Heart-related indices in experimental diaphragmatic hernia

Heart-related indices have been suggested as useful tools to evaluate left ventricular (LV) hypoplasia, which might predict the outcome of fetuses and infants with congenital diaphragmatic hernia (CDH). The current study analyzed the behavior of such indices in the nitrofen-induced CDH rat model.

Dated pregnant Wistar rats received at day 9.5 of gestation either a dose of 100 mg of nitrofen or just the vehicle. Body, lung, and heart weights were measured in 12 newborn rats not exposed to nitrofen (Ctrl group) and 68 animals exposed to nitrofen: 30 without CDH (non-CDH group) and 38 with left CDH (CDH group). Each heart was fragmented in 7-microm thick sections. Only hearts with no evidence of cardiac morphologic defects (CMD) were studied further to estimate right and left ventricular cavity volumes, septal, right, and left ventricular free wall masses. These parameters allowed the calculation of the cardio-ventricular (CVindex) and LV mass indices. The aorta-to-pulmonary artery ratio also was calculated.

Excluding fetuses with CMD, the heart-to-body weight ratio was reduced significantly in animals exposed to nitrofen, whereas no significant differences were observed between non-CDH versus CDH groups. Although the left and right ventricular cavity volumes were both reduced significantly in nitrofen-treated rats, they were not changed significantly by the existence of CDH, and the calculated CVindex was similar in the 3 groups. Estimated septal and LV masses were reduced markedly in the nitrofen-treated animals and further reduced by the presence of CDH. However, when LV mass was normalized (LV mass index) the difference became restricted to the animals exposed to nitrofen but was not influenced by the presence of CDH. Finally, the aorta-to-pulmonary artery ratio was similar in all studied groups.

The results of the current study suggest that, although nitrofen had been responsible by global heart hypoplasia, the presence of CDH was not associated with significant underdevelopment of the heart or of the LV in rat fetuses without CMD. Based on these results, we think that the evidence for prenatal counseling based on heart-related indices should be critically reconsidered.