The Lancet • Saturday 19 September 1964
COMPARATIVE PHYSIOLOGY OF OXYGEN
TRANSPORT JON MAMMALS*
Heinz Bartels
M.D. Tubingen
PROFESSOR OF APPLIED PHYSIOLOGY, UNIVERSITY OF TUBINGEN
Children can ask questions that place adults in quite
s predicament. Such as: " Why are there elephants ? ",
or " Why are mice so small ? " Examined more closely.
these questions are not so stupid as we are at first inclined
to suppose. Children have an unspoilt capacity for
wonder—the ©avaaleiv of Epicurus—which adults lose
iS too soon as their minds become saturated with facts.
Another question that might be asked, not by a child
3u: by an adult who is childish enough, concerns the
weight at birth of various mammals. Fig. 1 shows that
weight at birth tends to be related to the length of gestation.
Nevertheless, there must be considerable differences in the
rate of fcetal growth; for after the same gestation period
i newborn hippopotamus weighs fifty times as much as
i newborn chimpanzee.
Between seals and whales the difference is even greater.
After almost the same gestation period, a newborn whale
-s about two hundred times heavier than a newborn seal,
tet the life of all of these animals begins with two cells,
which do not vary significantly in size from mammal to
•aammal (Linzbach 1955). In fig. 2. constructed by
Huggett and Widdas (1951), the comparative differences
O fcetal growth-rate are made clear.
A modern philosopher has said: " It is an important
and necessary indication of intelligence to know just what
questions one judiciously should ask." The reason why
*"«- may think the question " Why are there elephants ? "
BW particularly intelligent is that we cannot conceive an
•-aswer for it.
Certainly I am not going to provide one. Instead, I
-^all modify the question and ask: " How is it possible
*«*» elephants and mice both live in the same environ
ment ? ". Both are mammals, and very similar in structure
and function; yet the intensity of their cellular metabolism
fied if, according to the law of diniinishing metabolism
(Zeuthen 1953, Lehmann 1956), the cells of a shrew
require, on the average, a hundred times more oxygen (per
gramme of tissue) than the cells of an elephant ? A corres
ponding increase in the size of heart and lungs is unthink
able; reckoning 1 litre as 1 kg., the lung volume alone
represents about 8% of the body-weight—which makes
a hundredfold increase impossible. The geometrically
similar structure of mammals reflects itself in a fairly
constant relation between lung volume and body-weight
as graphically plotted (fig. 4) from the work of Tenney
and Remmers (1963).
Since the organs which transport oxygen through the
body do not show any large adaptations of structure
enabling them to cope with more intense metabolism, we
must look for adaptations of function. If the differences
are functional, we should expect to find that lung ventila
tion and cellular blood-supply are proportional not to the
body-weight but to the intensity of the metabolism. As
lung capacity cannot be expanded sufficiently to meet the
metabolic demand for oxygen, we should expect to find
the rate of respiration increased. And in fact we do. As
fig. 5 shows, the respiration-rate increases in direct propor
tion to the metabolic rate; from which it follows that
ventilation increases with increasing metabolism.
^•cs to the second power and their body-weight to the
7*k (ng- 3) power. How can such very different metabolic
aemands be satisfied with the same son of lungs and
respiratory organs ?
I shall attempt to find an explanation by examining the
Process of oxygen transport in these animals from the air
10 the body cells.
Most mammals live in an environment which offers
theni oxygen at tensions from 120 to 150 mm. Hg. A
Pressure gradient between the oxygen tension of the
ac*nosphere and that of the body cells allows oxygen to
Pjss
from the atmosphere
to the
cells enters
withoutthe
expenditure
°t
energy—so
long as enough
oxygen
lungs and
*j*-ansported by the circulating blood to xhe capillaries.
^tow can the oxygen requirements of the cells be satisPfcial lecture given on invitation of the University of London
to April, 1964, at St. Mary's Medical School, W.2.
■£.7360
GESTATION PERIOD (days )
Fig. 1 —Birthweight in mammals as a function of gestation period.
