Sports Medicine

, Volume 39, Issue 5, pp 389–422 | Cite as

Exercise and Fatigue

  • Wim Ament
  • Gijsbertus J. Verkerke
Review Article


Physical exercise affects the equilibrium of the internal environment. During exercise the contracting muscles generate force or power and heat. So physical exercise is in fact a form of mechanical energy. This generated energy will deplete the energy stocks within the body. During exercise, metabolites and heat are generated, which affect the steady state of the internal environment. Depending on the form of exercise, sooner or later sensations of fatigue and exhaustion will occur. The physiological role of these sensations is protection of the exercising subject from the deleterious effects of exercise. Because of these sensations the subject will adapt his or her exercise strategy. The relationship between physical exercise and fatigue has been the scope of interest of many researchers for more than a century and is very complex.

The exercise intensity, exercise endurance time and type of exercise are all variables that cause different effects within the body systems, which in turn create different types of sensation within the subject’s mind during the exercise.

Physical exercise affects the biochemical equilibrium within the exercising muscle cells. Among others, inorganic phosphate, protons, lactate and free Mg2+ accumulate within these cells. They directly affect the mechanical machinery of the muscle cell. Furthermore, they negatively affect the different muscle cell organelles that are involved in the transmission of neuronal signals.

The muscle metabolites produced and the generated heat of muscle contraction are released into the internal environment, putting stress on its steady state. The tremendous increase in muscle metabolism compared with rest conditions induces an immense increase in muscle blood supply, causing an increase in the blood circulatory system and gas exchange. Nutrients have to be supplied to the exercising muscle, emptying the energy stocks elsewhere in body. Furthermore, the contracting muscle fibres release cytokines, which in their turn create many effects in other organs, including the brain. All these different mechanisms sooner or later create sensations of fatigue and exhaustion in the mind of the exercising subject. The final effect is a reduction or complete cessation of the exercise.

Many diseases speed up the depletion of the energy stocks within the body. So diseases amplify the effect of energy stock depletion that accompanies exercise. In addition, many diseases produce a change of mind-set before exercise. These changes of mind-set can create sensations of fatigue and exercise-avoiding behaviour at the onset of an exercise. One might consider these sensations during disease as a feed-forward mechanism to protect the subject from an excessive depletion of their energy stocks, to enhance the survival of the individual during disease.


Motor Neuron Motor Cortex Maximum Voluntary Contraction Chronic Fatigue Syndrome Internal Environment 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors acknowledge the assistance of Karin van der Borght and Izaak den Daas of the Department of Medical Writing of Xendo, in improving the English of this article.

No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.


  1. 1.
    Gandevia SC. Spinal and supraspinal factors in human muscle fatigue. Physiol Rev 2001; 81: 1725–89PubMedGoogle Scholar
  2. 2.
    Enoka RM, Stuart DG. Neurobiology of muscle fatigue. J Appl Physiol 1992; 72: 1631–48PubMedCrossRefGoogle Scholar
  3. 3.
    Human muscle fatigue: physiological mechanism. Ciba Foundation Symposium no. 82. London: Pitman Medical 1981Google Scholar
  4. 4.
    Borg G. Psychophysical scaling with applications in physical work and the perception of exertion. Scand J Work Environ Health 1990; 16 Suppl. 1: 55–8PubMedCrossRefGoogle Scholar
  5. 5.
    Lehninger AL. Contraction and motion (chapter 11). In: Lehninger AL, editor. Bioenergetics: the molecular basis of biological energy transformations. 2nd ed. New York: WA Benjamin Inc., 1971: 211–24 (ISBN 0-8053-6103-0)Google Scholar
  6. 6.
    Murray RK. Muscle (chapter 58). In: Murray RK, Granner DK, Mayes PA, et al., editors. Harper’s Biochemistry. 23rd ed. Norwalk (VA): Appleton & Lange, 1993: 647–64 (ISBN 0-8385-3658-1)Google Scholar
  7. 7.
    Chance B, Eleff S, Leigh Jr JS, et al. Mitochondrial regulation of phosphocreatine/inorganic phosphate ratios in exercising human muscle: a gated 31P NMR study. Proc Natl Acad Sci USA 1981; 78: 6714–8PubMedCrossRefGoogle Scholar
  8. 8.
    Minotti JR, Johnson EC, Hudson TL, et al. Forearm metabolic asymmetry detected by 31P-NMR during submaximal exercise. J Appl Physiol 1989; 67: 324–9PubMedGoogle Scholar
  9. 9.
    Molé PA, Coulson RL, Caton JR, et al. In vivo 31P-NMR in human muscle: transient patterns with exercise. J Appl Physiol 1985; 59: 101–4PubMedGoogle Scholar
  10. 10.
    Sapega AA, Sokolow DP, Graham TJ, et al. Phosphorus nuclear magnetic resonance: a non-invasive technique for the study of muscle bioenergetics during exercise. Med Sci Sports Exerc 1987; 19: 410–20PubMedGoogle Scholar
  11. 11.
    Cooke R. Actomyosin interaction in striated muscle. Physiol Rev 1997; 77: 671–9PubMedGoogle Scholar
  12. 12.
    Lionne C, Brune M, Webb MR, et al. Time resolved measurements show that phosphate release is the rate limiting step on myofibrillar ATPases. FEBS Lett 1995; 364: 59–62PubMedCrossRefGoogle Scholar
  13. 13.
    Lamb GD, Stephenson DG. Effects of intracellular pH and [Mg2+] on excitation-contraction coupling in skeletal muscle fibres of the rat. J Physiol 1994; 478: 331–9PubMedGoogle Scholar
  14. 14.
    Potma EJ, van Graas IA, Stienen GJM. Effects of pH on myofibrillar ATPase activity in fast and slow skeletal muscle fibres of the rabbit. Biophys J 1994; 67: 2404–10PubMedCrossRefGoogle Scholar
  15. 15.
    Karatzaferi C, Myburgh KH, Chinn MK, et al. Effect of an ADP analog on isometric force and ATPase activity of active muscle fibers. Am J Physiol 2003; 284: C816–25Google Scholar
  16. 16.
    Cooke R, Franks K, Luciani GB, et al. The inhibition of rabbit skeletal muscle contraction by hydrogen ions and phosphate. J Physiol 1988; 395: 77–97PubMedGoogle Scholar
  17. 17.
    Myburgh KH. Can any metabolites partially alleviate fatigue manifestations at the cross-bridge? Med Sci Sports Exerc 2004; 36: 20–7PubMedCrossRefGoogle Scholar
  18. 18.
    Westerblad H, Bruton JD, Lännergren J. The effect of intracellular pH on contractile function of intact, single fibres of mouse muscle declines with increasing temperature. J Physiol 1997; 500: 193–204PubMedGoogle Scholar
  19. 19.
    Cooke R, Pate E. The effects of ADP and phosphate on the contraction of muscle fibers. Biophys J 1985; 48: 789–98PubMedCrossRefGoogle Scholar
  20. 20.
    Metzger JM. Effects of phosphate and ADP on shortening velocity during maximal and submaximal calcium activation of the thin filament in skeletal muscle fibers. Biophys J 1996; 70: 409–17PubMedCrossRefGoogle Scholar
  21. 21.
    Millar NC, Homsher E. Kinetics of force generation and phosphate release in skinned rabbit soleus muscle fibers. Am J Physiol 1992; 262: C1239–45Google Scholar
  22. 22.
