AMER. ZOOL., 13:447-456 (1973).
High Altitude Adaptation in Mammals
CLAUDE LENFANT
National Heart and Lung Institute, National Institutes of Health,
Bethesda, Maryland 20014
SYNOPSIS. The physiological, morphological, and biochemical characteristics of several
species of mammals resident at high altitude are compared with those of their sea
level counterparts. The differences noted in these characteristics are in a direction
that facilitates the acclimatization of those living at high altitude. The differences
among species point to the fact that the mechanism of adaptation to altitude (i.e.,
hypoxia) is still not understood. This review emphasizes that the adaptive process
is complex and made up of several components, that these components are interrelated, and that neither the physiological nor morphological adaptations can fully
account for the tolerance to hypoxia. Although only superficially studied as yet,
the biochemical adaptations appear most important.
INTRODUCTION
"Altitude is a component of the physical
environment to which animals show adjustments" (Hall et al., 1936). Indeed, because increasing altitude is characterized
by decreasing oxygen availability in the environment without major changes in tissue (i.e., metabolic) requirements, any animal exposed to altitude must develop
adaptive mechanisms if it is to maintain
an adequate oxygen delivery to its tissue.
Although it is recognized that numerous
species of mammals have evolved at altitude or have adapted to it, there are relatively few studies of their adaptive mechanisms in species other than man. The
first comprehensive study of man's physiological response to altitude was in 1874
(Bert, 1874). The first studies of various
other animals' response seem to be those
of Muntz and of Viauk (Muntz, 1891;
Viault, 1891). These studies, however, were
very much limited since they were exclusively concerned with changes in hemoglobin concentration at altitude. "Comparative physiology in high altitudes" (Hall
et al., 1936) is probably the next landmark
in our understanding of adaptation to altitude. Hall's study stimulated considerable
and increasing interest in a comparative
approach to this important biological
phenomenon (Chiodi, 1962, 1970; Reeves
et al., 1963a; Banchero et al., 1971a; Lahiri
et al., 1971).
447
This presentation reviews and compares
the physiological, morphological, and biochemical adaptations of various species of
mammals to altitude.
PHYSIOLOGICAL ADAPTATIONS
Oxygen is transported from the environment to the cells by means of four linked
mechanisms (Lenfant and Sullivan, 1971):
ventilation, pulmonary diffusion, circulation, and tissue diffusion. Upon ascent to,
and during life at, altitude there are several physiological adjustments of these
mechanisms that compensate for the decrease in availability of environmental
oxygen. Although all four mechanisms
play an equally important role, not all of
them have been examined in species other
than man. For this comparative review, the
physiological responses to altitude will be
grouped into respiratory, circulatory, and
hematological adaptation.
Respiratory adaptations
In all mammalian species, minute ventilation is determined by oxygen demand,
and regulated by neural and chemical stimuli. One of the latter is the partial pressure of oxygen, a decrease of which is characteristic of altitude. Hence, it is no surprise that in man (Kellogg, 1968), as well
as in all other species of mammals that
have been examined, there is a significant
increase in ventilation upon acute exposure (Figs. 1, 2, 3). Figure 1 shows the in-
448
CLAUDE LENFANT
(MAN)
VENTILATION CHANGE AT ALTITUDE
(SOJOURNERSI
M0R0C0CHA
LaOROYA
J
PROLONGED EXPOSURE
ACUTE EXPOSURE
|MORE THAN 7 DAYS)
ILES5 THAN 2 DAVS)
SOJOURNERS
CALF
4900m
13 DAYS)
MAN
4710m
•» NATIVES
LLAMA
3420m
2000
3000
4000
5000
ALTITUDE, METERS
FIG. 1. Change in total ventilation after acute
and prolonged exposure to altitude. Data sources
are as follows: man: Torrance et al. (1970/71) ,
llama: Banchero et al. (1971a) ; goat: Lahiri et al.
(1971) ; calf: Bisgard et al. (1969) ; lamb: Reeves
et al. (1963d) .
