The heart in Duchenne muscular dystrophy: early detection of contractile performance alteration
Sören Wagner
Department of Anesthesiology, University of Heidelberg, Heidelberg, Germany
Department of cardio-thoracic surgery, University of Essen, Essen, Germany
Institute of Physiology & Pathophysiology, Department of Systems Physiology, University of Heidelberg, Heidelberg, Germany
Department of Anesthesiology, University Clinics of Erlangen, Friedrich-Alexander-University of Erlangen, Erlangen, Germany
Search for more papers by this authorStephan Knipp
Department of cardio-thoracic surgery, University of Essen, Essen, Germany
Search for more papers by this authorCornelia Weber
Institute of Physiology & Pathophysiology, Department of Systems Physiology, University of Heidelberg, Heidelberg, Germany
Search for more papers by this authorSelina Hein
Department of Anesthesiology, University of Heidelberg, Heidelberg, Germany
Institute of Physiology & Pathophysiology, Department of Systems Physiology, University of Heidelberg, Heidelberg, Germany
Search for more papers by this authorStefanie Schinkel
Department of Medicine III: Cardiology, Angiology and Pneumonology, University of Heidelberg, Heidelberg, Germany
Search for more papers by this authorAndreas Walther
Department of Anesthesiology, University of Heidelberg, Heidelberg, Germany
Search for more papers by this authorRaffi Bekeredjian
Department of Medicine III: Cardiology, Angiology and Pneumonology, University of Heidelberg, Heidelberg, Germany
Search for more papers by this authorOliver J Müller
Department of Medicine III: Cardiology, Angiology and Pneumonology, University of Heidelberg, Heidelberg, Germany
Search for more papers by this authorCorresponding Author
Oliver Friedrich
Institute of Physiology & Pathophysiology, Department of Systems Physiology, University of Heidelberg, Heidelberg, Germany
Institute of Medical Biotechnology, Friedrich-Alexander-University of Erlangen-Nuremberg, Erlangen, Germany
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: [email protected]
Search for more papers by this authorSören Wagner
Department of Anesthesiology, University of Heidelberg, Heidelberg, Germany
Department of cardio-thoracic surgery, University of Essen, Essen, Germany
Institute of Physiology & Pathophysiology, Department of Systems Physiology, University of Heidelberg, Heidelberg, Germany
Department of Anesthesiology, University Clinics of Erlangen, Friedrich-Alexander-University of Erlangen, Erlangen, Germany
Search for more papers by this authorStephan Knipp
Department of cardio-thoracic surgery, University of Essen, Essen, Germany
Search for more papers by this authorCornelia Weber
Institute of Physiology & Pathophysiology, Department of Systems Physiology, University of Heidelberg, Heidelberg, Germany
Search for more papers by this authorSelina Hein
Department of Anesthesiology, University of Heidelberg, Heidelberg, Germany
Institute of Physiology & Pathophysiology, Department of Systems Physiology, University of Heidelberg, Heidelberg, Germany
Search for more papers by this authorStefanie Schinkel
Department of Medicine III: Cardiology, Angiology and Pneumonology, University of Heidelberg, Heidelberg, Germany
Search for more papers by this authorAndreas Walther
Department of Anesthesiology, University of Heidelberg, Heidelberg, Germany
Search for more papers by this authorRaffi Bekeredjian
Department of Medicine III: Cardiology, Angiology and Pneumonology, University of Heidelberg, Heidelberg, Germany
Search for more papers by this authorOliver J Müller
Department of Medicine III: Cardiology, Angiology and Pneumonology, University of Heidelberg, Heidelberg, Germany
Search for more papers by this authorCorresponding Author
Oliver Friedrich
Institute of Physiology & Pathophysiology, Department of Systems Physiology, University of Heidelberg, Heidelberg, Germany
Institute of Medical Biotechnology, Friedrich-Alexander-University of Erlangen-Nuremberg, Erlangen, Germany
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: [email protected]
Search for more papers by this authorAbstract
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.
Supporting Information
| Filename | Description |
|---|---|
| jcmm1630-sup-0001-DataS1.docxWord document, 19.8 KB | Data S1 Supporting Materials and Methods related to preparation, in vitro motility assays and biochemistry. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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