THE SPECIFIC RÔLE OF ADRENIN IN COUNTERACTING THE
EFFECTS OF FATIGUE
As a muscle approaches its fatigue level, its contractions are
decreased in height. Higher contractions will again be elicited
if the stimulus is increased. Although these phenomena are well
known, no adequate analysis of their causes has been advanced. A
number of factors are probably operative in decreasing the height
of contraction: (1) The using up of available energy-producing
material; (2) the accumulation of metabolites in the fatigued muscle;
(3) polarization of the nerve at the point of repeated electrical
stimulation; and (4) a decrease of irritability. It may be that
there are interactions between these factors within the muscle, e.
g., the second may cause the fourth.
Variations of the Threshold Stimulus as a
Measure of Irritability
The last of the factors mentioned above--the effect of fatigue
on the irritability of the nerve-muscle combination, or on the
muscle alone--can be tested by determining variations in the least
stimulus capable of causing the slightest contraction, the so-called
“threshold stimulus.” As the irritability lessens, the threshold
stimulus must necessarily be higher. The height of the threshold is
therefore a measure of irritability. How does fatigue affect the
irritability of nerve-muscle and muscle? How is the irritability
of fatigued structures affected by rest? How is it influenced by
adrenin or by adrenal secretion? Answers to these questions were
sought in researches carried on by C. M. Gruber[85] in 1913.
The Method of Determining the Threshold Stimulus
The neuro-muscular arrangements used in these researches were in
many respects similar to those already described in the account
of experiments by Nice and myself. To avoid the influence of an
anesthetic some of the animals were decerebrated under ether and then
used as in the experiments in which urethane was the anesthetic. The
nerve (the _peroneus communis_) supplying the _tibialis anticus_
muscle was bared and severed; and near the cut end shielded platinum
electrodes were applied. These electrodes were used in fatiguing
the muscle. Between these electrodes and the muscle other platinum
electrodes could be quickly applied to determine the threshold
stimulus and the tissue resistance. These second electrodes were
removed except when in use, and when replaced were set always in
the same position. Care was taken, before replacing them, to wipe
off moisture on the nerve or on the platinum points.
For determining the threshold stimulus of the muscle the skin and
other overlying tissues were cut away from the _tibialis anticus_ in
two places about 5 centimeters apart. Through these openings platinum
needle electrodes could be thrust into the muscle whenever readings
were to be taken. Local polarization was avoided by reinserting
the needles into fresh points on the exposed areas whenever new
readings were to be taken.
The tendon of the _tibialis anticus_ was attached, as in the previous
experiments, by a strong thread passing about pulleys to a lever
which when lifted stretched a spring. During the determination of
the threshold the spring was detached from the lever, so that only
the pull of the lever itself (about 15 grams) was exerted on the
muscle.
The method of measuring the stimulating value of the electric current
which was used in testing the threshold was that devised by E. G.
Martin[*] of the Harvard Laboratory--a method by which the strength
of an induced electric shock is calculable in definite units.
If the tissue resistance enters into the calculation these are
called β units. When the threshold of the nerve-muscle was taken,
the apparatus for the determination was connected with the nerve
through the electrodes nearer the muscle. They were separated from
the fatiguing electrodes by more than 3 centimeters, and arranged
so that the kathode was next the muscle. When the threshold of
the muscle was taken directly the apparatus was connected with
the muscle through platinum needle electrodes thrust into it. The
position of the secondary coil of the inductorium, in every case,
was read by moving it away from the primary coil until the very
smallest possible contraction of the muscle was obtained. Four of
these readings were made, one with tissue resistance, the others
with 10,000, 20,000, and 30,000 ohms additional resistance in the
secondary circuit. Only break shocks were employed--the make shocks
were short-circuited. Immediately after the determination of the
position of the secondary coil, and before the electrodes were
removed or disconnected, three readings of the tissue resistance
were made. From these data four values for β were calculated.
*[Footnote: For a full account of Dr. Martin’s method of
calculating the strength of electric stimuli, see Martin: The
Measurement of Induction Shocks, New York, 1912.]
The strength of the primary current for determining the threshold
of the nerve-muscle was usually .01 ampere, but in a few cases
.05 ampere was used. For normal muscle it was .05 ampere and for
denervated muscle 1.0 ampere. The inductorium, which was used
throughout, had a secondary resistance of 1400 ohms. This was added
to the average tissue resistance in making corrections--corrections
were made also for core magnetization.
