ylaspartate
neurotoxicity.
Brain Res. 221:
1981.
7. Plaitakis,
A., S. Berl, and M. D. Yahr.
Neurological
disorders
associated
with
deficiency
of glutamate
dehydrogenase.
Ann. Neural.
15: 144-153,
1984.
8. Price, M. T., J. W. Olney,
L. Samson,
and
J. Labruyere.
Calcium
influx
accompanies but does not cause excitotoxin-induced neuronal
necrosis.
Brain Res. Bull.
In press.
9. Rothman,
S. Synaptic
release
of excitatory
amino
acid neurotransmitter
mediates anoxic neuronal
death. 1. Neurosci.
4: 1884-1891,
1984.
10. Rothman,
S. Excitatory
amino acid neurotoxicity
is produced
by passive chloride
influx.
J. Neurosci.
In press.
11. Shoulson,
I. Huntington’s
disease:
antineurotoxic
therapeutic
strategies.
In: Excitotoxins,
edited by K. Fuxe, P. Roberts,
207-210,
John B. West
The ascent of Mount Everest (altitude 8,848 m) by two climbers without
supplementary
oxygen in 1978 was a feat that astonished many
physiologists;
indeed, measurements
of maximal
oxygen uptake at
lower altitudes suggested that it would be impossible.
Data obtained in
1981 at extreme altitudes, including
the summit itself, showed that man
can tolerate the extreme hypoxia only by an enormous increase in
ventilation.
Even so, the arterial Paz is apparently
less than 30 Torr and
maximal
oxygen intake only about one liter per minute. Under these
conditions man is at the utmost limit of tolerance to hypoxia,
and even
day-by-day
variations
of barometric
pressure probably
affect
performance.
Climbing Mount Everest has always
been a symbol of the ultimate
in
human achievement.
But to climb
Mount Everest without supplementary oxygen is an even greater challenge. Yet in the spring of 1978 a
remarkable
physiological
event occurred when two climbers from Tyrol, Reinhold Messner and Peter Habeler, did just that.
Many physiologists with an interest in the effects of severe hypoxia
were astonished by this feat, and,
indeed, many had predicted that it
was impossible.
Certainly
there is
good reason to believe that reaching
the top of Mount Everest without
supplementary
oxygen is right at the
limit of human tolerance.
Prior to 1978 the most extensive
data on maximal exercise at extreme
altitude had been collected by Pugh
and his colleagues (3) principally
on
the Himalayan
Scientific and Mountaineering Expedition of 1960-61 led
by Sir Edmund
Hillary,
first conqueror of Everest. These data (Fig. 1,
lower line) showed that maximal oxygen uptake (Vo 2 max) declined precipitously
with increasing altitude
above about 5,400 m (barometric
pressure 400 Torr). In fact, extrapolation of the line relating Vozmax to
barometric
pressure strongly suggested that at the summit of Mount
Everest where the barometric
pressure was expected to be about 250
Torr, virtually
all the oxygen available would be needed for basal oxygen needs. Thus how Messner and
Habeler
could reach the summit
without supplementary
oxygen was
very intriguing.
That feat has since
been repeated some 10 times, including the most spectacular climb
of all, a solo ascent of Everest from
the difficult north side by Messner
in 1980,
john B. West is Professor
of Medicine
and
Physiology
in the Section of Physiology,
School
of Medicine,
University
of California
at San
Diego, La lolla, CA 92093.
0886- 17 14/86 S 1.50 CI 1986 Int Union
Physiol.
Sci/Am. Physiol.
Sot.
How is it possible for the oxygen
transport system to deliver enough
oxygen to the exercising muscles under these conditions of profound hypoxia? Not surprisingly,
the historic
1978 ascent prompted several theoretical studies, one of which was carried out by Dejours (1). He assumed
that a climber
could increase his
ventilation
to such an extent that the
alveolar Pco2 fell to only 11 Torr
(normal at sea level is 40). For an
assumed barometric pressure of 247
Torr and respiratory exchange ratio
of 0.9, this gave an alveolar Paz of 30
Torr. He took the alveolar-arterial
Po2 difference to be 8, which gave
an arterial Paz of only 22 Torr! In
spite of this extremely low value, it
possible to come up with a
I’
-------
Basal O2 Uptake
L-------
-----
50
INSPIRED
----4
100
PO, (torr)
FIGURE
1. Maximal
oxygen
uptake
against inspired Po2. Circles and lower line
show data available prior to the “oxygenless” ascent of Everest in 1978 (3). Subsequent
results, shown by the upper line, indicate
that with an inspired Po2 of 42.5 Torr, \jozmax
is about 1 l/min, just sufficient for a climber
to reach the Everest summit (4).