FIG. 3. Ventilatory equivalent as a function of altitude in natives and in sojourners. Data from
Torrance et al. (1970/71).
tilatory response to hypoxia stimuli has
been a question of great interest for many
years (Rahn and Otis, 1949). It is now well
established that in man the duration of
crease in total ventilation noted in several residence at altitude markedly affects the
species upon acute exposure and after a ventilatory response (Lenfant and Sullivan,
sojourn of at least several days. This figure 1971). Figure 3 shows the difference in realso shows that the magnitude of the in- sponse between sojourners and natives at
crease varies among species and that it is various altitudes. The data of Weil et al.
greatest immediately after ascent. Since the (1971) (Fig. 4) further demonstrate the atdemand for oxygen is the determining fac- tenuation of the hypoxic response in resitor in ventilation, it is possible that the dents at altitude as compared with those
species difference in ventilation increase at sea level and in natives compared with
may in part be accounted for by a change sojourners. Some studies have examined
in the oxygen requirement in some of these whether a similar attenuation exists in
species. The data shown in Figure 2 con- other species of mammals (Brooks and Tenfirm this possibility since the species differ- ney, 1968; Hornbein and Sorensen, 1969;
ences per unit of oxygen consumed are Lahiri et al., 1971). The results of these
less than the species difference in total ven- studies are presented in Figure 5 which
tilation.
shows the increase in total ventilation when
Whether the duration o£ exposure to
hypoxia affects the magnitude of the vcn30
(MAN)
VE/VO 2 CHANGE AT ALTITUDE
(SOJOURNERS = MORE THAN 7 DAYS)
E 20
SOJOURNERS
50 r
I.
LAMB
4710m
3900m
3735m
s; 25 -
NATIVES
LLAMA
n
3420m
STEER
n
3900m
FIG. '2. Change in ventilatory equivalent at altitude. Data from same sources as in Figure 1, plus
that for steer from Grover et al. (1963).
60
80
100
120
ALVEOLAR OXYGEN TENSION. mmHg
FIG. 4. Total ventilation as a function of alveolar
oxygen tension in sea level residents (two controls)
and in altitude natives and sojourners. Data from
Weil et al. (1971).
449
ADAPTATION TO ALTITUDE
HYPOXIC VENTILATORY RESPONSE
PAOj = 100—PAO2 = 45 mmHg
S I SOJ NAT
SL SOJ NAT
S I NAT
SL NAT
FIG. 5. Change in ventilation in various species
and in sea level residents (SL) and in altitude
sojourners (SOJ) and natives (NAT) when alveolar
P o is lowered from 100 to 45 mm Hg. Data sources
are as follows: man: Weil et al. (1971); goat: Lahiri
ct al. (1971); llama: Brook and Tenney (1968); cat:
Hornbein and Sorensen (1969).
alveolar P o , is suddenly decreased from 100
to 45 mm Hg in sea level residents, acclimatized sojourners, and natives of altitude who are studied at sea level. These
data on other mammals seem to indicate
that only man has an attenuation of his
hypoxia sensitivity with increasing duration of residence. The data also demonstrate that upon exposure, man's relative
hypoxic sensitivity is greater than that of
any other species studied.
ence to the behavioral differences between
man and llama and calf.
Figure 7 shows the ratio of blood flow
to oxygen consumption in several species
at sea level, after at least seven clays of
sojourn at altitude, and also in man native
of high altitude. In general, there are no
significant differences under these conditions. This clearly indicates that in all
species studied, the blood flow is regulated
by the O 2 demand (metabolism) and not
by tissue P 02 (Guyton, 1967). This differs
markedly from the ventilatory response,
which is determined by O2 demand and is
also modulated by blood P o ,.
The cardiac response during exercise at
altitude has been well studied only in man.
