title: Intravenous sildenafil lowers pulmonary vascular resistance in a model of neonatal pulmonary hypertension.
abstract: Persistent pulmonary hypertension secondary to meconium aspiration syndrome is an important cause of morbidity and mortality in the neonatal population. We investigated the use of the phosphodiesterase-5 inhibitor sildenafil, in its intravenous form, as a pulmonary vasodilator in a model of meconium aspiration syndrome. Pulmonary hypertension was induced in 18 piglets, by endotracheal instillation of human meconium, 6 piglets subsequently received an infusion of intravenous sildenafil for 2 hours, 6 received inhaled nitric oxide for 2 hours, and 6 control animals received no additional intervention. Meconium aspiration increased pulmonary vascular resistance by 70%, and increased oxygenation index by over 100%. Pulmonary vascular resistance remained elevated for the remainder of the study period in control animals. Inhaled nitric oxide reduced the pulmonary vascular resistance by 40% after 2 hours of treatment; intravenous sildenafil completely reversed the increase in pulmonary vascular resistance within 1 hour of commencing the infusion. Neither agent had an effect on systemic hemodynamics. Sildenafil also increased cardiac output by 30%, but while doing so did not adversely influence oxygenation. Intravenous sildenafil is a selective and highly effective pulmonary vasodilator, which is at least as effective as inhaled nitric oxide, in this model of neonatal persistent pulmonary hypertension.
authors.affiliation: Department of Cardiac Intensive Care, Great Ormond Street Hospital, London, United Kingdom. shekel@cryptic.rch.unimelb.edu.au
authors.forename: Lara S
authors.initials: LS
authors.lastname: Shekerdemian
authors.forename: Hanne B
authors.initials: HB
authors.lastname: Ravn
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Penny
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007231:Infant, Newborn; D007262:Infusions, Intravenous; D008471:Meconium Aspiration Syndrome / Q000150:complications; D009569:Nitric Oxide / Q000008:administration & dosage; D010547:Persistent Fetal Circulation Syndrome / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage*; D010879:Piperazines / Q000008:administration & dosage*; D011652:Pulmonary Circulation / Q000187:drug effects*; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D011687:Purines; D000068677:Sildenafil Citrate; D013450:Sulfones; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage
chemical_list: D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D009569:Nitric Oxide; D000068677:Sildenafil Citrate