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. 1978 Sep;62(3):593–600. doi: 10.1172/JCI109165

Human llamas: adaptation to altitude in subjects with high hemoglobin oxygen affinity.

R P Hebbel, J W Eaton, R S Kronenberg, E D Zanjani, L G Moore, E M Berger
PMCID: PMC371804  PMID: 29054

Abstract

To assess the adaptive value of the right-shift of the oxyhemoglobin dissociation curve (decreased affinity for oxygen) observed in humans upon altitude exposure, the short-term physiologic responses to altitude-induced hypoxia were evaluated in two subjects with a high oxygen affinity hemoglobin (Hb Andrew-Minneapolis) and in two of their normal siblings. In striking contrast to normal subjects, at moderately high altitude (3,100 m) the high affinity subjects manifested: (a) lesser increments in resting heart rate; (b) minimal increases in plasma and urinary erythropoietin; (c) no decrement in maximal oxygen consumption; and (d) no thrombocytopenia. There was no difference between subject pairs in 2,3-diphosphoglycerate response to altitude exposure. These results tend to contradict the belief that a decrease in hemoglobin oxygen affinity is of adaptive value to humans at moderate altitudes. Rather, they support the hypothesis that, despite disadvantages at low altitude, a left-shifted oxyhemoglobin dissociation curve may confer a degree of preadaptation to altitude.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adamson J. W., Finch C. A. Hemoglobin function, oxygen affinity, and erythropoietin. Annu Rev Physiol. 1975;37:351–369. doi: 10.1146/annurev.ph.37.030175.002031. [DOI] [PubMed] [Google Scholar]
  2. Adamson J. W., Parer J. T., Stamatoyannopoulos G. Erythrocytosis associated with hemoglobin Rainier: oxygen equilibria and marrow regulation. J Clin Invest. 1969 Aug;48(8):1376–1386. doi: 10.1172/JCI106103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Birks J. W., Klassen L. W., Gurney C. W. Hypoxia-induced thrombocytopenia in mice. J Lab Clin Med. 1975 Aug;86(2):230–238. [PubMed] [Google Scholar]
  4. Cerretelli P. Limiting factors to oxygen transport on Mount Everest. J Appl Physiol. 1976 May;40(5):658–667. doi: 10.1152/jappl.1976.40.5.658. [DOI] [PubMed] [Google Scholar]
  5. Clark B. J., Coburn R. F. Mean myoglobin oxygen tension during exercise at maximal oxygen uptake. J Appl Physiol. 1975 Jul;39(1):135–144. doi: 10.1152/jappl.1975.39.1.135. [DOI] [PubMed] [Google Scholar]
  6. Cooper G. W., Cooper B. Relationships between blood platelet and erythrocyte formation. Life Sci. 1977 May 1;20(9):1571–1579. doi: 10.1016/0024-3205(77)90450-7. [DOI] [PubMed] [Google Scholar]
  7. Eaton J. W., Brewer G. J., Grover R. F. Role of red cell 2,3-diphosphoglycerate in the adaptation of man to altitude. J Lab Clin Med. 1969 Apr;73(4):603–609. [PubMed] [Google Scholar]
  8. Eaton J. W. Oxygen affinity and environmental adaptation. Ann N Y Acad Sci. 1974 Nov 29;241(0):491–497. doi: 10.1111/j.1749-6632.1974.tb21905.x. [DOI] [PubMed] [Google Scholar]
  9. Eaton J. W., Skelton T. D., Berger E. Survival at extreme altitude: protective effect of increased hemoglobin-oxygen affinity. Science. 1974 Feb 22;183(4126):743–744. doi: 10.1126/science.183.4126.743. [DOI] [PubMed] [Google Scholar]
  10. Ekblom B., Goldbarg A. N., Gullbring B. Response to exercise after blood loss and reinfusion. J Appl Physiol. 1972 Aug;33(2):175–180. doi: 10.1152/jappl.1972.33.2.175. [DOI] [PubMed] [Google Scholar]
  11. Finch C. A., Lenfant C. Oxygen transport in man. N Engl J Med. 1972 Feb 24;286(8):407–415. doi: 10.1056/NEJM197202242860806. [DOI] [PubMed] [Google Scholar]
  12. Frisancho A. R. Functional adaptation to high altitude hypoxia. Science. 1975 Jan 31;187(4174):313–319. doi: 10.1126/science.1089311. [DOI] [PubMed] [Google Scholar]
  13. Gray G. W., Bryan A. C., Freedman M. H., Houston C. S., Lewis W. F., McFadden D. M., Newell G. Effect of altitude exposure on platelets. J Appl Physiol. 1975 Oct;39(4):648–652. doi: 10.1152/jappl.1975.39.4.648. [DOI] [PubMed] [Google Scholar]