The newcomer to altitude responds to any
given work load by a greater cardiac output than at sea level (Klausen, 1966), while
the long-term sojoumer as well as the native may respond by a lesser cardiac output increase than at sea level (Hartley et
CARDIAC
OUTPUT
HEART
RATE
501-
5
25
MAN
3800m
Circulatory adaptations
In man, immediately upon exposure to
altitude, the cardiac output abruptly increases (Klausen, 1966). This increase results solely from an increase in heart rate,
not from a change in stroke volume. Very
few other species of mammals have been
studied from the standpoint of cardiac output response to sudden hypoxia. Data from
the calf and the llama (Fig. 6) show that in
these species there is a marked increase in
heart rate, but only a moderate change in
cardiac output. This strongly suggests a
decrease in stroke volume, a response at
variance with that in man. In man a decrease in stroke volume at altitude is a delayed occurrence which causes the cardiac
output to return to its sea level value after
a few days of acclimatization (Klausen,
1966). It is tempting to relate this differ-
§
UJ
E 25
<
CALF
4900m
50
u 25
LLAMA
3420m
FIG. 0. Change in cardiac output and heart rate
immediately after exposure to hypoxia. Data sources
as follows: man: Klausen (1960) ; calf: Bisgard
et al. (1969) ; llama: Banchero et al. (1971b) .
450
CLAUDE LENFANT
Q/VO 2 CHANGE AT ALTITUDE
SOJOURNERS = MORE THAN 7 DAYS
30 1-
MAN
4509m
LLAMA
3420m
20
10
CAT
4300m
LAMB
3900m
F
10
FIG. 7. Cardiac output to oxygen consumption ratio
in various species and in sea level residents (SL)
and in altitude sojourners (SOJ) and natives
(NAT) . Sojourners are denned by more than 7
days stay. Data source as follows: man: Torrance
et al. (1970/71); llama: Banchero et al. (1971b);
lamb: Reeves et al. (1963a) ; steer: Grover et al.
(1963) ; cat and rabbit: Reeves et al. (1963b).
al., 1967). A recent study on the llama
indicates that the cardiac output response
to a work load increases with increasing
altitude (Banchero et al., 19716).
The absence of an increase in resting
cardiac output in long-term residents at
altitude is a distinct advantage in the sense
that there is no cardiac work increase. The
result could, however, be a limitation in
oxygen supply to those tissues that are sensitive to hypoxia. In man, this appears to
be prevented by a selective redistribution of
local blood flow (Lenfant and Sullivan,
1971). No similar observations have been
made in other species.
The hemodynamics of pulmonary circulation in various species at altitude has
received considerable attention with regard
to smooth muscle response to hypoxia. In
man, there is an increase in mean pulmonary artery pressure, the magnitude of
which is related to the altitude (CruzJiboja et al., 1964). This results in a more
uniform distribution of blood flow to the
lung at altitude (Fig. 8), and therefore, in
a decrease in the ventilation to perfusion
ratio unevenness. This, in addition to the
overall increase of the mean alveolar ventilation to pulmonary capillary perfusion
ratio, enhances gas exchange in the lung
(Lenfant and Sullivan, 1971). Figure 9
shows the pulmonary artery pressure
changes (or absence of change) in some
other species of mammal. Only cattle seem
to be experiencing a major increase in
mean pulmonary artery pressure. Similar
observations have been made in cats, while
rabbits (Reeves et al., 19636), like the lamb
and llama shown in Figure 9, experience a
much milder degree of hypertension. Although some of this species difference is explainable by smooth muscle distribution
and thickness differences, some other factors, such as autonomic regulatory mechanisms, may play an important role (Woodbury and Hamilton, 1941).
Hemalologic adaptations
The hematologic adaptations considered
in this review are blood oxygen-carrying
capacity and the hemoglobin affinity for
oxygen. As noted earlier, the increase in
oxygen-carrying capacity (i.e., increase in
hemoglobin concentration) was first observed by Muntz (1891) and Viault (1891).
This increase is the most consistent finding
in all of the species of mammals living at
altitude. It is also to be found in species
not living at altitude but nevertheless exposed to severe hypoxia, such as the diving
mammals whose adaptive characteristics
are extensively reported elsewhere (Lenfant et al., 1970; Kooyman, 1973).
Figure 10 illustrates the magnitude of
MAN
1000
2000
3000
4000
ALTITUDE. METERS
FIG. 8. Effect of altitude on mean pulmonary artery pressure in relation to lung hilum. Data from
Cruz-Jibaja et al. (1961) . (From Lenfant and Sullivan, 1971. Reproduced with permission of New
England Journal of Medicine.)
