5/20/2018 A Study of the Hering-breuer Reflex
1/19
A S T U D Y O F T H E H E R I N G - B R E U E R R E F L E X .
BY RICHMOND L. MOORE, M.D.
From the Hospital o f The Rockefeller Institute for Med ical Research.)
Received for publication, Jul y 26, 1927.)
xrrrRoo~cTio~r.
The observat ion has been made by several inves t igators tha t a rapid
respiratory rate depends on in tact vagal conduct ion. In exper iments
on anes thet ized rabbi ts , Sc ot t 1908) showed that an increase of carbon
dioxide not above 6 to 7 per cent) in the inspired air af ter the vagi had
been divided was fol lowed by an increase in the de pth of breathing, bu t
tha t the ra te remained pract ical ly unal tered. On the contrary , the
response of animals with in t act vagi was a n increase in ra te , as wel l as
in dept h of respiration. Por ter and Newbu rgh 1917) found tha t the
rapid respirat ions occurr ing in dogs in whom they had produced an
exper imental pneumonia became normal af ter cocainizing the vagus
nerves . Th ey had noted before th is tha t i f the vagal t runk s were
sect ioned previous to infect ing the animals the respirat ions d id not
becom e rapid 1916). Du nn 1920), and still later Bing er and his
coworkers 1924), dem onst rate d th at the rapi d mad shallow breathing ,
produced exper imental ly in animals by the in travenous in ject ion oI
a suspens ion of potato s tarch granules, d isappears immedia tely i f the
vagus nerves are d ivided or f rozen. I t was shown later tha t animals
in whom the vagi ha d been sect ioned several month s previous to the
inject ion of s tarch granules d id not accelerate their ra te Binger and
Moore, 1926) . I t would appear f rom the inves t igat ions of these
lat ter authors Dunn and Binger) tha t the Her ing-Breuer ref lex was
enormously exaggerated under the condi t ions of their exper iments .
Presumab ly sect ion of the vagi b locked the per ipheral s t imuli tha t were
essential to the rapid rate.
In spi te of the man y s tudies that have been mad e of the vagal inf lu-
ence on breathing, the m anne r in which the vagal nerve endings are
exci ted is not ye t c lear. Our in teres t in th is subject developed f rom
819
5/20/2018 A Study of the Hering-breuer Reflex
2/19
820
HERING-BREUER REFLEX
an effort to explain the rapid and shallow breathing seen clinically in
pneumonia, and produced experimentally in animals by the intrave-
nous injection of pota to starch granules. The experiments that will
be presented were designed to study the nature of the Hering-Breuer
stimulus.
Historical
Early last century Legsllois (1812) observed that section of the vagus nerves
is followed by slowing and deepening of the respirations.
Hering and Breuer (1868), in a series of experiments performed on dogs and
rabbits, both with and without anesthesia, showed that inflation of the lungs at
once produces a movement of expiration and deflation a movement of inspiration.
These observations were made both when the animals breathed naturally and when
the lungs were expanded or collapsed artificially. The influence was not present
when the vagi were divided. On the basis of their evidence Hering and Breuer
formulated a theory for the self-regulation of respiration. They concluded that
the respiratory center was continuously influenced through the vagi by the move-
ments of the lungs, expansion checking inspiration and initiating expiration, and
collapse checking expiration and initiating inspiration. Hering and Breuer also
described a pause in respiratory movement following distention of the lungs.
They explained this as an inspiratory inhibition due to vagsl excitation following
expansion.
The observations of Hering and Breuer were confirmed and elaborated by
Head (1889), and later by Christiansen and Haldane (1914), and Haldane and
Mavrogordato (1916). Head showed that inflation of the lungs produces an
instant and complete relaxation of the diaphragm, and that if air be sucked out
of the lungs the diaphmgra will go into a state of tonic contraction. Both of
these effects were absent if the vagi had been previously cut.
Christiansen and Haldane were the first to study the effect of distending the
lungs on the human respiration. Distention was provided at the end of expiration
by having the subjects breathe from a bag containing air, and so weighted that the
air was under a pressure of 6 to 8 cm. of water. The respirations were recorded
with a stethograph. When the lungs were distendedin this manner, the respiratory
movements invariably ceased, for usually about half a minute. 1 That the pause
was not due merely to lowering of the alveolar CO~ pressure was shown by the fact
that it was still produced when the air in the bag contained 7.3 per cent of CO2
and 8.2 per cent of (32. At this time, Christiansen and Haldane explained the
pause that they had observed in man as an Hering-Breuer inhibitory effect.
1 The pause in respiratory movements referred to here is the primary pause
and must be distinguished from a secondary pause that was also observed. This
latter was clearly shown to be related to a lowered CO2 percentage in the inspired
air and was described as a true chemical apnea.
5/20/2018 A Study of the Hering-breuer Reflex
3/19
RICHMOND L. MOORE
821
This interpretation, however, was subsequently changed by Haldane (1922),
and the pause has since been described as simply a prolonged expiratory effort .
