Abstract
My interest in acclimatization to hypocapnia or chronic low \(\text{PA}_{\text{CO}_\text{2} }\) arose as a byproduct of my long interest in acclimatization to high altitude hypoxia, one of the two most common causes of chronic hypocapnia. (The other is pregnancy.) I used to think that the ventilatory aspects of acclimatization to high altitude simply represented ventilatory acclimatization to chronic hypocapnia. The latter would be produced by the hyperventilation resulting from hypoxic stimulation of the peripheral chemoreceptors. This is a very old idea, certainly not original with me. The best evidence for it came from the classic studies of Brown, Hemingway, and Visscher [1950], who showed that 24 hr of passive hyperventilation in a body respirator caused a readjustment in the regulation of breathing such that the \(\text{PA}_{\text{CO}_\text{2} }\) was regulated at a lower level when spontaneous breathing was resumed. Such a shift in the regulation of Pco2 has become the classic sign of ventilatory acclimatization to hypocapnia, my subject for today. Since hypoxia stimulates hyperventilation and would produce chronic hypocapnia, it was thought that the shift in regulation of CO2 at altitude was simply the experiment of Brown et al., with hypoxia taking the role of the respirator. About a decade ago I wrote a review (KELLOGG [I960]) that strongly supported this view, and I have been forced to change my mind. I propose today to review the evidence that has changed my thinking.
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Bibliography
Brown, E. B., Jr., Hemingway, A., and Visscher, M. B., “Arterial blood pH and pCO2 changes in response to CO2 inhalation after 24 hours of passive hyperventilation.” J. Appl. Physiol. 2:544–48 (1950).
Chiodi, H., “Respiratory adaptations to chronic high altitude hypoxia.” J. Appl. Physiol. 10:81–87 (1957).
Cohen, P. J., Alexander, S. C., Smith, T. C., Reivich, M., and Wollman, H., “Effects of hypoxia and normocarbia on cerebral blood flow and metabolism in conscious man.” J. Appl. Physiol. 23:183–89 (1967).
Davenport, H. W., Brewer, G., Chambers, A. H., and Goldschmidt, S., “The respiratory responses to anoxemia of unanesthetized dogs with chronically denervated aortic and’ carotid chemoreceptors and their causes.’ Am. J. Physiol. 148:406–16 (1947).
Eger, E. I., II, Kellogg, R. H., Mines, A. H., Lima-Ostos, M., Morrill, C. G., and Kent, D. W., “Influence of CO2 on ventilatory acclimatization to altitude.” J. Appl. Physiol. 24:607–15 (1968).
Gilfillan, R. S., Hansen, J. T., Kellogg, R. H., Pace, N., and Cuthbertson, E. M., “Physiologic study of the chemoreceptor mechanism in the dog at sea level and at high altitude (12,600 ft.).” Circulation 18:724 (1958).
Kellogg, R. H., “Acclimatization to carbon dioxide.” Anesthesiology. 21:634–41 (1960).
Kellogg, R. H., “The role of CO2 in altitude acclimatization.” In The regulation of human respiration, D. J. C. Cunningham and B. B. Lloyd, eds. Oxford: Blackwell (1963).
Lloyd, B. B., Jukes, M. G. M., Cunningham, D. J. C., “The relation between alveolar oxygen pressure and the respiratory response to carbon dioxide in man.” Quart. J. Exptl. Physiol. 43:214–27 (1958).
Milledge, J. S., and Lahiri, S., “Respiratory control in lowlanders and Sherpa high-landers at altitude.” Resp. Physiol. 2:310–22 (1967).
Mines, A. H. Ventilatory regulation in goats at high altitude. (Ph.D. Dissertation). San Francisco: University of California (1968). [Dissertation Abstracts International B 31 (No. 1): 368B-69B, July 1970.]
Mines, A. H. and Sørensen, S. C., “Changes in the electrochemical potential difference for HCO3 − between blood and cerebrospinal fluid and in cerebrospinal fluid lactate concentration during isocarbic hypoxia.” Acta Physiol. Scand. 81:225–33 (1971).
Morrill, C. G., Cerebrospinal fluid changes and exercise effects in ventilatory acclimatization to hypoxia. (Ph.D. Dissertation). San Francisco: University of California (1970).
Plum, F., and Posner, J. B., “Blood and cerebrospinal fluid lactate during hyperventilation.” Am. J. Physiol. 212:864–70 (1967).
Plum, F., Posner, J. B., and Smith, W. W., “Effect of hyperbaric-hyperoxic hyperventilation on blood, brain, and CSF lactate.” Am. J. Physiol. 215:1240–44 (1968).
Severinghaus, J. W., Mitchell, R. A., Richardson, B. W., and Singer, M. M., “Respiratory control at high altitude suggesting active transport regulation of CSF.” J. Appl. Physiol. 18:1155–66 (1963).
Severinghaus, J. W., Bainton, C. R., and Carcelen, A., “Respiratory insensitivity to hypoxia in chronically hypoxic man.” Resp. Physiol. 1:308–34 (1966).
Siesjö, B. K, and Sorensen, S. C., eds. Ion homeostasis of the brain. Copenhagen, Munksgaard, and New York: Academic Press (1971).
