5269

AUGUST 23, 1924.

Oliber- Sharpey Lectues.Delivered before the Royal College of Physicians of

London

’BY A. V. HILL, Sc.D., F.R.S.,PROFESSOR OF PHYSIOLOGY, UNIVERSITY COLLEGE, LONDON.

LECTURE II.*—THE RECOVERY PROCESSIN MAN.

LACTIC ACID IN MAN.IT is a common observation that after exercise

breathing is deep and rapid-that recovery is necessary.The same process must occur as in the isolated muscle,complicated in this case by the presence of therespiratory and circulatory mechanism. It can beshown that lactic acid occurs in human muscles as itoccurs in isolated amphibian muscles. It had not been

realised, however, till recently, how extensive are thechanges connected with the lactic acid which isproduced in the human body during exercise. Whenan athlete is running as fast as he can, about 3 g. oflactic acid per second are being liberated in hismuscles! There are several signs of this lactic acidin the body. It occurs in the urine after prolongedhard exercise. In the blood of a resting man there is0-01 to 0-02 per cent. ; during and after severe exercisethere may be as much as 0-20 per cent. This may beestimated directly by chemical analysis, or it may beinferred, as Barcroft did, from the change it producesin the oxygen dissociation curve. There is a veryhigh respiratory quotient during, and especially justafter, severe exercise ; the lactic acid raises thehydrogen-ion concentration of tissues and blood ; thisstimulates the respiratory centre, with the result thatCO is eliminated by the lungs. In a later stage ofrecovery correspondingly the respiratory quotientfalls to very low values as the lactic acid is removed.The chief sign, however, of the amount of lactic acidpresent in the body after exercise is the magnitude ofthe so-called oxygen debt. A muscle which has beenactive requires oxygen to carry out the combustionsneeded to provide the energy for the restoration process.The oxygen used in recovery is a measure of themagnitude of that process-that is, of the amountof lactic acid removed. Assuming an efficiency ofrecovery of 5-2 : 1, one litre of oxygen consumed afterexercise is equivalent to 7 g. of lactic acid removed.The greatest oxygen debt hitherto recorded is one ofnearly 19 litres, which corresponds to a concentration

, of lactic acid of not far from 0-35 per cent. in all themuscles of the subject ; he was well-nigh exhausted.

STUDIES OF OXYGEN INTAKE.

The greater part of our knowledge of the eventsoccurring in human muscular exercise has beenarrived at by studies of the oxygen consumption.The measurement of oxygen intake is possible inmany ways, two of which have been widely used inrecent years. The first, which was employed byBenedict and Cathcart among others, involves thecontinuous circulation of oxygen in a closed systemwhich includes the lungs of the subject, the CO beingabsorbed and the diminution in volume owing toconsumption of O2 being recorded. The method isaccurate but inadaptable ; it is not capable ofanalysing the time course of the oxygen consumptionwhen the latter is changing rapidly, as at the beginningand end of exercise. For such purposes the techniqueof the Douglas bag, in which the subject expires intoa large bag carried on his back or in front of him, andthe expired gases are analysed and their volumemeasured, is just as accurate as the other method andis capable of following very rapid changes. It ispossible to use this method when walking, running,riding a bicycle, even swimming, and to plot thetime course of the oxygen consumption in intervals

1 Lecture I. appeared in THE LANCET of August 16th.5269

as short as half a minute. Under certain circumstanceseven quarter minute intervals may be employed.

THE " STEADY STATE."

In my previous lecture I spoke about the steadystate of an isolated muscle contracting in an atmos-phere of oxygen ; in such a muscle there is a balancebetween breakdown and recovery. Remember thatthe recovery process is more rapid when the totalamount of breakdown causing it is greater ; lacticacid is a sensitive governor of oxygen usage. Hence,if we start with a given rate of breakdown, as when aman suddenly begins to run at a given speed, therate of recovery, starting from zero, has to work upgradually until it balances the rate of breakdown. Itis necessary, moreover, in the intact animal for thecirculation and respiration to work up also. In a

