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Beta-Blockers, Left and Right Ventricular Function, and In-Vivo Calcium Influx in Muscular Dystrophy Cardiomyopathy

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      Abstract

      Beta-blockers are used to treat acquired heart failure in adults, though their role in early muscular dystrophy cardiomyopathy is unclear. We treated 2 different dystrophic mouse models which have an associated cardiomyopathy ( mdx: model for Duchenne Muscular Dystrophy, and Sgcd-/-: model for limb girdle muscular dystrophy type 2F) and wild type controls (C57 Bl10) with the beta blocker metoprolol or placebo for 8 weeks at an early stage in the development of the cardiomyopathy. Left and right ventricular function was assessed with cardiac magnetic resonance imaging (MRI) and in-vivo myocardial calcium influx with manganese enhanced MRI. In the mdx mice at baseline there was reduced stroke volume, cardiac index, and end-diastolic volume with preserved left ventricular ejection fraction. These abnormalities were no longer evident after treatment with beta-blockers. Right ventricular ejection fraction was reduced and right ventricular end-systolic volume increased in the mdx mice. With metoprolol there was an increase in right ventricular end-diastolic and end-systolic volumes. Left and right ventricular function was normal in the Sgcd-/- mice. Metroprolol had no significant effects on left and right ventricular function in these mice, though heart/body weight ratios increased after treatment. In-vivo myocardial calcium influx with MEMRI was significantly elevated in both models, though metoprolol had no significant effects on either. In conclusion, metoprolol treatment at an early stage in the development of cardiomyopathy has deleterious effects on right ventricular function in mdx mice and in both models no effect on increased in-vivo calcium influx. This suggests that clinical trials need to carefully monitor not just left ventricular function but also right ventricular function and other aspects of myocardial metabolism.

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      Author and article information

      Affiliations
      [1 ]Institute of Genetic Medicine, Newcastle University, International Centre for Life, Central Parkway, Newcastle upon Tyne, United Kingdom
      [2 ]Institute of Cellular Medicine and Newcastle Magnetic Resonance Centre, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, United Kingdom
      [3 ]Department of Cardiology, Freeman Hospital, Newcastle upon Tyne, United Kingdom
      University of Buenos Aires, Cardiovascular Pathophysiology Institute, Argentina
      Author notes

      Competing Interests: The authors have declared that no competing interests exist.

      Conceived and designed the experiments: A. Blain EG SL A. Blamire VS GAM. Performed the experiments: A. Blain EG A. Blamire GAM. Analyzed the data: A. Blain EG SL A. Blamire VS GAM. Contributed reagents/materials/analysis tools: A. Blain EG A. Blamire SL VS GAM. Wrote the paper: A. Blain EG AB SL VS GAM.

      Contributors
      Role: Editor
      Journal
      PLoS One
      PLoS ONE
      plos
      plosone
      PLoS ONE
      Public Library of Science (San Francisco, USA )
      1932-6203
      2013
      20 February 2013
      : 8
      : 2
      23437355
      3577707
      PONE-D-12-30652
      10.1371/journal.pone.0057260
      (Editor)

      This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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      Pages: 7
      Funding
      Funded in part by Heart Research UK grant RG 2585 and British Heart Foundation Clinical Leave Research Fellowship FS/11/89/29162 (both to GMG). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
      Categories
      Research Article
      Biology
      Model Organisms
      Animal Models
      Mouse
      Molecular Cell Biology
      Signal Transduction
      Signaling in Cellular Processes
      Calcium Signaling
      Medicine
      Cardiovascular
      Cardiomyopathies
      Cardiovascular Imaging
      Cardiovascular Pharmacology
      Heart Failure
      Hemodynamics
      Clinical Genetics
      X-Linked
      Duchenne Muscular Dystrophy
      Clinical Research Design
      Animal Models of Disease
      Neurology
      Muscular Dystrophies
      Radiology
      Diagnostic Radiology
      Magnetic Resonance Imaging

      Uncategorized

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