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[DEC. 26, 1936

ADDRESSES AND ORIGINAL ARTICLES

CARDIAC FAILURE*

BY BASIL PARSONS-SMITH, M.D., F.R.C.P. Lond.PHYSICIAN TO THE NATIONAL HOSPITAL FOR DISEASES OF

THE HEART, LONDON

I HAVE selected cardiac failure as the theme ofthis lecture for two reasons: first, because it isliable to develop in every case of cardiovascular disease,and secondly, because the subject is one on whichthere has been, and still is, a diversity of opinion.

Of the earlier theories that propounded by JamesHope15 in the early part of the last century deservesspecial mention because it provides the first authenticbasis of the so-called back-pressure type of heartfailure ; his introductory remark is of considerableinterest :-

" Order of succession in which the several compartmentsof the heart are rendered hypertrophous by an obstaclebefore them in the course of the circulation." "

and the following extracts are noteworthy:-"As an obstacle to the circulation operates on the

heart in a retrograde direction, the cavity situatedimmediately behind it is the first to suffer from itsinfluence.""When the distending pressure of the blood pre-

ponderates over the power of the (left) ventricle, its

contents, from not being duly expelled, constitute anobstacle to the transmission of the auricular blood ;hence the auricle becomes over-distended, and the obstruc-tion may be propagated backwards through the lungs to theright side of the heart and there occasion the same seriesof phenomena."" When the mitral orifice is contracted ... the left

auricle having to struggle against the contracted valvein front, and also to sustain the distending pressureof the blood flowing in from the lungs, invariably becomesthickened and dilated; the engorgement, extendingbackwards through the lungs to the right ventricle,occasions its hypertrophy and dilatation, the lungs suffer-ing in pre-eminent degree."

" When the impediment to the circulation is primitivelyseated in the lungs, the right ventricle, situated immediatelybehind them, is the first to experience its influence; andwhen the cavity is so far overpowered by the distendingpressure of the blood as to be incapable of adequatelyexpelling its contents, the obstruction extends to theauricle." "

" Obstruction in the right auricle, whether from thisor other cause, presents an obstacle to the return of thevenous blood and therefore ultimately causes retardationthroughout the whole venous system ; nor is this all;for the retardation is propagated throughout the capillariesto the arterial system and thus at length returns in acircle to the heart."

Hope’s classical observations were subsequentlymodified by the teaching of William Stokes, whoemphasised more particularly the supervention of

myocardial incompetence in valvular heart affections,and thus incidentally originated a theory which wasdestined for further development by cardiologists ageneration after his time.A brief extract from his treatise on Diseases of

the Heart and Aorta 25 summarises the viewpointwhich Stokes adopted in regard to cardiac failure :-

" It too often happens," he said, " when the existence of

a valvular disease is determined, that great labour isexpended in ascertaining the exact seat and nature of theaffection. Long and careful examinations are made to

* The St. Cyres lecture of the National Hospital for Diseasesof the Heart, London, delivered at the Royal Society ofMedicine on July 8th, 1936.

determine whether the disease exists at the right or leftside of the heart ; whether it be a lesion of the mitral,tricuspid, or the semilunar valves ; a contraction ; an

ossification ; a permanent patency or warty excrescence.Now, though in some, we might say in many cases, thesecases may be resolved with considerable accuracy, it isalso true that in a large number their determination is ofcomparatively trifling importance ; and the two greatpractical points to be attended to are, first whetherthe murmurs proceed from an organic cause, and next,what is the vital and physical condition of the muscularportions of the heart ; for it is upon these points thatprognosis and treatment must entirely depend."

" The practical physician, having satisfied himselfthat a valvular disease exists, will not devote too muchtime in ascertaining its exact nature ; but he will examineinto the vital and mechanical state of the heart’s cavities.He will ascertain the amount of vigour of the heart,whether its force is above or below the natural standard."

