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Loss of compensation by accessory muscles of breathing in advanced dystrophic disease
Author(s) -
O'Halloran Ken,
Burns David
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.04375
Subject(s) - respiratory system , diaphragm (acoustics) , medicine , hypercapnia , respiratory minute volume , duchenne muscular dystrophy , ventilation (architecture) , intercostal muscle , plethysmograph , tidal volume , anesthesia , mdx mouse , cardiology , anatomy , chemistry , dystrophin , mechanical engineering , physics , acoustics , loudspeaker , engineering
Peak inspiratory pressure‐generating capacity is preserved in mdx dystrophic mice, despite profound diaphragm muscle weakness and a reduction in peak diaphragm electromyogram activity 1 . Our data reveal a capacity for compensation afforded by accessory muscles of breathing, adequate to sustain peak respiratory system performance, at least in early dystrophic disease 1,2 . We hypothesise that compensation is lost during progressive dystrophic disease, culminating in respiratory failure, which is characteristic of Duchenne muscular dystrophy. Respiratory system performance was determined in male wild‐type (n=50) and mdx (n=48) mice at 4, 8, 12 and 16 months of age. Ventilation at rest and during hypoxic hypercapnic stimulation was determined in conscious mice using whole‐body plethysmography. In anesthetized mice, respiratory pressures and flow, peripheral oxygen saturation, end‐tidal carbon dioxide and electromyogram activities of the diaphragm, external intercostal, and parasternal intercostal muscles were recorded. Peak inspiratory pressure and respiratory electromyogram activities were measured before (baseline) and during sustained tracheal occlusion to generate maximal respiratory muscle activation. Minute ventilation during hypoxic hypercapnia was significantly lower in mdx mice at 16 months of age, due to reductions in tidal volume. Peak inspiratory pressure during airway obstruction was equivalent in wild‐type and mdx mice at 4, 8 and 12 months of age. At 16 months, there was a significant reduction in peak inspiratory pressure in mdx mice compared with wild‐type mice (‐44±11 cmH 2 O (n=9) vs. ‐57±17 cmH 2 O (n=11), mean±SD, P<0.05, Student's t test). Respiratory muscle electromyogram activities were lower in mdx compared with wild‐type at all ages, with evidence of significant reductions in baseline and peak activities from 8 months of age. Our results reveal a remarkable capacity for compensation of ventilatory and non‐ventilatory behaviours in mdx mice over the course of 12 months of dystrophic disease. In view of the relatively early decline in performance of the obligatory inspiratory muscles of breathing (diaphragm and intercostals), shown by decreased activation and intrinsic weakness, compensation is evidently provided by accessory muscles, which sustain ventilatory responsiveness and peak respiratory system performance until between 12‐16 months of age in mdx mice. Our findings have relevance to therapeutic strategies that aim to preserve respiratory system function in muscular dystrophy. References 1. 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. 2. Burns DP, Lucking EF, O'Halloran KD. Auxiliary compensation for diaphragm dysfunction in dystrophic disease. J. Physiol . 2019;597(15):4103‐4105.