Comprehensive Physiology Wiley Online Library
For Librarians For Authors Editors About

Lactate Transport and Exchange During Exercise

L. Bruce Gladden

10.1002/cphy.cp120114

Source: Supplement 29: Handbook of Physiology, Exercise: Regulation and Integration of Multiple Systems

Originally published: 1996

Published online: January 2011

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Why Does [La] Increase During Exercise?
1.1 Muscle Hypoxia: The Traditional Hypothesis
1.2 Evidence Against Muscle Hypoxia
1.3 Multiple Factors
1.4 Criticism of Evidence Against O2‐limitation
1.5 Near‐Equilibrium Steady State: A Unifying Hypothesis?
1.6 Summary
2 The Lactate Shuttle
3 Carrier‐Mediated Lactate Transport
3.1 Lactate Transport in Sarcolemmal Vesicles
3.2 Lactate Transport in Isolated Cells
3.3 Reconstitution of the Lactate Carrier
3.4 Lactate Transport In Situ
3.5 Summary
4 Muscle as a Consumer of Lactate: Regulating Factors
4.1 Lactate Concentration
4.2 Metabolic Rate
4.3 Blood Flow
4.4 Hydrogen Ion Concentration
4.5 Muscle Fiber Type
4.6 Exercise Training
4.7 Summary
5 Blood Transport of Lactate
5.1 Lactate Distribution between Plasma and RBCs
5.2 Comparative Aspects of Lactate Transport in RBCs
6 Altitude
6.1 The Lactate Paradox
6.2 Explanations for the Lactate Paradox
6.3 Summary
Figure 1. Figure 1.

Relationship between oxygen consumption and partial pressure of oxygen in mitochondria isolated from rat heart. Note that oxygen consumption is maximal down to very low partial pressures. Other techniques have shown that mitochondrial oxygen consumption is independent of oxygen partial pressure down to ∼0.5 mm Hg. See text for details.

Redrawn with permission from Rumsey, W. L., C. Schlosser, E. M. Nuutinen, M. Robiolio, and D. F. Wilson. Cellular energetics and the oxygen dependence of respiration in cardiac myocytes isolated from adult rat. J. Biol. Chem. 265: 15392–15399, 1990 172
Figure 2. Figure 2.

Schematic illustration of relationship between lactate rate of appearance, lactate rate of disappearance, and resulting blood [La] during progressive, incremental exercise.

Redrawn with permission from Brooks, G. A. Anaerobic threshold: review of the concept and directions for future research. Med. Sci. Sports Exerc. 17: 22–31, 1985 18
Figure 3. Figure 3.

Predicted dependence of mitochondrial oxygen consumption on partial pressure of oxygen at high‐ and low‐energy states with constant [NAD+]/[NADH] of 1.0. Note that oxygen independence is preserved to low partial pressures when energy state is low.

Based on mathematical models of, and redrawn with permission from, Wilson, D. F., C. S. Owen, and M. Erecinska. Quantitative dependence of mitochondrial oxidative phosphorylation on oxygen concentration: a mathematical model. Arch. Biochem. Biophys. 195: 494–504, 1979 212
Figure 4. Figure 4.

Predicted dependence of mitochondrial oxygen consumption on partial pressure of oxygen at high and low [NAD+]/[NADH] with constant [ATP]/[ADP][Pi] of 500 · M−1. Note that oxygen independence is preserved to low partial pressures when [NAD+]/[NADH] is low.

Based on mathematical models of, and redrawn with permission from, Wilson, D. F., C. S. Owen, and M. Erecinska. Quantitative dependence of mitochondrial oxidative phosphorylation on oxygen concentration: a mathematical model. Arch. Biochem. Biophys. 195: 494–504, 1979 212
Figure 5. Figure 5.

Relationship between energy state and oxygen uptake in dog gastrocnemius muscle in situ at rest and two stimulation rates for normoxemia, moderate hypoxemia, and severe hypoxemia. The important point is that a greater decrease in energy state is required in order to stimulate a given oxygen uptake when the oxygen delivery is low. Note especially the two points indicated by arrows. The oxygen uptake is approximately the same, but a much lower energy state is required with moderate hypoxemia in comparison to normoxemia.

Redrawn with permission from Hogan, M. C., P. G. Arthur, D. E. Bebout, P. W. Hochachka, and P. D. Wagner. Role of O2 in regulating tissue respiration in dog muscle working in situ. J. Appl. Physiol. 73: 728–736, 1992 94
Figure 6. Figure 6.

Illustration of a hypothetical intracellular lactate shuttle. Lactate produced in the cytosol might diffuse to mitochondria where the [La] is lower because of lactate consumption. At the mitochondria, the LDH reaction would operate to produce pyruvate and NADH from lactate and NAD+. Due to the higher concentration of lactate in comparison to pyruvate and NADH, such a shuttle might enhance the delivery of pyruvate and reducing equivalents to the mitochondria, particularly during exercise.
Figure 7. Figure 7.

L(+)‐lactate influx into sarcolemmal vesicles. Curve is best fit to Michaelis‐Menten hyperbolic function. Vmax = 139.4 nmol · mg−1 · min−1; Km = 40.1 mM.

Redrawn with permission from Roth, D. A., and G. A. Brooks. Lactate transport is mediated by a membrane‐bound carrier in rat skeletal muscle sarcolemmal vesicles. Arch. Biochem. Biophys. 279: 377–385, 1990 167
Figure 8. Figure 8.

Schematic of proposed model for the monocarboxylate carrier of lactate transport in red blood cells 161. Lactate transport in sarcolemmal vesicles has been proposed to be qualitatively similar 113,161. The various K's represent binding rates while the k's represent translocation rates. It is postulated that the carrier first binds H+ and then lactate. The carrier with only H+ bound is believed to be either immobile or else translocates only very slowly. See text for additional details.

Redrawn with permission from Poole, R. C., and A. P. Halestrap. Transport of lactate and other monocarboxylates across mammalian plasma membranes. Am. J. Physiol. 264 (Cell Physiol. 33): C761–C782, 1993 161
Figure 9. Figure 9.

Net lactate uptake by canine gastrocnemius in situ at rest and during contractions (twitches at 4 Hz) at a high metabolic rate with increasing plasma [La]. Two points are important: (1) with increasing [La], net lactate uptake approaches a plateau; and (2) net lactate uptake is higher with the higher metabolic rate of contractions.

Redrawn with permission from Gladden, L. B., R. E. Crawford, and M. J. Webster. Effect of lactate concentration and metabolic rate on net lactate uptake by canine skeletal muscle. Am. J. Physiol. 266 (Regulatory Integrative Comp. Physiol. 35): R1095–R1101, 1994 70
Figure 10. Figure 10.

Total lactate influx via all three parallel pathways of lactate transport in the RBCs of “athletic” (equine and canine) and “nonathletic” (bovine and caprine) species. Lactate influx was much more rapid in the RBCs of the “athletic” species.

Redrawn with permission from Skelton, M. S., D. E. Kremer, E. W. Smith, and L. B. Gladden. Lactate influx into red blood cells of “athletic” and “nonathletic” species. Am. J. Physiol. 268 (Regulatory Integrative Comp. Physiol. 37): R1121–R1128, 1995 177
Figure 11. Figure 11.

Blood [La] responses to exercise at high altitude in unacclimatized (acute hypoxia) and acclimatized subjects (chronic hypoxia) exposed to altitudes (429 mm Hg, unacclimatized; 347 mm Hg, acclimatized) resulting in the same arterial O2 pressure in both groups (33–35 mm Hg).

Based on data from Wagner et al. 197 and Sutton et al. 192 and redrawn with permission from Reeves, J. X, E. E. Wolfel, H. J. Green, R. S. Mazzeo, A. J. Young, J. R. Sutton, and G. A. Brooks. Oxygen transport during exercise at altitude and the lactate paradox: lessons from Operation Everest II and Pikes Peak. Exerc. Sport Sci. Rev. 20: 275–296, 1992 162
Figure 12. Figure 12.

Maximal blood [La] following exhaustive exercise in high‐altitude natives and acclimatized sea level natives (data combined). Note that maximal blood [La] declines as altitude increases.

