Exercise Hyperpnea
Susan A. Ward,
Susan A. Ward
University of Leeds, School of Sport and Exercise Sciences, Leeds, United Kingdom
Search for more papers by this authorSusan A. Ward,
Susan A. Ward
University of Leeds, School of Sport and Exercise Sciences, Leeds, United Kingdom
Search for more papers by this authorFirst published: 14 April 2006
Abstract
Control schemes of ventilation 
during moderate exercise [i.e., below the lactate threshold (θL)] have classically incorporated both proportional humoral feedback (carotid and central chemoreflex) and neurogenic feed forward (central command, muscle, cardiocirculatory) to provide stability of arterial PCO2 (PaCO2) pH (pHa), and PO2 (PaO2). In response to a step work-rate (WR) forcing from prior rest in the upright posture, 
increases abruptly for some 15–20 s, this being followed by a subsequent more-prominent exponential component (consistent with first-order kinetics). The lack of any sustained error signals in the mean levels of PaCO2, pHa, or PaO2, coupled with the dynamic matching of 
with pulmonary CO2 output 
but not O2 uptake or WR, suggests that the controller operates as if it incorporates an errorless humoral feedback element proportional to 
(or some close proxy). In addition, the 
controller seems to evidence considerable redundancy, with particular sensory deficits having little effect on the steady-state 
response to exercise or the stability of PaCO2 between rest and exercise. Above θL, 
kinetics become markedly nonlinear, with steady states being either delayed or not attained, which reflects the influence of the developing metabolic acidemia (1) indirectly, via bicarbonate-mediated body CO2 stores washout, which augments 
; and (2) directly, to effect respiratory compensation for the falling pHa (this being constrained by the falling PaCO2 that results from 
increasing out of proportion to 
). The carotid bodies are important in mediating this respiratory compensation, although with surprisingly slow kinetics, In conclusion, despite there now being general agreement regarding the overall characteristics of the 
response to exercise, the precise details of the control process(es) remain unresolved.
Bibliography
- 1P. M. Roget, Animal and Vegetable Physiology, vol. 2. London, UK: William Pickering, 1834, p. 333.
- 2B. J. Whipp, The control of exercise hyperpnea. In: T. Hornbein, ed., The Regulation of Breathing. New York: Dekker, 1981, pp. 1069–1139.
- 3K. Wasserman and R. Casaburi, Acid-base regulation during exercise in humans. In: B. J. Whipp and K. Wasserman, eds., Pulmonary Physiology and Pathophysiology of Exercise. New York: Dekker, 1991, pp. 405–448.
- 4J. A. Dempsey, H. V. Forster, and D. M. Ainsworth, The regulation of hyperpnea, hyperventilation and respiratory muscle recruitment during exercise. In: J. A. Dempsey and A. I. Pack, eds., Regulation of Breathing. New York: Dekker, 1995, pp. 1065–1134.
- 5T. G. Waldrop, F. L. Eldridge, G. A. Iwamoto, and J. H. Mitchell, Central neural control of respiration and circulation during exercise. In: L. B. Rowell and J. T. Shepherd, eds., Handbook of Physiology, Section 12, Exercise, Regulation and Integration of Multiple Systems. New York: Oxford University Press, 1996, pp. 333–380.
- 6S. A. Ward and B. J. Whipp, Co-ordination of circulation and respiration in exercise. In: R. Greger and U. Windhorst, eds., Comprehensive Human Physiology. Heidelberg: Springer-Verlag, 1996, pp. 2175–2198.
10.1007/978-3-642-60946-6_110 Google Scholar
- 7M. Hall, Quoted in P. Dejours. La regulation de la ventilation au course de l’exercise musculaire chez l’homme. J. Physiol. (Paris) 1959; 51: 163–261.
- 8F. Miescher-Rüsch, Bemerkungen zur Lehre von den Atembewegungen. Arch. Anat. Physiol. (Leipzig) 1885; 6: 355–380.
- 9J. Geppert and N. Zuntz, Über die Regulation der Atmung. Arch. ges. Physiol. 1888; 42: 189–244.
