Thorax (1962), 17, 244.

INHALATION OF BLOOD, SALIVA, AND ALCOHOL:CONSEQUENCES, MECHANISM, AND TREATMENT

BY

D. F. J. HALMAGYI, H. J. H. COLEBATCH,* AND B. STARZECKIFrom the Department of Medicine, University of Sydney, Sydney, N.S.W., Australia

(RECEIVED FOR PUBLICATION NOVEMBER 15, 1961)

The inhalation of body fluids as a main orcontributory cause of morbidity and death hasbeen recognized in only a few conditions.The aspiration of saliva and gastric content was

found to be the cause of death in 92 out of 11,000patients submitted to general anaesthesia (Edwards,Morton, Pask, and Wylie, 1956). Delayed gastricemptying during parturition was suggested toaccount for the relative frequency with whichaspiration of vomitus contributes to maternaldeath (Mendelson, 1946; Parker, 1954). Half themortality rate in severe head injuries is said to bedue to inhalation of saliva, vomitus, blood, andcerebrospinal fluid (Maciver, Frew, and Matheson,1958; Zundel, 1961). The respiratory distresssyndrome of the newborn (at present the maincause of perinatal mortality) is regarded by some(Barnett, 1959) as a consequence of amniotic fluidinhalation. Severe haemoptysis may occasionallyresult in respiratory failure (Brown, Nour-Eldin,and Wilkinson, 1960). A lack of response to100% oxygen breathing is a common and ill-understood feature in these severely cyanoticpatients.There is some indication that the real frequency

of body fluid inhalation may be much higher thanis generally recognized. In the absence of specificclinical signs suggestive of fluid inhalation thediagnosis is based on post-mortem findings.However, unless the fluid inhaled was excessivein volume, irritative to the tissues, or a carrier ofparticulate (or coagulable) material it is rapidlyabsorbed, leaving no structural changes behind.Pathologists therefore find it difficult to substan-tiate the clinical claim and feel justified in arguingthat the inhaled fluid, provided that there wassuch, had been disposed of before death and couldhardly have made a major contribution to theultimate outcome.

*Present address: Cardiovascular Research Institute, University ofCalifornia, Medical Center, San Francisco, Cal., U.S.A.

Inhaled water is absorbed within minutes acrossthe huge alveolo-capillary surface (Courtice andPhipps, 1946; Halmagyi, 1961), but the physio-logical alterations, which have been found to beindependent of the amount inhaled, remainunchanged for some time (Halmagyi andColebatch, 1961; Colebatch and Halmagyi,1961a). The finding that the pulmonary responseto inhaled water is predominantly reflex in nature(Colebatch and Halmagyi, 1961b) has resolvedthese apparent contradictions.The absorption from the lung of isotonic

solutions or of fluids containing protein is slowerthan that of water (Courtice and Phipps, 1946;Courtice and Simmonds, 1949; Halmagyi, 1961).The aspiration of alcohol is reported to haveproduced microscopical damage in the lungs(Moran and Hellstrom, 1957), but inhaled waterdid not. It seemed therefore of interest to deter-mine if inhaled fluids other than water would havesimilar effects and if the implications for treatmentarising out of the studies on water inhalation havea similar application.

EXPERIMENTAL DESIGNCardiac output, systemic and pulmonary arterial

pressure and resistance, venous admixture, venti-lation, lung compliance, mean frictional resistance,and elastic work of breathing were measured inlightly anaesthetized sheep before and five minutesafter the intratracheal administration of 1 ml./kg.blood, saliva, physiological saline, and dilutealcohol. Subsequently the lungs were inflated andlung compliance was repeatedly measured. Theeffect of the administration of atropine and ofisoproterenol was also studied in some animals.

METHODSSixteen sheep weighing 31 to 44 kg. were

used in these experiments. The supine animals wereanaesthetized with thiopentone, heparinized, and

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INHALATION OF BLOOD, SALIVA, AND ALCOHOL

intubated. A cardiac catheter was passed via thefemoral vein into the pulmonary artery, a cannulawas introduced into the femoral artery, and intra-pleural pressure was taken via a needle introducedinto the third or fourth interspace.

