MECHANICAL AND CHEMICAL CONTROL OF BREATH HOLDING

Q. Jl exp. Physiol. (1969) 54, 117-128

MECHANICAL AND CHEMICAL CONTROL OF BREATH HOLDING.By S. GODFREY and E. J. M. CAMPBELL. From the Department ofMedicine, Royal Postgraduate Medical School, DuCane Road, London,W. 12., England.

(Received for publication 13th June 1968)

A method is described for the study of breath holding in which the breath holdsare separated by rebreathing to enable accurate control of pCO2; its theoreticalbasis is discussed.

At the end of a breath hold, rebreathing a mixture such that the pCO2 continuesto rise, nevertheless permits the breath hold to be resumed. The number of breathsduring the rebreathing is unimportant and a single breath permits as long a resumedbreath hold as five breaths.

Healthy adult males held their breath at residual volume. The relationshipbetween breath holding time and pCO2 at the start or end of a breath hold was foundto be linear; the higher the pCO2 the shorter the breath holding time. The relation-ship was unaffected by ten minutes of isocapnic hyperventilation.

These findings imply that the duration of breath holding is directly related toPCO2 but is unaffected by the previous mechanical pattern of breathing.

MOST of the factors of importance in determining the breaking point ofbreath holding have been known for many years. Hill and Flack [1908]noted that if oxygen was breathed beforehand rather than air, the breathholding time was longer. They also noted that the alveolar pCO2 (hereafterreferred to as pCO2) was higher at breaking point after breath holding onoxygen; this was presumably due to the longer duration of breath holding.In the same paper they reported that their subjects could rebreathe expiredair from a bag for some two to four times as long as their maximum breathholding time on air. They thus demonstrated that ventilation of the lungsallowed the subject to tolerate a greater hypoxia and greater hypercapniathan occurred at the breaking point of breath holding. This finding, nowsome sixty years old, suggests that some form of interaction of chemicalland mechanical stimuli occurs during breath holding. Subsequent studiesdefined the roles of oxygen, CO2 and lung volume more clearly [Douglasand Haldane, 1909; Klocke and Rahn, 1959; Muxworthy, 1951] and thewhole subject has been reviewed by Mithoefer [1964].

The relationship between rebreathing and breath holding was furtherexplored by Fowler [1954]. He found that after subjects had reached thebreaking point of a breath hold, a few breaths of a gas mixture which did notimprove their blood gases allowed them to perform a second, shorter breathhold, and subsequently a third. He did not attempt to determine the numberof breaths necessary to allow the second (or third) breath hold of the series.

VOL. LIV, No. 2. 1969 117

118 Godfrey and Campbell

Cain [1957] reported that a single gasp of air at the end of a breath holdallowed a second period of breath holding, but of course the blood gaseswere altered by his procedure.

The present series of experiments were designed to investigate the inter-relationships of mechanical and chemical factors in breath holding.

METHODS

Breath-cluster experiments. - All the subjects used in this study were healthy adultmales whose physical characteristics are given in Table I. All of them had a goodknowledge of respiratory physiology in general but only S.G. had any detailedknowledge of breath holding. The subjects were kept totally unaware of theirperformances throughout the series of experiments.

TABLE 1. DETAILS OF SUTBJECTS.

Age Height WeightSubject years cm KgM.C. 42 183 80D.M. 36 180 78G.L. 30 175 75T.O. 29 168 72S.G. 28 179 81D.W. 28 188 82M.S. 24 180 85R.J. 26 179 76S.F. 30 183 80

For the first group of experiments, designed to investigate the effect of the numberof breaths on the duration of the second breath hold, the circuit illustrated in fig. 1was used. The subject rebreathed a gas mixture from a 6 1. rubber bag containedin a bottle. Ventilation was recorded by Bernstein spirometer connected to thebottle, a potentiometer on the spindle of the spirometer being used to obtain a record.End tidal pCO2 was recorded from the mouth piece by means of an infra-red CO2analyser (URAS). The gas was returned to the bag after passing through the cell.The analyser was calibrated with at least three gas mixtures before and after eachexperiment. Ventilation and pCO2 were displayed on a Mingograph recorder.

