Journal
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
Volume 45, Issue 6, Pages 754-760Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.yjmcc.2008.09.125
Keywords
mdx mouse heart; Right ventricular dysfunction; High-energy phosphate metabolism; Creatine uptake; Mitochondrion
Categories
Funding
- Clarendon Bursaries from University of Oxford
- Hong Kong Oxford Scholarship Fund Bursary
- British Heart Foundation
- British Heart Foundation [PS/02/002/14893, RG/07/004/22659] Funding Source: researchfish
- Medical Research Council [MC_U137761449, G0600829] Funding Source: researchfish
- MRC [MC_U137761449, G0600829] Funding Source: UKRI
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Patients with muscular dystrophy have abnormal cardiac function and decreased high-energy phosphate metabolism. Here, we have determined whether the 8 month old mdx mouse, an animal model of muscular dystrophy, also has abnormal cardiac function and energetics. In vivo cardiac MRI revealed 33% and 104% larger right ventricular end-diastolic and end-systolic volumes, respectively, and 17% lower right ventricular ejection fractions in mdx mice compared with controls. Evidence of left ventricular diastolic dysfunction included 18% lower peak filling rates in mdx mouse hearts. Abnormal cardiac function was accompanied by necrosis and lower citrate synthase activity in the mdx mouse heart, suggesting decreased mitochonchial content. Decreased mitochondrial numbers were associated with 38% lower phosphocreatine concentration, 22% lower total creatine, 36% higher cytosolic free ADP concentration and 1.3 kJ/mol lower free-energy available from ATP hydrolysis in whole isolated, perfused mdx Mouse hearts than in controls. Transsarcolemmal creatine uptake was 12% lower in mdx mouse hearts. We conclude that the absence of dystrophin in adult mdx mouse heart, as in the heart of human patient, is associated with right ventricular dilatation, left ventricular diastolic dysfunction and abnormal energy metabolism. (C) 2008 Elsevier Inc. All rights reserved.
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