    Stienen GJ, Roosemalen MC, Wilson MG, et al. Depression of force by phosphate in skinned skeletal muscle fibers of the frog. Am J Physiol 1990; 259: C349–57Google Scholar
  23. 23.
    Potma EJ, van Graas IA, Stienen GJM. Influence of inorganic phosphate and pH on ATP utilization in fastand slow skeletal muscle fibres. Biophys J 1995; 67: 2580–9CrossRefGoogle Scholar
  24. 24.
    Potma EJ, Stienen GJM. Increase in ATP consumption during shortening in skinned fibers from rabbit psoas muscle: effects of inorganic phosphate. J Physiol 1996; 496: 1–12PubMedGoogle Scholar
  25. 25.
    Coyle EF, Coggan AR, Hemmert MK, et al. Muscle glycogen utilization during prolonged strenuous exercise when fed carbohydrate. J Appl Physiol 1986; 61: 165–72PubMedGoogle Scholar
  26. 26.
    McArdle WD, Katch FI, Katch VL, editors. Exercise physiology: energy III and human performance. 4th ed. Baltimore (MD): Williams & Wilkins, 1996 (ISBN 0-683-05731-6)Google Scholar
  27. 27.
    Powers SK, Howley ET, editors. Exercise physiology: theory and application to fitness and performance. 2nd ed. Madison (WI) and Dubuque (IA): WCB Brown & Benchmark Publishers, 1994 (ISBN 0-697-12657-9)Google Scholar
  28. 28.
    Hayashi T, Wojtaszewski JF, Goodyear LJ. Exercise regulation of glucose transport in skeletal muscle. Am J Physiol 1997; 273: E1039–51Google Scholar
  29. 29.
    Frandsen U, Lopez-Figueroa M, Hellsten Y. Localization of nitric oxide synthase in human skeletal muscle. Biochem Biophys Res Commun 1996; 227: 88–93PubMedCrossRefGoogle Scholar
  30. 30.
    Bradley SJ, Kingwell BA, McConell GK. Nitric oxide synthase inhibition reduces leg glucose uptake but not blood flow during dynamic exercise in humans. Diabetes 1999; 48: 1815–21PubMedCrossRefGoogle Scholar
  31. 31.
    Mayes PA. Integration of metabolism and the provision of tissue fuels (chapter 29). In: Murray RK, Granner DK, Mayes PA, Rodwell PA, editors. Harper’s Biochemistry. 23rd ed. Norwalk (VA): Appleton & Lange, 1993: 279–92 (ISBN 0-8385-3658-1)Google Scholar
  32. 32.
    Jeukendrup AE. Carbohydrate intake during exercise and performance. Nutrition 2004; 20: 669–77PubMedCrossRefGoogle Scholar
  33. 33.
    Balog EM, Thomson LV, Fitts RH. Role of sarcolemma action potentials and excitability in muscle fatigue. J Appl Physiol 1994; 76: 2157–62PubMedCrossRefGoogle Scholar
  34. 34.
    Lännergren J, Westerblad H. Action potential fatigue in single skeletal muscle fibres of Xenopus. Acta Physiol Scand 1987; 129: 311–8PubMedCrossRefGoogle Scholar
  35. 35.
    Metzger JM, Fitts RH. Fatigue from high- and low-frequency muscle stimulation: role of sarcolemma action potentials. Exp Neurol 1986; 93: 320–33PubMedCrossRefGoogle Scholar
  36. 36.
    Juel C. Potassium and sodium shifts during in vitro isometric muscle contraction, and the time course of the ion-gradient recovery. Eur J Appl Physiol (Pflügers Arch) 1986; 406: 458–63CrossRefGoogle Scholar
  37. 37.
    Juel C. Muscle action potential propagation velocity changes during activity. Muscle Nerve 1988; 11: 714–9PubMedCrossRefGoogle Scholar
  38. 38.
    Lindström L, Kadefors R, Petersén I. An electromyographic index for localized muscle fatigue. J Appl Physiol 1977; 43: 750–4PubMedGoogle Scholar
  39. 39.
    de Luca CJ. Myoelectric manifestations of localized muscular fatigue in humans. Crit Rev Biomed Eng 1984; 11: 251–79PubMedGoogle Scholar
  40. 40.
    Ament W, Bonga GJ, Hof AL, et al. Electromyogram median power frequency in exhausting exercise. J Electromyogr Kinesiol 1993; 3: 214–20PubMedCrossRefGoogle Scholar
  41. 41.
    Ament W, Bonga GJ, Hof AL, et al. Electromyogram median power frequency in dynamic exercise at medium exercise intensities. Eur J Appl Physiol (Pflügers Arch) 1996; 74: 180–6Google Scholar
  42. 42.
    Jansen R, Ament W, Verkerke GJ, et al. Median power frequency of the surface electromyogram and blood lactate concentration in incremental cycle ergometry. Eur J Appl Physiol (Pflügers Arch) 1997; 75: 102–8Google Scholar
  43. 43.
    Buchthal F, Madsen A. Synchronous activity in normal and atrophic muscle. Electroencephalogr Clin Neurophysiol 1950; 2: 425–44PubMedCrossRefGoogle Scholar
  44. 44.
    Datta AK, Stephens JA. Synchronization of motor units activity during voluntary contraction in man. J Physiol 1990; 442: 397–419Google Scholar
  45. 45.
    Allen DG, Lamb GD, Westerblad H. Skeletal muscle fatigue: cellular mechanisms. Physiol Rev 2008; 88: 287–332PubMedCrossRefGoogle Scholar
  46. 46.
    Bigland-Ritchie B, Rice CL, Garland SJ, et al. Task-dependent factors in fatigue of human voluntary contractions (chapter 27). In: Gandevia SC, Enoka RM, McComas AJ, et al., editors. Fatigue: neural and muscular mechanisms–advances in medicine and biology (volume 384). New York & London: Plenum Press, 1995: 361–80 (ISBN 0-306-45139-5)Google Scholar
  47. 47.
    Garland SJ, Enoka RM, Serrano LP, et al. Behavior of motor units in human biceps brachii during a submaximal fatiguing contraction. J Appl Physiol 1994; 76: 2411–19PubMedGoogle Scholar
  48. 48.
    Fitts RH. Cellular mechanisms of muscle fatigue. Physiol Rev 1994; 74: 49–94PubMedCrossRefGoogle Scholar
  49. 49.
    Lännergren J, Westerblad H. Force and membrane potential during and after fatiguing, continuous high-frequency stimulation of single Xenopus muscle fibres. Acta Physiol Scand 1986; 128: 359–68PubMedCrossRefGoogle Scholar
  50. 50.
    Bergström M, Hultman E. Relaxation and force during fatigue and recovery of the human quadriceps muscle: relations to metabolite changes. Eur J Appl Physiol(Pflügers Arch) 1991; 418: 153–60Google Scholar
  51. 51.
    Pourmand R. Metabolic myopathies: a diagnostic evaluation. Neurol Clin 2000; 18: 1–13PubMedCrossRefGoogle Scholar
  52. 52.
    Tsujino S, Nonaka I, DiMauro S. Glycogen storage myopathies. Neurol Clin 2000; 18: 125–50PubMedCrossRefGoogle Scholar
  53. 53.
    Wolfe GI, Baker NS, Haller RG, et al. McArdle’s disease presenting with asymmetric, late-onset arm weakness. Muscle Nerve 2000; 23: 641–5PubMedCrossRefGoogle Scholar
  54. 54.
    Cady EB, Elshove H, Jones DA, et al. Themetabolic causes of slow relaxation in fatigued human skeletal muscle. J Physiol 1989; 418: 327–37PubMedGoogle Scholar
  55. 55.