At the start of an experiment the bag was filled with 6 1. of a mixture of approxi-mately 7 per cent CO2 and 93 per cent oxygen. The spirometer was so set that amark on the bell was placed 2 1. above the water line. The subject expired toresidual volume and then switched himself into the circuit and performed a vitalcapacity manoeuvre. After this he rebreathed from the bag at a rate of 16 breaths/min set by a metronome, but without any restrictions on his tidal volume. Afterthirty sec of rebreathing the subject was instructed to hold his breath for as longas possible with the mark on the spirometer at the water level. This meant thathe held his breath at approximately 2 1. above residual volume. At breaking pointthe subject expired to his residual volume.

After at least five minutes' rest the procedure was repeated, but the breathhold (B.H.1) was terminated by the operator. During B.H.1 sufficient CO2 wasadded to the bag by the operator to produce a pCO2 close to that anticipated in thelungs of the subject at the end of B.H.1. The operator terminated B.H.1 after80 per cent of the previously determined maximum breath holding time by givingthe command 'breathe'. The value of 80 per cent was selected to ensure a severestimulus but one which the subject would tolerate without breaking. The subject

Control of Breath Holding 119

started to breathe at a rate of 32 breaths/min with an unrestricted tidal volume,and continued to do so until the operator gave the instruction 'hold'. The numberof breaths in this 'cluster' taken by the subject was determined from random numbertables between one and five. The subject had no prior knowledge of the size ofthe cluster. At the command 'hold' he again held his breath with the mark on thespirometer at the water level and this time he continued breath holding as long aspossible. This period of breath holding is subsequently referred to as B. H.2. Eachsubject performed the experiment for all of the five cluster sizes and the wholegroup of experiments was repeated on another day. The experiment was alsoperformed on one subject who held his breath at residual volume on each occasion.Clusters of 1, 3 and 5 breaths were used at random, each cluster size being repeatedonce during a single session lasting one hour.

Filling port3-way J

Subject -

CO2 analyserTo spirometer

Fig. 1. Circuit used for rebreathing and breath holding.

Breath holding-CO2 Response Curves. - In this group of experiments the subjectagain rebreathed a gas mixture from a circuit similar to that shown in fig. 1; thecomposition of the mixture was the same as in the first group of experiments. Thesubject expired to residual volume and then switched himself into the circuit andrebreathed at will with no fixed rate or tidal volume being imposed. After approxi-mately 30 sec of rebreathing, the subject was instructed to expire to residual volumeand then hold his breath for as long as possible. When he reached breaking pointhe began rebreathing for about 20-30 sec and again held his breath as long aspossible. This procedure was repeated several times so that up to 6 breath holdswere interspersed during the period of rebreathing. A graph was constructedrelating breath holding time to the pCO2 in the lung/bag system.

In order to study the effect of hyperventilation on the breath holding-CO2 curve,the circuit was modified so that the subject could hyperventilate through the sidearm of the three way tap without altering his pCO2. This was achieved by connectingthe side arm to the partial rebreathing circuit described by Freedman [1966]. Thesubject was given a target ventilation to follow of 60 1./min and maintained thisrate for 10 min. His end tidal pCO2 was kept at the control level throughout byadjusting the level of rebreathing. At the end of this period he was switched intothe rebreathing bag and performed a residual volume CO2 response experimentexactly as described above, with the one exception that between breath holds hemaintained the same rate of ventilation, namely 60 I./min. After the completion ofthis experiment he rested for at least 10 min and then performed a resting breathholding-CO2 response experiment described above.

In all these experiments care was taken to ensure that the subjects were hyperoxicthroughout. This was achieved by using the high initial bag oxygen mixtures and


a check on the PCO2 in the system showed that it never fell below 400 mm Hg atany stage during the breath holding-CO2 response curves or during the clusterexperiments described earlier.