Haldane and Mavrogorda to demonstra ted in man tha t in te rrupt ion of ei ther
respiratory phase interrupts the previous rhyt hm of the respiratory center. If
expiration is interrupted, there follows a prolonged expiratory phase during which
the intrapulm onary pressure gradually rises. This is finally terminated b y an
inspiratory effort. If inspiration is obstructed, a prolonged inspiratory effort
follows, but under these conditions the intrapulmonary pressure falls and the
negative phase is terminated by an expiratory effort . Comm enting upon these
and the foregoing experiments, Haldane (1922) says: Th e respiratory center
does not act independently of the lung movements, but inspiratory or expiratory
discharge of the center goes hand in hand with actual inspiration or expiration, as
if the center were one piece with the lungs .
Boo thby an d B erry (1915) also studied the effects of distention of the lungs on
the respiratory rhythm in man, and extended their observations to normal and
vagotomized dogs. The lungs were distended by having the subjects breathe
from a spirometer so weighted tha t the air was und er a pressure of 8 to 16 cm. of
water. The dogs did not require anesthesia. The respiratory movem ents were
recorded qualitatively by means of a pneumograph, and quantitative curves of
the coordinated total respiratory move ments were written by the spirometer.
None of the curves tha t the y obtained showed a primary inspiratory inhibition.
In regard to the experiments of Hering and Breuer, they say: Th e pause noted
by Hering and Breuer is not at the top of inspiration but at the bottom of expira-
tion, that is, the next expiratory phase is prolonged and inspiration is delayed,
or, as they say, ' inhibited, ' by vagal stimulation. In experiments on dogs, in
which the pulmonary branches of both vagi had been divided, Boothby and Berry
obtained several instances of a short apnea on distention of the lungs. Th ey con-
cluded that the vagi do not transmit impulses which, according to Hering and
Breuer, arise from distention of the lungs and inhibit inspiration.
Einthoven (1908) studied the action currents in the peripheral end of the
divided vagus by means of a string galvanometer. Anesthetized dogs were used
and the vagus was divided high up in the neck. Records of the electrical changes
in the nerve were made by photographing the image of the galvanometer string.
When the animals breathed naturally curves were obtained that showed undula-
tions synchronous with the respiratory movements. Additional experiments
were carried out on the effects of insufflating and deflating the lungs. These
showed that the excitatory state of the vagus nerve endings was related to lung
volume and not to intrapulmo nary pressure. In other experiments of this type
Einthoven found that electrical changes occurred in the peripheral end of the cut
nerve that w ere synchronous with artificial deflation of the lungs. He accepted
his findings as evidence of the presence of two kinds of pulmo nary v agus fibres,
and concluded that his experiments gave support to the theor y on the self-
regulation of respiratory movements that had been advanced by Hering and
Breuer.
5/20/2018 A Study of the Hering-breuer Reflex
4/19
822
HERING-BREUER RE]~LEX
Schafer 1919) admits that respirations are affected by influences coming from
the lungs, but calls attention to the fact th at double vago tom y is not ahv ays
followed by cons tant effects. He believes that the results of vago tom y may be
influenced considerably by obstruction at the glottis from paralysis of the laryn-
geal muscles and a failing together of the thyroa ryteno id ligaments. When this
is avoided Schafer states t hat the slowing of breathing is often absent or transi-
tory, and that animals ma y survive section of the vagi indefinitely.
Pi Suffer and Bellido 1921) claim to have produ ced evidence to show tha t the
vagal nerve endings in the lungs are susceptible of being stimulated by high
concentrations of carbon dioxide in the alveolar air. This idea was not a new one,
for Tran be 1871) had supposed that carbon dioxide could act by directly stimu-
lating the pulmonary terminations of the vagi.
More recently Lums den 1923) advanced the theory that in easy breathing the
vagal endings are stimulated by the air currents passing in and ou t over the ciliated
tracheal mucous membrane. Lumsden, however, admits tha t extreme distention
and collapse of the lungs give rise to vagal impulses of a different kind.
It is obvious from this brief review of the li terature that our knowledge of the
true character of the Hering-Breuer stimulus is incomplete.
Method
The method used is similar to the one described by Churchill and Agassiz
1926). It permits separate recording of the respiratory mo vements of each
lung. Two brass tubes serve to divide the trachea into two separate compart-
ments. The tubes are 14 and 22 cm. long and both have an internal diameter of
6 ram. The longer one is l igated in the bronchus on one side. The shorter ex-
tends downward to the opp3site bronchus, but does not necessarily enter i t . Each
cannula connects with a separate respiration system including inspiratory and
expiratory valves, soda lime for removing CO2, and a smalls pirometer for recording
the changes in respiratory movements. Tracings of the respiratory curves were
made by equipping the spirometers with writing pens. Dogs anesthetized with
barbital-sodium were used, as previously described Moore and Bin ger 1927)).