    Lamb GD, Stephenson DG, Stienen GJM. Effects of osmolality and ionic strength on the mechanism of Ca2+ release in skinned skeletal muscle fibres of the toad. J Physiol 1993; 464: 629–48PubMedGoogle Scholar
  56. 56.
    Meissner G. Ryanodine receptor/Ca2+ release channels and their regulation by endogenous effectors. Annu Rev Physiol 1994; 56: 485–508PubMedCrossRefGoogle Scholar
  57. 57.
    Westerblad H, Allen DG. Myoplasmic free Mg2+ concentration during repetitive stimulation of single fibres from mouse skeletal muscle. J Physiol 1992; 453: 413–34PubMedGoogle Scholar
  58. 58.
    Allen DG, Westerblad H. Role of phosphate and calcium stores in muscle fatigue. J Physiol 2001; 536: 657–65PubMedCrossRefGoogle Scholar
  59. 59.
    Newton DW, Driscoll DF. Calcium and phosphate compatibility: revisited again. Am J Health Syst Pharm 2008; 65: 73–80PubMedCrossRefGoogle Scholar
  60. 60.
    Marx SO, Reiken S, Hismatsu Y, et al. Phosphorylation-dependent regulation of ryanodine receptors: a novel role for leucine/isoleucine zippers. J Cell Biol 2001; 153: 699–708PubMedCrossRefGoogle Scholar
  61. 61.
    Dulhunty AF, Laver D, Curtis SM, et al. Characteristics of irreversible ATP activation suggest that native skeletal ryanodine receptors can be phosphorylated via an endogenous CaMKII. Biophys J 2001; 81: 3240–52PubMedCrossRefGoogle Scholar
  62. 62.
    Sjøgaard G, McComas AJ. Role of interstitial potassium (chapter 4). In: Gandevia SC, Enoka RM, McComas AJ, et al., editors. Fatigue: neural and muscular mechanisms–advances in medicine and biology (volume 384). New York & London: Plenum Press, 1995: 69–80 (ISBN 0-306-45139-5)Google Scholar
  63. 63.
    Sjøgaard G, Adams RP, Saltin B. Water and ion shifts in skeletal muscle of humans with intense dynamic knee extension. Am J Physiol 1985; 248: R190–6Google Scholar
  64. 64.
    Busse MW, Maassen N. Effect of consecutive exercise bouts on plasma potassium concentration during exercise and recovery. Med Sci Sports Exerc 1989; 21: 489–93PubMedGoogle Scholar
  65. 65.
    Medbo JI, Sejersted OM. Plasma K+ changes during intense exercise in endurance-trained and sprint-trained subjects. Acta Physiol Scand 1994; 151: 363–71PubMedCrossRefGoogle Scholar
  66. 66.
    Kearney MT, Cotton JM, Richardson PJ, et al. Viral myocarditis and dilated cardiomyopathy: mechanisms, manifestations, and management. Postgrad Med J 2001; 77: 4–10PubMedCrossRefGoogle Scholar
  67. 67.
    Woodruff JF. Viral myocarditis: a review. Am J Pathol 1980; 101: 425–84PubMedGoogle Scholar
  68. 68.
    Gibson TC, Arnold J, Craige E, et al. Electrocardiographic studies in Asian influenza. Am Heart J 1959; 57: 661–8PubMedCrossRefGoogle Scholar
  69. 69.
    del Castillo J, Katz B. The effect of magnesium on the activity of motor nerve endings. J Physiol 1954; 124: 553–9Google Scholar
  70. 70.
    Smith DO. Acetylcholine storage, release and leakage at the neuromuscular junction of mature and aged rats. J Physiol 1984; 347: 161–76PubMedGoogle Scholar
  71. 71.
    Feltz A, Trautmann A. Desensitization at the frog neuromuscular junction: a biphasic process. J Physiol 1982; 332: 257–72Google Scholar
  72. 72.
    Bigland-Ritchie B, Kukulka CG, Lippold OCJ, et al. The absence of neuromuscular transmission failure in sustained maximal voluntary contractions. J Physiol 1982; 330: 165–78Google Scholar
  73. 73.
    Ghez C. Muscles: effectors of the motor systems (chapter 36). In: Kandel ER, Schwartz JH, Jessell TM, editors. Principles of neural science (3rd ed). London: Prentice-Hall International, 1991: 548–63 (ISBN 0-8385-8068-8)Google Scholar
  74. 74.
    Sandercock TG, Faulkner JA, Albers W, et al. Single motor unit and fiber action potentials during fatigue. J Appl Physiol 1985; 58: 1073–9PubMedGoogle Scholar
  75. 75.
    Sieck GC, Fournier M. Changes in diaphragm motor unit EMG during fatigue. J Appl Physiol 1990; 68: 1917–26PubMedGoogle Scholar
  76. 76.
    Burke RE. Motor units: anatomy, physiology, and functional organisation (chapter 10). In: Brookhart JM, Mountcastle VB, Brooks VB, editors. Handbook of physiology, section 1: the nervous system (volume II, part I), motor control. New York: Oxford University Press, 1981: 345–442 (ISBN 0-683-01105-7)Google Scholar
  77. 77.
    Kernell D. Organized variability in the neuromuscular system: a survey of task-related adaptations. Arch Ital Biol 1992; 130: 19–66PubMedGoogle Scholar
  78. 78.
    Pette D, Staron RS. Transitions of muscle fiber phenotypic profiles. Histochem Cell Biol 2001; 115: 359–72PubMedGoogle Scholar
  79. 79.
    Coupland ME, Puchert E, Ranatunga KW. Temperature dependence of active tension in mammalian (rabbit psoas) muscle fibres: effect of inorganic phosphate. J Physiol 2001; 536: 879–91PubMedCrossRefGoogle Scholar
  80. 80.
    Widrick JJ. Effect of P(i) on unloaded shortening velocity of slow and fast mammalian muscle fibers. Am J Physiol 2002; 282: C647–53Google Scholar
  81. 81.
    Lionikas A, Li M, Larsson L. Human skeletal muscle myosin function at physiological and non-physiological temperatures. Acta Physiol 2006; 186: 151–8CrossRefGoogle Scholar
  82. 82.
    Saltin B, Gagge AP, Stolwijk JAJ. Muscle temperature during submaximal exercise in man. J Appl Physiol 1968; 25: 679–88PubMedGoogle Scholar
  83. 83.
    Ariano MA, Armstrong RB, Edgerton VR. Hindlimb muscle fiber populations of five mammals. J Histochem Cytochem 1973; 21: 51–5PubMedCrossRefGoogle Scholar
  84. 84.
    Johnson MA, Polgar J, Weightman D, et al. Data on the distribution of fibre types in thirty-six human muscles: an autopsy study. J Neurol Sci 1973; 18: 111–29PubMedCrossRefGoogle Scholar
  85. 85.
    Bigland-Ritchie B, Johansson R, Lippold OC, et al. Changes in single motor unit firing rates during sustained maximal voluntary contractions. J Physiol 1982; 328: 27P–8PGoogle Scholar
  86. 86.
    Bigland-Ritchie B, Johansson R, Lippold OC, et al. Changes in motoneuron firing rates during sustained maximal voluntary contractions. J Physiol 1983; 340: 335–46PubMedGoogle Scholar
  87. 87.
    Sacco P, Newberry R, McFadden L, et al. Depression of human electromyography activity by fatigue of a synergistic muscle. Muscle Nerve 1997; 20: 710–7PubMedCrossRefGoogle Scholar
  88. 88.