Data are from Cerretelli et al. 31 and West et al. 208 and are redrawn with permission from West, J. B. Acid–base status and blood lactate at extreme altitude. In: Hypoxia, Metabolic Acidosis, and the Circulation, edited by A. I. Arieff. New York: Oxford University Press, 1992, p. 33–44 207
Figure 13. Figure 13.

Arterial blood [La] values at rest and during 45 min of submaximal exercise in control and β‐blocked subjects at sea level, acute, and chronic altitude exposure at 4300 m. Note that β‐blockade caused a reduction in [La] under all conditions including acute exposure. Also, note that acclimatization (chronic altitude) resulted in a decrease in [La] in both control and β‐blockade groups.

Redrawn with permission from Mazzeo, R. S., G. A. Brooks, G. E. Butterfield, A. Cymerman, A. C. Roberts, M. Selland, E. E. Wolfel, and J. T. Reeves. β‐Adrenergic blockade does not prevent the lactate response to exercise after acclimatization to high altitude. J. Appl. Physiol. 76: 610–615, 1994 135


Figure 1.

Relationship between oxygen consumption and partial pressure of oxygen in mitochondria isolated from rat heart. Note that oxygen consumption is maximal down to very low partial pressures. Other techniques have shown that mitochondrial oxygen consumption is independent of oxygen partial pressure down to ∼0.5 mm Hg. See text for details.

Redrawn with permission from Rumsey, W. L., C. Schlosser, E. M. Nuutinen, M. Robiolio, and D. F. Wilson. Cellular energetics and the oxygen dependence of respiration in cardiac myocytes isolated from adult rat. J. Biol. Chem. 265: 15392–15399, 1990 172


Figure 2.

Schematic illustration of relationship between lactate rate of appearance, lactate rate of disappearance, and resulting blood [La] during progressive, incremental exercise.

Redrawn with permission from Brooks, G. A. Anaerobic threshold: review of the concept and directions for future research. Med. Sci. Sports Exerc. 17: 22–31, 1985 18


Figure 3.

Predicted dependence of mitochondrial oxygen consumption on partial pressure of oxygen at high‐ and low‐energy states with constant [NAD+]/[NADH] of 1.0. Note that oxygen independence is preserved to low partial pressures when energy state is low.

Based on mathematical models of, and redrawn with permission from, Wilson, D. F., C. S. Owen, and M. Erecinska. Quantitative dependence of mitochondrial oxidative phosphorylation on oxygen concentration: a mathematical model. Arch. Biochem. Biophys. 195: 494–504, 1979 212


Figure 4.

Predicted dependence of mitochondrial oxygen consumption on partial pressure of oxygen at high and low [NAD+]/[NADH] with constant [ATP]/[ADP][Pi] of 500 · M−1. Note that oxygen independence is preserved to low partial pressures when [NAD+]/[NADH] is low.

Based on mathematical models of, and redrawn with permission from, Wilson, D. F., C. S. Owen, and M. Erecinska. Quantitative dependence of mitochondrial oxidative phosphorylation on oxygen concentration: a mathematical model. Arch. Biochem. Biophys. 195: 494–504, 1979 212


Figure 5.

Relationship between energy state and oxygen uptake in dog gastrocnemius muscle in situ at rest and two stimulation rates for normoxemia, moderate hypoxemia, and severe hypoxemia. The important point is that a greater decrease in energy state is required in order to stimulate a given oxygen uptake when the oxygen delivery is low. Note especially the two points indicated by arrows. The oxygen uptake is approximately the same, but a much lower energy state is required with moderate hypoxemia in comparison to normoxemia.

Redrawn with permission from Hogan, M. C., P. G. Arthur, D. E. Bebout, P. W. Hochachka, and P. D. Wagner. Role of O2 in regulating tissue respiration in dog muscle working in situ. J. Appl. Physiol. 73: 728–736, 1992 94


Figure 6.

Illustration of a hypothetical intracellular lactate shuttle. Lactate produced in the cytosol might diffuse to mitochondria where the [La] is lower because of lactate consumption. At the mitochondria, the LDH reaction would operate to produce pyruvate and NADH from lactate and NAD+. Due to the higher concentration of lactate in comparison to pyruvate and NADH, such a shuttle might enhance the delivery of pyruvate and reducing equivalents to the mitochondria, particularly during exercise.



Figure 7.

L(+)‐lactate influx into sarcolemmal vesicles. Curve is best fit to Michaelis‐Menten hyperbolic function. Vmax = 139.4 nmol · mg−1 · min−1; Km = 40.1 mM.

Redrawn with permission from Roth, D. A., and G. A. Brooks. Lactate transport is mediated by a membrane‐bound carrier in rat skeletal muscle sarcolemmal vesicles. Arch. Biochem. Biophys. 279: 377–385, 1990 167


Figure 8.

Schematic of proposed model for the monocarboxylate carrier of lactate transport in red blood cells 161. Lactate transport in sarcolemmal vesicles has been proposed to be qualitatively similar 113,161. The various K's represent binding rates while the k's represent translocation rates. It is postulated that the carrier first binds H+ and then lactate. The carrier with only H+ bound is believed to be either immobile or else translocates only very slowly. See text for additional details.

Redrawn with permission from Poole, R. C., and A. P. Halestrap. Transport of lactate and other monocarboxylates across mammalian plasma membranes. Am. J. Physiol. 264 (Cell Physiol. 33): C761–C782, 1993 161


Figure 9.

Net lactate uptake by canine gastrocnemius in situ at rest and during contractions (twitches at 4 Hz) at a high metabolic rate with increasing plasma [La]. Two points are important: (1) with increasing [La], net lactate uptake approaches a plateau; and (2) net lactate uptake is higher with the higher metabolic rate of contractions.

Redrawn with permission from Gladden, L. B., R. E. Crawford, and M. J. Webster. Effect of lactate concentration and metabolic rate on net lactate uptake by canine skeletal muscle. Am. J. Physiol. 266 (Regulatory Integrative Comp. Physiol. 35): R1095–R1101, 1994 70


Figure 10.

Total lactate influx via all three parallel pathways of lactate transport in the RBCs of “athletic” (equine and canine) and “nonathletic” (bovine and caprine) species. Lactate influx was much more rapid in the RBCs of the “athletic” species.

Redrawn with permission from Skelton, M. S., D. E. Kremer, E. W. Smith, and L. B. Gladden. Lactate influx into red blood cells of “athletic” and “nonathletic” species. Am. J. Physiol. 268 (Regulatory Integrative Comp. Physiol. 37): R1121–R1128, 1995 177


Figure 11.

Blood [La] responses to exercise at high altitude in unacclimatized (acute hypoxia) and acclimatized subjects (chronic hypoxia) exposed to altitudes (429 mm Hg, unacclimatized; 347 mm Hg, acclimatized) resulting in the same arterial O2 pressure in both groups (33–35 mm Hg).

Based on data from Wagner et al. 197 and Sutton et al. 192 and redrawn with permission from Reeves, J. X, E. E. Wolfel, H. J. Green, R. S. Mazzeo, A. J. Young, J. R. Sutton, and G. A. Brooks. Oxygen transport during exercise at altitude and the lactate paradox: lessons from Operation Everest II and Pikes Peak. Exerc. Sport Sci. Rev. 20: 275–296, 1992 162


Figure 12.

Maximal blood [La] following exhaustive exercise in high‐altitude natives and acclimatized sea level natives (data combined). Note that maximal blood [La] declines as altitude increases.

Data are from Cerretelli et al. 31 and West et al. 208 and are redrawn with permission from West, J. B. Acid–base status and blood lactate at extreme altitude. In: Hypoxia, Metabolic Acidosis, and the Circulation, edited by A. I. Arieff. New York: Oxford University Press, 1992, p. 33–44 207


Figure 13.

Arterial blood [La] values at rest and during 45 min of submaximal exercise in control and β‐blocked subjects at sea level, acute, and chronic altitude exposure at 4300 m. Note that β‐blockade caused a reduction in [La] under all conditions including acute exposure. Also, note that acclimatization (chronic altitude) resulted in a decrease in [La] in both control and β‐blockade groups.