451
ADAPTATION TO ALTITUDE
100
s
75
50
LAMB
...3?°.?.™
LLAMA
"""3420m"
1
2
3
4
5
6
7
8
9
tive increase in hemoglobin concentration
is greater in natives of high altitude than
in sojourners. Figure 11 shows that in man
it is closely related to altitude (or degree
of hypoxia) to which the subject is exposed. This figure also demonstrates the
difference between sojourners and natives.
The increase in hemoglobin concentration is undoubtedly a good index of impaired oxygen delivery to the tissues. However, it occurs quite slowly and, therefore,
TIME, WEEKS
FIG. 9. Mean pulmonary artery pressure as a function of duration of stay at altitude. Data sources
as follows: steer: Grover et al. (1963); lamb:
Reeves et al. (1963a) ; llama: Banchero et al.
(1971b) .
25
the increase in hemoglobin concentration
observed in several species of mammals acclimatized to altitude. In general, the rela-
NATIVES_
SOJOURNIRS
1000
20
-
RABBIT
3000
4000
FIG. 11. Hemoglobin concentration as a function
of altitude in altitude native and sojourner man.
Data from Torrance et al (1970/71) .
CHINCHILLA
15
2000
ALTITUDE, METERS
CAT
I
10
5
-
STEER
SHEEP
mmmm
M
10 5
M
GOAT
|—
P
H
1
FIC. 10. Hemoglobin concentration in sea level
and altitude sojourner or native specimens of various species. Data sources as follows: rabbit and
cat: Reeves et al. (19636) ; chinchilla: Hall (1965)
and Chiodi (1962); steer: Grover et al. (1963);
sheep: Hall et al. (1936); goat and llama: Chiodi
(1970); dog: Lenfant (unpublished). Normal sea
level values for goat and dog are from Wintrobe
(1949).
is not in contrast to the ventilatory and
circulatory responses—playing any role in
the adaptation to acute hypoxia states
(Finch and Lenfant, 1971).
An increase in hemoglobin concentration
augments the blood oxygen-carrying capacity. However, in hypoxic hypoxia* the
relative oxygen content of the blood and
the "loading" and "unloading" of oxygen
are determined by the hemoglobin affinity
for oxygen. Hemoglobin affinity for oxygen is determined by the position of the
oxygen dissociation curve; in turn, the
position of the curve is denned by the P50
(7.40; 37 C) which is the partial pressure of
oxygen corresponding to 50% oxygen
saturation of the hemoglobin at pH = 7.40
and temperature = 37 C. Figure 12 shows
some typical oxygen dissociation curves
from species of natives of high altitude and
from other species of sea level residents.
It can be seen that the latter have a markedly lower hemoglobin affinity for oxygen
* Hypoxic hypoxia is a state resulting from decreased P o . in the alveolar air; for instance, at altitude or in case of some respiratory diseases.
452
CLAUDE LENFANT
MORPHOLOGICAL ADAPTATIONS
NATIVES
VICUNA
ALPACA
LLAMA
GUANACO
SEA LEVEL
MAN
HORSE
DOG
RABBIT
PIG
5 «o
PECCARY
OX
SHEEP
pH = 7.4: T = 37 - 3 9 X
0
10
20
30
40
SO
60
70
80
90
100
OXYGEN TENSION. mniHi
FIG. 12. Typical oxygen dissociation causes of animals native of high altitude and of animals resident at sea level. Data from Hall et al. (1936) and
Chiodi (1970) .
(higher P50) than the former. The consequence of this difference in position of the
oxygen dissociation curve is that at any altitude (or Po,) the animal native to high
altitude has a higher oxygen saturation
than the sea level resident. This has been
considered by many as a distinct adaptive
characteristic rather than a coincidence
(Hall et al., 1936; Chiodi, 1962). This interpretation has been open to question by
the recent observation that human sea level
residents, when exposed to altitude, exhibit
a rapid displacement of their oxygen dissociation curve to the right of the sea level
position (Lenfant et al., 1969, 1970). Other
species, such as rat, rabbit, and dog, respond similarly, while still others, such as
sheep and goat, do not. These seemingly
contradictory observations provide evidence
that there is no simple way to achieve the
best adaptation to altitude, and also, that
no adaptive mechanism should be considered independently of the other. This is
well demonstrated by Hall's findings (1966)
that the hemoglobin affinity for O 2 is related to the critical P 02 or the minimal
tension at which utilizable oxygen can be
removed from the environment (Fig. 13).