Pressures were measured with Sanborn transducersand recorded on a Sanborn multi-channel direct-writing oscillograph. Intravascular pressures wereexpressed in mm. Hg and intrapleural pressure incm. H20 relative to atmosphere.

Oxygen saturation and haemoglobin content of thearterial and mixed venous blood were measuredspectrophotometrically. Oxygen uptake and ventila-tion were measured with a twin spirometer(" Pulmotest," Godart) while the animal was breathingair. Air flow rate and tidal volume for the lungmechanics measurements were obtained with a Godartpneumotachometer and integrator.Blood flows, ventilated volumes, and resistances

were expressed on the basis of 1 M.2 body surfacearea (B.S.A.). Lung compliance was expressed inml./cm. H20/kg., elastic work of breathing in kg.-m./min./l0-2, and mean frictional resistance in cm. H20/1. /sec.

Details of our techniques are described elsewhere(Halmagyi and Colebatch, 1961 ; Colebatch andHalmagyi, 1961a).

Statistical methods were used as recommended bySnedecor (1956).PROCEDURE.-After a control period a thin poly-

ethylene catheter attached to a syringe was passedjust beyond the distal end of the endotracheal tube.The following fluids, 1 ml./kg., were injected intra-

tracheally at a rapid rate: own heparinized blood(five sheep); own saliva (five sheep); a mixtureconsisting of three parts of saliva and one part ofabsolute alcohol (three sheep); and isotonic saline(three sheep).

Pressures were recorded continuously; measure-ments were repeated five minutes after the fluidaspiration. All animals were then subjected to lunginflation with a pressure of 30 mm. Hg followed byrepeated determinations of lung compliance.

Different types of treatment were then given in10 out of 16 sheep (three blood, five saliva, and twoalcohol). The animals were first given 0.2 to 0.3 mg./kg. atropine sulphate intravenously and the measure-ments were repeated after lung inflation. In five ofthese animals this regime was followed by theadministration of isoproterenol hydrochloride. Intwo sheep this substance (Isuprel, Winthrop) wasinjected as a continuous intravenous infusion (0.33pg./kg./min.), the lungs were inflated, and measure-ments repeated while the infusion was in progress.The infusion was then discontinued and the measure-ments were repeated 10 minutes later. Three animalswere subjected to a five-minute period of 1% Neo-epinine (Burroughs Wellcome) inhalation. Theaerosol was administered with a Mark 8 Birdrespirator using an inflating pressure of 20 cm. H20

and four to six inspirations at a pressure of 40 cm.H20. After this period the measurements wererepeated.

In one animal fluid inhalation was followed by aconstant intravenous infusion of 0.4 mg./kg./min.adrenaline; in one other the injection of atropinepreceded the inhalation of alcohol; in a furtheranimal the inhalation of alcohol was followed by thecontinuous breathing of 100% oxygen. Blood sampleswere taken after 12 minutes.

RESULTSThe results are summarized in Table I.

TABLE ICARDIORESPIRATORY EFFECTS OF THE INHALATION

OF BODY FLUIDS IN SHEEPFluid inhaledNo. of animalsCardiac output(I./min.im.2 B.S.A.)

Femoralartery mean pressure(mm. Hg)

Systemic arterial resistance(dynes-sec.-cm.-5/m.2 B.S.A.)

Pulmonary artery meanpressure (mm. Hg)

Pulmonary artery resistance(dynes-sec.-cm.-5'm.2 B.S.A.)

Arterial oxygensaturation (%)

Venous admixture(% of cardiac output)

Ventilation(I./min./m.2 B.S.A.)

Tidal volume(ml. /m.2 B.S.A.)

Rate of breathing(min.)

Mean frictional resistance(cm. H20/l./sec.)

Lung compliance(ml./cm. H20/kg.)

