Diaphragm muscle fiber function and structure in humans with hemidiaphragm paralysis

W. N. Welvaart, M. A. Paul, H. W H van Hees, G. J M Stienen, J. W M Niessen, F. S. de Man, Gary C Sieck, A. Vonk-Noordegraaf, C. A C Ottenheijm

Research output: Contribution to journalArticle

15 Citations (Scopus)

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 ubiquitinproteasome 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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume301
Issue number2
DOIs
StatePublished - Aug 2011

Fingerprint

Diaphragm
Paralysis
Muscles
Ubiquitin-Protein Ligases
Proteasome Endopeptidase Complex
Atrophy
Biopsy
Phrenic Nerve
Muscular Atrophy
Muscle Weakness
Artificial Respiration

Keywords

  • Contractile function
  • Diaphragm unloading
  • Mechanical ventilation
  • Phrenic nerve denervation

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology
  • Physiology

Cite this

Welvaart, W. N., Paul, M. A., van Hees, H. W. H., Stienen, G. J. M., Niessen, J. W. M., de Man, F. S., ... Ottenheijm, C. A. C. (2011). Diaphragm muscle fiber function and structure in humans with hemidiaphragm paralysis. American Journal of Physiology - Lung Cellular and Molecular Physiology, 301(2). https://doi.org/10.1152/ajplung.00040.2011

Diaphragm muscle fiber function and structure in humans with hemidiaphragm paralysis. / Welvaart, W. N.; Paul, M. A.; van Hees, H. W H; Stienen, G. J M; Niessen, J. W M; de Man, F. S.; Sieck, Gary C; Vonk-Noordegraaf, A.; Ottenheijm, C. A C.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 301, No. 2, 08.2011.

Research output: Contribution to journalArticle

Welvaart, WN, Paul, MA, van Hees, HWH, Stienen, GJM, Niessen, JWM, de Man, FS, Sieck, GC, Vonk-Noordegraaf, A & Ottenheijm, CAC 2011, 'Diaphragm muscle fiber function and structure in humans with hemidiaphragm paralysis', American Journal of Physiology - Lung Cellular and Molecular Physiology, vol. 301, no. 2. https://doi.org/10.1152/ajplung.00040.2011
Welvaart, W. N. ; Paul, M. A. ; van Hees, H. W H ; Stienen, G. J M ; Niessen, J. W M ; de Man, F. S. ; Sieck, Gary C ; Vonk-Noordegraaf, A. ; Ottenheijm, C. A C. / Diaphragm muscle fiber function and structure in humans with hemidiaphragm paralysis. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2011 ; Vol. 301, No. 2.
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