Universität zu Köln

Lewis, Phillip and O'Halloran, Ken D. (2016). Diaphragm Muscle Adaptation to Sustained Hypoxia: Lessons from Animal Models with Relevance to High Altitude and Chronic Respiratory Diseases. Front. Physiol., 7. LAUSANNE: FRONTIERS MEDIA SA. ISSN 1664-042X

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Abstract

The diaphragm is the primary inspiratory pump muscle of breathing. Notwithstanding its critical role in pulmonary ventilation, the diaphragm like other striated muscles is malleable in response to physiological and pathophysiological stressors, with potential implications for the maintenance of respiratory homeostasis. This review considers hypoxic adaptation of the diaphragm muscle, with a focus on functional, structural, and metabolic remodeling relevant to conditions such as high altitude and chronic respiratory disease. On the basis of emerging data in animal models, we posit that hypoxia is a significant driver of respiratory muscle plasticity, with evidence suggestive of both compensatory and deleterious adaptations in conditions of sustained exposure to low oxygen. Cellular strategies driving diaphragm remodeling during exposure to sustained hypoxia appear to confer hypoxic tolerance at the expense of peak force-generating capacity, a key functional parameter that correlates with patient morbidity and mortality. Changes include, but are not limited to: redox-dependent activation of hypoxia-inducible factor (HIF) and MAP kinases; time-dependent carbonylation of key metabolic and functional proteins; decreased mitochondrial respiration; activation of atrophic signaling and increased proteolysis; and altered functional performance. Diaphragm muscle weakness may be a signature effect of sustained hypoxic exposure. We discuss the putative role of reactive oxygen species as mediators of both advantageous and disadvantageous adaptations of diaphragm muscle to sustained hypoxia, and the role of antioxidants in mitigating adverse effects of chronic hypoxic stress on respiratory muscle function.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Lewis, Phillip UNSPECIFIED UNSPECIFIED UNSPECIFIED O'Halloran, Ken D. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-252635
DOI:	10.3339/fphys.2016.00623
Journal or Publication Title:	Front. Physiol.
Volume:	7
Date:	2016
Publisher:	FRONTIERS MEDIA SA
Place of Publication:	LAUSANNE
ISSN:	1664-042X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language OBSTRUCTIVE PULMONARY-DISEASE; CHRONIC HYPOBARIC HYPOXIA; SKELETAL-MUSCLE; OXIDATIVE STRESS; REACTIVE OXYGEN; INDUCIBLE FACTOR; RAT DIAPHRAGM; MITOCHONDRIAL-FUNCTION; NORMOBARIC HYPOXIA; FIBER DYSFUNCTION Multiple languages Physiology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/25263