subject starting to run, having been previously at rest,the oxygen intake rises to its full steady value in aperiod of about two to two and a half minutes (seeFig. 3). If the running be continued at a constant speedthe oxygen intake also remains constant thereafter-or almost constant-till the end of the exercise (Fig. 3,Curve 1.) ; the subject is in what we may call a" steady state." This state corresponds to a constantconcentration of lactic acid in the muscles, constantowing to a balance between formation and removal.As the exercise, however, is continued, the lactic acidpresent in the active muscles gradually passes, bydiffusion, into the blood and thence to other parts ofthe body. This is probably one explanation of thefatigue resulting from long-continued, moderateexercise, a matter now being more fully studied byLupton and Long. The oxidative removal of thelactic acid formed in one muscle may in this manneroccur in other distant muscles by its passage, via theblood, from the one to the other. As Barr in New Yorkhas found, the venous blood from a resting muscle,during the vigorous activity of others, may containless lactic acid than the arterial blood coming to it.Indeed, in this sense it is possible to recover in one’sarms from exercise taken in one’s legs ! This maybe an important factor in recovery from vigorousexercise taken by small portions of the muscularsystem ; it cannot have much effect in severe generalexercise.

It is to be noted that an apparent " steady statemay occur, during muscular exercise, in which theoxygen intake is constant, which is not, however,really " steady " at all; there is a continual onset offatigue. The oxygen intake may attain its maximum(Fig. 3, Curve II.) and remain constant merely becauseit cannot go any higher (e.g., to Curve III.) owingto the limitations of the circulatory and respiratorysystem. Such a condition causes an accumulation oflactic acid in the muscle and can end only in completeexhaustion.

. RECOVERY.

When the exercise terminates the lactic acid in themuscles must be removed and oxygen must be takenin to provide the necessary energy. The lag in theoxygen intake at the beginning of exercise, duringwhich the lactic acid was concentrating, must becompensated by an extra intake afterwards when it isdiminishing again. After a short bout of moderateexercise (Curve 1.) the oxygen intake falls in a periodof five to ten minutes to its resting value. Aftersevere or prolonged exercise (Curve III.) it may bean hour before the oxygen intake is normal again.The total amount of oxygen used in the recoveryprocess may be measured by collecting the whole ofthe expired gases over any desired interval, by anestimation of the total oxygen used in that interval,and subtraction of the amount of oxygen which thesubject would have used had he remained throughoutat rest.

" OXYGEN REQUIREMENT."It is desirable here to introduce a new term

-namely, the " oxygen requirement " of exercise.If the exercise be very mild (Fig. 4), then the oxygenrequirement may be met by the actual oxygen

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intake once the steady state has been attained.If, however, the exercise be severe the oxygenrequirement cannot be met, even when the heartand lungs have attained their maximum activity;

if the exercise be persisted in, the body necessarilyincurs what we may call an oxygen debt. Were itnot for the fact that the body is able to obtainits energy in this way, by using its necessary oxygenafterwards, severe exercise would be impossible inman. We should never be able to run upstairs, orto run on the flat at more than eight or nine milesan hour. We can do so only because Nature hasprovided us with an arrangement, like an accumulatorwhich can be run down at a very high rate, as instarting a car, and then must be recharged slowlyafterwards.The oxygen requirement of a given type of exercise,

or of a given isolated movement or series of move-ments, can always be measured. The oxygen require-ment may be much higher than any possible oxygenintake. If, however, the movement be carried outonly for a short time, and the total oxygen used duringit, and in recovery from it, be measured, then the totaloxygen so found is the requirement of that piece ofexercise. In this way it is possible to study theenergy requirement of even the most violent anddiscontinuous movements. To take an example,Lupton has measured the maximum efficiency ofthe process of climbing a staircase ; not for theintrinsic interest of that process, but in an endeavour

Ito show that there exists, for many muscular move-ments, a certain optimum, rate. IThe subject ascends the staircase i

once, at any required speed varying Ifrom very slow to extremely rapid. IThe oxygen used during the climb Iand in the succeeding 20 minutes, iafter subtraction of the resting ivalue for the same time, gives ’,the oxygen consumption produced Iby the exercise. This decreases at I

Example of " oxygen requirement." Rest 200 c.cm./min. ; min. exercise ; totaloxygen during exercise and in sutsaquent l4t min. (recovery assumed com-plete) = 10 litTes. Oxygen consumption due to the exercise 10 - 15 x 0’2 =7 litres = 14 litres per min. requirement.

