Early manifestation of alteration in cardiac function in dystrophin deficient mdx mouse using 3D CMR tagging.
BACKGROUND
Duchenne muscular dystrophy (DMD) is caused by the absence of the cytoskeletal protein, dystrophin. In DMD patients, dilated cardiomyopathy leading to heart failure may occur during adolescence. However, early cardiac dysfunction is frequently undetected due to physical inactivity and generalized debilitation. The objective of this study is to determine the time course of cardiac functional alterations in mdx mouse, a mouse model of DMD, by evaluating regional ventricular function with CMR tagging.


METHODS
In vivo myocardial function was evaluated by 3D CMR tagging in mdx mice at early (2 months), middle (7 months) and late (10 months) stages of disease development. Global cardiac function, regional myocardial wall strains, and ventricular torsion were quantified. Myocardial lesions were assessed with Masson's trichrome staining.


RESULTS
Global contractile indexes were similar between mdx and C57BL/6 mice in each age group. Histology analysis showed that young mdx mice were free of myocardial lesions. Interstitial fibrosis was present in 7 month mdx mice, with further development into patches or transmural lesions at 10 months of age. As a result, 10 month mdx mice showed significantly reduced regional strain and torsion. However, young mdx mice showed an unexpected increase in regional strain and torsion, while 7 month mdx mice displayed similar regional ventricular function as the controls.


CONCLUSIONS
Despite normal global ventricular function, CMR tagging detected a biphasic change in myocardial wall strain and torsion, with an initial increase at young age followed by progressive decrease at older ages. These results suggest that CMR tagging can provide more sensitive measures of functional alterations than global functional indexes in dystrophin-related cardiomyopathies.
Li
Wei
W
Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, USA. wei.li2@case.edu
Liu
Wei
W
Zhong
Jia
J
Yu
Xin
X
D000367:Age Factors; D000375:Aging; D000818:Animals; D002302:Cardiac Output; D002311:Cardiomyopathy, Dilated / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D018450:Disease Progression; D005355:Fibrosis; D007090:Image Interpretation, Computer-Assisted; D021621:Imaging, Three-Dimensional; D019028:Magnetic Resonance Imaging, Cine; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D020388:Muscular Dystrophy, Duchenne / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D009200:Myocardial Contraction; D009206:Myocardium / Q000473:pathology*; D013318:Stroke Volume; D013997:Time Factors; D054159:Torsion, Mechanical; D016277:Ventricular Function, Left