Metabolic Effects of Acute Hypoxia on Brain
187
acts were impaired in rats breathing 5 % O 2 in N 2 . It will be recalled that
no significant decrease in brain A TP concentration could be detected in
anesthetized rats breathing even lower oxygen concentrations for periods
of time approximateh c equal to those required for the tests of learning and
performance. Rats acclimatized to simulated high altitude showed much
less hypoxic impairment of learning and performance than did non-acclimatized animals, but rats made acutely polycythemic by transfusion of
erythrocyte suspensions showed no such superiority. Polycythemia apparently must be accompanied by a compensatory increase in tissue vascularization if oxygen transport is to be increased.
Discussion,' There is a continuing need for accurate means of detecting
hypoxia and of measuring its severity. Ideal tests should be applicable to
unanesthetized subjects and should differentiate the degree of oxygen deficiency in various organs and sYstems. The difficulties in achieving these
goals are conceptual as well as technical. It is necessary first to determine the
significance of the various intracellular responses to fluctuations in oxygen
supply before they can be used as test items. When this has been accomplished, the next step should be the devising of functional tests for individual
organs and sYstems which can be validated against the intracellular criteria
of oxygen deficiencv'.
The studies reviewed in this paper were directed toward both of these goals
as they applY to one organ, the brain. They lead to several conclusions
which may point the way to a more penetrating analysis of this complex
problem.
It is recognized that the most valuable single item of information in
studies on cellular hypoxia would be the intracellular oxygen tension. At
the present time this information is very incomplete and largely inferential.
Oxygen microclectrodes inserted blindly into tissues measure oxygen
tensions of unknown significance, since the spatial relations between electrode tip, blood vessels and cells are unknown. Substituting the term
"oxygen availabilitv" for "oxvgen tension" accomplishes little except to
emphasize the influence of blood flow on the measurements. It is now
technically possible to insert oxygen microelectrodes, having tip diameters
of 1 micron or less, directlv' into cells and to verify the intracellular position
by recording the potential change on penetration of the cell membrane.
In addition to measurements of intracellular oxygen tension it would be
highly desirable to have measurements of oxygen tension gradients along
the diffusion path from blood to cells; this will be a far more difficult problem, however, and it will probably require direct visualization techniques
similar to those used in kidney micropuncture studies.
The measurements of metabolic changes in the brain during hypoxia
highlight the semantic difficulties in defining intracellular hypoxia. When
is a cell hypoxic? The ATP concentration may be well-maintained when the
187
acts were impaired in rats breathing 5 % O 2 in N 2 . It will be recalled that
no significant decrease in brain A TP concentration could be detected in
anesthetized rats breathing even lower oxygen concentrations for periods
of time approximateh c equal to those required for the tests of learning and
performance. Rats acclimatized to simulated high altitude showed much
less hypoxic impairment of learning and performance than did non-acclimatized animals, but rats made acutely polycythemic by transfusion of
erythrocyte suspensions showed no such superiority. Polycythemia apparently must be accompanied by a compensatory increase in tissue vascularization if oxygen transport is to be increased.
Discussion,' There is a continuing need for accurate means of detecting
hypoxia and of measuring its severity. Ideal tests should be applicable to
unanesthetized subjects and should differentiate the degree of oxygen deficiency in various organs and sYstems. The difficulties in achieving these
goals are conceptual as well as technical. It is necessary first to determine the
significance of the various intracellular responses to fluctuations in oxygen
supply before they can be used as test items. When this has been accomplished, the next step should be the devising of functional tests for individual
organs and sYstems which can be validated against the intracellular criteria
of oxygen deficiencv'.
The studies reviewed in this paper were directed toward both of these goals
as they applY to one organ, the brain. They lead to several conclusions
which may point the way to a more penetrating analysis of this complex
problem.
It is recognized that the most valuable single item of information in
studies on cellular hypoxia would be the intracellular oxygen tension. At
the present time this information is very incomplete and largely inferential.
Oxygen microclectrodes inserted blindly into tissues measure oxygen
tensions of unknown significance, since the spatial relations between electrode tip, blood vessels and cells are unknown. Substituting the term
"oxygen availabilitv" for "oxvgen tension" accomplishes little except to
emphasize the influence of blood flow on the measurements. It is now
technically possible to insert oxygen microelectrodes, having tip diameters
of 1 micron or less, directlv' into cells and to verify the intracellular position
by recording the potential change on penetration of the cell membrane.
In addition to measurements of intracellular oxygen tension it would be
highly desirable to have measurements of oxygen tension gradients along
the diffusion path from blood to cells; this will be a far more difficult problem, however, and it will probably require direct visualization techniques
similar to those used in kidney micropuncture studies.
The measurements of metabolic changes in the brain during hypoxia
highlight the semantic difficulties in defining intracellular hypoxia. When
is a cell hypoxic? The ATP concentration may be well-maintained when the