    Fuglevand AJ, Keen DA. Re-evaluation of muscle wisdom in the human adductor pollicis using physiological rates of stimulation. J Physiol 2003; 549: 865–75PubMedCrossRefGoogle Scholar
  89. 89.
    Kleine BU, Stegeman DF. Stimulating motor wisdom. J Appl Physiol 2007; 102: 1737–38PubMedCrossRefGoogle Scholar
  90. 90.
    Brooks GA. Anaerobic threshold: review of the concept and directions for future research. Med Sci Sports Exerc 1985; 17: 22–34PubMedGoogle Scholar
  91. 91.
    Coyle EF, Coggan AR, Hopper MK, et al. Determinants of endurance in well-trained cyclists. J Appl Physiol 1988; 64: 2622–30PubMedGoogle Scholar
  92. 92.
    Heck H, Mader A, Hess G, et al. Justification of the 4mmol/L lactate threshold. Int J Sports Med 1985; 6: 117–30PubMedCrossRefGoogle Scholar
  93. 93.
    Goodman MN, Lowenstein JM. The purine nucleotide cycle. Studies of ammonia production by skeletal musclein situ and in perfused preparations. J Biol Chem 1977; 252: 5054–60Google Scholar
  94. 94.
    Lowenstein JM. The purine nucleotide cycle revised. Int J Sports Med 1990; 11 Suppl. 2: S37–47CrossRefGoogle Scholar
  95. 95.
    Di Prampero PE. Energetics of muscular exercise. Rev Physiol Biochem Pharmacol 1981; 89: 143–222PubMedCrossRefGoogle Scholar
  96. 96.
    Role LW, Kelly JP. The brain stem: cranial nerve nuclei and the monoaminergic systems (chapter 44). In: Kandel ER, Schwartz JH, Jessell TM, editors. Principles of neural science. 3rd ed. Glenview (IL): Prentice-Hall International, 1991: 683–99 (ISBN 0-8385-8068-8)Google Scholar
  97. 97.
    Dodd J, Role LW. The autonomic nervous system (chapter 49). In: Kandel ER, Schwartz JH, Jessell TM, editors. Principles of neural science. 3rd ed. Glenview (IL): Prentice-Hall International, 1991: 761–75 (ISBN 0-8385-8068-8)Google Scholar
  98. 98.
    Patla AE. Understanding the roles of vision in the control of human locomotion (review article). Gait Posture 1997; 5: 54–9CrossRefGoogle Scholar
  99. 99.
    Garland SJ, Kaufman MP. Role of muscle afferents in the inhibition of motoneurons during fatigue (chapter 19). In: Gandevia SC, Enoka RM, McComas AJ, et al., editors. Fatigue: neural and muscular mechanisms–advances inmedicine and biology (volume 384). New York & London: Plenum Press, 1995: 271–80 (ISBN 0-306-45139-5)Google Scholar
  100. 100.
    Hagbarth KE, Macefield VG. The fusimotor system: its role in fatigue (chapter 18). In: Gandevia SC, Enoka RM, McComas AJ, et al., editors. Fatigue: neural and muscular mechanisms–advances in medicine and biology (volume 384). New York & London: Plenum Press, 1995: 259–70 (ISBN 0-306-45139-5)Google Scholar
  101. 101.
    Windhorst U, Boorman G. Overview: potential role of segmental motor circuitry in muscle fatigue (chapter 17). In: Gandevia SC, Enoka RM, McComas AJ, et al., editors. Fatigue: neural and muscular mechanisms–advances inmedicine and biology (volume 384). New York & London: Plenum Press, 1995: 241–58 (ISBN 0-306-45139-5)Google Scholar
  102. 102.
    Bigland-Ritchie BR, Dawson NJ, Johansson RS, et al. Reflex origin for the slowing of motoneurone firing ratesin fatigue of human voluntary contractions. J Physiol 1986; 379: 451–9PubMedGoogle Scholar
  103. 103.
    Martin PG, Smith JL, Butler JE, et al. Fatigue-sensitive afferents inhibit extensor but not flexor motoneurons in humans. J Neurosci 2006; 26: 4796–802PubMedCrossRefGoogle Scholar
  104. 104.
    Martin PG, Weerakkody N, Gandevia SC, et al. Group III and IV muscle afferents differentially affect the motorcortex and motoneurons in humans: afferents inhibit extensor but not flexor motoneurons in humans. J Physiol 2008; 586: 1277–89PubMedCrossRefGoogle Scholar
  105. 105.
    Nielsen J, Petersen N. Is presynaptic inhibition distributed to corticospinal fibres in man? J Physiol 1994; 477: 47–58PubMedGoogle Scholar
  106. 106.
    Gandevia SC, Allen GM, Butler JE, et al. Supraspinal factors in human muscle fatigue: evidence for sub-optimal output from the motor cortex. J Physiol 1996; 490: 529–36PubMedGoogle Scholar
  107. 107.
    Westerblad H, Lee JA, Lännergren J, et al. Cellular mechanisms of fatigue in skeletal muscle. Am J Physiol 1991; 261: C195–209Google Scholar
  108. 108.
    Gandevia SC, Allen GM, McKenzie DK. Central fatigue: critical issues and practical implications (chapter 20). In: Gandevia SC, Enoka RM, McComas AJ, et al., editors. Fatigue: neural and muscular mechanisms–advances inmedicine and biology (volume 384). New York & London: Plenum Press, 1995: 281–94 (ISBN 0-306-45139-5)Google Scholar
  109. 109.
    Merton PA. Voluntary strength and fatigue. J Physiol 1954; 123: 553–64PubMedGoogle Scholar
  110. 110.
    Barker AT, Jalinous R, Freeston IL. Non-invasive magnetic stimulation of human motor cortex. Lancet 1985; 325 (8437): 1106–7CrossRefGoogle Scholar
  111. 111.
    Taylor JL, Butler JE, Allen GM, et al. Changes in motor cortical excitability during human muscle fatigue. J Physiol 1996; 490: 519–28PubMedGoogle Scholar
  112. 112.
    McCloskey DI. Corollary discharges: motor commands and perception. In: Brookhart JM, Mountcastle VB, Brooks VB, editors. Handbook of physiology, section 1: the nervous system (volume II, part II), Motor control. New York: Oxford University Press, 1981: 1415–48 (ISBN 0-683-01105-7)Google Scholar
  113. 113.
    Jones LA. The senses of effort and force during fatiguing contractions (chapter 22). In: Gandevia SC, Enoka RM, McComas AJ, et al., editors. Fatigue: neural and muscular mechanisms–advances in medicine and biology (volume 384). New York & London: Plenum Press, 1995: 305–13 (ISBN 0-306-45139-5)Google Scholar
  114. 114.
    Brengelmann GL. Body temperature regulation (chapter 80). In: Patton HD, Fuchs AF, Hille B, et al., editors. Textbook of physiology, volume II. 21st ed. Philadelphia (PA): W.B. Saunders Company, 1989: 1584–96 (ISBN 0-7216-2524-X)Google Scholar
  115. 115.
    Johnson JM, Brengelmann GL, Hales JRS, et al. Regulation of the cutaneous circulation. Fed Proc 1986; 45: 2841–50PubMedGoogle Scholar
  116. 116.
    Nagashima K, Nakai S, Tanaka M, et al. Neuronal circuits involved in thermo regulation. Auton Neurosci 2000; 85: 18–25PubMedCrossRefGoogle Scholar
  117. 117.