RESULTS

Breath-cluster experiments. - During the initial 30 sec of rebreathing, equi-librium was established between the PCO2 in mixed venous blood, alveolargas and bag gas. Since recirculation occurs in some 15 to 20 sec at rest,the PCO2 of the blood-lung-bag system had already begun to rise, but thisrate of rise was very constant at rest (see below). This process ensuredthat the pCO2 at the start of the first breath hold (B.H.1) was very constantfor any one subject throughout the various experiments. During the B.H.1

Pco2 Imm.Hg9 C02 added60 to bag50 ,40

CLUSTERTidal volume ll) BREATH HOLD 1 BREATH HOLD 20 Inspiration + F

62l~ ~ ~ ~ ~ ~~~~~~~~~~~I

0 30 60 90 120TIME IN SECS.

Fig. 2. Course of a typical experiment. A small amount of C02 was added to the bag during]the first breath hold by the operator and mixed by means of a piston.

and the subsequent period of rebreathing for the cluster, the pCO2 continuedto rise at the same rate. Since the duration of B.H.1 was constant and theclusters differed only a little in duration, the pCO2 at the start of the secondbreath hold (B.H.2) was also very constant (Table II). This second breathhold was continued as long as possible by the subject and was used to judgethe effect of clusters of different sizes. Because of the relatively low rateof rise of pCO2 (6 mm Hg/min) and the small differences in B.H.2 for any onesubject, the calculated pCO2 at breaking point of B.H.2 never varied by morethan 2-6 mm Hg.

The form of a typical experiment for a five breath cluster is shown infig. 2, and the results for all the experiments are summarized in Table II.For each subject, each of the clusters was repeated on a second occasionand both results are given (A and B in Table II). The time for the firstbreath hold was 80 per cent of the maximum breath holding time, andtherefore varied in any one subject depending upon his maximum breathholding time on the particular day of the experiment.


z

U)

0-A4

H

_-4

ce

0v)

C)

0

ce

0

0c

o Ca

0 ¢

4v

o0,

0P-

0 CO~LO

aq10 00a

o6 (5 cs

xoo

CO O

cs co CO a

O XsCO

w O~c: r

Ce

oc 100o

4 D10

cq C oo

_ CO CO CO

Ci CO CO

X CO OsCO Ci CO

m aq m m

COX CO D 10

6l60 t-:

100000

10o 100lo o to xo oa c; cq e

to14 l

'-4N0-

10 Ol

n CO CO

COO CO COee *n cc

X CO 04

0-r CO l

cq cs es cq aq

CO C O _ C_c 100o 10

CS 4

> C iC C1 10

10 r* lao z

CG1 s CO:

CO N-

o 1o 10

ce ,d d4o x W

a cN

eO _ c cq es

Cl1 c;z CO

ll Xo to o xo

co O co c) c)

o 00 0o

* 0*

m CON-

CO

F-4

1000

r t

0o10 0lf

O C) c)

OoO

1-41010o

o01 o

t- 1o00 00x 10 10 100 -4 = ON10J torCoo n= CZ r- :rw O co - = =Or-

C c O'j 4 10C;O '~-=1010101010oIC) ldq XO'xo t01 10o o "di 01a

"di 10 ~~ ~ ~ ~

4--- 4-D

c C

4-n O H m * _,

0H *4-~~~~~~~~~n


Because of the considerable variation in breath holding time betweenindividuals, these results have also been calculated on a proportionate scale,so that they could be grouped together. For any individual at any onesession the mean duration of all second breath holds plus clusters was takenas 100 per cent. The actual duration of the separate B.H.2 and cluster