A low hemoglobin affinity for O 2 may be
the best adaptive change in man who has
some specific physiological, morphological,
and biochemical adaptive features. But a
higher affinity may be better for the vicuna,
which has an entirely different set of
adaptive characteristics.
There are relatively few studies concerned with the morphological adaptation
to altitude. Three facets have, however,
been considered: body morphology, lung
development, and tissue capillary density.
Although none of these facets appear to
play an essential role, they all seem to
contribute to the profile of adaptation to
altitude.
Body morphology
In man, gross morphological differences
have been noted between sea level and
high altitude adult populations of the same
ethnic origin (Hurtado, 1932). The natives
of the high land have a significantly smaller
build (size and weight) than the low-landers. Further studies have confirmed these
differences during childhood (Frisancho,
1969) and have related them to measurements of lung volume and pulmonary
function. These latter studies have shown
a greater total lung capacity in children
at high altitude.
Differences in size and rate of growth
between sea level and high altitude specimens have also been observed in rabbits
(Muntz, 1891), in rats (Timaras et al.,
1957), and in guinea pigs (DelaquerrierRichardson, 1965). However, these may not
be general as there are no differences in
body size between sheep born at sea level
and at altitude (Metcalfe et al., 1962).
".17
1. PRAIRIE DOG
2. ROUND TAIL GROUND SQUIRREL
3. JACK RABBIT
4. 13STRIPPED GROUND SQUIRREL
5. CHINCHILLA
6. HAMSTER
7. GUINEA PIG
8. ANTELOPE GROUND SQUIRREL
9. COTTON TAIL RABBIT
10. GERB1L
11. GRAV SQUIRREL
12. ALBINO RAT
13. COTTON RAT
14. NORWAY RAT
15. JIRD
16. FLYING SQUIRREL
17. MOUSE
IB. KANGAROO RAT
10
20
30
40
CRITICAL P 0 2 , mmHg
FIG. 13. PM of several species of rodents as a function of their critical P o> . (Reproduced from Hall,
1966, with permission of the American Journal of
Physiology.)
453
ADAPTATION TO ALTITUDE
The mechanism of these gross morphological differences is not known; yet, an
understanding of them is an essential step
for the general understanding of adaptation to altitude.
RATS BORN AT DEFINED PO,
E
Lung development
The development and morphometric
evaluation of the lung have been the object of several studies. Studies on sheep
and guinea pigs showed a slightly greater
mean alveolar diameter, diffusing surface
area to lung volume ratio, and total lung
capacity in the altitude population (Tenney and Remmers, 1966). Another study,
by Bartlett (1970), showed that in hypoxic
rats mean lung weight, alveolar surface
area, and alveolar number were also slightly greater than in the normoxic animal.
However, only the study of Burri and
Weibel (1971) in rats demonstrated unequivocally that specific alveolar and specific capillary surface areas could be related to the oxygen tension of the environment in which the animals were born and
raised (Fig. 14). Hence, it appears as if
hypoxic environment inhibits total body
growth, a situation which enhances the
pulmonary gas exchange capacity. It is
worth noting that in lower vertebrates an
increase in total gas exchange area can be
induced by a reduction of the environmental oxygen concentration (Bond, 1960).
Tissue capillary density
Several studies have been made to determine whether the capillary density increases during chronic exposure to hypoxia.