Example of "oxygen debt." Rest 250 c.cm./min.; exercise; total oxygen in 32 min.following exercise =18 litres; subtract resting consumption 32 min. = 0’25 x 32 =8 litres. " Oxygen debt = 18 - 8 = 10 litres.

first as the speed is increased, and then increases again,showing that there is indeed an optimum speed.

This existence of an optimum speed does not occurin all types of exercise. In running the oxygenrequirement increases continuously as the speedincreases, though the actual oxygen intake reaches amaximum beyond which no effort can drive it.Once the oxygen requirement is larger than theoxygen intake (Fig. 3), a steady state is no longerpossible, and fatigue ensues more or less rapidly.

ATHLETIC RECORDS.Some of the most accurate, the most consistent,

physiological data available are contained, not inbooks on physiology, not even in books on medicine,but in the world’s records for running different

norizoniuai msmnces. jn one

plots the average speed atwhich the record was made,against the length of the race(compressed in some manner-as by taking its logarithm— ’to bring all the points onto the same diagram), thenLo IoIle same LUara111), Mien

a curve (Fig. 5) of almost perfect smoothness isobtained, in which a few points only lie just belowthe curve. These latter are for the races in whichathletes have not been so concerned to break therecord as in the rest. The relation shown in thecurve may be accepted practically as a natural constantfor the human race ; it would require almost a super-human effort to change one of the points by 2 per cent. ;and it is interesting to consider what determines theshape of this relation. At very short distances thespeed is constant; it is the maximum which a mancan attain, though it falls off a little as the accumula-tion of lactic acid in the muscles affects their speed ofrelaxation. At very long distances the speed againtends to become constant, practically a steady stateto be attained. It is determined by the maximumamount of oxygen which the athlete can take in,to provide his muscles with their necessary energy,and the economy with which he uses it. Speed atintermediate distances is determined, partly by themaximum oxygen debt which the body can incur,partly by its maximum oxygen intake. We assume,of course, that we are dealing with a man in perfectcondition, highly trained to carry out his movementsin the most economical manner possible, ready andwilling in a race to exhaust himself completely.In the magnitude of the oxygen debt, that is in theconcentration of lactic acid which his muscles cantolerate, we have what we may regard as a man’s" capital." In his oxygen intake, determined by thecapacity of his heart and lungs, we have what we mayregard as his " income." In a race an athlete will

finish-if he can, if the race be not too short-withthe whole of his reserves gone, having spent bothz " capital " and " income " completely. In a shortrace, therefore, he can spread his " capital " over ashorter time, he can expend energy more rapidly than

he can in a long one ; the form ofthe curve is determined mainly bythese factors.

"OXYGEX DEBT.’’

Recently we have made a num-ber of estimations of ’’oxygendebt." The most striking are

those (a) in which 23 seconds ofexercise led to a debt of 8-7 litres,(b) running for 33 minutes at amedium speed only of 7-9 litres,and (c)

" standing running " withextreme violence for 4 minutes of18-7 litres. The larger valuesmean enormous amounts of lacticacid accumulated in the body;how can this acid be tolerated ?Inside the muscle are three alkaliescapable of neutralising the acid,and the hydrogen-ion concentra-

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tion in the active muscle does not rise very far solong as the amount of these alkalies is adequate. Itwould seem probable that the limit to which it is

possible to press a muscle is determined by the

amount of alkali within it capable of neutralising theacid product of its activity.

CO2 ELIMINATION AND RETENTION.This sudden production of acid, as pointed out above,

is the explanation of the large amounts of CO thatcome off during the exercise (Fig. 6, lower half). Whenthe lactic acid is removed in recovery, the samequantity of C02 must be retained as was originallyeliminated; sodium lactate must become sodiumbicarbonate again. Consequently, we find very lowrespiratory quotients in the later stages of recovery.The C02 retained is a measure of the lactic acid gotrid of. The oxygen used in recovery is a measureof the carbohydrate (or lactic acid) oxidised. The com-parison of the two enables us to determine in man the‘‘ efficiency " of recovery. Again, we find that atmost a small fraction of the lactic acid has beenoxidised, the value determined for the " efficiency "of recovery is almost identical with that found inthe case of isolated frog’s muscle ; a sufficient rewardfor the faith that Nature isconsistent. I ^

Direct Measurement of LacticAcid.