Redrawn with permission from Mazzeo, R. S., G. A. Brooks, G. E. Butterfield, A. Cymerman, A. C. Roberts, M. Selland, E. E. Wolfel, and J. T. Reeves. β‐Adrenergic blockade does not prevent the lactate response to exercise after acclimatization to high altitude. J. Appl. Physiol. 76: 610–615, 1994 135
References
 1. El Abida, K., A. Duvallet, L. Thieulart, M. Rieu, and M. Beaudry. Lactate transport during differentiation of skeletal muscle cells: evidence for a specific carrier in L6 myotubes. Acta Physiol. Scand. 144: 469–471, 1992.
 2. Akerboom, T. P. M., R. Van Der Meer, and J. M. Tager. Techniques for the investigation of intracellular compartmentation. In: Techniques in the Life Sciences. Biochemistry. Techniques in Metabolic Research, edited by H. L. Rornberg, J. C. Metcalfe, and D. H. Northcote. Amsterdam: Elsevier, 1979, p. 1–33.
 3. Allen, P. J., and G. A. Brooks. Partial purification and re‐constitution of the sarcolemmal l‐lactate carrier from rat skeletal muscle. Biochem. J. 303: 207–212, 1994.
 4. Allen, W. K., D. R. Seals, B. F. Hurley, A. A. Ehsani, and J. M. Hagberg. Lactate threshold and distance‐running performance in young and older endurance athletes. J. Appl. Physiol. 58: 1281–1284, 1985.
 5. Andersen, P., and B. Saltin. Maximal perfusion of skeletal muscle in man. Physiol. (Lond.) 366: 233–249, 1985.
 6. Armstrong, R. B. Muscle fiber recruitment patterns and their metabolic correlates. In: Exercise, Nutrition, and Energy Metabolism, edited by E. S. Horton and R. L. Terjung. New York: Macmillan Publishing Company, 1988, p. 9–26.
 7. Arthur, P. G., M. C. Hogan, D. E. Bebout, P. D. Wagner, and P. W. Hochachka. Modeling the effects of hypoxia on ATP turnover in exercising muscle. J. Appl. Physiol. 73: 737–742, 1992.
 8. Asmussen, E. Observations on experimental muscular soreness. Acta Rheum. Scand. 2: 109–116, 1956.
 9. Baldwin, K. M., A. M. Hooker, and R. E. Herrick. Lactate oxidative capacity in different types of muscle. Biochem. Biophys. Res. Commun. 83: 151–157, 1978.
 10. Bassingthwaighte, J. B., I. S. J. Chan, and C. Y. Wang. Computationally efficient algorithms for convection‐permeation diffusion models for blood‐tissue exchange. Ann. Biomed. Eng. 20: 687–725, 1992.
 11. Beaudry, M., A. Duvallet, L. Thieulart, K. El Abida, and M. Rieu. Lactate transport in skeletal muscle cells: uptake in L6 myoblasts. Acta Physiol. Scand. 141: 379–381, 1991.
 12. Bender, P. R., B. M. Groves, R. E. McCullough, R. G. McCullough, S.‐Y. Huang, A. J. Hamilton, P. D. Wagner, A. Cymerman, and J. T. Reeves. Oxygen transport to exercising leg in chronic hypoxia. J. Appl. Physiol. 65: 2592–2597, 1988.
 13. Bender, P. R., B. M. Groves, R. E. McCullough, R. G. McCullough, L. Trad, A. J. Young, A. Cymerman, and J. T. Reeves. Decreased exercise muscle lactate release after high altitude acclimatization. J. Appl. Physiol. 67: 1456–1462, 1989.
 14. Bonen, A., and K. J. A. McCullagh. Effects of exercise on lactate transport into mouse skeletal muscles. Can. J. Appl. Physiol. 19: 275–285, 1994.
 15. Bonen, A., J. C. McDermott, and C. A. Hutber. Carbohy drate metabolism in skeletal muscle: an update of current concepts. Int. J. Sports Med. 10: 385–401, 1989.
 16. Bonen, A., J. C. McDermott, and M. H. Tan. Glycogenesis and glyconeogenesis in skeletal muscle: effects of pH and hormones. Am. J. Physiol. 258 (Endocrinol. Metab. 21): E693–E700, 1990.
 17. Bromberg, P. A., J. Theodore, E. D. Robin, and W. N. Jensen. Anion and hydrogen ion distribution in human blood. J. Lab. Clin. Med. 66: 464–475, 1965.
 18. Brooks, G. A. Anaerobic threshold: review of the concept and directions for future research. Med. Sci. Sports Exerc. 17: 22–31, 1985.
 19. Brooks, G. A. The lactate shuttle during exercise and recovery. Med. Sa. Sports Exerc. 18: 360–368, 1986.
 20. Brooks, G. A. Lactate production under fully aerobic conditions: the lactate shuttle during rest and exercise. Federation Proc. 45: 2924–2929, 1986.
 21. Brooks, G. A. Blood lactic acid: sports “bad boy” turns good. Gatorade Sports Science Exchange, No. 2, April, 1988.
 22. Brooks, G. A. Current concepts in lactate exchange. Med. Sci. Sports Exerc. 23: 895–906, 1991.
 23. Brooks, G. A., G. E. Butterfield, R. R. Wolfe, B. M. Groves, R. S. Mazzeo, J. R. Sutton, E. E. Wolfel, and J. T. Reeves. Decreased reliance on lactate during exercise after acclimatization to 4,300 m. J. Appl. Physiol. 71: 333–341, 1991.
 24. Brooks, G. A., and T. D. Fahey. Exercise Physiology: Human Bioenergetics and Its Applications. New York: John Wiley & Sons, 1984, p. 84–89, 208–213.
 25. Brooks, G. A., E. E. Wolfel, B. M. Groves, P. R. Bender, G. E. Butterfield, A. Cymerman, R. S. Mazzeo, J. R. Sutton, R. R. Wolfe, and J. T. Reeves. Muscle accounts for glucose disposal but not blood lactate appearance during exercise after acclimatization to 4,300 m. J. Appl. Physiol. 72: 2435–2445, 1992.
 26. Brown, M. A., and G. A. Brooks. Trans‐stimulation of lactate transport from rat sarcolemmal membrane vesicles. Arch. Biochem. Biophys. 313: 22–28, 1994.
 27. Burke, R. E. Motor units: anatomy, physiology, and functional organization. In: Handbook of Physiology, The Nervous System, Motor Control, edited by V. B. Brooks. Bethesda, MD: Am. Physiol. Soc., 1981, p. 345–422.
 28. Bylund‐Fellenius, A.‐C., J.‐P. Idström, and S. Holm. Muscle respiration during exercise. Am. Rev. Respir. Dis. 129 (Suppl.): S10–S12, 1984.
 29. Bylund‐Fellenius, A.‐C., P. M. Walker, A. Elander, S. Holm, J. Holm, and T. Scherstén. Energy metabolism in relation to oxygen partial pressure in human skeletal muscle during exercise. Biochem. J. 200: 247–255, 1981.
 30. Cerretelli, P. Gas exchange at high altitude. In: Pulmonary Gas Exchange, edited by J. B. West. New York: Academic Press, 1980, p. 97–147.
 31. Cerretelli, P., A. Veicsteinas, and C. Marconi. Anaerobic metabolism at high altitude: the lactacid mechanism. In: High Altitude Physiology and Medicine, edited by W. Brendel and R. A. Zink. New York: Springer‐Verlag, 1982, p. 94–102.
 32. Chance, B., and B. Quistorff. Study of tissue oxygen gradients by single and multiple indicators. Adv. Exp. Med. Biol. 94: 331–338, 1978.
 33. Chinkes, D. L., X.‐J. Zhang, J. A. Romijn, Y. Sakurai, and R. R. Wolfe. Measurement of pyruvate and lactate kinetics across the hindlimb and gut of anesthetized dogs. Am. J. Physiol. 267 (Endocrinol. Metab. 30): E174–E182, 1994.
 34. Clausen, J. P. Effect of physical training on cardiovascular adjustments to exercise and thermal stress. Physiol. Rev. 57: 779–815, 1977.
 35. Cohen, R. D. Clinical implications of the pathophysiology of lactic acidosis: the role of defects in lactate disposal. In: Hypoxia, Metabolic Acidosis, and the Circulation, edited by A. I. Arieff. New York: Oxford University Press, 1992, p. 85–98.
