title: The heart in Duchenne muscular dystrophy: early detection of contractile performance alteration.
abstract: Progressive cardiomyopathy is a major cause of death in Duchenne muscular dystrophy (DMD) patients. Coupling between Ca(2+) handling and contractile properties in dystrophic hearts is poorly understood. It is also not clear whether developing cardiac failure is dominated by alterations in Ca(2+) pathways or more related to the contractile apparatus. We simultaneously recorded force and Ca(2+) 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 Ca(2+) to additionally account for force decrements in mdx muscles. pCa-force relations revealed decreased mdx myofibrillar Ca(2+) 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.
authors.affiliation: Department of Anesthesiology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Sören
authors.initials: S
authors.lastname: Wagner
authors.forename: Stephan
authors.initials: S
authors.lastname: Knipp
authors.forename: Cornelia
authors.initials: C
authors.lastname: Weber
authors.forename: Selina
authors.initials: S
authors.lastname: Hein
authors.forename: Stefanie
authors.initials: S
authors.lastname: Schinkel
authors.forename: Andreas
authors.initials: A
authors.lastname: Walther
authors.forename: Raffi
authors.initials: R
authors.lastname: Bekeredjian
authors.forename: Oliver J
authors.initials: OJ
authors.lastname: Müller
authors.forename: Oliver
authors.initials: O
authors.lastname: Friedrich
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D006332:Cardiomegaly; D009202:Cardiomyopathies; D002478:Cells, Cultured; D004452:Echocardiography; D006321:Heart / Q000503:physiopathology*; D051379:Mice; D018101:Mice, Inbred mdx; D020388:Muscular Dystrophy, Duchenne / Q000503:physiopathology*; D009200:Myocardial Contraction; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D010210:Papillary Muscles / Q000503:physiopathology*
chemical_list: D002118:Calcium