IMPROVED CONTRACTION OF FATIGUED MUSCLE AFTER
SPLANCHNIC STIMULATION OF THE ADRENAL GLAND
In the older literature on the adrenal glands the deleterious effect
of their absence, or the beneficial effect of injected extracts,
on the contraction of skeletal muscle was not infrequently noted.
As evidence accumulated, however, tending to prove an important
relation between the extract of the adrenal medulla (adrenin) and
the sympathetic nervous system, the relations with the efficiency
of skeletal muscle began to receive less consideration.
The muscular weakness of persons suffering from diseased adrenals
(Addison’s disease) was well recognized before experimental work
on the glands was begun. Experiments on rabbits were reported in
1892 by Albanese,[70] who showed that muscles which were stimulated
after removal of the glands were much more exhausted than when
stimulated the same length of time in the same animal before the
removal. Similarly Boinet[71] reported, in 1895, that rats recently
deprived of their adrenals were much more quickly exhausted in a
revolving cage than were normal animals.
More direct evidence of the favorable influence of adrenal extract
on skeletal muscle was brought forward by Oliver and Schäfer.[72]
After injecting the extract subcutaneously into a frog they found
that the excised gastrocnemius muscle registered a curve of
contraction about 33 per cent higher and about 66 per cent longer
than the corresponding muscle not exposed to the action of the
extract. Similar prolongation of the muscle curve was observed
after injecting the extract intravenously into a dog. A beneficial
effect of adrenal extract on fatigued muscle, even when applied
to the solution in which the isolated muscle was contracting, was
claimed by Dessy and Grandis,[73] who studied the phenomenon in a
salamander.[*] Further evidence leading to the same conclusion was
offered in a discriminating paper by Panella.[74] He found that in
cold-blooded animals the active principle of the adrenal medulla
notably reënforced skeletal muscle, prolonging its ability to do
work, and improving its contraction when fatigued. In warm-blooded
animals the same effects were observed, but only after certain
experimental procedures, such as anesthesia and section of the bulb,
had changed them to a condition resembling the cold-blooded.
*[Footnote: These earlier investigations, in which an extract
of the entire gland was used, made no distinction between the
action of the medulla and that of the cortex. It may be that the
weakness following removal or disease of the adrenals is due to
absence of the cortex (see Hoskins and Wheelon: American Journal
of Physiology, 1914, xxxiv, p. 184). Such a possible effect,
however, should not be confused with the demonstrable influence
of injected adrenin (derived from the adrenal medulla alone) and
the similar effects from adrenal secretion caused by splanchnic
stimulation.]
The foregoing evidence indicates that removal of the adrenals has a
debilitating effect on muscular power, and that injection of extracts
of the glands has an invigorating effect. It seemed possible,
therefore, that increased secretion of the adrenal glands, whether
from direct stimulation of the splanchnic nerves or as a reflex
result of pain or the major emotions, might act as a dynamogenic
factor in the performance of muscular work. With this possibility in
mind L. B. Nice and I[75] first concerned ourselves in a research
which we conducted in 1912.
The general plan of the investigation consisted primarily in
observing the effect of stimulating the splanchnic nerves, isolated
from the spinal cord, on the contraction of a muscle whose nerve,
also isolated from the spinal cord, was rhythmically and uniformly
excited with break induction shocks. When a muscle is thus stimulated
it at first responds by strong contractions, but as time passes
the contractions become weaker, the degree of shortening of the
muscle becomes less, and in this state of lessened efficiency it
may continue for a long period to do work. The tired muscle which
is showing continuously and evenly its inability to respond as it
did at first, is said to have reached the “fatigue level.” This
level serves as an excellent basis for testing influences that may
have a beneficial effect on muscular performance, for the benefit
is at once manifested in greater contraction.
In the experimental arrangement which we used, only a connection
through the circulating blood existed between the splanchnic region
and the muscle--all nervous relations were severed. Any change in
muscular ability, therefore, occurring when the splanchnic nerve is
stimulated, must be due to an alteration in the quantity or quality
of the blood supplied to the laboring muscle.
Cats were used for most experiments, but results obtained with cats
were confirmed on rabbits and dogs. To produce anesthesia in the
cats and rabbits, and at the same time to avoid the fluctuating
effects of ether, urethane (2 grams per kilo body weight) was given
by a stomach tube. The animals were fastened back downward, over
an electric warming pad, to an animal holder. Care was taken to
maintain the body temperature at its normal level throughout each
experiment.
The Nerve-muscle Preparation
The muscle selected to be fatigued was usually the extensor of the
right hind foot (the _tibialis anticus_), though at times the common
extensor muscle of the digits of the same foot was employed. The
anterior tibial nerve which supplies these muscles was bared for
about two centimeters, severed toward the body, and set in shielded
electrodes, around which the skin was fastened by spring clips. Thus
the nerve could be protected, kept moist, and stimulated without
stimulation of neighboring structures. By a small slit in the skin
the tendon of the muscle was uncovered, and after a strong thread
was tied tightly about it, it was separated from its insertion. A
nerve-muscle preparation was thereby made which was still connected
with its proper blood supply. The preparation was fixed firmly to
the animal holder by thongs looped around the hock and the foot, i.
e., on either side of the slit through which the tendon emerged.