 36. Connett, R. J., T. E. J. Gayeski, and C. R. Honig. Lactate production in a pure red muscle in absence of anoxia: mechanisms and significance. Adv. Exp. Med. Biol. 159: 327–335, 1983.
 37. Connett, R. J., T. E. J. Gayeski, and C. R. Honig. Lactate accumulation in fully aerobic, working, dog gracilis muscle. Am. J. Physiol. 246 (Heart Circ. Physiol. 15): H120–H128, 1984.
 38. Connett, R. J., T. E. J. Gayeski, and C. R. Honig. Energy sources in fully aerobic rest‐work transitions: a new role for glycolysis. Am. J. Physiol. 248 (Heart Circ. Physiol. 17): H922–H929, 1985.
 39. Connett, R. J., T. E. J. Gayeski, and C. R. Honig. Lactate efflux is unrelated to intracellular Po2 in a working red muscle in situ. J. Appl. Physiol. 61: 402–408, 1986.
 40. Connett, R. J., C. R. Honig, T. E. J. Gayeski, and G. A. Brooks. Defining hypoxia: a systems view of Vo2, glycolysis, energetics, and intracellular Po2. J. Appl. Physiol. 68: 833–842, 1990.
 41. Constantinopol, M., J. H. Jones, E. R. Weibel, C. R. Taylor, A. Lindholm, and R. H. Karas. Oxygen transport during exercise in large mammals: II. Oxygen uptake by the pulmonary gas exchanger. J. Appl. Physiol. 67: 871–878, 1989.
 42. Corsi, A., M. Zatti, M. Midrio, and A. L. Granata. In situ oxidation of lactate by skeletal muscle during intermittent exercise. FEBS Lett. 11: 65–68, 1970.
 43. Davis, J. A., V. J. Caiozzo, N. Lamarra, J. F. Ellis, R. Van‐dagriff, C. A. Prietto, and W. C. McMaster. Does the gas exchange anaerobic threshold occur at a fixed blood lactate concentration of 2 or 4 mM? Int. J. Sports Med. 4: 89–93, 1983.
 44. Deuticke, B. The transmembrane exchange of chloride with hydroxyl and other anions in mammalian red blood cells. In: Oxygen Affinity of Hemoglobin and Red Cell Acid Base Status, edited by M. Rorth and P. Astrup. New York: Academic Press, 1972, p. 307–319.
 45. Deuticke, B. Monocarboxylate transport in erythrocytes. J. Membr. Biol. 70: 89–103, 1982.
 46. Deuticke, B. Monocarboxylate transport in red blood cells: kinetics and chemical modification. Methods Enzymol. 173: 300–329, 1989.
 47. Deuticke, B., E. Beyer, and B. Forst. Discrimination of three parallel pathways of lactate transport in the human erythrocyte membrane by inhibitors and kinetic properties. Biochim. Biophys. Acta 684: 96–110, 1982.
 48. Dobson, G. P., W. S. Parkhouse, J.‐M. Weber, E. Stuttard, J. Harman, D. H. Snow, and P. W. Hochachka. Metabolic changes in skeletal muscle and blood of greyhounds during 800‐m track sprint. Am. J. Physiol. 255 (Regulatory Integrative Comp. Physiol. 24): R513–R519, 1988.
 49. Dodd, S., S. K. Powers, T. Callender, and E. Brooks. Blood lactate disappearance at various intensities of recovery exercise. J. Appl. Physiol. 57: 1462–1465, 1984.
 50. Doll, E., J. Keul, and C. Maiwald. Oxygen tension and acid–base equilibria in venous blood of working muscle. Am. J. Physiol. 215: 23–29, 1968.
 51. Donovan, C. M., and G. A. Brooks. Endurance training affects lactate clearance, not lactate production. Am. J. Physiol. 244 (Endocrinol. Metab. 7): E83–E92, 1983.
 52. Donovan, C. M., and M. J. Pagliassotti. Endurance training enhances lactate clearance during hyperlactatemia. Am. J. Physiol. 257 (Endocrinol. Metab. 20): E782–E789, 1989.
 53. Donovan, C. M., and M. J. Pagliassotti. Enhanced efficiency of lactate removal after endurance training. J. Appl. Physiol. 68: 1053–1058, 1990.
 54. Drummond, G. I., J. P. Harwood, and C. A. Powell. Studies on the activation of phosphorylase in skeletal muscle by contraction and by epinephrine. J. Biol. Chem. 244: 4235–4240, 1969.
 55. Duboc, D., M. Muffat‐Joly, G. Renault, M. Degeorges, M. Toussaint, and J. R. Pocidalo. In situ NADH laser fluorimetry of rat fast and slow twitch muscles during tetanus. J. Appl. Physiol. 64: 2692–2695, 1988.
 56. Duhaylongsod, F. G., J. A. Griebel, D. S. Bacon, W. G. Wolfe, and C. A. Piantadosi. Effects of muscle contraction on cytochrome a,a3 redox state. J. Appl. Physiol. 75: 790–797, 1993.
 57. Erecińska, M., and D. F. Wilson. Regulation of cellular energy metabolism. J. Memb. Biol. 70: 1–14, 1982.
 58. Favier, R., H. Spielvogel, D. Desplanches, G. Ferretti, B. Kayser, and H. Hoppeler. Maximal exercise performance in chronic hypoxia and acute normoxia in high‐altitude natives. J. Appl. Physiol. 78: 1868–1874, 1995.
 59. Fitts, R. H. Cellular mechanisms of muscle fatigue. Physiol. Rev. 74: 49–94, 1994.
 60. Fitzsimons, E. J., and J. Sendroy, Jr.. Distribution of electrolytes in human blood. J. Biol. Chem. 236: 1595–1601, 1961.
 61. Foxdal, P., B. Sjödin, H. Rudstam, C. Östman, B. Östman, and G. C. Hedenstierna. Lactate concentration differences in plasma, whole blood, capillary finger blood and erythrocytes during submaximal graded exercise in humans. Eur. J. Appl. Physiol. 61: 218–222, 1990.
 62. Freminet, A., E. Bursaux, and C. F. Poyart. Effect of elevated lactataemia in the rates of lactate turnover and oxidation in rats. Pflugers Arch. 346: 75–86, 1974.
 63. Funder, J., and J. O. Wieth. Chloride and hydrogen ion distribution between human red cells and plasma. Acta Physiol. Scand. 68: 234–245, 1966.
 64. Gaesser, G. A., and G. A. Brooks. Metabolic bases of excess post exercise oxygen consumption: a review. Med. Sci. Sports Exerc. 16: 29–43, 1984.
 65. Garcia, C. K., J. L. Goldstein, R. K. Pathak, R. G. W. Anderson, and M. S. Brown. Molecular characterization of a membrane transporter for lactate, pyruvate, and other monocarboxylates: implications for the Cori cycle. Cell 76: 865–873, 1994.
 66. Gladden, L. B. Current “anaerobic threshold” controversies. Physiologist 27: 312–318, 1984.
 67. Gladden, L. B. Lactate uptake by skeletal muscle. Exerc. Sport Sci. Rev. 17: 115–155, 1989.
 68. Gladden, L. B. Net lactate uptake during progressive steady‐level contractions in canine skeletal muscle. J. Appl. Physiol. 71: 514–520, 1991.
 69. Gladden, L. B., R. E. Crawford, and M. J. Webster. Effect of blood flow on net lactate uptake during steady‐level contractions in canine skeletal muscle. J. Appl. Physiol. 72: 1826–1830, 1992.
 70. Gladden, L. B., R. E. Crawford, and M. J. Webster. Effect of lactate concentration and metabolic rate on net lactate uptake by canine skeletal muscle. Am. J. Physiol. 266 (Regulatory Integrative Comp. Physiol. 35): R1095–R1101, 1994.
 71. Gladden, L. B., R. E. Crawford, M. J. Webster, and P. W. Watt. Rapid tracer lactate influx into canine skeletal muscle. J. Appl. Physiol. 78: 205–211, 1995.
 72. Gladden, L. B., E. W. Smith, and M. S. Skelton. Lactate distribution in blood during passive and active recovery after intense exercise. Med. Sci. Sports Exerc. 26 (Suppl.): S35, 1994.
 73. Gladden, L. B., and J. W. Yates. Lactic acid infusion in dogs: effects of varying infusate pH. J. Appl. Physiol. 54: 1254–1260, 1983.