Volume 1/February 1986
NIPS
23
Downloaded from http://physiologyonline.physiology.org/ by 10.220.33.4 on June 15, 2017
Mount Everest
Without Oxygen
Climbing
and R. Schwartz.
London:
Macmillan,
1983, p. 343-354.
12. Simon, R. P., J. H. Swan, T. Griffiths,
and
B. S. Meldrum.
N-methyl-n-aspartate
receptor blockade
prevents
ischemic
brain
damage. Science 226: 850-852,
1984.
13. Watkins,
J. C. Excitatory
amino acids. In:
Kainic
Acid as a Tool in Neurobiology,
edited by E. G. McGeer,
J. W. Olney,
and
P. L. McGeer.
New York: Raven, 1978.
?kUiE
1 hleasuren
alveolar
gas ar,d
estln-tuted
is, above 8,000 m. The results
showed that the previous theoretical
analyses were inaccurate in several
respects. First, the degree of hyperventilation
on the summit was far
greater than had been predicted. Dr.
Christopher
Pizzo collected several
alveolar gas samples on the summit,
using specially designed equipment,
and additional
samples at altitudes
of 8,400 and 8,050 m. These showed
that alveolar iToXmax declined
approximately
linearly as barometric
pressure fell and that the value on
the summit
was the astonishingly
low value of 7.5 Torr (4). This means
that on the summit Pizzo increased
his alveolar ventilation
some five to
six times compared with sea level.
When the values for alveolar PcoZ
and PO, were plotted, an interesting
point emerged. As a climber
ascended to higher and higher altitudes, both the Pco? and the PO, fell,
the first because of increasing hyperventilation
and the second because
of the decreasing inspired PO,. However, our results showed that when
the alveolar Paz had fallen to about
35 Torr at an altitude of about 6,500
m. there was essentially no further
reduction
in PO, as altitude
increased. In other words, the successful climber was able to defend his
alveolar PoZ at about 35 Torr. His
increasing
hyperventilation
effectively isolated the PO, in his lung
from the declining value in the surrounding air. This appears to be one
of the most important ways in which
the body can protect itself against
the severe hypoxia of extreme altitudes.
L2!hat can be said of the arterial
PO, on the Everest summit? It is impossible to sample arterial blood in
this cold and hostile environment.
However, some information
can be
obtained by using the measured al-
urlerlai
r11c;d
va.~es
on the sumnut of Mount Everest
Barometric:
Pressure.
Torr
R.H48 m (summit)
253
760
SPti IPVCl
Alvrolar
24
lwqired
Po,.
Torr
43
149
PHP IS assumed to hc 47 Torr.
NIPS
Volume
l/February
Arterial
AlWOlX
1986
PO>.
Torr
PO,.
Torr
l’co,.
Torr
PH
35
100
2tl
95
7.5
40
>7 7
7.41)
veolar gas and blood values to calculate the change in PO, along the
pulmonary
capillary, using the classical Bohr integration.
The results
show the arterial PO* to be about 28
Torr. considerably
less than the alveolar value. The reason for the
large PO, difference between alveolar gas and end-capillary
blood is the
limited
diffusion properties of the
blood-gas barrier. Under these conditions the blood in the pulmonary
capillary remains very low on the
oxygen
dissociation
curve,
and
marked diffusion limitation
of oxygen transfer occurs (2, 5).
Information
on the acid-base status of the body under these conditions was obtained from the base excess measured on venous blood samples taken on two climbers the day
after they had reached the summit.
These measurements
showed that
for a PCO~ of 7.5 Torr on the summit,
the arterial pH was between 7.7 and
7.8, an extraordinary
degree of respiratory alkalosis. The very high pH
can be explained,
in part, by the
failure of the kidney to excrete bicarbonate at these great altitudes.
