THE HASTENING OF THE COAGULATION OF BLOOD IN
PAIN AND GREAT EMOTION
In the foregoing chapter evidence was presented that the intravenous
injection of minute amounts of adrenin hastens the clotting of
blood. The amounts used did not vary much above or below the amounts
discharged by the adrenal glands after brief stimulation of the
splanchnic nerves, as found by H. Osgood in the Harvard Laboratory,
and may therefore be regarded as physiological. Since injected
adrenin is capable of shortening the coagulation time, may not the
increased secretion of the adrenals likewise have that effect? The
answer to this question was the object of an investigation by W.
L. Mendenhall and myself.[109]
The blood was taken and its coagulation was recorded graphically
in the manner already described. In some instances the cats were
etherized, in others they were anesthetized with urethane, or were
decerebrated. The splanchnic nerves always were stimulated after
being cut away from connection with the spinal cord. Sometimes
the nerves were isolated unilaterally in the abdomen; sometimes,
in order to avoid manipulation of the abdominal viscera, they
were isolated in the thorax and stimulated singly or together. A
tetanizing current was used, barely perceptible on the tongue and
too weak to cause by spreading any contraction of skeletal muscles.
Coagulation Hastened by Splanchnic Stimulation
That splanchnic stimulation accelerates the clotting of blood, and
that the effects vary in different animals, are facts illustrated
in the following cases:
Oct. 25.--A cat was etherized and maintained in uniform ether
anesthesia. After forty minutes of preliminary observation the left
splanchnic nerves were stimulated in the abdomen. Following are
the figures which show the effects on the coagulation time:
3.00--4 minutes
.07--5.5 “
.14--4 “
.32--4.5 “
.39 to .40 Stimulation of left splanchnic.
.42--5 minutes
.49--5 “
.56--2 “
4.00--1 “
.03--2.5 “
.07--2.5 “
.11--3 “
.16--2 “
.20--1.5 “
.23--4 “
.29--5.5 “
.40--5.5 “
.50--5 “
In this instance at least ten minutes elapsed between the end of
stimulation and the beginning of faster clotting. The period of
faster clotting, however, lasted for about a half-hour, during
which the coagulation time averaged 2.1 minutes, only forty-three
per cent of the previous average of 4.8 minutes. It is noteworthy
that the curve (see Fig. 29), while lower, shows oscillations not
unlike those which follow injection of adrenin (see p. 155).
[Illustration: Figure 29.--Shortening of coagulation time after
stimulation of the left splanchnic nerves, 3:39-:40.]
The primary delay of the effect is not always, indeed it is not
commonly, present:
Nov. 6.--A cat was anesthetized (1.40 p.m.) with urethane, and later
(3.05) its brain was pithed. The following observations on the
coagulation time show the prompt effect of splanchnic stimulation:
3.36--7 minutes
.46--6 “
4.02 to .05 Stimulation of left splanchnic in abdomen.
.08--4 minutes
.10--3 “
.18--3.5 “
.23--6.5 “
In Fig. 30 is presented the original record of the shortening of
the coagulation after stimulation of the left splanchnic nerve
(Nov. 8) in a cat with brain pithed.
[Illustration: Figure 30.--About one-third original size. Record
of shortening of coagulation time after stimulation of the left
splanchnic nerves, 4:33-:35. The time before stimulation was 6
minutes, and afterwards, 3, 4, 4, 4.5, and 6 minutes.]
In the foregoing instances the coagulation time was reduced after
splanchnic stimulation to less than half what it was before. The
reduction was not always so pronounced.
Nov. 7.--A cat[*] maintained in uniform ether anesthesia with
artificial respiration had the following changes in the clotting
time of its blood as the result of stimulating the left splanchnic
nerve in the thorax:
3.40--5 minutes
.45--5 “
.51--5.5 “
.58 to 4.00 Stimulation of left splanchnic.
4.01--4.5 minutes
.06--3.5 “
.11--4 “
.16--3.5 “
.21--4 “
.26--4.5 “
.31--5 “
.36--6.5 “
*[Footnote: This animal had just passed through a period of
excitement with rapid clotting.]
In this case the average for about fifteen minutes before stimulation
was slightly over five minutes, and for twenty-five minutes
thereafter it was four minutes.
In all cases thus far the period of shortened coagulation lasted
from ten to thirty minutes. In other cases, however, the effect was
seen only in a single observation. If this had occurred only once
after splanchnic stimulation, it might be attributed to accident,
but it was not an infrequent result, e. g.:
Oct. 28.--A cat was etherized and decerebrated, and the splanchnic
nerves were isolated in the thorax. Following are two instances of
brief shortening of coagulation after splanchnic stimulation:
3.36--4.5 minutes
.42--4.5 “
.47 to .49 Splanchnic stimulation.
