ventricular stroke work index (4.6 (0.4) to 2.5 (0.3) g/m) and a tendency for the cardiac index to rise (2.1 (0.2) to 2.7 (0.6) l/min/kg/m(2)). This was associated with a well tolerated fall in the arterial partial pressure of oxygen (16.5 (4.1) to 12.4 (3.3) kPa) and mean systemic arterial pressure (57 (3) to 39 (3) mm Hg). CONCLUSIONS: ET(A) receptor antagonism in infants with postoperative pulmonary hypertension after corrective surgery for congenital heart disease led to significant improvement in pulmonary haemodynamic indices. However, these benefits were associated with reductions in systemic blood pressure and arterial oxygen saturation, the latter consistent with a ventilation-perfusion mismatch. On the basis of these results, studies in pulmonary hypertension will need to proceed with caution.