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Exercise physiology

David M Systrom, MD, FRCPC
Gregory D Lewis, MD
Section Editor
James K Stoller, MD, MS
Deputy Editor
Helen Hollingsworth, MD


Physical exercise requires the coordinated interaction of ventilation, cardiac output, and systemic and pulmonary blood flow to meet the metabolic demands of contracting muscles, as skeletal muscle metabolism can rise quickly to 50 times its resting rate during heavy exercise. To preserve cellular oxygenation and acid-base homeostasis during exercise, metabolic, cardiovascular, respiratory responses must adapt rapidly to these dramatic changes in tissue demands.

The normal physiologic response to exercise will be reviewed here. The role of exercise testing to evaluate reduced exercise tolerance due to dysfunction of the respiratory or cardiovascular systems is discussed separately. (See "Functional exercise testing: Ventilatory gas analysis" and "Exercise ECG testing: Performing the test and interpreting the ECG results" and "Approach to the patient with dyspnea".)


Minute ventilation – Volume of air exhaled per minute, VE

Oxygen uptake (L/min) – VO2

Maximum oxygen uptake – VO2max


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Literature review current through: Sep 2016. | This topic last updated: Jul 5, 2016.
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  1. Fry AC, Allemeier CA, Staron RS. Correlation between percentage fiber type area and myosin heavy chain content in human skeletal muscle. Eur J Appl Physiol Occup Physiol 1994; 68:246.
  2. Wasserman K, Hansen JE, Sue DY, et al. Physiology of exercise. In: Principles of exercise testing and interpretation: Including pathophysiology and clinical applications, 5th, Wolters Kluwer Lippincott Williams &Wilkins, 2011.
  3. Coffey VG, Hawley JA. The molecular bases of training adaptation. Sports Med 2007; 37:737.
  4. Meyer RA, Sweeney HL, Kushmerick MJ. A simple analysis of the "phosphocreatine shuttle". Am J Physiol 1984; 246:C365.
  5. Larson DE, Hesslink RL, Hrovat MI, et al. Dietary effects on exercising muscle metabolism and performance by 31P-MRS. J Appl Physiol (1985) 1994; 77:1108.
  6. Thompson CH, Kemp GJ, Sanderson AL, Radda GK. Skeletal muscle mitochondrial function studied by kinetic analysis of postexercise phosphocreatine resynthesis. J Appl Physiol (1985) 1995; 78:2131.
  7. Minotti JR, Johnson EC, Hudson TL, et al. Forearm metabolic asymmetry detected by 31P-NMR during submaximal exercise. J Appl Physiol (1985) 1989; 67:324.
  8. Maughan RJ, Greenhaff PL, Leiper JB, et al. Diet composition and the performance of high-intensity exercise. J Sports Sci 1997; 15:265.
  9. Whipp BJ, Ward SA. Will women soon outrun men? Nature 1992; 355:25.
  10. Gibala MJ, MacLean DA, Graham TE, Saltin B. Tricarboxylic acid cycle intermediate pool size and estimated cycle flux in human muscle during exercise. Am J Physiol 1998; 275:E235.
  11. Bowtell JL, Marwood S, Bruce M, et al. Tricarboxylic acid cycle intermediate pool size: functional importance for oxidative metabolism in exercising human skeletal muscle. Sports Med 2007; 37:1071.
  12. Lewis GD, Farrell L, Wood MJ, et al. Metabolic signatures of exercise in human plasma. Sci Transl Med 2010; 2:33ra37.
  13. MacLean DA, Graham TE, Saltin B. Stimulation of muscle ammonia production during exercise following branched-chain amino acid supplementation in humans. J Physiol 1996; 493 ( Pt 3):909.
  14. Kemp GJ, Sanderson AL, Thompson CH, Radda GK. Regulation of oxidative and glycogenolytic ATP synthesis in exercising rat skeletal muscle studied by 31P magnetic resonance spectroscopy. NMR Biomed 1996; 9:261.
  15. Putman CT, Spriet LL, Hultman E, et al. Skeletal muscle pyruvate dehydrogenase activity during acetate infusion in humans. Am J Physiol 1995; 268:E1007.
  16. Oliveira RK, Agarwal M, Tracy JA, et al. Age-related upper limits of normal for maximum upright exercise pulmonary haemodynamics. Eur Respir J 2016; 47:1179.