 74. Gladden, L. B., J. W. Yates, R. W. Stremel, and B. A. Stamford. Gas exchange and lactate anaerobic thresholds: interand intraevaluator agreement. J. Appl. Physiol. 58: 2082–2089, 1985.
 75. Gollnick, P. D., W. M. Bayly, and D. R. Hodgson. Exercise intensity, training, diet, and lactate concentration in muscle and blood. Med. Sci. Sports Exerc. 18: 334–340, 1986.
 76. Goodyear, L. J., M. F. Hirshman, P. A. King, E. D. Horton, C. M. Thompson, and E. S. Horton. Skeletal muscle plasma membrane glucose transport and glucose transporters after exercise. Appl. Physiol. 68: 193–198, 1990.
 77. Graham, T. E., J. K. Barclay, and B. A. Wilson. Skeletal muscle lactate release and glycolytic intermediates during hypercapma. J. Appl. Physiol. 60: 568–575, 1986.
 78. Graham, T. E., P. K. Pedersen, and B. Saltin. Muscle and blood ammonia and lactate responses to prolonged exercise with hyperoxia. J. Appl. Physiol. 63: 1457–1462, 1987.
 79. Granata, A. L., M. Midrio, and A. Corsi. Lactate oxidation by skeletal muscle during sustained contraction in vivo. Pflugers Arch. 366: 247–250, 1976.
 80. Green, H. J., J. R. Sutton, A. Cymerman, P. M. Young, and C. S. Houston. Operation Everest II: adaptations in human skeletal muscle. J. Appl. Physiol. 66: 2454–2461, 1989.
 81. Green, H. J., J. R. Sutton, E. E. Wolfel, J. T. Reeves, G. E. Butterfield, and G. A. Brooks. Altitude acclimatization and energy metabolic adaptations in skeletal muscle during exercise. J. Appl. Physiol. 73: 2701–2708, 1992.
 82. Green, H. J., J. Sutton, P. Young, A. Cymerman, and C. S. Houston. Operation Everest II: muscle energetics during maximal exhaustive exercise. J. Appl. Physiol. 66: 142–150, 1989.
 83. Grimditch, G. K., R. J. Barnard, S. A. Kaplan, and E. Sternlicht. Insulin binding and glucose transport in rat skeletal muscle sarcolemmal vesicles. Am. J. Physiol. 249: 398–408, 1985.
 84. Guezennec, C. Y., F. Lienhard, F. Louisy, G. Renault, M. H. Tusseau, and P. Portero. In situ NADH laser fluorimetry during muscle contraction in humans. Eur. J. Appl. Physiol. 63: 36–42, 1991.
 85. Halestrap, A. P. Transport of pyruvate and lactate into human erythrocytes. Biochem. J. 156: 193–207, 1976.
 86. Halestrap, A. P., R. D. Scott, and A. P. Thomas. Mitochondrial pyruvate transport and its hormonal regulation. Int. J. Biochem. 11: 97–105, 1980.
 87. Hargreaves, M., and E. A. Richter. Regulation of skeletal muscle glycogenolysis during exercise. Can. J. Sport Sci. 13: 197–203, 1988.
 88. Hill, A. V. The energy degraded in the recovery processes of stimulated muscles. J. Physiol. (Land.) 46: 28–80, 1913.
 89. Hochachka, P. W. The lactate paradox: analysis of underlying mechanisms. Ann. Sport Med. 4: 184–188, 1988.
 90. Hochachka, P. W. Muscle enzymatic composition and metabolic regulation in high altitude adapted natives. Int. J. Sports Med. 13 (Suppl. 1): S89–S91, 1992.
 91. Hochachka, P. W., and G. O. Matheson. Regulating ATP turnover rates over broad dynamic work ranges in skeletal muscles. J. Appl. Physiol. 73: 1697–1703, 1992.
 92. Hochachka, P. W., C. Stanley, G. O. Matheson, D. C. McKenzie, P. S. Allen, and W. S. Parkhouse. Metabolic and work efficiencies during exercise in Andean natives. J. Appl. Physiol. 70: 1720–1730, 1991.
 93. Hochachka, P. W., C. Stanley, D. C. McKenzie, A. Villena, and C. Monge. Enzyme mechanisms for pyruvate‐to‐lactate flux attenuation: a study of Sherpas, Quechuas, and hummingbirds. Int. J. Sports Med. 13 (Suppl. 1): S119–S122, 1992.
 94. Hogan, M. C., P. G. Arthur, D. E. Bebout, P. W. Hochachka, and P. D. Wagner. Role of O2 in regulating tissue respiration in dog muscle working in situ. J. Appl. Physiol. 73: 728–736, 1992.
 95. Hogan, M. C., R. H. Cox, and H. G. Welch. Lactate accumulation during incremental exercise with varied inspired oxygen fractions. J. Appl. Physiol. 55: 1134–1140, 1983.
 96. Hogan, M. C., S. Nioka, W. F. Brechue, and B. Chance. A 31P‐NMR study of tissue respiration in working dog muscle during reduced O2 delivery conditions. J. Appl. Physiol. 73: 1662–1670, 1992.
 97. Hogan, M. C., and H. G. Welch. Effect of altered arterial O2 tensions on muscle metabolism in dog skeletal muscle during fatiguing work. Am. J. Physiol. 251 (Cell Physiol. 20): C216–C222, 1986.
 98. Holloszy, J. O., and E. F. Coyle. Adaptations of skeletal muscle to endurance exercise and their consequences. J. Appl. Physiol. 56: 831–838, 1984.
 99. Holm, S., and A.‐C. Bylund‐Fellenius. Continuous monitoring of oxygen tension in human gastrocnemius muscle during exercise. Clin. Physiol. 1: 541–552, 1981.
 100. Honig, C. R., T. E. J. Gayeski, W. Federspiel, A. Clark, and P. Clark. Muscle O2 gradients from hemoglobin to cytochrome: new concepts, new complexities. Adv. Exp. Med. Biol. 169: 23–38, 1984.
 101. Horstman, D. H., M. Gleser, and J. Delehunt. Effects of altering O2 delivery on Vo2 of isolated, working muscle. Am. J. Physiol. 230: 327–334, 1976.
 102. Howald, H., D. Petté, J.‐A. Simoneau, A. Uber, H. Hoppeler, and P. Cerretelli, III.. Effects of chronic hypoxia on muscle enzyme activities. Int. J. Sports Med. 11 (Suppl. 1): S10–S14, 1990.
 103. Hundal, H. S., M. J. Rennie, and P. W. Watt. Characteristics of l‐glutamine transport in perfused rat skeletal muscle. J. Physiol. (Lond.) 393: 283–305, 1987.
 104. Idström, J.‐P., V. H. Subramanian, B. Chance, T. Scherstén, and A.‐C. Bylund‐Fellenius. Oxygen dependence of energy metabolism in contracting and recovering rat skeletal muscle. Am. J. Physiol. 248 (Heart Circ. Physiol. 17): H40–H48, 1985.
 105. Issekutz, B., Jr., W. A. S. Shaw, and A. C. Issekutz. Lactate metabolism in resting and exercising dogs. J. Appl. Physiol. 40: 312–319, 1976.
 106. Jöbsis, F. F., and W. N. Stainsby. Oxidation of NADH during contractions of circulated mammalian skeletal muscle. Respir. Physiol. 4: 292–300, 1968.
 107. Johnson, J. M. Circulation to skeletal muscle. In: Textbook of Physiology, Vol. 2, edited by H. D. Patton, A. F. Fuchs, B. Hille, A. M. Scher, and R. Steiner. Philadelphia: W. B. Saunders Company, 1989, p. 887–897.
 108. Johnson, R. E., H. T. Edwards, D. B. Dill, and J. W. Wilson. Blood as a physicochemical system: the distribution of lactate. J. Biol. Chem. 157: 461–473, 1945.
 109. Jones, D. P. Intracellular diffusion gradients of O2 and ATP. Am. J. Physiol. 250 (Cell Physiol. 19): C663–C675, 1986.
 110. Jones, J. H., K. E. Longworth, A. Lindholm, K. E. Conley, R. H. Karas, S. R. Kayar, and C. R. Taylor. Oxygen transport during exercise in large mammals: I. Adaptive variation in oxygen demand. J. Appl. Physiol. 67: 862–870, 1989.
 111. Juel, C. Intracellular pH recovery and lactate efflux in mouse soleus muscles stimulated in vitro: the involvement of sodium/proton exchange and a lactate carrier. Acta Physiol. Scand. 132: 363–371, 1988.