    Gonzalez-Alonso J, Teller C, Andersen SL, et al. Influence of body temperature on the development of fatigue during prolonged exercise in the heat. J Appl Physiol 1999; 86: 1032–9PubMedGoogle Scholar
  118. 118.
    Nielsen B, Hyldig T, Bidstrup F, et al. Brain activity and fatigue during prolonged exercise in the heat. Eur J Physiol (Pflügers Arch) 2001; 442: 41–8CrossRefGoogle Scholar
  119. 119.
    Nielsen B, Nybo L. Cerebral changes during exercise in the heat. Sports Med 2003; 33: 1–11PubMedCrossRefGoogle Scholar
  120. 120.
    Todd G, Butler JE, Taylor JL, et al. Hyperthermia: a failure of the motor cortex and the muscle. J Physiol 2005; 563: 621–31PubMedCrossRefGoogle Scholar
  121. 121.
    Reza MF, Ikoma K, Chuma T, et al. Mechanomyographic response to transcranial magnetic stimulation from biceps brachii and during transcutaneous electrical nerve stimulation of extensor carpi radialis. J Neurosci Methods 2005; 49: 164–71CrossRefGoogle Scholar
  122. 122.
    Lacerda AC, Marubayashi U, Coimbra CC. Nitric oxide pathway is an important modulator of heat loss in rats during exercise. Brain Res Bull 2005; 67: 110–6PubMedCrossRefGoogle Scholar
  123. 123.
    Lacerda AC, Marubayashi U, Balthazar CH, et al. Evidence that brain nitric oxide inhibition increases metabolic cost of exercise, reducing running performance in rats. Neurosci Lett 2006; 393: 260–3PubMedCrossRefGoogle Scholar
  124. 124.
    Cheung SS, Sleivert GG. Multiple triggers for hyperthermic fatigue and exhaustion. Exerc Sport Sci Rev 2004; 32: 100–6PubMedCrossRefGoogle Scholar
  125. 125.
    Newsholme EA, Blomstrand E. Tryptophan 5-hydroxytryptamine and a possible explanation for central fatigue (chapter 23). In: Gandevia SC, Enoka RM, McComas AJ, et al., editors. Fatigue: neural and muscular mechanisms–advances in medicine and biology (volume 384). New York & London: Plenum Press, 1995: 315–20 (ISBN 0-306-45139-5)Google Scholar
  126. 126.
    Blomstrand E, Moller K, Secher NH, et al. Effect of carbohydrate ingestion on brain exchange of amino acids during sustained exercise in human subjects. Acta Physiol Scand 2005; 185: 203–9PubMedCrossRefGoogle Scholar
  127. 127.
    Cheuvront SN, Carter 3rd R, Kolka MA, et al. Branched-chain amino acid supplementation and human performance when hypohydrated in the heat. J Appl Physiol 2004; 97: 1275–82PubMedCrossRefGoogle Scholar
  128. 128.
    Ostrowski K, Hermann C, Bangash A, et al. A trauma-like elevation of plasma cytokines in humans in response to treadmill running. J Physiol 1998; 513: 889–94PubMedCrossRefGoogle Scholar
  129. 129.
    Ostrowski K, Rohde T, Zacho M, et al. Evidence that interleukin-6 is produced by skeletal muscle during prolonged exercise. J Physiol 1998; 503: 949–53CrossRefGoogle Scholar
  130. 130.
    Ostrowski K, Schjerling P, Pedersen BK. Physical activity and plasma interleukin-6 in humans: effect of intensity of exercise. Eur J Appl Phsyiol (Pflügers Arch) 2000; 83: 512–5Google Scholar
  131. 131.
    Steensberg A, van Hall G, Osada T, et al. Production of interleukin-6 in contracting human skeletal muscles can account for the exercise-induced increase in plasma interleukin-6. J Physiol 2000; 529: 237–42PubMedCrossRefGoogle Scholar
  132. 132.
    Febbraio MA, Steensberg A, Keller C, et al. Glucose ingestion attenuates interleukin-6 release from contracting muscle in humans. J Physiol 2003; 549: 607–12PubMedCrossRefGoogle Scholar
  133. 133.
    Helge JW, Stallknecht B, Pedersen BK, et al. The effect of graded exercise on IL-6 release and glucose uptake in human skeletal muscle. J Physiol 2003; 546: 299–305PubMedCrossRefGoogle Scholar
  134. 134.
    Pedersen BK, Hoffman-Goetz L. Exercise and the immune system: regulation, integration and adaptation. Physiol Rev 2000; 80: 1055–81PubMedGoogle Scholar
  135. 135.
    Keller C, Steensberg A, Hansen AK, et al. Effect of exercise, training, and glycogen availability on IL-6 receptor expression in human skeletal muscle. J Appl Physiol 2005; 99: 2075–9PubMedCrossRefGoogle Scholar
  136. 136.
    Clarkson PM, Hubal MJ. Exercise-induced muscle damage in humans. Am J Phys Med Rehabil 2002; 81Suppl. 11: S52–69CrossRefGoogle Scholar
  137. 137.
    Petersen AMW, Pedersen BK. The anti-inflammatory effect of exercise. J Appl Physiol 2005; 98: 1154–62PubMedCrossRefGoogle Scholar
  138. 138.
    Pedersen BK. Exercise and cytokines. Immunol Cell Biol 2000; 78: 523–35PubMedCrossRefGoogle Scholar
  139. 139.
    Ostrowski K, Rohde T, Asp S, et al. Pro- and anti-inflammatory cytokine balance in strenuous exercise in humans. J Physiol 1999; 515: 287–91PubMedCrossRefGoogle Scholar
  140. 140.
    Tomiya A, Aizawa T, Nagatomi R, et al. Myofibers express IL-6 after eccentric exercise. Am J Sports Med 2004; 32: 503–8PubMedCrossRefGoogle Scholar
  141. 141.
    Nieman DC, Davis JM, Henson DU, et al. Muscle cytokine mRNA changes after 2.5 h of cycling: influence of carbohydrate. Med Sci Sports Exerc 2005; 37: 1283–90PubMedCrossRefGoogle Scholar
  142. 142.
    Nieman DC, Davis JM, Walberg-Rankin J, et al. Carbohydrate ingestion influences skeletal muscle cytokine mRNA and plasma cytokine levels after 3-h run. J Appl Physiol 2003; 94: 1917–25PubMedGoogle Scholar
  143. 143.
    Kapsimalis F, Richardson G, Opp MR, et al. Cytokines and normal sleep. Curr Opin Pulm Med 2005; 11: 481–4PubMedCrossRefGoogle Scholar
  144. 144.
    Blatteis CM, Li S, Li Z, et al. Cytokines, PGE2 and endotoxic fever a re-assessment (review). Prostaglandins Other Lipid Mediat 2005; 76: 1–8PubMedCrossRefGoogle Scholar
  145. 145.
    Robson-Ansley PJ, de Milander L, Collins M, et al. Acute interleukin-6 administration impairs athletic performance in healthy, trained male runners. Can J Appl Physiol 2004; 29: 411–8PubMedCrossRefGoogle Scholar
  146. 146.
    Dantzer R. Cytokine-induced sickness behaviour: a neuroi-mmune response to activation of innate immunity. Eur J Pharmacol 2004; 500: 399–411PubMedCrossRefGoogle Scholar
  147. 147.
    Vollmer-Conna U, Fazou C, Cameron B, et al. Production of pro-inflammatory cytokines correlates with the symptoms of acute sickness behaviour in humans. Psychol Med 2004; 34: 1289–97PubMedCrossRefGoogle Scholar
  148. 148.