Indeed, base excess appeared not to
fall in climbers
when they went
above 6.300 m. The reasons are obscure but mav be related to the volume contracfion.
which apparently
was a feature of the climbers while
living at 6.300 m even with unlimited opportunities
for fluid intake. It
is known that the kidney is reluctant
to excrete bicarbonate
in the presence of chronic dehydration.
Measurements
of %‘oz ,,,d, were obtained using a bicycle ergom:ter. It
was even possible to simulate Vo, ,,,i,Y
on the summit itself in the laboratory at ti.300 m by giving the subjects
gas mixtures with low inspired oxygen concentrations.
These were prepared by collecting
expired gas.
scrubbing out the CO,, and adjusting
the PO, to the desired value. As Fig.
1 (top line) shows, when the inspired
PO, was 42.5 Torr (equivalent to the
Everest summit)
VoZmax was just
over 1 l/min. Although this is only
20-259;
of the ‘?02,,, at sea level,
calculations show that it is probably
just sufficient to allow an 80-kg man
to climb at the rate reported by
Messner near the summit. He stated
that the last 100 m of vertical distance took over an hour!
These data obtained at extreme
Downloaded from http://physiologyonline.physiology.org/ by 10.220.33.4 on June 15, 2017
high as 560 ml/min
by
2m.,r
as
assuming a cardiac output of 12 l/
min.
However, there is little evidence
to support such a high cardiac output
at such a low work level. In fact,
Pugh showed that the relationship
between cardiac output and work
level at 5,800 m altitude
was the
same as at sea level in acclimatized
subjects.
Nevertheless,
Dejours’
analysis was valuable in showing
how increased
blood convection
could make up, in part, for the reduced gas convective flow.
\Ve independently
carried out another theoretical analysis (5). We assumed a slightly higher barometric
pressure of 250 Torr and even more
extreme hyperventilation
to reduce
the alveolar PCO~ to 10 Torr. However, it was still not possible to find
a solution that gave a iro2 m,,xexceeding 700 ml/min. which is equivalent
to walking slowly on level ground. It
seemed highly unlikely that this was
sufficient to allow a climber to reach
the Everest summit.
The opportunity
to obtain additional data came with the American
Medical Research Expedition
to Everest in 1981. The expedition
included
six expert climbers,
six
‘*climbing
scientists,” i.e., physiologists who were also outstanding
climbers, and eight additional
scientists to man the two laboratories.
One was set up at an altitude of 6,300
m where a heated laboratory
provided a warm environment
with
electrical
power and sophisticated
equipment.
Additional
measurements were made at the highest
camp, altitude 8,050 m. and even on
the summit itself, altitude 8,848 m
(Table 1).
The primary aim of the expedition
was to obtain information
on human
physiology at extreme altitudes, that
vo
turn results from convective
and radiation phenomena.
The summit of
Everest at 28"N enjoys this higher
pressure which confers an enormous
physiological
advantage
on the
climber who is not using supplementary oxygen. Indeed, it is easy to
show that if the barometric
pressure
on the summit were not increased
by this climatic
idiosyncrasy,
it
would be impossible
for humans to
reach the highest
point on earth
while breathing ambient air.
0886- 17 14/86 $1 50 0 1986 Int Unwon Physlol
Sci/Am
Physrol
References
1. Dejours.
breathing
P. Mount
Everest
and beyond:
air. In: A Companion
to Animal
Physiology,
edited
by C. R. Taylor,
K.
Johansen,
and L. Bolis. New York: Cambridge Univ. Press, 1982.
Piiper, J., and P. Scheid.
Model
for capillary-alveolar
equilibrium
with
special
reference
to O2 uptake in hypoxia.
Respir.
Physiol. 46: 193-208,
1981.
Pugh, L. G. C. E. Animals
in high altitude:
man above 5000
meters-mountain
exploration.
In: Handbook
of Physiology.
Adaptation
to the Environment.
Washington, DC: Am. Physiol.
Sot., 1964, sect. 4,
chapt. 55, p. 861-868.
West, J. B. Human
physiology
at extreme
altitudes
on Mount
Everest.
Science
VVash. DC 223: 784-788,
1984.
