Reprinted from the American Journal of Physiology. 
Vol. Xlll.—June r, 1905. —No. V. 
ON THE UNION OF A SPINAL NERVE WITH THE 
VAGUS NERVE. 
JOSEPH ERLANGER. 
[From the Physiological Laboratory of the Johns Hopkins University.] Reprinted from the American Journal of Physiology. 
Vol. Xlll.—June i, 1905. No. V. 
ON THE UNION OF A SPINAL NERVE WITH THE 
VAGUS NERVE. 
By JOSEPH ERLANGER. 
[From the Physiological Laboratory of the Johns Hopkins University.] 
Introduction. 
IN a recently published article on nerve union, Langley and Ander- 
son 1 have formulated the law that “ the central end of any efferent 
somatic2 fibre can make functional union with the peripheral end 
of any preganglionic fibre. . . .” But according to their review 
of the literature, it would appear that no conclusive evidence has 
as yet been obtained that motor fibres will make functional con- 
nection with the preganglionic fibres in the vagus nerve. Indeed, as 
late as 1900, Langley3 stated that “ a recovery of function, after 
section of the vagus nerve, has not been observed so far as regards 
its autonomic fibres. ...” 
But few attempts have been made to obtain union of efferent 
somatic fibres with the preganglionic fibres of the vagus nerve. 
Flourens4 seems to have been the first investigator to have undertaken 
it. In 1828 he reported some experiments in which the fifth cervical 
nerve was sewn to the peripheral end of the vagus. He obtained no 
signs of functional union. In 1885 Rawa6 sutured the hypoglossal 
to the vagus nerve in several species of animals. The physio- 
logical tests for regeneration were made from eighteen to twenty 
months after the operation and some days after cutting the vagus 
and hypoglossal nerves of the opposite side. He found that the 
sutured nerve behaved, so far as concerned its action on the heart, in 
every respect like a normal vagus nerve. Through it both direct and 
1 Langley and Anderson : Journal of physiologj', 1904, xxxi, p. 365. 
2 Italicized words have been substituted for letters in the original. 
3 Langley ; Schafer’s Text-book of physiology, London, 1900, ii, p. 66j. 
4 Flourens : Ref., Langley and Anderson, Loc. cit. 
5 Rawa : Archiv fiir Physiologic, 1885, p. 296. Union of a Spinal Nerve with the Vagus Nerve. 
373 
reflex inhibition of the heart were obtained, and through it the central 
nervous system exercised a tonic inhibitory control over the heart. 
But Langley and Anderson raise the valid objection to the work 
of Rawa that, in his final tests, cognizance bad not been taken of the 
possibility of a downgrowth of fibres from the central stump of 
the divided vagus nerve. But although these experiments do not 
demonstrate conclusively that fibres of the hypoglossal nerve may 
usurp the functions of vagus fibres, still they prove that functional 
regeneration of the visceral fibres of the vagus nerve does occur. 
The experiments of Henri and Calugareanu,1 who cross-sutured 
the hypoglossal and vagus nerves, are open to the same objection, 
and their results have the same significance as Rawa’s. 
It was, therefore, to be expected that the negative results, reported 
by Langley and others, of experiments testing the power of the vagus 
to regenerate itself, would be accounted for by the brevity of the time 
allowed for regeneration. This was actually demonstrated in Lang- 
ley’s laboratory by Tuckett,2 who found, in the rabbit, that three years 
after operation sutured vagi respond to stimulation almost normally. 
While reviewing the literature on the subject of regeneration of 
the vagus nerve, we were impressed by the comparative sluggishness 
in the return of function after unions with it, a sluggishness which 
seems to be out of all proportion to the length of the nerve. At this 
time two possible explanations suggested themselves: (a) The small 
raedullated fibres which occur in the vagus nerve, and which are 
probably its preganglionic fibres, may not grow as rapidly as large 
medullated fibres, (b) In the process of regeneration, fibres which are 
normally short may not extend beyond their normal length as rapidly 
as fibres whose normal length more nearly approximates that required 
of them in the regeneration. 
We have no experimental evidence in support of the first possibility. 
Indeed Langley and Anderson3 state, we think, however, without 
sufficient justification, “ that small nerve fibres can much more readily 
unite with large ones than large ones with small.’’ 
With regard to the second possibility, if there is any truth in the 
1 Henri and CalugarLanu ; Comptes rendus de la societe de biologie, igoo, 
lii, p. 503 ; Journal de la physiologic et de la pathologic generate, igoo, ii, p. yog. 
2 Tuckett : Journal of physiology, rBg6, xix, p. 2gy. In this article negative 
results are reported. The completed work is reported in Journal of physiology, 
igoo, xxv, p. 303. 
3 Langley and Anderson : Loc. cit., p. syg. 374 
Joseph Erlonger. 
statement made by Langley1 that “ the axon process of each cell 
wherever it is cut will, in favorable conditions, grow to its own length, 
neither more nor less,” it is hardly to be expected that the short 
fibres of the hypoglossal could grow down to the heart. And the 
hypoglossal is the only nerve that has been used for this purpose 
in recent years. Although the latest work of Langley and Anderson 2 
does not bear out tacitly the above-stated dictum, nevertheless we 
might be justified in expecting that the union of efferent spinal fibres 
with the vagus nerve would offer better chances of functional regen- 
eration than the union of hypoglossal with vagus. 
Furthermore we hoped that should signs of functional regeneration 
be obtained after the union of a spinal nerve with the vagus nerve, 
the interpretation of the results would not offer so many difficul- 
ties as in the case of union of one cranial nerve with another. 
For these reasons it was decided to try, in the dog, the effect 
of uniting one of the branches of the cervical plexus with the 
peripheral end of the vagus nerve. 
Methods. 
With this object in view six dogs were prepared. In all excepting 
one the vagus nerve was cut at a point about 2 cm. above the in- 
ferior cervical ganglion, and the peripheral stump was sutured to the 
central stump of the most accessible branch of the brachial plexus. 