  14. Grover R. F., Alexander J. K. Cardiac performance and the coronary circulation of main in chronic hypoxia. Cardiology. 1971;56(1):197–206. doi: 10.1159/000169361. [DOI] [PubMed] [Google Scholar]
  15. Grover R. F., Reeves J. T., Grover E. B., Leathers J. E. Muscular exercise in young men native to 3,100 m altitude. J Appl Physiol. 1967 Mar;22(3):555–564. doi: 10.1152/jappl.1967.22.3.555. [DOI] [PubMed] [Google Scholar]
  16. Hebbel R. P., Kronenberg R. S., Eaton J. W. Hypoxic ventilatory response in subjects with normal and high oxygen affinity hemoglobins. J Clin Invest. 1977 Nov;60(5):1211–1215. doi: 10.1172/JCI108874. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hermansen L., Osnes J. B. Blood and muscle pH after maximal exercise in man. J Appl Physiol. 1972 Mar;32(3):304–308. doi: 10.1152/jappl.1972.32.3.304. [DOI] [PubMed] [Google Scholar]
  18. Keitt A. S. Reduced nicotinamide adenine dinucleotide-linked analysis of 2,3-diphosphoglyceric acid: spectrophotometric and fluorometric procedures. J Lab Clin Med. 1971 Mar;77(3):470–475. [PubMed] [Google Scholar]
  19. Langdon J. R., McDonald T. P. Effects of chronic hypoxia on platelet production in mice. Exp Hematol. 1977 May;5(3):191–198. [PubMed] [Google Scholar]
  20. Lenfant C., Sullivan K. Adaptation to high altitude. N Engl J Med. 1971 Jun 10;284(23):1298–1309. doi: 10.1056/NEJM197106102842305. [DOI] [PubMed] [Google Scholar]
  21. Lenfant C., Torrance J., English E., Finch C. A., Reynafarje C., Ramos J., Faura J. Effect of altitude on oxygen binding by hemoglobin and on organic phosphate levels. J Clin Invest. 1968 Dec;47(12):2652–2656. doi: 10.1172/JCI105948. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. PUGH L. G., GILL M. B., LAHIRI S., MILLEDGE J. S., WARD M. P., WEST J. B. MUSCULAR EXERCISE AT GREAT ALTITUDES. J Appl Physiol. 1964 May;19:431–440. doi: 10.1152/jappl.1964.19.3.431. [DOI] [PubMed] [Google Scholar]
  23. Rowell L. B. Human cardiovascular adjustments to exercise and thermal stress. Physiol Rev. 1974 Jan;54(1):75–159. doi: 10.1152/physrev.1974.54.1.75. [DOI] [PubMed] [Google Scholar]
  24. Thorling E. B., Erslev A. J. The "tissue" tension of oxygen and its relation to hematocrit and erythropoiesis. Blood. 1968 Mar;31(3):332–343. [PubMed] [Google Scholar]
  25. Torrance J. D., Lenfant C., Cruz J., Marticorena E. Oxygen transport mechanisms in residents at high altitude. Respir Physiol. 1970;11(1):1–15. doi: 10.1016/0034-5687(70)90098-8. [DOI] [PubMed] [Google Scholar]
  26. Turek Z., Kreuzer F., Hoofd L. J. Advantage or disadvantage of a decrease of blood oxygen affinity for tissue oxygen supply at hypoxia. A theoretical study comparing man and rat. Pflugers Arch. 1973 Aug 27;342(3):185–197. doi: 10.1007/BF00591367. [DOI] [PubMed] [Google Scholar]
  27. Wood S. C., Johansen K. Adaptation to hypoxia by increased HbO 2 affinity and decreased red cell ATP concentration. Nat New Biol. 1972 Jun 28;237(78):278–279. doi: 10.1038/newbio237278a0. [DOI] [PubMed] [Google Scholar]
  28. Wood S. C., Johansen K., Weber R. E. Effects of ambient PO2 on hemoglobin-oxygen affinity and red cell ATP concentrations in a benthic fish, Pleuronectes platessa. Respir Physiol. 1975 Dec;25(3):259–267. doi: 10.1016/0034-5687(75)90002-x. [DOI] [PubMed] [Google Scholar]
  29. Zak S. J., Brimhall B., Jones R. T., Kaplan M. E. Hemoglobin Andrew-Minneapolis alpha 2 A beta 2 144 Lys leads to Asn: a new high-oxygen-affinity mutant human hemoglobin. Blood. 1974 Oct;44(4):543–549. [PubMed] [Google Scholar]
  30. Zanjani E. D., Lutton J. D., Hoffman R., Wasserman L. R. Erythroid colony formation by polycythemia vera bone marrow in vitro. Dependence on erythropoietin. J Clin Invest. 1977 May;59(5):841–848. doi: 10.1172/JCI108706. [DOI] [PMC free article] [PubMed] [Google Scholar]

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