SEPTEMBER 19, 1964
ORIGINAL ARTICLES
ventilation of various animals yields some
interesting information. The work of Agostoni m
n a c " m . i . . * . -■ * . - • , . . * * * ' • « . j i
• ? Whale
330
390
takes five breaths
two hundred, mear
fluctuation in alveolar as well "as in arterST"
ter-" - ~"- ■--■■--■
tic
the size of the animal, and the greater fluctuation.
alveolar zas concenrrarinn i<* h**fFV>r-»r* k~
i Hipp op ot cuni/s
Rhinoceros
(Red deer)-
12 \ ! Uon'/PIg aw ^Rot-deer
• Puma /• Macacus -7*~ Chimpanzee
' "Mandrill
1lg^- - Moschus
Uistiti
toat ,
ou
120
180
2
40
300
360
420
480
540
mcreased residual capacity.
To achieve their greater respiratory ventilation
small animals must perform more work in breathi**
per gramme of body-weight (Crosfill and Widd?
combe 1961). But, as the entire metabolic proce*
is more intense in small animals, they do not spend
any greater proportion of their energy on respiratorneeds.
Thus we see that the varying oxygen requirement!
of large and small animals, with similar lung capacitv
are served by differences in ventilation. The qu^
tion now arises whether the increase in ventilation
of the lung is in fact related to increased oxvgenaucc
of the blood.
The degree to which the lung is permeable to
oxygen is called the oxygen capacity of the lung.
It is expressed in millilitres of oxygen per minute!
and millimetres of mercury. This figure is obtained
Opossum
F i g . 2 - P. o t o f c u b e - r o o t o f b i x - t h w e i g h t ' a g a L t g e . t . t l o n - t l m e l e s s t h e ^ ^ ^ T " ^ f t C o e f fi c i e n t o f O x y g e n
estimate of t„. (For further information see the original paper of "J*™51011 "** -Ung tlSSUe and lung Capillaries. Thus
Huggett and widdas 1951.) ' ' a material constant, as well as the diffusion distance
TIn„ addition,
„ , . . „ . a• rise
. . in
. «hearr-rarp, . , a n h=>nH<*
d * - * " - < ro
- • ->
s u rk'<--Tn<Mf a c e a r e ar-™A\nr.
o f t h e „„„„
l u ni g., ..i s „ a,.v a„i l a° b.l e.. f ."*
or
output. The smaller the animal, the higher the heart-rate; surface.
so the heart-rate is also roughly proportional to the In man, the diffusion capacity is 20-30 ml. oxygen per
intensity of the metabolism. mni.Hg per minute, and the exchange surface is assumed
dot N •Maun
Manatee ,/
Bear % / •Cow
pig */ Porpoise
Goat.*/Man
I ..o
Oog
Raccoon .
Cat
*/
-Slope = 102
NSor-ef-p/j* N. N
*»■*• ^w>->A--y«\ *Oog\
S
Cat*
Rabbit
\
\
•
^V
\
\
>v
\
»Pctrpc/se
Goat*\
N
RatiA Gumeo-pig
*w . \ •
v
a-or*
Man
•
\
»Cow
Mmto • \.
%
. *• ^
Dugana
/ % Mouse
^*Shrew
\Bat
0-0001
0*01
BODY-WEIGHT (g.)
b ody-wc ight.
I
0-1
1
10
1
10
1
100
I
1000
I
10.000
BODY-WEIGHT (kg.)
g. 4—Logarithmic plot of lung volume a« a function'
weight (after Tenhey and Remmers 1963).
;
-EMBER 19* 1964
THE LANCET
ORIGINAL ARTICLES
BREATHS per min.
y '
Whole /,
1000
S l o p e '■h O s ^ /
Pig
Coat \
Man
Dog /
100
10 r ~
.•Cow
Bear/
* /* Porpoise
*/*. Manatee
Ougotuj
o n - . - . ; - R a b b i t• /, R
t / .a c c o o n
Armadillo •,/ car
Woodchucks • Monkey
1*0
Rot /•Bumea-py
0-1
0-01
/ /M
• •o uSs he r e w
Bat
1
1
1
!
1
1
1000 10.000
Oj ( ml per kg per min.)
STROKES per mm.
Fig. 6—Logarithmic plot of alveolar surface area, a function of
whole-body oxygen consumption (after Tenney and Remmers
1963).
5—Metabolic rate (ml. 0: per kg. per min.) as a function of
tquencics of respiration and the heart respectively.
.ncrease the amount of oxygen taken up by the blood,
ess there is also an increase in the diffusion surface or
decrease in the diffusion distance. During physical
ivity. the diffusion capacity of the lung does indeed
rease, because more blood flows through the lung itself.