10.1007/BF01669357 Google Scholar
- 10A. Krogh and J. Lindhard, The regulation of respiration and circulation during the initial stages of muscular work. J. Physiol. (Lond.) 1913; 47: 112–136.
- 11A. Krogh and J. Lindhard, A comparison between voluntary and electrically induced muscular work in man. J. Physiol. (Lond.) 1917; 51: 182–201.
- 12J. S. Haldane and J. G. Priestley, The regulation of the lung-ventilation. J. Physiol. (Lond.) 1905; 32: 225–266.
- 13H. Winterstein, Die Regulierung der Atmung durch das Blut. Pflüg. Arch. Ges. Physiol. 1911; 138: 167–184.
- 14C. Heymans, J. J. Bouckaert, and L. Dautrebande, Sinus carotidien et réflexes respiratoires, Pt. II. Influences respiratoires réflexes de l’acidose, de l’alcalose, de l’anhydride carbonique, de l’ion hydrogéne, et de l’anoxémie, Échanges respiratoires dans les poumons et au delà des poumons. Arch. Intern. Pharmacodyn. 1930; 39: 400–445.
- 15R. A. Mitchell, H. H. Loeschcke, W. H. Massion, and J. W. Severinghaus, Respiratory responses mediated through superficial chemo-sensitive areas on the medulla. J. Appl. Physiol. 1963; 18: 523–533.
- 16T. R. Harrison, W. G. Harrison, J. A. Calhoun, and J. P. Marsh, Congestive heart failure, XVII, The mechanism of dyspnea on exertion. Arch. Intern. Med. 1932; 50: 690–720.
10.1001/archinte.1932.00150180043004 Google Scholar
- 17J. S. Gray, The multiple factor theory and the control of ventilation. Science 1946; 103: 739–744.
- 18F. S. Grodins, J. S. Gray, K. R. Schroeder, A. L. Norens, and R. W. Jones, Respiratory responses to CO2 inhalation. A theoretical study of a nonlinear biological regulator. J. Appl. Physiol. 1954; 7: 283–308.
- 19J. G. Defares, Principles of feedback control and their application to the respiratory control system. In: W. O. Fenn and H. Rahn, eds., Handbook of Physiology, Respiration, Vol I. Washington, D.C.: Am. Physiol. Soc., 1964, pp. 649–680.
- 20F. S. Grodins and S. Yamashiro, Respiratory Function of the Lung and its Control. New York: MacMillan Publishing Co., 1978.
- 21L. E. Farhi and H. Rahn, Gas stores of the body and the unsteady state, J. Appl. Physiol. 1955; 7: 472–484.
- 22L. E. Farhi and H. Rahn, Dynamics of changes in carbon dioxide stores. Anesthesiology 1960; 21: 604–614.
- 23N. S. Cherniack and G. S. Longobardo, Oxygen and carbon dioxide gas stores of the body. Physiol. Rev. 1970; 50: 196–243.
- 24A. ElHefnawy, G. M. Saidel, and N. S. Cherniack, CO2 control of the respiratory system: plant dynamics and stability analysis. Ann. Biomed. Eng. 1988; 16: 445–461.
- 25F. S. Grodins, Some simple principles and complex realities of cardiopulmonary control in exercise. Circ. Res. 1967; XX-XXI(suppl.): I-171–I-178.
- 26F. S. Grodins, Questions and answers about the control of breathing. In: A. S. Iberall and A. C. Guyton, eds., Regulation and Control in Physiological Systems. Pittsburgh, PA: Instrument Society of America, 1973, pp. 278–283.
- 27P. Dejours, Control of respiration in muscular exercise. In: W. O. Fenn and H. Rahn, eds., Handbook of Physiology, Section 3, Respiration, Vol. 1. Washington, D.C.: Am. Physiol. Soc., 1964; pp. 631–648.
- 28M. P. Kaufman and H. V. Forster, Reflexes controlling circulatory, ventilatory and airway responses to exercise. In: Handbook of Physiology, Section 12, Exercise, Regulation and Integration of Multiple Systems. New York: Oxford University Press, 1996, pp. 381–447.
