Endocardial fibroelastosis in chick model of hypoplastic left heart syndrome

Endocardial fibroelastosis (EFE) is a diffuse thickening of the ventricular endocardium, causing myocardial dysfunction and presenting as unexplained heart failure in infants and children. It is supposed to be due to persistent and increased wall tension in the ventricles. Its frequent association with hypoplastic left heart syndrome (HLHS) lead us to hypothesize that abnormal hemodynamic loading is an important factor in its pathogenesis. We have tested this theory in a chick model of HLHS induced by left atrial ligation (LAL). At ED 8 and ED 12 modifications of myocardial architecture and fibrosis were studied by histology and immunoconfocal microscopy, and the amount of collagen was quantified by image analysis.

Histology with H&E/Alcian Blue staining did not reveal any significant fibrosis in the LAL hearts with the exception of cardiac skeleton and valves. Immunohistochemistry with collagen I antibody clearly showed a thickening of the layer of subendocardial fibrous tissue. Quantification of staining area normalized by endocardial circumference showed a significant increase at ED 12, but not ED 8 in the LAL group. We conclude that abnormal hemodynamic loading stimulates fibrous production in the subendocardium of the hypoplastic left ventricle. Therefore, EFE in HLHS clearly appears to be a secondary effect of abnormal hemodynamics.

Supported by Ministry of Education, PRVOUK-P35/LF1/5, Academy of Sciences RVO: 67985823, and Grant Agency of the Czech Republic P302/11/1308 and 13–12412S.