5. West, J. B., and P. D. Wagner.
Predicted
gas exchange
on the summit
of Mt. Everest. Respir. Physiol. 42: l-16,
1980.
Fever: A Hot Topic
Matthew
J. Kluger
Fever is the regulation
of body temperature
at an elevated “set point.”
Contact with a variety of pathogens,
such as viruses or bacteria, will
result in the release of a small protein, endogenous
pyrogen or
interleukin
1, from the host’s white blood cells. This protein circulates to
the brain where it is thought to raise the temperature
set point via the
production
of a prostaglandin.
Fevers occur throughout
the vertebrates.
The cold-blooded
vertebrates (fishes, amphibians,
reptiles) raise their
body temperature
by behaviorally
selecting a warmer microhabitat.
Warm-blooded
vertebrates (birds and mammals)
use both physiological
and behavioral
means to raise core temperature.
Over the past decade
data from both in vitro and in vivo studies support the hypothesis that
moderate fevers are beneficial
to the host; that is, fever has evolved as
an adaptation
to reduce the severity of infection.
The regulation
temperature
of body
Virtually
all biochemical
processes
are affected by changes in temperature. Metabolic
rate speeds up or
slows down, depending on whether
body temperature
is rising or falling.
The ability to maintain a relatively
constant
internal
temperature
has
allowed birds, mammals,
and some
species of insects to be relatively free
of the influence of fluctuations
in the
temperature
of their environment.
This regulation
of body temperaMattherzr
J. Kjuger is Professor
of Physiology
the Department
of Physiology,
University
Michigan
Medical
School,
Ann
Arbor,
48109.
Sot
in
of
MI
ture within
a narrow
range, homeothermy,
is a result of numerous
physiological
and behavioral
adaptations. For example, when a person
is exposed to a warm environmental
temperature,
excess heat is carried
to the skin by increased skin blood
flow. Large amounts of heat are lost
from the skin surface by a variety of
with
evaporation
of
processes,
sweat,
secreted
by specialized
glands, being the most important
heat-dissipating
tiechanism,
In addition, a large number of behavioral
responses
are triggered;
these may
include searching for a cooler microclimate (e.g., the shade of a tree),
removing
excess layers of clothing,
and spraying the body with water to
facilitate evaporative
cooling. As a
Volume
1/February
1986
NIPS
25
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altitudes
showed
that the earlier
theoretical analyses were in error in
at least three respects. First, the degree of hyperventilation
was much
greater than we had expected; this
has a powerful
effect on raising the
alveolar and therefore
the arterial
Po2. Next, the pH of the arterial
blood was much higher than expected. This appears to be advantageous at these great altitudes
because the left-shifted
oxygen dissociation curve enhances
loading of
oxygen in the pulmonary
capillary
under conditions
of diffusion
limitation more than it interferes
with
unloading in peripheral
capillaries.
(5) .
Finally, the barometric
pressure
was higher than predicted. Pizzo obtained the first direct measurement
on the summit,
and the value was
253 Torr. It can be shown
that
ii0 2 rnax
is exquisitely
sensitive
to
barometric
pressure
at these great
altitudes because this pressure
determines
the inspired, PO,. Indeed,
this is probably the most critical factor, and a climber who plans to go to
the summit without
supplementary
oxygen might do well first to consult
his barometer
on the morning of the
climb!
The relationship
between
barometric pressure and altitude is interesting in its own right. Many years
ago, Pugh (3) pointed out that barometric pressures
in the Himalayas
are considerably
higher than predicted by the standard altitude-pressure tables that are routinely
used
for calibrating
low-pressure
chambers and for predicting
the hypoxia
of high-altitude
exposure
in the
aviation
industry.
In fact, Pizzo’s
measurement
of 253 Torr on the
summit was 17 Torr higher than the
value of 236 Torr predicted
by the
International
Civil Aviation Organization Standard Atmosphere.
The reason for this disparity is that
the Standard Atmosphere
is a model
that averages pressures over all parts
of the world.
However,
barometric
pressures
in the range of 8-10 km
altitude are markedly
latitude dependent; the pressure
is considerably higher at the equator than the
poles. This is because there is a large
mass of cold, heavy air in the stratosphere above the equator; paradoxically the coldest air in the atmosphere is above the tropics. This in