The Lessening of Neuro-muscular Irritability by Fatigue
The threshold for the _peroneus communis_ nerve in decerebrate
animals varied from 0.319 to 2.96 units, with an average in sixteen
experiments of 1.179.[*] This average is the same as that found by
E. L. Porter[86] for the radial nerve in the spinal cat. For animals
under urethane anesthesia a higher average was obtained. In these
it varied from .644 to 7.05, or an average in ten experiments of
3.081.
*[Footnote: For the detailed data of these and other quantitative
experiments, the reader should consult the tables in the original
papers.]
The threshold for the _tibialis anticus_ muscle varied in the
decerebrate animals from 6.75 units to 33.07, or an average in
fifteen experiments of 18.8. Ten experiments were performed under
urethane anesthesia and the threshold varied from 12.53 to 54.9,
with an average of 29.84 β units. From these results it is evident
that anesthesia notably affects the threshold.
E. L. Porter proved, by experiments carried on in the Harvard
Physiological Laboratory, that the threshold of an undisturbed
nerve-muscle remains constant for hours, and his observation was
confirmed by Gruber (see Fig. 19). If, therefore, after fatigue, a
change exists in the threshold, this change is necessarily the result
of alterations set up by the fatigue process in the nerve-muscle
or muscle.
After fatigue the threshold of the nerve-muscle, in sixteen
decerebrate animals, increased from an average of 1.179 to 3.34--an
increase of 183 per cent. In ten animals under urethane anesthesia
the threshold after fatigue increased from a normal average of 3.08
to 9.408--an increase of 208 per cent.
An equal increase in the threshold stimulus was obtained from the
normal muscle directly. In decerebrate animals the normal threshold
of 18.8 units was increased by fatigue to 69.54, or an increase
of 274 per cent. With urethane anesthesia the threshold increased
from 29.849 to 66.238, or an increase of 122 per cent.
Fig. 18, plotted from the data of one of the many experiments, shows
the relative heights of the threshold before and after fatigue. The
correspondence of the two readings of the threshold, one from the
nerve supplying the muscle and the other from the muscle directly,
served as a check on the electrodes. The broken line in the figure
represents the threshold (in units) of the nerve-muscle, and the
continuous line that of the muscle. The threshold values of the
nerve-muscle have been magnified ten times in order to bring the
two records close together. In this experiment the threshold of
the muscle after fatigue (i. e., at 2) is 167 per cent higher than
the normal threshold (at 1), while that of the nerve-muscle after
fatigue is 30.5 per cent higher than its normal.
[Illustration: Figure 18.--A record plotted from the data of one
experiment. The time intervals in minutes are registered on the
abscissa; the value of the threshold in units is registered on
the ordinate. The continuous line is the record of the muscle,
the broken line that of the nerve-muscle. The values for the
nerve-muscle have been magnified ten times, those for the muscle
are normal.
(1) Normal values of the threshold.
(2) Fatigue thresholds after one hour’s work, lifting 120 grams
240 times a minute.
(3 and 4) The threshold after rest.]
Evidently a direct relation exists between the duration of work and
the increase of threshold. For instance, the threshold is higher
after a muscle is fatigued for two hours than it is at the end of
the first hour. The relation between the work done and the threshold
is not so clear. In some animals the thresholds were higher after
120 grams had been lifted 120 times a minute for 30 minutes than
they were in others in which 200 grams had been lifted 240 times
a minute for the same period. The muscle in the latter instances
did almost four times as much work, yet the threshold was lower.
The difference may be due to the general condition of the animal.
A few experiments were performed on animals in which the nerve
supplying the muscle was cut seven to fourteen days previous to the
experiment. The muscle, therefore, had within it no living nerve
fibres. The average normal threshold for the denervated muscle in
6 animals was 61.28 units. As in the normal muscle, the percentage
increase due to fatigue was large.
The Slow Restoration of Fatigued Muscle to
Normal Irritability by Rest
That rest decreases the fatigue threshold of both nerve-muscle and
muscle can be seen in Fig. 18. The time taken for total recovery,
however, is dependent upon the amount of work done, but this change,
like that of fatigue, varies widely with different individuals. In
some animals the threshold returned to normal in 15 minutes; in
others, in which the same amount of work was done, it was still
above normal even after 2 hours of rest. This may be due to the
condition of the animals--in some the metabolites are probably
eliminated more rapidly than in others. There were also variations
in the rate of restoration of the normal threshold when tested on
the nerve and when tested on the muscle in the same animal. In
Fig. 18 (at 3) the nerve-muscle returned to normal in 30 minutes,
whereas the muscle (at 4) after an hour’s rest had not returned
to normal by a few β units. This, however, is not typical of all
nerve-muscles and muscles. The opposite condition--that in which
the muscle returned to normal before the nerve-muscle--occurred
in as many cases as did the condition just cited. The failure of
the two tissues to alter uniformly in the same direction may be
explained as due to variations in the location of the electrodes
when thrust into the muscle at different times (e. g., whether near
nerve filaments or not). The results from observations made on the
nerve are more likely to be uniform and reliable than are those
from the muscle.
