Heart-Related Indices in Experimental Diaphragmatic Hernia By Jorge Correia-Pinto, Maria J. Baptista, J. Este ˆ va ˜ o-Costa, Jose ´ L. Carvalho, Ame ´ lia Ferreira, Jose ´ C. Areias, and Adelino F. Leite-Moreira Porto, Portugal Background: 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. Methods: 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-m 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 (CV index ) and LV mass indices. The aorta-to-pulmonary artery ratio also was calculated. Results: 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 signifi- cantly in nitrofen-treated rats, they were not changed signif- icantly by the existence of CDH, and the calculated CV index 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. Conclusions: The results of the current study suggest that, although nitrofen had been responsible by global heart hy- poplasia, the presence of CDH was not associated with sig- nificant 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. J Pediatr Surg 35:1449-1452. Copyright © 2000 by W.B. Saunders Company. INDEX WORDS: Congenital diaphragmatic hernia, heart, ni- trofen, prognostic factors, rat. D ESPITE INTENSIVE RESEARCH and sophisti- cated perinatal care the prognosis of infants with congenital diaphragmatic hernia (CDH) remains ad- verse. 1 The association with congenital cardiac malfor- mations further reduces their chances of survival. 2 Even in the absence of cardiac morphologic defects, the heart may be underdeveloped because of left ventricular (LV) “smallness” or hypoplasia. 3 The clinical relevance of this entity is still unknown, but some investigators considered it as the “missing link” in the pathophysiology of CDH. 4 During the last decade, various heart-related indices had been proposed to assess the degree of LV hypoplasia to predict the outcome of fetuses and infants with CDH. 5-9 The echocardiographic evaluation of cardiac ventricular disproportion in fetuses 5-7 as well as the estimation of left ventricular mass 8,9 and aorta-to-pulmo- nary artery ratio 6 in newborns was suggested to be useful in predicting the outcome of CDH in humans. In animal models, heart weight was even correlated with lung hypoplasia. 10-12 Despite these reports, the application of such criteria to the management of fetuses and infants with CDH did not become a current clinical practice. It is not yet clear to what extent the cardiovascular system contributes to the natural history of CDH. In a previous study, we found that in nitrofen-induced CDH, heart weight reduc- tion was mainly caused by nitrofen and not the presence of CDH. 13 The current study analyzed, in the same experimental model, the influence either of nitrofen or of CDH in various heart-related indices. MATERIALS AND METHODS The investigation conforms with the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH Publication No. 85-23, revised 1996). Animal Model Wistar female rats (225 g, Criffa, SA, Barcelona) were pregnant after overnight mating, and the finding of vaginal plug was counted as day From the Departments of Physiology and Pediatric Surgery, Faculty of Medicine, Porto, Portugal. This work was supported by grants from PRAXIS XXI (2/2.1/SAU/ 1386/95) and PRAXIS/C/SAU/11301/98 through Unidade I&D Cardio- vascular n°51/94/FCT. Address reprint requests to Jorge Correia-Pinto, MD, Servic ¸o de Fisiologia, Faculdade de Medicina da Universidade do Porto, Al Prof Herna ˆni Monteiro, 4200-319 Porto, Portugal. Copyright © 2000 by W.B. Saunders Company 0022-3468/00/3510-0010$03.00/0 doi:10.1053/jpsu.2000.16411 1449 Journal of Pediatric Surgery, Vol 35, No 10 (October), 2000: pp 1449-1452