Intensive Care Medicine

, Volume 29, Issue 9, pp 1515–1527 | Cite as

Electrophoretic determination of the myosin/actin ratio in the diagnosis of critical illness myopathy

  • Helena Stibler
  • Lars Edström
  • Karsten Ahlbeck
  • Sten Remahl
  • Tor Ansved



To develop a rapid method to quantify myosin in muscle biopsy specimens from patients with critical illness myopathy (CIM).


Percutaneous muscle biopsy specimens at different stages of CIM were examined by light microscopy and transmission electron microscopy (TEM) and by horizontal pore gradient SDS electrophoresis (SDS-PAGE). The myosin/actin ratio was calculated densitometrically. Neurophysiological examinations were performed at various times during the course of CIM.


All patients were treated in intensive care units at Karolinska Hospital.

Patients and participants

We studied 11 patients with CIM, 5 patients with axonal neuropathies, and 42 control individuals.

Measurements and results

The histopathological changes included in all cases muscle fiber atrophy, degeneration, regeneration, nuclear changes, and reduction in myofibrillar ATPase activity in both type I and II fibers. In severely affected muscles fiber type differentiation was lost. On TEM preferential loss of thick filaments was the dominant finding. In some patients changes were present only in parts of the specimen. The neurophysiological examinations indicated myopathy in five patients and combined myopathy and neuropathy in five and suggested neuropathy in one. The SDS-pore PAGE used showed a technical variation of 4–5%. Quantitative results were obtained within 1 day and night. The mean value of the myosin/actin ratio in controls was 1.37±0.21 and in CIM patients 0.37±0.17, without overlapping with the control values.


Considering the diagnostic difficulty using morphological and neurophysiological methods, especially in early stages of CIM, we suggest including SDS-pore PAGE to determine the myosin/actin ratio for rapid diagnosis of CIM.


Critical illness myopathy Electrophoresis Morphology Myosin/actin ratio Neurophysiology 


