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Metabolic Defense Adaptations to Hypobaric Hypoxia in Man

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Abstract

The sections in this article are:

1 Adaptation and its Interplay with Time
2 Hypoxia Adaptations in Muscle Metabolism
3 Adaptation of Output and of Regulation
4 Hypoxia Adaptations in Cardiac Metabolism
5 Hypoxia Adaptations in Brain Metabolism
6 Hypoxia Adaptation in Man: Toward Unraveling the Integrated Response
7 Evaluating Tissue‐Specific Metabolic Adaptations Against Hypoxia
References
 1. Arthur, P. G., M. C. Hogan, D. E. Bebout, P. D. Wagner, and P. W. Hochachka. Modelling effects of hypoxia on ATP turnover in exercising muscle. J. Appl. Physiol. 73: 737–742, 1992.
 2. Balaban, R. S. Regulation of oxidative phosphorylation in the mammalian cell. Am. J. Physiol. 258 (Cell Physiol. 27): C377–C389, 1990.
 3. Barrett, E. J., R. G. Schwartz, C. K. Francis, and B. L. Zaret. Regulation by insulin of myocardial glucose and fatty acid metabolism in the conscious dog. J. Clin. Invest. 74: 1073–1079.
 4. Brindle, K. M., M. J. Blackledge, R. A. J. Challis, G. K. Radda. 31P NMR Magnetization transfer measurements of ATP turnover during steady‐state isometric muscle contraction in the rat hind limb in vivo. Biochemistry 28: 4887–4893, 1989.
 5. Callow, M. A., M. Morton, and M. Guppy. Marathon fatigue: the role of plasma free fatty acids, muscle glycogen, and blood glucose. Eur. J. Appl. Physiol. 55: 654–661, 1986.
 6. Cerretelli, P., B. Kayser, H. Hoppeler, D. Pette. Muscle morphometry and enzymes in acclimatization. In: Hypoxia—The Adaptations edited by Sutton, J. R., G. Coates, and J. E. Remmers. Toronto: B. C. Decker, 1990, p. 220–224.
 7. Connett, R. J. Analysis of metabolic control: new insights using scaled creatine kinase model. Am. J. Physiol. 254 (Regulatory Integrative Comp. Physiol. 23): R949–R959, 1988.
 8. Connett, R. J., and C. R. Honig. Regulation of V.O2max. Do current biochemical hypotheses fit the in vivo data? Am. J. Physiol. 256 (Regulatory Integrative Comp. Physiol. 25): R898–R906, 1989.
 9. Daut, J., and G. Elzinga. Substrate dependence of energy metabolism in isolated guinea pig cardiac muscle: a microcalorimetric study. J. Physiol. 413: 379–387, 1989.
 10. Drake, A. Substrate utilization in the myocardium. Basic Res. Cardiol. 19: 1–11, 1985.
 11. Edwards, H. T. Lactic acid in rest and work at high altitude. Am. J. Physiol. 116: 367–375, 1936.
 12. From, A. H. L., S. D. Zimmer, S. P. Michurski, P. Mohanakrishnan, V. K. Ulstad, W. J. Thomas, and K. Ugurbil. Regulation of oxidative phosphorylation in the intact cell. Biochemistry 29: 3733–3743, 1990.
 13. Funk, C. I., A. Clark, Jr., R. J. Connett. A simple model of metabolism: applications to work transitions in muscle. Am. J. Physiol. 258 (Cell Physiol. 27): C995–C1005, 1990.
 14. 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.
 15. Harik, S. I., R. E. Behmand, and J. C. Lamanna. Chronic hypobaric hypoxia increases the density of cerebral capillaries and their glucose transporter protein. J. Cerebr. Blood Flow Metab. 11: 5496, 1991.
 16. Henes, C. G., S. R. Bermann, M. N. Walsh, B. E. Sobel, and E. M. Geltman. Assessment of myocardial oxidative metabolic reserve with positron emission tomography and carbon‐II acetate. J. Nucl. Med. 30: 1489–1499, 1989.
 17. Hermansen, L., and O. Vaga. Lactate disappearance and glycogen synthesis in human muscle after maximal exercise. Am. J. Physiol. 233 (Endocrinol. Metab. Gastrointest. Physiol. 2): E422–E429, 1977.