 112. Juel, C. Human muscle lactate transport can be studied in sarcolemmal giant vesicles made from needle‐biopsies. Acta Physiol. Scand. 142: 133–134, 1991.
 113. Juel, C. Muscle lactate transport studied in sarcolemmal giant vesicles. Biochim. Biophys. Acta 1065: 15–20, 1991.
 114. Juel, C., J. Bangsbo, T. Graham, and B. Saltin. Lactate and potassium fluxes from human skeletal muscle during and after intense, dynamic, knee extensor exercise. Acta Physiol. Scand. 140: 147–159, 1990.
 115. Juel, C., A. Honig, and H. Pilegaard. Muscle lactate transport studied in sarcolemmal giant vesicles: dependence on fibre type and age. Acta Physiol. Scand. 143: 361–365, 1991.
 116. Juel, C., S. Kristiansen, H. Pilegaard, J. Wojtaszewski, and E. A. Richter. Kinetics of lactate transport in sarcolemmal giant vesicles obtained from human skeletal muscle. J. Appl. Physiol. 76: 1031–1036, 1994.
 117. Juel, C., and F. Wibrand. Lactate transport in isolated mouse muscles studied with a tracer technique—kinetics, stereospecificity, pH dependency and maximal capacity. Acta Physiol. Scand. 137: 33–39, 1989.
 118. Kaplan, N. O., and J. Everse. Regulatory characteristics of lactate dehydrogenases. Adv. Enzyme Regul. 10: 323–336, 1972.
 119. Katz, A., and K. Sahlin. Effect of decreased oxygen availability on NADH and lactate content in human skeletal muscle during exercise. Acta Physiol. Scand. 131: 119–128, 1987.
 120. Katz, A., and K. Sahlin. Regulation of lactic acid production during exercise. J. Appl. Physiol. 65: 509–518, 1988.
 121. Katz, A., and K. Sahlin. Role of oxygen in regulation of glycolysis and lactate production in human skeletal muscle. Exerc. Sport Sci. Rev. 18: 1–28, 1990.
 122. Kayser, B., G. Ferretti, B. Grassi, T. Binzoni, and P. Cerretelli. Maximal lactic capacity at altitude: effect of bicarbonate loading. J. Appl. Physiol. 75: 1070–1074, 1993.
 123. Kennedy, F. G., and D. P. Jones. Oxygen dependence of mitochondrial function in isolated rat cardiac myocytes. Am.J. Physiol. 250 (Cell Physiol. 19): C374–C383, 1986.
 124. Klip, A., T. Ramlal, D. A. Young, and J. O. Holloszy. Insulin‐induced translocation of glucose transporters in rat hindlimb muscles. FEBS Lett. 224: 230, 1987.
 125. Knight, D. R., W. Schaffartzik, D. C. Poole, M. C. Hogan, D. E. Bebout, and P. D. Wagner. Effects of hyperoxia on maximal leg O2 supply and utilization in men. J. Appl. Physiol. 75: 2586–2594, 1993.
 126. Krisanda, J. M., T. S. Moreland, and M. J. Kushmerick. ATP supply and demand during exercise. In: Exercise, Nutrition, and Energy Metabolism, edited by E. S. Horton and R. L. Terjung. New York: Macmillan Publishing Company, 1988, p. 27–44.
 127. Krützfeldt, A., R. Spahr, S. Mertens, B. Siegmund, and H. M. Piper. Metabolism of exogenous substrates by coronary endothelial cells in culture. J. Mol. Cell. Cardiol. 22: 1393–1404, 1990.
 128. Kuikka, J., M. Levin, and J. B. Bassingthwaighte. Multiple tracer dilution estimates of d‐ and 2‐deoxy‐d‐glucose uptake by the heart. Am. J. Physiol. 250 (Heart Circ. Physiol. 19): H29–H42, 1986.
 129. Kushmerick, M. J. Energetics of muscle contraction. In: Handbook of Physiology, Skeletal Muscle, edited by L. D. Peachey. Bethesda, MD: Am. Physiol. Soc., 1983, p. 189–236.
 130. Linnarsson, D., J. Karlsson, N. Fagraeus, and B. Saltin. Muscle metabolites and oxygen deficit with exercise in hypoxia and hyperoxia. J. Appl. Physiol. 36: 399–402, 1974.
 131. MacLaren, D. P. M., H. Gibson, M. Parry‐Billings, and R. H. T. Edwards. A review of metabolic and physiological factors in fatigue. Exerc. Sport Sci. Rev. 17: 29–66, 1989.
 132. MacRae, H. S.‐H., S. C. Dennis, A. N. Bosch, and T. D. Noakes. Effects of training on lactate production and removal during progressive exercise in humans. J. Appl. Physiol. 72: 1649–1656, 1992.
 133. Matheson, G. O., P. S. Allen, D. C. Ellinger, C. C. Hanstock, D. Gheorghiu, D. C. McKenzie, C. Stanley, W. S. Parkhouse, and P. W. Hochachka. Skeletal muscle metabolism and work capacity: a 31P‐NMR study of Andean natives and lowlanders. J. Appl. Physiol. 70: 1963–1976, 1991.
 134. Mazzeo, R. S., P. R. Bender, G. A. Brooks, G. E. Butterfield, B. M. Groves, J. R. Sutton, E. E. Wolfel, and J. T. Reeves. Arterial catecholamine responses during exercise with acute and chronic high‐altitude exposure. Am. J. Physiol. 261 (Endocrinol. Metab. 24): E419–E424, 1991.
 135. Mazzeo, R. S., G. A. Brooks, G. E. Butterfield, A. Cymerman, A. C. Roberts, M. Selland, E. E. Wolfel, and J. T. Reeves. β‐Adrenergic blockade does not prevent the lactate response to exercise after acclimatization to high altitude. J. Appl. Physiol. 76: 610–615, 1994.
 136. Mazzeo, R. S., G. A. Brooks, D. A. Schoeller, and T. F. Budinger. Disposal of blood [1‐13C]lactate in humans during rest and exercise. J. Appl. Physiol. 60: 232–241, 1986.
 137. Mazzeo, R. S., and P. Marshall. Influence of plasma catecholamines on the lactate threshold during graded exercise. J. Appl. Physiol. 67: 1319–1322, 1989.
 138. McCartney, N., G. J. F. Heigenhauser, and N. L. Jones. Effects of pH on maximal power output and fatigue during short‐term dynamic exercise. J. Appl. Physiol. 55: 225–229, 1983.
 139. McCullagh, K. J. A., and A. Bonen. L(+)‐Lactate binding to a protein in rat skeletal muscle plasma membranes. Can. J. Appl. Physiol. 20: 112–124, 1995.
 140. McDermott, J. C., and A. Bonen. Lactate transport by skeletal muscle sarcolemmal vesicles. Mol. Cell. Biochem. 122: 113–121, 1993.
 141. McDermott, J. C., and A. Bonen. Endurance training increases skeletal muscle lactate transport. Acta Physiol. Scand. 147: 323–327, 1993.
 142. McDermott, J. C., and A. Bonen. Lactate transport in rat sarcolemmal vesicles and intact skeletal muscle, and after muscle contraction. Acta Physiol. Scand. 151: 17–28, 1994.
 143. McLane, J. A., and J. O. Holloszy. Glycogen synthesis from lactate in the three types of skeletal muscle. J. Biol. Chem. 254: 6548–6553, 1979.
 144. Meyer, R. A., and J. M. Foley. Testing models of respiratory control in skeletal muscle. Med. Sci. Sports Exerc. 26: 52–57, 1994.
 145. Moritani, T., T. Takaishi, and T. Matsumoto. Determination of maximal power output at neuromuscular fatigue threshold. J. Appl. Physiol. 74: 1729–1734, 1993.
 146. Morrow, J. A., R. D. Fell, and L. B. Gladden. Respiratory alkalosis: no effect on blood lactate decline or performance. Eur. J. Appl. Physiol. 58: 175–181, 1988.
 147. Nagesser, A. S., W. J. van der Laarse, and G. Elzinga. Lactate efflux from fatigued fast‐twitch muscle fibres of Xenopus laevis under various extracellular conditions. J. Physiol. (Lond.) 481: 139–147, 1994.
 148. Nesher, R., I. E. Karl, and D. M. Kipnis. Dissociation of effects of insulin and contraction on glucose transport in rat epitrochlearis muscle. Am. J. Physiol. 249 (Cell Physiol. 18): C226–C232, 1985.
 149. Newgard, C. B., L. J. Hirsch, D. W. Foster, and J. D. McGarry. Studies on the mechanism by which exogenous glucose is converted into liver glycogen in the rat. A direct or an indirect pathway? J. Biol. Chem. 258: 8046–8052, 1983.
 150. Newman, E. V., D. B. Dill, H. T. Edwards, and F. A. Webster. The rate of lactic acid removal in exercise. Am. J. Physiol. 118: 457–462, 1937.
 151. Newsholme, E. A., and A. R. Leech. Biochemistry for the Medical Sciences. New York: John Wiley & Sons, 1983, p. 204–207.
 152. Paddle, B. M. A cytoplasmic component of pyridine nucleotide fluorescence in rat diaphragm: evidence from comparisons with flavoprotein fluorescence. Pflugers Arch. 404: 326–331, 1985.
 153. Pagliassotti, M. J., and C. M. Donovan. Influence of cell heterogeneity on skeletal muscle lactate kinetics. Am. J. Physiol. 258 (Endocrinol. Metab. 21): E625–E634, 1990.
 154. Pagliassotti, M. J., and C. M. Donovan. Role of cell type in net lactate removal by skeletal muscle. Am. J. Physiol. 258 (Endocrinol. Metab. 21): E635–E642, 1990.
 155. Pagliassotti, M. J., and C. M. Donovan. Glycogenesis from lactate in rabbit skeletal muscle fiber types. Am. J. Physiol. 258 (Regulatory Integrative Comp. Physiol. 27): R903–R911, 1990.
 156. Pilegaard, H., J. Bangsbo, E. A. Richter, and C. Juel. Lactate transport studied in sarcolemmal giant vesicles from human muscle biopsies: relation to training status. J. Appl. Physiol. 77: 1858–1862, 1994.
 157. Pilegaard, H., C. Juel, and F. Wibrand. Lactate transport studied in sarcolemmal giant vesicles from rats: effect of training. Am. J. Physiol. 264 (Endocrinol. Metab. 27): E156–E160, 1993.
 158. Podolin, D. A., P. A. Munger, and R. S. Mazzeo. Plasma catecholamines and lactate response during graded exercise with varied glycogen conditions. J. Appl. Physiol. 71: 1427–1433, 1991.
 159. Poole, D. C., L. B. Gladden, S. Kurdak, and M. C. Hogan. l‐(+)‐Lactate infusion into working dog gastrocnemius: no evidence lactate per se mediates Vo2 slow component. J. Appl. Physiol. 76: 787–792, 1994.
 160. Poole, R. C., and A. P. Halestrap. Identification and partial purification of the erythrocyte l‐lactate transporter. Biochem. J. 283: 855–862, 1992.
 161. Poole, R. C., and A. P. Halestrap. Transport of lactate and other monocarboxylates across mammalian plasma membranes. Am. J. Physiol. 264 (Cell Physiol. 33): C761–C782, 1993.
 162. Reeves, J. T., E. E. Wolfel, H. J. Green, R. S. Mazzeo, A. J. Young, J. R. Sutton, and G. A. Brooks. Oxygen transport during exercise at altitude and the lactate paradox: lessons from Operation Everest II and Pikes Peak. Exerc. Sport Sci. Rev. 20: 275–296, 1992.
 163. Richter, E. A., B. Kiens, B. Saltin, N. J. Christensen, and G. Savard. Skeletal muscle glucose uptake during dynamic exercise in humans: role of muscle mass. Am. J. Physiol. 254 (Endocrinol. Metab. 17): E555–E561, 1988.
 164. Roos, A. Intracellular pH and distribution of weak acids across cell membranes. A study of D‐ and L‐lactate and of DMO in rat diaphragm. J. Physiol. (Lond.) 249: 1–25, 1975.
 165. Rosser, B. W. C., and P. W. Hochachka. Metabolic capacity of muscle fibers from high‐altitude natives. Eur. J. Appl. Physiol. 67: 513–517, 1993.
 166. Roth, D. A. The sarcolemmal lactate transporter: transmembrane determinants of lactate flux. Med. Sci. Sports Exerc. 23: 925–934, 1991.
 167. Roth, D. A., and G. A. Brooks. Lactate transport is mediated by a membrane‐bound carrier in rat skeletal muscle sarcolemmal vesicles. Arch. Biochem. Biophys. 279: 377–385, 1990.
 168. Roth, D. A., and G. A. Brooks. Lactate and pyruvate transport is dominated by a pH gradient‐sensitive carrier in rat skeletal muscle sarcolemmal vesicles. Arch. Biochem. Biophys. 279: 386–394, 1990.
 169. Roth, D. A., and G. A. Brooks. Training does not affect zero‐trans lactate transport across mixed rat skeletal muscle sarcolemmal vesicles. J. Appl. Physiol. 75: 1559–1565, 1993.
 170. Rowell, L. B. Human cardiovascular adjustments to exercise and thermal stress. Physiol. Rev. 54: 75–159, 1972.
 171. Rowell, L. B., J. R. Blackmon, M. A. Kenny, and P. Escourrou. Splanchnic vasomotor and metabolic adjustments to hypoxia and exercise in humans. Am. J. Physiol. 247 (Heart Circ. Physiol. 16): H251–H258, 1984.
 172. Rumsey, W. L., C. Schlosser, E. M. Nuutinen, M. Robiolio, and D. F. Wilson. Cellular energetics and the oxygen dependence of respiration in cardiac myocytes isolated from adult rat. J. Biol. Chem. 265: 15392–15399, 1990.
 173. Sahlin, K. NADH in human skeletal muscle during short‐term intense exercise. Pflugers Arch. 403: 193–196, 1985.
 174. Sahlin, K., A. Katz, and J. Henriksson. Redox state and lactate accumulation in human skeletal muscle during dynamic exercise. Biochem. J. 245: 551–556, 1987.
 175. Saltin, B., E. Nygaard, and B. Rasmussen. Skeletal muscle adaptation in man following prolonged exposure to high altitude. Acta Physiol. Scand. 109: 31A, 1980.
 176. Shiota, M., S. Golden, and J. Katz. Lactate metabolism in the perfused rat hindlimb. Biochem. J. 222: 281–292, 1984.
 177. Skelton, M. S., D. E. Kremer, E. W. Smith, and L. B. Gladden. Lactate influx into red blood cells of athletic and non‐athletic species. Am. J. Physiol. 268 (Regulatory Integrative Comp. Physiol. 37): R1121–R1128, 1995.
 178. Slentz, C. A., E. A. Gulve, K. J. Rodnick, E. J. Henriksen, J. H. Youn, and J. O. Holloszy. Glucose transporters and maximal transport are increased in endurance‐trained rat soleus. J. Appl. Physiol. 73: 486–492, 1992.
 179. Smith, E. W., M. S. Skelton, and L. B. Gladden. Plasma to red blood cell lactate distribution in high and low intensity steady‐state exercise. Med. Sci. Sports Exerc. 26 (Suppl.): S35, 1994.
 180. Smith, E. W., M. S. Skelton, D. E. Kremer, and L. B. Gladden. Effect of increment duration on blood lactate distribution during graded exercise. FASEB J. 9: A359, 1995.
 181. Spriet, L. L. Phosphofructokinase activity and acidosis during short‐term tetanic contractions. Can. J. Physiol. Pharmacol. 69: 298–304, 1991.
 182. Spriet, L. L., M. I. Lindinger, G. J. F. Heigenhauser, and N. L. Jones. Effects of alkalosis on skeletal muscle metabolism and performance during exercise. Am. J. Physiol. 252 (Regulatory Integrative Comp. Physiol. 21): R833–R839, 1986.
 183. Spriet, L. L., C. G. Matsos, S. J. Peters, G. J. F. Heigenhauser, and N. L. Jones. Effects of acidosis on rat muscle metabolism and performance during heavy exercise. Am. J. Physiol. 248 (Cell Physiol. 17): C337–C347, 1985.
 184. Stainsby, W. N., and G. A. Brooks. Control of lactic acid metabolism in contracting muscles and during exercise. Exerc. Sport Sci. Rev. 18: 29–63, 1990.