During and after exercise lacticacid occurs in the blood ; duringthe steady state of continued exer-cise this lactic acid accumulates toa constant concentration char-acteristic of the violence of theexercise. In my last lecture Ishowed that the speed of therecovery process depends upon themagnitude of the breakdown fromwhich recovery is necessary. Therate of recovery, given an adequatesupply of oxygen, is proportionalroughly to the square of the con-centration of lactic acid in theactive muscle. The lactic acid isa sensitive governor of oxidation.If we regard the resting oxygenconsumption of man as being dueto recovery from very smallamounts of exercise, slight bodilymovements, movements of heartand lungs, muscular tone, thenror tour times tne oxygen consumption, sucn as

occurs in a steady state of ordinary walking, weshould expect not four times the lactic acid con-

centration in the blood, but only twice; for 16 timesthe oxygen consumption-the limit approached

during hard exercise-we should expect not 16times, but four times the lactic acid concentra-tion in the blood. Recent experiments by Long, stillonly preliminary, tend to some degree to confirm this.expectation. It will be a very fortunate thing forthe body if, when we take 16 times as much exercise,the lactic acid concentration in our blocd only risesfour times ; it would have been very awkward had itbeen the other way round t It would seem almost aprovision of Nature, an adaptation to a requirement,only that it is difficult to conceive how even evolutioncould have evaded the laws governing bi-molecular reac-tions. Perhaps it merely took advantage of one whichhappened to be available. The fact, in any case, is aninteresting example of the application to man of one ofthe by-products of experiments first performed on frogs.The lactic acid, however, is more interesting when

we are not dealing with the steady state. After verysevere exercise the lactic acid in the muscles cannot fallvery rapidly owing to the inadequacy of the oxygensupply. It diffuses out, therefore, into the blood andall round the body. It reaches its maximum in theblood some ten minutes after it has attained itsmaximum in the muscles (Fig. 6, upper half). Hencethe maximum in the blood is lower than in the muscles.At the particular moment, however, when it is at itsmaximum in the blood, we may be sure that it is thesame in the muscles ; equally it is certain to be thesame in both at the end of recovery, when bothare becoming constant. It is possible, therefore, by adirect analysis of lactic acid in the blood to ascertainthe concentration in the muscles at two moments :(1) about ten minutes after exercise, and (2) towardsthe end of recovery. By such direct analyses it ispossible to determine directly-if somewhat roughly-the amount of lactic acid which has disappeared in therecovery process. This may be compared, as in thecase of the lactic acid calculated from the CO 2retention, with the oxygen used in that removal, andit is found, as in the frog’s isolated muscle, that theacid is not oxidised ; only about one-sixth of theoxygen is used which would be required were allthe lactic acid broken down to C02 and water. Thesame ratio for the " efficiency " of recovery is attainedin man as in the isolated muscle.

FACTORS AFFECTING SPEED OF RECOVERY.

The speed of the recovery process depends in ahealthy man on the oxygen supplied to the active

muscles. This is limited by two factors : first, thetotal oxygen that can be taken through the lungs intothe blood and circulated by the heart; second, thelocal circulation to the part involved. Many observa-tions have been made of the oxygen intake of a man

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undergoing various forms of severe muscular exercise.The highest value recorded while breathing air is4-2 litres per minute ; breathing 50 per cent. oxygen, ]very nearly six litres has been reached. The only ipossible reason why more oxygen can be taken in, 1when breathing oxygen, is that the blood is not ]completely saturated during very severe exercisewhen breathing air ; the greater saturation, however,of the coronary blood, when breathing oxygen, maythen result in greater cardiac activity. The magnitude 4of the oxygen intake is determined mainly by thecapacity of the heart, and I give later a calculationshowing what this number means in heart output.The other factor determining the speed of the recoveryprocess is the local supply of blood to the musclesactually involved in the work. Lindhard showedthat in such exercise as holding the body with armsbent, on rings in a gymnasium, the blood-supply tothe active muscles of the arm is almost completelycut off. The whole of the oxygen required had to beused after the exertion was over. In running the supplyof blood to the active muscles is particularly easy,as they are never rigid and their movements are rapid.In rowing the supply of blood to the muscles mustbe much more difficult; the muscles are rigid forlonger periods, and their movements are relativelyslow; they exert less pumping action on theveins; consequently rowing places a greater strainon the heart.

