Age‐Dependent Myocardial Sheet Dysfunction from 3 to 16 months in Duchenne Muscular Dystrophy Mice (mdx) Defined by Diffusion Tensor Magnetic Resonance Imaging (DTI)

Abstract

INTROCardiomyocytes are organized in laminar structures (aka, sheets) that contribute to wall thickening/thinning. Diffusion tensor MRI (DTI) measures the sheet reorientation function in intact hearts. We have reported that hearts of 16‐mo old mdx mice exhibit abnormal Ca transients & Ca‐dependent sheet dysfunction at the base but not apex. Because Ca mishandling in isolated mdx cardiomyocytes is age dependent, we hypothesized that sheet dysfunction in intact mdx hearts may also be age dependent.METHODSExcised hearts from 3 & 16 mo old mdx and wildtype were prepared for Langendorff perfusion, and sequentially arrested in diastole then systole for DTI (Varian 11.7 T). The diastolic arrest was achieved with either normal [Ca] (1.2 mM, noted as NC) or low [Ca] (0.078 mM, noted as LC) cardioplegic solution to test the Ca dependency. The systolic arrest was achieved with barium.RESULTSSystolic |β| (defined below) was similar between WT and mdx, whereas diastolic |β| in mdx‐NC was lower for age matched WT‐NC at the base but not apex, indicating a regional failure to fully relax. Low [Ca] (mdx‐LC) perfusion restores the diastolic |β| to normal values at both ages. The Δ|β| (i.e., |β| of each group ‐ |β| of age matched WT‐NC) is 50% larger in 16 mo than for 3 mo old mice, indicating that Ca dependent sheet dysfunction is age dependent and regionally manifest despite the ubiquitous dystrophin deficiency.