Skip to main content
PMC home page
Thorax logoLink to Thorax
. 2005 Jul 29;60(11):932–936. doi: 10.1136/thx.2004.038802

Adenine nucleotide loss in the skeletal muscles during exercise in chronic obstructive pulmonary disease

M Steiner 1, R Evans 1, S Deacon 1, S Singh 1, P Patel 1, J Fox 1, P Greenhaff 1, M Morgan 1
PMCID: PMC1747228  PMID: 16055624

Abstract

Background: Skeletal muscle adenine nucleotide loss has been associated with fatigue during high intensity exercise in healthy subjects but has not been studied in patients with chronic obstructive pulmonary disease (COPD). Changes in adenine nucleotides and other metabolites in the skeletal muscles were measured in patients with COPD and age matched healthy volunteers by obtaining biopsy samples from the quadriceps muscle at rest and following a standardised exercise challenge.

Methods: Eighteen patients with COPD (mean (SD) forced expiratory volume in 1 second 38.1 (16.8)%) and eight age matched healthy controls were studied. Biopsy samples were taken from the vastus lateralis muscle at rest and immediately after a 5 minute constant workload cycle test performed at 80% peak work achieved during a maximal incremental cycle test performed previously.

Results: The absolute workload at which exercise was performed was substantially lower in the COPD group than in the controls (56.7 (15.9) W v 143.2 (26.3) W, p<0.01). Despite this, there was a significant loss of adenosine triphosphate (mean change 4.3 (95% CI –7.0 to –1.6), p<0.01) and accumulation of inosine monophosphate (2.03 (95% CI 0.64 to 3.42), p<0.01) during exercise in the COPD group that was similar to the control group (–4.8 (95% CI –9.7 to 0.08), p = 0.053 and 1.6 (95% CI 0.42 to 2.79), p<0.01, respectively).

Conclusions: These findings indicate that the ATP demands of exercise were not met by resynthesis from oxidative and non-oxidative sources. This suggests that significant metabolic stress occurs in the skeletal muscles of COPD patients during whole body exercise at low absolute workloads similar to those required for activities of daily living.