Backward or Forward Failure

The above extracts deserve careful considerationbecause they constitute the original conceptions oftwo opposing theories, the one characterised byso-called forward failure, the other by back-pressurephenomena. It t is common knowledge that the

original doctrine of back pressure was universallyadopted in this country, and that all the leadingcardiologists continued to approve its significanceuntil the early part of the present century. Aboutthat time the general trend of opinion underwentmaterial revision, and cardiac failure began to beassessed in terms of myocardial incompetence, its

derangement being more especially concerned withimpairment in the efficiency of the heart’s drivingpower and output rather than with the developmentof back-pressure effects as described hitherto. Thelate Sir James Mackenzie was a staunch advocateof the forward-failure hypothesis; in his view aninsufficient blood-supply to the organs was theessential factor underlying the development of

circulatory incompetence and all the signs and symp-toms of failure indicated defective ventricular out-put. He assumed, in other words, that breathless-ness, dropsy, engorgement of the liver, and renalcongestion were accounted for by deficient cardiacoutput into the systemic circulation, and that a

similar discrepancy in the lesser circuit was respon-sible for pulmonary cedema. Mackenzie’s viewscoincided in broad principle with those of his con-temporaries in this country, and the theory of for-ward failure still meets the approval of our modernwriters. In brief, the general consensus of opinionassociates the development of failure with diminu-tion of the cardiac output to such an extent thatthe blood-supply to the tissues becomes insufficientfor their requirements ; but there are also otherfactors relative to variations in the blood chemistryinduced by the retarded flow in the capillaries, bywhich the carbon dioxide pressure and the hydrogen-ion concentration in the tissues and respiratorycentre are abnormally raised, and the oxygen contentbecomes relatively deficient for the normal processesof metabolism. The above principles have beensummarised by Sir Thomas Lewis as follows:-

" Breathlessness, the first indication of failure, is to beascribed to a deficiency in flow of aerated blood to thehead and neck."" When the output declines blood begins to collect on

the venous side and the patient manifests signs of congestedveins, enlargement of the liver, cyanosis, scanty urine,ascites, dropsy of the lower members and congestion andoedema of the lungs."

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The physiological principles were ably interpretedby Starling 24 in his 1915 Linacre lecture, and thoughhis observations were based on experimental evidencetheir significance in clinical medicine cannot be denied.He emphasised the adaptability of the heart to the

requirements of the body as a whole ; he showedthat, within physiological limits, the outflow remainedconstant whatever the arterial pressure, and thatwith an increased venous inflow the outflow was

pari passu augmented; he found moreover thatsimilar powers of adaptation obtained in heart-lungspecimens which were so prepared as to imitate disease ;and he was of opinion that the compensatory mecha-nism, as such, originated in the muscle-fibres them-selves, the results being similar whether the nervousconnexions were severed or intact ; he regarded alengthening of the muscle-fibres as the first mani-festation of cardiac fatigue ; and he recognised anincreased contractile energy in direct proportion tothe fibre lengthening, the cardiac output remainingconstant at the expense of the greater diastolicvolume and the raised venous pressure which as arule characterise the failure process.

Deficiency of OutputA series of valuable researches in recent years

make it essential that we revise our views to someextent in regard to the significance of output defi-ciencies in cardiac failure. Various methods for theestimation of output have from time to time beenadopted and much has been written on the subject ;but a brief mention of certain of the typical recordswill suffice here.

Kroetz 19 studied 16 patients by the acetylenemethod of Grollman, his chief conclusions indicatinga slightly reduced volume output in compensatedcases which was not appreciably increased when

congestive failure supervened. Eppinger, von Papp,and Schwarz 6 investigated 10 decompensated patientsby the oxygen-Fick method ; in 5 of these the cardiacoutput was above and in the remainder withinnormal limits. Eppinger 5 and his co-workersrecorded a further series of 9 decompensated cases,6 of which showed outputs above and 3 below thefigures of their normal controls.A further series of cases was published by Harrison

and his colleagues 10 in 1934, and their findings areparticularly important because they were obtainedby the improved acetylene method introduced byGrollman.8 The analysis included 27 patients withuncomplicated cardiac disease, 19 with congestivefailure, and 18 normal controls, and the results maybe briefly summarised as follows z

(1) The output per minute of the heart, though as a rulesubnormal in cardiac patients, may in certain instancesreach the normal range.(2) The output range of uncomplicated cardiac casesis similar to that of cases with congestive failure, andrelief from congestive manifestations may be associatedwith an increase, a decrease, or no change in the cardiacoutput per minute, though as a general rule obviousimprovement is associated with a slight rise in the outputper beat.

(3) Remedial measures which produce obvious benefitin patients with congestive heart failure do not as a

rule increase the cardiac output.