The operative procedure was the same in all experiments. When satisfactory
anesthesia had been obtained the trachea was exposed in the neck and the right a nd
left vagus trunks were isolated. The trachea was then opened and the metal tubes
introduced and temporarily anchored in place by a l igature. After this mechanical
respiration was provided separately for each lung by forcing air intermittently
under slight presure into the two tubes. The air escaped through one branch of
a Y-shaped tube connected with the system. The dog was placed on the side
with the forelegs extended and the thorax w as opened through the 5 th intercostal
space, right or left as the occasion demanded. During the operative procedures
within the thorax the ribs were held apart by a mechanical retractor and the
Iungs retracted from the field by cotton packs soaked in warm, physiological
sodium chloride solution. In isolating the bronchus blu nt dissection was used
5/20/2018 A Study of the Hering-breuer Reflex
5/19
RICHMOND L. MOOR 823
as much as possible in order to lessen the danger of nerve injury. After placing
a ligature beneath the bronchus the long cannula was manipulated into position,
and tied firmly in place. Expansion of all lobes subsequent to this indicated that
the correct position had been obtained. The further procedure depended on the
nature of the experiment and will be mentioned in the descriptions of the individual
experiments. Before completely closing the thorax the lungs were expanded to
expel the air from the chest. Closure was accomplished by suturing the inter-
costal muscles. Placing of ligatures about the ribs was purposely avoided for fear
of limiting the free motion of the thoracic wall . When closure was complete the
opening in the trachea was made tight after the manner described by Churchill
and Agassiz, and the animal connected with the two respiration systems. All
animals breathed 90 to 95 per cent oxygen throughout the period of observation.
During operation the animals were kept warm by an electric pad and the rectal
temperature was recorded at repeated intervals. During the period of observa-
tion the animals were surrounded by warm air.
EXPERIMENTAL.
I. The Effect of Cutting O ne V agus Nerve on the Respiratory Movements
of Each Lung.
Schafer 1919) calls att ent ion to the possibility of vaga l section
leading to a collapse of the smaller bronchial tubes from paralysis of
their muscular layer. If such were the case, cutting the vagus nerve
on one side might seriously interfere with the passage of air into and
out of the respiratory bronchioles of the lu ngon the sideof vagal section.
Under these conditions one would expect less air to enter the lung,
the vagus of which has been divided. The following experiment
No. 1) was made to test this point.
Experiment/. An animal, anesthetized with barbital-sodium, breathed during
the control period at the rate of 28 per minute. The tidal air of the right lung
was 44 cc. and the tidal air of the left lung was 56 cc. Immediately following
section of the right vagus nerve the respiratory rate dropped to 14, the tidal air
of the right lung rose to 55 cc., and the tidal air of the left lung to 72 ec. These
figures show that unilateral vagotomy was accompanied by an increase in the
tidal air of both lungs. A similar, but exaggerated response was noted after
cutting the left vagus. When the left vagus was cut the right and left lungs
showed an increase in tidal air to 100 and 138 cc., respectively. The experimental
data are brought out in Table I and the respiratory curves are reproduced in
Fig. 1.
5/20/2018 A Study of the Hering-breuer Reflex
6/19
824
H ERING BREI/ER REFLEX
)
0
4..a
~ ~ ~ ~
0) ~_ O o ~ 0) ~ ~
o ~ ~ e~
~ o .~ 4-
~ >. ~_ o o .-
5/20/2018 A Study of the Hering-breuer Reflex
7/19
RICHMOND L. MOORE
825
This experiment was repeated, and similar results were obtained.
As a corollary to these experiments, the effect of partial obstruction
of the bronchus of one lung on the tidal air of each lung has been
studied. The right bronchus was gradually occluded by means of a
specially constructed meta l tap, previously described by us Moore
and Binger, 1927) which was introduced into the system between the
bronchial cannula and the respiration valves. Blalock, Harrison, and
Wilson 1926) found, in their studies on morphinized dogs, that partial
obstruction of the trachea in both phases of respiration causes slow,
shallow breathing. In the light of these findings it was antic ipated
TABLE I.
Experim ent 1 The Effect of Cutti~tg One Vagus Nerve on the Rest~iratory
Movements of Each Lung
Weight of dog, 17.5 kilos. Tota l barbita l-sodium, 0.33 gm. per kilo body
weight.
Time
3.12
3.14
3.15
3.15
3.17
3.18
3.19
Procedu re
Dog breathing 90-95 per cent
O2 throughout experiment
Cut right vagus
Cut left vagus
Resp i ra to ry ]
r a t e p e r m i n u t e l
28
28
14
15
9
Tida l a i r
R igh t lung
cc
44
44
55
51
I00
Lef t lung
CC
56
56
7
64
138
that resistance to the passage of air into and out of one lung would
decrease the depth of respiration of the lung on the side of the resist-
ance and probably increase the depth of breathing of the opposite
lung. In Experiment 2, Fig. 2, during the period of resistance on the
right side the tidal air of the right lung dropped from 61 to 20 cc.,
whereas the tidal air of the left lung increased from 79 to 116 cc.
Similar results were obtained on two other occasions.
The results of the experiments in this group, then, may be summar-
ized as follows: The effect of unilateral vagotomy on the character of
5/20/2018 A Study of the Hering-breuer Reflex
8/19
826
HERING BREUER REF LEX
brea th ing is the same in bo th lungs, namely : There occurs an equiva-
len t s lowing and deepening of resp i ra tory movement . This would
suggest tha t the var ia t ion in resp i ra tory movem ent tha t fo llows vagal
section is not due directly to local changes in the lungs. Th e evidence
ra ther suppor ts the v iew tha t i s now genera l ly he ld , namely , tha t
cu t t ing the vagus nerves b locks per iphera l impluses tha t re f lex ly
modify the charac ter o f b rea th ing . The resu l ts tha t we ob ta ined are
in harm ony wi th Ein thov en s (1892) exper iments . Ein tho ven meas-
ured the changes in in t ra t racheal p ressure in anesthe t ized dogs when
artif icial respiration was provided by blowing in and sucking out a
constan t vo lume of a i r a t each resp i ra t ion . In s ix exper iments the
changes in in t ra t racheal p ressure af te r cu t t ing the vagus nerves were
as follows: Three animals showed a drop that was less than 1 mm.
H~O, and the othe r three anim als showed decreases of 7, 24, and 2 mm .
H,O, respect ive ly . Ein thoven accep ted these find ings as ev idence tha t
sec t ion of the vagus nerves does no t cause any no t iceab le change in
the cross-sec t ion area of the bronchioles . He concluded tha t , w hen
the bronchia l muscles a re a t res t , the vag i exer t l i t t le o r no ton ic e f fec t
upon them.
H The Effect of Blocking One Bronchus on the Respiratory Movements
Recorded by the Opposite Lung
In four exper iments , us ing the technique descr ibed , the bronchus
to one lung was comple te ly obst ruc ted whi le ob ta in ing graphic t rac ings
of the resp i ra tory movements o f the opposi te lung. In each instance
the r igh t b ronchus was the one b locked . The resu l t o f th is mance uver
was a slowing and deepenin g of the respirations in the functioning lung.
On thre e occasions, af ter a brief interval, the animals bec ame a noxemic
and the resp ira t ions acce lera ted . This may be seen in Exper iment 3 ,
Fig . 3, and in Exper iment 4 , Fig . 4 . Havi ng estab l ished the type of
response to obstruction of one bronchus we were then in a posit ion to
stud y the ef fec ts o f th is p lus vagoto my on the cor responding s ide .
This wi l l be dea l t wi th presen t ly .
In the meanwhi le , i t should be inc iden ta l ly ment ioned tha t the
response of the funct ion ing lung was in f luenced by the posi t ion of the
opposite lung a t the t ime i t s b ronchus was b locked . Whe n the r igh t
bronchus was b locked a t the end of exp ira t ion the nex t movement o f
5/20/2018 A Study of the Hering-breuer Reflex
9/19
RICHMOND L. ~OORE 8 7
t h e l e f t l u n g w a s a r e l a t i v e l y d e e p i n s p i r a t i o n F i g . 4 ) ; w h e n , o n t h e
o t h e r h a n d , t h e r i g h t b r o n c h u s w a s b l o c k e d a t t h e e n d o f i n s p i r a t i o n ,
t h e n e x t m o v e m e n t o f t h e l e ft l u n g w as a r e l a t i v e l y d ee p e x p i r a t i o n
F ig . 3 ) .
FIG. 2. FIG. 3.
FIG. 2 . Exper iment 2 . Ef fec t o f par t i a l occ lus ion of the r igh t bronchus on the
resp ira tory movemen ts of each lung . The curve passes f rom le f t to r igh t . Upper
trac ing made by the r igh t lung . Lower t r ac ing made by the le f t lung . Insp ira -
t ion down and expira t ion up in both t r ac ings . In the upper t r ac ing an excurs ion
of 0.9 cm. represents a 100 cc. change in the volume of the recording spirometer .
In the lower t r ac ing , wr i t ten by a smalle r sp iromete r , a vo lum e change of 100 cc.
causes an excursion of 1.88 cm. At E the cross-section area of the top was
f ina l ly r educed to 0.1 sq . cm. This caused the t ida l a i r o f the r igh t lung to
decrease from 56 to 20 cc. and the tidal air of the lef t lung to increase from 87 to
116 cc. At F the obs truc t ion was removed and the t ida l a i r o f each lung re turned
imm edia te ly to the contro l leve l. Time in te rva l 2 seconds .
FIG. 3 . E xper iment 3 . Ef fec t o f b locking the r igh t bronchus on the resp ira tory
movements r ecorded by the le f t lung . The curve passes f rom le f t to r igh t . Upper
trac ing made by the r igh t lung . Lower t r ac ing made by the le f t lung . Insp ira -
t ion down and expira t ion up in both t r ac ings . In the upper t r ac ing an excursion
of 0.9 cm. represents a 100 cc. change in the volume of the recording spirometer .
In the lower t r ac ing , wr i t ten by a smalle r sp iromete r , a vo lume change of 100 cc .
causes an excnrsion of 1.88 cm. At A the r ight bronchus was co mpl etely occluded
a t the end of insp ira t ion . The next m ovement of the le f t lung was a deep expira -
t ion . The resp ira tory ra te immedia te ly s lowed, bu t with in 3 minutes acce le ra ted
to 38, 11 breat hs above the control level. Tim e in seconds.