    Herholz K, Buskies W, Rist M, et al. Regional cerebral blood flow in man at rest and during exercise. J Neurol 1987; 234: 9–13PubMedCrossRefGoogle Scholar
  149. 149.
    Ide K, Horn A, Secher NH. Cerebral metabolic response to submaximal exercise. J Appl Physiol 1999; 87: 1604–8PubMedGoogle Scholar
  150. 150.
    Dalsgaard MK, Ide K, Cai Y, et al. The intent to exercise influences the cerebral O2/carbohydrate uptake ratio in humans. J Physiol 2002; 540: 681–9PubMedCrossRefGoogle Scholar
  151. 151.
    Noakes TD. Maximal oxygen uptake: “classical” versus “contemporary” viewpoints: a rebuttal. Med Sci Sports Med 1998; 30: 1381–98Google Scholar
  152. 152.
    Noakes TD. The Central Governor Model of exercise regulation applied to the marathon. Sports Med 2007; 37: 374–7PubMedCrossRefGoogle Scholar
  153. 153.
    Noakes TD, St Clair Gibson A. From catastrophe to complexity: a novel model of integrative central neural regulation of effort and fatigue during exercise in humans: summary and conclusions. Br J Sports Med 2004; 38: 511–4PubMedCrossRefGoogle Scholar
  154. 154.
    Nybo L, Nielsen B. Middle cerebral artery blood velocity is reduced with hyperthermia during prolonged exercise in humans. J Physiol 2001; 534: 279–86PubMedCrossRefGoogle Scholar
  155. 155.
    Madsen PL, Sperling BK, Warming T, et al. Middle cerebral artery blood velocity and cerebral blood flow and O2 uptake during dynamic exercise. J Appl Physiol 1993; 74: 245–50PubMedGoogle Scholar
  156. 156.
    Hasselbalch SG, Madsen PL, Hageman LP, et al. Changes in cerebral blood flow and carbohydrate metabolism during hyperketonemia. Am J Physiol 1996; 270: E746–51Google Scholar
  157. 157.
    Ide K, Schmalbruch IK, Quistorff B, et al. Lactate, glucose and O2 uptake in human brain during recovery from maximal exercise. J Physiol 2000; 522: 159–64PubMedCrossRefGoogle Scholar
  158. 158.
    Kemppainen J, Aalto S, Fujimoto T, et al. High intensity exercise decreases global brain glucose uptake in humans. J Physiol 2005; 568: 323–32PubMedCrossRefGoogle Scholar
  159. 159.
    Kernell D. Neuromuscular frequency-coding and fatigue (chapter 9). In: Gandevia SC, Enoka RM, McComas AJ, et al., editors. Fatigue: neural and muscular mechanisms–advances in medicine and biology (volume 384). New York & London: Plenum Press, 1995: 135–45 (ISBN 0-306-45139-5)Google Scholar
  160. 160.
    Lévesque M, Charara A, Gagnon S, et al. Corticostriatal projections from layer V cells in rat are collaterals of long-range corticofugal axons. Brain Res 1996; 709: 311–5PubMedCrossRefGoogle Scholar
  161. 161.
    Parent M, Parent A. Single-axon tracing study of corticostriatal projections arising from primary motor cortexin primates. J Comp Neurol 2006; 496: 202–13PubMedCrossRefGoogle Scholar
  162. 162.
    Reiner A, Jiao Y, del Mar N, et al. Differential morphology of pyramidal tract-type and intratelencephalically projecting-type corticostriatal neurons and their intrastriatal terminals in rats. J Comp Neurol 2003; 457: 420–40PubMedCrossRefGoogle Scholar
  163. 163.
    St Clair Gibson A, Baden DA, Lambert MI, et al. The conscious perception of the sensation of fatigue. Sports Med 2003; 33: 167–76PubMedCrossRefGoogle Scholar
  164. 164.
    Laureys S, Owen AM, Schiff ND. Brain function in coma, vegetative state, and related disorders. Lancet Neurol 2004; 3: 537–46PubMedCrossRefGoogle Scholar
  165. 165.
    Cavanna AE, Trimble MR. The precuneus: a review of its functional anatomy and behavioural correlates. Brain 2006; 129: 564–83PubMedCrossRefGoogle Scholar
  166. 166.
    Borg GAV. Physical performance and perceived exertion. Dissertation Lund University (Sweden), 1962Google Scholar
  167. 167.
    Borg E, Borg G. A comparison of AME and CR 100 for scaling perceived exertion. Acta Psychol (Amst) 2002; 190: 157–75CrossRefGoogle Scholar
  168. 168.
    Allman BL, Rice CL. Perceived exertion is elevated in old age during an isometric fatigue task. Eur J Appl Physiol 2003; 89: 191–7PubMedCrossRefGoogle Scholar
  169. 169.
    Hummel A, Läubli T, Pozzo M, et al. Relationship between perceived exertion and mean power frequency of the EMG signal from the upper trapezius muscle during isometric shoulder elevation. Eur J Appl Physiol 2005; 95: 321–6PubMedCrossRefGoogle Scholar
  170. 170.
    Hampson DB, St Clair Gibson A, Lambert MI, et al. The influence of sensory cues on the perception of exertion during exercise and central regulation of exercise performance. Sports Med 2001; 31: 935–52PubMedCrossRefGoogle Scholar
  171. 171.
    Davies CT, Sargeant AJ. The effects of atropine and practolol on the perception of exertion during treadmill exercise. Ergonomics 1979; 22: 1141–6PubMedCrossRefGoogle Scholar
  172. 172.
    Ekblom B, Goldbarg AN. The influence of physical training and other factors on the subjective rating of perceived exertion. Acta Physiol Scand 1971; 83: 399–406PubMedCrossRefGoogle Scholar
  173. 173.
    Eston R, Connolly D. The use of ratings of perceived exertion for exercise prescription in patients receiving β-blocker therapy. Sports Med 1996; 21: 176–90PubMedCrossRefGoogle Scholar
  174. 174.
    Tesch PA, Kaiser P. Effects of β-adrenergic blockade on O2 uptake during submaximal and maximal exercise. J Appl Physiol 1983; 54: 901–5PubMedGoogle Scholar
  175. 175.
    Pandolf KB, Noble BJ. The effect of pedaling speed and resistance changes on perceived exertion for equivalent power outputs on the bicycle ergometer. Med Sci Sports 1973; 5: 132–6PubMedGoogle Scholar
  176. 176.
    Kohler G, Boutellier U. The generalized force-velocity relationship explains why the preferred pedalling rate of cyclists exceeds the most efficient one. Eur J Appl Physiol 2005; 94: 188–95PubMedCrossRefGoogle Scholar
  177. 177.
    Baron R. Aerobic and anaerobic power characteristics of off-road cyclists. Med Sci Sports Exerc 2001; 33: 1387–93PubMedCrossRefGoogle Scholar
  178. 178.
    Ulmer H-V. Concept of extracellular regulation ofmuscular metabolic rate during heavy exercise in humans by psychophysiological feedback. Experientia 1996; 52: 416–20PubMedCrossRefGoogle Scholar
  179. 179.
    Eston R, Faulkner J, St Clair Gibson A, et al. The effect of antecedent fatiguing activity on the relationship between perceived exertion and physiological activity during a constant load exercise task. Psychophysiology 2007; 44: 779–86PubMedCrossRefGoogle Scholar
  180. 180.
    Eston RG, Lamb KL, Parfitt G. The validity of predicting maximal oxygen uptake from a perceptually-regulated graded exercise test. Eur J Appl Physiol 2005; 94: 221–7PubMedCrossRefGoogle Scholar
  181. 181.
    Weir JP, Beck TW, Cramer JT, et al. Is fatigue all in your head? A critical review of the central governor model. Br J Sports Med 2006; 40: 573–86Google Scholar
  182. 182.
    Jones DA, Round JM. Training for power (chapter 6) In: Jones DA, Round JM, editors. Skeletal muscle in health and disease. Manchester: Manchester University Press, 1990 (ISBN 0-719031648)Google Scholar
  183. 183.
    Ferreira LF, McDonough P, Behnke BJ, et al. Blood flow and O2 extraction as a function of O2 uptake in muscles composed of different fiber types. Respir Physiol Neurobiol 2006; 153: 237–49PubMedCrossRefGoogle Scholar
  184. 184.
    Marsh RL, Ellerby DJ. Partitioning locomotor energy use among and within muscles: muscle blood flow as a measure of muscle oxygen consumption. J Exp Biol 2006; 209: 2385–94PubMedCrossRefGoogle Scholar
  185. 185.
    Butler AB, Hodos W. Comparative vertebrate neuroanatomy. Butler AB, Hodos W, editors. 2nd ed. Hoboken (NY): John Wiley & Sons Inc., 2005: 139–55, 221-39Google Scholar
  186. 186.
    Lacalli TC. New perspectives on the evolution of protochordate sensory and locomotory systems, and the origin of brains and head. Phil Trans R Soc 2001; 356: 1565–73CrossRefGoogle Scholar
  187. 187.
    Bone Q. Evolutionary patterns of axial muscle systems in some invertebrates and fish. Am Zoologist 1989; 29: 5–18Google Scholar
  188. 188.
    Wicht H, Lacalli TC. The nervous system of amphioxus: structure, development, and evolutionary significance. Can J Zool 2005; 83: 122–50CrossRefGoogle Scholar
  189. 189.
    Rohmert W. Ermittlung von Erholungspause für statische Arbeit des Menschen. Int Z Angew Physiol 1960; 18: 123–64PubMedGoogle Scholar
  190. 190.
    Barcroft H, Millen JLE. The blood flow through muscle during sustained contraction. J Physiol 1939; 97: 17–31PubMedGoogle Scholar
  191. 191.
    Lind AR, Taylor SH, Humpreys PW, et al. The circulatory effects of sustained voluntary muscle contraction. Clin Sci 1964; 27: 229–44PubMedGoogle Scholar
  192. 192.
    Kanemaki T, Kitade H, Kaibori M, et al. Interleukin 1β and interleukin 6, but not tumor necrosis factor α, inhibit insulin-stimulated glycogen synthesis in rat hepatocytes. Hepatology 1998; 27: 1296–303PubMedCrossRefGoogle Scholar
  193. 193.
    Febbraio MA, Hiscock N, Sacchetti M, et al. Interleukin-6 is a novel factor mediating glucose homeostasis during skeletal muscle contraction. Diabetes 2004; 53: 1643–8PubMedCrossRefGoogle Scholar
  194. 194.
    Abdelmalki A, Merino D, Bonneau D, et al. Administration of a GABAB agonist baclofen before running to exhaustion in the rat: effects on performance and on some indicators of fatigue. Inter J Sports Med 1997; 18: 75–8CrossRefGoogle Scholar
  195. 195.
    Nathan C. Points of control in inflammation. Nature 2002; 420: 846–52PubMedCrossRefGoogle Scholar
  196. 196.
    Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. New Engl J Med 1999; 340: 448–54PubMedCrossRefGoogle Scholar
  197. 197.
    Maier SF, Watkins LR. Cytokines for psychologists: implications of bidirectional immune-to-brain communication for understanding behavior, mood and cognition. Psychol Rev 1998; 105: 83–107PubMedCrossRefGoogle Scholar
  198. 198.
    Kent S, Bluthe RM, Dantzer R, et al. Different receptor mechanisms mediate pyrogenic and behavioral effects of interleukin-1. Proc Natl Acad Sci USA 1992; 89: 9117–20PubMedCrossRefGoogle Scholar
  199. 199.
    Wang J, Ando T, Dunn AJ. Effect of homologous interleukin-1, interleukin-6 and tumor necrosis factor-alpha on the core body temperature of mice. Neuro-immunomodulation 1997; 4: 230–6Google Scholar
  200. 200.
    Blatteis CM. Endotoxic fever: new concepts of its regulation suggest new approaches to its management. Pharmacol Ther 2006; 111: 194–223PubMedCrossRefGoogle Scholar
  201. 201.
    Lewis MI, Monn SA, Sieck GC. Effect of corticosteroids on diaphragm fatigue, SDH activity, and muscle fiber size. J Appl Physiol 1992; 72: 293–301PubMedGoogle Scholar
  202. 202.
    Topp KS, Painter PL, Walcott S, et al. Alterations in skeletal muscle structure are minimized with steroid withdrawal after renal transplantation. Transplantation 2003; 76: 667–73PubMedCrossRefGoogle Scholar
  203. 203.
    Tarnopolsky MA, MacDougall JD, Atkinson SA. Influence of protein intake and training status on nitrogen balance and lean body mass. J Appl Physiol 1988; 64: 187–93PubMedGoogle Scholar
  204. 204.
    Mishra DK, Fridén J, Schmitz MC, et al. Anti-inflammatory medication after muscle injury: a treatment resulting in short-term improvement but subsequent loss of muscle function. J Bone Joint Surg Am 1995; 77: 1510–9PubMedGoogle Scholar
  205. 205.
    Discussion between Swaak (physician) and Mishra (et al.). J Bone Joint Surg (Am) 1997; 79: 1270–1Google Scholar
  206. 206.
    Belardinelli R, Barstow T, Nguyen P, et al. Skeletal muscle oxygenation and oxygen uptake kinetics following constant work rate exercise in chronic congestive heart failure. Am J Cardiol 1997; 80: 1319–25PubMedCrossRefGoogle Scholar
  207. 207.
    Lele SS, Macfarlane D, Morrison S, et al. Determinants of exercise capacity in patients with coronary artery disease and mild to moderate systolic dysfunction. Eur Heart J 1996; 17: 204–12PubMedCrossRefGoogle Scholar
  208. 208.
    Wasserman K. Diagnosing cardiovascular and lung pathophysiology from exercise gas exchange. Chest 1997; 112: 1091–101PubMedCrossRefGoogle Scholar
  209. 209.
    Rus HG, Vlaicu R, Niculescu F. Interleukin-6 and interleukin- 8 protein and gene expression in human arterial atherosclerotic wall. Atherosclerosis 1996; 127: 263–71PubMedCrossRefGoogle Scholar
  210. 210.
    Rus HG, Niculescu F, Vlaicu R. Tumor necrosis factoralpha in human arterial wall with atherosclerosis. Atherosclerosis 1991; 89: 247–54PubMedCrossRefGoogle Scholar
  211. 211.
    Ridker PM, Rifai N, Stampfer MJ, et al. Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation 2000; 101: 1767–72PubMedCrossRefGoogle Scholar
  212. 212.
    Johnson JM. Circulation to skeletal muscle. In: Patton HD, Fuchs AF, Hille B, et al., editors. Textbook of physiology, vol. 2. 21st ed. Philadelphia (PA): W.B. Saunders Company, 1989: 87–889 (ISBN 0-7216-2524-X)Google Scholar
  213. 213.