B*ABABABABABABABABABABABAI

Blood53-293-52119121

3,0052,924

1617$394413t80-662 It3554t

10-21392542754149

1-74440t2-891-26t2-00

Saliva Alcohol5 2256 4-414 06t$ 5 76109 102116 110

3,694 1,8602,722 1,526

13 1418 19

441 256411$ 27092-8 88-4697t 539

7 2042t 649-7 8-515 9t 10-8235 265316t 22436 3245 71

2-24 2-005-72 8-603-20 2-020-95 0-651-15 0-97

Elastic work of breathing B 12 10 15(kg.-m./min.l10-2) A 42 79t 77* B =before, A= 5 min. after fluid inhalation; I = after inflation of

lung: t difference from control value (B) statistically significant(P< 005);*difference from corresponding change after fresh waterinhalation statistically significant (P< 005).

CIRCULATORY RESPONSEFresh Water. -The immediate circulatory

response to the inhalation of 1 ml. /kg. fresh wateris shown in Fig. 1.Blood.-The inhalation of blood had no

immediate (Fig. 2) or delayed (Table I) effect onthe pulmonary circulation.

Saliva.-There was no abrupt change (Fig. 3),only a small gradual rise (Table I) in pulmonaryarterial pressure after the inhalation of saliva.Pulmonary arterial resistance was unchanged afterfive minutes. This was significantly different fromthe corresponding changes obtained after freshwater inhalation (Halmagyi and Colebatch, 1961).The inhalation of saliva resulted in a marked

increase in cardiac output from 2.56 to 4.06

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40r- ;1CC 200

£TE

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Lau -8-- , > 8 s, z;, ! f I j J I # I; ! b I I #00~~~~Aui- tt\ e' \;A ''''

cr J -6 = s t ' ; ', B,i

FIG. 2.-Effect ofthe inhalation of 1 ml./kg. heparinized blood. Biack box at the bottom shows time of'b.ood inhalation.PL= intrapleural pressure. Paper speed as in Fig. 1.

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INHALATION OF BLOOD, SALIVA, AND ALCOHOL

w.Dcc

w

a -w.

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TIME [min.)FIG. 3.-Effect of the inhalation of 1 ml./kg. saliva.

pleural pressure.

I./min./m.2 B.S.A.; this was significantlydifferent from the corresponding change afterwater inhalation. Because of the slight increasein the mean average pulmonary arterialpressure from 13 to 18 mm. Hg and the grossrise in cardiac output, right ventricular activitywas significantly increased.

Saliva and Alcohol.-The changes werevirtually identical with those caused by salivaalone.

Physiological Saline. - The intratrachealadministration of physiological saline wasfollowed by a pulmonary hypertensive response(Fig. 4) similar to that caused by the inhalationof water.

CHANGES IN BLOOD OXYGEN AND VENOUSADMIXTURE.-The increase in venous admixtureand the fall in arterial oxygen saturation wereessentially similar in all four types of fluidinhalation. There was a gross arterial hypox-aemia, and venous admixture in several animalsexceeded 50% of the cardiac output.

PL=intl

In the one animal which had beengiven 100% oxygen breathing afteralcohol inhalation arterial oxygensaturation increased from 64.5% toonly 75.6%.VENTILATORY RESPONSE.-In about

half of the animals the inhalation ofblood or saliva caused transient apnoea.The inhalation of alcohol resulted ina transient apnoea in two out of

..- two untreated animals. BreathingX-LA always returned spontaneously.

An increased rate and depth of_4 'M breathing resulted in a varying degree

of hyperventilation after the inhalationof all four types of fluid. A significantrise in ventilation and tidal volumeoccurred only after the inhalation ofsaliva.CHANGES IN THE MECHANICS OF

BREATHING.-A rise in the intrapleuralpressure swing was obtained in all cases.This occurred rapidly when preceded byapnoea and more progressively in otheranimals. The mean average intrapleural

1"' pressure swing five minutes after saliva2 inhalation was 17 cm. H20, and five

minutes after blood inhalation it was12 cm. H,O.

rn_-

>- 40--

2 0-

6 Cc I0

ag 50-ai~ 50

I lerX E .....