  17. Whipp BJ, Wasserman K. Oxygen uptake kinetics for various intensities of constant-load work. J Appl Physiol 1972; 33:351.
  18. Poole DC, Gaesser GA. Response of ventilatory and lactate thresholds to continuous and interval training. J Appl Physiol (1985) 1985; 58:1115.
  19. Gaesser GA, Poole DC. Lactate and ventilatory thresholds: disparity in time course of adaptations to training. J Appl Physiol (1985) 1986; 61:999.
  20. Sue DY, Hansen JE. Normal values in adults during exercise testing. Clin Chest Med 1984; 5:89.
  22. Blomqvist CG, Saltin B. Cardiovascular adaptations to physical training. Annu Rev Physiol 1983; 45:169.
  23. Mahler DA, Matthay RA, Snyder PE, et al. Volumetric responses of right and left ventricles during upright exercise in normal subjects. J Appl Physiol (1985) 1985; 58:1818.
  24. Shepherd JT. Circulatory response to exercise in health. Circulation 1987; 76:VI3.
  25. Manyari DE, Kostuk WJ. Left and right ventricular function at rest and during bicycle exercise in the supine and sitting positions in normal subjects and patients with coronary artery disease. Assessment by radionuclide ventriculography. Am J Cardiol 1983; 51:36.
  26. Reeves JT, Moon RE, Grover RF, Groves BM. Increased wedge pressure facilitates decreased lung vascular resistance during upright exercise. Chest 1988; 93:97S.
  27. Stray-Gundersen J, Musch TI, Haidet GC, et al. The effect of pericardiectomy on maximal oxygen consumption and maximal cardiac output in untrained dogs. Circ Res 1986; 58:523.
  28. Wade O, Bishop J, eds. Cardiac Output and Regional Blood Flow: FA Davis, 1962.
  29. Dempsey JA. J.B. Wolffe memorial lecture. Is the lung built for exercise? Med Sci Sports Exerc 1986; 18:143.
  30. Borlaug BA, Melenovsky V, Russell SD, et al. Impaired chronotropic and vasodilator reserves limit exercise capacity in patients with heart failure and a preserved ejection fraction. Circulation 2006; 114:2138.
  31. Kawaguchi M, Hay I, Fetics B, Kass DA. Combined ventricular systolic and arterial stiffening in patients with heart failure and preserved ejection fraction: implications for systolic and diastolic reserve limitations. Circulation 2003; 107:714.
  32. Borlaug BA, Melenovsky V, Redfield MM, et al. Impact of arterial load and loading sequence on left ventricular tissue velocities in humans. J Am Coll Cardiol 2007; 50:1570.
  33. Haykowsky MJ, Tomczak CR, Scott JM, et al. Determinants of exercise intolerance in patients with heart failure and reduced or preserved ejection fraction. J Appl Physiol (1985) 2015; 119:739.
  34. Kosmala W, Holland DJ, Rojek A, et al. Effect of If-channel inhibition on hemodynamic status and exercise tolerance in heart failure with preserved ejection fraction: a randomized trial. J Am Coll Cardiol 2013; 62:1330.
  35. Kitzman DW, Higginbotham MB, Cobb FR, et al. Exercise intolerance in patients with heart failure and preserved left ventricular systolic function: failure of the Frank-Starling mechanism. J Am Coll Cardiol 1991; 17:1065.
  36. Santos M, Opotowsky AR, Shah AM, et al. Central cardiac limit to aerobic capacity in patients with exertional pulmonary venous hypertension: implications for heart failure with preserved ejection fraction. Circ Heart Fail 2015; 8:278.
  37. Reeves JT, Groves BM, Cymerman A, et al. Operation Everest II: cardiac filling pressures during cycle exercise at sea level. Respir Physiol 1990; 80:147.
  38. Francis GS. Hemodynamic and neurohumoral responses to dynamic exercise: normal subjects versus patients with heart disease. Circulation 1987; 76:VI11.
  39. Rowell LB, O'Leary DS. Reflex control of the circulation during exercise: chemoreflexes and mechanoreflexes. J Appl Physiol (1985) 1990; 69:407.
  40. Clausen JP. Circulatory adjustments to dynamic exercise and effect of physical training in normal subjects and in patients with coronary artery disease. Prog Cardiovasc Dis 1976; 18:459.
