Respiratory EMG responsiveness to hypercapnic hypoxia in mdx mice

Abstract

Duchenne muscular dystrophy (DMD) is a fatal neuromuscular disease characterised by the absence of the structural protein dystrophin. Respiratory failure is the leading cause of premature death in DMD. Although respiratory insufficiency is recognized as a hallmark of DMD, respiratory control is relatively understudied. We hypothesized that enhanced drive in accessory respiratory motor pathways preserves ventilatory capacity compensating for severe respiratory muscle weakness.We utilised the C57BL/10ScSn‐Dmdmdx/J (mdx) mouse model. Respiratory flow recordings were performed in freely‐behaving wild‐type (WT, n=9) and mdx (n=7) mice at ~8 weeks of age using whole‐body plethysmography to determine ventilation (VE), oxygen consumption (VO2) and carbon dioxide production (VCO2). Baseline recordings were performed in normoxia, followed by chemostimulation using hypercapnic hypoxic gas challenge (FiO2=0.10; FiCO2=6; balance N2). In urethane (1.6 g/kg) anaesthetised WT (n=13) and mdx (n=14) mice, diaphragm, intercostal and genioglossus EMG and motor unit recordings were performed during baseline conditions and in response to chemostimulation.Plethysmographic recordings revealed that during chemostimulation, minute ventilation (VE) is equivalent in WT and mdx mice, highlighting a considerable ventilatory reserve in young mdx despite substantial diaphragm muscle weakness. Moreover, diaphragm, intercostal and genioglossus EMG responsiveness to hypercapnic hypoxia was equivalent in WT and mdx mice.Despite substantial diaphragm weakness and evidential muscle fibre damage and remodelling, freely behaving mdx mice can achieve enhanced ventilation during chemostimulation to levels equivalent to that of WT animals. We found no evidence of enhanced activity in respiratory muscle EMGs. Assessment of the motor unit population will allow for the comparison of the phenomena of rate coding and recruitment during increased respiratory muscle activation. Our study suggests that respiratory muscle weakness in young mdx does not compromise ventilator behaviour but is likely to have considerable impact on airway protective behaviours.Support or Funding InformationDepartment of Physiology, University College Cork, Cork, IrelandThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.