title: Intravenous sildenafil is a potent pulmonary vasodilator in children with congenital heart disease.
abstract: BACKGROUND
  Increased pulmonary vascular resistance (PVR) because of congenital heart disease (CHD) may be caused by a dysfunction in endogenous pulmonary endothelial nitric oxide (NO) production. In other forms of pulmonary vascular disease with increased PVR, an elevated activity of a phosphodiesterase type 5 (PDE-5), responsible for the degradation of cyclic guanidine monophosphate (cGMP), the second messenger of endothelially produced NO, has been demonstrated. This study compares the effects of inhaled NO before and after the specific inhibition of the PDE-5 by intravenous sildenafil (Viagra) in pre- and postoperative children with increased PVR because of CHD.
  
  
  RESULTS
  12 children with congenital heart disease (age 0.2 to 15.7 years, median 2.4 years) and increased mean pulmonary arterial pressure, and 12 postoperative children (age 0.11 to 0.65 years, median 0.32 years) with increased PVR (8.3+/-1.0 Wood Units*m2) were studied during cardiac catheterization ("cath laboratory"), or within 2 hours after return from cardiac surgery ("post op"), respectively. All were sedated, tracheally intubated and paralyzed. During alveolar hyperoxygenation (FiO2=0.65), the effects of inhaled NO (20 ppm) were compared before and after the stepwise infusion of sildenafil ("cath laboratory", 1 mg/kg; post op, 0.25 mg/kg). Intravenous sildenafil more effectively reduced PVR than NO (11.5% versus 4.3% in the "cath laboratory" patient group, P<0.05, and 25.8% versus 14.6% in the post op patient group, P=0.09. The increase in cGMP in response to NO was potentiated (2- to 2.4-fold) by PDE-5 inhibition. While the vasodilating effects of sildenafil showed pulmonary selectivity, its infusion was associated with increased intrapulmonary shunting in the postoperative patients (Qs/Qt=16.5+/-4.7% to 25.5+/-18.2% P=0.04).
  
  
  CONCLUSIONS
  Intravenous sildenafil is as effective as inhaled NO as a pulmonary vasodilator in children with congenital heart disease. Although clinically insignificant in this study, increased intrapulmonary shunting with sildenafil may be disadvantageous in some patients after CHD surgery.
authors.affiliation: Abteilung für Angeborene Herzfehler, Deutsches Herzzentrum Berlin, Berlin, Germany.
authors.forename: Ingram
authors.initials: I
authors.lastname: Schulze-Neick
authors.forename: Paulina
authors.initials: P
authors.lastname: Hartenstein
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.forename: Brigitte
authors.initials: B
authors.lastname: Stiller
authors.forename: Nicole
authors.initials: N
authors.lastname: Nagdyman
authors.forename: Michael
authors.initials: M
authors.lastname: Hübler
authors.forename: Ghazwan
authors.initials: G
authors.lastname: Butrous
authors.forename: Andy
authors.initials: A
authors.lastname: Petros
authors.forename: Peter
authors.initials: P
authors.lastname: Lange
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Redington
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000280:Administration, Inhalation; D000293:Adolescent; D001794:Blood Pressure / Q000187:drug effects; D006328:Cardiac Catheterization; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D006152:Cyclic GMP / Q000097:blood; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D006330:Heart Defects, Congenital / Q000188:drug therapy / Q000503:physiopathology* / Q000601:surgery; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007223:Infant; D007262:Infusions, Intravenous; D009569:Nitric Oxide / Q000008:administration & dosage / Q000627:therapeutic use; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D010879:Piperazines / Q000008:administration & dosage / Q000627:therapeutic use*; D011184:Postoperative Period; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology; D011652:Pulmonary Circulation / Q000187:drug effects*; D011687:Purines; D000068677:Sildenafil Citrate; D013450:Sulfones; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D009569:Nitric Oxide; D000068677:Sildenafil Citrate; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517381:PDE5A protein, human; D006152:Cyclic GMP