Chronic Intermittent Hypoxia Enhances Respiratory Muscle Weakness in Dystrophindeficient mdx Mice

Sleep‐disordered breathing (SDB) is a prominent feature of neuromuscular disease, likely due to pharyngeal dilator muscle weakness. Boys with Duchenne muscular dystrophy (DMD) experience nocturnal desaturation during sleep as a result of obstructive and central apnoea. We have previously described maladaptive changes in respiratory muscle structure and function in rodent models of chronic intermittent hypoxia (CIH), a hallmark feature of SDB driving many pathologies. We hypothesized that CIH exacerbates respiratory muscle dysfunction in muscular dystrophy. We sought to explore the effects of CIH on respiratory muscle structure and function in wild‐type (WT) and dystrophin‐deficient mdx mice. Six week old male WT and mdx mice were exposed to CIH, consisting of alternating bouts of hypoxia (90s; 5–6.5% O 2 at the nadir) and normoxia (210s, 21% O 2 ) for 12 cycles per hour, 8 hours per day for 14 days. Sham animals were exposed to normoxia in parallel. The diaphragm and sternohyoid (representative pharyngeal dilator) muscles were excised and functional parameters were examined ex vivo . Substantial muscle weakness was observed in dystrophic diaphragm and sternohyoid muscle compared with WT muscles. Exposure to CIH elicited significant muscle weakness in the diaphragm and sternohyoid of WT mice. In mdx mice, exposure to CIH resulted in further weakness in the compromised diaphragm. CIH‐induced potentiation of muscle weakness was less robust in the sternohyoid. We have recently established the essential role of NADPH oxidase in CIH‐induced respiratory muscle weakness. We are currently exploring the molecular mechanisms of CIH‐induced respiratory muscle weakness in WT and mdx mice. Our findings demonstrate that exposure to CIH exacerbates respiratory muscle weakness in the mdx model of muscular dystrophy. Since SDB is a feature of DMD, we reason that SDB may accelerate respiratory insufficiency in DMD. An understanding of the pathogenic factors driving CIH‐induced muscle weakness in mdx may help inform therapeutic strategies that may have relevance to DMD boys. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .