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Ensemble Input of Group III/IV Muscle Afferents to CNS: A Limiting Factor of Central Motor Drive During Endurance Exercise from Normoxia to Moderate Hypoxia

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Hypoxia

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 903))

Abstract

We recently hypothesized that across the range of normoxia to severe hypoxia the major determinant of central motor drive (CMD) during endurance exercise switches from a predominantly peripheral origin to a hypoxic-sensitive central component of fatigue. We found that peripheral locomotor muscle fatigue (pLMF) is the prevailing factor limiting central motor drive and therefore exercise performance from normoxia to moderate hypoxia (SaO2 > 75 %). In these levels of arterial hypoxemia, the development of pLMF is confined to a certain limit which varies between humans—pLMF does not develop to this limit in more severe hypoxia (SaO2 < 70 %) and exercise is prematurely terminated presumably to protect the brain from insufficient O2 supply. Based on the observations from normoxia to moderate hypoxia, we outlined a model suggesting that group III/IV muscle afferents impose inhibitory influences on the determination of CMD of working humans during high-intensity endurance exercise with the purpose to regulate and restrict the level of exercise-induced pLMF to an “individual critical threshold.” To experimentally test this model, we pharmacologically blocked somatosensory pathways originating in the working limbs during cycling exercise in normoxia. After initial difficulties with a local anesthetic (epidural lidocaine, L3–L4) and associated loss of locomotor muscle strength we switched to an intrathecally applied opioid analgesic (fentanyl, L3–L4). These experiments were the first ever to selectively block locomotor muscle afferents during high-intensity cycling exercise without affecting maximal locomotor muscle strength. In the absence of opioid-mediated neural feedback from the working limbs, CMD was increased and end-exercise pLMF substantially exceeded, for the first time, the individual critical threshold of peripheral fatigue. The outcome of these studies confirm our hypothesis claiming that afferent feedback inhibits CMD and restricts the development of pLMF to an individual critical threshold as observed from normoxia up to moderate hypoxia.

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References

  1. Adams RP, Welch HG. Oxygen uptake, acid-base status, and performance with varied inspired oxygen fractions. J Appl Physiol. 1980;49:863–8.

    CAS  PubMed  Google Scholar 

  2. Amann M, Calbet JA. Convective oxygen transport and fatigue. J Appl Physiol. 2008;104:861–70.

    Article  PubMed  Google Scholar 

  3. Amann M, Dempsey JA. The concept of peripheral locomotor muscle fatigue as a regulated variable. J Physiol. 2008;586:2029–30.

    Article  CAS  PubMed Central  Google Scholar 

  4. Amann M, Dempsey JA. Locomotor muscle fatigue modifies central motor drive in healthy humans and imposes a limitation to exercise performance. J Physiol. 2008;586(1):161–73.

    Article  CAS  PubMed  Google Scholar 

  5. Amann M, Dempsey JA. Peripheral muscle fatigue from hyperoxia to moderate hypoxia - a carefully regulated variable? Physiology News. 2007;66:28–9.

    Google Scholar 

  6. Amann M, Eldridge MW, Lovering AT, Stickland MK, Pegelow DF, Dempsey JA. Arterial oxygenation influences central motor output and exercise performance via effects on peripheral locomotor muscle fatigue. J Physiol. 2006;575(3):937–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Amann M, Hopkins WG, Marcora SM. Similar sensitivity of time to exhaustion and time trial to changes in endurance. Med Sci Sports Exerc. 2008;40:574–8.

    Article  PubMed  Google Scholar 

  8. Amann M, Pegelow DF, Jacques AJ, Dempsey JA. Inspiratory muscle work in acute hypoxia influences locomotor muscle fatigue and exercise performance of healthy humans. Am J Physiol Regul Integr Comp Physiol. 2007;293:R2036–45.

