a study of the hering-breuer reflex

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


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.


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.


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


5/19

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.


6/19

824

H ERING BREI/ER REFLEX

)

0

4..a

~ ~ ~ ~

0) ~_ O o ~ 0) ~ ~

o ~ ~ e~

~ o .~ 4-

~ >. ~_ o o .-


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


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


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.


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


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


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


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


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


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


O2 throughout experiment



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


02 throughout experiment



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-


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 -


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


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


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.


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.

a study of the hering-breuer reflex

Documents

teres t

inves t igators tha

tha t i f

binger tha t

t act vagi

condi t ions

vagal t runk s

sc ot t