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Fetal surgical interventions and the development of the heart in congenital diaphragmatic hernia
H L Karamanoukian1, S J O'Toole, J R Rossman
1Buffalo Institute of Fetal Therapy, Children's Hospital of Buffalo, School of Medicine and Biomedical Sciences, State University of New York at Buffalo 14222, USA.
Insights
Congenital diaphragmatic hernia (CDH) causes left ventricular hypoplasia. Surgical repair of CDH corrects this cardiac defect, but tracheal ligation does not, suggesting lung overgrowth may impede heart development.
Area of Science:
- Fetal surgery
- Congenital diaphragmatic hernia
- Cardiac development
Background:
- Congenital diaphragmatic hernia (CDH) is associated with selective left ventricular hypoplasia.
- Herniated viscera are hypothesized to impede fetal cardiac development.
- The impact of fetal surgical interventions on cardiac development in CDH requires investigation.
Purpose of the Study:
- To evaluate the effects of fetal tracheal ligation (TL) and diaphragmatic repair on cardiac development in a CDH lamb model.
- To determine if surgical correction of CDH can reverse associated cardiac anomalies.
Main Methods:
- Congenital diaphragmatic hernia (CDH) was surgically induced in lambs at 80 days gestation.
- Fetal interventions included tracheal ligation (CDH + TL) or diaphragmatic repair (CDH + repair) at 110 days gestation.
- Cardiac anatomy and component weights were assessed at term (141 days gestation) and compared to controls.
Main Results:
- CDH lambs exhibited significantly reduced total heart, left ventricular, septal, and atrial weights compared to controls.
- Diaphragmatic repair in CDH lambs normalized heart and cardiac chamber weights to control levels.
- Tracheal ligation in CDH lambs did not alter cardiac weights, despite reversing pulmonary hypoplasia.
Conclusions:
- Surgical repair of congenital diaphragmatic hernia (CDH) effectively corrects associated left ventricular hypoplasia.
- Tracheal ligation, while addressing pulmonary hypoplasia, does not improve cardiac development in CDH.
- Enlarging lungs post-tracheal ligation may act as space-occupying lesions, adversely affecting cardiac growth.
Abstract:
Selective left ventricular hypoplasia is a recognized feature of congenital diaphragmatic hernia (CDH). It is speculated that the herniated viscera act as a space occupying lesion that inhibit normal cardiac development. The purpose of this study was to determine the effect of two separate fetal surgical interventions on subsequent cardiac development in CDH. CDH lambs were created at 80 days gestation and underwent either tracheal ligation (CDH + TL) or diaphragmatic repair (CDH + repair) at 110 days gestation. At term (141 days gestation) the hearts were harvested and fixed in 4% paraformaldehyde solution. Anatomic dissections were performed and component heart weights determined. Fresh specimens were analyzed for DNA and protein content. All weights are expressed in grams/kilogram body weight and all data as mean +/- SEM. All measurements are compared to control and CDH tissues. There were seven CDH lambs, five control lambs, five CDH + TL lambs, and five CDH + repair lambs. There were no differences in body weight (kg) between CDH, CDH + TL, CDH + repair, and control littermates. CDH lambs have significantly decreased total heart (4.88 +/- .25* vs 6.75 +/- .49, P < 0.05), left ventricular (1.65 +/- .11* vs 2.15 +/- .19, P < 0.05), septal (1.29 +/- .11* vs 1.99 +/- .21, P < 0.05), and combined atrial (0.68 +/- .06* vs 1.14 +/- .15, P < 0.05) weights (g/kg lamb) without differences in RV weights (1.26 +/- .07 vs 1.57 +/- .17, P = NS) when compared to littermate controls. No differences were found in total heart (4.82 +/- 0.38 vs 4.88 +/- 0.25), left ventricular (1.48 +/- 0.13 vs 1.65 +/- 0.11), septal (1.26 +/- 0.17 vs 1.29 +/- 0.11), combined atrial weights (0.56 +/- 0.07 vs 0.68 +/- 0.06), and right ventricular (1.52 +/- 0.12 vs 1.26 +/- 0.07) between CDH + TL and CDH lambs. There were no differences in total heart (6.60 +/- 0.29 vs 6.75 +/- 0.49), left ventricular (2.10 +/- 0.15 vs 2.15 +/- 0.19), septal (1.97 +/- 0.18 vs 1.99 +/- 0.21), combined atrial (1.10 +/- 0.10 vs 1.14 +/- 0.15), or right ventricular (1.52 +/- 0.12 vs 1.57 +/- 0.17) weights between CDH + repair and control lambs. LV and RV wall thicknesses (cm), as well as total protein and DNA content, and DNA/total protein ratios were identical in all groups. CDH lambs have a significant reduction in total heart weights mainly caused by hypoplasia of the left ventricle (left ventricular "smallness") and the interventricular septum. Removal of the herniated viscera and repair of the diaphragmatic defect correct this abnormality, but tracheal ligation does not. We speculate that although tracheal ligation reverses pulmonary hypoplasia, the enlarging lungs act as space occupying lesions that adversely affect cardiac development. Further investigations are necessary to determine the functional significance of these findings.