The time required for the restoration of the threshold from fatigue
to normal, in denervated muscles, is approximately the same as that
for the normal muscle.
The Quick Restoration of Fatigued Muscle to
Normal Irritability by Adrenin
The foregoing observations showed that fatigue raises the normal
threshold of a muscle, on the average, between 100 and 200 per cent
(it may be increased more than 600 per cent); that this increase
is dependent on the time the muscle works, but also varies with
the animal; that rest, 15 minutes to 2 hours, restores the normal
irritability; and that this recovery of the threshold depends upon
the time given to rest, the duration of the work, and also upon
the condition of the animal. The problem which was next attacked
by Gruber was that of learning whether the higher contractions of
fatigued muscle after splanchnic stimulation could be attributed
to any influence which adrenal secretion might have in restoring
the normal irritability. To gain insight into the probabilities he
tried first the effects of injecting slowly into the jugular vein
physiological amounts of adrenin.[*]
*[Footnote: The form of adrenin used in these and in other
injections was fresh adrenalin made by Parke, Davis & Co.]
The normal threshold of the _peroneus communis_ nerve varied in the
animals used in this series of observations from 0.35 to 5.45 units,
with an average in nine experiments of 1.3, a figure close to the
1.179 found in the earlier series on the effect of fatigue. For the
_tibialis anticus_ muscle, in which the nerve-endings were intact,
the threshold varied from 6.75 to 49.3 units, with an average in
the nine experiments of 22.2. This is slightly higher than that
cited for this same muscle in the earlier series. By fatigue the
threshold of the nerve-muscle was increased from an average of 1.3
to an average of 3.3 units, an increase of 154 per cent. The muscle
increased from an average of 22.2 to an average of 59.6, an increase
of 169 per cent. After an injection of 0.1 to 0.5 cubic centimeters
of adrenin (1:100,000) the fatigue threshold was decreased _within
five minutes_ in the nerve-muscle from an average of 3.3 to 1.8,
a recovery of 75 per cent, and in the muscle from an average of
59.6 to 42.4, a recovery of 46 per cent. To prove that this effect
of adrenin is a _counteraction of the effects of fatigue_, Gruber
determined the threshold for muscle and nerve-muscle in non-fatigued
animals before and after adrenin injection. He found that in these
cases no lowering of threshold occurred, a result in marked contrast
with the pronounced and prompt lowering induced by this agent in
muscles when fatigued.
Figs. 19 and 20, plotted from the data of two of the experiments,
show the relative heights of the threshold before and after an
injection of adrenin. The close correspondence of the two readings
of the threshold, one from the nerve supplying the muscle, the other
from the muscle directly, served to show that there was no fault
in the electrodes. The continuous line in the Figures represents
the threshold (in units) of the muscle, the broken line that of the
nerve-muscle. The threshold of the nerve-muscle is magnified 100
times in Fig. 19 and 10 times in Fig. 20. In Fig. 19 (at 2 and 4)
the threshold was taken after an intravenous injection of 0.1 and
0.2 cubic centimeter of adrenin respectively.
These examples show that adrenin does not affect the threshold of
the normal non-fatigued muscle when tested either on the muscle
directly or on the nerve-muscle. In Fig. 19 (at 3) the observation
taken after two hours of rest illustrates the constancy of the
threshold under these circumstances.
In Fig. 19 the normal threshold was increased by fatigue (at 5)--the
muscle had been pulling 120 times a minute for one hour on a spring
having an initial tension of 120 grams--from 30.0 to 51.6 units,
an increase of 72 per cent; and in the nerve-muscle from 0.62 to
0.89 units, an increase of 46 per cent. The threshold (at 6) was
taken _five minutes_ after injecting 0.1 cubic centimeter of adrenin
(1:100,000). The threshold of the muscle was lowered from 51.6 to
38.0 units, a recovery of 62 per cent; that of the nerve-muscle
from 0.89 to 0.79 units, a recovery of 37 per cent. After another
injection of 0.5 cubic centimeter of adrenin the thresholds (at
7) were taken; that of the nerve-muscle dropped to normal--0.59
units--a recovery of 100 per cent, and that of the muscle remained
unaltered--26 per cent above its normal threshold.