120 Cluster1 25B.H.2

CJ100

~80C',

__J ~60

40

~200

0 0 1 2 3 4 5

NUMBER OF BREATHS IN CLUSTERFig. 3. The relationship between cluster size and theduration of the second breath hold. Each open columnrepresents the group mean value for B.H.2±1 S.D. afterthe cluster of breaths indicated below. An arbitrary scaleis used in which the 100 per cent is the duration of the meanB.H.2 plus cluster time for each subject. The shadedcolumns represents the duration of the cluster, which mustobviously increase with its size, but the small differencesin B.H.2 are not significant.

times were then calculated as fractions of this 100 per cent. The resultsfor breath holds at the larger lung volume expressed in this way are shownin fig. 3. Each column represents the mean percentages for all subjectswith one standard deviation for B.H.2. The total height of the columnsincreases with the number of breaths in the cluster, but it can be seen thatthis is due to an increase in the duration of the cluster rather than any signifi-cant increase in B.H.2. It is obvious that with a fixed rate of breathing,the duration of the cluster had to increase with the number of breaths inthe cluster, but it is the lack of change in B.H.2 that is of particular interest.The results contained in fig. 3 were also submitted to an analysis of variance,which confirmed the impression that there was no significant change in


the duration of B.H.2 after clusters containing different numbers of breaths;and even between the 1 breath and 5 breath clusters, the differencein mean duration of B.H.2 was not significant (P=0 20). It should beremembered that the duration of B.H.1 was fixed by the design of the experi-ment and does not therefore come into this analysis.

Further experience with breath holding led us to believe that the smallerthe lung volume, the more reproducible were the results, and we thereforerepeated the cluster experiment in one subject using residual volume (TableII, S.G.). Once again the duration of B.H.2 was very constant irrespectiveof cluster size, confirming the observations made at the larger lung volume.

60S. G. M.C.

50 _......* Beginningo End

40

030 -

<20 -

10

(o l l l I l l l l l50 55 60 65 70 75 45 50 55 60 65 70

PCO2 (mm.Hg.)Fig. 4. The relationship between breath holding time and pCO2 at the start (0) and end (0)of a series of breath holds at residual volume, separated by rebreathing, in two subjects. Theshaded area represents the rise of pCO2 during the breath hold. Note the approximately linearrelationship between breath holding time and either value for pCO2, and the convergence on athreshold value at which the breath holding time is zero.

Breath holding-CO2 Response Curves. - Because the rebreathing approachpermitted a series of breath holds to be performed at progressively higherlevels of pCO2, it was possible to construct a graph relating breath holdingtime to the PCO2 at either the start or end of the breath holds (fig. 4). Thecurves illustrated were obtained in two subjects for breath holds begun atresidual volume. The pCO2 at the end of the breath holds (breaking point)was calculated from the known rate of rise of pCO2 during breath holdingfor each subject, since expiration at the end of a residual volume breathhold was impossible. This rate of rise of pCO2 was obtained from the endtidal pCO2 at the start and end of breath holds performed at larger lungvolumes. In fact we have found that the rate of rise of pCO2 during breathholding is virtually independent of lung volume and is only slightly higher


than during simple rebreathing under the conditions described in theseexperiments (Table III). It also shows little inter-subject variation.

In any one subject, the form of the curve relating breath holding timeto the pCO2 at the start or end of the breath holds remained relatively

TABLE III. RATE OF RISE OF pCO2 (mm Hg/min)

Mean S.D. n1. Rebreathing before breath holding at T.L.C. = 5-87 0-56 62. During breath hold at T.L.C. - 622 0.76 63. Rebreathing before breath holding at F.R.C. = 605 0-63 64. During breath hold at F.R.C. = 683 1*01 6

The rate of rise of pCO2 for rebreathing preceding a breath hold and for the breathhold itself are given for breath holds at two different lung volumes. Differences betweenthem were not significant.

constant and could be described by a straight line to a close approximation.The form of such a line can be described by its slope (SBH) and intercept,that is the PCO2 at which the breath holding time is zero (BBH); these termsare comparable with those introduced by Lloyd, Jukes and Cunningham

* Before hyperventilation o 10 mins. after hyperventilation x Immediately after hyperventilation

M.S. x D.W R.J.

