• Open Access

The heart in Duchenne muscular dystrophy: early detection of contractile performance alteration

Authors

  • Sören Wagner,

    1. Department of Anesthesiology, University of Heidelberg, Heidelberg, Germany
    2. Department of cardio-thoracic surgery, University of Essen, Essen, Germany
    3. Institute of Physiology & Pathophysiology, Department of Systems Physiology, University of Heidelberg, Heidelberg, Germany
    4. Department of Anesthesiology, University Clinics of Erlangen, Friedrich-Alexander-University of Erlangen, Erlangen, Germany
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  • Stephan Knipp,

    1. Department of cardio-thoracic surgery, University of Essen, Essen, Germany
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  • Cornelia Weber,

    1. Institute of Physiology & Pathophysiology, Department of Systems Physiology, University of Heidelberg, Heidelberg, Germany
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  • Selina Hein,

    1. Department of Anesthesiology, University of Heidelberg, Heidelberg, Germany
    2. Institute of Physiology & Pathophysiology, Department of Systems Physiology, University of Heidelberg, Heidelberg, Germany
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  • Stefanie Schinkel,

    1. Department of Medicine III: Cardiology, Angiology and Pneumonology, University of Heidelberg, Heidelberg, Germany
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  • Andreas Walther,

    1. Department of Anesthesiology, University of Heidelberg, Heidelberg, Germany
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  • Raffi Bekeredjian,

    1. Department of Medicine III: Cardiology, Angiology and Pneumonology, University of Heidelberg, Heidelberg, Germany
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  • Oliver J Müller,

    1. Department of Medicine III: Cardiology, Angiology and Pneumonology, University of Heidelberg, Heidelberg, Germany
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  • Oliver Friedrich

    Corresponding author
    1. Institute of Physiology & Pathophysiology, Department of Systems Physiology, University of Heidelberg, Heidelberg, Germany
    2. Institute of Medical Biotechnology, Friedrich-Alexander-University of Erlangen-Nuremberg, Erlangen, Germany
    • Department of Anesthesiology, University of Heidelberg, Heidelberg, Germany
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Correspondence to: Oliver FRIEDRICH, Institute of Medical Biotechnology, Friedrich-Alexander-University of Erlangen-Nuremberg, Erlangen, Germany.

Tel.:+49-9131-85-23004

Fax: +49-9131-85-23002

E-mail: Oliver.Friedrich@mbt.uni-erlangen.de

Abstract

Progressive cardiomyopathy is a major cause of death in Duchenne muscular dystrophy (DMD) patients. Coupling between Ca2+ handling and contractile properties in dystrophic hearts is poorly understood. It is also not clear whether developing cardiac failure is dominated by alterations in Ca2+ pathways or more related to the contractile apparatus. We simultaneously recorded force and Ca2+ transients in field-stimulated papillary muscles from young (10–14 weeks) wild-type (wt) and dystrophic mdx mice. Force amplitudes were fivefold reduced in mdx muscles despite only 30 % reduction in fura-2 ratio amplitudes. This indicated mechanisms other than systolic Ca2+ to additionally account for force decrements in mdx muscles. pCa-force relations revealed decreased mdx myofibrillar Ca2+ sensitivity. ‘In vitro’ motility assays, studied in mdx hearts here for the first time, showed significantly slower sliding velocities. mdx MLC/MHC isoforms were not grossly altered. Dystrophic hearts showed echocardiography signs of early ventricular wall hypertrophy with a significantly enlarged end-diastolic diameter ‘in vivo’. However, fractional shortening was still comparable to wt mice. Changes in the contractile apparatus satisfactorily explained force drop in mdx hearts. We give first evidence of early hypertrophy in mdx mice and possible mechanisms for already functional impairment of cardiac muscle in DMD.

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