title: Diaphragm and ventilatory dysfunction during cancer cachexia.
abstract: Cancer cachexia is characterized by a continuous loss of locomotor skeletal muscle mass, which causes profound muscle weakness. If this atrophy and weakness also occurs in diaphragm muscle, it could lead to respiratory failure, which is a major cause of death in patients with cancer. Thus, the purpose of the current study was to determine whether colon-26 (C-26) cancer cachexia causes diaphragm muscle fiber atrophy and weakness and compromises ventilation. All diaphragm muscle fiber types were significantly atrophied in C-26 mice compared to controls, and the atrophy-related genes, atrogin-1 and MuRF1, significantly increased. Maximum isometric specific force of diaphragm strips, absolute maximal calcium activated force, and maximal specific calcium-activated force of permeabilized diaphragm fibers were all significantly decreased in C-26 mice compared to controls. Further, isotonic contractile properties of the diaphragm were affected to an even greater extent than isometric function. Ventilation measurements demonstrated that C-26 mice have a significantly lower tidal volume compared to controls under basal conditions and, unlike control mice, an inability to increase breathing frequency, tidal volume, and, thus, minute ventilation in response to a respiratory challenge. These data demonstrate that C-26 cancer cachexia causes profound respiratory muscle atrophy and weakness and ventilatory dysfunction.
authors.affiliation: Department of Physical Therapy, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Brandon M
authors.initials: BM
authors.lastname: Roberts
authors.forename: Bumsoo
authors.initials: B
authors.lastname: Ahn
authors.forename: Ashley J
authors.initials: AJ
authors.lastname: Smuder
authors.forename: Monsour
authors.initials: M
authors.lastname: Al-Rajhi
authors.forename: Luther C
authors.initials: LC
authors.lastname: Gill
authors.forename: Adam W
authors.initials: AW
authors.lastname: Beharry
authors.forename: Scott K
authors.initials: SK
authors.lastname: Powers
authors.forename: David D
authors.initials: DD
authors.lastname: Fuller
authors.forename: Leonardo F
authors.initials: LF
authors.lastname: Ferreira
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Judge
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002100:Cachexia / Q000209:etiology / Q000503:physiopathology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000150:complications / Q000503:physiopathology*; D003964:Diaphragm / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D015870:Gene Expression; D007150:Immunohistochemistry; D051379:Mice; D009124:Muscle Proteins / Q000235:genetics; D018908:Muscle Weakness / Q000209:etiology / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009133:Muscular Atrophy / Q000209:etiology / Q000503:physiopathology*; D018995:Myosin Heavy Chains / Q000378:metabolism; D012131:Respiratory Insufficiency / Q000209:etiology / Q000503:physiopathology*; D012132:Respiratory Muscles / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics; D000070584:Tripartite Motif Proteins; D014335:Tropomyosin / Q000378:metabolism; D014336:Troponin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics
chemical_list: D000199:Actins; D009124:Muscle Proteins; D000070584:Tripartite Motif Proteins; D014335:Tropomyosin; D014336:Troponin; C486691:Fbxo32 protein, mouse; D044843:SKP Cullin F-Box Protein Ligases; C499084:Trim63 protein, mouse; D044767:Ubiquitin-Protein Ligases; D018995:Myosin Heavy Chains
keywords: C-26; limb muscle; muscle function; respiratory muscles; single fiber