Heart hypoplasia in an animal model of congenital diaphragmatic hernia

Abstract

Purpose:In previous papers, we described a new experimental model of congenital diaphragmatic hernia in rabbits, and we also reported noninvasive therapeutic strategies for prevention of the functional and structural immaturity of the lungs associated with this defect. In addition to lung hypoplasia, pulmonary hypertension, biochemical, and structural immaturity of the lungs, the hemodynamics of infants and animals with congenital diaphragmatic hernia are markedly altered. Hence, cardiac hypoplasia has been implicated as a possible cause of death in patients with congenital diaphragmatic hernia, and it is hypothesized to be a probable consequence of fetal mediastinal compression by the herniated viscera. Cardiac hypoplasia has also been reported in lamb and rat models of congenital diaphragmatic hernia. The purpose of the present experiment was to verify the occurrence of heart hypoplasia in our new model of surgically produced congenital diaphragmatic hernia in fetal rabbits.Methods: Twelve pregnant New Zealand rabbits underwent surgery on gestational day 24 or 25 (normal full gestational time -31 to 32 days) to create left-sided diaphragmatic hernias in 1 or 2 fetuses per each doe. On gestational day 30, all does again underwent surgery, and the delivered fetuses were weighed and divided into 2 groups: control (non-surgically treated fetuses) (n = 12) and congenital diaphragmatic hernia (n = 9). The hearts were collected, weighed, and submitted for histologic and histomorphometric studies.Results: During necropsy, it was noted that in all congenital diaphragmatic hernia fetuses, the left lobe of the liver herniated throughout the surgically created defect and occupied the left side of the thorax, with the deviation of the heart to the right side, compressing the left lung; consequently, this lung was smaller than the right one. The body weights of the animals were not altered by congenital diaphragmatic hernia, but heart weights were decreased in comparison to control fetuses. The histomorphometric analysis demonstrated that congenital diaphragmatic hernia promoted a significant decrease in the ventricular wall thickness and an increase in the interventricular septum thickness.Conclusion: Heart hypoplasia occurs in a rabbit experimental model of congenital diaphragmatic hernia. This model may be utilized for investigations in therapeutic strategies that aim towards the prevention or the treatment of heart hypoplasia caused by congenital diaphragmatic hernia. DESCRIPTORS: Congenital diaphragmatic hernia. Heart. Hypoplasia. Fetus.In previous papers, we have described a new experimental model of congenital diaphragmatic hernia (CDH) in rabbits, and we also have reported on studies of noninvasive therapeutic strategies for prevention of functional and structural immaturity of lungs associated with this defect. These strategies consist of prenatal intra-amniotic administration of porcine surfactant or dexamethasone and prenatal tracheal ligation (TL), an invasive method that effectively treats or prevents pulmonary...

Effects of prenatal vitamins A, E, and C on the hypoplastic hearts of fetal rats with diaphragmatic hernia

“…These findings are in agreement with those from the lamb [7] and rabbit surgical models of CDH [37].…”

Effect of corticosteroids and lung ventilation in the VEGF and NO pathways in congenital diaphragmatic hernia in rats

“…9400 magnification/scale bar 50 lm to arterioles). C control, CV control ventilated, CDx control exposed to dexamethasone, CVDx ventilated control exposed to dexamethasone, CDH exposed to nitrofen with hernia, CDHV exposed to nitrofen with hernia ventilated, CDHDx CDH exposed to dexamethasone, CDHVDx ventilated CDH exposed to dexamethasone reducing the deleterious effects of hypoplasia and hypertension [22,23].…”

Cardiac fetal ultrasonographic parameters for predicting outcomes of isolated left-sided congenital diaphragmatic hernia

“…Small left heart structures have been observed in newborns with left-sided CDH in both human and experimental animal studies [9][10][11][12][13]. We therefore speculated that left heart hypoplasia might have a significant impact on the outcomes of patients with severe CDH.…”

“…Although these parameters are excellent indicators that facilitate lung volume predictions, they share the limitation of being structural measurements that do not offer information about lung vasculature and function. Until functional predictors are identified, the prognostic information concerning fetal CDH will remain incomplete [8].Small left heart structures have been observed in newborns with left-sided CDH in both human and experimental animal studies [9][10][11][12][13]. We therefore speculated that left heart hypoplasia might have a significant impact on the outcomes of patients with severe CDH.…”