FIG. 4.-Lffe.t of tne tinnaution of 1 mi./kg. 0.8.% physiotogicalsaline. Black box at the bottom shows time of admin-istration of saline.

At6wim"AWLitmah AWIW

q x T'Tlz illititil Pr --.

247

ra-

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D. F. J. HALMAGYI, H. J. H. COLEBATCH, and B. STARZECKI

CONTROL SALIVA INFL. ATROP. ISUPR. CONTROL

CARDIAC OUTPUT

c I./min./m2 ) 3 . 0

1 2 5> FEMORAL ARTERYat

7 5

E 18

%25 PULMONARY ARTERY 51 2

g ARTERIAL OXYGEN 8060

SATURATION %/o 40

20VENTILATION

5

E I./min./m2/ B.T.PS.) 0

3 0

LUNG COMPLIANCE2 0

C ml. /cm. H20/Kg.j

I 0

I...I

LLELASTICITY 2 5

DUURING BREATHING

C K%-m/min./IO-2) 1

25 -

FIG. 5.-The effect of inflation of the lung (infl.) and the injection of atropine (atrop.) and isoproterenol(isupr.) after the inhalation of saliva. Mean values obtained in three experiments. " Elasticityof breathing " means the elastic work of breathing.

A gross fall in lung compliance resulted fromthe inhalation of all types of fluid. After theinhalation of blood this fall appeared to be some-

what less marked and inflation of the lung seemedto restore compliance more readily than in theother groups; the difference was, however, notstatistically significant. The correlation betweencompliance fall and increase in venous admixturewas identical with that already described for waterinhalation (Colebatch and Halmagyi, 1961a).The rise in mean frictional resistance appeared

to be more marked after the inhalation of bloodthan after that of water, and more marked afterthe inhalation of saliva than after that of blood.The difference between the rise in mean frictionalresistance after water and after saliva inhalationwas statistically significant. The gross rise in theaverage value of mean frictional resistance after

the inhalation of alcohol was due to an excessiveincrease in one animal and a small rise in theother.

Elastic work of breathing increased significantlyin all groups. The smallest rise occurred after theinhalation of blood; the difference was, however,not statistically significant.EFFECT OF THERAPEUTIC PROCEDURES. The

effect of the administration of atropine andisoproterenol is illustrated in Fig. 5. The diagramrepresents mean values obtained in three experi-ments. The injection of atropine was followedin this case by a marked rise in ventilation, lungcompliance, and arterial oxygen saturation. Thesechanges were further augmented by the infusionof isoproterenol which also caused a markedincrease in cardiac output. When the infusion ofisoproterenol was discontinued cardiac output

..Ii

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INHALATION OF BLOOD, SALIVA, AND ALCOHOL

returned to normal, ventilation decreased, andthere was a slight diminution of lung compliance.Elastic work of breathing decreased graduallythroughout the entire procedure.

In one sheep, in which the inhalation of alcoholwas preceded by the administration of atropine,lung compliance decreased from 1.59 ml. / cm.H20/kg. to only 1.33 ml./cm. H20/kg.

DISCUSSIONThese studies re-emphasize the severity of the

arterial hypoxaemia that invariably follows theinhalation of even small amounts of fluids. Itsonset and extent seem to be largely independentof the chemical composition or origin of the fluidinhaled.Pulmonary hypertension, a characteristic

response to the inhalation of water, wascompletely absent after the inhalation of blood.Iso-osmocity could hardly account for the absenceof this reaction, as the inhalation of physiologicalsaline had effects similar to those of water. Theincrease in pulmonary arterial pressure after theinhalation of saliva was accompanied by a risein cardiac output. As a result, pulmonary arterialresistance remained unchanged. In normalcircumstances a similar increase in flow is unlikelyto affect pulmonary arterial pressure. We suggesttherefore that an increase in pulmonary arterialtone has occurred. We cannot at this stage offerany explanation for these remarkable differencesin the pulmonary vascular reaction.

