Metabolic Effects of Acute Hypoxia on Rat and Turtle Brain
A. T. MILLER, JR.
Abstract
According to one definition, hypoxia exists when, because of inadequate
oxygen supply, various cellular oxidation-reduction systems must shift toward a
more reduced state. This definition was tested in experiments on rat and turtle
brain by comparing hypoxic changes in two oxidation-reduction systems (lactate:
pyruvate and NADH-NAD I) with changes in tissue Po" ATP and creatine
phosphate. The results indicate that: (1) measurements of tissue Po, are most
useful when the electrode tip is intracellular, (2) creatine phosphate and lactate:
pyruvate ratio are sensitive indicators of cellular hypoxia, (3) ATP and NADH:
NAD+ ratio change significantly only in severe hypoxia, (4) tests of learning and
performance show impairment at levels of hypoxia which do not significantly
lower brain ATP concentration. It is concluded that intracellular hypoxia cannot
be defined solely in terms of increased reduction of cellular oxidation-reduction
systems.
HUCKABEE [2] has defined hypoxia as "the condition which exists when
the supply of oxygen to the interior of living cells is reduced to a rate
insufficient for their current metabolic needs, with the result that various
cellular oxidation-reduction systems must shift toward a more reduced
state". The object of this study was to test this definition by comparing
changes in oxidation-reduction systems with other changes occurring in
hypoxic cells. The brain was selected for study because of its vulnerability
to hypoxia, and the influence of polycythemia was examined because of the
conflicting opinions concerning its value to hypoxic subjects.
Experimental: Albino rats and water turtles (Pseudemys scripta) were
anesthetized with urethane and pump-ventilated with gas mixtures differing
in oxygen concentration. Brain oxygen tension was recorded from microelectrodes [1] inserted into the cerebral cortex. The experiments were terminated by immersing the animal's head in liquid propane (-180°C) and the
frozen brain was removed and analyzed for A TP, creatine phosphate, lactate, pyruvate, N AD+ and N ADH.
Brain oxygen tension values recorded in rats breathing air were extremely variable despite precautions to avoid inserting the electrodes near
visible surface blood vessels. The electrode tip was probably extracellular
in most experiments, and would therefore be influenced by its proximity to
blood vessels as well as to metabolizing brain cells. The range of brain
A. T. MILLER, JR.
Abstract
According to one definition, hypoxia exists when, because of inadequate
oxygen supply, various cellular oxidation-reduction systems must shift toward a
more reduced state. This definition was tested in experiments on rat and turtle
brain by comparing hypoxic changes in two oxidation-reduction systems (lactate:
pyruvate and NADH-NAD I) with changes in tissue Po" ATP and creatine
phosphate. The results indicate that: (1) measurements of tissue Po, are most
useful when the electrode tip is intracellular, (2) creatine phosphate and lactate:
pyruvate ratio are sensitive indicators of cellular hypoxia, (3) ATP and NADH:
NAD+ ratio change significantly only in severe hypoxia, (4) tests of learning and
performance show impairment at levels of hypoxia which do not significantly
lower brain ATP concentration. It is concluded that intracellular hypoxia cannot
be defined solely in terms of increased reduction of cellular oxidation-reduction
systems.
HUCKABEE [2] has defined hypoxia as "the condition which exists when
the supply of oxygen to the interior of living cells is reduced to a rate
insufficient for their current metabolic needs, with the result that various
cellular oxidation-reduction systems must shift toward a more reduced
state". The object of this study was to test this definition by comparing
changes in oxidation-reduction systems with other changes occurring in
hypoxic cells. The brain was selected for study because of its vulnerability
to hypoxia, and the influence of polycythemia was examined because of the
conflicting opinions concerning its value to hypoxic subjects.
Experimental: Albino rats and water turtles (Pseudemys scripta) were
anesthetized with urethane and pump-ventilated with gas mixtures differing
in oxygen concentration. Brain oxygen tension was recorded from microelectrodes [1] inserted into the cerebral cortex. The experiments were terminated by immersing the animal's head in liquid propane (-180°C) and the
frozen brain was removed and analyzed for A TP, creatine phosphate, lactate, pyruvate, N AD+ and N ADH.
Brain oxygen tension values recorded in rats breathing air were extremely variable despite precautions to avoid inserting the electrodes near
visible surface blood vessels. The electrode tip was probably extracellular
in most experiments, and would therefore be influenced by its proximity to
blood vessels as well as to metabolizing brain cells. The range of brain