Obligatory and accessory respiratory muscle physiology in advanced dystrophic disease
Authors: Slyne Aoife D , Wöller Karina , May Amandine , Dowd Roisin , Drummond Sarah E , O'Halloran Ken D 
Published: May 2023

Duchenne muscular dystrophy (DMD) is a genetic neuromuscular disorder, characterized by severe and progressive skeletal muscle weakness, which extends to the respiratory muscles. We have determined that ventilatory capacity and peak inspiratory pressure-generating capacity are preserved in early dystrophic disease in the mdx mouse model of muscular dystrophy, despite profound diaphragm muscle weakness and reduced peak diaphragm electromyogram (EMG) activitya, thus revealing a capacity for compensation afforded by extra-diaphragmatic muscles of breathing. We hypothesise that peak inspiratory pressure-generating capacity is impaired in advanced dystrophic disease in mdx mice, due to loss of compensation afforded by accessory respiratory muscles.Inspiratory pressure-generating capacity and obligatory and accessory respiratory muscle structure were examined in male wild-type and mdx mice in early (4 month old) and advanced (16 month old) dystrophic disease. Inspiratory pressure was recorded in urethane (1.7g/kg i.p.) anaesthetised, spontaneously breathing mice during baseline and sustained tracheal occlusion (maximal muscle activation). Histology and immunofluorescence were used to assess the form of obligatory (diaphragm and parasternal) and accessory (sternomastoid and cleidomastoid) respiratory muscles.Our study revealed preserved peak inspiratory pressure generating capacity in early dystrophic disease. Peak inspiratory pressure generating capacity is impaired in advanced dystrophic disease. We reason that this is due to the loss of compensation afforded by accessory respiratory muscles. The relative area of collagen deposition (fibrosis) is significantly increased in mdx obligatory and accessory respiratory muscles in early dystrophic disease. The relative area of collagen deposition in mdx obligatory and accessory respiratory muscles increased with disease progression, but interestingly the increase was most pronounced in the diaphragm muscle. Myofibre remodelling is evident in mdx diaphragm muscle, but not extra-diaphragmatic muscles in early dystrophic disease. Mean minimal Feret’s diameter is reduced (relative atrophy) in all muscles in advanced dystrophic disease.Following characterisation of respiratory system performance and obligatory and accessory muscle physiology in early dystrophic disease, studies are now being extended to assess ventilatory capacity and obligatory and accessory respiratory muscle contractile function and EMG activities in advanced dystrophic disease. Characterisation of the fundamental control of breathing in mdx mice should provide a comprehensive vista of the disease, potentially revealing novel therapeutic targets. References a Burns DP, Murphy KH, Lucking EF, O'Halloran KD. Inspiratory pressure-generating capacity is preserved during ventilatory and non-ventilatory behaviours in young dystrophic mdx mice despite profound diaphragm muscle weakness. J. Physiol. 2019;597(3):831-848.

Eli Lilly & Science Foundation Ireland (19/FFP/6628).

This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.