Further factors which have been intimately asso-ciated with the diminished output theory include avariety of disorders of the blood chemistry, thedevelopment of an increased hydrogen-ion concentra-tion, and alterations in the oxygen and carbondioxide pressures. Recent investigations have largelydiscounted the significance of these changes. The

researches of Fraser,7 who reviewed the subject atlength in his 1927 Goulstonian lectures, were basedon analyses of arterial blood from patients withcardiac disease, and his conclusions were briefly asfollows :-

(1) The oxygen saturation of the arterial blood incardiac failure remains within normal limits unless

pulmonary complications coexist.(2) In cases with pulmonary disease and in cases of

severe failure with secondary changes in the lungs thecarbon dioxide pressure and also the hydrogen-ion concen.tration in the blood may be above normal limits.

These observations have been confirmed and

amplified by the studies of Cullen and his co-workers.3They obtained specimens of blood from the medianbasilic vein before and after mild exertion whichincreased the ventilation 100 per cent. or more, and theyfound that neither the cardiac patient nor the normalcontrols showed any significant changes in the oxygencontent, the carbon dioxide pressure, or the hydrogen.ion content of the blood. Very similar results wereobtained by the analyses of arterial blood and ofspecimens taken from the internal jugular veinbefore and immediately after exercise, the onlyvariations being a slightly lowered carbon dioxidepressure and a slightly raised oxygen pressure, bothin all probability the outcome of the increased venti-lation induced by the test exercise. It seems fairtherefore to assume in the light of these investigationsthat the increased ventilation which develops withmoderate exertion in cardiac patients cannot beattributed to chemical defects in the cerebral bloodstream ; we may summarise the above conclusionsas follows :-

(1) The output per minute of the failing heart, thoughfrequently defective, may be within normal limits.

(2) Inability to increase the cardiac output may some-times be a responsible factor in the symptom-complexof failure, the maximum oxygen intake being subnormal.

(3) Except in its terminal stages the failure symptomsof cardiac disease are not related to alterations in the

oxygen, carbon dioxide, or reaction of the venous or

arterial blood.

A reasonable inference from these statements isthat the manifestations of cardiac failure cannot beentirely accounted for by the diminished-outputtheory or by alterations in the blood chemistry;other factors must obviously be concerned in the

process and evidence is gradually accumulating thatcertain of these may be essentially back-pressurephenomena.

Vital Capacity and Respiratory ReserveBreathlessness, one of the standard symptoms of

a failing myocardium, may be mentioned as a suitableillustration ; and, passing over for the moment allsuch changes in the blood chemistry as are heldresponsible for its development in the severe andterminal stages of heart disease, we may considerits significance in early and uncomplicated cases.

As the result of extensive investigation, both experi-mental and clinical, we are nowadays in a positionto associate the diminished respiratory reserve ofcardiac patients with two developments of funda-mental importance-namely, decreased vital capacityand increased rate of ventilation. Though intimatelyassociated, each of these merits special reference inthe present context. The significance of a decreasedvital capacity was clearly demonstrated by FrancisPeabody 22 and, in collaboration with his colleaguesDrinker and Blumgart,4 he correlated its develop-ment with the pulmonary congestion and diminishedpulmonary expansion experimentally produced in

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animals by partial occlusion of the pulmonary veins.He also pointed out the intimate relationship, in

patients with heart disease, of the vital capacity tothe degree of the dyspnoea, the latter as a generalrule varying in inverse proportion to the extent ofthe former.These findings not only emphasise defects in

the vital capacity of cardiac patients but serve

to show its close association with pulmonary con-gestion. In regard to the second development-viz., the increased rate of ventilation-it is commonknowledge that both the volume and the rate ofbreathing are increased in conditions of cardiacfailure, and it was shown by Harrison and his col-leagues 2 that congestion of the lungs is largelyresponsible for these respiratory variations. Theirinvestigations were based on the experiments of

Legallois,2° who observed a diminished rate and anincreased amplitude of breathing after vagal section,and on the experimental findings of Hering andBreuer,13 who showed that artificial pulmonaryinflation induced expiratory movements which failedto develop following bilateral vagotomy.