Sørensen, S. C., and Mines, A. H., “Ventilatory responses to acute and chronic hypoxia in goats after sinus nerve section.” J. Appl. Physiol. 28:832–35 (1970).
Sørensen, S. C., and Mines, A. H., “Ventilatory acclimatization to hypoxia in rabbits after denervation of peripheral chemoreceptors.” J. Appl. Physiol. 28:836–39 (1970).
Bibliography
Astrup, P., Jørgensen, K., Siggard Andersen, O., and Engel, K., “The acid-base metabolism. A new approach.” Lancet 1:1035–39 (1960).
Böning, D., “Veränderungen der CO2-Bindungs- kurve des Blutes bei akuter respiratorisches Acidose und ihre Ursachen. I. Untersuchungen an Hunden.” Pflüg. Arch. Physiol. 302:133–48 (1968).
Böning, D, and Heinrich, K. W., “Veränderungen der CO2-Bindungskurve des Blutes bei akuter respiratorischer Acidose und ihre Ursachen. II. Untersuchungen am Menschen.” Pflüg. Arch. Physiol. 303:162–72 (1968).
Döring, G. K., and Loeschcke, H. H., “Atmung und Säure-Basengleichgewicht in der Schwangerschaft.” Pflüg. Arch. Ges. Physiol. 249:437–51 (1947).
Eger, E. I., II, Kellogg, R. H., Mines, A. H., Lima-Ostos, M., Morrill, C. G., and Kent, D. W., “Influence of CO2 on ventilatory acclimatization to altitude.” J. Appl. Physiol. 24:607–15 (1968).
Eichenholz, A., Mulhausen, R. O., Anderson, W. E., and MacDonald, F. M., “Primary hypocapnia: a cause of metabolic acidosis.” J. Appl. Physiol. 17:283–88 (1962).
Engel, K, Kildeberg, P., and Winters, R. W., “Quantitative displacement of blood acid- base status in acute hypocapnia.” Scand. J. Clin. Lab. Invest. 23:5–17 (1969).
Kellogg, R. H., “The role of CO2 in altitude acclimatization.” pp. 379–85 in: The Regulation of Human Respiration, edited by D. J. C. Cunningham and B. B. Lloyd. Oxford: Blackwell (1963).
Kronenberg, R. S., and Cain, S. M., “Effects of acetazolamide and hypoxia on cerebrospinal fluid bicarbonate.” J. Appl. Physiol. 24:17–20 (1968).
Michel, C. C., Lloyd, B. B., and Cunningham, D. J. C., “The in vivo carbon dioxide dissociation curve of true plasma.” Resp. Physiol. 1:121–37 (1966).
Mines, A. H., and Sorensen, S. C., “Changes in the electrochemical potential difference for HCO3” between blood and cerebrospinal fluid and in cerebrospinal fluid lactate concentration during isocarbic hypoxia.” Acta Physiol. Scand. 81:225–33 (1971).
Morrill, C. G., “Cerebrospinal fluid changes and exercise effects in ventilatory acclimatization to hypoxia.” Doctoral dissertation. San Francisco: University of California (1970).
Papadopoulos, C. N., and Keats, A. S., “The metabolic acidosis of hyperventilation produced by controlled respiration.” Anesthesiology 20:156–61 (1959).
Pappenheimer, J. R., Fencl, V., Heisey, S. R., and Held, D., “Role of cerebral fluids in control of respiration as studied in unanes- thetized goats.” J. Appl. Physiol. 208:436–50 (1965).
Prys-Roberts, C., Kelman, G. R., and Nunn, J. F., “Determination of the in vivo carbon dioxide titration curve of anaesthetized man.” Brit. J. Anaesth. 38:500–509 (1966).
Riley, R. L., and Houston, C. S., “Composition of alveolar air and volume of pulmonary ventilation during long exposure to high altitude.” J. Appl. Physiol. 3:526–34 (1951).
Schneider, E. C., “Physiological observations following descent from Pike's Peak to Colorado Springs.” Am. J. Physiol. 32:295–308 (1913).
Shaw, L. A., and Messer, A. C., “The transfer of bicarbonate between the blood and tissues caused by alterations of the carbon dioxide concentration in the lungs.” Am. J. Physiol. 100:122–36 (1932).
Siggaard-Andersen, O., “Acute experimental acid-base disturbances in dogs. An investigation of the acid-base and electrolyte content of blood and urine.” Scand. J. Clin. Lab. Invest. 14, Suppl. 66:1–20 (1962).
Sørensen, S. C., and Mines, A. H., “Ventilatory responses to acute and chronic hypoxia in goats after sinus nerve section.” J. Appl. Physiol. 28:832–35 (1970).
Sørensen, S. C., and Mines, A. H.. “Ventilatory acclimatization to hypoxia in rabbits after denervation of peripheral chemoreceptors.” J. Appl. Physiol. 28:836–39 (1970).
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Kellogg, R.H. (1974). Adaptation to Hypocapnia and its Role in Adaptation to Hypoxia. In: Nahas, G., Schaefer, K.E. (eds) Carbon Dioxide and Metabolic Regulations. Topics In Environmental Physiology And Medicine. Springer, New York, NY. https://doi.org/10.1007/978-1-4612-9831-1_28
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DOI: https://doi.org/10.1007/978-1-4612-9831-1_28
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