Such exposure would result in a decrease
of the distance between capillaries, a condition that compensates for the reduction
at altitude of the oxygen tension difference between the capillary blood and the
mitochondria. This increase in number of
capillaries has been demonstrated for rabbits (Cassin et al., 1966), guinea pigs
Valdivia, 1965-66), and rats (Tenney and
Ou, 1970). The increase in capillary density
may result from the development of new
capillaries or from the opening of preexisting ones. This latter possibility has
been shown to occur in some specialized
OXYGEN
TENSION. mmHg
100 150 300
FIG. 14. Specific alveolar and capillary surface in
rats born and raised at different environmental
Po.,. Data from Burri and Weibel (1971) .
tissue, such as myocardium (Martini, 1969;
Poupa, 1971-72). It is quite evident that
the role allegedly played by an increase in
capillary density in the adaptation to altitude is far from being established. This is,
however, an extremely important question
that only further comparative studies will
answer. Such studies should attempt to integrate this factor with others which are
also part of the adaptive process. For example, it has been shown that those species
with a relatively higher metabolic rate also have the highest capillary density
(Schmidt-Nielsen and Pennycuik, 1961). Tt
is also known that these species have a low
hemoglobin affinity for oxygen (SchmidtNielsen and Larimer, 1958) which in turn
has been associated with relatively high
critical P o , (Hall, 1966). Hence, it is
tempting to postulate that species with a
relatively high initial Po., also have a high
capillary density; such association is indeed a distinct advantage.
BIOCHEMICAL ADAPTATIONS
Although there are only very few studies
addressed to the biochemical processes during life at altitude, there is overwhelming
evidence that some significant subcellular
changes and alterations of the metabolic
pathways are taking place.
Oxygen requirements
Whether the total oxygen demand is affected at altitude has not been extensively
454
CLAUDE LENFANT
studied. There is, however, some sparse
evidence that hypoxic environments may
cause a slight decrease in oxygen requirements in mammals. This phenomenon,
known as "respiratory dependence," is consistently observed in lower vertebrates; i.e.,
the metabolic activity is—to a point—directly related to the availability of oxygen.
Figure 15 illustrates some of the data obtained in mammals. Results from the lamb
show a significant decrease of the oxygen
consumption per minute and per kilo of
body weight. In man, the results indicate a
trend, but the difference is not statistically
significant. The data from the steer also
show a significant difference in total oxygen consumption at sea level and at altitude. However, as body weight sometimes
decreased at altitude, it is not certain that
this significance would pertain if the data
were expressed per unit weight. As for
many other aspects of the adaptive process
to altitude, the question of whether oxygen
demand changes is still unanswered. Yet,
it is too important a question to be overlooked.
Myoglobin concentration
The role of myoglobin in facilitating the
transport of oxygen within the tissues is
now well established. A recent study in diving mammals has shown that they have a
higher myoglobin concentration than terrestrial mammals. It was also shown that
the concentration increases with the diving
OXYGEN CONSUMPTION
10.0 7.5
UMB
3420m
-
STEER
3420m
1.500
MAN
4340m
2.5
2.000 -
1 1 1
1 II
c
E
E 1.000 -
s
500
FIG. 15. Oxygen consumption, per kilo or total, at
sea level (slatted blocks) and after acclimatization
at altitude (stippled blocks). Data sources as follows: man: Tonante et al. (1970/71) ; lamb:
Reeves ct al. (1936c) ; steer: Grover et al. (1963).
HUMAN SARTORIUS MUSCLE
75i
s -~
=-
BEEF HEART TISSUE
3
r
£ 2
I
5 S3
o
i
SL
NAT
DPNH
DPNH
cyto C
DEHYDROGENASE
REDUCTASE
FIG. 16. Comparison of various "biochemical parameters" at sea level (SL) and in. natives of high
altitude (NAT) . Data sources as follows: myoglobin concentration: Reynafarje (1962) ; mitochondria count and enzymes (measured by a change in
optical density) : Ou and Tenney (1970) .
ability, i.e., the tolerance to hypoxia (Lenfant et al., 1970). Two studies have shown
an increase in myoglobin concentration in
high altitude natives as compared to their
sea level counterparts: one study was concerned with humans (Reynafarje, 1962),
and the other with the llama (CuracaPena, 1970). All these reports seem to indicate that myoglobin concentration is an
important component of the adaptation to
chronic hypoxia.