: an increase in perfusion and ventilation during physiactivity is unlikely to be the single way in which small
mals meet their higher oxygen needs. For, even at rest,
small animal—in comparison to the large animal—is
a relative state of work.
Probably- therefore, energy is conserved in small
mals by improvement in the diffusion of oxygen in the
■gs. Since the material constants cannot be altered, this
^rovement can be achieved only by shortening the
rusion distance or by a relative increase in the diffusion
p02 (mm.Hg )
"face area. Macklin and Hartroft '1940) found that the
Fig. 7—Oxygen dissociation curve of human blood, saturation per
eolar diameter of the shrew is smaller to the second
cent as c function of oxygen tension, at pK 7-2-7-6.
wet than that ofthe manatee. This means an increase in
eoli per unit of lung diffusion surface.
glob in concentration of an animal's blood and the intensity
II one roughly assumes the alveolar surface to be fully of its metabolism. The oxygen capacity of blood, an
-"'jpied with capillaries, there appears to be a rather good expression of its haemoglobin concentration, ranges from
"elation between the total alveolar surface and the
16 to 25 ml. oxygen per 100 ml. blood. But cats have
-nsity of the particular animal's metabolism (fig. 6). the same oxygen capacity as elephants.
*e smaller animals achieve their fmer rate of metabolism not only by
-ive increases in ventilation and -2 •»w*
elation but also by relative enlarge- £ 35
-nt of the lung surface involved in ^"
:-ous
exchange.
S,o
'^hen oxygen is taken up by the $ ^ 30
"°d in the lung capillaries, it is trans- c *:
• Go/ der* hdmster^.
r-ed to the tissue capillaries. The '~ -•Guntc-pig
-"•sport medium, blood, is a physico- ^ -mically specialised fluid that is far g 25
-'er suited for gas transport than j;
y other fluid we could think of. <_
Qxygen is loosely bound to the c*>
"otnoprotein haemoglobin. One nor- »•*• 21
% finds 12-19 g. of haemoglobin 10
BODY-WEIGHT ( g.)
*00 ml. blood. No correlation is p. g_Half.tatura
Fig. 8—Half-saturation oxygen tension (T„) as a function of body-weight. All animals'
parent, however, between the haemo- blood
bloodcorrected
corrected tot pH 7-4 and 37°C.
602 SEPTEMBER 19, 1964
ORIGINAL ARTICLES
tensions are plotted in relation to 1
< *"". ™ ON
small animals have a definitely higher half-satur,
tension.
"
^*t*
j *-nis manner of representation was chc-w
So80U*-30%
''/Shrew ,32VC
; ]2\^7i/Shrew [ J l«gues and I have added the values for v'
elephant (Bartels et al. 1963a). It is evident Sf
il/ : A. Krogh foretold, the larger animals wim reS!
80
100
0
2o
p02
p U (mm.Hg.)
2lmmHg)
1 80 100
meless there are many exceptions. For",
^TlSSofathdl"rUtl0nTV"* (Wlth """^ P« cent and volume. *? ^ ™* « body-weight of 50 kg., has
5»*?r^sa«aasr -«—— X^^s8'^^^^ r"
TT-,» ;«,«^-»— -i . ... _ . dehverv of the shrew. rnmn-ir»ri „r,ru .i ,
globin bond is that with a sufficient amount of oxveen in HrrhT .i-* !*&*** tCnSI°n m *■ dssues of » te
the lung, haemoglobin can become saturated andwl"en 2*2? S^te Sri" "V"* desa^2
transport the oxveen ro -hP ri«i„. *«iui. ...-.._. agamst oo 0 for the shrew. In addition the mZ
given_off to the cells. The oxygen dissociation lJt
[tig. /) presents this relationship quite simply. With mak
a mammal to oxygenate the blood in its lung capillaries arterv
sufficiently at altitudes of about 12,000 ft. as well as at
sea level. But, at lower oxygen tensions, between 50 and
1U mm. Hg, the oxygen-binding ability of hemoglobin
decreases sharply. This means that when blood saturated
with oxygen enters a tissue capiUary where the oxygen
tension averages only 30 mm. Hg, almost half the chemic
ally bound oxygen can be given off to the tissue. The
quotient AS2/'Ap02 rises as oxygen tension falls. Hence,
for particular pressure differences, more and more oxygen
can
be
given
off.