It appeared reasonable to suppose that cardiacdyspnoea might under certain circumstances dependupon nervous reflexes originating in the lung tissue,and this hypothesis was substantiated in due courseby Harrison and his colleagues. 9 They devised atechnique which made it possible to produce anydegree of pulmonary congestion at will and with itthey noted a definitely increased rate of breathingafter the introduction of blood into the lung vessels,this effect being absent moreover after bilateral vagalsection. In, a further series of experiments theydemonstrated a definite inter-relationship betweenthe respiratory rate and alterations in the venous

pressure, it having been previously ascertained bySchott 23 that exertion brought about a greater risein venous pressure in patients suffering from cardiacfailure than in normal controls. Of these experi-mental findings the following are of material interesthere :-

.

(1) That a rise in venous pressure, induced by a venoustransfusion or by the inflation of a small rubber ballooninserted through the external jugular vein into the rightauricle, causes a well-marked increase in the rate of

breathing.(2) That for the increased rate of breathing so produced

it is essential that the vagal connexions shall be intact,no such variation occurring following their section.

These results may be interpreted as proving thereflex nervous origin of increased respiration-ratespromoted by elevations of venous pressure, and theauthors suggest that the reflex stimulation ariseseither in the heart or the great veins, the afferentpathway being by the vagus nerves.The above investigations may be summarised as

follows. In the advanced stages of heart disease andafter severe exercise there may be discrepancies inthe cardiac output and in the blood chemistry whichamply explain the failure symptoms ; but suchchanges are not manifest in the earlier uncomplicatedstages of the condition when breathlessness andmoderate deficiencies of exercise tolerance are inti-

mately associated with variations in venous pressureand reflex nervous stimuli arising in the lungs, theheart itself, and elsewhere.That the majority of such patients have some

diminution of the vital capacity has been emphasisedby Harrison 11 and other workers ; their unanimousopinion favours pulmonary congestion as the under-lying factor concerned, and it has been clearly shownthat a similar congestion is responsible for the

increased ventilation rates which are observed evenat rest in failure cases and which depend upon vagalreflexes set up in the congested lung tissue. These

processes explain the diminished range of the respira-tory reserve at rest and the further extent of itsdiminution with muscular exercise is equally clearin that there is an exaggerated rise in the venouspressure, with further pulmonary congestion andincreased respiratory ventilation secondary thereto.

Part Played by Back PressureThe above considerations serve to establish the

very material significance of pulmonary congestionin the symptomatology of cardiac failure, more

particularly in regard to the production of breath-lessness which as a rule is the outstanding subjectivefeature of the condition. As previously outlined,widely divergent views have been formulated to

explain these phenomena. According to the forward-failure theory, of which Mackenzie was a staunchexponent, congestion in the lesser circulation indicatesright ventricular failure, just as the comparableconditions of venous stasis in the systemic circulation(cedema, serous effusions, &c.) are manifestationsof left ventricular impairment. These views, how-ever, have been much criticised in modern times and,although it is generally admitted that the effectiveoutput of a failing heart may be limited, the availableevidence, some of which has been alluded to, tendsto suggest that such a development cannot be solelyresponsible for the symptoms. There must obviouslybe an alternative explanation and that which firstcommends itself is the development of back-pressuremanifestations. The fundamental basis of these is anaccumulation of blood in the vascular areas whichdrain in the direction of an affected chamber ; undersuch circumstances the sequence of events is a directconverse to that which characterises the forward-failure state, and in its essential conceptions, therefore,the back-pressure mechanism associates pulmonarycongestion with failure of the left ventricle, andvenous stasis in the systemic circulation withincompetence involving the right heart chambers.

Several well-recognised conditions, notably thefailure syndromes of certain valvular diseasesand hypertensive heart disease, comply with thesestandards, the recognition of back-pressure phenomenabeing amply justified both by the clinical signs andthe post-mortem findings. Of the valvular diseases,mitral stenosis is especially worthy of comment inthis connexion ; as the lesion gradually developswell-marked changes in the circulatory mechanismbecome increasingly obvious.