    Article  CAS  PubMed  Google Scholar 

  9. Amann M, Proctor LT, Sebranek JJ, Eldridge MW, Pegelow DF, Dempsey JA. Somatosensory feedback from the limbs exerts inhibitory influences on central neural drive during whole body endurance exercise. J Appl Physiol. 2008;105:1714–24.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Amann M, Proctor LT, Sebranek JJ, Pegelow DF, Dempsey JA. Opioid-mediated muscle afferents inhibit central motor drive and limit peripheral muscle fatigue development in humans. J Physiol. 2008;587:271–83.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Amann M, Romer LM, Subudhi AW, Pegelow DF, Dempsey JA. Severity of arterial hypoxaemia affects the relative contributions of peripheral muscle fatigue to exercise performance in healthy humans. J Physiol. 2007;581:389–403.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Arbogast S, Vassilakopoulos T, Darques JL, Duvauchelle JB, Jammes Y. Influence of oxygen supply on activation of group IV muscle afferents after low-frequency muscle stimulation. Muscle Nerve. 2000;23:1187–93.

    Article  CAS  PubMed  Google Scholar 

  13. Asmussen E, Johansen SH, Jorgensen M, Nielsen M. On the nervous factors controlling respiration and circulation during exercise. Experiments with curarization. Acta Physiol Scand. 1965;63:343–50.

    Article  CAS  PubMed  Google Scholar 

  14. Barclay JK. A delivery-independent blood flow effect on skeletal muscle fatigue. J Appl Physiol. 1986;61:1084–90.

    CAS  PubMed  Google Scholar 

  15. Boushel R, Calbet JA, Radegran G, Sondergaard H, Wagner PD, Saltin B. Parasympathetic neural activity accounts for the lowering of exercise heart rate at high altitude. Circulation. 2001;104:1785–91.

    Article  CAS  PubMed  Google Scholar 

  16. Buskirk ER, Kollias J, Akers RF, Prokop EK, Reategui EP. Maximal performance at altitude and on return from altitude in conditioned runners. J Appl Physiol. 1967;23:259–66.

    CAS  PubMed  Google Scholar 

  17. Calbet JA, Boushel R, Radegran G, Sondergaard H, Wagner PD, Saltin B. Why is VO2 max after altitude acclimatization still reduced despite normalization of arterial O2 content? Am J Physiol Regul Integr Comp Physiol. 2003;284:R304–16.

    Article  CAS  PubMed  Google Scholar 

  18. Calbet JA, De Paz JA, Garatachea N, Cabeza De Vaca S, Chavarren J. Anaerobic energy provision does not limit Wingate exercise performance in endurance-trained cyclists. J Appl Physiol. 2003;94:668–76.

    Article  CAS  PubMed  Google Scholar 

  19. Calbet JAL. The rate of fatigue accumulation as a sensed variable. J Physiol. 2006;575:688–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Chaudhuri A, Behan PO. Fatigue and basal ganglia. J Neurol Sci. 2000;179:34–42.

    Article  CAS  PubMed  Google Scholar 

  21. Cibella F, Cuttitta G, Romano S, Grassi B, Bonsignore G, Milic-Emili J. Respiratory energetics during exercise at high altitude. J Appl Physiol. 1999;86:1785–92.

    Article  CAS  PubMed  Google Scholar 

  22. Dempsey JA, Romer L, Rodman J, Miller J, Smith C. Consequences of exercise-induced respiratory muscle work. Respir Physiol Neurobiol. 2006;151:242–50.

    Article  PubMed  Google Scholar 

  23. Dempsey JA, Wagner PD. Exercise-induced arterial hypoxemia. J Appl Physiol. 1999;87:1997–2006.

    CAS  PubMed  Google Scholar 

  24. Duhamel TA, Green HJ, Sandiford SD, Perco JG, Ouyang J. Effects of progressive exercise and hypoxia on human muscle sarcoplasmic reticulum function. J Appl Physiol. 2004;97:188–96.

    Article  CAS  PubMed  Google Scholar 

  25. Ferretti G, Moia C, Thomet JM, Kayser B. The decrease of maximal oxygen consumption during hypoxia in man: a mirror image of the oxygen equilibrium curve. J Physiol. 1997;498(Pt 1):231–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Fitts RH. The cross-bridge cycle and skeletal muscle fatigue. J Appl Physiol. 2008;104:551–8.