5/20/2018 A Study of the Hering-breuer Reflex
10/19
.o ~ ~ ~'n
~-~ ~ ~.~
o ~ ~ ~ : ~
0
0
. . ~ ~ . ~ o ~
o ~ ~ ~ ~J
~ ~-~ .~ o ~
.~-~
~ ~
..~ ~ ~ ~ o ~ ~
o ~ ~
~ o ~n ~:
~:~ .~ ~c~ ~ ~
o ~ ~ ~ ~
~ ._9 o o. .~ o
~
~. o. ~ ~ o~ ~
~.o
o ~ ~ ~ .
828
5/20/2018 A Study of the Hering-breuer Reflex
11/19
RICHMOND L. MOORE
829
H I The Effect of Occlusion of the Right Bronchus Plu s Right Sided
Vagotomy on the Ventilation of the Le ft Lung
The ob jec t o f th i s p rocedure was to l earn whether o r no t the charac-
t e r i st i c response o f un i l a t e ra l vago tom y which we have jus t descr ibed
i s in f luenced by the m ot ions o f the lung the vagus o f which has been
sec t ioned . I t has p rev iou s ly been assumed tha t the Her ing-B reuer
reflex is set off by the al tern ate expansion and col lapse of the lungs.
TABLE I I .
Experim ent 4 The Effect of Occlusion of the Right Bronchus Plus Right Sided
Vagotomy on the Ventilation of the Lef t Lu ng
W e i g h t o f d o g , 2 0 k i l o s. T o t a l b a r b i t a l - s o d i u m , 0 .3 2 g i n . p e r k i lo b o d y w e i g h t .
Time
1.07
1.14
1.18
1 . 1 9
1.20
1.22
1.25
1.28
1.32
1.35
1 . 3 8
1.39
1.42
rocedure
Dog bre a th ing 90-95 pe r c e nt
O~ throu gho ut e xpe r im e nt
R i g h t b r o n c h u s b l o c ke d
Right va gus d iv ide d w i th
scissors
espiratory
rate per minute
21
22
21
26
34
35
35
32
22
24
Tidal air
Right lung Left lung
Co CO
86 27
86 30
86 30
0 56
0 159
0 127
0 114
0 109
0 109
0 116
0 130
The exper iment s descr ibed under th i s head ing were des igned fo r the
purpose o f inqu i ring in to th i s po in t . I t is adm i t t ed tha t the i r some-
wha t compl ica ted and unnatu ra l charac ter i s ob jec t ionab le bu t by
them we were ab le to observe the resp i ra to ry movem ents o f one
re la t ive ly normal lung whi le i ts fe l low was rendered funct ion less by
b lock ing i t s b ronchus and cu t t ing o r f reez ing i t s vagus nerve . Fou r
exper iment s o f th i s type were per fo rmed o f which one is re por ted in
5/20/2018 A Study of the Hering-breuer Reflex
12/19
830
HERING-BREUER RE FLEX
more or less detai l . In two the vagus nerves were cut ; in the other
two frozen. Bot h meth ods gave s imilar resul ts .
Experiment 4. -- In this experiment during the control period the animal
breathed at the rate of 21 per minute. The tidal air of the right lung was 86 ce.
and the tidal air of the left lung was 30 cc. When the right bronchus was blocked
the tidal air of the left lung increased to 56 cc. with the very next breath. 2
minutes later it had risen to 159 cc. The respira tory rate slowed immediately
after the bronchus was blocked but within 3 minutes increased to 26. 3 minutes
after this the animal was cyanotic the rate had accelerated to 34 and the tida l
TABLE I I I .
Experim ent 5 The Effect of Occlusion of the Right Bronchus Plus Right
Side d Vago tomy on the Ventilation of the Lef t Lung after
Division of the Right Phre nic Nerve
Weight of dog 1 kilos. Tot al barb ital -sodi um 0.35 gin. per kilo body weight.
Time
12.35
12.38
12.39
12.41
12.44
12.46
12.47
12.53
12.59
1.03
Procedure
Dog breathing 90-95 per cent
02 throughout experiment
Right bronchus blocked
Section of right vagus
Respiratory
rate per minute
32
32
38
38
29
27
24
23
Tidal air
Right lung Left lung
CC CC
20 30
20 35
0 41
0 36
0 38
0 38
0 40
0 40
air of the left lung had decreased to 127 cc. 10 minutes later the respiratory rate
was 32 and the tidal air of the left lung was 109 cc. At this point the right vagus
was cut. The rate immediately dropped to 22 and the tidal air of the left lun g
increased to 116 cc. During the next 3 minutes the tidal air of the left lung
increased to 130 cc. These changes are brought out in Table II and Fig. 4.
They
show that the response to one sided vagolom y is not altered by previously preventing
respiratory motions in the vagotomized lung
This is opposed to the view which
is generally held as to the na ture of the Hering-Breuer reflex.
Before d rawing conclus ions f rom our own observat ions we mus t
consider two possibi l i t ies which ma y be of impor tanc e. Firs t does
5/20/2018 A Study of the Hering-breuer Reflex
13/19
R I C t t ~ O N D L M O O R E
831
blocking the bronchus actually prevent lung motion? Second, could
the slowing of respirations be explained on the basis of crossed inner-
vation of the vagus fibres?