.51--4.5 minutes
.57--2 “
4.01--4 “
.07--4.5 “
.12--5.5 “
.19 to .22 Splanchnic stimulation.
.23--3.5 minutes
.27--4 “
.33--5 “
In the foregoing instance it is noteworthy that the degree of
acceleration is not so great after the second stimulation of the
splanchnics as it was after the first. This reduction of effect as
the nerves were repeatedly stimulated was frequently noted. The
following case presents another illustration:
Nov. 12.--A cat was etherized (2.35 p.m.) and the medulla was
punctured (piqûre) at 3.12. The operation was without effect. The
loss or lessening of effectiveness on second stimulation of the
left splanchnic nerves is to be compared with the persistence of
effectiveness on the right side:
3.40--4.5 minutes
.45--4.5 “
.54 to .56 Stimulation of left splanchnic in abdomen.
4.00--3 minutes
.05--2 “
.10--5.5 “
.16--5 “
.22 to .27 Stimulation of left splanchnic in abdomen.
.30--4 minutes
.34--4 “
.39--4 “
.44--4 “
.48--4 “
.55 to .57 Stimulation of right splanchnic.
.59--3 minutes
5.02--2.5 “
.07--3 “
.11--3 “
.15--5.5 “
.22--5.5 “
The experiments above recorded show that stimulation of the
splanchnic nerves results immediately, or after a brief period,
in a shortening of the coagulation time of the blood--an effect
which in different animals varies in duration and intensity, and
diminishes as the stimulation is repeated. The next question was
whether this effect is produced through the adrenal glands.
Coagulation Not Hastened by Splanchnic Stimulation
if the Adrenal Glands are Absent
The manner in which splanchnic stimulation produces its effects is
indicated in the following experiments:
Nov. 28.--A cat was etherized, and through the orbit the central
nervous system was destroyed to the midthorax. The blood vessels
of the _left_ adrenal gland were then quickly tied and the gland
removed. The readings for a half hour before the left splanchnic
nerve was stimulated averaged seven minutes, then--
4.38 to .40 Stimulation of left splanchnic (glandless).
.42--7 minutes
.50--7 “
5.02 to .04 Stimulation of right splanchnic.
.06--4 minutes
.10--7 “
.18--7 “
.26--7 “
Dec. 4.--A cat was etherized and pithed through the orbit to the
neck region. The right and left splanchnic nerves were tied and cut
in the thorax. The _left_ adrenal gland was then carefully removed.
These operations consumed about a half-hour. The following records
show the effect of stimulating the left and right splanchnic nerves:
4.10--5 minutes
.16--4.5 “
.25 to .28 Stimulation of left splanchnic (glandless).
.30--4.5 minutes
.35--4.5 “
.40--7.5 “
.49 to .51 Stimulation of right splanchnic.
.55--4.5 minutes
5.00--2.5 “
.14--6 “
.23 to .25 Stimulation of right splanchnic.
.26--6 minutes
.33--4.5 “
.38--3.5 “
.43--4.5 “
.49--5 “
.55--6 “
The results in this experiment are represented graphically in Fig.
31.
[Illustration: Figure 31.--Results of stimulating the left
splanchnic nerves, 4:25-:28, after removal of the left adrenal
gland; and of stimulating the right splanchnic nerves, 4:49-:51
and 5:23-:25, with right adrenal gland present.]
Elliott’s evidence that in the cat the splanchnic innervation of the
adrenals is not crossed has already been mentioned. If the gland
is removed on one side, therefore, stimulation of the nerves on
that side causes no discharge from the opposite gland. As the above
experiments clearly show, splanchnic stimulation on the glandless
side results in no shortening of the coagulation time; whereas,
in the same animals, stimulation of the nerves on the other side
(still connected with the adrenal gland) produces a sharp hastening
of the clotting process.
The splanchnics innervate the intestines and liver even though the
adrenal gland is removed. The foregoing experiments indicate that
the nerve impulses delivered to these organs do not influence them
in any direct manner to accelerate the speed of coagulation. Indeed,
in one of the experiments (Dec. 4, see Fig. 31) a high reading about
ten minutes after splanchnic stimulation on the glandless side
suggests the possibility of an opposite effect. Direct stimulation
of the hepatic nerves on one occasion was followed by a change of
the clotting time from 4.5, 5, 4.5, 4.5 minutes during twenty-five
minutes before stimulation to 4.5, 7, and 6 minutes during twenty
minutes after stimulation.
Since with the adrenals present stimulation of hepatic nerves
induces alteration of glycogen in the liver and quick increase of
blood sugar,[110] just as splanchnic stimulation does, the failure
of the blood to clot faster after stimulation of the hepatic nerves
confirms the evidence already offered that faster clotting when
adrenin is increased in the blood is not due to a larger amount of
sugar present (see p. 159).
The liver and intestines cannot be made to shorten clotting time by
stimulation of their nerves, but, as has already been shown (see
p. 157), neither can adrenin act by itself to hasten the clotting
process. Apparently the effect is produced by coöperation between
the adrenals and the liver (and possibly also the intestines).
Somewhat similar coöperation is noted in the organization of sugar
metabolism; splanchnic stimulation in the absence of the adrenal
glands does not increase blood sugar,[111] and in the absence of
the liver adrenin is without influence.[112]
The variations of effect noted after splanchnic stimulation can be
accounted for by variations in the adrenin content of the glands.
Elliott[113] found, as previously stated, that animals newly brought
into strange surroundings may have a considerably reduced amount
of adrenin in their adrenals. The animals used in our experiments
had been for varying lengths of time in an animal house in which
barking dogs were also kept, and were therefore subject to influences
which would be likely to discharge the glands.
The evidence that stimulation of splanchnic nerves, with accompanying
increase of adrenal secretion, results in more rapid clotting of
blood is especially interesting in relation to the experiments
previously described, which showed that in pain and emotional
excitement there is an increased secretion of adrenin into the
blood. Does the adrenin thus liberated have any effect on the rate
of coagulation? The observations here recorded were made in order
to obtain an answer to that question.
Coagulation Hastened by “Painful” Stimulation
In the experiments on the action of stimuli which in the
unanesthetized animal would cause pain, it will be recalled that
faradic stimulation of a large nerve trunk (the stump of the cut
sciatic) and operation under light anesthesia were the methods used
to affect the afferent nerves. Elliott[114] found that repeated
excitation of the sciatic nerve was especially efficient in
exhausting the adrenal glands of their adrenin content, and also
that this reflex persisted after removal of the cerebral hemispheres.
It was to be expected, therefore, that with well-stored glands,
sciatic stimulation, even in the decerebrate animal, would call
forth an amount of adrenal secretion which would decidedly hasten
clotting. The following case illustrates such a result:
Dec. 12.--A cat was anesthetized with ether at 3.45 and the left
sciatic nerve was bared. Decerebration was completed at 3.57. The
clotting time of the blood began to be tested six minutes later:
4.03--4 minutes
.08--3.5 “
.13--3.5 “
.18--4.5 “
.23 to .25 Stimulation of left sciatic.
4.26--2.5 minutes
.29--3.5 “
.34--4 “
.40--5 “
.45 to .50 Stimulation of left sciatic.
4.53--2.5 minutes
.57--7 “
5.06--7.5 “
.15 to .17 Stimulation of left sciatic.
5.17--4 minutes
.22--4.5 “
.27--5.5 “
.36--5.5 “
.46--7 “
The results obtained in this case, which were similar to results in
other cases, are represented graphically in Fig. 32. The coagulation
time was becoming gradually more prolonged, but each excitation
of the sciatic nerve was followed by a marked shortening. The
strength of stimulation was not determined with exactness, but it
is worthy of note that the current used in the first and the third
stimulations was weaker than could be felt on the tongue, whereas
that used in the second was considerably stronger, though it did
not produce reflex spasms.
[Illustration: Figure 32.--Three shortenings of coagulation time
after stimulation of the left sciatic nerve, at 4:23-:25, at
4:45-:50 (stronger), and at 5:15-:17.]
Mere tying of the nerve is capable of producing a marked shortening
of coagulation, as the following figures show:
Oct. 21.--10.57 cat under ether, and urethane given:
11.11--8.5 minutes
.23--8.5 “
.32 to .35 Left sciatic bared and tied.
.37--1.5 minutes
.41--5.5 “
.50--7 “
12.02--8.5 “
Stimulation of the crural nerve had similar effects, reducing the
clotting time in one instance from a succession of 3, 3, and 3.5
minutes to 1.5 minutes shortly after the application of the current,
with a return to 3.5 minutes at the next test.
