title: Early therapeutic experience with the endothelin antagonist BQ-123 in pulmonary hypertension after congenital heart surgery.
abstract: 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.
  
  
  METHODS
  Open label, preliminary study.
  
  
  METHODS
  Tertiary paediatric cardiothoracic surgical centre.
  
  
  METHODS
  Three infants (aged 3 weeks, 7 weeks, and 8 months) with postoperative pulmonary hypertension unresponsive to conventional treatment, including inhaled nitric oxide.
  
  
  METHODS
  Patients received incremental intravenous infusions (0.1 to 0.3 mg/kg/h) of the ET(A) receptor antagonist BQ-123.
  
  
  METHODS
  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.
authors.affiliation: Department of Cardiac Surgery, Royal Hospital for Sick Children, Sciennes Road, Edinburgh EH9 1LF, UK.
authors.forename: B
authors.initials: B
authors.lastname: Prendergast
authors.forename: D E
authors.initials: DE
authors.lastname: Newby
authors.forename: L E
authors.initials: LE
authors.lastname: Wilson
authors.forename: D J
authors.initials: DJ
authors.lastname: Webb
authors.forename: P S
authors.initials: PS
authors.lastname: Mankad
mesh_terms: D065128:Endothelin Receptor Antagonists; D005260:Female; D006330:Heart Defects, Congenital / Q000097:blood / Q000503:physiopathology / Q000601:surgery*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010100:Oxygen / Q000097:blood; D010456:Peptides, Cyclic / Q000627:therapeutic use*; D011183:Postoperative Complications / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D018709:Statistics, Nonparametric; D013318:Stroke Volume / Q000187:drug effects
chemical_list: D065128:Endothelin Receptor Antagonists; D010456:Peptides, Cyclic; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D010100:Oxygen