Document Detail

Cardiovascular malformations in experimental congenital diaphragmatic hernia.
MedLine Citation:
PMID:  10466596     Owner:  NLM     Status:  MEDLINE    
BACKGROUND/PURPOSE: Newborns with congenital diaphragmatic hernia (CDH) frequently have associated anomalies that have a major impact on survival rate independent of pulmonary hypoplasia and pulmonary hypertension. Cardiovascular malformations (CVM) represent a major group of lethal extrapulmonary abnormalities that often assume greatest prognostic significance in most CDH studies. Animal models resembling human CDH may aid knowledge of the basic embryology that leads to the coexpression of CDH and CVM. This study, therefore, analyzed the incidence and spectrum of CVM in fetal rats with CDH. METHODS: Left-sided CDH (LCDH) was induced in fetal rats by the maternal administration of 100 mg of nitrofen by gavage on day 9.5 gestation (term, day 22). Control animals received olive oil (OO) and were used for comparative analysis. Fetal rats were harvested by cesarean section on day 21.5 or day 22, histologically processed and examined for CVM. RESULTS: A significant number of CVM were observed in 15 of 60 (25%) LCDH rats compared with 4 of 60 (6.7%) nitrofen non-CDH rats (P = .01). The spectrum of abnormalities in CDH included ventricular septal (VSD) defects (n = 6), vascular rings (n = 4), anomalous subclavian arteries (n = 3), atrioventricular septal defects (n = 1) and Fallot's tetralogy (n = 1). A VSD (n = 1), double-outlet right ventricle VSD (n = 1) and Fallot's tetralogy (n = 2) were noted in nitrofen non-CDH rats. Control (OO) fetal rats (n = 60) displayed no malformations. CONCLUSIONS: These results confirm a significant incidence and spectrum of CVM in a teratogenic CDH model similar to that seen in humans with CDH. The findings of this study reinforce the validity of the nitrofen model as a research tool to uncover the genetic and molecular mechanisms responsible for the genesis of CDH and allied malformations.
P D Losty; M G Connell; R Freese; S Laval; B O Okoye; A Smith; D Kluth; D A Lloyd
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of pediatric surgery     Volume:  34     ISSN:  0022-3468     ISO Abbreviation:  J. Pediatr. Surg.     Publication Date:  1999 Aug 
Date Detail:
Created Date:  1999-10-07     Completed Date:  1999-10-07     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0052631     Medline TA:  J Pediatr Surg     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1203-7     Citation Subset:  IM    
Department of Paediatric Surgery, Institute of Child Health, Alder Hey Children's Hospital, The University of Liverpool, England.
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MeSH Terms
Heart Defects, Congenital / chemically induced,  complications*
Hernia, Diaphragmatic / chemically induced,  complications,  congenital*
Phenyl Ethers
Rats, Sprague-Dawley
Reg. No./Substance:
0/Phenyl Ethers; 1836-75-5/nitrofen

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