Operative procedures performed under light anesthesia (i. e.,
with the more persistent reflexes still present), or reduction of
anesthesia soon after operation, resulted in a remarkable shortening
of the coagulation time:
Nov. 8.--A cat was etherized and tracheotomized. The abdomen was
then opened and a ligature was drawn around the hepatic nerves. The
operation was completed at 2.25. At 2.50 the etherization became
light and the rate of clotting began to be faster:
2.50--6 minutes
3.00--5.5 “
.10--3.5 “
.15--3.5 “
.20--4.5 “
.30--7.5 “
Nov. 11.--A female cat, very quiet, was placed in the holder at
1.55. The animal was not excited. At 2.10 etherization was begun;
the animal was then tracheotomized, and the femoral artery was
exposed.
2.21--4.5 minutes
.26--4.5 “ Anesthesia lessened.
.32--3.5 “ “ light.
.35 Abdomen opened.
.47--1.5 minutes.
.52--1 “
.55 Ligature passed around hepatic nerves.
.57--1.5 minutes. Anesthesia light; corneal reflex present.
3.02--3 “
.07--3 “ Some hepatic nerves cut.
.12--4.5 “ Rest of hepatic nerves cut.
.22--5 “
The results of this experiment are shown graphically in Fig. 33.
[Illustration: Figure 33.--Shortening of coagulation time during an
operation under light anesthesia. At 2:35 the abdomen was opened,
at 2:55 a ligature was passed around the hepatic nerves.]
Nov. 13.--A cat was etherized at 1.55, tracheotomized, and the
femoral artery laid bare. As soon as these preparations were
completed, the ether was removed and anesthesia became light. The
blood clotted thus:
2.08--6 minutes
.15--4 “ Anesthesia light.
.20--2 “
.24--1 “ Etherization begun again.
.27--2.5 “
.30--3.5 “
.35--5.5 “
.50--5.5 “
In the foregoing and in other similar instances, a condition of
surgical injury, whether just made or being made, was accompanied
by more rapid clotting of blood when the degree of anesthesia was
lessened. This condition was one which, if allowed to go further in
the same direction, would result in pain. Both direct electrical
stimulation and also surgical operation of a nature to give pain in
the unanesthetized animal result, therefore, in faster clotting.
It is worthy of note that after decerebration clotting apparently
occurred no faster because the abdomen had been opened, although
in the decerebrate state etherization was suspended. The mechanism
for reflex control of the adrenals may not be higher than the
corpora quadrigemina, as Elliott has shown, but the discharge from
the glands seems to be more certain to occur when the cerebrum is
present and is permitted even slightly to operate.
Coagulation Hastened in Emotional Excitement
The evidence for emotional secretion of the adrenal glands has
already been presented. As was noted in my earlier observations on
the motions of the alimentary canal (see p. 14), cats differ widely
in their emotional reaction to being bound; some, especially young
males, become furious; others, especially elderly females, take the
experience quite calmly. This difference of attitude was used with
positive results, the reader will recall, in the experiments on
emotional glycosuria; there seemed a possibility likewise of using
it to test the effect of emotions on blood clotting. To plan formal
experiments for that purpose was not necessary, because in the
ordinary course of the researches here reported, the difference in
effects on the blood between the violent rage of vigorous young males
and the quiet complacency of old females was early noted. Indeed,
the rapid clotting which accompanied excitement not infrequently
made necessary an annoying wait till slower clotting would permit
the use of experimental methods for shortening the process.
The animals used on November 11 and 13 (see pp. 175, 176) are
examples of calm acceptance of being placed on the holder;
and furthermore, these animals were anesthetized without much
disturbance. As the figures indicate, the clotting from the first
occurred at about the average rate.
In sharp contrast to these figures are those obtained when a vigorous
animal is angered:
Oct. 30.--A very vigorous cat was placed on the holder at 9.08.
It at once became stormy, snarling, hissing, biting, and lashing
its big tail. At 9.12 etherizing was begun and that intensified
the excitement. By 9.15 the femoral artery was tied. The clotting
time of the blood for an hour after the ether was first given was
as follows:
9.18--0.5 minute
.19--1 “
.22--1 “
.24--1 “
.26--1 “
.28--1.5 “
.31--1 “
.33--0.5 “
.35--0.5 “
.38--0.5 “
.39--0.5 “
.41--1 “
.43--1 “
.45--0.5 “
.49--0.5 “
.52--0.5 “
.54--0.5 “
.57--1 “
10.00--0.5 “
.02--0.5 “
.06--1 “
.09--0.5 “
.11--0.5 “
.13--1 “
Twenty-four observations made during the hour showed that the
clotting time in this enraged animal averaged three-fourths of a
minute and was never longer than a minute and a half. The clots were
invariably a solid jelly. The persistence of the rapid clotting
for so long a period after anesthesia was started may have been in
part due to continued, rather light, etherization, for Elliott[115]
found that etherization itself could reduce the adrenin content of
the adrenal glands.
The shortened clotting did not always persist so long as in the
foregoing instance. The brief period of faster clotting illustrated
in the following case was typical of many:
Nov. 18.--A cat that had been in stock for some time was placed
on the holder at 2.13, and was at once enraged. Two minutes later
etherization was started. The hairs on the tail were erect. The
clotting was as follows:
2.25--1 minute.
.27--0.5 “
.28--2 “
.31--4.5 “
.37--3.5 “
.47--4.5 “
It seems probable that in this case just as in some of the cases
in which the splanchnic nerves were stimulated (see p. 166), the
adrenals had been well-nigh exhausted because of the cat’s being
caged near dogs, and that the emotional flare-up practically
discharged the glands, for repeated attempts later to reproduce
the initial rapid clotting by stimulation of the splanchnic nerves
were without result.
Evidence presented in previous chapters makes wholly probable the
correctness of the inference that the faster coagulation which
follows emotional excitement is due to adrenal discharge from
splanchnic stimulation. In this relation the effect of severance of
the splanchnics on emotional acceleration of the clotting process
is of interest. The following cases are illustrative:
Oct. 29.--A cat was left on the holder for ten minutes while the
femoral artery was uncovered under local anesthesia. The blood
removed was clotted in a half-minute. The animal was much excited.
It was now quickly etherized and the brain pithed forward from the
neck. The tests resulted as follows:
10.51--1 minute.
.53--0.5 “
.55--0.5 “
.57--0.5 “
11.07 Cut left splanchnic.
.12 “ right splanchnic.
.21--3.5 minutes.
.26--3.5 “
The original record of this case is given in Fig. 34.
[Illustration: Figure 34.--About two-thirds original size. Record
of rapid clotting (less than a half-minute) after emotional
excitement. At 11:07 the left, at 11:12 the right splanchnic
nerves were cut; the clotting then required 3:5 minutes. The marks
below the time record indicate the moments when the samples were
drawn.]
Nov. 5.--A cat was etherized at 2.35. At 2.39 artificial respiration
by tracheal cannula was begun, the air passing through an ether
bottle. The clotting occurred thus:
2.53--1.5 minutes
.57--1.5 “
3.05--1.5 “
.15--1.5 “
.25 Both splanchnics cut and tied in thorax.
.35--4.5 minutes
.55--4.5 “
Nov. 7.--A cat was etherized at 1.55 under excitement and with tail
hairs erect. At 2.13 the animal was showing reflexes. The figures
show the course of the experiment:
2.15--1.5 minutes
.21--1 “
.26--1 “
.31--1 “
.36--1 “
.41--1 “
.46--2 “
.51--2 “
3.06--2 “
.11--2.5 “
.26 Cut left splanchnic in thorax.
.35 Cut right splanchnic in thorax.
.40--5 minutes
.45--5 “
.51--5.5 “
In this instance the subsequent stimulation of the splanchnic nerves
resulted again in faster clotting--a reduction from 5.5 minutes to
3.5 minutes (see experiment Nov. 7, p. 164). The results from this
experiment are expressed graphically in Fig. 35.
[Illustration: Figure 35.--Rapid clotting after emotional
excitement, with slowing of the process when the splanchnic nerves
were cut in the thorax (the left at 3:26, the right at 3:35).]
The data presented in this chapter show that such stimulation
as in the unanesthetized animal would cause pain, and also such
emotions as fear and rage, are capable of greatly shortening the
coagulation time of blood. These results are quite in harmony with
the evidence previously offered that injected adrenin and secretion
from the adrenal glands induced by splanchnic stimulation hasten
clotting, for painful stimulation and emotional excitement also
evoke activity of the adrenals. Here, then, is another fundamental
change in the body, a change tending to the conservation of its
most important fluid, wrought through the adrenal glands in times
of great perturbation. This bodily change and the others which
occur under the same circumstances are next to be examined with
reference to their significance.
REFERENCES
[Footnote 109: Cannon and Mendenhall: American Journal of Physiology,
1914, xxxiv, p. 251.]
[Footnote 110: Macleod: Diabetes: its Pathological Physiology,
London, 1913, pp. 68-72.]
[Footnote 111: Gautrelet and Thomas: Comptes Rendus, Société de
Biologie, 1909, lxvii, p. 233.]
[Footnote 112: Bang: Der Blutzucker, Wiesbaden, 1913, p. 87.]
[Footnote 113: Elliott: Journal of Physiology, 1912, xliv, p. 379.]
[Footnote 114: Elliott: _Loc. cit._, pp. 406, 407.]
[Footnote 115: Elliott: _Loc. cit._, p. 388.]