The thread tied to the tendon was passed over a pulley and down to
a pivoted steel bar which bore a writing point. Both the pulley
and this steel writing lever were supported in a rigid tripod. In
the earliest experiments the contracting muscle was made to lift
weights (125 to 175 grams); in all the later observations, however,
the muscle pulled against a spring attached below the steel bar.
The tension of the spring as the muscle began to lift the lever
away from the support was, in most of the experiments, 110 grams,
with an increase of 10 grams as the writing point was raised 4.5
millimeters. The magnification of the lever was 3.8.
The stimuli delivered to the anterior tibial nerve were, in most
experiments, single break shocks of a value barely maximal when
applied to the fresh preparation. The rate of stimulation varied
between 60 and 300 per minute, but was uniform in any single
observation. A rate which was found generally serviceable was 180
per minute.
Since the anterior tibial nerve contains fibres affecting blood
vessels, as well as fibres causing contraction of skeletal muscle,
the possibility had to be considered that stimuli applied to it might
disturb the blood supply of the region. Constriction of the blood
vessels would be likely to produce the most serious disturbance, by
lessening the blood flow to the muscle. The observations of Bowditch
and Warren,[76] that vasodilator rather than vasoconstrictor effects
are produced by single induction shocks repeated at intervals of
not more than five per second, reassured us as to the danger of
diminishing the blood supply, for the rate of stimulation in our
experiments never exceeded five per second and was usually two or
three. Furthermore, in using these different rates we have never
noted any result which could reasonably be attributed to a diminished
circulation.
The Splanchnic Preparation
The splanchnic nerves were stimulated in various ways. At first
only the left splanchnics in the abdomen were prepared. The nerves,
separated from the spinal cord, were placed upon shielded electrodes.
The form of electrodes which was found most satisfactory was that
illustrated in Fig. 10. The instrument was made of a round rod of
hard wood, bevelled to a point at one end, and grooved on the two
sides. Into the grooves were pressed insulated wires ending in
platinum hooks, which projected beyond the bevelled surface. Around
the rod was placed an insulating rubber tube which was cut out so
as to leave the hooks uncovered when the tube was slipped downward.
[Illustration: Figure 10.--The shielded electrodes used in
stimulating the splanchnic nerves. For description see text.]
In applying the electrodes the left splanchnic nerves were first
freed from their surroundings and tightly ligatured as close as
possible to their origin. By means of strong compression the
conductivity of the nerves was destroyed central to the ligature.
The electrodes were now fixed in place by thrusting the sharp end
of the wooden rod into the muscles of the back. This was so done
as to bring the platinum hooks a few millimeters above the nerves.
With a small seeker the nerves were next gently lifted over the
hooks, and then the rubber tube was slipped downward until it came
in contact with the body wall. Absorbent cotton was packed about
the lower end of the electrodes, to take up any fluid that might
appear; and finally the belly wall was closed with spring clips. The
rubber tube served to keep the platinum hooks from contact with the
muscles of the back and the movable viscera, while still permitting
access to the nerves which were to be stimulated. This stimulating
apparatus could be quickly applied, and, once in place, needed no
further attention. In some of the experiments both splanchnic nerves
were stimulated in the thorax. The rubber-covered electrode proved
quite as serviceable there as in the abdomen.
The current delivered to the splanchnic nerves was a rapidly
interrupted induced current of such strength that no effects of
spreading were noticeable. That splanchnic stimulation causes
secretion of the adrenal glands has been proved in many different
ways which have already been described (see p. 41).
The Effects of Splanchnic Stimulation on the
Contraction of Fatigued Muscle
When skeletal muscle is repeatedly stimulated by a long series of
rapidly recurring electric shocks, its strong contractions gradually
grow weaker until a fairly constant condition is reached. The record
then has an even top--the muscle has reached the “fatigue level.”
The effect of splanchnic stimulation was tried when the muscle had
been fatigued to this stage. The effect which was often obtained by
stimulating the left splanchnic nerves is shown in Fig. 11. In this
instance the muscle while relaxed supported no weight, and while
contracting lifted a weight of 125 grams. The rate of stimulation
was 80 per minute.
[Illustration: Figure 11.--Upper record, contraction of the
_tibialis anticus_, 80 times a minute, lifting a weight of 125
grams. Lower record, stimulation of the left splanchnic nerves,
two minutes. Time, half minutes.]
The muscle record shows a brief initial rise from the fatigue
level, followed by a drop, and that in turn by another, prolonged
rise. The maximum height of the record is 13.5 millimeters, an
increase of 6 millimeters over the height recorded before splanchnic
stimulation. Thus the muscle was performing for a short period 80
per cent more work than before splanchnic stimulation, and for a
considerably longer period exhibited an intermediate betterment of
its efficiency.
