Correia-Pinto J, Baptista M J, Estêvão-Costa J, Carvalho J L, Ferreira A, Areias J C, Leite-Moreira A F
Department of Physiology, Faculty of Medicine, Porto, Portugal.
J Pediatr Surg. 2000 Oct;35(10):1449-52. doi: 10.1053/jpsu.2000.16411.
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.
心脏相关指标已被认为是评估左心室(LV)发育不全的有用工具,这可能预测先天性膈疝(CDH)胎儿和婴儿的预后。本研究分析了此类指标在硝呋烯腙诱导的CDH大鼠模型中的表现。
妊娠第9.5天的成年Wistar大鼠,一组给予100mg硝呋烯腙,另一组仅给予赋形剂。测量12只未接触硝呋烯腙的新生大鼠(对照组)以及68只接触硝呋烯腙的动物的体重、肺重量和心脏重量:30只无CDH(非CDH组)和38只左CDH(CDH组)。将每颗心脏切成7微米厚的切片。仅对无心脏形态学缺陷(CMD)证据的心脏进行进一步研究,以估计右心室和左心室腔容积、室间隔、右心室和左心室游离壁质量。这些参数可用于计算心-心室(CV指数)和左心室质量指数。还计算了主动脉与肺动脉比值。
排除有CMD的胎儿后,接触硝呋烯腙的动物心脏与体重之比显著降低,而非CDH组与CDH组之间未观察到显著差异。虽然硝呋烯腙处理的大鼠左、右心室腔容积均显著减小,但CDH的存在并未使其发生显著变化,且计算出的CV指数在三组中相似。硝呋烯腙处理的动物室间隔和左心室质量估计值明显降低,CDH的存在使其进一步降低。然而,当左心室质量进行标准化(左心室质量指数)时,差异仅限于接触硝呋烯腙的动物,但不受CDH存在的影响。最后,所有研究组的主动脉与肺动脉比值相似。
本研究结果表明,尽管硝呋烯腙导致了整体心脏发育不全,但在无CMD的大鼠胎儿中,CDH的存在与心脏或左心室的显著发育不全无关。基于这些结果,我们认为应严格重新考虑基于心脏相关指标进行产前咨询的证据。