In most instances this was probably the trunk formed by the union 
of twigs from the fifth and sixth cervical nerves. In the case of the 
first dog operated upon, the central end of the hypoglossal nerve was 
united with the peripheral end of the vagus nerve. The cut surfaces 
of the nerves were secured to one another by two fine silk sutures 
passed on opposite sides of the nerve. No attempt was made to keep 
the sutures within the limits of the sheath of the nerves. In each 
instance, excepting the case of union of hypoglossus with vagus, a 
piece 4 to 5 cm. long was excised from the central stump of the 
vagus. The operations were performed aseptically, and none of the 
wounds became infected. Morphine and ether were used as anaes- 
thetics. At the preliminary operations, the ether was administered 
through a cone; at the final operations, it was administered through 
a tracheal cannula. 
1 Langley : Journal of physiology, 1900, xxv, p. 417. 
2 Langley and Anderson ; Loc. cit. Union of a Spinal Nerve with the Vagus Nerve. 
375 
In order to test whether or not regeneration had occurred, a second 
and sometimes a third operation was performed, at which the sutured 
nerve was exposed and stimulated. The effect of this upon the pulse- 
rate was determined graphically with the aid of the sphygmomano- 
meter devised by the author.1 
In each experiment the nerves were examined histologically. As 
a rule cross-sections of the nerves were stained by the methods of 
van Giesen and of Weigert. 
The experiments will be presented in the order in which the final 
tests for regeneration were made. 
Experiments. 
Dog No. 2. Union of the peripheral end of the right vagus nerve 
with a branch of the right cervical plexiLs.— Operation Feb. 26, 1904. 
At the second operation, performed 80 days later (May 16), it was 
found that the two nerves had united beautifully. The central end 
of the vagus terminated in a bulbous enlargement. Stimulation of 
the sutured vagus nerve distal to the point of union had no influence 
upon the heart-rate. We were about to close the wound when the 
animal died as the result of careless anaesthetization. 
Histological examination. The vagus nerve just below the point 
of union is a solid mass of large medullated nerve fibres. The re- 
current laryngeal nerve near its point of origin from the vagus con- 
sists of medullated fibres which appear to be somewhat smaller than 
those seen in the vagus. The fifth cervical nerve just central of the 
suture appears to be normal. 
Dog No. 3. Union of the peripheral end of the right vagus nerve 
with a branch of the right cervical plexus. Operation March 1, 1904. 
The second operation was performed 109 days after the nerves had 
been united (on June 17, 1904). The result of stimulation of the 
sutured nerve was totally negative so far as the rate of the heart-beat 
was concerned. But while the dog was lightly anaesthetized, sensory 
effects, such as hurried respirations and whining, were observed. 
Stimulation of the opposite vagus with the secondary coil at 14.5 
gave complete cardiac inhibition. 
During the course of this operation it occurred to us that the exis- 
tence of the normal connection of the heart with the central nervous 
system through the intact vagus nerve of the opposite side might 
1 Erlanger : Johns Hopkins hospital reports, 1904, xii, p. 53. 376 
Joseph Erlanger. 
exert some deleterious influence upon the establishment of new periph- 
eral connections. Therefore a piece of the left vagus nerve 4 cm. 
long was excised. This was associated with the usual effects of 
section of both vagi, namely, a marked increase in the heart-rate 
and a marked slowing of the respirations. The wound was then 
closed. After recovery from the anaesthetic, and until the animal’s 
death five days later, the respirations remained slow and labored, and 
apparently none of the food ingested was retained. 
At autopsy it was found that the sutured nerves had united 
nicely. The central stump of the vagus terminated in a bulbous 
enlargement. 
Histological examination. The vagus nerve some distance from 
the point of suture and the recurrent laryngeal nerve near its origin 
from the vagus contain medium sized medullated nerve fibres and 
very many nuclei. 
Dog No. 6. Union of the peripheral end of the right vagus nerve 
zvith a branch of the right cervical plexus. Operation March 4, 1904. 
The dog was found dead on October 14, 1904, i. e., 224 days after the 
first operation. At autopsy it was found that the sutured nerves had 
united nicely. The central stump of the cut vagus nerve ended in a 
bulbous enlargement. 
Histological examination. —The fifth cervical nerve, the vagus nerve 
distal to the point of union, and the recurrent laryngeal nerve con- 
tain large medullated fibres. 
Dog No. 5. Union of the peripheral end of the right vagus nerve 
zvith a branch of the right cervical plexus. This dog was a fully 
grown, active fox terrier. At the first operation, which was per- 
formed on March 3, 1904, the peripheral end of the right vagus 
nerve was united with what appeared to be the uppermost trunk of 
the right cervical plexus. The second operation was performed on 
December 31, 1904, 303 days after the first operation. 'At this time 
it was found that apparently good union had occurred between the 
sutured nerves. The central stump of the right vagus nerve had not 
grown down along the carotid artery. Stimulation of the right vagus 
nerve distal to the point of union with the cervical nerve resulted in 
partial inhibition of the heart with the secondary coil at 10. With 
the secondary coil at 6, complete inhibition was obtained, which, 
however, did not last longer than the time occupied by two heart- 
beats. The effect of stronger stimulation was not tested. Stimu- 
lation of the left vagus nerve with the coil at 12 gave complete Union of a Spinal Nerve with the Vagus Nerve. 
377 
inhibition, from which the heart soon escaped. Upon cutting the 
left vagus nerve, the respirations at once became slow. The heart- 
rate was not materially affected. Thus before section of the left 
vagus nerve 54 pulsations were inscribed upon a given space of 
record; 55 pulsations were inscribed in the same space after section 
of the nerve. It was doubtful if reflex inhibition now occurred upon 
stimulation of the central end of the left vagus nerve. After excising 
a piece of the left vagus nerve the wound was closed. 
Immediately after the operation the dog did well. The respira- 
tions were slow, but the animal seemed to be perfectly comfortable. 
Food was taken with apparent relish, and on the first day, at least, 
it was retained when given in small quantities. But, on the second 
day after the operation, retching and vomiting began and gradually 
increased in intensity. The weight of the animal increased for eleven 
days and then began to fall off. On January 20, twenty-one days 
after section of the left vagus nerve, and 324 days after the first 
operation, it was decided to make the final test, because it was thought 
the animal’s appearance did not warrant further delay. 