- 29F. L. Eldridge and T. G. Waldrop, Neural control of breathing. In: B. J. Whipp and K. Wasserman, eds., Pulmonary Physiology and Pathophysiology of Exercise. New York: Dekker, 1991, pp. 309–370.
- 30B. J. Whipp and S. A. Ward, Control of ventilatory dynamics during exercise. Int. J. Sports Med. 1981; 1: 146–159.
10.1055/s-2008-1034653 Google Scholar
- 31H. V. Forster, J. A. Dempsey, J. Thompson, E. Vidruk, and G. A. Dopico, Estimation of arterial PO2, PCO2, pH and lactate from arterialized venous blood. J. Appl. Physiol. 1972; 32: 134–137.
- 32P. McLoughlin, P. Popham, R. A. F Linton, R. C. H. Bruce, and D. M. Band, Use of arterialized venous blood sampling during incremental exercise tests. J. Appl. Physiol. 1992; 73: 937–940.
- 33J. H. Milsum, Biological Control Systems Analysis. New York: McGraw-Hill, 1966.
- 34Y. Fujihara, J. R. Hildebrandt, and J. Hildebrandt, Cardiorespiratory transients in exercising man. I, Tests of superposition. J. Appl. Physiol. 1973; 3: 58–67.
- 35N. Lamarra, B. J. Whipp, S. A. Ward, and K. Wasserman, Effect of interbreath fluctuations on characterizing exercise gas-exchange kinetics. J. Appl. Physiol. 1987; 62: 2003–2012.
- 36B. J. Whipp, S. A. Ward, N. Lamarra, J. A. Davis, and, K. Wasserman, Parameters of ventilatory and gas exchange dynamics during exercise. J. Appl. Physiol. 1982; 52: 1506–1513.
- 37O. Wigertz, Dynamics of respiratory and circulatory adaptation to muscular exercise in man: A systems analysis approach. Acta Physiol. Scand. 1971; 353(suppl.): 1–32.
- 38R. Casaburi, B. J. Whipp, K. Wasserman, W. L. Beaver, and S. N. Koyal, Ventilatory and gas exchange dynamics in response to sinusoidal work. J. Appl. Physiol.: Respir. Environ. Exer. Physiol. 1977; 42: 300–311.
- 39H. K. Bakker, R. S. Struikenkamp, and G. A. De Vries, Dynamics of ventilation, heart rate, and gas exchange: Sinusoidal and impulse work loads in man. J. Appl. Physiol. Respir. Environ. Exer. Physiol. 1980; 48: 289–301.
- 40R. M. Engeman, G. D. Swanson, and R. H. Jones, Optimal frequency locations for estimating model parameters in studies on respiratory control. Comput. Biomed. Res. 1983; 16: 531–536.
- 41F. M. Bennett, P. Reischl, F. S. Grodins, S. M. Yamashiro, and W. E. Fordyce, Dynamics of ventilatory response to exercise in humans. J. Appl. Physiol. 1981; 52: 194–203.
- 42E. C. Greco, H. Baier, and A. Saez, Transient ventilatory and heart rate responses to moderate nonabrupt pseudorandom exercise. J. Appl. Physiol. 1986; 60: 1524–1534.
- 43H. C. Xing, J. E. Cochrane, Y. Yamamoto, and R. L. Hughson, Frequency domain analysis of ventilation and gas exchange kinetics in hypoxic exercise. J. Appl. Physiol. 1991; 7: 2394–2401.
- 44N. L. Jones and J. E. Jurkowski, Body carbon dioxide storage capacity in exercise. J. Appl. Physiol. 1979; 48: 811–815.
- 45B. J. Whipp, Dynamics of pulmonary gas exchange during exercise in man. Circulation 1987; VI: 18–28.
- 46J. F. Nunn, Applied Respiratory Physiology. London, UK: Butterworths, 1977.
- 47K. Wasserman, A. L. VanKessel, and G. G. Burton, Interaction of physiological mechanisms during exercise. J. Appl. Physiol. 1967; 22: 71–85.
