Question: 

Progressive cardiomyopathy is a major cause of death in Duchenne muscular dystrophy (DMD). Contractile and Ca²⁺ handling properties in dystrophic hearts are poorly understood.

Methodology: 

We recorded force and Ca²⁺ transients in field-stimulated (1-4 Hz) papillary muscles from young (10–14 wks) wild-type (wt) and dystrophic mdx mice. Contractile properties were assessed in pCa-force recordings in skinned muscle strips. Motor protein interactions were studied in cardiac 'in vitro' motility assays in mdx hearts here for the first time. SDS PAGE of myosin heavy and light chains were performed. 'In vivo' recordings of cardiac performance in mdx mice completed the study.

Result: 

Force amplitudes were five-fold reduced in mdx muscles despite only 30 % reduction in fura-2 amplitudes. Ca²⁺:force gains were markedly reduced in mdx muscles. pCa-force recordings showed vast reduction of myofibrillar Ca²⁺ sensitivity in mdx hearts. Additionally, cardiac 'in vitro' motility assays showed significantly slowed down sliding velocities in mdx myosin extracts that were paralleled by increases in slow ß-MHC isoforms. On the organ level, mdx septum and posterior walls were significantly increased while fractional shortening was not different in both strains.

Conclusion: 

The changes in the contractile apparatus fully explain the force drop in mdx hearts. Despite the cellular changes, contractility on the organ level was still well compensated. At this early disease stage, signs of hypertrophy were already detected. We give first evidence of early hypertrophy in mdx mice and the possible mechanisms for early functional impairment of cardiac muscle in DMD.