    Article  CAS  PubMed  Google Scholar 

  27. Fulco CS, Rock PB, Cymerman A. Maximal and submaximal exercise performance at altitude. Aviat Space Environ Med. 1998;69:793–801.

    CAS  PubMed  Google Scholar 

  28. Gandevia SC. Spinal and supraspinal factors in human muscle fatigue. Physiol Rev. 2001;81:1725–89.

    CAS  PubMed  Google Scholar 

  29. Gandevia SC, Macefield G, Burke D, McKenzie DK. Voluntary activation of human motor axons in the absence of muscle afferent feedback. The control of the deafferented hand. Brain. 1990;113(Pt 5):1563–81.

    Article  PubMed  Google Scholar 

  30. Garland SJ, Kaufman MP. Role of muscle afferents in the inhibition of motoneurons during fatigue. In: Gandevia SC, Enoka RM, McComas AJ, Stuart DG, Thomas CK, editors. Fatigue: neural and muscular mechanisms. New York, NY: Plenum Press; 1995. p. 271–8.

    Chapter  Google Scholar 

  31. Gore CJ, Hahn AG, Scroop GC, Watson DB, Norton KI, Wood RJ, Campbell DP, Emonson DL. Increased arterial desaturation in trained cyclists during maximal exercise at 580 m altitude. J Appl Physiol. 1996;80:2204–10.

    CAS  PubMed  Google Scholar 

  32. Haddad GG, Jiang C. O2 deprivation in the central nervous system: on mechanisms of neuronal response, differential sensitivity and injury. Prog Neurobiol. 1993;40:277–318.

    Article  CAS  PubMed  Google Scholar 

  33. Hansen AJ. Effect of anoxia on ion distribution in the brain. Physiol Rev. 1985;65:101–48.

    CAS  PubMed  Google Scholar 

  34. Harik SI, Busto R, Martinez E. Norepinephrine regulation of cerebral glycogen utilization during seizures and ischemia. J Neurosci. 1982;2:409–14.

    CAS  PubMed  Google Scholar 

  35. Harms CA, Babcock MA, McClaran SR, Pegelow DF, Nickele GA, Nelson WB, Dempsey JA. Respiratory muscle work compromises leg blood flow during maximal exercise. J Appl Physiol. 1997;82:1573–83.

    CAS  PubMed  Google Scholar 

  36. Harms CS, McClaran S, Nickele GA, Pegelow DF, Nelson WB, Dempsey JA. Effect of exercise-induced arterial O2 desaturation on VO2max in women. Med Sci Sports Exerc. 2000;32:1101–8.

    Article  CAS  PubMed  Google Scholar 

  37. Haseler LJ, Richardson RS, Videen JS, Hogan MC. Phosphocreatine hydrolysis during submaximal exercise: the effect of FIO2. J Appl Physiol. 1998;85:1457–63.

    CAS  PubMed  Google Scholar 

  38. Hill JM, Pickar JG, Parrish MD, Kaufman MP. Effects of hypoxia on the discharge of group III and IV muscle afferents in cats. J Appl Physiol. 1992;73:2524–9.

    CAS  PubMed  Google Scholar 

  39. Hogan MC, Richardson RS, Haseler LJ. Human muscle performance and PCr hydrolysis with varied inspired oxygen fractions: a 31P-MRS study. J Appl Physiol. 1999;86:1367–73.

    CAS  PubMed  Google Scholar 

  40. Hogan MC, Welch HG. Effect of varied lactate levels on bicycle ergometer performance. J Appl Physiol. 1984;57:507–13.

    CAS  PubMed  Google Scholar 

  41. Kayser B. Why is endurance performance decreased at high altitude? Schweizerische Zeitschrift für Sportmedizin und Sporttraumatologie. 2005;53:54–60.