    Pijls NHJ, deBruyne B. The coronary circulation (chapter 2). In: Coronary pressure. 2nd ed. Boston (MA): Kluwer Academic Publishers, 2000 (ISBN 0-792361709)Google Scholar
  214. 214.
    Shankaran V, Ikeda H, Bruce AT, et al. IFNγ and lymphocytes prevent primary tumour development and shape tumor immunogenicity. Nature 2001; 410: 1107–11PubMedCrossRefGoogle Scholar
  215. 215.
    Smyth MJ, Dunn GP, Schreiber RD. Cancer immuno-surveillance and immunoediting: the roles of immunity in suppressing tumor development and shaping tumor immunogenicity. Adv Immunol 2006; 90: 1–50PubMedCrossRefGoogle Scholar
  216. 216.
    Bui JD, Schreiber RD. Cancer immunosurveillance, immunoediting and inflammation: independent or interdependent processes? Curr Opin Immunol 2007; 19: 203–8PubMedCrossRefGoogle Scholar
  217. 217.
    Dunn GP, Old LJ, Schreiber RD. The three Es of cancer immunoediting. Annu Rev Immunol 2004; 22: 329–60PubMedCrossRefGoogle Scholar
  218. 218.
    Luo JL, Kamata H, Karin M. IKK/ NK-κB signaling: balancing life and death–a new approach to cancer therapy. J Clin Invest 2005; 115: 2625–32PubMedCrossRefGoogle Scholar
  219. 219.
    Luo JL, Maeda S, Hus LC, et al. Inhibition of NK-κB in cancer cells converts inflammation-induced tumor growth mediated by TNFα to TRIAL-mediated tumor regression. Cancer Cell 2004; 6: 297–305PubMedCrossRefGoogle Scholar
  220. 220.
    Langowski JL, Zhang X, Wu L, et al. IL-23 promotes tumour incidence and growth. Nature 2006 Jul 27; 442 (7101): 461–5PubMedCrossRefGoogle Scholar
  221. 221.
    Peake JM, Suzuki K, Hordern M, et al. Plasma cytokine changes in relation to exercise intensity and muscle damage. Eur J Appl Physiol 2005; 95: 514–21PubMedCrossRefGoogle Scholar
  222. 222.
    Kim S, Keku TO, Martin C, et al. Circulating levels of inflammatory cytokines and risk of colorectal adenomas. Cancer Res 2008; 68: 323–8PubMedCrossRefGoogle Scholar
  223. 223.
    Nery LE, Wasserman K, Andrews JD, et al. Ventilatory and gas exchange kinetics during exercise in chronic airways obstruction. J Appl Physiol 1982; 53: 1594–602PubMedGoogle Scholar
  224. 224.
    Hlastala MP. Gas transport and exchange (chapter 53). In: Patton HD, Fuchs AF, Hille B, et al., editors. Textbook of physiology, volume II. 21st ed. Philadelphia (PA): W.B. Saunders Company, 1989: 1012–25 (ISBN 0-7216-2524-X)Google Scholar
  225. 225.
    American Thoracic Society and European Respiratory Society. Skeletal muscle dysfunction in chronic obstructive pulmonary disease. Am J Respir Crit Med 1999; 159: S1–40Google Scholar
  226. 226.
    Hamaoka T, McCully KK, Quaresima V, et al. Near infrared spectroscopy/imaging for monitoring muscle oxygenation in healthy and diseased humans. J Biomedical Optics 2007; 12: 062105Google Scholar
  227. 227.
    Bazelmans E, Bleijenberg G, Van Der Meer JW, et al. Is physical deconditioning a perpetuating factor in chronic fatigue syndrome? A controlled study on maximal exercise performance and relations with fatigue, impairment and physical activity. Psychol Med 2001; 31: 107–14Google Scholar
  228. 228.
    Jammes Y, Steinberg JG, Mambrini O, et al. Chronic fatigue syndrome: assessment of increased oxidative stressand altered muscle excitability in response to incremental exercise. J Intern Med 2005; 257: 299–310PubMedCrossRefGoogle Scholar
  229. 229.
    Sargent C, Scroop GC, Nemeth PM, et al. Maximal oxygen uptake and lactate metabolism are normal in chronic fatigue syndrome. Med Sci Sports Exerc 2002; 34: 51–6PubMedGoogle Scholar
  230. 230.
    Wallman KE, Morton AR, Goodman C, et al. Physiological responses during a submaximal cycle test in chronic fatigue syndrome. Med Sci Sports Exerc 2004; 36: 1682–8PubMedCrossRefGoogle Scholar
  231. 231.
    Cannon JG, Angel JB, Ball RW, et al. Acute phase responses and cytokine secretion in chronic fatigue syndrome. J Clin Immunol 1999; 19: 414–21PubMedCrossRefGoogle Scholar
  232. 232.
    Peterson PK, Sirr SA, Grammith FC, et al. Effects of mild exercise on cytokines and cerebral blood flow in chronic fatigue syndrome. Clin Diagn Lab Immunol 1994; 1: 222–6PubMedGoogle Scholar
  233. 233.
    Tomoda A, Joudoi T, Rabab E-M, et al. Cytokine production and modulation: comparison of patients with chronic fatigue syndrome and normal controls. Psychiatry Res 2005; 134: 101–4PubMedCrossRefGoogle Scholar
  234. 234.
    Di Giorgio A, Hudson M, Jerjes W, et al. 24-Hour pituitary and adrenal hormone profiles in chronic fatigue syndrome. Psychosom Med 2005; 67: 433–40PubMedCrossRefGoogle Scholar
  235. 235.
    de Lange FP, Kalkman JS, Bleijenberg G, et al. Gray matter volume reduction in the chronic fatigue syndrome. Neuroimage 2005; 26: 777–81PubMedCrossRefGoogle Scholar
  236. 236.
    Schwarz L, Kindermann W. β-Endomorphin, catecholamines, and cortisol during exhaustive endurance exercise. Int J Sports Med 1989; 10: 324–8PubMedCrossRefGoogle Scholar
  237. 237.
    Lehmann M, Foster C, Dickhuth H-H. Gastmann. Autonomic imbalance hypothesis and overtraining syndrome. Med Sci Sports Exerc 1998; 30: 1140–5Google Scholar
  238. 238.
    Urhausen A, Gabriel HHW, Kindermann W. Impaired pituitary hormonal response to exhaustive exercise in overtrained endurance athletes. Med Sci Sports Exerc 1998; 30: 407–14PubMedCrossRefGoogle Scholar
  239. 239.
    Smith LL. Cytokine hypothesis of overtraining: a physiological adaptation to excessive stress? Med Sci Sports Exerc 2000; 32: 317–31PubMedCrossRefGoogle Scholar
  240. 240.
    Steinacker JM, Lormes W, Reissnecker S, et al. New aspects of the hormone and cytokine response to training. Eur J Appl Physiol 2004; 91: 382–91PubMedCrossRefGoogle Scholar
  241. 241.
    Kuipers H, Keizer HA. Overtraining in elite athletes: review and directions for the future. Sports Med 1988; 6: 79–92PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2009

Authors and Affiliations

  1. 1.Department of Biometrics, Faculty of Health and TechnologyZuyd UniversityHeerlenthe Netherlands
  2. 2.Department of Biomedical EngineeringUniversity Medical Center Groningen, University of GroningenGroningenthe Netherlands
  3. 3.Department of Biomechanical EngineeringUniversity of TwenteEnschedethe Netherlands

Personalised recommendations