Back Pressure in Mitral Stenosis

In its earlier stages the outstanding effect ofobstruction at the mitral orifice is engorgement of thepulmonary circuit, which not only accounts for varyingdegrees of deficiency in the vital capacity, but alsofor the vascular complications (e.g., hoemoptysis,infarction, and oedema) which characterise theprogress of the disease. The significance, moreover,of the early reduction in vital capacity is partlyexplained by comparative estimates of its valuesin mitral stenosis and aortic lesions, the averagevital capacity in mitral cases being lower than thatobtaining in the presence of aortic affections ; suchresults, moreover, are understandable in view of thefact that the former are, and the latter are not,associated with back-pressure stasis in the pulmonarycircuit.As might reasonably be supposed, the post-mortem

findings confirm the reduced vital capacity in patients

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with mitral stenosis, and some degree of stagnationin the pulmonary circuit is obviously the outstandingfeature of the disease. The left auricle is alwaysdilated-in extreme cases to a capacity of 20 oz. ormore-and according to most authorities its wall

may be the seat of definite hypertrophy. Varyinggrades of pulmonary congestion and stasis characterisethe disease in all its stages: there is well-markeddilatation of the venous trunks ; the capillaries arewidened and tortuous and there may be extensiveatheromatous changes in the pulmonary artery andits branches. Further manifestations of the back-

pressure stasis include pulmonary fibrosis, embolisa-tion, infarction, areas of broncho-pneumonia, andvarying grades of oedema.

These phenomena provide ample testimony of theretarded circulation and raised pressure which areinduced by obstructive lesions at the mitral orifice;and the back-pressure theory, which appears tooffer a reasonable solution of these processes, is furtherconfirmed by the dysfunction of the right heart whichinvariably develops as the disease progresses. Byreason of the raised tension in the pulmonary circuitsome degree of ventricular hypertrophy is likely tobe an obvious finding and signs of stasis in the rightauricle and systemic venous circuit can usually berecognised more particularly in the later stages.From the foregoing description it is fair to assume

that the manifestations of mitral stenosis chieflyarise from inefficiency of the left auricle, the pulmonarycircuit, and the entire right heart. The left ventricleis actually atrophied in certain cases and this may bethe reason for its deficiency of output as apparent inthe small pulse, the cold extremities, and the tendencyto premature physical fatigue. Otherwise the

sequence of events in mitral stenosis can be summarisedas a progressively developing series of back-pressurechanges primarily affecting the pulmonary circuit,extending later to the right ventricle and to the

systemic venous system, and finally spreading to thecapillaries, where the raised tension is largelyresponsible for oedema and serous effusions.

Heart Failure in Aortic Disease

From the above description the effects of mitralstenosis seem to vindicate the back-pressure theoryof failure ; and confirmatory evidence is not far toseek. Two conditions-viz., aortic valve disease andhypertension-are particularly noteworthy in thisconnexion. Both involve dilatation and overloadingof the left ventricle and in the terminal stages ofboth there are, more often than not, defects in thevital capacity and paroxysmal breathlessness whichmay take the form of orthopncea, cardiac asthma,or periodic breathing. Widely opposed theories havebeen put forward in regard to these respiratoryembarrassments, but nowadays they are generallyattributed to congestion in the lesser circuit andvarying degrees of pulmonary codema, the underlyingmechanical defect being back pressure from an

incompetent left. ventricle which, by failing to disposeadequately of its venous load, is directly responsiblefor inducing stasis in the pulmonary vessels. The

significance of vascular congestion in the lungs hasbeen amply emphasised, its outstanding effects being(1) a reduction in the vital capacity and (2) anincreased rate of ventilation, which are togetherresponsible for the various forms of breathlessnessoccurring in left ventricular failure and which dependfundamentally upon nervous, mechanical, and chemicalderangements. The idea of a nervous origin ofbreathlessness is based upon well-recognised reflexeswhich are transmitted centrally from various sources,

including muscles in activity, lung tissue in a stateof congestion, and certain of the great veins, possiblyeven the heart itself when conditions of high-pressurestasis develop in full form. Otherwise the breath-lessness of left ventricular failure in its terminal

stages may depend upon a variety of mechanical andchemical complications. The mechanical ones include

hydrothorax, ascites, and pericardial effusions, allof which tend to raise the venous pressure, to diminishthe vital capacity, and to increase the ventilation;while in the same category mention should also bemade of the mechanical effect per se of a highlyplaced diaphragm irrespective of the immediate causeof its displacement, and of the respiratory obstructioncaused by oedema of the bronchial walls in conditionsof advanced pulmonary stasis. The chemical com.plications include changes in the hydrogen-ionconcentration of the blood and variations in itsoxygen and carbon dioxide contents, either of whichmay intensify the breathlessness of circulatory failurein the final stages.