6
Not only is the numerical value of this quotient a
deciding factor in the delivery of oxygen from blood to
tissue, but so also is the oxygen capacity of the blood and
the relationship of the quotient to the dissociation curve
At what oxygen tension does the oxygenated hemoglobin
begin to undergo drastic deoxygenation ? This point is by
no means the same in all ammmals. One can make
comparisons by determining at what oxygen tension half
the hemoglobin is saturated with oxygen. This is known
as the half-saturation tension. If these half-saturation
though whether the shrew acrua.
s pulmon-,-
11 / 3 1
WW/A
Eleohant fcetus
( '2 months )
30
Po-> (mm.Hg)
/ / -j Fi»-n—Oxygen dissociation curves of k
/ / - Another feature of the respiratory function of mac7 / M mdian biood concerns the intra-erythrocvte hemogtocr
II ' eventration. M
a m m33°„
a l i ahemoglobin,
n e r y t h r o cand
y t e sit was
gene
r a l l y that
c o n ndo
=
about
thought
figure varied very little. In shrews, white mice, and golde
• ranging from 45 to 48% (Ulrich et al. 1963), the ware
content being appreciably lower. These high hemoglofc
/ h a m s t e r s , h o w e v e r, w e f o u n d h e m o g l o b i n c o n c e n t r a r i c e
ou /u a io 20.30 40 so eo ?b Www «K>raarocm in conjunction with a high^ "Jaj*
o2 pressure -,-:, - . ^1^* ™.?^Probably evolved as a result of hyV
iiii im^mmmmn
-
-
2c£SS3S-£*-
ORIGINAL ARTICLES
TEMBE.t
Similarly high hemoglobin concentrations were found
the red cell of the camel and the llama (Bartels et al.
53a), which belong to the same family. Perhaps some; will be able to find a correlation with the extreme
rdens placed upon the fluid balance of these animals.
Dxygen-binding characteristics differ not only between
•ious mammals but also during the life-span of the
iividual. The oxygen affinity of the blood is increased
"ore birth, and decreases after it. In all cases it falls
tow the value for the adult. The half-saturation tension
blood is 2-10 mm. Hg lower in the fcetus than in the
alt (Bartels et al. 1964). Only with a 5 months' elephant
rjs in Uganda did we find a virtually identical dissociaD curve in both mother and fcetus. In an elephant fcetus
about 12 months the dissociation curve was shifted to
: left, as in all other mammals investigated (fig. 10).
The shift in the dissociation curve is much greater in
wborn goats than in the elephant or human. The pur
se of this mechanism seems (fig. 11) to be to increase
ygen uptake from the mother's blood in the placenta.
After birth, the intake of oxygen is achieved more
.ciently through lung respiration. The blood no longer
90
3C
Oz- Capacity
o Elephant
Horse .
\ *k.oX« Cattle
. • English. Sette*
Haemoglobin
< Solution
Blood x*
\
"Goneo-Pic
°Golder. Homster
Shrew
t White Mouse
-0-4
-0-5
-0-6 -0-7 -0-8
A log. Pq,
-0-9
-1*0
& pH
Fig. 13—Logarithmic plot of body-weight as a function of the Bohr
effect in hemoglobin solutions and in blood. Compiled after
results of Riggs (1960), Hilpen etal. (1963), Baumann et al. (1963),
and Ulrich et al. (1963).
s.hdoy . «ssue.
as0;-27% Simultaneously with this shift there are
* *'0vo1-* _ changes in oxygen capacity: the two values
1 seem to be closely related. Which is
80
28
$
3« 70
,6
J? 60
&
THE LANCET
1 needs to have so high an oxygen affinity-,
and the resulting shift to the right improves
>" " the dissociation of oxygen from blood to
100
32
*
mmmmmmmm*
50
primary and which secondary I shall not
20th doy
t, S0,-3B% tT t0 decide; but the picture is to some
liTso^MX
— *«3-e'vo:
3-8vol. % % - extent clarified by the observation that the
40
oxygen tension of venous blood is one
■ of the factors regulating erythropoiesis
22
20
(Tribukait 1963). When blood has a rela7C 80 tively low oxygen affinity-, comparativelyp02 ( mm.Hg )
high tensions occur in venous blood, slowhalf-saturation oxygen tension (T,6), and,i, arteriovenous
arteriovenous ing down erythropoiesis. Thus it may be
5th and 20th day (after Bartels et al. 1963b).