Alveolar oxygen tension was invariably normalafter the inhalation of 1 ml./kg. water (Halmagyiand Colebatch, 1961) and there was a markeddrop in the saturation of the arterial and mixedvenous blood. It has been suggested, as sum-marized by Fishman (1961), that pulmonaryprecapillary resistance increases not only duringalveolar hypoxia but also after a marked dropof the saturation of arterial or mixed venousblood. Our experiments failed to confirm thishypothesis. The oxygen saturation decreasedsignificantly after the inhalation of blood, yetpulmonary hypertension was absent. This isconsistent with our previous conclusion thatpulmonary hypertension caused by the inhalationof water is unrelated to hypoxaemia.No explanation is offered for the marked rise

in cardiac output after the inhalation of saliva.In these animals the extent of arterial hypoxaemia,a possible stimulus for increased blood flow, wascomparable to that of other groups.A gross fall in lung compliance was the most

important physiological consequence of the

inhalation of these small amounts of fluid. Thechanges in lung mechanics were essentially similarto those described after fresh water aspiration(Colebatch and Halmagyi, 1961a) and seem toaccount for the severe respiratory embarrassmentand cyanosis encountered in clinical fluidinhalation (Gardner, 1958).

Because the anaesthetized animal tends tobreathe at a fixed tidal volume, i.e., a constanttranspulmonary pressure swing, compliance islikely to remain reduced until a large inflation isperformed. The apparent duration of the stimulusresponsible for the fall in compliance, or, alter-natively, the effect of any therapeutic procedure,can only be assessed by the effect of inflation onthe restoration of compliance.

Inflation of the lung was hardly effective afterthe inhalation of saliva or alcohol and restoredcompliance only partially after the inhalation ofblood. The amount of fluid administered wasonly 5% of the resting lung volume of the sheepand could hardly account for the sustained depres-sion of lung compliance amounting to 30 to 70%.

Inflation after the administration of atropine,isoproterenol, or both resulted in a significantincrease in lung compliance. This effect is similarto that seen after water inhalation (Colebatch andHalmagyi, 1961b). We suggest therefore that theinhalation of these fluids caused an intrinsicreaction in the lung similar to that caused by water,consisting of a reflex constriction of the muscula-ture in the terminal (unsupported) airways. Theairway closure reduced the amount of lung, i.e.,the number of distensible units participating inexpansion, and was measured as a fall in lungcompliance. The continued perfusion of non-ventilated areas produced a shunt of venous bloodto the systemic circulation which was responsiblefor hypoxaemia and could be represented asvenous admixture.

Breathing of 100% oxygen after alcoholinhalation failed to restore arterial oxygen satura-tion. This is consistent with the effect of self-breathing of oxygen after water inhalation(Colebatch and Halmagyi, 1961a) and indicatesthat a diffusion defect or uneven ventilation couldhardly account for the severe hypoxaemia.

In the majority of experiments the injection ofatropine resulted in a satisfactory improvement iDarterial oxygen saturation and elastic work ofbreathing. In some cases, however, the responsewas unsatisfactory and isoproterenol was moreeffective. The reason for this occasionalunresponsiveness to atropine has to be furtherinvestigated.

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D. F. J. HALMAGYI, H. J. H. COLEBATCH, and B. STARZECKI

Assuming that fluid aspiration in humans haseffects similar to those we have described in lightlyanaesthetized sheep, then the implications of ourfindings for clinical management can be brieflyoutlined. The essential measurement for assess-ment and as a guide to the efficiency of treatmentis arterial oxygen saturation.

It follows from the mechanism of hypoxaemiathat the collapsed areas of the lung must bereinflated, otherwise the persistence of a highvenous admixture will prevent satisfactory levelsof arterial oxygen saturation being attained. Themaximum safe inflating pressure should be avail-able for artificial respiration or assisted breathing;30 mm. Hg is a reasonable upper limit. Largeinflations should be given at a relatively slow (8to 12 per minute) rate. In these circumstances theexpiratory phase may be four to six times as longas inspiration. This ensures a low mean airwaypressure, and so avoids any significant depressionof cardiac output. For restoration of normaloxygen saturation in the arterial blood a combina-tion of 100% oxygen with intermittent positivepressure breathing is essential (Colebatch andHalmagyi, 1961a). The additional 2 volumes %of physically dissolved oxygen in the arterial bloodis only one factor of the effect of oxygen; it alsorelieves pulmonary vasoconstriction and facilitatesairway opening.The dose of atropine that was effective in

