Intravenous sildenafil lowers pulmonary vascular resistance in a model of neonatal pulmonary hypertension.
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.
Shekerdemian
Lara S
LS
Department of Cardiac Intensive Care, Great Ormond Street Hospital, London, United Kingdom. shekel@cryptic.rch.unimelb.edu.au
Ravn
Hanne B
HB
Penny
Daniel J
DJ
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
D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D009569:Nitric Oxide; D000068677:Sildenafil Citrate