 185. Stainsby, W. N., and P. D. Eitzman. Lactic acid output of cat gastrocnemius‐plantaris during repetitive twitch contractions. Med. Sci. Sports Exerc. 18: 668–673, 1986.
 186. Stainsby, W. N., and H. G. Welch. Lactate metabolism of contracting dog skeletal muscle in situ. Am. J. Physiol. 211: 177–183, 1966.
 187. Stanley, W. C., E. W. Gertz, J. A. Wisneski, D. L. Morris, R. A. Neese, and G. A. Brooks. Systemic lactate kinetics during graded exercise in man. Am. J. Physiol. 249 (Endocrinol. Metab. 12): E595–E602, 1985.
 188. Stanley, W. C., E. W. Gertz, J. A. Wisneski, R. A. Neese, D. L. Morris, and G. A. Brooks. Lactate extraction during net lactate release by the exercising legs of man. J. Appl. Physiol. 60: 1116–1120, 1986.
 189. Stone, H. L., and I. Y. S. Liang. Cardiovascular response and control during exercise. Am. Rev. Respir. Dis. 129 (Suppl.): S13–S16, 1984.
 190. Sussman, I., M. Erecinska, and D. F. Wilson. Regulation of cellular energy metabolism: the Crabtree effect. Biochim. Biophys. Acta 591: 209–223, 1980.
 191. Sutton, J. R., N. L. Jones, and L. G. C. E. Pugh. Exercise at altitude. Annu. Rev. Physiol. 45: 427–437, 1983.
 192. Sutton, J. R., J. T. Reeves, P. D. Wagner, B. M. Groves, A. Cymerman, M. K. Malconian, P. B. Rock, P. M. Young, S. D. Walter, and C. S. Houston. Operation Everest II: oxygen transport during exercise at extreme simulated altitude. J. Appl. Physiol. 64: 1309–1321, 1988.
 193. Taylor, C. R., R. H. Karas, E. R. Weibel, and H. Hoppeler. Adaptive variation in the mammalian respiratory system in relation to energetic demand: II. Reaching the limits to oxygen flow. Respir. Physiol. 69: 7–26, 1987.
 194. Unkefer, C. J., R. M. Blazer, and R. E. London. In vivo determination of the pyridine nucleotide reduction charge by carbon‐13 nuclear magnetic resonance spectroscopy. Science 222: 62–85, 1983.
 195. Vogel, J. A., and M. A. Gleser. Effect of carbon monoxide on oxygen transport during exercise. J. Appl. Physiol. 32: 234–239, 1972.
 196. Waddell, W. J., and R. G. Bates. Intracellular pH. Physiol. Rev. 49: 285–329, 1969.
 197. Wagner, P. D., G. E. Gale, R. E. Moon, J. R. Torre‐Bueno, B. W. Stolp, and H. H. Saltzman. Pulmonary gas exchange in humans exercising at sea level and simulated altitude. J. Appl. Physiol. 61: 260–270, 1986.
 198. Wasserman, K. The anaerobic threshold measurement to evaluate exercise performance. Am. Rev. Respir. Dis. 129 (Suppl.): S35–S40, 1984.
 199. Wasserman, K. Anaerobiosis, lactate, and gas exchange during exercise: the issues. Federation Proc. 45: 2904–2909, 1986.
 200. Wasserman, K., B. J. Whipp, S. N. Koyal, and W. L. Beaver. Anaerobic threshold and respiratory gas exchange during exercise. J. Appl. Physiol. 35: 236–243, 1973.
 201. Watt, P. W., L. B. Gladden, H. S. Hundal, and R. E. Crawford. Effects of flow and contraction on lactate transport in the perfused rat hindlimb. Am. J. Physiol. 267 (Endocrinol. Metab. 30): E7–E13, 1994.
 202. Watt, P. W., P. A. MacLennan, H. S. Hundal, C. M. Kuret, and M. J. Rennie. L(+)‐Lactate transport in perfused rat skeletal muscle: kinetic characteristics and sensitivity to pH and transport inhibitors. Biochim. Biophys. Acta 944: 213–222, 1988.
 203. Welch, H. G. Hyperoxia and human performance: a brief review. Med. Sci. Sports Exerc. 14: 253–262, 1982.
 204. Welch, H. G., F. Bonde‐Petersen, T. Graham, K. Clausen, and N. Secher. Effects of hyperoxia on leg blood flow and metabolism during exercise. J. Appl. Physiol. 44: 385–390, 1977.
 205. Wendt, I. R., and J. B. Chapman. Fluorometric studies of recovery metabolism of rat fast‐ and slow‐twitch muscles. Am. J. Physiol. 230: 1644–1649, 1976.
 206. West, J. B. Lactate during exercise at extreme altitude. Federation Proc. 45: 2953–2957, 1986.
 207. West, J. B. Acid–base status and blood lactate at extreme altitude. In: Hypoxia, Metabolic Acidosis, and the Circulation, edited by A. I. Arieff. New York: Oxford University Press, 1992, p. 33–44.
 208. West, J. B., S. J. Boyer, D. J. Graber, P. H. Hackett, K. H. Maret, J. S. Milledge, R. M. Peters, Jr., C. J. Pizzo, M. Samaja, F. H. Sarnquist, R. B. Schoene, and R. M. Winslow. Maximal exercise at extreme altitudes on Mount Everest. J. Appl. Physiol. 55: 688–698, 1983.
 209. Wibrand, F., and C. Juel. Reconstitution of the lactate carrier from rat skeletal‐muscle sarcolemma. Biochem. J. 299: 533–537, 1994.
 210. Wilson, D. F. Factors affecting the rate and energetics of mitochondrial oxidative phosphorylation. Med. Sci. Sports Exerc. 26: 37–43, 1994.
 211. Wilson, D. F., M. Erecińska, C. Drown, and I. A. Silver. The oxygen dependence of cellular energy metabolism. Arch. Biochem. Biophys. 195: 485–493, 1979.
 212. Wilson, D. F., C. S. Owen, and M. Erecinska. Quantitative dependence of mitochondrial oxidative phosphorylation on oxygen concentration: a mathematical model. Arch. Biochem. Biophys. 195: 494–504, 1979.
 213. Wolfel, E. E., B. M. Groves, G. A. Brooks, G. E. Butterfield, R. S. Mazzeo, L. G. Moore, J. R. Sutton, P. R. Bender, T. E. Dahms, R. E. McCullough, R. G. McCullough, S.‐Y. Huang, S.‐F. Sun, R. F. Grover, H. N. Hultgren, and J. T. Reeves. Oxygen transport during steady‐state submaximal exercise in chronic hypoxia. J. Appl. Physiol. 70: 1129–1136, 1991.
 214. Woodson, R. D., R. E. Wills, and C. Lenfant. Effect of acute and established anemia on transport at rest, submaximal and maximal work. J. Appl. Physiol. 44: 36–43, 1978.
 215. Young, A. J., W. J. Evans, A. Cymerman, K. B. Pandolf, J. J. Knapik, and J. T. Maher. Sparing effect of chronic high‐altitude exposure on muscle glycogen utilization. J. Appl. Physiol. 52: 857–862, 1982.
 216. Young, A. J., W. J. Evans, E. C. Fisher, R. L. Sharp, D. L. Costill, and J. T. Maher. Skeletal muscle metabolism of sea‐level natives following short‐term high‐altitude residence. Eur. J. Appl. Physiol. 52: 463–466, 1984.
 217. Young, A. J., P. M. Young, R. E. McCullough, L. G. Moore, A. Cymerman, and J. T. Reeves. Effect of beta‐adrenergic blockade on plasma lactate concentration during exercise at high altitude. Eur. J. Appl. Physiol. 63: 315–322, 1991.
 218. Yudilevich, D. L., and G. E. Mann. Unidirectional uptake of substrates at the blood side of secretory epithelia: stomach, salivary gland, pancreas. Federation Proc. 41: 3045–3053, 1982.

Contact Editor

Submit a note to the editor about this article by filling in the form below.

* Required Field

Article Title: Lactate Transport and Exchange During Exercise
 

How to Cite

L. Bruce Gladden. Lactate Transport and Exchange During Exercise. Compr Physiol 2011, Supplement 29: Handbook of Physiology, Exercise: Regulation and Integration of Multiple Systems: 614-648. First published in print 1996. doi: 10.1002/cphy.cp120114