Intravenous sildenafil lowers pulmonary vascular resistance in a model of neonatal pulmonary hypertension

Am J Respir Crit Care Med. 2002 Apr 15;165(8):1098-102. doi: 10.1164/ajrccm.165.8.2107097.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Animals
  • Hemodynamics / drug effects
  • Humans
  • Infant, Newborn
  • Infusions, Intravenous
  • Meconium Aspiration Syndrome / complications
  • Nitric Oxide / administration & dosage
  • Persistent Fetal Circulation Syndrome / drug therapy*
  • Persistent Fetal Circulation Syndrome / etiology
  • Persistent Fetal Circulation Syndrome / physiopathology
  • Phosphodiesterase Inhibitors / administration & dosage*
  • Piperazines / administration & dosage*
  • Pulmonary Circulation / drug effects*
  • Pulmonary Wedge Pressure / drug effects
  • Purines
  • Sildenafil Citrate
  • Sulfones
  • Swine
  • Vascular Resistance / drug effects*
  • Vasodilator Agents / administration & dosage


  • Phosphodiesterase Inhibitors
  • Piperazines
  • Purines
  • Sulfones
  • Vasodilator Agents
  • Nitric Oxide
  • Sildenafil Citrate