Inspiratory pressure‐generating capacity is preserved during ventilatory and non‐ventilatory behaviours despite profound diaphragm muscle weakness in young adult dystrophic (mdx) mice

Abstract

Diaphragm dysfunction is recognized in the mdx mouse model of muscular dystrophy, however there is a paucity of information concerning the neural control of dystrophic respiratory muscles. In young adult (8 weeks of age) male wild‐type and mdx mice, we assessed ventilatory capacity, neural activation of the diaphragm and external intercostal (EIC) muscles and inspiratory pressure‐generating capacity during ventilatory and non‐ventilatory behaviours. We hypothesized that respiratory muscle weakness is associated with impaired peak inspiratory pressure‐generating capacity in mdx mice.Ventilatory responsiveness to hypercapnic hypoxia was determined in conscious mice by whole‐body plethysmography. Diaphragm isometric and isotonic contractile properties were determined ex vivo. In anaesthetized mice, thoracic oesophageal pressure, and diaphragm and EIC electromyogram (EMG) activities were recorded during baseline conditions and sustained tracheal occlusion for 30–40s.Despite substantial diaphragm weakness, mdx mice retain the capacity to enhance ventilation during hypercapnic hypoxia. Peak volume‐ and flow‐related measures were also maintained in anaesthetized, vagotomized mdx mice. Peak inspiratory pressure was remarkably well preserved during chemoactivated breathing, augmented breaths, and maximal sustained efforts during airway obstruction in mdx mice. Diaphragm and EIC EMG activities were lower during airway obstruction in mdx compared with wild‐type mice.We conclude that ventilatory capacity is preserved in young mdx mice. Despite profound respiratory muscle weakness and lower diaphragm and EIC EMG activities during high demand in mdx mice, peak inspiratory pressure is preserved, owing to sufficient compensatory recruitment of accessory muscles beyond the primary muscles of inspiration. We suggest that a loss of compensation during progressive disease, combined with diaphragm dysfunction, underpins the development of respiratory system morbidity in dystrophic diseases.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.