[Illustration: Figure 19.--A record plotted from the data of
one experiment. The time intervals in hours and minutes are
represented on the abscissa; the values of the threshold in β
units are represented on the ordinate. The continuous line is the
record of the muscle, the broken line that of the nerve-muscle.
The nerve-muscle record is magnified 100 times; that of the muscle
is normal.
(1) Normal threshold stimulus. (2) Threshold five minutes after
an intravenous injection of 0.1 cubic centimeter of adrenin
(1:100,000) without previous fatigue. (3) Threshold after a rest
of two hours. (4) Threshold five minutes after an injection of 0.2
cubic centimeter of adrenin (1:100,000) without previous fatigue.
(5) Threshold after one hour’s fatigue. The muscle contracted
120 times per minute against a spring having an initial tension
of 120 grams. (6) Threshold five minutes after an injection (0.1
cubic centimeter) of adrenin (1:100,000). (7) Threshold five
minutes after another injection of adrenin (0.5 cubic centimeter
of a 1:100,000 solution).]
In Fig. 20 the threshold (at 5) was taken five minutes after an
injection of 0.1 cubic centimeter of adrenin. The drop here was as
large as that shown in Fig. 19. The threshold taken from the muscle
directly was lowered from 30.6 to 18 units, a recovery of 61 per
cent; the nerve-muscle from 1.08 to 0.87 units, a recovery of 51
per cent. That this sudden decrease cannot be due to rest is shown
in the same Figure (at 3 and 4). These readings were made after 60
and 90 minutes’ rest respectively. The sharp decline in the record
(at 5) indicates distinctly the remarkable restorative influence
of adrenin in promptly lowering the high fatigue threshold of
neuro-muscular irritability.
[Illustration: Figure 20.--A record plotted from the data of
one experiment. The time intervals in hours and minutes are
registered on the abscissa; the values of the threshold in units
are registered on the ordinate. The continuous line is the record
of the muscle, the broken line that of the nerve-muscle. The
record of the nerve-muscle is magnified ten times; that of the
muscle is normal.
(1) Normal threshold. (2) The threshold after one hour’s fatigue.
The muscle contracted 120 times per minute against a spring having
an initial tension of 120 grams. (3 and 4) Thresholds after rest;
after 60 minutes (3), and after 90 minutes (4). (5) Threshold
five minutes after an injection of adrenin (0.1 cubic centimeter
of a 1:100,000 solution). (6 and 7) Thresholds after rest; after
60 minutes (6), and after 90 minutes (7).]
The Evidence that the Restorative Action of
Adrenin is Specific
As stated in describing the effects of arterial blood pressure,
an increase of pressure is capable of causing a decided lowering
of the neuro-muscular threshold after fatigue. Is it not possible
that adrenin produces its beneficial effects by bettering the
circulation?
Nice and I had argued that the higher contractions of fatigued
muscle, that follow stimulation or injection of adrenin, could not
be wholly due to improved blood flow through the muscle, for when by
traction on the aorta or compression of the thorax arterial pressure
in the hind legs was prevented from rising, splanchnic stimulation
still caused a distinct improvement, the initial appearance of
which coincided with the point in the blood-pressure curve at which
evidence of adrenal secretion appeared. And, furthermore, the
improvement was seen also when adrenin was given intravenously in
such weak solution (1:100,000) as to produce a _fall_ instead of a
rise of arterial pressure. Lyman and I had shown that this fall of
pressure was due to a dilator effect of adrenin. Since the blood
vessels of the fatigued muscle were dilated by severance of their
nerves when the nerve trunk was cut, and, besides, as previously
stated (see p. 86), were being stimulated through their nerves at
a rate favorable to relaxation, it seemed hardly probable that
adrenin could produce its beneficial effect by further dilation
of the vessels and by consequent flushing of the muscle with an
extra supply of blood.[87] The lowering of blood pressure had
been proved to have no other effect than to impair the action of
the muscle (see p. 103). Although the chances were thus against an
interpretation of the beneficial influence of adrenin through action
on the circulation, it was thought desirable to test the possibility
by comparing its effect with that of another vasodilator--amyl
nitrite.
Figs. 21 and 22 are curves obtained from the left _tibialis anticus_
muscle. The rate of stimulation was 240 times a minute.