- 48N. L. Jones, D. G. Robertson, and J. W. Kane, Difference between end-tidal and arterial PCO2 in exercise. J. Appl. Physiol. 1979; 47: 954–960.
- 49B. J. Whipp, N. Lamarra, S. A. Ward, J. A. Davis, and K. Wasserman, Estimating arterial PCO2 from flow-weighted and time-averaged alveolar PCO2 during exercise. In: G. D. Swanson and F. S. Grodins, eds., Respiratory Control: Modelling Perspective. New York: Plenum Press, 1990, pp. 91–99.
- 50W. J. Fawcett, S. A. Ward, and B. J. Whipp, Wash-out and wash-in kinetics of carbon dioxide at rest and exercise. Fed. Proc. 1994; 8(4): A288.
- 51W. Stringer, K. Wasserman, R. Casaburi, J. Porszasz, K. Maehara, and W. French, Lactic acidosis as a facilitator of oxyhemoglobin dissociation during exercise. J. Appl. Physiol. 1994; 76: 1462–1467.
- 52S. A. Ward and B. J. Whipp, Influence of body CO2 stores on ventilatory-metabolic coupling during exercise. In: Y. Honda, Y. Miyamoto, K. Konno, and J. G. Widdicombe, eds., Control of Breathing and Its Modeling Perspective. New York: Plenum Press, 1992, pp. 425–431.
10.1007/978-1-4757-9847-0_74 Google Scholar
- 53F. Özyener, S. A. Ward, and B. J. Whipp, Influence of exercise intensity on the kinetics of pulmonary CO2 output. Proc. Eur. Coll. Sports Sci. 2002, p. 213.
- 54D. J. C. Cunningham, P. A. Robbins, and C. B. Wolff, Integration of respiratory responses to changes in alveolar partial pressures of CO2 and O2 and in arterial pH. In: N. S. Cherniack and J. G. Widdicombe, eds., Handbook of Physiology, Section 3, The Respiratory System, Vol. II, Control of Breathing, part 2. Bethesda, MD: Am. Physiol. Soc., 1986, pp. 475–528.
- 55S. A. Ward, Peripheral and central chemoreceptor control of ventilation during exercise. Canad. J. Appl. Physiol. 1994; 19: 305–333.
- 56F. F. Kao, An experimental study of the pathways involved in exercise hyperpnoea employing cross-circulation techniques. In: D. J. C. Cunningham and B. B. Lloyd, eds., The Regulation of Human Respiration. Oxford, UK: Blackwell, 1963, pp. 461–502.
- 57U. Tibes, Reflex inputs to the cardiovascular and respiratory centers from dynamically working canine muscles. Circ. Res. 1977; 4: 332–341.
10.1161/01.RES.41.3.332 Google Scholar
- 58B. J. Whipp and S. A. Ward, The coupling of ventilation to pulmonary gas exchange during exercise. In: B. J. Whipp and K. Wasserman, eds., Pulmonary Physiology and Pathophysiology of Exercise. New York: Dekker, 1991, pp. 271–307.
- 59S. A. Ward, Control of the exercise hyperpnea: A modelling perspective. Respir. Physiol. 2000; 122: 149–166.
- 60P. Haouzi, A. Huszczuk, J. Porszasz, B. Chalon, K. Wasserman, and B. J. Whipp, Femoral vascular occlusion and ventilation during recovery from heavy exercise. Respir. Physiol. 1993; 94: 137–150.
- 61D. Weiler-Ravell, D. M. Cooper, B. J. Whipp, and K. Wasserman, The control of breathing at the start of exercise as influenced by posture. J. Appl. Physiol. 1983; 55: 1460–1466.
- 62G. D. Swanson, Input stimulus design for model discrimination in human respiratory control. In: E. R. Carson, D. J. C. Cunningham, R. Herczynski, D. J. Murray-Smith, and E. S. Petersen, eds., Modelling of a Biological Control System, The Regulation of Breathing. Oxford, UK: Institute of Measurement and Control, 1978, p. 165.