  1. 1.
    Bolton CF, Gilbert JJ, Hahn AF, Sibbald WJ (1984) Polyneuropathy in critically ill patients. J Neurol Neurosurg Psychiatry 47:1223–1231PubMedGoogle Scholar
  2. 2.
    Sher JH, Shafiq SA, Scutta HS (1979) Acute myopathy with selective lysis of myosin filaments. Neurology 29:100–106PubMedGoogle Scholar
  3. 3.
    Hirano M, Ott BR, Raps EC, Minetti C, lennihan L, Libbey NP, Bonilla E, Hays AP (1992) Acute quadriplegic myopathy: a complication of treatment with steroids, nondepolarizing blocking agents, or both. Neurology 42:2082–2087PubMedGoogle Scholar
  4. 4.
    Lacomis D, Smith TW, Chad DA (1993) Acute myopathy and neuropathy in status asthmaticus: case report and literature review. Muscle Nerve 16:84–90PubMedGoogle Scholar
  5. 5.
    Zochodne DW, Ramsay DA, Saly V, Shelley S, Moffat S (1994) Acute necrotizing myopathy of intensive care: electrophysiological studies. Muscle Nerve 17:285–292PubMedGoogle Scholar
  6. 6.
    Sander HW, Golden M, Danon MJ (2002) Quadriplegic areflexic ICU illness: selective thick filament loss and normal nerve histology. Muscle Nerve 26:499–505CrossRefPubMedGoogle Scholar
  7. 7.
    Faragher MW, Day BJ, Dennet X (1996) Critical care myopathy: an electrophysiological and histological study. Muscle Nerve 19:516–518CrossRefPubMedGoogle Scholar
  8. 8.
    Lacomis D, Zochodne DW, Bird SJ (2000) Critical illness myopathy. Muscle Nerve 23:1785–1788CrossRefPubMedGoogle Scholar
  9. 9.
    Gutmann L, Gutmann L (1999) Critical illness neuropathy and myopathy. Arch Neurol 56:527–528CrossRefPubMedGoogle Scholar
  10. 10.
    Coakley JH, Nagendran K, Yarwood GD, Honavar?, Hinds CJ (1998) Patterns of neurophysiological abnormality in prolonged critical illness. Intensive Care Med 24:801–807Google Scholar
  11. 11.
    Lacomis D, Giuliani M, Van Cott A, Kramer DJ (1996) Acute myopathy of intensive care: clinical, electromyographic and pathologic aspects. Ann Neurol 40:645–654PubMedGoogle Scholar
  12. 12.
    Rich MM, Teener JW, Raps EC, Schotland DL, Bird SJ (1996) Muscle is electrically inexitable in acute quadriplegic myopathy. Neurology 46:731–736PubMedGoogle Scholar
  13. 13.
    Rich MM, Bird SJ, Raps EC, McCluskey LF, Teener JW (1997) Direct muscle stimulation in acute quadriplegic myopathy. Muscle Nerve 20:665–673CrossRefPubMedGoogle Scholar
  14. 14.
    Hanson P, Dive A, Brucher J-M, Bisteau M, Dangoisse M, Deltombe T (1997) Acute corticosteroid myopathy in intensive care patients. Muscle Nerve 20:1371–1380CrossRefPubMedGoogle Scholar
  15. 15.
    Helliwell TR, Wilkinson A, Griffiths RD, McClelland P, Palmer TEA, Bone JM (1998) Muscle fibre atrophy in critically ill patients is associated with loss of myosin filaments and the presence of lysosomal enzymes and ubiquitin. Neuropathol Appl Neurobiol 24:507–517CrossRefPubMedGoogle Scholar
  16. 16.
    Larsson L, Xiaopeng L, Edström L, Eriksson LI, Zachrisson H, Argentini C, Schiaffino S (2000) Acute quadriplegia and loss of muscle myosin in patients treated with nondepolarizing neuro-muscular blocking agents and corticosteroids: mechanisms at the cellular and molecular levels. Crit Care Med 28:34–45PubMedGoogle Scholar
  17. 17.
    Matsumoto N, Nakamura T, Yasui Y, Torii J (2000) Analysis of muscle proteins in acute quadriplegic myopathy. Muscle Nerve 23:1270–1276CrossRefPubMedGoogle Scholar
  18. 18.
    Moore FA, Moore EE (1995) Evolving concepts in the pathogenesis of postinjury multiple organ failure. Surg Clin North Am 75:257PubMedGoogle Scholar
  19. 19.
    Dubowitz V (1985) Muscle biopsy: a practical approach. Bailliere-Tindall, LondonGoogle Scholar
  20. 20.
    Brooke M, Kaiser K (1970) Muscle fibre types: how many and what kind? Arch Neurol 23:369–379Google Scholar
  21. 21.
    Görg A, Postel W, Westermeir R, Righetti PG, Ek K (1981) One and two dimensional electrophoresis performed horizontally in ultrathin SDS pore-gradient gels. LKB Application Note 320:1–12Google Scholar
  22. 22.
    Stibler H, Edström L, Olsson AM (1993) Improved electrophoretic method for the analysis of dystrophin in human muscle. Scand J Clin Lab Invest 53:73–82PubMedGoogle Scholar
  23. 23.
    Zifko UA, Zipko HT, Bolton CF (1998) Clinical and electrophysiological findings in critical illness polyneuropathy. J Neurol Sci 159:186–193PubMedGoogle Scholar
  24. 24.
    Trojaborg W, Weimer LH, Hays AP (2001) Electrophysiologic studies in critical illness associated with weakness: myopathy or neuropathy—a reappraisal. Clin Neurophysiol 112:1586–1593Google Scholar
  25. 25.
    Marie-An C, de Letter J, Paul I, Schmitz M, Visser L, Freek A, Verheul M, Ronald L, Schellens LA, Dolf A, Op de Coul W, Frans G, van der Meche'M (2001) Risk factors for the development of polyneuropathy and myopathy in critically ill patients. Crit Care Med 29:2281–2288Google Scholar
  26. 26.
    Danon MJ, Carpenter S (1991) Myopathy with thick filament (myosin) loss following prolonged paralysis with vecuronium during steroid treatment. Muscle Nerve 14:1131–1139PubMedGoogle Scholar
  27. 27.
    DeJonghe B, Sharshar T, Lefaucher JP, Authier FJ, Durand-Zales I, Boussarsar M, Cerf C, Renaud E, Mesrati F, Carlet J, Raphael JC, Outin H, Bastuji-Garin S (2002) Paresis acquired in the intensive care unit: a prospective multicenter study. JAMA 288:2859–2867PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Helena Stibler
    • 1
  • Lars Edström
    • 1
  • Karsten Ahlbeck
    • 2
  • Sten Remahl
    • 3
  • Tor Ansved
    • 1
  1. 1.Department of NeurologyKarolinska HospitalStockholmSweden
  2. 2.Department of AnestesiologyKarolinska HospitalStockholmSweden
  3. 3.Department of NeurophysiologyKarolinska HospitalStockholmSweden

Personalised recommendations