Heart Output from Oxygen Inta7,ce.The values of the oxygen intake during severe

exercise allow a striking-if approximate-calculationof the output of the heart. Assuming, as was the casein the subject who consumed 5-9 litres of oxygen perminute, an oxygen capacity of 21 c.cm. per 100 c.cm.of blood, and an average utilisation coefficient of75 per cent. (a value as high as has ever been recorded),then the actual oxygen taken in must have required37.5 litres of blood per minute to carry it. This amountof blood has been ejected from the heart twice, fromthe right side once, and from the left side once; Ialtogether, therefore, 75 litres of blood-about

I

17 gallons, about 120 times the heart’s own volumehave been pumped out in every minute. Evenassuming a utilisation coefficient of 100 per cent.,56 litres (12t gallons) of blood must have been pumpedtogether from the two sides of the heart. Comparethese volumes with the amount of water which a bathtap can pour out in a minute, even when turned fullon ! In such exercise the heart-rate-recorded witha string-galvanometer--is about 180, which meansthat each side of the heart ejects some 200 c.cm. perbeat. There is no possible flaw in the argument orcalculation, otherwise it would be difficult to believethe conclusion. It is little wonder that the heartsometimes cannot stand the strain.

Energy Requirement of Heart.It is possible, by an approximate calculation, to

determine the oxygen consumption of the heartduring such exercise. The calculated output of blood,multiplied by the blood pressure, gives us the workdone ; assuming an efficiency of 20 per cent., which isa high value under such conditions, the total energyused by the heart can be calculated. The provisionof this energy requires the consumption of oxygen, ,,and it would appear that the oxygen requirement ofthe heart during such exercise as that described aboveis about 300 c.om. per minute-about half its ownvolume. Assuming a utilisation coefficient of 75 percent. and an oxygen capacity as before, this requirestwo litres of blood to pass through the coronaryvessels of the heart per minute. This volume ofoxygen, aetually used by the heart, is equal to thatrequired but never obtained by voluntary muscleduring the most violent exercise. The muscle hasto stop within a minute, owing to oxygen-want;the heart, however, owing to its better oxygen-supply, when the coronary circulation is efficient,is able to keep up an output of this order for longperiods.

Other Factors in Recovery.The recovery process depends also on other factors.

In my last lecture I showed how in the isolated muscleit depends on the hydrogen-ion concentration. Deepbreathing, therefore, sweeping away the CO2 andkeeping the body alkaline, may be essential to thequickness of the recovery process. It must dependalso upon the presence of oxidative catalysts. Recentwork by Hopkins has shown the presence in tissuesof a di-sulphide compound, glutathione, which actspractically as an oxidative catalyst. The discoveryof similar substances has been made independentlyby Meyerhof. I need not discuss the mechanism ofglutathione now, otherwise than to say that in itsdi-sulphide form it seems to act as a hydrogen acceptorand so to liberate oxygen for the oxidation of somethingelse, and then itself to be oxidised, by molecularoxygen or otherwise, to its original di-sulphide form.

- S-S- + H2O —s. -S-B:+H:-S-+0-S-H + H-S- + 2 O - -S-S- + H2O.