  41. Hickner RC, Fisher JS, Ehsani AA, Kohrt WM. Role of nitric oxide in skeletal muscle blood flow at rest and during dynamic exercise in humans. Am J Physiol 1997; 273:H405.
  42. Skinner NS Jr, Costin JC. Role of O2 and K+ in abolition of sympathetic vasoconstriction in dog skeletal muscle. Am J Physiol 1969; 217:438.
  43. Koller A, Huang A, Sun D, Kaley G. Exercise training augments flow-dependent dilation in rat skeletal muscle arterioles. Role of endothelial nitric oxide and prostaglandins. Circ Res 1995; 76:544.
  44. Stringer W, Wasserman K, Casaburi R, et al. Lactic acidosis as a facilitator of oxyhemoglobin dissociation during exercise. J Appl Physiol (1985) 1994; 76:1462.
  45. Roca J, Hogan MC, Story D, et al. Evidence for tissue diffusion limitation of VO2max in normal humans. J Appl Physiol (1985) 1989; 67:291.
  46. Li Y, Dash RK, Kim J, et al. Role of NADH/NAD+ transport activity and glycogen store on skeletal muscle energy metabolism during exercise: in silico studies. Am J Physiol Cell Physiol 2009; 296:C25.
  47. Kane DW, Tesauro T, Koizumi T, et al. Exercise-induced pulmonary vasoconstriction during combined blockade of nitric oxide synthase and beta adrenergic receptors. J Clin Invest 1994; 93:677.
  48. Lewis GD, Bossone E, Naeije R, et al. Pulmonary vascular hemodynamic response to exercise in cardiopulmonary diseases. Circulation 2013; 128:1470.
  49. Tolle JJ, Waxman AB, Van Horn TL, et al. Exercise-induced pulmonary arterial hypertension. Circulation 2008; 118:2183.
  50. Wasserman K, Whipp BJ. Excercise physiology in health and disease. Am Rev Respir Dis 1975; 112:219.
  51. Hey EN, Lloyd BB, Cunningham DJ, et al. Effects of various respiratory stimuli on the depth and frequency of breathing in man. Respir Physiol 1966; 1:193.
  52. Hagberg JM, King DS, Rogers MA, et al. Exercise and recovery ventilatory and VO2 responses of patients with McArdle's disease. J Appl Physiol (1985) 1990; 68:1393.
  53. Dempsey JA. Exercise hyperpnea. Chairman's introduction. Adv Exp Med Biol 1995; 393:133.
  54. Gozal D, Hathout GM, Kirlew KA, et al. Localization of putative neural respiratory regions in the human by functional magnetic resonance imaging. J Appl Physiol (1985) 1994; 76:2076.
  55. Eldridge FL. Central integration of mechanisms in exercise hyperpnea. Med Sci Sports Exerc 1994; 26:319.
  56. Evans AB, Tsai LW, Oelberg DA, et al. Skeletal muscle ECF pH error signal for exercise ventilatory control. J Appl Physiol (1985) 1998; 84:90.
  57. Oelberg DA, Evans AB, Hrovat MI, et al. Skeletal muscle chemoreflex and pHi in exercise ventilatory control. J Appl Physiol (1985) 1998; 84:676.
  58. Caiozzo VJ, Davis JA, Ellis JF, et al. A comparison of gas exchange indices used to detect the anaerobic threshold. J Appl Physiol Respir Environ Exerc Physiol 1982; 53:1184.
  59. Medoff BD, Oelberg DA, Kanarek DJ, Systrom DM. Breathing reserve at the lactate threshold to differentiate a pulmonary mechanical from cardiovascular limit to exercise. Chest 1998; 113:913.
  60. Balady GJ, Arena R, Sietsema K, et al. Clinician's Guide to cardiopulmonary exercise testing in adults: a scientific statement from the American Heart Association. Circulation 2010; 122:191.
  61. Carter R, Peavler M, Zinkgraf S, et al. Predicting maximal exercise ventilation in patients with chronic obstructive pulmonary disease. Chest 1987; 92:253.
  62. Campbell SC. A comparison of the maximum voluntary ventilation with the forced expiratory volume in one second: an assessment of subject cooperation. J Occup Med 1982; 24:531.
  63. Dillard TA, Hnatiuk OW, McCumber TR. Maximum voluntary ventilation. Spirometric determinants in chronic obstructive pulmonary disease patients and normal subjects. Am Rev Respir Dis 1993; 147:870.
