title: Ibuprofen-induced patent ductus arteriosus closure: physiologic, histologic, and biochemical effects on the premature lung.
abstract: OBJECTIVE
  The goal was to study the pulmonary, biochemical, and morphologic effects of a persistent patent ductus arteriosus in a preterm baboon model of bronchopulmonary dysplasia.
  
  
  METHODS
  Preterm baboons (treated prenatally with glucocorticoids) were delivered at 125 days of gestation (term: 185 days), given surfactant, and ventilated for 14 days. Twenty-four hours after birth, newborns were randomly assigned to receive either ibuprofen (to close the patent ductus arteriosus; n = 8) or no drug (control; n = 13).
  
  
  RESULTS
  After treatment was started, the ibuprofen group had significantly lower pulmonary/systemic flow ratio, higher systemic blood pressure, and lower left ventricular end diastolic diameter, compared with the control group. There were no differences in cardiac performance indices between the groups. Ventilation index and dynamic compliance were significantly improved with ibuprofen. The improved pulmonary mechanics in ibuprofen-treated newborns were not attributable to changes in levels of surfactant protein B, C, or D, saturated phosphatidylcholine, or surfactant inhibitory proteins. There were no differences in tracheal concentrations of cytokines commonly associated with the development of bronchopulmonary dysplasia. The groups had similar messenger RNA expression of genes that regulate inflammation and remodeling in the lung. Lungs from ibuprofen-treated newborns were significantly drier (lower wet/dry ratio) and expressed 2.5 times more epithelial sodium channel protein than did control lungs. By 14 days after delivery, control newborns had morphologic features of arrested alveolar development (decreased alveolar surface area and complexity), compared with age-matched fetuses. In contrast, there was no evidence of alveolar arrest in the ibuprofen-treated newborns.
  
  
  CONCLUSIONS
  Ibuprofen-induced patent ductus arteriosus closure improved pulmonary mechanics, decreased total lung water, increased epithelial sodium channel expression, and decreased the detrimental effects of preterm birth on alveolarization.
authors.affiliation: Department of Pediatrics, University of Texas Health Science Center, San Antonio, Texas, USA.
authors.forename: Donald
authors.initials: D
authors.lastname: McCurnin
authors.forename: Steven
authors.initials: S
authors.lastname: Seidner
authors.forename: Ling-Yi
authors.initials: LY
authors.lastname: Chang
authors.forename: Nahid
authors.initials: N
authors.lastname: Waleh
authors.forename: Machiko
authors.initials: M
authors.lastname: Ikegami
authors.forename: Jean
authors.initials: J
authors.lastname: Petershack
authors.forename: Brad
authors.initials: B
authors.lastname: Yoder
authors.forename: Luis
authors.initials: L
authors.lastname: Giavedoni
authors.forename: Kurt H
authors.initials: KH
authors.lastname: Albertine
authors.forename: Mar Janna
authors.initials: MJ
authors.lastname: Dahl
authors.forename: Zheng-ming
authors.initials: ZM
authors.lastname: Wang
authors.forename: Ronald I
authors.initials: RI
authors.lastname: Clyman
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004374:Ductus Arteriosus, Patent / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D053503:Epithelial Sodium Channels / Q000378:metabolism; D015633:Extravascular Lung Water / Q000378:metabolism; D005260:Female; D005325:Fetal Organ Maturity / Q000187:drug effects; D006439:Hemodynamics; D007052:Ibuprofen / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000033:anatomy & histology / Q000187:drug effects* / Q000196:embryology / Q000502:physiology; D008297:Male; D048531:Papio papio; D010713:Phosphatidylcholines / Q000378:metabolism; D037661:Pulmonary Surfactant-Associated Proteins / Q000378:metabolism; D012119:Respiration
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D053503:Epithelial Sodium Channels; D018836:Inflammation Mediators; D010713:Phosphatidylcholines; D037661:Pulmonary Surfactant-Associated Proteins; D007052:Ibuprofen