Chronic Pulmonary DiseaseIn conclusion brief reference may be made to the

question of heart failure in chronic disease of thelungs. The time-honoured belief, which survives inmost of the modern text-books, is that conditionssuch as emphysema promote vascular changes whichobstruct the blood flow in the lesser circuit and areultimately responsible for dilatation and failure ofthe right ventricle, as evidenced by venous stagna-tion in the hepatic and portal systems, dependentoedema, and serous effusions. Recent investigations,however, tend to discount the practical significanceof the above-mentioned theory, for it has been shownexperimentally that back-pressure phenomena are

not necessarily found in obstructive emphysema,and that in such a condition right-heart failure is anexceptional finding.These conclusions are based on experimental

research and clinical observation.

Kountz and his colleagues 17 estimated the circulationrate through the lungs of dogs in which emphysema hadbeen artificially induced, and the results they obtainedwere confirmatory of a normal rate of flow through thevessels of emphysematous lungs. Kretz 18 investigatedthe effects of emphysema in experimental dogs and con.cluded that the condition per se could not be held

responsible for hypertrophy processes in the right heart.Heinbecker 12 showed that, with moderate distension ofthe lungs, the rate of blood flow in the pulmonary vesselswas accelerated owing to the straightening of certain ofthe capillaries and possibly also the opening of new ones,and that, when the lungs were further distended, therate of flow was, to some extent, diminished. Alexander,Luten, and Kountz 1 analysed 50 cases of asthma, themajority complicated by varying degrees of emphysema,and found remarkably little evidence of cardiac injury orcirculatory complications.A further communication on the subject has recently

been published by Miller. 21 He refers to the fact that in

patients with extensive pulmonary fibrosis the functionalefficiency of the lungs is often almost unimpaired, and hisexplanation is that, in the absence of such complicationsas congestive heart failure and pulmonary hypertension,the velocity of the blood flow in the lungs remains normal,the capillary alveolar bed being relatively spared by thefibrotic process.

It is obviously impossible to reconcile the abovestatements, which emphasise widely divergent viewsof circulatory disabilities in chronic pulmonarydisease; and final solution of the whole problem mustbe deferred. Meanwhile, however, it may be advis-able to comment briefly on certain of the viewswhich have lately been advanced in regard to the

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incidence and clinical interpretation of so-calledcardio-pulmonary disease.

In a personal communication Clifford Hoyleremarks on the singularly low rate of mortality fromcongestive heart failure in chronic lung disease, andhis estimate-approximately 3-4 per cent.-is espe-cially noteworthy in contrast with those of earlierauthorities, some of whom associated the terminalstages of all chronic pulmonary disease with thedevelopment of right-heart failure. Hoyle furtherstates that when heart failure develops in cases ofchronic lung disease it is of the congestive type, andhe divides the post-mortem appearances into twomain groups : (1) those showing enlargement of theright heart with varying degrees of dilatation of thepulmonary conus, the main pulmonary artery andits branches; and (2) those showing a general enlarge-ment of the whole heart, with little if any dispro-portionate hypertrophy of the right side. The lattergroup is of particular interest because opinion is notyet unanimous about the factor or factors responsiblefor such general enlargement of the heart as occursin chronic pulmonary disorders. Certain authoritieshave suggested peripheral hypertension ; Hoover,14on the other hand, considered that, owing to faultyoxygenation in the lungs, a condition of relativeischaemia developed in the myocardium, and Kountzand his colleagues 17 contend that the aetiology ofthe general enlargement, which often characteriseschronic cardio-pulmonary disease, has not yet beenadequately explained.The above investigations suggest that we may need

to modify the view hitherto adopted in regardto heart failure in chronic pulmonary disease. Ofthe evidence at present available the following detailsare especially noteworthy in the present context :-

(1) Right-heart failure and back pressure phenomenaare rare developments in chronic pulmonary disease.

(2) As a general rule, if the heart is affected in chronicpulmonary disease, both the right and the left ventricleswill be involved in the process.