- 63H. K. Bakker, R. S. Struikenkamp, and G. A. De Vries, Dynamics of ventilation, heart rate, and gas exchange, sinusoidal and impulse work loads in man. J. Appl. Physiol. Respir. Environ. Exer. Physiol. 1980; 48: 289–301.
- 64Y. Miyamoto, Kinetics of respiratory and circulatory responses to step, impulse, sinusoidal and ramp forcings of exercise load in humans. Front. Med. Biol. Eng. 1992; 4: 3–18.
- 65K. Wasserman, B. J. Whipp, and J. Castagna, Cardiodynamic hyperpnea: Hyperpnea secondary to cardiac output increase. J. Appl. Physiol. 1974; 36: 457–464.
- 66B. J. Whipp and S. A. Ward, Cardiopulmonary coupling during exercise. J. Exp. Biol. 1982; 100: 175–193.
- 67A. R. C. Cummin, V. I. Tyawe, and K. B. Saunders, Ventilation and cardiac output during the onset of exercise and during voluntary hyperventilation in humans. J. Physiol. (Lond.) 1986; 370: 567–583.
- 68L. Adams, A. Guz, J. A. Innes, and K. Murphy, The early circulatory and ventilatory responses to voluntary and electrically-induced exercise in man. J. Physiol. (Lond.) 1987; 383: 19–30.
- 69Y. Miyamoto, Neural and humoral factors affecting ventilatory response during exercise. Jpn. J. Physiol. 1989; 39: 199–214.
- 70J. A. Loeppky, E. R. Greene, D. E. Hoekenga, A. Caprihan, and U. C. Luft, Beat-by-beat stroke volume assessment by pulsed Doppler in upright and supine exercise. J. Appl. Physiol. 1981; 50: 1173–1182.
- 71D. Leyk, D. Essfeld, K. Baum, and J. Stegemann, Early leg blood flow adjustment during dynamic foot plantarflexions in upright and supine body position. Int. J. Sports Med. 1994; 15: 447–452.
- 72W. B. Jones, R. N. Finchun, R. O. Russell, Jr., and T. J. Reeves, Transient cardiac output response to multiple levels of supine exercise. J. Appl. Physiol. 1970; 28: 183–189.
- 73D. R. Kostreva, E. J. Zuperku, R. V. Purtock, R. L. Coon, and J. P. Kampine, Sympathetic afferent nerve activity of right heart origin. Am. J. Physiol. 1975; 229: 911–915.
- 74A. Huszczuk, P. W. Jones, A. Oren, E. C. Shors, L. E. Nery, B. J. Whipp, and K. Wasserman, Venous return and ventilatory control. In: B. J. Whipp and D. M. Wiberg, eds., Modelling and Control of Breathing. New York: Elsevier, 1983, pp. 78–85.
- 75J. Theodore, A. J. Morris, C. M. Burker, A. R. Glanville, A. VanKessel, J. C. Baldwin, E. B. Stinson, N. E. Shumway, and E. D. Robin, Cardiopulmonary function at maximum tolerable constant work rate exercise following human heart-lung transplantation. Chest. 1987; 92: 433–439.
- 76N. Banner, A. Guz, R. Heaton, J. A. Innes, K. Murphy, and M. Yacoub, Ventilatory and circulatory responses at the onset of exercise in man following heart or heart-lung transplantation. J. Physiol. (Lond.) 1988; 399: 437–449.
- 77B. Grassi, G. Ferretti, L. Xi, M. Rieu, M. Meyer, C. Marconi, and P. Cerretelli, Ventilatory response to exercise after heart and lung denervation in humans. Respir. Physiol. 1993; 92: 289–304.
- 78A. Huszczuk, B. J. Whipp, T. D. Adams, A. G. Fisher, R. O. Crapo, G. C. Elliott, K. Wasserman, and D. B. Olsen, Ventilatory control during exercise in calves with artificial hearts. J. Appl. Physiol. 1990; 68: 2604–2611.
