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

Cardiovasc Res. 2008 Sep 1;79(4):652-61. doi: 10.1093/cvr/cvn131. Epub 2008 May 20.


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 delta-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adrenal Cortex Hormones / administration & dosage
  • Adrenal Cortex Hormones / adverse effects
  • Adrenal Cortex Hormones / pharmacology*
  • Adrenergic beta-Agonists / administration & dosage
  • Animals
  • Body Weight / drug effects
  • Cardiomyopathy, Dilated / drug therapy*
  • Cardiomyopathy, Dilated / pathology
  • Cardiomyopathy, Dilated / physiopathology
  • Disease Models, Animal
  • Dobutamine / administration & dosage
  • Fibrosis
  • Hemodynamics / drug effects*
  • Infusions, Intravenous
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myocardial Contraction / drug effects
  • Myocardium / metabolism
  • Myocardium / pathology*
  • Prednisolone / administration & dosage
  • Prednisolone / adverse effects
  • Prednisolone / pharmacology*
  • RNA, Messenger / metabolism
  • Sarcoglycans / deficiency*
  • Sarcoglycans / genetics
  • Stroke Volume / drug effects
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • Ventricular Function, Left / drug effects*
  • Ventricular Pressure / drug effects


  • Adrenal Cortex Hormones
  • Adrenergic beta-Agonists
  • RNA, Messenger
  • Sarcoglycans
  • Tumor Necrosis Factor-alpha
  • Dobutamine
  • Prednisolone