    Google Scholar 

  42. Kayser B, Narici M, Binzoni T, Grassi B, Cerretelli P. Fatigue and exhaustion in chronic hypobaric hypoxia: influence of exercising muscle mass. J Appl Physiol. 1994;76:634–40.

    CAS  PubMed  Google Scholar 

  43. Kniffki KD, Mense S, Schmidt RF. Responses of group IV afferent units from skeletal muscle to stretch, contraction and chemical stimulation. Exp Brain Res. 1978;31:511–22.

    Article  CAS  PubMed  Google Scholar 

  44. Koskolou MD, Calbet JA, Radegran G, Roach RC. Hypoxia and the cardiovascular response to dynamic knee-extensor exercise. Am J Physiol. 1997;272:H2655–63.

    CAS  PubMed  Google Scholar 

  45. Koskolou MD, Roach RC, Calbet JA, Radegran G, Saltin B. Cardiovascular responses to dynamic exercise with acute anemia in humans. Am J Physiol. 1997;273:H1787–93.

    CAS  PubMed  Google Scholar 

  46. Lagier-Tessonnier F, Balzamo E, Jammes Y. Comparative effects of ischemia and acute hypoxemia on muscle afferents from tibialis anterior in cats. Muscle Nerve. 1993;16:135–41.

    Article  CAS  PubMed  Google Scholar 

  47. Lannergren J, Westerblad H. Force decline due to fatigue and intracellular acidification in isolated fibres from mouse skeletal muscle. J Physiol. 1991;434:307–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Mense S. Nervous outflow from skeletal muscle following chemical noxious stimulation. J Physiol. 1977;267:75–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Mense S. Sensitization of group IV muscle receptors to bradykinin by 5-hydroxytryptamine and prostaglandin E2. Brain Res. 1981;225:95–105.

    Article  CAS  PubMed  Google Scholar 

  50. Nauta WJH. The relationship of basal ganglia to the limbic system. In: Vinken PJ, Bruyn GW, editors. Handbook of clinical neurology. Amsterdam: Elsevier Science; 1986. p. 19–32.

    Google Scholar 

  51. Noakes TD, Peltonen JE, Rusko HK. Evidence that a central governor regulates exercise performance during acute hypoxia and hyperoxia. J Exp Biol. 2001;204:3225–34.

    CAS  PubMed  Google Scholar 

  52. Nybo L, Secher NH. Cerebral perturbations provoked by prolonged exercise. Prog Neurobiol. 2004;72:223–61.

    Article  PubMed  Google Scholar 

  53. Reeves JT, Groves BM, Sutton JR, Wagner PD, Cymerman A, Malconian MK, Rock PB, Young PM, Houston CS. Operation Everest II: preservation of cardiac function at extreme altitude. J Appl Physiol. 1987;63:531–9.

    CAS  PubMed  Google Scholar 

  54. Roach RC, Maes D, Sandoval D, Robergs RA, Icenogle M, Hinghofer-Szalkay H, Lium D, Loeppky JA. Exercise exacerbates acute mountain sickness at simulated high altitude. J Appl Physiol. 2000;88:581–5.

    CAS  PubMed  Google Scholar 

  55. Romer LM, Haverkamp HC, Amann M, Lovering AT, Pegelow DF, Dempsey JA. Effect of acute severe hypoxia on peripheral fatigue and endurance capacity in healthy humans. Am J Physiol Regul Integr Comp Physiol. 2007;292:R598–606.

    Article  CAS  PubMed  Google Scholar 

  56. Romer LM, Haverkamp HC, Lovering AT, Pegelow DF, Dempsey JA. Effect of exercise-induced arterial hypoxemia on quadriceps muscle fatigue in healthy humans. Am J Physiol Regul Integr Comp Physiol. 2006;290:R365–75.

    Article  CAS  PubMed  Google Scholar 

  57. Rotto DM, Kaufman MP. Effect of metabolic products of muscular contraction on discharge of group III and IV afferents. J Appl Physiol. 1988;64:2306–13.

