Accessory Muscle Support of Breathing in Young Dystrophin-deficient mdx Mice.

Duchenne muscular dystrophy (DMD) is a genetic neuromuscular disorder that occurs due to the absence of the structural protein dystrophin and secondary consequences. DMD is characterized by severe and progressive skeletal muscle weakness, which extends to the respiratory muscles. In young dystrophin-deficient mdx mice, peak inspiratory pressure-generating capacity is preserved despite diaphragm muscle weakness and reduced electromyogram (EMG) activity . Our overarching hypothesis is that accessory muscle compensation limits ventilatory deficit in early dystrophic disease. Four-month-old male wild-type (n=39) and mdx (n=41) mice were studied. Breathing was assessed in conscious mice using whole body plethysmography during normoxia and chemochallenge (10% O /6% CO ). Thoracic oesophageal pressure and obligatory (diaphragm and external intercostal) respiratory muscle EMG activities were recorded in urethane (1.7g/kg i.p.) anaesthetised spontaneously breathing mice during baseline and sustained tracheal occlusion (maximal muscle activation). Diaphragm and scalene (accessory respiratory muscle) force output were examined ex vivo. Data were statistically compared using unpaired Student's t test or two-way ANOVA with Bonferroni post hoc test. Peak diaphragm force ex vivo (P < 0.0001) and baseline diaphragm EMG activity (P = 0.01) were significantly lower in mdx compared with wild-type. Minute ventilation was equivalent in age-matched wild-type and mdx mice during baseline and chemochallenge (P = 0.1). Peak diaphragm (P < 0.0001) and external intercostal (P = 0.01) EMG activities during obstruction were significantly lower in mdx mice compared to wild-type, while peak inspiratory pressure was equivalent (P = 0.4). Interestingly, peak scalene muscle force ex vivo was preserved in 4-month-old mdx mice (P = 0.8). Despite a decline in diaphragm muscle performance (decreased EMG activity and mechanical weakness) at baseline, ventilatory capacity is preserved in mdx mice. Furthermore, despite lower peak electrical activation of the obligatory muscles of breathing and diaphragm muscle functional deficit, peak inspiratory pressure is preserved in 4-month-old mdx mice, confirming our previous findings in 2-month-old mice . Our finding of preserved scalene muscle force suggests that compensation may be provided by accessory muscles to support ventilatory and non-ventilatory behaviours in early dystrophic disease. Current studies are examining the EMG activity of accessory respiratory muscles (e.g. scalene, sternomastoid, cleidomastoid and trapezius) in early and advanced dystrophic disease in mdx mice. 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.