Poster abstracts

Poster number 28 submitted by Lucas Citro

Cardiac magnetic resonance imaging of the Ts65Dn murine model of Down Syndrome

Lucas A. Citro (Internal Medicine, The Ohio State University), Sarah E. Sansom (Davis Heart and Lung Research Institute, The Ohio State University), Mahmood Khan (Internal Medicine, The Ohio State University), Mickey M. Martin (Davis Heart and Lung Research Institute, The Ohio State University), Periannan Kuppusamy (Internal Medicine, The Ohio State University), Terry S. Elton (Davis Heart and Lung Research Institute, The Ohio State University)

Abstract:
In humans, Down syndrome is associated with a trisomy of human chromosome 21, Hsa21 [1]. Congenital heart defects occur in 40-60% of patients with DS, with complete atrioventricular septal defect being the most common defect [1]. The Ts65Dn mouse is the most-studied of the murine models for DS phenotypes and the observed congenital heart defects have only been characterized by histological and immunohistochemistry analyses [2,3]. Thus, we have utilized, for the first time, cardiac magnetic resonance imaging (MRI) to assess the functional defects of the left and right ventricles (LV and RV) of Ts65Dn mice.

Ts65Dn dams (B6EiC3Sn a/A-Ts(1716)65Dn) were bred to B6Eic x C3Sn F1 male mice [2,3]. MR imaging was performed using a Bruker 11.7T MRI system. T1-weighted gradient echo FLASH-cine axial images were completed (gated, TR/TE=8/1.4;=15o; FOV=3 cm). From the images, LV and RV mass, ejection fraction (EF), cardiac output (CO), septal volume (IVS), and end-systolic, end-diastolic and stroke volumes (ESV, EDV, SV) were calculated.

The ED and ES LV masses was significantly larger for the wild-type (WT) mice (67.5, 79.4 vs. 50.4, 56.1 mg, respectively). Likewise, LV ESV, EDV, and SV were larger for the WT mice (0.01, 0.05, 0.04 ml, respectively) compared with the Ts65Dn mice (0.01, 0.04, and 0.03 ml, respectively). WT RV EF (63.0 %) decreased relative to Ts65Dn values (69.0 %). A significant increase in ED RV mass was also observed for the WT mice (28.9 vs. 35.4 mg). A significant increase in ED IVS volume was observed for the WT mice, when compared with the Ts65Dn mice (26.2 vs. 21.2 mm3).

In this study, WT mice displayed significant increases in ED IVS volume, LV mass (ED and ES), SV, EDV, and ESV, when compared with the Ts65Dn DS mice. Thus, Ts65Dn mice present extensive cardiac functional abnormalities similar to those observed in Down syndrome patients and these cardiac defects can easily be detected using high-field cardiac magnetic resonance imaging.

References:
1. Epstein CJ. The Consequences of Chromosome Imbalance: Principles,
Mechanism and Models. New York, NY: Cambridge University Press,
1986:2[4].
2. Williams AD, et al., DD, 2008.
3. Moore CS, MG: G&P, 2006.53-59.

Keywords: High-field Cardiac MRI, Down Syndrome (Ts65Dn), Intra-ventricular Septal Defects