The First Rise in the Muscle Record
The brief first elevation in the muscle record when registered
simultaneously with arterial blood pressure is observed to occur at
the same time with the sharp initial rise in the blood-pressure
curve (see Fig. 12). The first sharp rise in blood pressure is due
to contraction of the vessels in the area of distribution of the
splanchnic nerves, for it does not appear if the alimentary canal
is removed, or if the celiac axis and the superior and inferior
mesenteric arteries are ligated. The betterment of the muscular
contraction is probably due directly to the better blood supply
resulting from the increased pressure, for if the adrenal veins are
clipped and the splanchnic nerves are stimulated, the blood pressure
rises as before and at the same time there may be registered a
higher contraction of the muscle.
[Illustration: Figure 12.--Top record, arterial blood pressure
with membrane manometer. Middle record, contractions of _tibialis
anticus_ loaded with 125 grams and stimulated 80 times a minute.
Bottom record, splanchnic stimulation (two minutes). Time, half
minutes.]
The Prolonged Rise in the Muscle Record
As Fig. 12 shows, the initial quick uplift in the blood-pressure
record is quickly checked by a drop. This rapid drop does not
appear when the adrenal veins are obstructed. A similar difference
in blood-pressure records has been noted before and after excision
of the adrenal glands. As Elliott,[77] and as Lyman and I[78] have
shown, this sharp drop after the first rise, and also the subsequent
elevation of blood pressure, are the consequences of liberation of
adrenal secretion into the circulation. Fig. 12 demonstrates that
the prolonged rise of the muscle record begins soon after this
characteristic drop in blood pressure.
If after clips have been placed on the adrenal veins so that no
blood passes from them, the splanchnic nerves are stimulated, and
later the clips are removed, a slight but distinct improvement in
the muscular contraction occurs. As in the experiments of Young
and Lehmann,[79] in which the adrenal veins were tied for a time
and then released, the release of the blood which had been pent
in these veins was quickly followed by a rise of blood pressure.
The volume of blood thus restored to circulation was too slight to
account for the rise of pressure. In conjunction with the evidence
that splanchnic stimulation calls forth adrenal secretion, the rise
may reasonably be attributed to that secretion. The fact should be
noted, however, that in this instance the prolonged improvement in
muscular contraction did not appear until the adrenal secretion
had been admitted to the general circulation.
Many variations in the improvement of activity in fatigued muscle
after splanchnic stimulation were noted in the course of our
investigation. The improvement varied in degree, as indicated by
increased height of the record. In some instances the height of
contraction was doubled--a betterment by 100 per cent; in other
instances the contraction after splanchnic stimulation was only a
small fraction higher than that preceding the stimulation; and in
still other instances there was no betterment whatever. Never,
in our experience, were the augmented contractions equal to the
original strong contractions of the fresh muscle.
The improvement also varied in degree as indicated by persistence of
effect. In some instances the muscle returned to its former working
level within four or five minutes after splanchnic stimulation
ceased (see Fig. 11); and in other cases the muscle continued
working with greater efficiency for fifteen or twenty minutes after
the stimulation.
The Two Factors: Arterial Pressure and Adrenal Secretion
The evidence just presented has shown that splanchnic stimulation
improves the contraction of fatigued muscle. Splanchnic stimulation,
however, has two effects--it increases general arterial pressure
and it also causes a discharge of adrenin from the adrenal glands.
The questions now arise--Does splanchnic stimulation produce the
improvement in muscular contraction by increasing the arterial
blood pressure and thereby flushing the laboring muscles with fresh
blood? Or does the adrenin liberated by splanchnic stimulation act
itself, specifically, to improve the muscular contraction? Or may
the two factors coöperate? These questions will be dealt with in
the next two chapters.
REFERENCES
[Footnote 70: Albanese: Archives Italiennes de Biologie, 1892,
xvii, p. 243.]
[Footnote 71: Boinet: Comptes rendus, Société de Biologie, 1895,
xlvii, pp. 273, 498.]
[Footnote 72: Oliver and Schäfer: Journal of Physiology, 1895, xviii,
p. 263. See also Radwánska, Anzeiger der Akademie, Krakau, 1910,
pp. 728-736. Reviewed in Zentralblatt für Biochemie und Biophysik,
1911, xi, p. 467.]
[Footnote 73: Dessy and Grandis: Archives Italiennes de Biologie,
1904, xli, p. 231.]
[Footnote 74: Panella: Archives Italiennes de Biologie, 1907,
xlviii, p. 462.]
[Footnote 75: Cannon and Nice: American Journal of Physiology,
1913, xxxii, p. 44.]
[Footnote 76: Bowditch and Warren: Journal of Physiology, 1886,
vii, p. 438.]
[Footnote 77: Elliott: Journal of Physiology, 1912, xliv, p. 403.]
[Footnote 78: Cannon and Lyman: American Journal of Physiology,
1913, xxxi, p. 376.]
[Footnote 79: Young and Lehmann: Journal of Physiology, 1908,
xxxvii, p. liv.]