title: Diaphragm muscle fiber function and structure in humans with hemidiaphragm paralysis.
abstract: Recent studies proposed that mechanical inactivity of the human diaphragm during mechanical ventilation rapidly causes diaphragm atrophy and weakness. However, conclusive evidence for the notion that diaphragm weakness is a direct consequence of mechanical inactivity is lacking. To study the effect of hemidiaphragm paralysis on diaphragm muscle fiber function and structure in humans, biopsies were obtained from the paralyzed hemidiaphragm in eight patients with hemidiaphragm paralysis. All patients had unilateral paralysis of known duration, caused by en bloc resection of the phrenic nerve with a tumor. Furthermore, diaphragm biopsies were obtained from three control subjects. The contractile performance of demembranated muscle fibers was determined, as well as fiber ultrastructure and morphology. Finally, expression of E3 ligases and proteasome activity was determined to evaluate activation of the ubiquitin-proteasome pathway. The force-generating capacity, as well as myofibrillar ultrastructure, of diaphragm muscle fibers was preserved up to 8 wk of paralysis. The cross-sectional area of slow fibers was reduced after 2 wk of paralysis; that of fast fibers was preserved up to 8 wk. The expression of the E3 ligases MAFbx and MuRF-1 and proteasome activity was not significantly upregulated in diaphragm fibers following paralysis, not even after 72 and 88 wk of paralysis, at which time marked atrophy of slow and fast diaphragm fibers had occurred. Diaphragm muscle fiber atrophy and weakness following hemidiaphragm paralysis develops slowly and takes months to occur.
authors.affiliation: Department of Surgery, Vrije Universiteit University Medical Center/Institute for Cardiovascular Research, The Netherlands.
authors.forename: W N
authors.initials: WN
authors.lastname: Welvaart
authors.forename: M A
authors.initials: MA
authors.lastname: Paul
authors.forename: H W H
authors.initials: HW
authors.lastname: van Hees
authors.forename: G J M
authors.initials: GJ
authors.lastname: Stienen
authors.forename: J W M
authors.initials: JW
authors.lastname: Niessen
authors.forename: F S
authors.initials: FS
authors.lastname: de Man
authors.forename: G C
authors.initials: GC
authors.lastname: Sieck
authors.forename: A
authors.initials: A
authors.lastname: Vonk-Noordegraaf
authors.forename: C A C
authors.initials: CA
authors.lastname: Ottenheijm
mesh_terms: D000368:Aged; D019412:Anatomy, Cross-Sectional; D003964:Diaphragm / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D009119:Muscle Contraction; D018656:Muscle Fibers, Fast-Twitch; D018485:Muscle Fibers, Skeletal / Q000201:enzymology / Q000473:pathology*; D018657:Muscle Fibers, Slow-Twitch; D009124:Muscle Proteins / Q000378:metabolism; D018908:Muscle Weakness / Q000209:etiology / Q000503:physiopathology; D009133:Muscular Atrophy / Q000209:etiology / Q000473:pathology; D010243:Paralysis / Q000150:complications / Q000175:diagnosis* / Q000209:etiology / Q000503:physiopathology*; D010791:Phrenic Nerve / Q000601:surgery; D011183:Postoperative Complications; D046988:Proteasome Endopeptidase Complex; D013902:Radiography, Thoracic; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: D009124:Muscle Proteins; D000070584:Tripartite Motif Proteins; C440907:FBXO32 protein, human; D044843:SKP Cullin F-Box Protein Ligases; C440908:TRIM63 protein, human; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex