Journal Article

Steroid treatment causes deterioration of myocardial function in the δ-sarcoglycan-deficient mouse model for dilated cardiomyopathy

R. Bauer, G.A. MacGowan, A. Blain, K. Bushby and V. Straub

in Cardiovascular Research

Published on behalf of European Society of Cardiology

Volume 79, issue 4, pages 652-661
Published in print September 2008 | ISSN: 0008-6363
Published online May 2008 | e-ISSN: 1755-3245 | DOI: http://dx.doi.org/10.1093/cvr/cvn131
Steroid treatment causes deterioration of myocardial function in the δ-sarcoglycan-deficient mouse model for dilated cardiomyopathy

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Aims

As oral corticosteroids have a beneficial effect on muscle strength in Duchenne muscular dystrophy, it has been suggested that they may also be a useful treatment in the pathologically related sarcoglycanopathies. The δ-sarcoglycan-deficient mouse (Sgcd-null) is a model for both limb girdle muscular dystrophy 2F (LGMD2F) and dilated cardiomyopathy.

Methods and results

To study the effect of oral corticosteroids on cardiac function, we treated 8-week-old Sgcd-null mice with prednisolone (1.5 mg/kg body weight/day orally) for 8 weeks. In vivo cardiac function was assessed by pressure–volume loops using a conductance catheter. We found a well-compensated cardiomyopathy at baseline in Sgcd-null mice with decreased myocardial contractility, increased preload, and decreased afterload, maintaining a high cardiac output. Cardiac haemodynamics, surprisingly, did not improve in prednisolone-treated mice, but instead deteriorated with evidence of ventricular stiffening. On histology, after steroid treatment there was increased myocardial cell damage and increased myocardial fibrosis.

Conclusion

Prednisolone led to a decompensation of cardiac haemodynamics in Sgcd-null mice and induced additional cardiac damage. On the basis of these findings, although mouse models may not completely replicate the human situation for LGMD2F, we conclude that careful cardiac monitoring is clearly indicated in patients on long-term corticosteroids.

Keywords: Dilated cardiomyopathy; Muscular dystrophy; Corticosteroids; Delta-sarcogylcan

Journal Article.  5827 words.  Illustrated.

Subjects: Cardiovascular Medicine

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