That lung motion is prevented by blocking the bronchus is probably
true, since all access of air to the lung has been excluded, and since
at autopsy the occluded lung presents a picture of complete collapse.
It is unlikely tha t an atelectatic lung could follow the movements of
the diaphragm and chest wall. In this connection an experiment
No. 5) was performed in which the expansion of the right lung was
severely limited from the start by cutting the right phrenic nerve in
the chest. Presumably the limited expansion was due to partial or
complete paralysis of the right half of the diaphragm. Under these
conditions the tidal air of the right lung was only 20 cc. The tidal air
of the left lung was 35 cc. The respiratory rate was 32. The dog
was anoxemic as indicated by the dark color of its tongue. 5 minutes
after blocking the righ t bronchus the respiratory rate was 38 and the
tidal air of the left lung was 36 cc. The right vagus nerve was cut at
this point. The rate immediately slowed, but the amplitude of the
respirations of the opposite lung was practically unaltered. The
results of this experment are presented in Table III. With air unable
to enter the lung, and with the right half of the diaphragm paralyzed,
it is difficult to conceive that there could have been any lung motion.
Nevertheless, the respiratory rate slowed when the right vagus was
cut. The experiment is of additional interest because it shows that
slowing of respirations which follows after occlusion of the right bron-
chus and section of the right vagus nerve still occurs even though the
phrenic nerve on the same side has been divided. This indicates that
the slowing of respirations following unilateral vagotomy does not
depend upon the interruption of impulses arising from the contraction
and relaxation of the diaphragm.
Regarding the second possibility, the existence of crossed vagal
innervation has been recognized for some time. This has recently
been demonstra ted for the sensory fibres by Larsell 1921).
To control the influence of crossed innervation on our results, we
have devised a technique whereby the vagal fibres to the left lung were
divided at the hilum. By this procedure we were able to observe
the effect of right sided bronchial occlusion and vagotomy on the
5/20/2018 A Study of the Hering-breuer Reflex
14/19
832
HERING=BREUER REFLEX
TABLE IV.
Experiment 6 The Effect of Occlusion of the Right Bronchus Plus Right
Sided Vagotomy after Division o f the Pulmonary Branches
of the Left Vagus Nerve
Weight of dog 18.5 kilos. Tota l barbital-sodium 0.3 grn. per kilo body weight.
Time
3.13
3.17
3.18
3.19
3.22
3.24
3.30
3.33
3.35
Procedure
Dog breathing 90-95 per cent
O2 throughout experiment
Right bronchus blocked
Section of right vagus
Respiratory
rate per minute
22
22
24
32
33
16
19
Tidal air
Right lung
cc
64
66
0
0
0
0
0
Left lung
6C.
64
67
8
28
2
160
155
TABLE V.
Experiment 7 The Effect of Occlusion of the Right Bronchus Plus Right
Sided Vagotoray after Division o f the Pulmon ary Branches
of the Left Vagus Nerve
Weight of dog 17.5 kilos. Total barbital-sodium 0.3 gin. per kilo body weight.
Time
2.49
2.51
2.52
2.55
2.58
3.00
3.01
Procedure
Dog breathing 90-95 per cent
02 throughout experiment
Right bronchus blocked
Section of right vagus
espiratory
rate per minute
47
37
43
4O
27
Tidal
air
Right lung
CG
4O
Left lung
G ,
4
66
66
66
105
motions of the left lung which had been previously denerva ted with
respect to its vaga l fibres. Ther e could therefore be no quest ion
of crossed innervation. This experiment was done twice with identi-
5/20/2018 A Study of the Hering-breuer Reflex
15/19
RICHMOND L MOORE
833
c a l r e su l ts w h i c h a r e p r e s e n t e d i n T a b e s I V a n d V . T h e u p s h o t o f
t h e s e e x p e r i m e n t s w a s e n t i r e l y a n a l a g o u s t o t h a t o f o u r p r e v i o u s o n e s
s h o w i n g t h a t c r o ss e d i n n e r v a t i o n o f v a g a l f ib r e s w a s n o t r e s p o n s i b l e
f o r t h e r e s u l t s o b t a i n e d .
IV Is the Response to Unilateral Vagotomy Dependent upo n an Intac t
Puhno nary Circulation ?
W e h a v e s e e n t h u s f a r t h a t t h e s l o w in g a n d d e e p e n i n g o f t h e r e s p i ra -
t o r y m o v e m e n t s o f o n e l u n g w h e n t h e v a g a l i m p u l s e s f r o m t h e o t h e r
FIG. 5. E xperiment 8. Effect of cutting the right vagus nerve on the respira-
tory movem ents of each lung after ligation of the right puhno nary artery. The
arter y was ligated within the pericardium. The curve passes from left to right.
Upper tracing made by the right lung. Lower tracing made by the left lung.
Inspiration down and expiration up in both tracings. In the upper tracing an
excursion of 0.9 cm. represents a 100 cc. change in the volume of the recording
spirometer. In the lower tracing written by a smaller spirometer a volume
change of 100 cc. causes an excursion of 1.88 cm. Du ring th e control period the
tidal air of the right lung was 30 cc. and the tidal air of the left lung was 36 cc.
