Abstract
Duchenne muscular dystrophy (DMD) is characterized by respiratory muscle injury and weakness, ultimately leading to respiratory failure. Impaired respiratory muscle performance, fibrosis and inflammation in early disease are evident in the dystrophin-deficient mdx mouse model of DMD. Prednisone or similar treatment is the current standard of care for DMD and exerts its benefits via an anti-inflammatory action, but chronic treatment is associated with side-effects. A recent study demonstrated improved function in mdx limb muscle with weekly glucocorticoid treatment compared with daily treatment. Herein, we investigated the effect of weekly α-methylprednisolone (PRED) treatment alone and the effect of PRED in combination with daily intake of the antioxidant N-acetyl cysteine, NAC (PREDNAC) on respiratory performance. One-month-old male mdx mice received PRED (0.8 mg/kg methylprednisolone i.p. weekly) or PREDNAC (0.8 mg/kg methylprednisolone i.p. weekly and 1% NAC in drinking water daily) for 3 months. At 4 months of age, conscious breathing was measured in vivo by whole-body plethysmography. Under urethane general anaesthesia, respiratory EMG and inspiratory pressure were measured at baseline and during maximal activity. The intrinsic force-generating capacity of the diaphragm was determined ex vivo. Neither PRED nor PREDNAC influenced breathing or diaphragm force-generating capacity in mdx mice. There was a significant increase in diaphragm and parasternal EMG activity, but inspiratory pressure was unchanged with treatment. We conclude that neither PRED nor PREDNAC has a major beneficial effect on respiratory system performance in the mdx mouse model of DMD. Weekly administration of glucocorticoids is inadequate to protect respiratory performance in mdx mice, which might reflect the higher duty cycle of respiratory muscles compared with limb muscles.