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


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.


CONCLUSIONS
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.
Bauer
R
R
Institute of Human Genetics, Newcastle University, International Center for Life, Newcastle upon Tyne NE1 3BZ, UK.
Macgowan
G A
GA
Blain
A
A
Bushby
K
K
Straub
V
V
D000284:Administration, Oral; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004280:Dobutamine / Q000008:administration & dosage; D005355:Fibrosis; D006439:Hemodynamics / Q000187:drug effects*; D007262:Infusions, Intravenous; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D011239:Prednisolone / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D049031:Sarcoglycans / Q000172:deficiency* / Q000235:genetics; D013318:Stroke Volume / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D016277:Ventricular Function, Left / Q000187:drug effects*; D017725:Ventricular Pressure / Q000187:drug effects
D000305:Adrenal Cortex Hormones; D000318:Adrenergic beta-Agonists; D012333:RNA, Messenger; D049031:Sarcoglycans; D014409:Tumor Necrosis Factor-alpha; D004280:Dobutamine; D011239:Prednisolone