Antenatal sildenafil treatment improves neonatal pulmonary hemodynamics and gas exchange in lambs with diaphragmatic hernia.
Animals
Autopsy
/ methods
Blood Gas Analysis
/ methods
Female
Fetal Therapies
/ methods
Fetus
Hemodynamics
/ drug effects
Hernias, Diaphragmatic, Congenital
/ drug therapy
Lung
/ blood supply
Models, Animal
Phosphodiesterase 5 Inhibitors
/ administration & dosage
Pregnancy
Prenatal Care
Pulmonary Gas Exchange
/ drug effects
Sheep
Sildenafil Citrate
/ administration & dosage
congenital abnormality
fetal therapy
neonatal transition
pulmonary hypertension
pulmonary vascular development
Journal
Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology
ISSN: 1469-0705
Titre abrégé: Ultrasound Obstet Gynecol
Pays: England
ID NLM: 9108340
Informations de publication
Date de publication:
Oct 2019
Oct 2019
Historique:
received:
25
05
2019
revised:
06
07
2019
accepted:
11
07
2019
pubmed:
1
8
2019
medline:
17
3
2020
entrez:
1
8
2019
Statut:
ppublish
Résumé
Infants with congenital diaphragmatic hernia (CDH) are predisposed to pulmonary hypertension after birth, owing to lung hypoplasia that impairs fetal pulmonary vascular development. Antenatal sildenafil treatment attenuates abnormal pulmonary vascular and alveolar development in rabbit and rodent CDH models, but whether this translates to functional improvements after birth remains unknown. We aimed to evaluate the effect of antenatal sildenafil on neonatal pulmonary hemodynamics and lung function in lambs with diaphragmatic hernia (DH). DH was surgically induced at approximately 80 days' gestation in 16 lamb fetuses (term in lambs is approximately 147 days). From 105 days' gestation, ewes received either sildenafil (0.21 mg/kg/h intravenously) or saline infusion until delivery (n = 8 fetuses in each group). At approximately 138 days' gestation, all lambs were instrumented and then delivered via Cesarean section. The lambs were ventilated for 120 min with continuous recording of physiological (pulmonary and carotid artery blood flow and pressure; cerebral oxygenation) and ventilatory parameters, and regular assessment of arterial blood gas tensions. Only lambs that survived until delivery and with a confirmed diaphragmatic defect at postmortem examination were included in the analysis; these comprised six DH-sildenafil lambs and six DH-saline control lambs. Lung-to-body-weight ratio (0.016 ± 0.001 vs 0.013 ± 0.001; P = 0.06) and dynamic lung compliance (0.8 ± 0.2 vs 0.7 ± 0.2 mL/cmH Sustained maternal antenatal sildenafil infusion reduced pulmonary arterial pressure and increased pulmonary blood flow in DH lambs for the first 120 min after birth. These findings of improved pulmonary vascular function are consistent with improved pulmonary vascular structure seen in two previous animal models. The data support the rationale for a clinical trial investigating the effect of antenatal sildenafil in reducing the risk of neonatal pulmonary hypertension in infants with CDH. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.
Substances chimiques
Phosphodiesterase 5 Inhibitors
0
Sildenafil Citrate
BW9B0ZE037
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
506-516Subventions
Organisme : Cabrini Foundation
Organisme : CDH Australia
Organisme : Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) Foundation
Organisme : Victorian Government's Operational Infrastructure Support Program
Informations de copyright
Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.
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