- 79P. W. Jones, W. French, M. L. Weissman, and K. Wasserman, Ventilatory responses to cardiac output changes in patients with pacemakers. J. Appl. Physiol. 1981; 51: 1103–1107.
- 80P. Haouzi, B. Chenuel, and A. Huszczuk, Sensing vascular distension in skeletal muscle by slow conducting afferent fibers: Neurophysiological basis and implication for respiratory control. J. Appl. Physiol. 2004; 96: 407–418.
- 81D. Linnarsson, Dynamics of pulmonary gas exchange and heart rate changes at start and end of exercise. Acta Physiol. Scand. 1974; 415(suppl.): 1–68.
- 82R. L. Hughson, Exploring cardiorespiratory control mechanisms through gas exchange dynamics. Med. Sci. Sports Exerc. 1990; 22: 72–79.
- 83L. Adams, H. Frankel, J. Garlick, A. Guz, K. Murphy, and S. J. G. Semple, The role of spinal cord transmission in the ventilatory response to exercise in man. J. Physiol. (Lond.) 1984; 355: 85–97.
- 84S. A. Ward and J. W. Bellville, Peripheral chemoreflex suppression by hyperoxia during moderate exercise in man. In: B. J. Whipp and D. M. Wiberg, eds., Modelling and Control of Breathing. New York: Elsevier, 1983, pp. 54–61.
- 85B. J. Whipp, Peripheral chemoreceptor control of the exercise hyperpnea in humans. Med. Sci. Sports Exerc. 1994; 26: 337–347.
- 86T. L. Griffiths, L. C. Henson, and B. J. Whipp, Influence of peripheral chemoreceptors on the dynamics of the exercise hyperpnea in man. J. Physiol. (Lond.) 1986; 380: 387–403.
- 87I. H. Young and A. J. Woolcock, Changes in arterial blood gas tensions during unsteady–state exercise. J. Appl. Physiol. 1978; 44: 93–96.
- 88F. A. Oldenburg, D. W. McCormack, J. L. C. Morse, and N. L. Jones, A comparison of exercise responses in stairclimbing and cycling. J. Appl. Physiol. 1979; 46: 510–516.
- 89B. J. Whipp, K. Wasserman, R. Casaburi, C. Juratsch, M. L. Weissman, and R. W. Stremel, Ventilatory control characteristics of conditions resulting in isocapnic hyperpnea. In: R. Fitzgerald, S. Lahiri, and H. Gautier, eds., Control of Respiration During Sleep and Anesthesia. New York: Plenum Press, 1978, pp. 335–342.
- 90D. J. Paterson, Potassium and ventilation in exercise. J. Appl. Physiol. 1992; 72: 811–820.
- 91P. C. G. Nye, Identification of peripheral chemoreceptor stimuli. Med. Sci. Sports Exerc. 1994; 26: 311–318.
- 92R. Casaburi, W. W. Stringer, and E. Singer, Comparison of arterial potassium and ventilatory dynamics during sinusoidal work rate variation in man. J. Physiol. (Lond.) 1995; 485: 571–580.
- 93W. S. Yamamoto, Mathematical analysis of the time course of alveolar CO2. J. Appl. Physiol. 1960; 15: 215–219.
- 94D. M. Band, C. B. Wolff, J. Ward, G. M. Cochrane, and J. G. Prior, Respiratory oscillations in arterial carbon dioxide tension as a control signal in exercise. Nature 1980; 283: 84–85.
- 95K. B. Saunders, Oscillations of arterial CO2 tension in a respiratory model, some implications for the control of breathing in exercise. J. Theor. Biol. 1980; 84: 163–179.
- 96B. A. Cross, R. P. Stidwell, K. R. Hughes, R. Peppin, and S. J. G. Semple, A comparative study of aortic pH oscillations in conscious humans and anaesthetised cats and rabbits. Respir. Physiol. 1995; 102: 51–62.
- 97F. L. Eldridge and D. E. Millhorn, Oscillation, gating and memory in the respiratory control system. In: J. G. Widdicombe, and N. Cherniack, eds., Handbook of Physiology, Respiration (Control). Washington, D.C.: Am. Physiol. Soc., 1986, pp. 93–114.
