Pathophysiology of congenital diaphragmatic hernia. XI: Anatomic and biochemical characterization of the heart in the fetal lamb CDH model.
OBJECTIVE
The purpose of this study was to determine whether the presence of bowel in the chest during development in the fetal lamb model of congenital diaphragmatic hernia (CDH) results in structural and/or biochemical hypoplasia of the left venticle.


METHODS
The model was created at 80 days' gestation and delivered at term. The hearts were fixed in 4% formaldehyde solution, components weighed, and right ventricular (RV) and left ventricular (LV) wall thicknesses and both aortic (Ao) and pulmonary artery (PA) root diameters were measured. Fresh specimens were analyzed for protein, DNA, hydroxyproline, and elastin content. All CDH measurements are compared with littermate control tissues.


RESULTS
There were no differences in body weight (kg) between CDH and control littermates (4.25 +/- 0.26 versus 3.71 +/- 0.24, P = NS). CDH lambs have significantly decreased total heart (4.88 +/- .25 versus 6.75 +/- .49, P < .05), left ventricular (1.65 +/- .11 versus 2.15 +/- .19, P < .05), septal (1.29 +/- .11 versus 1.99 +/- .21, P < .05), and combined atrial (0.68 +/- .06 versus 1.14 +/- .15, P < .05) weights (g/kg lamb) without differences in RV weights (1.26 +/- .07 versus 1.57 +/- .17, P = NS). LV and RV wall thickness, and Ao root diameters (cm) were found to be identical in both CDH and control lambs. However, PA root diameters (0.47 +/- .01 versus 0.38 +/- .01, P < .005) and ductus arteriosus diameters were increased in CDH (0.35 +/- .01 versus 0.22 +/- .02, P < .005). Total protein, DNA collagen, and elastin content and DNA/total protein ratios were identical in RV and LV in both CDH and control lambs.


CONCLUSIONS
Newborn lambs with left-sided CDH have a significantly lower total heart, LV, septal, and atrial weights without differences of RV weight or ventricular wall thicknesses. Given these findings, the unchanged DNA/protein ratio implies that the left ventricle is hypoplastic in CDH. Ao/PA root ratios suggest that LV hypoplasia in utero may result in increased left atrial pressures, decreased right-to-left shunting through the foramen ovale, and increased PA pressures and flow, resulting in increased PA root and ductus arteriosus diameters. This model simulates the clinical data from human fetuses/neonates with CDH. Further investigations are necessary to determine the functional significance of these findings.
D000818:Animals; D001011:Aorta / Q000473:pathology; D001794:Blood Pressure; D003094:Collagen / Q000032:analysis; D004247:DNA / Q000032:analysis; D004195:Disease Models, Animal; D004374:Ductus Arteriosus, Patent / Q000473:pathology; D004549:Elastin / Q000032:analysis; D005260:Female; D006325:Heart Atria / Q000473:pathology; D006330:Heart Defects, Congenital / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D006344:Heart Septal Defects, Atrial / Q000473:pathology; D006346:Heart Septum / Q000473:pathology; D006352:Heart Ventricles / Q000002:abnormalities / Q000473:pathology; D006548:Hernia, Diaphragmatic / Q000503:physiopathology*; D065630:Hernias, Diaphragmatic, Congenital; D006801:Humans; D006909:Hydroxyproline / Q000032:analysis; D009929:Organ Size; D011247:Pregnancy; D011506:Proteins / Q000032:analysis; D011651:Pulmonary Artery / Q000473:pathology; D012756:Sheep
D011506:Proteins; D003094:Collagen; D004247:DNA; D004549:Elastin; D006909:Hydroxyproline