 18. Hicks, R. J., W. H. Herman, V. Halff, E. Molina, E. R. Wolfe, G. Hutchins, and M. Schwaiger. Quantitative evaluation of regional substrate metabolism in the human heart by positron emission tomography. J. Am. Coll. Cardiol. 18: 101–111, 1991.
 19. Hochachka, P. W. Exercise limitations at high altitude: the metabolic problem and search for its solution. In: Circulation, Respiration, and Metabolism, edited by R. Gilles. Berlin: Springer‐Verlag, 1985, p. 240–249.
 20. Hochachka, P. W. The lactate paradox: analysis of underlying mechanisms. Ann. Sports Med. 4: 184–188, 1988.
 21. Hochachka, P. W. Metabolic biochemistry and the making of a mesopelagic mammal. Experientia 48: 570–575, 1992.
 22. Hochachka, P. W. The Monge legacy: learning from hypoxia adapted animals and man. In: Hipoxia—Investigaciones Basicas y Clinicas. Homenaje a Carlos Monge Cassinelli, edited by Leon‐Velarde, F., and A. Arregui, Lima: UPCH, 1993, p. 361–374.
 23. Hochachka, P. W., C. M. Clark, W. D. Brown, C. Stanley, C. Stone, R. J. Nickles, G. G. Zhu, P. S. Allen, J. E. Holden. The brain at high altitude: Hypometabolism as a defense against chronic hypoxia? J. Cerebr. Blood Flow Metab., 14: 671–679, 1994.
 24. Hochachka, P. W., and M. Guppy. Metabolic Arrest and the Control of Biological Time. Cambridge, MA: Harvard University Press, 1987, p. 1–227.
 25. Hochachka, P. W., T. P. Mommsen, J. H. Jones, and C. R. Taylor. Substrate and O2 fluxes during rest and exercise in a high‐altitude‐adapted animal, the llama. Am. J. Physiol. 253 (Regulatory Integrative Comp. Physiol. 22): R298–R305, 1987.
 26. Hochachka, P. W., and G. N. Somero. Biochemical Adaptation. Princeton University Press, Princeton, 1984, p. 1–537.
 27. 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.
 28. Hochachka, P. W., C. Stanley, D. C. McKenzie, A. Villena, and C. Monge. Enzyme mechanisms for pyruvate‐to‐lactate flux attentuation; a study of Sherpas, Quechuas, and Hummingbirds. Int. J. Sports Med. 23: S119–S122, 1992.
 29. Holden, J. E., W. D. Brown, C. Stone, C. Stanley, R. J. Nickles, and P. W. Hochachka. Enhanced cardiac metabolism of plasma glucose in high altitude natives. J. Appl. Physiol., 1995, in press.
 30. Hurtado, A., T. Velasquez, C. Reynafarje, R. Lozano, R. Chavez, H. A. Salazar, B. Reynafarje, C. Sanchez, and J. Munoz. Mechanisms of Natural Acclimatization. Studies on the Native Resident of Morococha, Peru, at an Altitude of 14,900 Feet. Randolph AFB, Texas: USAF School of Aviation Medicine, 1956, p. 1–62 (Rep. 56–1).
 31. Hutter, J. F., H. M. Piper, and P. G. Spieckermann. Effect of fatty acid oxidation on efficiency of energy production in rat heart. Am. J. Physiol. 249 (Heart Circ. Physiol. 18): H723–H728, 1985.
 32. Kanno, T., K. Sudo, I. Takeuchi, S. Kanda, N. Honda, and K. Oyama. Hereditary deficiency of lactate dehydrogenase M‐subunit. Clin. Chim. Acta 108: 267–276, 1980.
 33. Kayser, B., H. Hoppler, H. Classen, and P. Cerretelli. Muscle ultrastructure and performance capacities of Himalayan Sherpas. J. Appl. Physiol. 70: 1938–1942, 1991.
 34. Kollias, J., E. R. Buskirk, R. F. Akers, E. K. Prokop, P. T. Baker, and E. Picon‐Reatequi. Work capacity of longtime residents and newcomers to altitude. J. Appl. Physiol. 24: 792–799, 1968.
 35. Little, M. A., and J. M. Hanna. The response of high altitude populations to cold and other stresses. In: The Biology of High Altitude Peoples, edited by P. T. Baker. Cambridge, UK: Cambridge Univ. Press, 1978, p. 251–298.
