Intensive Care Medicine

, Volume 29, Issue 5, pp 825–833 | Cite as

Detrimental effects of short-term mechanical ventilation on diaphragm function and IGF-I mRNA in rats

  • Ghislaine Gayan-Ramirez
  • Kristel de Paepe
  • Pascal Cadot
  • Marc DecramerEmail author



Because respiratory muscle weakness appears to play an important role in weaning from mechanical ventilation, we developed an animal model of mechanical ventilation with appropriate controls in order to determine whether 24 h of mechanical ventilation already affected diaphragmatic function.

Design and interventions

Fifty-two male Wistar rats were randomized into three groups: a non-anesthetized control group (C, n=10), an anesthetized spontaneously breathing group (SB, n=9 out of 26), and an anesthetized and mechanically ventilated group (MV, n=12 out of 16).


After 24 h, in vitro diaphragmatic force was decreased in SB group but even more so in MV group (i.e., 80 Hz: −15% in SB, P<0.005 vs C and −34% in MV group, P<0.005 vs C and SB). This was associated with a significant decrease in the diaphragm type I and type IIa dimensions in the SB group, which was more pronounced in the MV group. Interestingly, diaphragm IGF-I mRNA was decreased in the SB group (−14%, P<0.05 vs C), but more so in MV group (−29%, P<0.001 vs C and P<0.01 vs SB). Moreover, there was a significant correlation between diaphragm force and IGF-I mRNA (at 80 Hz r=0.51, P=0.0056).


We conclude that 24 h of mechanical ventilation in rats, independently of anesthesia, already significantly reduced diaphragm force, fiber dimensions, and its IGF-I mRNA levels.


Mechanical ventilation Diaphragm Contractile properties IGF-I Weaning 



The authors sincerely thank Dr Naima Viirès for her helpful and relevant advice regarding the experimental set-up.