At A the right vagus nerve was divided. The respirations of each lung immedi-
atel y becam e slower and deeper. Tim e in seconds.
l u n g a re i n t e r c e p t ed d o e s n o t d e p e n d u p o n t h e m o t i o n s o f t h e v a g o t o -
m i z e d l u n g n o r u p o n t h e e x i s t en c e o f c r o ss e d i n n e r v a t i o n o f v a g a l
f i b re s . I t r e m a i n e d t o d i s c o v e r w h e t h e r b l o c k i n g t h e c i r c u l a t i o n o f
b l o o d t h r o u g h t h e p u l m o n a r y a r t e r y o f t he v a g o t o m i z e d l u n g w o u l d
i n f l u en c e t h e r e s p o n s e o f t h e o t h e r l u n g t o v a g a l s e ct i o n . T h e
r e a s o n f o r r e g a r d i n g t h i s a s a p o s s i b i l i t y w a s t h o u g h t t o li e i n t h e
s t a t e m e n t e n c o u n t e r e d f r o m t im e to t i m e i n t h e l i t e r a tu r e a n d p r e -
5/20/2018 A Study of the Hering-breuer Reflex
16/19
834
t IERING BREUER REFLEX
viously al luded to , that the vagal endings in the lung are local ly
sensi t ive to carbon dioxide. Indeed, a mech anism has been suggested
where in the f luc tua t ion in t ens ion o f a lveo lar carbon d iox ide has be en
conceive d as the exci tatory s t imulu for the H ering- Breu er reflex.
Adeq uate exper imenta l ev idence fo r the ex i s tence o f such a mechan i sm
is, however , no t a t hand . By obs t ruc t ing the f low of b lood th rough
the pu lmonary ar t e ry o f the lung whose vagus was subsequen t ly
divided , we rendered this lung fun ct ionless in re spect to i ts gas
exchange. No normal f luctuat ions in the alveolar carbon dioxide
tension of such a lung could occur and in t ime the alveolar carbon
dioxide tension would be mu ch reduced. In Exp erim ent 8 Fig. 5)
samples o f a lveo lar a i r were wi thdrawn f rom each lung a few minu tes
af t e r the vagus nerve had been cu t . Th i s was accompl ished by pass -
ing a smal l catheter deep into the bronchus and col lect ing the gas in
sampling tubes . The ai r from the left lung contained 7.18 per cent of
carbon d ioxide, whereas tha t f rom the r igh t, whose pu lmo nary ar t e ry
had bee n l igated, contained only 1.16 per cent of carbon dioxide. I t
was found tha t vago tomy under these c i rcumstances resu l t ed in the
same s lowing and deepening of respirat ions recorded by the other lung,
as occurred when the pu lmonary c i rcu la t ion to the vago tomized lung
was intact . This is shown in Fig. 5 . I t m ay be concluded, therefore,
tha t the charac ter is t i c resu lt s o f un i l a te ra l vago tom y do no t depend
upon an in tac t pu lmonary c i rcu la t ion .
DISCUSSION.
In the in t roduct ion o f th i s paper we descr ibed the exper iment s o f
several invest igators to i l lus t rate the point that a rapid respiratory
ra te , exper imenta l ly p roduced in an imals , d i sappears immedia te ly i f
the vagus nerves are divided. Our own experiences in this f ield had
led us fo r some t ime to a t t ach more and more impor tance to the loca l
exci tat ion of vagal nerve endings in the lungs as the most l ikely expla-
nat ion of the rapid rates . The l i terature on this subjec t was convinc-
ing in on ly one respec t , namely , tha t exc i t a t ion o f the pu lmonary
terminat ions o f the vagus nerves i s re l a t ed to the a l t e rna te expans ion
and co l l apse o f the lungs . The exper iment s tha t we have descr ibed
are unique in having shown that the vagal influence is s t i l l present
af t e r lung mot ion has been p reven ted . In th is respec t they modi fy
5/20/2018 A Study of the Hering-breuer Reflex
17/19
RICHMOND L. MOORE
835
our knowledge of the nervous contro l o f b rea th ing . The exper iments
are incomple te in tha t they do no t exp lain the or ig in of the reflex tha t
we have s tud ied .
The in ferences drawn f rom our exper iments a re sound in so far as
one is wil l ing to admi t th a t the s lowing and deepening of resp i ra t ions
tha t fo llow uni la tera l vago tomy ind ica te an in ter rup t ion of a f feren t
impulses tha t normal ly t ravel th is pa th . One wil l avo id confusion in
~ol lowing the arg umen t by co nstan t ly bear ing in mind t ha t the s lowing
and deepening of b rea th ing af te r vago tom y means we be l ieve tha t
a normal re f lex has been in ter rup ted .
SIYM ~ARY AND CONCLUSIONS .
1. C ut t ing one vagus nerve whi le recording the pu lmon ary ven t i la -
t ion of each lung separa te ly has no un ique ef fec t on the ve n t i la t ion of
the den ervated lung . Both lungs respond to un ila te ra l vagotom y by
an equ iva len t s lowing and deepening of resp i ra tory movem ent .