    CAS  PubMed  Google Scholar 

  58. Rybicki KJ, Waldrop TG, Kaufman MP. Increasing gracilis muscle interstitial potassium concentrations stimulate group III and IV afferents. J Appl Physiol. 1985;58:936–41.

    Article  CAS  PubMed  Google Scholar 

  59. Sandiford SD, Green HJ, Duhamel TA, Schertzer JD, Perco JD, Ouyang J. Muscle Na-K-pump and fatigue responses to progressive exercise in normoxia and hypoxia. Am J Physiol Regul Integr Comp Physiol. 2005;289:R441–9.

    Article  CAS  PubMed  Google Scholar 

  60. Schultz W, Dayan P, Montague PR. A neural substrate of prediction and reward. Science. 1997;275:1593–9.

    Article  CAS  PubMed  Google Scholar 

  61. Stary CM, Hogan MC. Impairment of Ca(2+) release in single Xenopus muscle fibers fatigued at varied extracellular PO(2). J Appl Physiol. 2000;88:1743–8.

    CAS  PubMed  Google Scholar 

  62. Steinhagen C, Hirche HJ, Nestle HW, Bovenkamp U, Hosselmann I. The interstitial pH of the working gastrocnemius muscle of the dog. Pflugers Arch. 1976;367:151–6.

    Article  CAS  PubMed  Google Scholar 

  63. Suarez J, Alexander JK, Houston CS. Enhanced left ventricular systolic performance at high altitude during Operation Everest II. Am J Cardiol. 1987;60:137–42.

    Article  CAS  PubMed  Google Scholar 

  64. Subudhi AW, Dimmen AC, Roach RC. Effects of acute hypoxia on cerebral and muscle oxygenation during incremental exercise. J Appl Physiol. 2007;103:177–83.

    Article  CAS  PubMed  Google Scholar 

  65. Subudhi AW, Lorenz MC, Fulco CS, Roach RC. Cerebrovascular responses to incremental exercise during hypobaric hypoxia: effect of oxygenation on maximal performance. Am J Physiol Heart Circ Physiol. 2008;294:H164–71.

    Article  CAS  PubMed  Google Scholar 

  66. Vogiatzis I, Georgiadou O, Koskolou M, Athanasopoulos D, Kostikas K, Golemati S, Wagner H, Roussos C, Wagner PD, Zakynthinos S. Effects of hypoxia on diaphragmatic fatigue in highly trained athletes. J Physiol. 2007;581:299–308.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Volianitis S, Fabricius-Bjerre A, Overgaard A, Stromstad M, Bjarrum M, Carlson C, Petersen NT, Rasmussen P, Secher NH, Nielsen HB. The cerebral metabolic ratio is not affected by oxygen availability during maximal exercise in humans. J Physiol. 2008;586:107–12.

    Article  CAS  PubMed  Google Scholar 

  68. Waldrop TG, Eldridge FL, Iwamoto GA, Mitchell JH. Central neural control of respiration and circulation during exercise. In: Rowell LB, Shepherd JT, editors. Handbook of physiology. Section 12: Exercise: Regulation and Integration of Multiple Systems. New York, NY: Oxford University Press; 1996. p. 333–80.

    Google Scholar 

  69. Wehrlin JP, Hallen J. Linear decrease in VO2max and performance with increasing altitude in endurance athletes. Eur J Appl Physiol. 2006;96:404.

    Article  PubMed  Google Scholar 

  70. Westerblad H, Allen DG, Lannergren J. Muscle fatigue: lactic acid or inorganic phosphate the major cause? News Physiol Sci. 2002;17:17–21.

    CAS  PubMed  Google Scholar 

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Amann, M., Dempsey, J.A. (2016). Ensemble Input of Group III/IV Muscle Afferents to CNS: A Limiting Factor of Central Motor Drive During Endurance Exercise from Normoxia to Moderate Hypoxia. In: Roach, R., Hackett, P., Wagner, P. (eds) Hypoxia. Advances in Experimental Medicine and Biology, vol 903. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-7678-9_22

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