title: Dypiridamole, a cGMP phosphodiesterase inhibitor, transiently improves the response to inhaled nitric oxide in two newborns with congenital diaphragmatic hernia.
abstract: BACKGROUND
  Congenital diaphragmatic hernia (CDH) remains a frustrating cause of respiratory failure associated with persistent pulmonary hypertension of the newborn (PPHN). Although inhaled nitric oxide (iNO) is effective in many infants with PPHN, it often fails to improve oxygenation in infants with CDH. As the increase in vascular smooth muscle cyclic guanosine monophosphate (cGMP) in response to iNO may be impeded by increased phosphodiesterase type-V (PDE-V) activity, it has been suggested that PDE-V blockade potentiates the efficiency of iNO.
  
  
  METHODS
  We used dypiridamole (Persantine), a specific PDE-V inhibitor, in two patients with CDH. Prenatal diagnosis showed a left-sided CDH at 23 weeks of gestation (GA) with intrathoracic stomach and left heart underdevelopment in the one infant and a right-sided CDH at 26 weeks GA with intrathoracic liver in the other. After antenatal corticoids, planned delivery was performed by the vaginal route at 38 weeks GA. Preoperative stabilization was achieved by high frequency oscillation, iNO and inotropic support over 24 h. Both had early pneumothorax drained by a chest tube. Despite optimization of ventilatory and hemodynamic support with surfactant replacement, iNO and adrenaline, oxygenation worsened progressively. Dypiridamole was introduced intravenously at 27 and 40 h, respectively, and improved oxygenation over the next 12 h. However, oxygenation again deteriorated and both patients died.
  
  
  CONCLUSIONS
  Dypiridamole enhanced the response to iNO in PPHN associated with CDH, although this effect was transient. Combined therapy of iNO with PDE-V inhibitors may improve pulmonary vasodilation in some forms of PPHN which do not respond to iNO, thereby reducing the need for extracorporeal membrane oxygenation (ECMO) and improving outcome.
authors.affiliation: Service de Pédiatrie-Réanimation, Hôpital Robert Debré, Université Paris VII - Faculté de Médecine Xavier-Bichat, Paris, France. bthebaud@club-internet.fr
authors.forename: B
authors.initials: B
authors.lastname: Thébaud
authors.forename: C
authors.initials: C
authors.lastname: Saizou
authors.forename: C
authors.initials: C
authors.lastname: Farnoux
authors.forename: J F
authors.initials: JF
authors.lastname: Hartman
authors.forename: J C
authors.initials: JC
authors.lastname: Mercier
mesh_terms: D000280:Administration, Inhalation; D004176:Dipyridamole / Q000494:pharmacology*; D017809:Fatal Outcome; D006548:Hernia, Diaphragmatic / Q000628:therapy*; D065630:Hernias, Diaphragmatic, Congenital; D006801:Humans; D007231:Infant, Newborn; D009569:Nitric Oxide / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010100:Oxygen / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D010726:Phosphodiesterase Inhibitors; D014665:Vasodilator Agents; D009569:Nitric Oxide; D004176:Dipyridamole; D010100:Oxygen