60

60 -=~~~~~~~~~~~~~~~~~~~

Ec 20-N,

0

50 60 70 50 60 70 50 60 70END TIDAL Pco2 AT START OF BREATH HOLDING

Fig. 5. The effect of isocapnic hyperventilation on the breath holding-CO2 relationship in threesubjects. The three curves for each subject do not differ consistently.

[1958] to describe the ventilatory response to pCO2. Such relationshipscould equally well be applied to the initial or final pCO2, but for the reasonsgiven below we have chosen to use the initial pCO2 as our standard reference.We have measured the parameters in many subjects, and found much inter-subject but little intra-subject variation, much as has been found for theventilatory response to pCO2. In one subject (D.W.) studied on five separateoccasions, SBH varied from 3-6 to 5.4 sec/mm Hg (mean = 4*4 + 0-4 S.D.)


and BBE. varied from 62 to 68 mm Hg (mean = 64 + 2 S.D.), giving coefficientsof variation of 8-6 per cent and 2-8 per cent respectively.

Residual volume breath holding-CO2 response curves were obtainedin three subjects before, immediately after, and ten minutes after hyper-ventilation at constant pCO2 (isocapnic hyperventilation). For any one subject,no difference was found in the relationship between breath holding timeand pCO2 (fig. 5) as a result of hyperventilation.

DIscusSION

It is well known that under ordinary circumstances, the breath holdingtime varies from individual to individual, and that this is due in some degreeto the subjects' will power. Other factors known to affect the breath holdingtime include lung volume and blood gases, acting as interrelated stimuli[Mithoefer, 1959]. Most of the studies on breath holding previously reported,have been complicated by varying more than one of these factors at a time.This has probably resulted in greater variations in breath holding timesthan need have occurred, and may indeed have masked real changes.

In the present study we have attempted to control the various factorsby using the rebreathing method. The high initial 02 tension in the bagensured that the P02 of the subjects never fell to levels low enough to affectbreath holding [Otis et al., 1948]. In all our experiments, the lung volumewas always the same at the start of the breath hold for any given type ofstudy. The remaining factor, pCO2, has been allowed to vary in a controlledmanner.

It is the control of pCO2 which forms the essential part of the rebreathingmethod we describe (sometimes called an 'open-loop' approach). It isnow well established that rebreathing of a gas with a pCO2 close to mixedvenous pCO2 results in rapid equilibrium between mixed venous blood,alveolar gas and bag gas [Campbell and Howell, 1960; Collier, 1956]. Afterpassage through the lungs, the blood enters the systemic circulation withthe elevated level of pCO2 and then picks up a new load of CO2 from thetissues. This means that after recirculation the pCO2 of the blood-lung-bagsystem will rise. It has been shown that the rate of rise of pCO2 is verysteady after the first 20 sec of rebreathing [Read, 1967] and moreover,the bag pCO2 is a very good index of chemoreceptor pCO2 [Read and Liugh,1967]. It has also been shown that the rate of rise of pCO2 during rebreathingis independent of the size of the bag up to about 10 1. [Fowle andCampbell, 1964]. Once the pCO2 of the system has begun to rise, it willnot matter if the subject holds his breath, since the situation for gas exchangewill be the same, i.e., the excretion of CO2 is prevented. The only differencebetween breath holding and rebreathing under these circumstances willbe due to the volume of the gas phase. The actual quantity of CO2 requiredto raise the pCO2 of the gas phase by the resting rate of 6 mm Hg per minwill be only a little greater during rebreathing, which accounts for ourobservations that the rate of rise of pCO2 is virtuallv independent of the


volume of gas in the system. All these remarks only apply to rebreathingor breath holding under hyperoxic conditions.