2. Wh en the br onchu s to one lung is blocked the f irst effect is a
s lowing and deepening of the resp i ra tory movem ents recorded by the
opposi te lung . As oxygen wan t develops these mov eme nfs become
rapid and shallow.
3. W ith a com bination of these two conditions i .e . when the bron-
chus to one lung is blocked and i ts vagus nerve is severed the pulm o-
nary ven t i la t ion recorded by the opposi te lung exhib i ts the same
changes as ma y resu lt f rom uni la tera l vagoto my a lone unaccompanied
by occlusion of the bronchus.
4 . From these fac ts i t may be concluded tha t the s lowing and
deepening of b rea th ing which fo l lows un i la tera l vagotomy does no t
depend for i t s occur rence upon the passage of a i r in and ou t o f the
bronchus of th e lung whose vagus ne rve has been sec t ioned .
5. The slowing of respirations af ter occlusion of the bronchus to one
lung and section of the corresponding vagus nerve sti l l occurs even
though the phren ic nerve on the same s ide has been d iv ided. This
ind ica tes tha t the s lowing of resp i ra tions fo l lowing un i la tera l vago tomy
does no t depend on the movements o f the d iaphragm on the s ide of
vagal section.
6 . When the pu lmon ary ar te ry to one lung has been l iga ted and the
vagus nerve on the same s ide cu t the response of the o ther lung is the
5/20/2018 A Study of the Hering-breuer Reflex
18/19
836
H E R I N G B R E U E R R E F L E X
same as has been descr ibed , namely , i t s resp i ra tory movemen ts become
slower and deeper . This i s taken as ev idence tha t the resu l ts o f un i -
l a t e r a l v ag o to m y a r e n o t d ep en d en t u p o n an in t ac t p u lm o n a r y
circulation.
7. The general conclusions from these experiments are that the
slowing and deepening of respirations following unilateral vagotomy
do not depend upon: a ) Passage of a i r in and ou t o f the t rachea .
b) Expans ion and collapse of the lung. c) Existen ce of a norm al
pulmo nary c i rcula t ion in the vagotomized lung. d ) Norm al f luc tua-
tions in alveolar carbon dioxide tension. e) Cont raction and relaxa-
t ion of the d iaphragm on the s ide of vagotomy .
8. The slowing and deepenin g of respirations, alluded to, ma y be
presumed to ind ica te tha t a normal re flex the Her ing-Breuer re flex)
has been interrupted. Since this interruptio n occurs in spite of all the
condi tions enumera ted un der Parag raph 7 , we must conclude tha t
none of these conditions is essential to the existence of this ref lex.
I ta ke grea t p leasure in expressing thanks to Dr . Car l A. L . Binger
for valuable suggestions, and for his helpful interest in the course of
this investigation.
BIBLIOGRAPHY.
Biuger, C. A. L., Brow, G. R., and Branch, A.,
J. Ctin. Inv. 1924, i, 127.
Binger, C. A. L., a nd Moore, R. L., 1926, unpublished experiments.
Blalock, A., Harrison, T. R., and W ilson, C. P.,
Arch. Surg.
1926, xiii, 81.
Boothby, W. M., and Berry, F. B.,
Am. J. Physiol.
1915, xxxvii, 433.
Christiansen, J., and Haldane,
J. S. J. Physiol.
1914, xlviii, 272.
Churchill, E. D., and Agassiz, A., Am. J. Physiol. 1926, Lxxvi,6.
Dunn, J. S.,
Quart. J. Med.
1920, xiii, 129.
Einthoven, W., Arch. ges. Physiol. 1892, li, 367.
Einthoven, W., Arch. ges. Physiol. 1908, cxxiv, 246; Quart. J. Exp. Physiol.~
1908, i, 243.
Haldane, J. S., and M avrogordato, A.,
J. Physiol.
1916,1, p. xli.
Haldane, J. S., Respiration, New Haven, 1922, 46.
Head,
H. J. Physiol.
1889, x, 1.
Hering, E., and Breue r, J., Sitzungsber. k. Aka d. W issench. Ma th.- naturw. Cl.
Wien
1868, lvii , pt. 2, 672; Iviii, pt. 2, 909.
Larsell, O., and Mason, M. L. J. Comp. Neurol. 1921, xxxiii, 509.
Legallois, C. J. J.,
Experiences sur la principe de la vie
Paris, 1812.
Lumsden,
T. J. Physiol.
1923, lviii, 111.
5/20/2018 A Study of the Hering-breuer Reflex
19/19
I~ICtt ~OND L. M'OORE
8 7
Moore, R. L., and Binger,
C. A. L., J. Exp. M ed.,
1927, xlv, 1065.
Porter, W. T., and Newburgh, L. H.,
Am . J. Physiol.,
1916, xUi, 175.
Porter, W. T., and N ewburgh, L. H., Am. J. Physiol., 1917, xliii, 455.
Schafer, E. S., Quart. J. Exp. Physiol., 1919, xii, 231.
Scott, F. W., J. Physiol., 1908, xxxvii, 301.
Suffer, P. A., and Bellido, J. M., J. phys. et path. n. , 1921, xix, 214.
Traube, L., Ges. Beitr. P ath. u . Physiol., 1871, ii, 882.
Top Related