title: Doppler parameters of fetal lung hypoplasia and impact of sildenafil.
abstract: OBJECTIVE
  Congenital diaphragmatic hernia (CDH) is clinically challenging because of associated lung hypoplasia (LH). There have been no validated parameters to evaluate fetal LH severity. Sildenafil has been shown to improve LH mass in nitrofen-induced pulmonary artery (PA) models, but the pulmonary vascular tone has not been evaluated in vivo. The aim of this study was to identify the PA Doppler parameter that best predicts LH severity and to investigate the efficacy of antenatal sildenafil treatment in experimental CDH.
  
  
  METHODS
  Nitrofen (50-60% CDH in offspring) or vehicle on E9.5 and sildenafil or vehicle on E11.5-20.5 were administrated to pregnant rats. On E20.5, PA Doppler indices were investigated with and without maternal hyperoxia. The presence/absence of CDH, lung/body weight ratio and radial saccular count were assessed at E20.5.
  
  
  RESULTS
  At baseline, CDH rats had lower PA Doppler acceleration/ejection time ratios and pulsatility index (PI). Maternal hyperoxia resulted in a significant decrease in the PA/PI suggesting pulmonary vasodilation. In contrast, in CDH fetuses, the ipsilateral PA/PI showed little or no response to hyperoxia (P > .05), and in those with LH, PI response to maternal hyperoxia correlated positively with hernia, lung/body weight ratio (r = 0.70, P = .01). Maternal sildenafil therapy significantly improved PA response to hyperoxia and lung growth in CDH fetuses (P < .01).
  
  
  CONCLUSIONS
  Pulmonary vasodilation that occurs in E20.5 fetal rats in response to maternal hyperoxia is blunted in CDH. Change in PA/PI with hyperoxia is a useful predictor of LH severity. Sildenafil improves pulmonary vascular response and lung growth in fetal CDH.
authors.affiliation: Fetal and Neonatal Cardiology Program, Division of Pediatric Cardiology, Department of Pediatrics, Stollery Children's Hospital, Women & Children's Health Research Institute, Cardiovascular Research Centre, and Mazankowski Alberta Heart Institute, Faculty of Medicine, University of Alberta, Edmonton, AB.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Division of Neonatology, Department of Pediatrics, Stollery Children's Hospital, Women & Children's Health Research Institute, Cardiovascular Research Centre, and Mazankowski Alberta Heart Institute, Faculty of Medicine, University of Alberta, Edmonton, AB.
authors.forename: Bernard
authors.initials: B
authors.lastname: Thebaud
authors.affiliation: Division of Neonatology, Department of Pediatrics, Stollery Children's Hospital, Women & Children's Health Research Institute, Cardiovascular Research Centre, and Mazankowski Alberta Heart Institute, Faculty of Medicine, University of Alberta, Edmonton, AB.
authors.forename: Arul
authors.initials: A
authors.lastname: Vadivel
authors.affiliation: Division of Neonatology, Department of Pediatrics, Stollery Children's Hospital, Women & Children's Health Research Institute, Cardiovascular Research Centre, and Mazankowski Alberta Heart Institute, Faculty of Medicine, University of Alberta, Edmonton, AB.
authors.forename: Farah
authors.initials: F
authors.lastname: Eaton
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, University of Alberta, Edmonton, AB.
authors.forename: Venu
authors.initials: V
authors.lastname: Jain
authors.affiliation: Fetal and Neonatal Cardiology Program, Division of Pediatric Cardiology, Department of Pediatrics, Stollery Children's Hospital, Women & Children's Health Research Institute, Cardiovascular Research Centre, and Mazankowski Alberta Heart Institute, Faculty of Medicine, University of Alberta, Edmonton, AB; Department of Obstetrics and Gynecology, Faculty of Medicine, University of Alberta, Edmonton, AB. Electronic address: lisa.hornberger@albertahealthservices.ca.
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Hornberger
mesh_terms: D000818:Animals; D005260:Female; D006548:Hernia, Diaphragmatic / Q000188:drug therapy; D065630:Hernias, Diaphragmatic, Congenital; D018496:Hyperoxia / Q000503:physiopathology; D008168:Lung / Q000002:abnormalities* / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D011247:Pregnancy; D011651:Pulmonary Artery / Q000502:physiology*; D011687:Purines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology*; D014664:Vasodilation
chemical_list: D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate
keywords: congenital diaphragmatic hernia; fetal ultrasound; lung hypoplasia; pulmonary artery; sildenafil