The muscle in Fig. 21 contracted against a spring having an initial
tension of 120 grams, and that in Fig. 22 against an initial tension
of 100 grams. In Fig. 21, at the point indicated on the base line,
0.4 cubic centimeter of adrenin (1:100,000) was injected into the
left external jugular vein. There resulted a fall of 25 millimeters
of mercury in the arterial pressure and a concurrent betterment of
15 per cent in the height of contraction, requiring two minutes
and fifteen seconds of fatigue (about 540 contractions) before it
returned to the former level. In Fig. 22, at the point indicated by
the arrow, a solution of amyl nitrite was injected into the right
external jugular vein. There resulted a fall of 70 millimeters of
mercury in arterial pressure and a betterment of 4.1 per cent in
the height of muscular contraction, requiring fifteen seconds of
fatigue (about 60 contractions) to decrease the height of contraction
to its former level. In neither case did the blood pressure fall
below the critical region (see p. 104).[*]
*[Footnote: In some cases after injection of amyl nitrite the
normal blood pressure, which was high, dropped sharply to a point
below the critical region. There resulted a primary increase in
muscular contraction due to the betterment in circulation caused
by the dilation of the vessels before the critical region was
reached. During the time that the pressure was below the critical
region the muscle contraction fell. As the blood pressure again
rose to normal the muscle contraction increased coincidently.]
[Illustration: Figure 21.--Top record, blood pressure with
mercury manometer. Middle record, contractions of the _tibialis
anticus_ muscle 240 times per minute against a spring with an
initial tension of 120 grams. Bottom record (zero blood pressure),
injection of 0.4 cubic centimeter of adrenin (1:100,000). Time
in half minutes.]
[Illustration: Figure 22.--Top record, blood pressure with mercury
manometer. Middle record, contractions of _tibialis anticus_
muscle 240 per minute against a spring with an initial tension
of 100 grams direct load. Bottom record (zero blood pressure),
time in half minutes. The arrow indicates the point at which a
solution of amyl nitrite was injected.]
Although the fall in arterial pressure caused by dilation of the
vessels due to amyl nitrite was almost three times as great as that
produced by the adrenin, yet the resultant betterment was only
about one-fourth the percentage height and lasted but one-ninth the
time. In all cases in which these solutions caused an _equal_ fall
in arterial pressure, adrenin caused higher contractions, whereas
amyl nitrite caused _no appreciable change_.
The Point of Action of Adrenin in Muscle
From the evidence presented in the foregoing pages it is clear that
adrenin somehow is able to bring about a rapid recovery of normal
irritability of muscle after the irritability has been much lessened
by fatigue, and that the higher contractions of a fatigued muscle
after an injection of adrenin are due, certainly in part, to some
specific action of this substance and not wholly to its influence
on the circulation. Some of the earlier investigators of adrenal
function, notably Albanese,[88] and also Abelous and Langlois,[89]
inferred from experiments on the removal of the glands that the
rôle they played in the bodily economy was that of neutralizing,
destroying or transforming toxic substances produced in the organism
as a result of muscular or nervous work. It seemed possible that
the metabolites might have a checking or blocking influence at the
junction of the nerve fibres with the muscle fibres, and might
thus, like curare, lessen the efficiency of the nerve impulses.
Radwánska’s observation[90] that the beneficial action of adrenin
is far greater when the muscle is stimulated through its nerve than
when stimulated directly, and Panella’s discovery[91] that adrenin
antagonizes the effect of curare, were favorable to the view that
adrenin improves the contraction of fatigued muscle by lessening
or removing a block established by accumulated metabolites.
The high threshold of fatigued denervated muscle, however, Gruber
found was quite as promptly lowered by adrenin as was that of normal
muscles stimulated through their nerves. Fig. 23 shows that the
height of contraction, also, of the fatigued muscle is increased
when adrenin is administered. In this experiment the left _tibialis
anticus_ muscle was stimulated directly by thrusting platinum
needle electrodes into it. The _peroneus communis_ nerve supplying
the muscle had been cut and two centimeters of it removed nine
days previous to the experiment. The rate of stimulation was 120
times per minute and the initial tension of the spring about 120
grams. At the point indicated by the arrow an injection of 0.1
cubic centimeter of adrenin (1:100,000) was made into a jugular
vein. A fall in arterial pressure from 110 to 86 millimeters of
mercury and a simultaneous betterment of 20 per cent in the height
of contraction were obtained. It required four minutes of fatigue
(about 480 contractions) to restore the muscle curve to its former
level. Results similar to this were obtained from animals in which
the nerve had been cut 7, 9, 12, 14, and 21 days. In all instances
the nerve was inexcitable to strong faradic stimulation.
