Sensorimotor control of breathing in the mdx mouse model of Duchenne muscular dystrophy

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dc.check.date2018-09-26
dc.check.infoAccess to this article is restricted until 12 months after publication by request of the publisheren
dc.contributor.authorBurns, David P.
dc.contributor.authorRoy, Arijit
dc.contributor.authorLucking, Eric F.
dc.contributor.authorMcDonald, Fiona B.
dc.contributor.authorGray, Sam
dc.contributor.authorWilson, Richard J.
dc.contributor.authorEdge, Deirdre
dc.contributor.authorO'Halloran, Ken D.
dc.contributor.funderUniversity College Corken
dc.contributor.funderAlberta Innovates - Health Solutionsen
dc.contributor.funderCanadian Institutes for Health Researchen
dc.date.accessioned2018-05-30T12:28:17Z
dc.date.available2018-05-30T12:28:17Z
dc.date.issued2017-09-26
dc.date.updated2018-05-30T11:30:55Z
dc.description.abstractPatients with Duchenne muscular dystrophy (DMD) hypoventilate with consequential arterial blood gas derangement relevant to disease progression. Whereas deficits in DMD diaphragm are recognized, there is a paucity of knowledge in respect of the neural control of breathing in dystrophinopathies. We sought to perform an analysis of respiratory control in a model of DMD, the mdx mouse. In 8-week-old male wild-type and mdx mice, ventilation and metabolism, carotid body afferent activity, diaphragm muscle force-generating capacity, and muscle fibre size, distribution and centronucleation were determined. Diaphragm EMG activity and responsiveness to chemostimulation was determined. During normoxia, mdx mice hypo-ventilated, owing to a reduction in tidal volume. Basal CO2 production was not different between wild-type and mdx mice. Carotid sinus nerve responses to hyperoxia were blunted in mdx, suggesting hypoactivity. However, carotid body, ventilatory and metabolic responses to hypoxia were equivalent in wild-type and mdx mice. Diaphragm force was severely depressed in mdx mice, with evidence of fibre remodelling and damage. Diaphragm EMG responses to chemoactivation were enhanced in mdx mice. We conclude that there is evidence of chronic hypoventilation in young mdx mice. Diaphragm dysfunction confers mechanical deficiency in mdx resulting in impaired capacity to generate normal tidal volume at rest and decreased absolute ventilation during chemoactivation. Enhanced mdx diaphragm EMG responsiveness suggests compensatory neuroplasticity facilitating respiratory motor output, which may extend to accessory muscles of breathing. Our results may have relevance to emerging treatments for human DMD aiming to preserve ventilatory capacity.en
dc.description.sponsorshipUniversity College Cork (Department of Physiology)en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationBurns, D. P., Roy A., Lucking E. F., McDonald F. B., Gray S., Wilson R. J., Edge D. and O'Halloran K. D. (2017) 'Sensorimotor control of breathing in the mdx mouse model of Duchenne muscular dystrophy', Journal of Physiology, 595(21), pp. 6653-6672. doi:10.1113/JP274792en
dc.identifier.doi10.1113/JP274792
dc.identifier.endpage6672en
dc.identifier.issn0022-3751
dc.identifier.issued21en
dc.identifier.journaltitleJournal of Physiologyen
dc.identifier.startpage6653en
dc.identifier.urihttps://hdl.handle.net/10468/6208
dc.identifier.volume595en
dc.language.isoenen
dc.publisherJohn Wiley & Sons, Inc.en
dc.rights© 2017, The Authors. The Journal of Physiology © 2017, The Physiological Society. This is the peer reviewed version of the following article: Burns, D. P., Roy A., Lucking E. F., McDonald F. B., Gray S., Wilson R. J., Edge D. and O'Halloran K. D. (2017) 'Sensorimotor control of breathing in the mdx mouse model of Duchenne muscular dystrophy', Journal of Physiology, 595(21), pp. 6653-6672. doi:10.1113/JP274792 which has been published in final form at doi:10.1113/JP274792. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.en
dc.subjectDuchenne muscular dystrophyen
dc.subjectMdxen
dc.subjectHypoventilationen
dc.subjectCarotid bodyen
dc.subjectDiaphragmen
dc.subjectEMGen
dc.titleSensorimotor control of breathing in the mdx mouse model of Duchenne muscular dystrophyen
dc.typeArticle (peer-reviewed)en
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