restoring lung compliance in these experimentswas many times more than that used in clinicalmedicine. Smaller amounts, even when given asa constant intravenous infusion, as suggested byUrsillo (1961), were considerably less effective.However, the effect of a smaller relative doseshould be assessed in man.The amount of isoproterenol found to be

effective in these experiments was well within thehuman therapeutic range. A particularly favour-able feature of its effect was full efficiency inaerosol form. This, when combined with inter-mittent positive pressure breathing using 100%oxygen, would appear to represent the mostefficient method in the management of patientswho have inhaled any type of fluid.

SUMMARYThe cardiorespiratory effects of the inhalation

of 1 ml. /kg. blood, saliva, and alcohol werestudied in sheep. The effect of different types oftreatment was also assessed.

The inhalation of blood failed to affect thepulmonary circulation; a minor rise in pulmonaryarterial pressure was observed after the inhalationof saliva. This contrasted with the markedpulmonary hypertension following waterinhalation.The intratracheal administration of these small

quantities of all three types of fluid caused amarked fall in lung compliance resulting in severearterial hypoxaemia. The injection of atropineand the injection or inhalation of isoproterenolgreatly reduced these changes.The implications of these findings in the

management of patients who have inhaled fluidare discussed.

D.F.J.H. is Adolph Basser research fellow of theRoyal Australasian College of Physicians; H.J.H.C.was research fellow of the Joint Coal Board ofN.S.W.; B.S. is Roche research fellow of the RoyalAustralasian College of Physicians.

This study was supported in part by grants fromthe National Health and Medical Research Councilof Australia, the Postgraduate Medical Foundation.and the Consolidated Medical Research Fund of theUniversity of Sydney.

Invaluable assistance was given by Mr. P. Donnelly,by Miss Maureen Woodward, and by Mr. R. Sheen,members of the technical staff of the department.We are indebted to the Department of Illustration

of the University of Sydney for photographs anddrawings.

It was a privilege to enjoy Professor C. R. B.Blackburn's constant interest and support.

REFERENCESBarnett, R. P. (1959). J. Amer. med. Ass., 169, 1325.Brown, B., Nour-Eldin, F., and Wilkinson, J. F. (1960). J. Laryng.,

74, 166.Colebatch, H. J. H., and Halmagyi, D. F. J. (1961a). J. appl.

Physiol., 16, 684.(1961b). Physiologist, 4, No. 3, p. 20.

Courtice, F. C.,andPhipps,P. J. (1946). J. Physiol.(Lond.),105, 186.-and Simmonds, W. J. (1949). Ibid., 109, 103.Edwards, G., Morton, H. J. V., Pask, E. A., and Wylie, W. D.

(1956). Anaesthia, 11, 194.Fishman, A. P. (1961). Physiol. Rev., 41, 214.Gardner, A. M. N. (1958). Quart. J. Med., 27, 227.Halmagyi, D. F. J. (1961). J. appl. Physiol., 16, 41.-and Colebatch, H. J. H. (1961). Ibid., 16, 35.Maciver, I. N., Frew, I. J. C., and Matheson, J. G. (1958). Lancet,

1, 390.Mendelson, C. L. (1946). Amer. J. Obstet. Gynec., 52, 191.Moran, T. J., and Hellstrom, H. R. (1957). Amer. J. clin. Path., 27,

300.Parker, R. B. (1954). Brit. med. J., 2, 65.Snedecor, G. W. (1956). Statistical Methods Applied to Experiments

in Agriculture and Biology, 5th ed. Iowa State College Press.Ursillo, R. C. (1961). J. Pharm. exp. Ther., 131, 231.Zundel, S. (1961). Dtsch. GesundhWes.,16, 152.

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