186
A. T. MILLER, JR.
oxygen tensions was 7-40 mm Hg, with most of the values in the range
20-30 mm Hg. When rats breathed 5 % 02 in N2 for 3 min the final brain
oxygen tension was always less than 10 mm Hg and often as low as 1-5
mm Hg. Rats made polycythemic by transfusion, cobalt administration or
altitude exposure had no higher brain oxygen tension than did normocythemic controls when the inspired gas mixture was 4 % 02 in N 2 . When,
however, 5 % CO 2 was added to the inspired gas, the polycythemic animals
were able to maintain a higher brain oxygen tension than were their controls. These results are believed to reflect the opposing influences of increased oxygen capacity and increased viscosity of the blood, as well as the
variability in oxygen tensions recorded from extracellular oxygen electrodes.
Extracellular oxygen tension measurements are probably of little value in
predicting intracellular oxygen tension changes because of the varying
diffusion distances from electrode tips to cells. The use of intracellular
oxygen microelectrodes should give more meaningful results.
When rats breathed 4 % 02 in N2 for 9 min, brain creatine phosphate
concentration was reduced and lactate : pyruvate ratio was elevated, but
A TP concentration and NADH: NAD+ ratio remained virtually unchanged. Brain A TP was thus nearly normal even when the cortical oxygen
tension was reduced to 1-5 mm Hg.
Cobalt-treated rats, with moderately elevated hematocrits, maintained
slightly higher creatine phosphate concentration and lower NADH : NAD+
ratio than did their controls, when 4 % 02 in N2 was breathed. Altitudeexposed animals, with much higher hematocrits, showed no such superiority. When, however, 5 % CO 2 was added to the low 02 mixture, both cobalttreated and altitude-exposed animals were definitely superior to their
controls with respect to creatine phosphate concentration and lactate:
pyruvate ratio. It is suggested that cerebral vasodilatation induced by CO 2
mitigates the unfavorable influence of polycythemia on blood viscosity
and flow, and reveals the beneficial effect of the increased oxygen carrying
capacity of the blood.
When turtles breathed 4 % 02 in N2 for 9 min there was no change in
any of the chemical constituents, and after 1 hr the changes were smaller
than those observed after 9 min in rats. After 1 hr in nitrogen, severe brain
hypoxia in the turtle was indicated by changes in creatine phosphate, lactate : pyruvate ratio and NADH: NAD+ ratio. Nevertheless, the brain
A TP concentration remained virtually unchanged. Thus hypoxia is manifested not so much by the end-result of reduction in high energy stores as
by the evidence that the A TP concentration is maintained at the expense of
anaerobic metabolism, which is ultimately a self-limited source.
One of the reasons for selecting the brain for studies on hypoxia is that
changes in function can readily be detected and compared with metabolic
changes. We observed that both learning and the performance of learned
A. T. MILLER, JR.
oxygen tensions was 7-40 mm Hg, with most of the values in the range
20-30 mm Hg. When rats breathed 5 % 02 in N2 for 3 min the final brain
oxygen tension was always less than 10 mm Hg and often as low as 1-5
mm Hg. Rats made polycythemic by transfusion, cobalt administration or
altitude exposure had no higher brain oxygen tension than did normocythemic controls when the inspired gas mixture was 4 % 02 in N 2 . When,
however, 5 % CO 2 was added to the inspired gas, the polycythemic animals
were able to maintain a higher brain oxygen tension than were their controls. These results are believed to reflect the opposing influences of increased oxygen capacity and increased viscosity of the blood, as well as the
variability in oxygen tensions recorded from extracellular oxygen electrodes.
Extracellular oxygen tension measurements are probably of little value in
predicting intracellular oxygen tension changes because of the varying
diffusion distances from electrode tips to cells. The use of intracellular
oxygen microelectrodes should give more meaningful results.
When rats breathed 4 % 02 in N2 for 9 min, brain creatine phosphate
concentration was reduced and lactate : pyruvate ratio was elevated, but
A TP concentration and NADH: NAD+ ratio remained virtually unchanged. Brain A TP was thus nearly normal even when the cortical oxygen
tension was reduced to 1-5 mm Hg.
Cobalt-treated rats, with moderately elevated hematocrits, maintained
slightly higher creatine phosphate concentration and lower NADH : NAD+
ratio than did their controls, when 4 % 02 in N2 was breathed. Altitudeexposed animals, with much higher hematocrits, showed no such superiority. When, however, 5 % CO 2 was added to the low 02 mixture, both cobalttreated and altitude-exposed animals were definitely superior to their
controls with respect to creatine phosphate concentration and lactate:
pyruvate ratio. It is suggested that cerebral vasodilatation induced by CO 2
mitigates the unfavorable influence of polycythemia on blood viscosity
and flow, and reveals the beneficial effect of the increased oxygen carrying
capacity of the blood.
When turtles breathed 4 % 02 in N2 for 9 min there was no change in
any of the chemical constituents, and after 1 hr the changes were smaller
than those observed after 9 min in rats. After 1 hr in nitrogen, severe brain
hypoxia in the turtle was indicated by changes in creatine phosphate, lactate : pyruvate ratio and NADH: NAD+ ratio. Nevertheless, the brain
A TP concentration remained virtually unchanged. Thus hypoxia is manifested not so much by the end-result of reduction in high energy stores as
by the evidence that the A TP concentration is maintained at the expense of
anaerobic metabolism, which is ultimately a self-limited source.
One of the reasons for selecting the brain for studies on hypoxia is that
changes in function can readily be detected and compared with metabolic
changes. We observed that both learning and the performance of learned