Full Text

The Full Text of this article is available as a PDF (85.0 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bergstrom J. Percutaneous needle biopsy of skeletal muscle in physiological and clinical research. Scand J Clin Lab Invest. 1975 Nov;35(7):609–616. [PubMed] [Google Scholar]
  2. Broberg S., Sahlin K. Adenine nucleotide degradation in human skeletal muscle during prolonged exercise. J Appl Physiol (1985) 1989 Jul;67(1):116–122. doi: 10.1152/jappl.1989.67.1.116. [DOI] [PubMed] [Google Scholar]
  3. Constantin-Teodosiu D., Greenhaff P. L., McIntyre D. B., Round J. M., Jones D. A. Anaerobic energy production in human skeletal muscle in intense contraction: a comparison of 31P magnetic resonance spectroscopy and biochemical techniques. Exp Physiol. 1997 May;82(3):593–601. doi: 10.1113/expphysiol.1997.sp004049. [DOI] [PubMed] [Google Scholar]
  4. Harris R. C., Hultman E., Nordesjö L. O. Glycogen, glycolytic intermediates and high-energy phosphates determined in biopsy samples of musculus quadriceps femoris of man at rest. Methods and variance of values. Scand J Clin Lab Invest. 1974 Apr;33(2):109–120. [PubMed] [Google Scholar]
  5. Hultman E., Sjöholm H. Energy metabolism and contraction force of human skeletal muscle in situ during electrical stimulation. J Physiol. 1983 Dec;345:525–532. doi: 10.1113/jphysiol.1983.sp014994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Jakobsson P., Jorfeldt L., Brundin A. Skeletal muscle metabolites and fibre types in patients with advanced chronic obstructive pulmonary disease (COPD), with and without chronic respiratory failure. Eur Respir J. 1990 Feb;3(2):192–196. [PubMed] [Google Scholar]
  7. Kutsuzawa T., Shioya S., Kurita D., Haida M., Ohta Y., Yamabayashi H. Muscle energy metabolism and nutritional status in patients with chronic obstructive pulmonary disease. A 31P magnetic resonance study. Am J Respir Crit Care Med. 1995 Aug;152(2):647–652. doi: 10.1164/ajrccm.152.2.7633721. [DOI] [PubMed] [Google Scholar]
  8. Maltais F., Jobin J., Sullivan M. J., Bernard S., Whittom F., Killian K. J., Desmeules M., Bélanger M., LeBlanc P. Metabolic and hemodynamic responses of lower limb during exercise in patients with COPD. J Appl Physiol (1985) 1998 May;84(5):1573–1580. doi: 10.1152/jappl.1998.84.5.1573. [DOI] [PubMed] [Google Scholar]
  9. Maltais F., LeBlanc P., Whittom F., Simard C., Marquis K., Bélanger M., Breton M. J., Jobin J. Oxidative enzyme activities of the vastus lateralis muscle and the functional status in patients with COPD. Thorax. 2000 Oct;55(10):848–853. doi: 10.1136/thorax.55.10.848. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Murray C. J., Lopez A. D. Alternative projections of mortality and disability by cause 1990-2020: Global Burden of Disease Study. Lancet. 1997 May 24;349(9064):1498–1504. doi: 10.1016/S0140-6736(96)07492-2. [DOI] [PubMed] [Google Scholar]
  11. Möller P., Bergström J., Fürst P., Hellström K., Uggla E. Energy-rich phosphagens, electrolytes and free amino acids in leg skeletal muscle of patients with chronic obstructive lung disease. Acta Med Scand. 1982 May;211(3):187–193. doi: 10.1111/j.0954-6820.1982.tb01925.x. [DOI] [PubMed] [Google Scholar]
  12. Pouw E. M., Schols A. M., van der Vusse G. J., Wouters E. F. Elevated inosine monophosphate levels in resting muscle of patients with stable chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1998 Feb;157(2):453–457. doi: 10.1164/ajrccm.157.2.9608064. [DOI] [PubMed] [Google Scholar]
  13. Quanjer P. H., Tammeling G. J., Cotes J. E., Pedersen O. F., Peslin R., Yernault J. C. Lung volumes and forced ventilatory flows. Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society. Eur Respir J Suppl. 1993 Mar;16:5–40. [PubMed] [Google Scholar]
  14. Sahlin K., Broberg S., Ren J. M. Formation of inosine monophosphate (IMP) in human skeletal muscle during incremental dynamic exercise. Acta Physiol Scand. 1989 Jun;136(2):193–198. doi: 10.1111/j.1748-1716.1989.tb08652.x. [DOI] [PubMed] [Google Scholar]
  15. Sala E., Roca J., Marrades R. M., Alonso J., Gonzalez De Suso J. M., Moreno A., Barberá J. A., Nadal J., de Jover L., Rodriguez-Roisin R. Effects of endurance training on skeletal muscle bioenergetics in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1999 Jun;159(6):1726–1734. doi: 10.1164/ajrccm.159.6.9804136. [DOI] [PubMed] [Google Scholar]
  16. Spriet L. L., Söderlund K., Bergström M., Hultman E. Anaerobic energy release in skeletal muscle during electrical stimulation in men. J Appl Physiol (1985) 1987 Feb;62(2):611–615. doi: 10.1152/jappl.1987.62.2.611. [DOI] [PubMed] [Google Scholar]
  17. Steiner M. C., Barton R. L., Singh S. J., Morgan M. D. L. Nutritional enhancement of exercise performance in chronic obstructive pulmonary disease: a randomised controlled trial. Thorax. 2003 Sep;58(9):745–751. doi: 10.1136/thorax.58.9.745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Whittom F., Jobin J., Simard P. M., Leblanc P., Simard C., Bernard S., Belleau R., Maltais F. Histochemical and morphological characteristics of the vastus lateralis muscle in patients with chronic obstructive pulmonary disease. Med Sci Sports Exerc. 1998 Oct;30(10):1467–1474. doi: 10.1097/00005768-199810000-00001. [DOI] [PubMed] [Google Scholar]
  19. Wynants J., Van Belle H. Single-run high-performance liquid chromatography of nucleotides, nucleosides, and major purine bases and its application to different tissue extracts. Anal Biochem. 1985 Jan;144(1):258–266. doi: 10.1016/0003-2697(85)90114-9. [DOI] [PubMed] [Google Scholar]

Articles from Thorax are provided here courtesy of BMJ Publishing Group

RESOURCES