The animal was anaesthetized in the usual way, and the pressure 
in the femoral artery and the respirations were recorded. The 
sutured vagus nerve, including the neuroma at the point of union, 
was dissected free from the surrounding tissue and placed on shielded 
electrodes. 
The results which follow demonstrate that, so far as its action on 
the heart .is concerned, the sutured vagus nerve behaved in every 
respect like a normal vagus nerve. 
In the first place it should be stated that stimulation of the central 
stump of the right vagus nerve did not slow the heart-rate. 
By direct stimulation of the sutured vagus nerve any degree of 
inhibition could be obtained. In one trial the heart was held in 
complete inhibition for seventeen and three-fourths seconds before it 
escaped, and for more than a minute thereafter the heart-rate 
remained slow. The fall of blood-pressure that often follows the 
recovery from inhibition occurred regularly. Thus in one instance 
(Fig. 1) the mean blood-pressure before stimulation was 106.5 mm- Hg. 
Immediately after the heart had recovered from inhibition, the blood- 
pressure rose to 107, but fell secondarily to 75. 
Weak stimulation of the central end of the left (unsutured) vagus 
nerve gave no perceptible changes in the heart-rate or blood-pressure. 
But strong stimulation of this nerve gave reflex slowing of the heart. Joseph Erlanger. 
As is illustrated in Fig. 2, after a latent period of about two heart- 
beats, the heart-rate was distinctly slowed. Thus, before stimulation, 
Figure 1. One-fourth the original size. Showing the effect on the heart-rate, blood 
pressure, and respiratory rate of stimulating the sutured vagus nerve. Dog No. 5. 
T Time in seconds; R Respiration ; P = Pressure in femoral artery; B Base- 
line and signal. 
23.5 pulse-waves were recorded in ten seconds (141 per minute). 
During the first 8.75 seconds of stimulation, 13 waves were recorded 
(89 per minute), but the rate gradually increased so that during the 
last five seconds of stimulation 11.5 beats were recorded (138 per 
minute). 
The blood-pressure before stimulation was 87.5 mm. Hg. While 
the nerve was being stimulated, it rose to 122.$ mm. Hg; twenty 
Figure 2. One-third the original size. Showing the effect on the heart-rate, blood-pres- 
sure, and respiratory rate of stimulating the central end of the left vagus nerve. Dog 
No. 5. T= Time in seconds; R = Respiration; P Pressure in femoral artery; 
B Base-line and signal. Union of a Spinal Nerve with the Vagus Nerve. 
379 
seconds after stimulation it was 71 mm. Hg; and it then gradually 
rose to the level it had had previous to stimulation of the nerve. 
An effect of the respirations upon the heart-rate was perceptible 
in but limited regions of a long record. At such places the heart- 
rate during inspiration was distinctly faster than during expiration. 
An instance of this is shown in Fig. 3. 
The central nervous system exercised a tonic inhibitory control 
over the heart through the sutured nerve. For when the sutured 
Figure 3. One-fourth the original size. Showing the effect of the respiration on the 
heart-rate before and after ligation of the sutured nerve, and the effect of the ligation 
on the heart-rate. Dog No. 5. T = Time in seconds; R Respiration; P = Pres- 
sure in femoral artery; B = Base-line and signal. 
nerve was ligated (cut) the heart-rate, after a preliminary slowing, 
was distinctly increased (see Fig. 3). Immediately before ligation of 
the nerve the heart-rate was 66.5 to the half minute (133 per minute). 
Some time before ligation the rate was 68.5 per half minute (137 per 
minute). After the slowing which was associated with the mechani- 
cal stimulation of ligation had passed off, the heart-rate was 8r to the 
half minute (162 per minute). Before ligation of the nerve the blood- 
pressure was 96.5 mm. Hg. After ligation it gradually rose, and 
one and one-half minutes later it was 106 mm. Hg. 
After ligation of the sutured vagus nerve, the effect of the 
respirations on the heart-rate described above disappeared (see 
Fig. 3). Furthermore, reflex inhibition of the heart could not now be 
obtained by stimulation of the central end of the left vagus nerve 
although thereby the blood-pressure was increased. Stimulation of 
the peripheral end of the sutured vagus still gave the usual cardiac 
inhibition. Stimulation of the central stump had no effect on the 
heart-rate, but it increased the blood-pressure. Joseph Erlanger. 
The results obtained with regard to the relation of the sutured 
vagus nerve to the respiratory system were not definite. At the 
beginning of the experiment the respiratory rate was remarkably 
slow, 13.5 per minute. Just before section of the sutured vagus 
nerve, the animal was breathing 12 times per minute. Immediately 
after section of the sutured vagus nerve, the respiratory rate was 14 
per minute, and this rate was maintained until the close of the experi- 
ment. Strong stimulation of the central end of the sutured vagus 
nerve increased both the rate and amplitude of the respirations. 
Stimulation with weak currents was without effect. 
It was found at autopsy that the central stumps of both vagi were 
terminated by bulbous enlargements. They had made no attempt to 
grow down the neck. The branch of the cervical plexus which had 
been united with the peripheral end of the vagus nerve derived its 
fibres from the fifth and sixth cervical nerves, each of which sent a 
twig into it. The point of union of the sutured nerves was marked 
by a small fusiform swelling.1 
Histological examination. The following were removed for histo- 
logical examination : A piece of the sutured vagus nerve about 1 cm. 
above the inferior cervical ganglion, a piece of the recurrent laryngeal 
nerve, and a piece of the fifth cervical nerve. The vagus and recur- 
rent laryngeal nerves were found to consist of solid masses of uni- 
formly large medullated fibres. The fifth cervical nerve appeared to 
be perfectly normal. 
Dog. No 4. Union of the peripheral end of the right vagus nerve 
with a branch of the right cervical plexus. March 11, 1904. Dog 
No. 4 was a large but young mongrel. On January 24, 1905, i. e., 
319 days after the first operation, a preliminary operation was per- 
formed in order to determine whether or not functional regenera- 
tion had occurred. The portion of the vagus nerve that had been 
united with the cervical nerve was placed on shielded electrodes. 
1 With regard to the viscera the following note may be made. The lungs and 
heart were normal. The oesophagus was not especially dilated. It contained 
material which was similar to the stomach contents. The cardiac orifice was 
patulous, so that there was perfectly free communication between the oesophagus 
and the stomach. The stomach was relaxed and distended with a bile-stained 
material of a semi-fluid consistency in which a granular material and rather large 
pieces of bone were suspended. The pylorus was so tightly contracted that con- 
siderable pressure was required to express the gastric contents into the duodenum. 
The small intestines were relaxed and almost empty. All but the uppermost 
3 cm. of the large intestines were filled with a hard scybalous mass. Union of a Spinal Nerve with the Vagus Nerve. 
As indicated by the sphygmomanometer attached to the animal’s leg, 
partial inhibition of the heart was obtained when the nerve was stim- 
ulated with the secondary coil at 8 and at 6. A piece of the left 
vagus nerve 3 cm. long was then removed. Now stimulation of the 
sutured nerve gave but very slight inhibition. The results obtained 
at this preliminary test were not so decided as were those obtained 
at the similar test made on Dog No. 5. 
The wound healed quickly, and the sutures were removed on the 
seventh day. But the animal did not do well. Food given by mouth 
was retained but a very few moments. Retching and vomiting were 
almost incessant. When neither food nor drink was given, the dog 
vomited a stiff, frothy material which probably consisted of swallowed 
saliva.1 
In nine days following the operation the animal lost over 3 kgm. in 
weight. At this time his condition appeared to be so serious that it 
was decided to make the final test for regeneration, although it was 
surmised that a sufficient interval of time had not elapsed since the 
section of the left vagus nerve to permit of a readjustment to the new 
conditions. 
The methods used in the final tests follow. A continuous record 
was made of the pressure in the femoral artery, of the respirations and 
of the time in two second intervals. The positions of the stimulations 
were indicated with a stimulating marking pen, which was also used 
to inscribe the base-line. After obtaining a normal record, the effect 
was tested of stimulating with the induced current the sutured (right) 
vagus nerve distal of the point of union, the central stump of the left 
vagus nerve, and the sixth cervical nerve of the left side. The cen- 
tral stump of the cervical nerve that had been united with the vagus 
was too short to be dissected out and stimulated. Then an attempt 
was made to establish a block to the passage of impulses through the 
sutured nerve by freezing it. For this purpose the following simple 
device was used. A piece of glass tubing of 5 mm. bore was bent 
sharply on itself until the two arms were parallel to one another and 
1 An attempt to feed the animal through a stomach tube resulted in failure. 
Apparently the tube passed into the stomach without meeting with any obstruction, 
but the material injected was immediately regurgitated. Then rectal feeding was 
begun, but although the enemata were well retained, the animal continued to lose 
in weight. As the vomitus was always of an alkaline reaction, it was thought 
that the addition of an acid to the food given by mouth might help to empty the 
stomach through the pylorus. But this likewise was of no avail. 382 
yoseph Erlanger. 
TABLE OF RESULTS. —Dog No. 4. 
Remarks. 
Procedure. 
Pulse- 
rate per 
min. 
Blood-pressure. 
Respirations 
per min. 
Max. 
Min. 
Normal at beginning of 
147.6 
123 
94 
11.5 
exp. 
(Period of stim. too brief 
Before 
133.7 
117 
89 
for estimation of resp. 
Stim. sutured vagus: 
rate) 
coil at 11 
During 
115.8 
116 
82 
Rate incr. 
slightly. 
Before 
143.6 
128 
97 
Same : coil at 9 
During 
117.4 
100 
80 
Before 
150.0 
124 
96 
Same : coil at 8 
During 
112.9 
113 
80 
Rate incr. 
markedly. 
Before 
143.2 
126 
98 
Same : coil at 6 
During 
126.8 
106 
83 
Same. 
10.5 
Before 
129.7 
121 
Stim. central end left 
vagus : coil at 10 
During 
126.0 
169 
Exp. tetanus. 
Before 
140.5 
148 
Same : coil at 8 
(Period of slowest pulse- 
During 
127.6 
211 
Exp. tetanus 
rate) 
then incr. 
rate. 
Before 
128.6 
152 
138 
Stim. left 6th cerv. 
* 
coil at 12 
During 
108.9 
136 
118 
Rate incr. 
slightly. 
Before 
121.6 
134 
117 
Same : coil at 10 
During 
109.6 
126 
103 
Same. 
Before 
124.9 
127 
106 
Same : coil at 8 
During 
112.9 
118 
96 
Same. 
6.5 
Test before cooling su- 
Before 
141.6 
108 
91 
tured nerve 
Stim. sutured vagus; 
coil at 7 
During 
120.0 
98 
80 
Rate incr. 
markedly. Union of a Spinal Nerve with the Vagus Nerve. 
383 
TABLE OF RESULTS.—Dog No. 4 (Continued). 
Remarks. 
Procedure. 
Pulse- 
rate per 
min. 
Blood-pressure. 
Respirations 
per min. 
Max. 
Min. 
Normal just before cool- 
126.4 
114 
92 
7 
mg 
Nerve cooled to 1° C. 
134.0 
121 
103 
10 
Before 
134.2 
121 
103 
Nerve cooled 
Stim. sutured vagus : 
coil at 7 
During 
130.3 
101 
86 
No change. 
Before 
129.2 
127 
Nerve cooled 
Stim. left vagus : coil 
at 7 
During 
133.3 
196 
Exp. tetanus 
then rate 
incr. 
Before 
129.3 
132 
117 
Nerve cooled 
Stim. left 6th cerv.: 
coil at 7 
During 
126.6 
114 
100 
Rate incr. 
slightly. 
Nerve warmed: normal 
124.0 
116 
100 
7.5 
Nerve warmed 
Stim. sutured vagus: 
104.4 
85 
73 
Exp. tetanus. 
coil at 7 
Some bleeding: resp. 
stopped: art. resp. 
during rest of exp. 
Before 
109.5 
106 
90 
Before cutting cord 
Stim. sutured vagus : 
coil at 7 
During 
101.7 
86 
72 
Before 
116.2 
112 
102 
Same : coil at 7 
During 
103.6 
95 
82 
Mean 
Before 
104.5 
42 
Cord cut in upper cervi- 
Same : coil at 7 
cal region 
During 
80.0 
44 
Before 
97.9 
40 
Same : coil at 7 
During 
88.2 
42 
Before 
94.4 
Not ap- 
Stim. left '6th cerv.: 
preci- 
coil at 7 
ably 
During 
93.2 
changed. 
Before 
90.0 
Same : coil at 5 
During 
94.0 
Same. Joseph Erlonger. 
TABLE OF RESULTS. —Dog No. 4 (Continued). 
Remarks. 
Procedure. 
Pulse- 
rate per 
min. 
Blood-pressure. 
Respirations 
per min. 
Max. 
Mean. 
Before 
104.3 
32 
Stim. central end left 
vagus : coil at 5 
During 
105.4 
34 
Before 
97.8 
30 
Stim. left 7th cerv.: 
coil at 5 
During 
97.0 
32 
Before cooling sutured 
96.0 
30 
nerve 
After cooling 
73.0 
26 
Nerve cooled 
During stim. sutured 
66.3 
30 
vagus : coil at 7 
Before 
71.2 
26 
Nerve cooled 
Stim. sutured vagus: 
coil at 7 
During 
67.5 
30 
After warming 
79.2 
24 
Stim. sutured vag. 
62.1 
28 
Before 
80.3 
24 
Same : coil at 7 
During 
63.6 
27 
Nerve cooled 
66.4 
24 
Nerve cooled 
Same: during stim. 
64.6 
26 
Before 
66.5 
22 
Same: coil at 7 
During 
66.0 
26 
After warming 
77.4 
25 
Same: during stim. 
59.3 
27 
Before 
78.5 
25 
Stim. left 7th cerv.; 
coil at 7 
During 
79.3 
27 
separated by an interval of 2 mm. One arm of this U tube was then 
cut off within 6 mm. of the concavity of the bend. After the nerve 
had been slipped into the concavity of the bend, the inflow tube was Union of a Spinal Nerve with the Vagits Nerve. 
385 
fastened into the short arm of the U tube. The temperature of the 
circulating medium was determined as it issued from the cooling 
tube. 
This cooling apparatus was placed on the sutured nerve just distal 
of the shielded electrodes with which the nerve was stimulated. 
After having cooled the nerve to i°-0.5° C., the order of stimulation 
that had been employed before cooling was repeated. The results 
obtained are given on pages 382 to 384 in tabular form. 
Upon inspection of this Table, it may be seen that undoubted partial 
inhibition of the heart was obtained both by direct stimulation of the 
Figure 4. Oxie-third the original size. Showing the effect on the heart-rate, blood- 
pressure, and respiratory rate of stimulating the sutured vagus nerve. Dog No. 4. 
7'= Time in 2 seconds; otherwise legend same as in preceding figures. 
vagus nerve that had been sutured to the cervical nerve (Fig. 4) and 
reflexly, through this nerve, upon stimulation of the central stump of 
the opposite vagus nerve (Fig. 5), and of the cervical nerve opposite 
to the one that had been sutured to the vagus nerve. 
It was not possible to obtain complete inhibition of the heart by 
stimulating the sutured nerve, but thereby the heart-rate was mate- 
rially reduced. Special attention should be called to the fact that be- 
fore section of the cord stimulation of the sixth left cervical nerve gave 
reflex inhibition which was fully as marked as, if not more marked 
than, the reflex inhibition that resulted from stimulation of the 
central stump of the left vagus nerve. Thus with the secondary coil 
at 12 (not included in the Table) and at 10, stimulation of the cen- 
tral stump of the left vagus nerve produced practically no inhibition 
of the heart. The maximum effect, which was obtained with the coil 
at 8, was a reduction of the heart-rate from 140.5 to 127.6 beats per 386 
Joseph Erlanger. 
minute. Stimulation of the sixth left cervical nerve with the coil at 
12 reduced the heart-rate from 128.6 to 108.9 beats per minute. 
When the strength of the stimulus was increased, the inhibitory effect 
diminished, but it still remained as marked as that obtained by stimu- 
lation of the central end of the vagus. Thus, with the coil at 10, the 
rate was reduced from 121.6 to 109.6, and with the coil at 8 it was 
reduced from 124.9 to 112.9 beats per minute. 
Figure 5. One-fourth the original size. Showing the effect on the heart-rate, blood- 
pressure, and respiratory rate of stimulating the central end of the left vagus nerve 
Dog No. 4. Legend same as in Fig. 4. 
When the sutured nerve was cooled to i° C., there was good reason 
for believing that functional connection of the heart with the central 
nervous system through this nerve, was practically severed. For 
now stimulation of the sutured nerve reduced the heart-rate less than 
4 beats per minute, whereas, before cooling, stimulation had regu- 
larly reduced the heart-rate more than 20 beats per minute. The 
effect of such functional section of the sutured vagus was to increase 
the heart-rate from 126.4 beats per minute to 134. Subsequently, 
upon warming the nerve, the rate became 124. It would, therefore 
appear, although the result is by no means striking, that the central 
nervous system had assumed tonic inhibitory control over the heart 
through the sutured nerve. 
The effect upon the blood-pressure of cooling the sutured vagus 
nerve may perhaps be taken as additional evidence of the existence 
of such tonic activity. For before cooling and after warming the Union of a Spina f Nerve with the Vagus Nerve. 
nerve the pressures were 114-92 and 116-100, respectively, and while 
the nerve was cooled, it was 121-103 mm. Hg. 
Cooling the sutured nerve practically stopped all reflex cardio-in- 
hibition which before cooling had been obtained upon stimulation of 
the central stump of the left vagus nerve and of the sixth left cervical 
nerve. The slight effects upon the heart-rate here seen probably fall 
within the error of the methods employed. The effects upon the 
blood-pressure can be of no assistance in this case, because they may 
have resulted through action of the stimuli upon the vasomotor 
centres. 
The results obtained after cutting the cord were totally negative in 
so far as they concern the influence exerted by the cord upon cardio- 
inhibition. Section of the cord had no perceptible effect upon the 
heart-rate. It is true that the number of beats per minute was 
smaller after section than before. But examination of the table will 
make it appear probable that the reduction of the heart-rate seen here 
is merely a progressive continuation of the slowing that had begun 
earlier in the experiment. However, the fact that section of the cord 
was not followed by cardio-acceleration might at first sight seem to in- 
dicate that the cord had exercised no inhibitory control over the heart, 
or, in other words, that the medulla was to be held responsible for the 
tonic inhibition which the earlier experiments had demonstrated to 
be present. But this view is not supported by the facts. For after 
section of the cord, functional section of the sutured vagus nerve by 
cooling did not increase the heart-rate ; indeed, it had just the oppo- 
site effect. Thus, upon alternate warming and coaling of the 
sutured nerve, the following heart-rates were recorded: 96, 73, 79.2, 
66.4, and 77.4. This result is sharp and incontestable. However, we 
have not the data upon which a satisfactory explanation might be 
based. That the slowing of t-he heart-rate was the result of the slight 
rise of blood-pressure which was always associated with the stimula- 
tions, seems improbable. 
It is also worthy of remark that, after section of the cord, stimula- 
tion of the sutured nerve, whether cooled or not, causes a slight but 
constant rise of the blood-pressure, this rise being approximately the 
same, irrespective of the effect upon the heart-rate. 
After the cord had been cut, it was still possible to obtain well- 
marked cardio-inhibition by direct stimulation of the sutured vagus 
nerve. But now stimulation of the left sixth and seventh cervical 
nerves and of the central stump of the left vagus, gave no reflex slow- 
ing of the heart. 388 
Joseph Erlanger. 
It is interesting to note that in this experiment, as well as in the 
other successful experiment of this investigation, the normal influence 
of the respiration on the heart-rate is occasionally seen. Thus at 
one place, in equal intervals of time, 8.5 heart-beats were regularly 
recorded during expiration to 9 beats during inspiration. 
Likewise, in this animal, the presence in the sutured nerve of sen- 
sory fibres influencing the respiratory centre was demonstrated. 
Thus by stimulation of the sutured nerve it was possible to elicit both 
expiratory tetanus and an increase in the respiratory rate (see the 
figures). But, as in the case of Dog No. 5, these sensory fibres had 
not acquired their normal function of regulating the respiratory rate. 
For when, at the second operation, the left vagus nerve was cut, the res- 
pirations at once became slow and deep. This condition persisted at 
the time of the final operation, nine days later. At the beginning of 
the experiment, the respiratory rate was 11.5 per minute. At a later 
period, it was 6.5 per minute. Immediately before cooling the sut- 
ured nerve, it was 7 per minute. Upon cooling the nerve, it increased 
to 10 per minute, returning to 7.5 when the block was removed. 
Therefore, in both experiments, functional severance of the sutured 
nerve increased the rate of respirations. As this phenomenon was 
not associated with any constant change in the blood-pressure, it is 
impossible to account for it from known facts. 
In the case of neither animal was there any obvious evidence of a 
restoration of the normal innervation of other organs in which the 
vagus nerve is distributed. The bark of all the animals remained 
hoarse, and in those in which the left vagus nerve was severed per- 
sistent retching and vomiting indicated either that the regenerating 
fibres had not yet reached the organs of the gastro-intestinal canal, or 
that, if they had grown into them, they had not assumed the normal 
functions of vagus fibres. It is also interesting to note that although, 
after section of the second vagus nerve, the appetite remained unim- 
paired, the vomitus which, from the evidence we have obtained, appar- 
ently came from the stomach, always had an alkaline reaction. 
At autopsy it was found that the nerve that had been sutured to 
the peripheral end of the vagus was one of the two trunks of the sixth 
cervical nerve. The point of union was marked by a spindleformed 
swelling. This was considerably larger than the one found in the 
case of Dog No. 5, indicating that the suture had not been as neatly 
made. It is possible that this may have accounted for the greater 
intensity, in Dog No. 4, of the symptoms which followed section of Union of a Spinal Nerve with the Vagus Nerve. 
389 
the left vagus, and for the impossibility of obtaining complete cardio- 
inhibition by stimulation of the sutured nerve. 
A neuroma about the size of a pea had developed on the central 
stump of the right vagus nerve at the place of section. From the 
distal end of this neuroma a tapering projection, about 3 cm. long, 
extended peripherally along the course of the carotid artery. The base 
of the projection was about 1 mm. in diameter, and had the appearance 
of a nerve trunk. Peripherally it seemed to fork, although at this 
point it became so frail that it was difficult to distinguish it from the 
surrounding connective tissue. One branch appeared to follow the 
carotid artery for a short distance, but every trace of it had disap- 
peared while still at a distance of about 4 cm. from the neuroma on 
the sutured nerve. The other branch seemed to pass into the sterno- 
mastoid muscle. Two pieces of this outgrowth, one just distal of the 
neuroma, the other 1 cm. further from it, together with a piece of the 
sutured nerve near the inferior cervical ganglion, were removed for 
histological examination.1 
Histological examination.—The piece of the sutured vagus nerve 
taken from a point near the inferior cervical ganglion was made up 
largely of connective tissue through which there was scattered a con- 
siderable number of large medullated nerve fibres. The proximal 
piece of the outgrowth from the central stump of the right vagus 
nerve was composed of medullated fibres which were somewhat 
smaller than those seen in the sutured nerve. The tissue taken from 
the more distal position contained no nerve fibres. 
Dog No. l. Union of the central end of the right hypoglossal nerve 
with the peripheral end of the right vagus nerve. —At the first opera- 
tion, which was performed on February 24, 1904, the hypoglossal and 
vagus nerves were sewn together, and a piece of the central stump of 
the vagus about 1.5 cm. long was excised. After the operation the 
dog developed a severe keratitis, but otherwise his recovery was 
uneventful. 
1 Post-mortem examination of the rest of the organs was negative. The 
oesophagus was somewhat dilated. The fundic portion of the stomach was con- 
tracted and contained a small amount of a bile-stained fluid of an alkaline reaction. 
The cavity of the stomach was in free communication with the lumen of the 
oesophagus which was filled with the same material seen in the stomach. The 
pylorus was so tightly contracted that the gastric contents could be expressed into 
the duodenum only with the greatest of difficulty. The gall-bladder was distended 
with bile. The intestines presented nothing remarkable. The lungs and heart 
were apparently normal. 390 
Joseph Erlanger. 
On May 14, 1904, eighty days after the first operation, the sutured 
nerve was exposed below the point of union, and stimulated. The 
result was totally negative. On February 9, 1905, 351 days after the 
first operation, the physiological test for regeneration was repeated, 
but the results were again negative. No slowing of the heart-rate 
was obtained with the secondary coil at o. And with the secondary 
coil at 5 the rate of the respirations was1 not affected. Stimulation 
of the left (unsutured) nerve with the secondary coil at 15 gave com- 
plete inhibition of the heart. 
A third test was made on March 15, 1905, 385 days after the 
nerves had been united, and again the results were totally negative. 
At this operation a piece was excised from the vagus nerve of the 
opposite side. Section of this nerve was associated with a slowing of 
the respirations and an increase of the heart-rate. After this opera- 
tion the dog did quite well; indeed, very much better than any of the 
other dogs in which both vagi had been cut. Although this dog had 
more or less constant vomiting, the vomitus was always reingested, 
and finally it was retained. In twenty-one days the animal lost but 
0.8 kgm. in weight. At this time the respiratory rate was 10 per 
minute. 
On May 5, 1905, 406 days after the first operation, stimulation of 
the sutured nerve again gave totally negative results. The dog died 
on the table after all of the tests had been made. 
At autopsy it was found that the central stump of the vagus nerve 
had made no visible attempt to grow down the neck. The usual neuro- 
mata were found, one at the place of union of the sutured nerves, the 
other on the central stump of the vagus nerve. These were separated 
by a distance of about 1.5 cm., and were connected by some dense tis- 
sue. This tissue, together with two pieces of the sutured nerve, one 
taken from a place near the point of union, the other from a place 
near the inferior cervical ganglion, were removed for histological 
examination.1 
Histological examination. The tissue obtained from this dog was 
fixed in osmic acid and teased on the slide. In the tissue that 
united the two neuromata was found a bundle of medullated fibres. 
The size of the fibres was very variable ; roughly, the frequency of 
1 The oesophagus was somewhat dilated, but the cardiac orifice of the stomach, 
as well as the pylorus, were closed. The stomach was distended with large pieces 
of undigested meat. In the left ventricle was found a comparatively fresh, large, 
white thrombus. Union of a Spincd Nerve with the Vagus Nerve. 
391 
large and small fibres was approximately equal. As the bundle was 
torn in teasing, no estimate could be made of its size, but it un- 
doubtedly contained a considerable number of fibres. 
The hypoglossal vagus nerve near the point of union contained 
medullated fibres, most of which were of the large variety. Likewise, 
medullated fibres were found in it near the inferior cervical ganglion, 
but here mosbof the fibres were of the small variety. 
Although the results of this experiment are negative, in so far as 
they concern functional regeneration, still they are of interest in at 
least two particulars. In the first place, they serve to indicate that, 
in experiments on cross-suturing of nerves, resection of a piece of a 
central stump which is left free in the wound may not suffice to pre- 
vent a re-establishment of normal innervation. 
In the second place, it is interesting to note that, although vagus 
fibres had undoubtedly united with the sutured nerve, they had not 
yet assumed control of vagus functions. This apparent sluggishness 
might be accounted for in one of three ways: (a) It is of course 
possible that the connection of vagus with vagus had not been es- 
tablished long enough to allow of functional regeneration, (b) Vagus 
fibres might not regenerate as rapidly as other fibres, (c) The 
presence in the regenerating nerve of fibres derived from two sources 
might in some way have interfered with the process of regeneration. 
The data of this experiment do not suffice for a discussion of the 
relative importance of these possibilities. 
The results of the experiments herein described demonstrate that 
when the central end of a spinal nerve is sewn to the peripheral end 
of the vagus nerve the fibres of the former may make functional con- 
nection with the vagus end-apparatus in the heart, if sufficient time 
be allowed for regeneration. Complete inhibition of the heart may 
be obtained by direct stimulation of such regenerated fibres. Such 
fibres may serve as the efferent path of cardiac reflexes which are 
associated with the act of respiration, and of reflexes started by elec- 
trical stimulation of afferent nerves. And finally through these fibres 
the central nervous system may exercise a tonic inhibitory control 
over the heart. 
Summary and Discussion. 
In one of the instances of successful union, an attempt was made 
to locate the inhibitory centre, that is, to determine whether the 
reflex centre still maintained its normal position in the medulla, or 392 
Joseph Erlanger. 
whether it had moved to the cells of origin of the spinal nerve which 
was performing the functions of the vagus. It will be recalled that, 
after cutting the cord in the upper cervical region, stimulation of the 
central end of the unsutured vagus nerve or of the sixth cervical nerve, 
no longer caused reflex cardiac inhibition. But this does not prove 
that the reflex centre had not moved into the cord. Nor is the situ- 
ation of the centre in the medulla proved by the fact that after trans- 
section of the cord in the upper cervical region no acceleration of the 
heart-rate followed functional section of the sutured nerve. For it is 
possible that transsection of the cord ma}' have produced spinal shock, 
a condition in which, according to Sherrington,1 the portion of the 
cord aboral of the mechanical injury suffers a more or less complete 
suppression of nervous function. 
The only evidence which favors the location of the reflex centre in 
the cord consists in the observation that reflex inhibition of the heart 
was more easily obtained by stimulation of a cervical nerve than by 
stimulation of the central end of the vagus nerve. However, this 
evidence can be considered suggestive only, for under normal circum- 
stances reflex inhibition of the heart may be obtained by stimulation 
of any afferent nerve in the body. 
As these experiments have failed to locate positively the so-called 
cardio-inhibitory centre, a discussion of the way in which the central 
nervous system has adapted itself to the changed conditions resulting 
from union of a spinal nerve with the vagus nerve could not be ex- 
pected to lead to a positive conclusion. Nevertheless a discussion 
of the possibilities might not be out of place. 
From what is known of regenerative processes within the central 
nervous system, it is highly improbable that axons of the cells of the 
vagus centre could grow through the cord and cervical nerve and so 
reach the heart. And there is no evidence, even if we admit Bethe’s 
hypothesis,2 that a growth of fibres could occur along the same 
course in the reverse direction. 
But it is possible that the resistance to the passage of impulses 
along descending fibres, which probably connect the vagus centre 
with spinal nuclei, might have been diminished as a result of their 
unwonted activity. In this way they might have become the natural 
path of discharge of the normal cardio-inhibitory centre. 
1 Sherrington: Schafer’s Text-book of physiology, London, 1900, ii, p. 846. 
2 Bethe; Allgemeine Anatomic und Physiologic des Nervensystems, Leipzig, 
1903, p. 182. Union of a Spinal- Nerve with the Vagus Nerve. 
393 
Finally it might be assumed, and it will be remembered that we 
have obtained some evidence in favor of this view, that the inhibitory 
centre has actually taken its abode in the nucleus of origin of the 
cervical nerve. In this connection attention should be called to the 
opinion first expressed by Bernstein1 that the tone of the inhibitory 
centre is probably not the result of automatic activity of the centre, 
but rather the result of the continual arrival in it of afferent impulses. 
Whether or not the cardio-inhibitory centre selects and adapts affer- 
ent impulses so as to make them subserve the best interests of the 
organism, it is impossible to state. The great differences in the re- 
sponse of the inhibitory centre to stimulation of various afferent 
nerves might, perhaps, be taken as evidence of such a selective 
action. But here it is again possible that, through inheritance or 
exercise, certain tracts have become the paths of least resistance. 
It is, therefore, not necessary to assume that the cardio-inhibitory 
centre possesses automaticity. The facts do not debar the view that 
the continual variations in the tone of the cardio-inhibitory centre 
are the result merely of the arrival and spread of impulses of all kinds 
in the central nervous system. And it might, in addition, be admitted 
that when the vagus nerve connects the heart with the central ner- 
vous system, this spread of impulses, modified to some extent by the 
resistance offered to their passage along the various paths, affects 
the heart through the cells of origin of the vagus fibres. But should 
the axis cylinders of any other group of cells in the central nervous 
system make connection with the inhibitory mechanism in the heart, 
then the spread of impulses might affect the heart in the same way 
and with an intensity which might vary with the efficiency of the 
impulses acting upon the cells of origin of the nerve fibres. In other 
words, such a group of cells might become the reflex centre for cardio- 
inhibition. Therefore, in the case of the cardio-inhibitory centre it 
would not be necessary to conclude with Rawa2 that “the nerve 
centres will perform just those functions which are demanded of 
them by the peripheral organs with which they are connected.” 
Our observation that the transmission of reflexes to peripheral 
organs along fibres which do not normally make connection with 
such organs is not unique. As has been stated, Rawa’s instances 
are not perfectly clear. It is possible that in his experiments vagus 
1 Bernstein: Archiv fur Anatomic und Physiologic, 1864, p. 633. 
2 Rawa : Loc. cit. 394 
Joseph Erlanger. 
fibres may have resumed their normal connections. But Mislavsky 1 
has undoubtedly obtained reflex contraction of the laryngeal muscles 
after union of the thoracic end of the cervical sympathetic with the 
recurrent laryngeal nerve. Perhaps the most striking instance of 
this kind is seen in the case reported by Cushing,2 in which, after 
union of the central end of the spinal accessory nerve with the periph- 
eral end of the facial nerve in man, the subject gradually regained 
voluntary control of individual facial muscles. It should be stated 
here that Cunningham3 maintains that in the dog normal control 
is never regained over abnormally innervated voluntary muscles. 
Furthermore, the recovery of voluntary control in such a case might 
not be comparable to the recovery of a reflex control. In the former 
case the recovery of function might he facilitated by training; in the 
latter case training could not play a part. 
Our experiments do not permit of the formulation of a positive 
conclusion with regard to the rate of regeneration of fibres of differ- 
ent origin when united with the vagus nerve. Nevertheless, when 
viewed in conjunction with the experiments of others, they do indi- 
cate that spinal fibres make functional connection more rapidly than 
fibres of the hypoglossal and vagus nerves. In our most successful 
case, complete inhibition of the heart was obtained 303 days after the 
cervical and vagus nerves had been sutured. In one instance of 
union of the hypoglossal (and vagus ?) with the vagus nerve, no signs 
of functional regeneration were obtained 406 days after sewing the 
nerves together. However, Henri and Calugareanu4 describe one 
instance in which complete inhibition of the heart was obtained 170 
days after the same operation. Many investigators have tested the 
power of the vagus to regenerate itself. All final tests made within 
a year of the operation have yielded negative results.5 
Neither has conclusive evidence been obtained with regard to the 
influence which an intact vagus nerve exerts upon the rate with which 
a regenerating vagus nerve will make functional connection with the 
end apparatus in the heart. However, one fact seems to indicate 
that it has a retarding influence. At the last preliminary operation 
1 Mislavsky: Comptes rendus de la societe de biologie, 1902, liv, p. 841. 
2 Cushing: Journal of nervous and mental diseases, 1903, xxx, p. 367. 
8 Cunningham: This journal, 1898, i, p. 239. 
4 Henri and Calugareanu : Loc. cit. These authors do not give the results 
of post-mortem examinations. 
5 Tuckett : Loc. cit. Union of a Spinal Nerve with the Vagus Nerve. 
395 
in Experiment 5, it was found that strong stimulation of the sutured 
nerve had but a slight effect upon the heart-rate. The inhibition that 
resulted did not last longer than the time occupied by two heart-beats. 
Only twenty-one days later strong stimulation of the sutured nerve 
held the heart in complete inhibition for seventeen and seven-tenths 
seconds. It is rather improbable that this sudden change in the 
response of the heart to vagus stimulation would have occurred in 
the course of an uninfluenced regeneration. 
Finally, it might not be superfluous to state that the fact that im- 
pulses carried to the heart through spinal fibres may bring the heart 
to rest, favors the view that cardiac inhibition results from the action 
of ordinary nerve impulses upon a peculiar end-apparatus.