Because of these very special relationships, the pCO2 in the lungs duringour experiments rises at a steady rate whether the subject is rebreathingor breath holding. It is true that during a breath hold the pCO2 in the bagceases to rise, but the small difference between lung and bag pCO2 at the endof the breath hold is rapidly removed by the first two or three breaths.

The rebreathing 'open-loop' situation implies that:

1. The pCO2 at the beginning and end of a breath hold can be accuratelyknown without taking arterial blood.

2. Since the inspired-expired pCO2 difference is virtually removed(being only 1-7 mm Hg in our experiments), inspired gas does notdilute alveolar C02, and so the pCO2 is independent of lung volume.

3. It is possible to perform serial rebreathing and breath holding in oneexperiment, with the pCO2 rising steadily and predictably.

By means of this approach we were able to standardize the first (stressing)breath hold in the cluster experiments, both in terms of duration and ofpCO2, and to present each subject with a uniform experience at the startof the different sized clusters. The similar duration of B.H.2 whateverthe cluster size meant that breaking point pCO2 was virtually constantfor any subject. The fact that the breath holds (B.H.2) did not differsignificantly means that a single breath is as effective as five breaths inallowing the resumption of breath holding. There was a certain degree ofvariability in the performance of individual subjects. This was probablydue in part to the larger lung volumes and less definite end points in theearlier experiments, as well as to lack of experience. However, the resultswith residual volume breath holding confirmed the earlier findings. Weknow of no previous work to define the number of breaths required to permita breath hold.

Our subsequent use of the rebreathing 'open-loop' situation was todefine the relationship between breath holding time and pCO2 so that itcould be compared under different conditions. Fowler [1954] first showedthat serial breath holding and rebreathing was possible, but his subjectswere also hypoxic and he made no attempt to quantitate the relationship.As we have shown (fig. 4), there is an almost linear relationship for eitherinitial or final pCO2. This follows from the fact that the rise of pCO2 duringthe breath hold is itself a linear function of the breath holding time. It isclear that no single level of pCO2 will exist at the breaking point of a breathhold, the final pCO2 depending on the initial pCO2. For this reason wehave chosen to relate the breath holding time to the initial pCO2 ratherthan the more conventional final pCO2. We believe that the pCO2 mayaffect the breath hold right from its beginning; in most sensory experienceduration is as important as intensity.

The lines relating breath holding time to initial and final pCO2 convergeas the breath holding time falls and they would meet at a pCO2 at which


breath holding is impossible (BBH). This pCO2, usually about 70 to 80mm Hg, could reasonably be considered as the true PCO2 threshold; or ratherthe sensation due to CO2 has now reached the breaking point thresholdfor total sensation during breath holding [Godfrey and Campbell, 1968].It is very uncomfortable for the subject at these levels of pCO2, but inexperiments where this has been achieved the breath holding time falls

25 * Serial breath holdsx Single breath holds

, 20

- 15 x S.F.

-= 10_X

10

48 50 52 54 56 58 60

INITIAL PCO2 (mm.Hg.)Fig. 6. Breath holding-CO2 response curves in one subject obtained byserial breath holds separated by rebreathing ( * -0 ), or by entirelyseparate experiments in which the subject rebreathed up to the desiredPCO2 and then held his breath (x-x). The curves are essentially similar.

to one or two sec and it is impossible to distinguish between breath holdingand rebreathing.

It did seem possible that the fall in breath holding time during theexperiments might have been partly due to fatigue. We therefore allowedone subject (S.F.) to rebreathe to various levels of pCO2 before beginningthe breath hold: We found his breath holding time was the same as whenthere had been a preceding breath hold(s) interspersed with the rebreathing(fig. 6).

As the level of pCO2 rises during the experiment, so a ventilatory responseoccurs and the ventilation increases during the rebreathing periods. Ithas been shown that hyperventilation may cause the central respiratorymechanisms to habituate to a new level of ventilation even when the pCO2is prevented from falling [Smith et al., 1961]. In our experiments, a shortperiod of severe isocapnic hyperventilation did not displace the breathholding-CO2 response curve, which suggests that the pattern of breathinghas little effect on a subsequent breath hold.