- 98R. W. Torrance, Prolegomena, chemoreception upstream of transmitters. Adv. Exp. Med. Biol. 1996; 410: 13–38.
- 99S. A. Ward, L. G. Swain, and S. Frye-Kryder, Phase-coupling of arterial blood gas oscillations and ventilatory kinetics during exercise in humans. In: S. J. G. Semple, L. Adams, and B. J. Whipp, eds., Modelling and Control of Ventilation. New York: Plenum Press, 1995, pp. 219–224.
10.1007/978-1-4615-1933-1_41 Google Scholar
- 100E. S. Petersen, B. J. Whipp, D. B. Drysdale, and D. J. C. Cunningham, The relation between arterial blood gas oscillations in the carotid region and the phase of the respiratory cycle during exercise in man. In: R. Fitzgerald, H. Gautier, and S. Lahiri, eds., Regulation of Respiration in Sleep and Anesthesia. New York: Plenum Press, 1978, pp. 335–342.
10.1007/978-1-4613-4009-6_36 Google Scholar
- 101S. A. Shea, L. P. Andrews, D. C. Shannon, and R. B. Banzett, Ventilatory responses to exercise in humans lacking ventilatory chemosensitivity. J. Physiol. (Lond.) 1993; 469: 623–640.
10.1113/jphysiol.1993.sp019792 Google Scholar
- 102C. S. Poon, S. A. Ward, and B. J. Whipp, Influence of inspiratory assistance on ventilatory control during moderate exercise. J. Appl. Physiol. 1987; 62: 551–560.
- 103B. Krishnan, T. Zintel, C. McParland, and C. G. Gallagher, Lack of importance of respiratory muscle load in ventilatory regulation during heavy exercise in humans. J. Physiol. (Lond.) 1996; 490: 537–550.
- 104J. Y. Paton, S. Swaminathan, C. W. Sargent, A. Hawksworth, and T. G. Keens, Ventilatory response to exercise in children with congenital central hypoventilation syndrome. Am. Rev. Respir. Dis. 1993; 147: 1185–1191.
- 105J. Barcroft, Features in the Architecture of Physiological Function. Cambridge, UK: Cambridge University Press, 1934, p. 312.
- 106W. S. Yamamoto, Computer simulation of ventilatory control by both neural and humoral CO2 signals. Am. J. Physiol. 1980; 238: R28–R35.
- 107G. D. Swanson, Redundancy structures in respiratory control. In: Y. Honda, Y. Miyamoto, K. Konno, and J. G. Widdicombe, eds., Control of Breathing and its Modelling Perspective. New York: Plenum Press, 1992, pp. 171–177.
10.1007/978-1-4757-9847-0_31 Google Scholar
- 108C. S. Poon, Optimal control of ventilation in hypercapnia and exercise, an extended model. In: G. Benchetrit and J. Demongeot, eds., Concepts and Formalizations in the Control of Breathing. Manchester, UK: University of Manchester Press, 1983, pp. 119–127.
- 109G. D. Swanson and P. A. Robbins, Optimal respiratory controller structures. IEEE Trans. Biomed. Eng. 1986; 33: 677–680.
- 110C.-S. Poon, Ventilatory control in hypercapnia and exercise, optimization hypothesis. J. Appl. Physiol. 1987; 62: 2447–2459.
- 111D. L. Young and C.-S. Poon, Hebbian covariance learning. Adv. Exp. Med. Biol. 1998; 450: 73–83.
- 112C.-S. Poon and M. S. Siniaia, Plasticity of cardiorespiratory neural processing: Classification and computational functions. Respir. Physiol. 2000; 122: 83–109.
- 113P. A. Martin and G. S. Mitchell, Long-term modulation of the exercise ventilatory response in goats. J. Physiol. (Lond.) 1993; 470: 601–617.
- 114D. L. Turner, K. B. Bach, P. A. Martin, E. B. Olsen, M. Brownfield, K. T. Foley, and G. S. Mitchell, Modulation of ventilatory control during exercise. Respir. Physiol. 1997; 110: 277–825.
