Abstract 9791: Distention of the Immature Left Ventricle Triggers Development of Endocardial Fibroelastosis - An Animal Model Introducing Morpho-Pathological Features of Evolving Hypoplastic Left Heart Syndrome in Human Fetuses -
Background: Endocardial fibroelastosis (EFE), characterized by diffuse endocardial thickening through collagen and elastin fibers, develops in the human fetal heart restricting growth of the left ventricle (LV). Although it has been speculated that an early hemodynamic insult to the fetal heart would play a key role in the development of EFE, its precise pathogenesis has not been elucidated. Recent advances in fetal imaging indicated that EFE development is directly associated with a distended, poorly contractile LV in evolving hypoplastic left heart syndrome. To test this hypothesis, we developed an animal model introducing this LV morpho-pathology to an immature rat heart.
Methods: Femoral heterotopic rat heart transplantation, using neonatal donor hearts, was developed to facilitate postoperative echocardiographic evaluation of valvar and ventricular function. In one set (n=10), we created aortic regurgitation (AR), compared to a second set (n=14), where the aortic valve remained competent (no-AR). EFE was determined by histological staining and graded semi-quantitatively on a scale of 0-4 two weeks postoperatively. Student’s t-test was used for analysis and data are expressed as mean±SEM
Results: In AR, the LV was significantly dilated compared to no-AR (LVDd(mm); 3.33±0.47 vs. 1.35±0.09, p<0.01). All AR cases developed grade 2-4 EFE (AR: 2.90±0.26 vs. no-AR: 0.29±0.21, p<0.01). Comparison within the AR cases revealed that the severest degree of EFE (grade 4) developed in the most significantly dilated (LVDd(mm); AR with grade 4 EFE: 5.24±0.54 vs. AR with grade 2 or 3 EFE: 2.51±0.29, p<0.01), and poorly contractile LVs (FS(%); AR with grade 4 EFE: 3.15±1.28 vs. AR with grade 2 or 3 EFE: 25.0±2.77, p<0.01).
Conclusion: In this study we could show that the severity of LV distention and dysfunction is directly associated with the degree of EFE formation. Thus, this animal model can serve as a robust tool to develop therapeutic strategies to inhibit EFE development in the immature/fetal heart.
Author Disclosures: S. Shimada: None. B. Illigens: None. C. Robles: None. A. Casar Berazaluce: None. P.J. del Nido: None. I. Friehs: None.
- © 2014 by American Heart Association, Inc.