 36. Marwick, T. H., W. J. MacIntyre, E. E. Salcedo, R. T. Go, G. Saha, and A. Beachler. Identification of ischemic and hibernating myocardium: feasibility of post‐exercise F‐18 deoxyglucose positron emission tomography. Cathet. Cardiovasc. Diagn. 22: 100–106, 1991.
 37. 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.
 38. Mayekawa, M., K. Sudo, S. S. Li, and T. Kanno. Genotypic analysis of families with lactate dehydrogenase A (M) deficiency by selective DNA amplification. Hum. Genet. 88: 34–38, 1991.
 39. McKenzie, C. D., L. S. Goodman, B. Davidson, C. C. Nath, G. O. Matheson, W. S. Parkhouse, P. W. Hochachka, P. S. Allen, C. Stanely, and W. Ammann. Cardiovascular adaptations in Andean natives after 6 wk of exposure to sea level. J. Appl. Physiol. 70: 2650–2655, 1991.
 40. McLellan, T., I. Jacobs, and W. Lewis. Acute altitude exposure and altered acid‐base status. I. Effects on exercise ventilation and blood lactate responses. Eur. J. Appl. Physiol. 57: 435–444, 1988.
 41. Monge, C. M. Acclimatization in the Andes. Baltimore, MD: John Hopkins University Press, 1948.
 42. Monge, C. M., and F. Leon‐Velarde. Physiological adaptation to high altitude: Oxygen transport in mammals and birds. Physiol. Rev. 71: 1135–1172, 1991.
 43. Moret, P. Myocardial metabolism: acute and chronic adaptation to hypoxia. Med. Sport Sci. 19: 48–63, 1985.
 44. Nioka, S., Z. Argov, G. P. Dobson, R. E. Forster, H. V. Subramanian, R. L. Veech, and B. Chance. Substrate regulation of mitochondrial oxidative phosphorylation in hypercapnic rabbit muscle. Am. J. Physiol. 72: 521–528, 1991.
 45. Rumsey, W. L., C. Schlosser, E. M. Nuutinen, M. Robiollo, and D. F. Wilson. Cellular energetics and the oxygen dependence of respiration in cardiac myocytes isolated from adult rate. J. Biol. Chem. 265: 15392–15402, 1990.
 46. Sutton, J. R. The hormonal responses to exercise at sea level and at altitude. In: Hypoxia, Exercise, and Altitude. New York: Liss, 1983, p. 325–358 (Proc. 3rd Banff Int. Hypoxia Symp.).
 47. 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.
 48. Van Hardeveld, C. Effects of thyroid hormone on oxygen consumption, heat production, and energy economy. In: Thyroid Hormone Metabolism, edited by G. Hennemann. New York: Dekker, 1986, p. 579–608.
 49. Vik‐Mo, H., and O. D. Mjos. Influence of free fatty acids on myocardial oxygen consumption and ischemic injury. Am. J. Cardiol. 48: 361–365, 1981.
 50. Way, A. B. Exercise capacity of high altitude Peruvian Quechua Indians migrant to low altitude. Hum. Biol. 48: 175–191, 1976.
 51. West, J. Lactate during exercise at extreme altitudes. Federation Proc. 45: 2953–2957, 1986.
 52. Winslow, R. M., and C. C. Monge. Hypoxia, Polycythemia and Chronic Mountain Sickness. Baltimore, MD: Johns Hopkins University Press, 1987.
 53. Young, A. J., W. J. Evans, A. Cymerman, K. B. Pandolf, J. J. Knapik, and J. T. Maher. Sparing effects of chronic high‐altitude exposure on muscle glycogen utilization. J. Appl. Physiol. 52: 857–862, 1982.
 54. Young, P. M., P. B. Rock, C. S. Fulco, L. A. Trad, V. A. Forte, Jr., and A. Cymerman. Altitude acclimation attenuates plasma ammonia accumulation during submaximal exercise. J. Appl. Physiol. 63: 758–764, 1988.
 55. Zivin, J. A., and D. W. Choi. Stroke therapy. Sci. Am. 265: 56–63, 1991.

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How to Cite

P. W. Hochachka. Metabolic Defense Adaptations to Hypobaric Hypoxia in Man. Compr Physiol 2011, Supplement 14: Handbook of Physiology, Environmental Physiology: 1115-1123. First published in print 1996. doi: 10.1002/cphy.cp040248