Effects of Simvastatin on Fetal Cardiac Impairment in the Diaphragmatic Experimental Hernia Model.
Animals
Female
Fetal Development
Hernias, Diaphragmatic, Congenital
/ chemically induced
Hydroxymethylglutaryl-CoA Reductase Inhibitors
/ adverse effects
Phosphodiesterase 5 Inhibitors
/ adverse effects
Pregnancy
Rats
Rats, Sprague-Dawley
Sildenafil Citrate
/ adverse effects
Simvastatin
/ administration & dosage
X-Ray Microtomography
Cardiac remodeling
Congenital diaphragmatic hernia
Fetal growth
Simvastatin
Treatment
Journal
Fetal diagnosis and therapy
ISSN: 1421-9964
Titre abrégé: Fetal Diagn Ther
Pays: Switzerland
ID NLM: 9107463
Informations de publication
Date de publication:
2019
2019
Historique:
received:
21
12
2017
accepted:
16
05
2018
pubmed:
11
9
2018
medline:
28
1
2020
entrez:
11
9
2018
Statut:
ppublish
Résumé
Statins and sildenafil have been shown to exert beneficial effects in cardiac injury. We hypothesized that antenatal maternal administration of simvastatin and/or sildenafil might also promote benefits in cardiac remodeling of congenital diaphragmatic hernia (CDH). Therefore, we performed micro-CT image analysis and histology of the heart after antennal treatment in experimental nitrofen-induced CDH. At 9.5 days post conception (dpc), pregnant rats were exposed to nitrofen. At 16 and 20 dpc fetuses were treated with simvastatin and/or sildenafil. At 21 dpc postmortem micro-CT and autopsy were performed. All nitrofen-treated fetuses had a lower birth weight compared to controls; in the simvastatin-treated group, a significant improvement in CDH was noted. Impairment of the lung and liver was also noted in CDH. Compared to controls, CDH rats showed lower ventricular mass, with greater left ventricular thickness; simvastatin decreased the ventricular mass and improved wall thickness. CDH rats exhibited myocardial hypotrophy, severe vascular depression in the left ventricle, and intense interstitial edema compared to controls and nitrofen-exposed animals without CDH. In CDH, the cardiac morphology appeared deformed with left ventricular wall verticalization. Simvastatin improved cardiac myocyte appearance and heart morphology. The potential to treat CDH with antenatal simvastatin may improve the management of this malformation.
Sections du résumé
BACKGROUND
BACKGROUND
Statins and sildenafil have been shown to exert beneficial effects in cardiac injury. We hypothesized that antenatal maternal administration of simvastatin and/or sildenafil might also promote benefits in cardiac remodeling of congenital diaphragmatic hernia (CDH). Therefore, we performed micro-CT image analysis and histology of the heart after antennal treatment in experimental nitrofen-induced CDH.
METHODS
METHODS
At 9.5 days post conception (dpc), pregnant rats were exposed to nitrofen. At 16 and 20 dpc fetuses were treated with simvastatin and/or sildenafil. At 21 dpc postmortem micro-CT and autopsy were performed.
RESULTS
RESULTS
All nitrofen-treated fetuses had a lower birth weight compared to controls; in the simvastatin-treated group, a significant improvement in CDH was noted. Impairment of the lung and liver was also noted in CDH. Compared to controls, CDH rats showed lower ventricular mass, with greater left ventricular thickness; simvastatin decreased the ventricular mass and improved wall thickness. CDH rats exhibited myocardial hypotrophy, severe vascular depression in the left ventricle, and intense interstitial edema compared to controls and nitrofen-exposed animals without CDH. In CDH, the cardiac morphology appeared deformed with left ventricular wall verticalization. Simvastatin improved cardiac myocyte appearance and heart morphology.
CONCLUSION
CONCLUSIONS
The potential to treat CDH with antenatal simvastatin may improve the management of this malformation.
Identifiants
pubmed: 30199868
pii: 000490144
doi: 10.1159/000490144
doi:
Substances chimiques
Hydroxymethylglutaryl-CoA Reductase Inhibitors
0
Phosphodiesterase 5 Inhibitors
0
Simvastatin
AGG2FN16EV
Sildenafil Citrate
BW9B0ZE037
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
28-37Informations de copyright
© 2018 S. Karger AG, Basel.