title: Beneficial effect of oral sildenafil therapy on childhood pulmonary arterial hypertension: twelve-month clinical trial of a single-drug, open-label, pilot study.
abstract: BACKGROUND
  Pulmonary arterial hypertension (PAH) is a progressive and fatal disease. Sildenafil is a type 5 phosphodiesterase inhibitor and pulmonary vasodilator. Therefore, we hypothesized that sildenafil would improve distance walked in 6 minutes and hemodynamics in children with PAH.
  
  
  RESULTS
  After baseline assessment of hemodynamics by cardiac catheterization and distance walked in 6 minutes, we administered oral sildenafil at 0.25 to 1 mg/kg 4 times daily to 14 children (median age, 9.8 years; range, 5.3 to 18). Diagnoses were primary (n=4) and secondary (n=10) PAH. We repeated the 6-minute walk test at 6 weeks and at 3, 6, and 12 months (n=14) and cardiac catheterization (n=9) after a median follow-up of 10.8 months (range, 6 to 15.3). During sildenafil therapy, the mean distance walked in 6 minutes increased from 278+/-114 to 443+/-107 m over 6 months (P=0.02), and at 12 months, the distance walked was 432+/-156 m (P=0.005). A plateau was reached between 6 and 12 months (P=0.48). Mean pulmonary artery pressure decreased from a median of 60 mm Hg (range, 50 to 105) to 50 mm Hg (range, 38 to 84) mm Hg (P=0.014). Median pulmonary vascular resistance decreased from 15 Wood units m2 (range, 9 to 42) to 12 Wood Units m2 (range, 5 to 29) (P=0.024).
  
  
  CONCLUSIONS
  Oral sildenafil has the potential to improve hemodynamics and exercise capacity for up to 12 months in children with PAH. Confirmation of these results in a randomized, controlled trial is essential.
authors.affiliation: Department of Critical Care Medicine, Hospital for Sick Children and University of Toronto Medical School, Toronto, Canada.
authors.forename: Tilman
authors.initials: T
authors.lastname: Humpl
authors.forename: Janette T
authors.initials: JT
authors.lastname: Reyes
authors.forename: Helen
authors.initials: H
authors.lastname: Holtby
authors.forename: Derek
authors.initials: D
authors.lastname: Stephens
authors.forename: Ian
authors.initials: I
authors.lastname: Adatia
mesh_terms: D000293:Adolescent; D001794:Blood Pressure; D002648:Child; D002675:Child, Preschool; D005080:Exercise Test; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D010865:Pilot Projects; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D011651:Pulmonary Artery / Q000503:physiopathology; D011687:Purines; D000068677:Sildenafil Citrate; D013450:Sulfones; D016896:Treatment Outcome; D014655:Vascular Resistance; D014665:Vasodilator Agents; D016138:Walking
chemical_list: D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate