EFFECT ON RESPIRATION, BLOOD PRESSURE AND CAROTID
PULSE OF VARIOUS INHALED AND INSUFFLATED VAPORS
WHEN STIMULATING ONE CRANIAL NERVE AND VARIOUS
COMBINATIONS OF CRANIAL NERVES
II. VAGUS AND VAGOTOMY EXPERIMENTS
BY
WILLIAM F. ALLEN
From the Department of Anatomy of the University of Oregon Medical School,
Portland, Oregon
REPRINTED FROM THE AMERICAN JOURNAL OF PHYSIOLOGY
VOL. LXXXVII, No.3, JANUAIW, 1929
Reprinted from THE Al\IERICAN JOURNAL OLi' PHYSIOLOGY
Yol. 87, No.3, January, 1929
EFFECT 0 RESPIRATION, BLOOD PRESSURE AND CAROTLi).
PULSE OF VARIOUS INHALED AND INSUFFLATED VAPORS·
WHEN STIMULATING ONE CRANIAL NERVE AND VARIOUS
COMBINATIONS OF CRANIAL NERVES
II. VAGUS AND V AGO'l'OMY EXPEltlMEN'l'S
WILLIAM F. ALLEN
From· the Department of Anatomy of the University of Oregon Medical Schuul,
,Purtland, Oregon
Received for publication October 22, 1928
The purpose of this investigation is threefold: first, to determine thc
effect of inhaling strong and weak irritating vapors on respiration and cir-
culation in a vagal animal, by which is meant an animal deprived of all
effective sensory nerves supplying its upper respiratory passages (olfac-
tory and trigeminal); second, to ascertain if there is any alteration of
respiration and circulation during the inhalation of irritants in a vagal
rabbit after double vagotomy; third, to repeat the experiments of several
previous investigators on insufflation of irritating vapors into the trachea
of vagotomized animals in which both positive and negative results have
been obtained.
In attempting to solve the first problem suggested above, there is appar-
ently no available technique (unless it be some complicated modification
of the isolated head technique) for completely eliminating the possibility
of humoral and secondary mechanical stimulation of the periphery or of
humoral stimulation of the medulla centers. If negative results are ob~'
tained in the experiments of the second and third problems suggested,
it may be inferred that humoral medulla-spinal stimulation is not a factor
in th~ first problem. A previous paper and especially one to follow iIidi-
cate that humoral and secondary mechanical factors take but little part
in the alteration of respiration and circulation where these vapors were,
inhaled for relatively short periods of time. ' ' ,
The vagus changes in respiration following the blowing of an irritant
into the trachea, as demonstrated by Zagari, consists of a considerable de-
pression and acceleration. As reported by Roger, Mayer Magne and
Plantefol, Craigie, Larsell and Burget, it includes a period of violent
coughing or spasm followed by apnea or shallow respiration. Brodie and·
Russell's and Roger's blood pressure tracings show a distinct drop 'arid ~
558
559 PATHWAY OF STIMULUS OF INHALED VAPORS
strengthening of the pulse, and Craigie's tracings disclose a fall at the time
of stimulation.
Effect of various inhalants on respiration, blood presSU,re and carotid pulse
in vagal rabbits. Several days before these tests were made the olfactory
tracts, the naso-ciliary and maxillary nerves were sectioned in the manner
described in a previous report; severance of these nerves was previously
found to be as effective in blocking trigeminal impulses from inhalations
as division of the trigeminal roots intracranially. Thoracic respiratory
and blood pressure tracings were taken as described previously with the
animal under veronal-sodium hypnosis.
Fig. 1 A. Vagal rabbit, stimulation by inhalation, thoracic-respiratory graph,
inspiration upstroke, time in 5 seconds; Band C, vagal rabbit, inhalation stimulation,
thoracic-respiratory and blood pressure tracings, time in seconds; in C, depressors,
vagi, and cervical sympathetics were cut.
In the first rabbit (563) the graphs were confined to respiratory tracings
taken during the inhalation of ammonia, benzol and xylol from cones satu-
rated with these substances. The ammonia cone was held about 7 em.
from the nostrils, the benzol about 4 em., and the xylol about 3 em. The
benzol graph (fig. 1, A) reveals three distinct changes taking place in
respiration. First, there is a short interval of depression. This gives way
to a sudden expansion of the chest, starting during an expiration, it con-
tinues as a series of coughs or spasm. The extreme height of these forced
movements of the lever was purposely stopped by a bar. This important
phase is abruptly followed by a period of shallow and somewhat acccler-
WILLIAM F. ALLEN 560
ated excursions and a gradual return to normal. The graphs obtained
during the inhalation of ammonia and xylol were somewhat similar. The
chief difference is in the time of appearance of the altered respiration and
the duration time of the coughing spell. The change appears within 9
seconds in the ammonia tracing, within 10 secones in the benzol record,
and not until 20 seconds in the xylol graph. The coughing spell is longest
in the ammonia record and shortest in the xylol. In the ammonia record
there is some inhibition as well as depression in the first period, and only a
moderate depression of the excursions following the coughing period.
In the second part of this experiment the depressors, vagi, and cervical
sympathetics were sectioned at, the level of the larynx, and respiratory
tracings obtained during the inhalation of ammonia, benzol and acetic
acid for periods of fifty seconds, as shown by the benzol graph (fig. 2, A),
reveal respiration unchanged.
Both parts of this experiment were repeated in two other vagal rabbits
with like results.
In vagal rabbits (571 and 572) this experiment was repeated and its
scope was enlarged to include blood pressure tracings. The respiratory
responses obtained during the inhalation of ammonia, aromatic spirits of
ammonia, acetic acid, chloroform, oil of mustard, wintergreen, benzol and
xylol are very similar to those obtained in the previous animals. Every
record shows a considerable drop in blood pressure accompanied, usually,
by some slowing and strengthening of the pulse.
In one graph (fig. 1, B) an ammonia cone was purposely held close to
the nostrils to elicit a maximum stimulation. It is apparent that the reac-
tion is concerned almost entirely with the interval of coughing, which
appears in 9 seconds and lasts for 20 seconds.' There is no~ depression or
inhibition of the excursions preceding the period of coughing and only an
acceleration of a few excursions immediately following. Meanwhile the
blood pressure tracing discloses a drop of 20 mm. and there appears to be
some slowing and strengthening of the pulse.
As in the previous animals the xylol reaction is the weakest and slowest
in appearing. "
After sectioning the depressors, vagi and cervical sympathetics, the same
vapors inhaled for periods of 50 seconds evoke no change in respiration or
pulse or any drop in blood pressure (see ammonia graph fig. 1, C). The
apparent inhibition of respiration during the last part of this tracing is
shown to be due to a speeding up of the drum. It is obvious from the
blood pressure tracing (fig. 1, C) that there is no change for 32 seconds, the
slight rise which occurs a little later may come from humoral stimulation
of the medulla.
Effect from inhalation of weak and very weak irritants in vagal animals.
It was stated in the previous experiment that xylol was one of the weakest
561 PATHWAY OF STIMULUS OF INHALED VAPORS
~tiJ;llulal1ts of the, vagus, so that a weak xylol stimulation should yield a
very weak vag~l reaction, if it produces any at all. Figure 2, B was ob-
tained while a cone, saturated with xylol, was held at some distance from
the nostrils for 40 seconds. After 32 seconds of inhalation (allowance
being made for the oIl1itted portion of the record) there is a slight inhibi-
tion of respiration and a small drop in blood pressu~e without any change
in the pulse. These changes are not thought to be of humoral medulla-
spinal cord origin for the reason that none of the writer's graphs taken
from, vagotomized vagal rabbits show any alteration of respiration and
blood pressure from inhalations of much stronger xylol vapor for a con-
Fig. 2 A. Same as 1 A, except that depressors, vagi, and cervical sympathetics
were severed; Band C, vagal rabbit, stimulations by low and very low concentra-
tions of xylol inhaled, thoracic-respiration and blood pressure tracings (omitted
portion in B represents 7 seconds), time in seconds.
siderably longer time. Also the drop in blood pressure speaks for a vagal
stimulation.
A stronger xylol stimulus obtained from holding the cone closer to the
nostrils \(fig. 2, C) demonstrates the changes in respiration and blood
pressure appearing within 16 seconds. The respiratory response, in the
upper tracing, i!lhows a cough reflex or spasm preceded and followed by
short periods of depression. There is considerable drop in blood pressure
and some slowing and strengthening of the pulse.
A typical vagal respiratory and circulatory response was obtained in a
tracheotomized vagal rabbit with the laryngeal branch of the vagus intact
by blowing large quantities of ammonia into both nostrils. Later when
WlLLIAM F. ALLEN 562
the pharynx was slit above the larynx so that little or no ammonia reached
the larynx, no vagus reaction was obtained from insufflation into the' nos-
trils. This is apparently confirmatory of Kratschmer's results obtained
by blowing an irritant directly into an isolated larynx.
Effect oj insufflation oj ammonia and other vapors into the trachea oj
vagotomized rabbits. Of the investigators who have stimulated the lower
respiratory passages of vagotomized animals by blowing irritants into the
trachea, Zagari, Mayer, Magne and Plantefol, and Larsell and Burget
report no respiratory reaction; while Roger and Craigie obtained definite
respiratory and blood pressure changes. Roger's figure 10 portrays con-
siderable depression and inhibition in respiration and a drop in blood
pressure during chloroform insufflation, and Craigie's graphs disclose the
normal vagus changes slightly weakened. After a study of these publica-
tions it appeared likely that the difference in results might be largely at-
tributed to variations in technique.
This experiment or problem passed through three different stages as
unforeseen factors were encountered.
First,-a number of thoracic respiratory and blood pressure tracings
were made from several vagotomized rabbits during the time that am-
monia vapor was blown into the tracheal cannula through which the
animal was breathing. These records demonstrate a varying amount of
expansion of the thorax, a depression of respiration, and a fall in blood
pressure. It was evident that these changes might be explained by local
pulmonary changes offering a greater resistance to the respiratory move-
ments of the thorax, due possibly to an increased expansion of the lungs
from the insufflations or to a spasm of the constrictor muscles of the
trachea and bronchi. With these possibilities in mind it became necessary
to pay more attention to air controls and to the amount of pressure used
during insufflation.
Second,-the previous procedure of taking thoracic and blood pressure
records during insufflations into the trachea of rabbits deprived of their
depressors, vagi, and cervical sympathetics was repeated and expanded to
include a respiratory tracing taken from the trachea. The apparatus for
obtaining the tracheal record consisted of a Y-shaped tracheal cannula,
one external arm of which was connected to a previously described blowing
bottle by a rubber tube with a pinch clamp, and the other external
arm was in direct communication with a large air bottle and recording
tambour. The bottle in addition to supplying some air for ventilation
served as a sort of buffer. The wounds in the neck, the mouth, and t.he
nostrils were covered with cotton.
The procedure of insufflation was as follows: the animal breathed from
the air chamber for a short interval, then air and insufflated vapor for
periods of from 3 to 17 seconds, and finally from the air chamber. In. !l..
563 PATHWAY OF STIMULUS OF INHALED VAPORS
few tests this technique was varied by the attachment of two blowing
bottles to one arm of the cannula, so that air blown from the first bottle
into the trachea could be followed immediately by an irritating vapor
from the second. A large number of simultaneous thoracic-respiratory,
tracheal-respiratory, and blood pressure tracings were obtained from five
rabbits during the insufflation of ammonia, acetic acid, ether, and especially
air, under great variations of pressure.
These records reveal that there is a direct relationship between any
given tracheal respiratory excursion and the corresponding thoracic ex-
Fig. 3. Vagotomized rabbit, tracheal insufflation, thoracic-respiratory, tracheal-
respiratory, and blood pressure tracings, time in seconds.
cursion, and it is immaterial whether this record is from insufflation of an
irritant or air. An air control graph (fig. 3) demonstrates that a slight
increase in air pressure is followed by some increase in the depth of the
first thoracic respiratory excursion. After a certain point has been
reached in the expansion of the lungs and thorax, a gradual increase in
pressure elicits a gradual expansion of the thorax and a gradual reduction
in the depth of thoracic respiration. In some records this has been in-
creased to the extent of bringing pulmonary and thoracic respiration to a
standstill. By varying the pressure in an air control graph, it is possible
to duplicate any graph obtained from any irritant.
WILLIAM F. ALLEN 564
With the technique employed there is some indication of greater ex-
pansion in the lungs by some vapors (ether) than there is with some others
under the same pressure.
Practically all of these records show soine drop in blood pressure and no
pulse change. In general, there is a considerably greater drop in the
graphs obtained during the insufflation of an irritant than there is for air.
The contour of the blood pressure curve appears to conform very closely
to the curve of the general expansion of the thorax as is shown in figure 3.
Third,-in two rabbits the above stimulation technique was consider-
ably modified. In place of insufflating the vapors into the tracheal can-
nula, the bulb was removed from the blowing bottle and the animal was
permitted to inhale through the cannula air saturated with ammonia,
acetic acid, and ether for periods of from 12 to 18 seconds. After each
inhalant, air was inhaled through water for the same length of time. There
can be no question but that this mode of procedure flooded the lungs with
large quantities of air well saturated with these vapors. A comparison
of any irritant graph with its air control discloses no difference. Both
respiratory tracings of all the records show some expansion during the
time of inhalation. Ordinarily blood pressure shows no changes in either
record, but sometimes there is a slight drop in both tracings.
Comment. Two deductions appear to be fairly well warranted by the
results obtained from the foregoing experiments-a, that certain nerves,
supposed by Barry, Pike and Coombs, and Mollgaard to carry impulses
from the lungs to spinal cord by way of the upper thoracic and lower
cervical spinal nerves, are not stimulated to produce respiratory changes
by large quantities of air containing a high concentration of very irritating
vapors; b, that relatively short inhalations or insufflations of very irritat-
ing vapors do not cause a humoral medulla-spinal stimulation affecting
respiration.
SUMMAHY AND CONCLUSIONS
Moderately strong inhalations of various irritating vapors by way of
the nose in the so-called vagal rabbits, animals having no protection from
the olfactory or trigeminal nerves, produce somewhat similar respiratory
and vascular changes to those described by others from blowing these
irritants into the trachea.
This alteration of thoracic respiration consists of 1, a short period of
depression or depression and inhibition; 2, a spasm or period of coughing,
depending in length and strength on the irritant used; 3, a period of more
or less depression with a gradual return to normal. The important char-
.acter is the period of coughing.
Blood pressure drops in. proportion to the strength of the irritant used
and to the general expansion of the thorax. There is generally some slow-
ing and strengthening of the carotid pulse.
565 PATHWAY OF STIMULUS OF INHALED VAPORS
A very powerful thoracic respiratOl:y reaction from inhalations in' a
vagaltabbit consists of the immediate appearance of the coughing spell; •
while a very weak reaction shows only a slight inhibition of respiration, a·
little dl'op in blood pressure and no pulse changes.
Changes in respiration and circulation are elicited from inhalations of·
ammonia, acetic acid, formalin, oil of l1"iustard, wintergreen,chloroform,~
ether, benzol and xylol.
After sectioning the depressors, vagi, and cervical sympathetics at thE)·
level of the larynx, any of the above vapors could be inhaled through the
nostrils by a vagal rabbit for fifty seconds without any alteration of respira-
tion or drop in blood pressure.
Insufflation of irritating vapors into the trachea of vagotomized rabbits·
is followed by a response in respiration and circulation very similar to
that described by Roger for chloroform, consisting of a general expansion
of the thorax, a depression of respiration, and a drop in blood pressure;
Evidence is produced which shows that those respiratory changes in the
writer's animals are probably caused by an increase in the intrapulmonary
pressure resulting from the insufflatiol'ls.
Vagotomized rabbits, inhaling through the trachea large quantities of
air containing a high concentration of irritating vapors, show no greater
respiratory and circulatory changes than when inhaling unmixed air under
the> same .conditions.
BIBLIOGRAPHY
ZAGARI: Arch. f. (Anat u.) Physiol., 1891, 37.
RodER:· La presse medicale, 1917, xxv, 73.
MAYER, MAGNE ET PLANTEFOL: Compt. rend.; 1920, cIxx, 1347.
CRAIGIE: This Journal, 1922, !ix, 346.
LARSELL AND BURGET: This Journal, 1924, lxx, 311.
BRODIE AND RUSSELL: Journ. Physiol., 1900, xxvi, 92.
KRATSCHMER: Sitzungsb. d. Wiener. Akad.d. Wissen., 1870, lxii, 147.
BARRY: Journ. Physiol., 1913, xlv, 473. .
PIKE AND COOMBS: This Journal, 1922, lix, 472.
MOLLGAARD: Skand. Arch.·Physiol., 1912, xxvi, 315.
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