Recent experiments by Hartree have suggested thatan isolated muscle left in Ringer’s solution has itsspeed of recovery diminished ; this may be a timeeffect, but it is possibly due to the washing away ofoxidative catalysts from the muscle by the Ringer’ssolution surrounding it. Clearly the experiment mustbe tried on muscles carefully perfused before use. Itis likely, in any case, that the oxidising faculty oftissues will vary from individual to individual. Itmay be, therefore, that important divergencies fromthe normal will be found in persons suffering fromvarious forms of dyspnoea, in respect of their oxidativemetabolic power. Possibly athletes, and peopleaccustomed to heavy work, will develop this side oftheir metabolic activities. Recent work by MissRobinson in Hopkins’s laboratory has shown thathaemoglobin has a very distinct catalysing power inthe oxidation of unsaturated fats. The dyspnoea sooften associated with anaemia may in some cases bedue to the absence not only of an adequate oxygen-supply, but of an adequate amount of some oxidisingcatalyst. Recent work by Warburg and his colleagueshas shown that many forms of biological oxidationprobably occur as surface phenomena, catalysed byiron atoms embedded in the surface ; the absence ofthe iron, or its removal from activity by physical orchemical means, will hinder or prevent oxidation, asalso will displacement of the oxidisable bodies, bynarcotics or other substances, from the active surfaceswhere oxidation goes on. Imperfect metabolism ofiron, excretion of it, its combination with abnormalmetabolites, the displacement of the bodies to beoxidised away from the oxidising surfaces might alllead, therefore, to an imperfect and slow recovery fromexertion, to dyspnoea associated with exercise.

APPLICATIONS.All of us can suffer from dyspnoea and all of us can

exhaust ourselves very rapidly ; the finest athlete inthe world may be almost incapable of movement within60 seconds from the beginning of a race. The samedegree, however, of exhaustion may be produced bya much lower level of exercise, no more rapidly butjust as effectively, in a person of lower oxidativefaculty or with poorer buffers in his tissue. When Iwas lecturing recently in Holland on this subject itwas remarked, after one of my lectures, that it wastypical of an Englishman, when he had found aninteresting bit of physiology, immediately to want toapply it to sport. Perhaps some of you will sympathisewith the motive-there are worse ones-even if it betrue. There is a better motive, however; athletesand healthy men give us the cleanest experiments.If one took a patient from the hospital and made himwork till he could barely move, one could never besure (a) that he had really driven himself to hislimit-it requires an athlete to know how to exhausthimself ; (b) that one would not kill him ; and (c) whatthe cause of his stopping was. With young athletes

, one may be sure-if one knows one’s men-that theyreally have gone " all out," moderately certain of

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not killing them, and practically certain that theirstoppage is due to oxygen-want and to lactic acidin their muscles. Quantitatively the phenomena ofexhaustion may be widely different, qualitatively theyare the same, in your athlete, in your normal man, inyour dyspnoeic patient. You can only observe yourpatient, but you can experiment with your athlete ;you can " try out " on him the facts and theories youhave reached with frogs. There I must leave it, and I,be grateful if the young athletes in their turn cansuggest further experiments on frogs. I should beafraid to try such experiments as I have described onyour patients, and I do not for a moment supposethat they, or you, would let me. The fact, however,that you have done me the honour to invite me togive these lectures is a sign, I am happy to think,that you believe in some future application, to yourown urgent problems, of the study of the recoveryprocess in normal man. Even such experiments asthese may lead, in the end, to the alleviation of humansuffering. After all, it is a much longer trail from asmall portion of a frog to a young athlete, than it isfrom him to a patient in a hospital. Faith in theconsistency of nature has been rewarded on the onetrail; it cannot fail to be rewarded on the other.

CHLORIDE METABOLISM IN RONTGENRAY THERAPY.

BY A. T. CAMERON, B.SC., F.I.C., F.R.S.C.,PROFESSOR OF BIOCHEMISTRY, FACULTY OF MEDICINE,UNIVERSITY OF MANITOBA; ASSOCIATE IN BIOCHEMISTRY,

WINNIPEG GENERAL HOSPITAL;AND

J. C. MCMILLAN, M.D. MANIT., F.A.C.P.,LECTURER IN RADIOLOGY, DEPARTMENT OF INTERNAL MEDICINE,

UNIVERSITY OF MANITOBA; MEDICAL DIRECTOR, X RAYDEPARTMENT, WINNIPEG GENERAL HOSPITAL.