- 115D. Helbling, U. Boutellier, and C. M. Spengler, Modulation of the ventilatory increase at the onset of exercise in humans. Respir. Physiol. 1997; 109: 219–229.
- 116D. R. McCrimmon, M. S. Dekin, and G. S. Mitchell, Glutamate, GABA, and serotonin in ventilatory control. In: J. A. Dempsey and A. I. Pack, eds., Regulation of Breathing. New York: Dekker, 1995; pp. 151–218.
- 117G. G. Somjen, The missing error signal—regulation beyond negative feedback. NIPS 1992; 7: 184–185.
- 118S. H. Moosavi, A. Guz, and L. Adams, Repeated exercise paired with “imperceptible” dead space loading not alter
of subsequent exercise in humans. J. Appl. Physiol. 2002; 92: 1159–1168.
- 119D. L. Turner and D. P. Sumners, Associative conditioning of the exercise ventilatory response in humans. Respir. Physiol. Neurobiol. 2002; 132: 159–168.
- 120A. Cathcart, N. Herrold, A. P. Turner, J. Wilson, and S. A. Ward, Absence of long-term modulation in response to external dead-space loading during moderate exercise in humans. Eur. J. Appl. Physiol. 2005; 93: 411–420.
- 121S. M. Rausch, B. J. Whipp. K. Wasserman, and A. Huszczuk, Role of the carotid bodies in the respiratory compensation for the metabolic acidosis of exercise in humans. J. Physiol. (Lond.) 1991; 444: 567–578.
- 122B. J. Whipp, J. A. Davis, and K. Wasserman, Ventilatory control of the “isocapnic buffering” region in rapidly incremental exercise. Respir. Physiol. 1989; 76: 357–368.
- 123Y. Honda, S. Myojo, S. Hasegawa, and J. W. Severinghaus, Decreased exercise hyperpnea in patients with bilateral carotid chemoreceptor resection. J. Appl. Physiol. 1979; 46: 908–912.
- 124B. W. Scheuermann and J. M. Kowalchuk, Attenuated respiratory compensation during rapidly incremented ramp exercise. Respir. Physiol. 1988; 114: 227–238.
- 125K. J. Buckler and R. D. Vaughan-Jones, Role of intracellular pH and [Ca2+]i in acid chemoreception in Type-I cells of the carotid body. Adv. Exp. Med. Biol. 1995; 360: 41–55.
- 126K. J. Buckler, B. A. Williams, and E. Honore, An oxygen-, acid- and anaesthetic-sensitive TASK-like background potassium channel in rat arterial chemoreceptor cells. J. Physiol. (Lond.) 2000; 525: 135–142.
- 127S. A. Ward, Models of ventilatory control during exercise: Peripheral chemoreflex considerations. Int. J. Computer Sci. 2003; 2: 52–65.
- 128L. J. Teppema, P. W. J. A. Barts, and J. A. M. Evers, Effects of metabolic arterial pH changes on medullary ecf pH, csf pH and ventilation in peripherally chemodenervated cats with intact blood-brain barrier. J. Physiol. (Lond.) 1982; 58: 123–136.
- 129J. M. Hagberg, E. F. Coyle, J. E. Carroll, J. M. Miller, W. H. Martin, and M. H. Brooke, Exercise hyperventilation in patients with McArdle's disease. J. Appl. Physiol. 1982; 52: 991–994.
- 130J. M. Hagberg, D. S. King, M. A. Rogers, S. J. Montain, S. M. Jilka, W. M. Kohrt, and S. L. Heller, Exercise and recovery ventilatory and
responses of patients with McArdle's disease. J. Appl. Physiol. 1990; 68: 1393–1398.
- 131M. Riley, D. P. Nicholls, A. M. Nugent, I. C. Steele, N. Bell, P. M. Davies, C. F. Stanford, and V. H. Patterson, Respiratory gas exchange and metabolic responses during exercise in McArdle's disease. J. Appl. Physiol. 1993; 75: 745–754.