The experiments described in this paper imply that there is no breakingpoint threshold for pCO2, the only true threshold being the pCO2 at whichbreath holding becomes impossible. The duration of a breath hold is directlyrelated to pCO2 below this true threshold, whether the initial or final valueis considered, and it is independent of the size of previous mechanical experi-ence. In the following paper, the relevance of lung shrinkage during breathholding is considered.

ACKNOWLEDGEMENT

We thank our colleagues who acted as subjects for these experiments.

REFERENCES

CAIN, S. M. (1957). 'Breaking point of two breath holds separated by a single inspiration',J. appl. Physiol. 11, 87-90.

CAMPBELL, E. J. M. and HowELL, L. B. J. (1960). Simple rapid methods forestimating arterial and mixed venous PCO2', Br. med. J. 1. 458-462.

COLLIER, C. R. (1956). 'Determination of mixed venous CO2 tensions by rebreathing',J. appl. Physiol. 9, 25-29.

DOUGLAS, C. G., and HALDANE, J. S. (1909). 'The regulation of normal breathing',J. Physiol. (Lond.), 38, 420-440.

FOWLE, A. S. E., and CAMPBELL, E. J. M. (1964). 'TThe immediate carbon dioxidestorage capacity of man', Clin. Sci. 27, 41-49.

FOWLER, W. S. (1954). 'Breaking point of breath holding', J. appl. Physiol. 6, 539-545.FREEDMAN, S. (1966). 'Prolonged maximum voluntary ventilation', J. Physiol. (Lond.),

184, 42-44.GODFREY, S., and CAMPBELL, E. J. M. (1968). 'The control of breath holding', Resp.

Physiol. 5, 385-400.HILL, L., and FLACK, M. (1908). 'The effect of excess carbon dioxide and of want of

oxygen upon the respiration and the circulation', J. Physiol. (Lond.), 37, 77-111.KLOCKE, F. J., and RAHN, J. (1959). 'Breath holding after breathing oxygen', J. appl.

Physiol. 14, 689-693.LLOYD, B. B., JUKES, M. G. M., and CUNNINGHAM, D. J. C. (1958). 'The relationship

between alveolar oxygen pressure and the respiratory response to carbon dioxidein man', Q. Ji exp. Physiol., 43, 214-227.

MITHOEFER, J. C. (1959). 'Lung volume restriction as a ventilatory stimulus duringbreath holding', J. appl. Physiol., 14, 701-705.

MITHOEFER, J. C. (1964). Breath holding. In Handbook of Physiology. Section 3:Respiration. Vol.II,pp. 1011-1025. AmericanPhysiologicalSociety. WashingtonD.C.

MUXWORTHY, J. F. JR. (1951). Breath holding studies: relationship to lung volume.A. F. Tech. Rep. 6528, 452-456, Wright-Patterson Air Force Base, Dayton, Ohio.

OTIS, A. B., RAHN, H., and FENN, W. 0. (1948). 'Alveolar gas changes during, breathholding', Am. J, Physiol., 152, 674-686.

READ, D. J. C. (1967). 'A clinical method for assessing the ventilatory response to carbondioxide', Aust. Ann. Med., 16, 20-32.

READ, D. J. C., and LEIGH, J., (1967) 'Blood-brain tissue pCO2 relationships andventilation during rebreathing', J. appl. Physiol., 23, 53-70.

SMITH, A. C., SPALDING, J. M. K., and WATSON, W. E. (1961). 'Ventilation volumeas a stimulus to spontaneous ventilation after prolongecl artificial ventilation',J. Physiol. (Lond.), 160, 22-31.

MECHANICAL AND CHEMICAL CONTROL OF BREATH HOLDING

Documents

Transcript of MECHANICAL AND CHEMICAL CONTROL OF BREATH HOLDING