Dodds and Webster 1 have recently summarised theliterature of radiation sickness in THE LANCET, andSchmitz 2 at the same time published a similarsummary in Radiology. The three cases of sicknessexamined by the first-named authors showed nometabolic disturbance. Schmitz’s summary is incon-clusive as to the cause of the sickness. Dodds andWebster do not appear to have seen a paper by Coriand Pucher 3 which appeared in September last, andin which the results appear to indicate that Rontgenradiation produces a definite chloride retention, moremarked when sickness occurs. Since they themselvesobtained a transient increase in chloride excretion,while our own results confirm those of Cori and Pucher,it seems desirable to give a brief preliminary accountof our work, which is directed primarily to the problemindicated in the title to this note.The only other paper that we have been able to

find bearing directly on this problem is by Schlagint-weit and Sielmann, who state (we have only seen anabstract) that in severe disturbances following largedoses of X rays there is a decrease in the chloridecontent of the blood, and that sodium chloride givenin any form gives full relief. Dodds and Webstergive no details as to the X ray dosage they employed,and we are unable to suggest an explanation for thedisagreement between our results and theirs.We have studied so far 12 cases. The first three,

a case of sarcoma of the superior maxilla, a case ofuterine fibroid, and one of carcinoma of the uterusinvolving the whole pelvis, were studied- especially tosee if there was any change of pH value of the urinewhich might indicate an acidosis. No such change wasobserved in these or the later cases ; we have observed i

no production of ketonuria : and the second and thirdcases were examined specially for lactic acid excretion,and no increase was found. Our evidence tends toshow no production of acidosis.

Conclusions as to Effects of Rontgen Ray Therapy.At this time we saw Cori and Pucher’s paper, and

the remaining nine eases have been examinedespecially with a view to testing the accuracy of

their results with chloride excretion. Our data will bepublished in full shortly. We do not yet regard themas sufficient to permit definite statements, but wehave drawn certain tentative conclusions, and wequote below several abbreviated case reports supportingthese conclusions, which are :-

1. Rontgen ray therapy in massive doses producesa definite lowering of urine excretion (confirmation ofDodds and Webster) and a definite chloride retention(confirmation of Cori and Pucher) when the upperabdomen is rayed. Radiation of other parts of thebody produces less effect.

2. With radiation of the upper abdomen, where theprevious chloride excretion is low, the tendency tosickness, other things being equal, is greater.

3. Preliminary feeding of sodium chloride daily, sothat the chloride excretion is raised to ten or moregrammes per day before treatment is commenced, withcontinued administration during treatment, preventsor lessens the sickness.

4. The blood chloride is not invariably affected,though sometimes the percentage is lowered.

Total nitrogen and phosphate results were tooinconstant to permit conclusions, but there was usuallya slightly greater nitrogen excretion during theradiation period.

Case Reports in Support of <7oMcso?t.s.CASE I.-C. L., male, aged 58, with carcinoma of the

first part of the transverse colon, the mass extendingupwards in the region of the gall-bladder, with markedglandular involvement, was given X ray treatment con-fined to the right side of the abdomen. Two 13 cm. portsof entry were used, one anterior and one posterior.150 k.v. with filters consisting of 0’75 mm. Cu and 1 mm.Al were used on the anterior port, and 200 k.v. with 1 mm.each Cu and Al on the posterior port. In all 16 m.a. hourswere given by the fractional method, in six treatmentsspread over eight days. The chemical findings are shownin Table I.

TABLE I.

The patient was not sick and ate well throughoutthe treatment. The results show a definite chlorideretention, but the lowest excretion figure (penultimateday of treatment) was still 3-82 g.CASE 2.-Mrs. A. M.,aged 40, with carcinoma of cervix,

had had treatment six months previously with radium.Deep X ray therapy was advised to the whole pelvis. Hergeneral condition was good. The " cross-fire " method offractional dosage was entployed, using two 10 cm. portsanteriorly and one 13 cm. port posteriorly. The factorsused were 200 k.v., and a filter of 1 mm. each Cu and Al,with target skin distance 50 cm. In all 18 m.a. hours weregiven, divided into six treatments spread over eight days.The chemical findings are shown in Table II.

TABLE II.

The patient ate well throughout the treatment andwas not sick. There was at most a slight transientlowering of urine volume and chloride excretion.The effect was much less than in Cases 1, 3, and 5 ;the upper abdomen was not rayed.CASE 3.-H. P., aged 57, had a mass in the epigastrium,

and X ray examination with a barium meal showed alarge gastric filling defect, involving the lower two-thirds ofthe antrum of the stomach, and suggesting an extensivenew growth, with possible involvement of the liver. He