  64. Rochester DF. Tests of respiratory muscle function. Clin Chest Med 1988; 9:249.
  65. Olafsson S, Hyatt RE. Ventilatory mechanics and expiratory flow limitation during exercise in normal subjects. J Clin Invest 1969; 48:564.
  66. Kanarek DJ, Hand RW. The response of cardiac and pulmonary disease to exercise testing. Clin Chest Med 1984; 5:181.
  67. American Thoracic Society, American College of Chest Physicians. ATS/ACCP Statement on cardiopulmonary exercise testing. Am J Respir Crit Care Med 2003; 167:211.
  68. Jones NL. Normal values for pulmonary gas exchange during exercise. Am Rev Respir Dis 1984; 129:S44.
  69. Hansen JE, Sue DY, Wasserman K. Predicted values for clinical exercise testing. Am Rev Respir Dis 1984; 129:S49.
  70. Casaburi R, Daly J, Hansen JE, Effros RM. Abrupt changes in mixed venous blood gas composition after the onset of exercise. J Appl Physiol (1985) 1989; 67:1106.
  71. Lindinger MI. Origins of [H+] changes in exercising skeletal muscle. Can J Appl Physiol 1995; 20:357.
  72. Arena R, Myers J, Abella J, et al. Development of a ventilatory classification system in patients with heart failure. Circulation 2007; 115:2410.
  73. Dempsey JA, Hanson PG, Henderson KS. Exercise-induced arterial hypoxaemia in healthy human subjects at sea level. J Physiol 1984; 355:161.
  74. Hsia CC. Respiratory function of hemoglobin. N Engl J Med 1998; 338:239.
  75. ERS Task Force, Palange P, Ward SA, et al. Recommendations on the use of exercise testing in clinical practice. Eur Respir J 2007; 29:185.
  76. Oldham WM, Lewis GD, Opotowsky AR, et al. Unexplained exertional dyspnea caused by low ventricular filling pressures: results from clinical invasive cardiopulmonary exercise testing. Pulm Circ 2016; 6:55.
  77. Oliveira RK, Waxman AB, Agarwal M, et al. Pulmonary haemodynamics during recovery from maximum incremental cycling exercise. Eur Respir J 2016; 48:158.
  78. Maron BA, Cockrill BA, Waxman AB, Systrom DM. The invasive cardiopulmonary exercise test. Circulation 2013; 127:1157.
  79. Berry NC, Manyoo A, Oldham WM, et al. Protocol for exercise hemodynamic assessment: performing an invasive cardiopulmonary exercise test in clinical practice. Pulm Circ 2015; 5:610.
  80. Malhotra R, Bakken K, D'Elia E, Lewis GD. Cardiopulmonary Exercise Testing in Heart Failure. JACC Heart Fail 2016; 4:607.
  81. Fishman A, Martinez F, Naunheim K, et al. A randomized trial comparing lung-volume-reduction surgery with medical therapy for severe emphysema. N Engl J Med 2003; 348:2059.
  82. Wensel R, Opitz CF, Anker SD, et al. Assessment of survival in patients with primary pulmonary hypertension: importance of cardiopulmonary exercise testing. Circulation 2002; 106:319.
  83. Kawut SM, O'Shea MK, Bartels MN, et al. Exercise testing determines survival in patients with diffuse parenchymal lung disease evaluated for lung transplantation. Respir Med 2005; 99:1431.
  84. Bassett DR Jr, Howley ET. Limiting factors for maximum oxygen uptake and determinants of endurance performance. Med Sci Sports Exerc 2000; 32:70.
  85. Koch B, Schäper C, Ittermann T, et al. Reference values for cardiopulmonary exercise testing in healthy volunteers: the SHIP study. Eur Respir J 2009; 33:389.
  86. Jones NL, Makrides L, Hitchcock C, et al. Normal standards for an incremental progressive cycle ergometer test. Am Rev Respir Dis 1985; 131:700.
  87. Vogel JA, Patton JF, Mello RP, Daniels WL. An analysis of aerobic capacity in a large United States population. J Appl Physiol (1985) 1986; 60:494.
  88. Hermansen L, Saltin B. Oxygen uptake during maximal treadmill and bicycle exercise. J Appl Physiol 1969; 26:31.
  89. Faulkner JA, Roberts DE, Elk RL, Conway J. Cardiovascular responses to submaximum and maximum effort cycling and running. J Appl Physiol 1971; 30:457.