*3b). that a mechanism not yet fully understood
first changes the oxygen affinity- of the
blood and then increases or decreases the
(Vot.X)
rate of erythropoiesis.
in, oxygen
■ Human
placenta
u
m
a
n
p
l
a
c
e
n
t a In man.
.
* ther changes
,
.
.
. , affinity
,
Shrew
and
capacity
after
birth
are
such
that a
White mouse
ter given difference in arterial and venous
oxygen tensions during the first month of
life coincides with a constant difference in
the arterial-venous oxygen content (Bartels
et al. 1960). This would mean that the
oxygen supply is maintained constant
.* despite the anzemia of the newborn result
30 ■•
AGE (doys)
t 12—Oxygen capacity,
iiflerences in kids at the
Ya k
▶
Dog -+O50
Cow
t
Guineo pig
Goat
Camel
G°lden hamster
Rabbit
)
■Newborn human
•«—Sheep } Lan
—Pig
White mouse
Elephant.
Elephant
ing from reduced oxygen affinity.
00 fo understand how the growing organ
ism benefits from these changes, it is
necessary not only to investigate the
respiratory function of the blood but also
to obtain the actual in-vivo blood-gas
obblt values in arterial and venous blood. To
be significant, these measurements should
be made on non-an£esthetised animals.
Guinea
ur*opigpig Tq explain ^g meaning of these changes
.. . . wea m
have
effort
to
s t e made
r
, every
_young
, lambs
, obtain
,and _useful
„„,„
' information
from
goats
Golden
o l ahamster
enn
naJep (Bartels et al. 1963b). We placed indwelling
catheters in the pulmonary artery and aorta.
The animals were then observed for days
**• 14—Bohr effect and "effective Bohr effect" In mammals1 (after
(aftcr HUpert
mipert
w * 1M3, and Ulrich et al. 1963).
M2
SEPTEMBER 19, 1964
ORIGINAL ARTICLES
or weeks while they respired through a tracheal cannula or
mask attached to a spirometer. In this manner we could
follow the oxygen consumption, the blood gases, the car
diac output, and the respiration from the first to about the
thirtieth day after birth. From the first to the twentieth
day, the half-saturation tension, as an expression of the
shift to the right of the dissociation curve, increased from
20 to 31 mm. Hg. Simultaneously, the oxygen. capacity
decreased almost 30% (fig. 12). On the right side of the
figure two in-vivo dissociation curves are shown. At an
almost unchanged mixed venous oxygen tensions, an
increase in dissociation resulting in better tissue oxida
tion occurred. Despite a reduced oxygen capacity,
the difference between arterial-venous oxygen content
remained essentially the same.
Also important for oxygen transport in blood is the
Bohr effect. The oxygen-binding ability of haemoglobin
is influenced by the amount of carbon dioxide bound to
the haemoglobin, as well as by the pH of the blood. We
have enough experimental evidence to form ideas as to me
possible purpose of this mechanism 'Manwell I960,
Riggs 1960, Hilpert et al. 1963).
Working with haemoglobin in solution, Riggs ''I960)
found a good correlation between the magnitude of the
Bohr effect and body-weight 'fig. 13). Accordingly, die
elephant has the smallest, and the mouse the largest
Bohr effect. One can see from this that the lower oxygen
affinity is a further adaptation of the small animal to its
intensive metabolism.
When, however, one examines our findings on the
extent of the Bohr effect as it actually occurs in the
blood (fig. 13), the preceding correlation is found to be
somewhat diminished. To understand the working of the
Bohr effect in vivo, it must be interpreted in combination
with the oxygen capacity and affinity of the blood. We call
this the " effective Bohr effect " (Hilpert et al. 1963)—
defined as the volume per cent given off by 100 ml. blood
at 50% saturation, on acidification by 0-1 pH unit without
a change in oxygen tension. When we look at the results
of these measurements and calculations in fig. 14, our
original joy disappears; for we no longer see any correlation
with the intensity of metabolism.
To complete this discussion, a word must be said about
the nature of the blood-supply and extent of capillarisation
in the organs of various animals.
