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

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dc.contributor.author Burns, David P.
dc.contributor.author Murphy, Kevin H.
dc.contributor.author Lucking Eric F.
dc.contributor.author O'Halloran, Ken D.
dc.date.accessioned 2019-01-09T16:08:07Z
dc.date.available 2019-01-09T16:08:07Z
dc.date.issued 2018-12-20
dc.identifier.citation Burns, D. P., Murphy, K. H., Lucking, E. F. and O'Halloran, K. D. 'Inspiratory pressure-generating capacity is preserved during ventilatory and non-ventilatory behaviours in young dystrophic mdx mice despite profound diaphragm muscle weakness', The Journal of Physiology, In Press, doi: 10.1113/JP277443 en
dc.identifier.startpage 1 en
dc.identifier.endpage 38 en
dc.identifier.issn 0022-3751
dc.identifier.uri http://hdl.handle.net/10468/7277
dc.identifier.doi 10.1113/JP277443
dc.description.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, revealing adequate compensation in support of respiratory system performance, at least early in dystrophic disease. We suggest that a progressive loss of compensation during advancing disease, combined with diaphragm dysfunction, underpins the development of respiratory system morbidity in dystrophic diseases. en
dc.description.sponsorship University College Cork (Department of Physiology) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Wiley en
dc.relation.uri https://physoc.onlinelibrary.wiley.com/doi/10.1113/JP277443
dc.rights © 2018 The Physiological Society. Published by Wiley. This is the peer reviewed version of the following article: (2019), Inspiratory pressure‐generating capacity is preserved during ventilatory and non‐ventilatory behaviours in young dystrophic mdx mice despite profound diaphragm muscle weakness. J Physiol. Accepted Author Manuscript, which has been published in final form at https://doi.org/10.1113/JP277443. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. en
dc.subject Breathing en
dc.subject Diaphragm en
dc.subject DMD en
dc.subject EMG en
dc.subject Intercostal en
dc.subject mdx en
dc.subject Oesophageal pressure en
dc.subject Duchenne muscular dystrophy (DMD) en
dc.subject Respiratory muscle weaknes en
dc.title Inspiratory pressure-generating capacity is preserved during ventilatory and non-ventilatory behaviours in young dystrophic mdx mice despite profound diaphragm muscle weakness en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Ken O'Halloran, Physiology, University College Cork, Cork, Ireland. +353-21-490-3000 Email: k.ohalloran@ucc.ie en
dc.internal.availability Full text available en
dc.check.info Access to this article is restricted until 12 months after publication by request of the publisher. en
dc.check.date 2019-12-20
dc.date.updated 2019-01-09T15:57:12Z
dc.description.version Accepted Version en
dc.internal.rssid 465912035
dc.contributor.funder University College Cork en
dc.description.status Peer reviewed en
dc.identifier.journaltitle The Journal of Physiology en
dc.internal.copyrightchecked No !!CORA!! en
dc.internal.licenseacceptance Yes en
dc.internal.IRISemailaddress k.ohalloran@ucc.ie en
dc.internal.bibliocheck In Press Jan 2019. Update citation, copyright statement, page numbers. Add volume, issue. en


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