Heart hypoplasia in experimental congenital diaphragmatic hernia

Background/Purpose: Heart hypoplasia is associated with congenital diaphrag matic hernia (CDH) and decisively influences survival rate. This study exam ines whether nitrofen-exposed fetal rats have heart hypoplasia. Methods: Pregnant rats received either 100 mg nitrofen or vehicle on gestat ional day 9.5. The hearts recovered near full term were either formalin fix ed for anatomic studies or snap-frozen for biochemical studies. Heart weigh t, ventricular chamber diameters and aortic-to-pulmonary root diameter rati os were measured in fixed hearts. Protein and DNA were determined in frozen hearts. Analysis of variance (ANOVA) and correlation-regression studies we re used for statistical assessment. Results: All control fetuses were normal, whereas 61% of those exposed to n itrofen had CDH. Cardiovascular malformations were found in 73% of CDH and in 50% of non-CDH animals. Wet and fixed heart weights in percent of fetal weight, left-to-right ventricular diameter ratio, and aortic-to-pulmonary r oot diameter ratio were significantly decreased in fetuses with CDH in comp arison with controls. Only wet heart was significantly decreased in nitrofe n-treated fetuses without CDH, although all other variables showed a trend in the same direction. Protein to DNA ratios were similar in the three grou ps. The structure of the myocytes was histologically similar in all groups. Conclusions: The spectrum of lesions in the nitrofen model of CDH encompass es heart hypoplasia, further validating its use for research on this condit ion. Heart hypoplasia is related to cardiopulmonary compression, but its pr esence in treated animals without CDH demonstrates that the teratogen itsel f participate directly in its pathogenesis, and this finding invites furthe r research on this line. Copyright (C) 1999 by W.B. Saunders Company.