Just as an increase in ventilation does not necessarily
mean a ereater intake of oxvcen bv rh*» bInnH_ <*n an
increased blood-supply to the tissue does not necessarily
mean a greater supply of oxygen to the tissue. In studies
of the skeletal muscle of the horse, dog, and guineapig
August Krogh (1919a and b) found that the smaller the
animal the greater the number of capillaries per square
millimetre of muscle tissue. Other researchers have
further investigated these findings. Recently SchmidtNielsen and Pennycuik (1961) published measurements on
the capillary density in animals ranging in body-weight
from 9 to 450,000 g. These findings agree only roughly
with those of Krogh (1919a), for there is only a slight
difference in the capillary density in such widely dis
similar animals as the rat and the pig (fig. 15). The concept
is partially supported by the astoundingly high density of
capillaries in the bat. Results are still lacking for such
large animals as the elephant.
Finally, it has also been found that compared with
larger animals, smaller ones have higher tissue cytochrome
oxidase activity (Kunkel and Campbell 1952, Kunkel
THE LA*
~—|
-
100
!000
CAPILLARIES (persq.mm.)
Fig. 15—Logarithmic plot of body-weight as a function of capilu.
per sq. mm. in gastrocnemius muscle (data from Schm
Nielsen and Pennycuik 1961).
et al. 1946) and cytochrome-C concentration (Drabk
1950). This further enables smaller animals with increas
metabolic intensity to meet the demands of thi
metabolism.
Conclusion
As a starting-point for our discussion we took the law
diminishing metabolism, and asked die question: How
it possible, with geometrically similar structures, for ;
smallest animal to have a metabolic intensity a huncir
times greater than that of the largest animal ?
We considered the part played by oxygen transport, asaw that in smaller animals ventilation and perfusi.
become relatively greater with increasing metabo
intensity. As metabolism grows more intense, the dema;
for more gas transport can be satisfied by increased at
fusion only when the gaseous exchange surfaces oft
alveoli and tissues enlarge. We have also seen th
improvement in the delivery of oxygen to the tissues
achieved through lowered oxygen affinity of the blood.
It will be very valuable if, through new comparati
experimentation, deviations from these concepts appes
By more objective scrutiny we may eventually attain full
understanding of that part of Nature of which we ourselv
are a part.
As Goethe once said: " The reason I ultimately pre:
to commune with Nature, is because she is always righ:the error can only be on my side."
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Bartels, H., Buss, I., Kleihauer, E., Luck, C, Metcalfe, J., Riegel, i
(toK.,
beBetke,
published).
—Wright,
Hilpert, P.
P.,(1964)
Barbey,
K., Riegel, K., Lang, E. M., Metcalfe
(1963a)
Amer.
J.
Physiol.
205,ges.
331.Physiol. 271, 169.
— — Riegel, K. (1960) Arch.
— — — (1963b)ibid. 277,6.
Baumann, P., Hilpert, P., Bands, H. (1963) ibid. p. 120.
Crosfill, M. L., Widdicombe, J. G. (1961) J. Physiol. 158, 1.
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Hilpert, P., Fleischmann, R., Kempe, D., Bartels, H. (1963) Amer. J. PhyHuggett', A. St. G., Widdas, W. F. (1951) 7. Physiol. 114, 306.
Krogh, A. (1919a) ibid. 52, 409.
— (1919b) ibid. p. 457.
— (1940) Comparative Physiology of Respiratory Mechanisz
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Kunkel, H. O., Campbell, I. E., Jr. (1952) J. biol. Chem. 198, 229.
— Spalding, I. F., de Franciscis, G., Futrell, M. F. (1956) Amer.
Physiol. 186, 203.
Lehmann, G. (1956) Das Gesetz der Stotfwechselproduktion: Handbu
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Linzbach, A. J. (1955) Handbuch der allgemeinen Pathologic, vol. vi, pa
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Manwell, C. (I960) Ann. Rev. Physiol. 22, 191.
Riggs, A. J. (1960) J. gen. Physiol. 43, 737.
Schmidt-Nielsen,
Larimer,
J. 200,
L. (1958)
— Pennycuik, P.K,(1961)
ibid.
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Tenney, S. M., Remmers, J. E. (1963) Nature, Land. 197, 54.
Tribukait, B. (1963) Acta Physiol, scand. 57, 1.
Ulrich, S., Hilpert, P., Bartels, H. (1963) Arch. tej. Physiol. 205, 331.
Zeuthen, E. (1953) Quart. Rev. Biol. 28, 1.