title: Nitric oxide precursors and congenital heart surgery: a randomized controlled trial of oral citrulline.
abstract: OBJECTIVE
  The study sought to determine whether citrulline supplementation, a precursor to nitric oxide synthesis, is safe and efficacious in increasing plasma citrulline concentrations and decreasing the risk of postoperative pulmonary hypertension.
  
  
  METHODS
  Forty children, undergoing cardiopulmonary bypass and at risk for pulmonary hypertension, were randomized to receive 5 perioperative doses (1.9 g/m2 per dose) of either oral citrulline or placebo. Plasma citrulline and arginine concentrations were measured at 5 time points. Measurements of systemic blood pressure and presence of pulmonary hypertension were collected.
  
  
  RESULTS
  Median citrulline concentrations were significantly higher in the citrulline group versus the placebo group immediately postoperatively (36 micromol/L vs 26 micromol/L, P = .012) and at 12 hours postoperatively (37 micromol/L vs 20 micromol/L, P = .015). Mean plasma arginine concentrations were significantly higher in the citrulline group versus the placebo group by 12 hours postoperatively (36 micromol/L vs 23 micromol/L, P = .037). Mean systemic blood pressure did not differ between groups (P = .53). Postoperative pulmonary hypertension developed in 9 patients, 6 of 20 (30%) in the placebo group and 3 of 20 (15%) in the citrulline group (P = .451), all of whom had plasma citrulline concentrations less than age-specific norms. Postoperative pulmonary hypertension did not develop in patients who demonstrated plasma citrulline concentrations in excess of 37 mumol/L (P = .036).
  
  
  CONCLUSIONS
  Oral citrulline supplementation safely increased plasma citrulline and arginine concentrations compared with placebo after cardiopulmonary bypass. Postoperative pulmonary hypertension did not occur in children with naturally elevated citrulline levels or elevations through supplementation. Oral citrulline supplementation may be effective in reducing postoperative pulmonary hypertension.
authors.affiliation: Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tenn, USA. heidi.smith@vanderbilt.edu
authors.forename: Heidi A B
authors.initials: HA
authors.lastname: Smith
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Canter
authors.forename: Karla G
authors.initials: KG
authors.lastname: Christian
authors.forename: Davis C
authors.initials: DC
authors.lastname: Drinkwater
authors.forename: Frank G
authors.initials: FG
authors.lastname: Scholl
authors.forename: Brian W
authors.initials: BW
authors.lastname: Christman
authors.forename: Geraldine D
authors.initials: GD
authors.lastname: Rice
authors.forename: Frederick E
authors.initials: FE
authors.lastname: Barr
authors.forename: Marshall L
authors.initials: ML
authors.lastname: Summar
mesh_terms: D000284:Administration, Oral; D001120:Arginine / Q000097:blood; D001794:Blood Pressure; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D002675:Child, Preschool; D002956:Citrulline / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D018729:Fontan Procedure; D006801:Humans; D006976:Hypertension, Pulmonary / Q000517:prevention & control*; D007223:Infant; D008297:Male; D015999:Multivariate Analysis; D010865:Pilot Projects; D011183:Postoperative Complications / Q000517:prevention & control*
chemical_list: D002956:Citrulline; D001120:Arginine