  90. Woodson RD, Wills RE, Lenfant C. Effect of acute and established anemia on O2 transport at rest, submaximal and maximal work. J Appl Physiol Respir Environ Exerc Physiol 1978; 44:36.
  91. Wilson JR, Martin JL, Schwartz D, Ferraro N. Exercise intolerance in patients with chronic heart failure: role of impaired nutritive flow to skeletal muscle. Circulation 1984; 69:1079.
  92. Lewis GD, Shah R, Shahzad K, et al. Sildenafil improves exercise capacity and quality of life in patients with systolic heart failure and secondary pulmonary hypertension. Circulation 2007; 116:1555.
  93. Klausen K, Secher NH, Clausen JP, et al. Central and regional circulatory adaptations to one-leg training. J Appl Physiol Respir Environ Exerc Physiol 1982; 52:976.
  94. Graham TE, Saltin B. Estimation of the mitochondrial redox state in human skeletal muscle during exercise. J Appl Physiol (1985) 1989; 66:561.
  95. Casaburi R, Bhasin S, Cosentino L, et al. Effects of testosterone and resistance training in men with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2004; 170:870.
  96. Fitts RH. Cellular mechanisms of muscle fatigue. Physiol Rev 1994; 74:49.
  97. Hainaut K, Duchateau J. Muscle fatigue, effects of training and disuse. Muscle Nerve 1989; 12:660.
  98. Systrom DM, Kanarek DJ, Kohler SJ, Kazemi H. 31P nuclear magnetic resonance spectroscopy study of the anaerobic threshold in humans. J Appl Physiol (1985) 1990; 68:2060.
  99. Metzger JM, Fitts RH. Role of intracellular pH in muscle fatigue. J Appl Physiol (1985) 1987; 62:1392.
  100. Lindinger MI, Heigenhauser GJ, McKelvie RS, Jones NL. Blood ion regulation during repeated maximal exercise and recovery in humans. Am J Physiol 1992; 262:R126.
  101. Meyer RA, Dudley GA, Terjung RL. Ammonia and IMP in different skeletal muscle fibers after exercise in rats. J Appl Physiol Respir Environ Exerc Physiol 1980; 49:1037.
  102. Graham TE, Turcotte LP, Kiens B, Richter EA. Effect of endurance training on ammonia and amino acid metabolism in humans. Med Sci Sports Exerc 1997; 29:646.
  103. Lewis SF, Haller RG, Cook JD, Nunnally RL. Muscle fatigue in McArdle's disease studied by 31P-NMR: effect of glucose infusion. J Appl Physiol (1985) 1985; 59:1991.
  104. Rogers MA, Evans WJ. Changes in skeletal muscle with aging: effects of exercise training. Exerc Sport Sci Rev 1993; 21:65.
  105. Chiappa GR, Roseguini BT, Alves CN, et al. Blood lactate during recovery from intense exercise: impact of inspiratory loading. Med Sci Sports Exerc 2008; 40:111.
  106. Timmons JA. Variability in training-induced skeletal muscle adaptation. J Appl Physiol (1985) 2011; 110:846.
  107. Kiens B, Essen-Gustavsson B, Christensen NJ, Saltin B. Skeletal muscle substrate utilization during submaximal exercise in man: effect of endurance training. J Physiol 1993; 469:459.
  108. Röckl KS, Witczak CA, Goodyear LJ. Signaling mechanisms in skeletal muscle: acute responses and chronic adaptations to exercise. IUBMB Life 2008; 60:145.
  109. Phillips SM, Green HJ, Tarnopolsky MA, et al. Effects of training duration on substrate turnover and oxidation during exercise. J Appl Physiol (1985) 1996; 81:2182.
  110. Joyner MJ, Green DJ. Exercise protects the cardiovascular system: effects beyond traditional risk factors. J Physiol 2009; 587:5551.
  111. Gielen S, Schuler G, Adams V. Cardiovascular effects of exercise training: molecular mechanisms. Circulation 2010; 122:1221.
  112. Hambrecht R, Wolf A, Gielen S, et al. Effect of exercise on coronary endothelial function in patients with coronary artery disease. N Engl J Med 2000; 342:454.
  113. Spence AL, Carter HH, Murray CP, et al. Magnetic resonance imaging-derived right ventricular adaptations to endurance versus resistance training. Med Sci Sports Exerc 2013; 45:534.