[Illustration: Figure 23.--Top record, blood pressure with mercury
manometer. Middle record, contractions of a denervated muscle
(_tibialis anticus_) 240 per minute against a spring having an
initial tension of 120 grams (_peroneus communis_ nerve was cut
nine days before this record was taken). Bottom record (zero blood
pressure), time in half minutes. At the point indicated by an
arrow 0.1 cubic centimeter of adrenin (1:100,000) was injected
intravenously.]
In Radwánska’s experiments, mentioned above, the muscle was
stimulated directly when the nerve endings were intact. It seems
reasonable to suppose, therefore, that in all cases he was
stimulating nerve tissue. Since a muscle is more irritable when
stimulated through its nerve than when stimulated directly (nerve
and muscle), a slight change in the irritability of the muscle by
adrenin would naturally result in a greater contraction when the
nerve was stimulated. Panella’s results also are not inconsistent
with the interpretation that the effect of adrenin is on the muscle
substance rather than on the nerve endings. A method which has long
been used to separate muscle from nerve is that of blocking the
nervous impulses by the drug curare. Gruber found that when curare
is injected the threshold of the normal muscle is increased as was
to be expected from the removal of the highly efficient nervous
stimulations. And also, as was to be expected on that basis, curare
did not increase the threshold in a muscle in which the nerve endings
had degenerated. Adrenin antagonizes curare with great promptness,
decreasing the heightened threshold of a curarized muscle, in five
minutes or less, in some cases to normal. From this observation it
might be supposed that curare and fatigue had the same effect, and
that adrenin had the single action of opposing that effect. But
fatigue raises the threshold of a _curarized_ muscle, and adrenin
then antagonizes this fatigue. Langley[92] has argued that curare
acts upon a hypothetical “receptive substance” in muscle. If so,
probably curare acts upon a substance, or at a point, different from
that upon which fatigue acts; for, as the foregoing evidence shows,
fatigue increases the threshold of a muscle whether deprived of its
nerve supply by nerve section and degeneration or by curare, whereas
curare affects only the threshold of a muscle in which the nerve
endings are normal.[93] And since adrenin can oppose the effects
of both curare and fatigue, it may be said to have two actions, or
to act on two different substances or at two different points in
the muscle.
The evidence adduced in the last chapter indicated that the greater
“head” of arterial pressure produced by the more rapid heart beat
and the stronger contraction of many arterioles in times of great
excitement would be highly serviceable to the organism in any
extensive muscular activity which the excitement might involve. By
assuring an abundant flow of blood through the enlarged vessels
of the working muscle, the waste products resulting from the wear
and tear in contraction would be promptly swept away and thus would
be prevented from impairing the muscular efficiency. The adrenin
discharge at such times would, as was pointed out, probably reënforce
the effects of sympathetic impulses. The evidence presented in
this chapter shows that adrenin has also another action, a very
remarkable action, that of restoring to a muscle its original
ability to respond to stimulation, after that has been largely
lost by continued activity through a long period. What rest will
do only after an hour or more, adrenin will do in five minutes or
less. The bearing of this striking phenomenon on the functions of
the organism in times of great need for muscular activity will be
considered in a later discussion.
REFERENCES
[Footnote 85: Gruber: American Journal of Physiology, 1913, xxxii,
p. 437.]
[Footnote 86: E. L. Porter: American Journal of Physiology, 1912,
xxxi, p. 149.]
[Footnote 87: Cannon and Nice: American Journal of Physiology,
1913, xxxii, p. 55.]
[Footnote 88: Albanese: Archives Italiennes de Biologie, 1892,
xvii, p. 239.]
[Footnote 89: Abelous and Langlois: Archives de Physiologie, 1892,
xxiv, pp. 269-278, 465-476.]
[Footnote 90: Radwánska: Anzeiger der Akademie, Krakau, 1910, pp.
728-736. Reviewed in the Centralblatt für Biochemie und Biophysik,
1911, xi, p. 467.]
[Footnote 91: Panella: Archives Italiennes de Biologie, 1907, xlvii,
p. 30.]
[Footnote 92: Langley: Proceedings of the Royal Society of London,
1906, lxxviii, B, p. 181. Journal of Physiology, 1905-6, xxxiii,
pp. 374-413.]
[Footnote 93: See Gruber: American Journal of Physiology, 1914,
xxxiv, p. 89.]