Subcellular adaptations
Since oxygen is consumed at the subcellular level, i.e., by the mitochondria, it is
important to determine whether the
mitochondria and some of the metabolic
substrates are modified. There are, as yet,
very few studies that have been concerned
with this aspect of high altitude adaptation. A recent review (Poupa, 1972) summarizes the major metabolic shifts in the
mammalian heart acclimated to high altitude. Figure 16 shows some other data
on the mitochondria number and on enzymes intervening in oxygen utilization.
The increase in mitochondria number enhances the intracellular diffusion process
while the increase in en/yme concentration
suggests a higher rate of oxygen utiliza-
ADAPTATION TO ALTITUDE
455
fluence que les modifications de la pression barometrique exercent sur les phenomenes de la vie.
Masson, Paris.
Bisgard, G. E., H. G. Alvarez, and R. F. Grover.
1969. Decreased ventilatory response to hypoxia
during acute polycythemia in the calf. Resp.
Physiol. 7:369-382.
CONCLUSIONS
Bond, A. N. 1960. An analysis o£ the response of
salamander gills to changes in the oxygen conThis review of the high altitude adaptive
centration of the medium. Develop. Biol. 2:1-20.
mechanisms in mammals leads to several
Brooks, J. G., and S. M. Tenney. 1968. Ventilatory
response of llama to hypoxia at sea level and
conclusions:
high altitude. Resp. Physiol. 5:269-278.
1) As a whole, the adaptive process is
Burri, P. H., and E. R. Weibel. 1971. Morphometric
extremely complex, being made up of sevestimation of pulmonary diffusion capacity. II:
eral components that are either physiologic,
Effect of PO2 on the growing lung. Resp. Physiol.
morphologic, or biochemical in nature.
11:247-264.
Cassin, S., R. D. Gilbert, and E. M. Johnson. 1962.
The respective importance of these comCapillary development during exposure to
ponents varies among species.
chronic hypoxia. USAF School of Aerospace
2) No single component can explain the
Medicine SAM-TR-66-16.
completeness of the species adaptation,
Chiodi, H. 1962. Oxygen affinity of the hemoglobin
of high altitude mamals. Acta Physiol. Latinowhether newcomer or native. Each comAmer. 12:208-209.
ponent must be considered as an element
Chiodi, H. 1970. Comparative study of the blood
of an interdigitated system. It is clearly
gas transport in high altitude and sea level
evident that one form of adaptation incamelidae and goats. Resp. Physiol. 11:84-93.
fluences the next one. This is exemplified
Cruz-Jibaja, J., N. Banchero, F. Sime, D. Penaloza,
R. Gamboa, and E. Marticorena. 1964. Correlaby the position of the oxygen dissociation
tion between pulmonary artery pressure and
curve (physiological adaptation) that is corlevel of altitude. Dis. Chest 46:446-451.
related to the capillary density (morphoCuraca-Pena, A. A. 1970. Determination de miological adaptation) and to the critical P 0 2
hemoglobina en musculo estriado de glama Lama
Pacos. Arch. Inst. Biol. Andina Lima 3:112-121.
(biochemical adaptation).
Delaquerriere-Richardson, L., S. Forkes, and E.
3) It appears that neither physiological
Valdivia. 1965. Effect of simulated high altitude
nor morphological changes can fully exon the growth rate of the albino guinea pigs.
plain the mechanisms of adaptation to alJ. Appl. Physiol. 20:1022-1025.
Finch, C. A., and C. Lenfant. 1972. Oxygen transtitude. Although our knowledge of the
port in man. N. Engl. J. Med. 286:407-415.
biochemical alteration at altitude is still
Frisancho, A. R. 1969. Human growth and pulsuperficial, there is clear evidence that the
monary function of a high altitude Peruvian
most potent basis of adaptation may be at
Quechua population. Hum. Biol. 41:365-379.
the subcellular level. This is illustrated by
Crover, R. F., J. T. Reeves, D. H. Will, and S. G.
Blount. 1963. Pulmonary vasoconstriction in
the extreme tolerance of the diving mamsteers at high altitude. 18:567-574.
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