  1. 1.
    Tahvanainen J, Salmenpera M, Nikki P (1983) Extubation criteria after weaning from intermittent mandatory ventilation and continuous positive airway pressure. Crit Care Med 11:702–707CrossRefGoogle Scholar
  2. 2.
    Jabour ER, Rabil DM, Truwit JD, Rochester DF (1991) Evaluation of a new weaning index based on ventilatory endurance and the efficiency of gas exchange. Am Rev Respir Dis 144:531–537CrossRefGoogle Scholar
  3. 3.
    Krachman SL, Martin U, D'Alonzo GE (2001) Weaning from mechanical ventilation: an update. J Am Osteopath Assoc 101:387–390PubMedGoogle Scholar
  4. 4.
    Sporn PH, Morganroth M (1988) Discontinuation from mechanical ventilation. Clin Chest Dis 9:113–126Google Scholar
  5. 5.
    Zakynthinos SG, Vassilakopoulos T, Roussos C (1995) The load of inspiratory muscles in patients needing mechanical ventilation. Am J Respir Crit Care Med 152:1248–1255CrossRefGoogle Scholar
  6. 6.
    Goldstone JC, Green M, Moxham J (1994) Maximum relaxation rate of the diaphragm during weaning from mechanical ventilation. Thorax 49:54–60CrossRefGoogle Scholar
  7. 7.
    Dos Santos CC, Slutsky AS (2000) Cellular responses to mechanical stress. Invited review: mechanisms of ventilator-induced lung injury: a perspective. J Appl Physiol 89:1645–1655CrossRefGoogle Scholar
  8. 8.
    Anzueto A, Peters JI, Tobin MJ, De Los Santos R, Seidenfeld JJ, Moore G, Cox WJ, Coalson JJ (1997) Effect of prolonged controlled mechanical ventilation on diaphragmatic function in healthy adult baboon. Crit Care Med 25:1187–1190CrossRefGoogle Scholar
  9. 9.
    Le Bourdelles G, Viirès N, Boczkowski J, Seta N, Pavlovic D, Aubier M (1994) Effects of mechanical ventilation on diaphragmatic contractile properties in rats. Am J Respir Crit Care Med 149:1539–1544CrossRefGoogle Scholar
  10. 10.
    Yang L, Luo J, Bourdon J, Lin MC, Gottfried SB, Petrof BJ (2002) Controlled mechanical ventilation leads to remodelling in the rat diaphragm. Am J Respir Crit Care Med 166:1135–1140CrossRefGoogle Scholar
  11. 11.
    Radell PJ, Remahl S, Nichols DG, Eriksson LI (2002) Effects of prolonged mechanical ventilation and inactivity on piglet diaphragm function. Intensive Care Med 28:358–364CrossRefGoogle Scholar
  12. 12.
    Powers SK, Shaneley RA, Coombes JS, Koesterer TJ, McKenzie M, Van Gammeren D, Cicale M, Dodd SL (2002) Mechanical ventilation results in progressive contractile dysfunction in the diaphragm. J Appl Physiol 92:1851–1858CrossRefGoogle Scholar
  13. 13.
    Sassoon CSH, Caiozzo VJ, Manka A, Sieck GC (2002) Altered diaphragm contractile properties with controlled mechanical ventilation. J Appl Physiol 92:2585–2595CrossRefGoogle Scholar
  14. 14.
    Shanely RA, Lennon SL, Yimlamai T, Dodd S, Zergeroglu AM, Sugiura T, Enns D, Belcastro A, Powers SK (2002) Mechanical ventilation-induced diaphragmatic atrophy is associated with oxidative injury and increased proteolytic activity. Am J Respir Crit Care Med 165:1369–1374CrossRefGoogle Scholar
  15. 15.
    Adams GR, Haddad F (1996) The relationships among IGF-I, DNA content, and protein accumulation during skeletal muscle hypertrophy. J Appl Physiol 81:2509–2516CrossRefGoogle Scholar
  16. 16.
    Adams GR, McCue SA (1998) Localized infusion of IGF-I results in skeletal muscle hypertrophy in rats. J Appl Physiol 84:1716–1722CrossRefGoogle Scholar
  17. 17.
    Goldspink G (1999) Changes in muscle mass and phenotype and the expression of autocrine and systemic growth factors by muscle in response to stretch and overload. J Anat 194:323–334CrossRefGoogle Scholar
  18. 18.
    Gayan-Ramirez G, Vanderhoydonc F, Verhoeven G, Decramer M (1999) Acute treatment with corticosteroids decreases IGF-I and IGF-II expression in the rat diaphragm and gastrocnemius. Am J Respir Crit Care Med 159:283–289CrossRefGoogle Scholar
  19. 19.
    Chrysis D, Zhang J, Underwood LE (2002) Divergent regulation of proteasomes by insulin-like growth factor I and growth hormone in skeletal muscle of rats made catabolic with dexamethasone. Growth hormone, IGf research 2002:434–441Google Scholar
  20. 20.
    Yang H, Alnaqeeb M, Simpson H, Goldspink G (1997) Changes in muscle fibre type, muscle mass and IGF-I gene expression in rabbit skeletal muscle subjected to stretch. J Anat 190:613–622CrossRefGoogle Scholar
  21. 21.
    Dekhuijzen PNR, Gayan-Ramirez G, De Bock V, Dom R, Decramer M (1993) Triamcinolone and prednisolone affect contractile properties and histopathology of rat diaphragm differently. J Clin Invest 92:1534–1542CrossRefGoogle Scholar
  22. 22.
    Chirgwin JM, Przybyla AE, McDonald RJ, Rutter WJ (1979) Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry 18:5294–5299CrossRefGoogle Scholar
  23. 23.
    Aubier M, Viirès N, Piquet J, Murciano D, Blanchet F, Marty C, Gherardi R, Pariente R (1985) Effects of hypocalcemia on diaphragmatic strength generation. J Appl Physiol 58:2054–2061CrossRefGoogle Scholar
  24. 24.
    Lepage R, Légaré G, Racicot C, Brossard J-H, Lapointe R, Dagenais M, D'Amour P (1999) Hypocalcemia induced during major and minor abdominal surgery in humans. J Clin Endocrinol Metab 84:2654–2658CrossRefGoogle Scholar
  25. 25.
    Taylor RG, Abresch RT, Lieberman JS, Fowler WR, Portwood MM (1984) Effect of pentobarbital on contractility of mouse skeletal muscle. Exp Neurol 83:254–263CrossRefGoogle Scholar
  26. 26.
    Ingalls CP, Warren GL, Lowe DA, Boorstein DB, Armstrong RB (1996) Differential effects of anesthetics on in vivo skeletal muscle contractile function in the mouse. J Appl Physiol 80:332–340CrossRefGoogle Scholar
  27. 27.
    Fujii Y, Hoshi T, Takahashi S, Toyooka H (1999) Propofol decreases diaphragmatic contractility in dogs. Anesth Analg 89:1557–1560PubMedGoogle Scholar
  28. 28.
    Warner DO (1994) Anaesthesia and chest wall function. Ann Acad Med Singapore 23:566–571PubMedGoogle Scholar
  29. 29.
    Bisschop A, Gayan-Ramirez G, Rollier H, Dekhuijzen PNR, Dom R, De Bock V, Decramer M (1997) Effects of nandrolone decanoate on respiratory and peripheral muscles in male and female rats. J Appl Physiol 82:1112–1118CrossRefGoogle Scholar
  30. 30.
    Ballard FJ, Read LC, Francis GL, Bagley CJ, Wallace JC (1986) Binding properties and biological potencies of insulin-like growth factors in L6 myoblasts. Biochem J 233:223–230CrossRefGoogle Scholar
  31. 31.
    Carlson CJ, Booth FW, Gordon SE (1999) Skeletal muscle myostatin mRNA expression is fiber-type specific and increases during hindlimb unloading. Am J Physiol 277: R601-R606PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Ghislaine Gayan-Ramirez
    • 1
  • Kristel de Paepe
    • 1
  • Pascal Cadot
    • 2
  • Marc Decramer
    • 1
    Email author
  1. 1.Respiratory Muscle Research Unit, Laboratory of Pneumology and Respiratory Rehabilitation and Respiratory DivisionUniversity Hospitals, Katholieke Universiteit LeuvenLeuvenBelgium
  2. 2.Laboratory of Experimental ImmunologyUniversity Hospitals, Katholieke Universiteit LeuvenBelgium

Personalised recommendations