(3) The later stages of chronic pulmonary disease maybe characterised by certain symptoms which have hithertobeen interpreted as typical manifestations of cardiacfailure. These symptoms include breathlessness, cyanosis,and cedema, the former two being adequately explainedby the diminished vital capacity, the latter (the cedema)by the anoxsemic processes and the raised venous pressure,all of which are incidental to chronic pulmonaryaffections.16

Conclusion

It only remains to make a brief summary of someof the factors apparently responsible for heart failure.The rival theories of back pressure and defectiveoutput have been in turn adopted and rejected,and it is evident that the prolonged conflict of

opinion has obscured an effective issue; apart fromwhich it is noteworthy that there has been a tendencyfor cardiologists, in exploiting either of the two

opposing theories, simultaneously to discredit theother. The situation is admittedly very complex,but certain conclusions appear to be already justifiedby the results of experimental and clinical research.Thus it has been clearly established that heart failureinvolves some degree of defective output capacity,and it is equally certain, on the other hand, thatback pressure may be concerned in the process.Such being the accepted findings, I suggest thatthe much criticised back-pressure theory of heartfailure should not only be recognised, but that weshould be prepared to associate the development ofback-pressure phenomena with varying degrees of

defect in the output capacity. Thus we may accepttwo well-defined circulatory abnormalities as funda-mental to our conception of cardiac failure in so faras its strictly mechanical origin is concerned.

REFERENCES

1. Alexander, H. L., Lutem, D., and Kountz, W. B.: Jour.Amer. Med. Assoc., 1927, lxxxviii., 882.

2. Calhoun, J. A., Cullen, G. E., Harrison, T. R., Wilkins,W. E., and Tims, M. M.: Jour. Clin. Invest., 1931,x., 833.

3. Cullen, G. E., Harrison, T. R., Calhoun, J. A., Wilkins,W. E., and Tims, M. M.: Ibid., p. 807.

4. Drinker, C. K., Peabody, F. W., and Blumgart, H. L.:Jour. Exper. Med., 1922, xxxv., 77.

5. Eppinger, H., Kisch, Fr., and Schwartz, H.: Das Versagendes Kreislaufes, Berlin, 1927.

6. Eppinger, H., von Papp, L., and Schwartz, H.: DasAsthma Cardiale, Berlin, 1924.

7. Fraser, F. R.: THE LANCET, 1927, i., 529, 589, 643.8. Grollman, A., Friedman, B., Clark, G., and Harrison, T. R.:

Jour. Clin. Invest., 1933, xii., 751.9. Harrison, T. R., Calhoun, J. A., Cullen, G. E., Wilkins,

W. E., and Pilcher, C.: Ibid., 1932, xi., 133.10. Harrison, T. R., Friedman, B., Clark, G., and Resnik, H.,

jun.: Arch. Internal Med., 1934, liv., 239.11. Harrison, T. R., Turley, F., Jones, E., and Calhoun, J. A.:

Ibid., 1931, xlviii., 377.12. Heinbecker, P.: Amer. Jour. Physiol., 1927, lxxxi., 170.13. Hering, E., and Breuer, I.: Sitzungsb. d. Akad. Wien,

Mathem-naturw., 1868, lviii., 909.14. Hoover, C. F. : Blumer’s System of Medicine, New York,

1928, vol. ii., p. 172.15. Hope, J.: A Treatise on the Diseases of the Heart, London,

1832.16. Kountz, W. B., Alexander, H. L., and Dowell, D.: Jour.

Amer. Med. Assoc., 1929, xciii., 1369.17. Kountz, W. B., Alexander, H. L., and Prinzmetal, M.:

Amer. Heart Jour., 1936, ii., 163.18. Kretz, J.: Wien. Arch. f. inn. Med., 1924, vii., 535.19. Kroetz, C.: Klin. Woch., 1930, ix., 966.20. Legallois, C. J. J. : Experiences sur le Principe de la Vie,

Paris, 1812.21. Miller, H. R.: Amer. Jour. Med. Sci., 1936, cxci., 334.22. Peabody, F., et al.: Arch. Internal Med., 1915-22.23. Schott, E.: Deut. Arch. f. klin. Med., 1912, cviii., 537.24. Starling, E. H.: The Linacre Lecture on the Law of the

Heart, London, 1918.25. Stokes, W.: The Diseases of the Heart and Aorta, Dublin

1854.

EXCRETION OF

GONADOTROPIC SUBSTANCES INTHE URINE DURING PREGNANCY

BY J. S. L. BROWNE, M.D., Ph.D.LECTURER IN MEDICINE AT McGILL UNIVERSITY ; AND

ELEANOR M. VENNING, Ph.D.RESEARCH ASSISTANT

(From the McGill University Clinic, Royal VictoriaHospital, Montreal, Canada)

Aschheim and Zondek’s demonstration 1 that

pregnancy urine contains gonadotropic substances hasbeen widely applied for the detection of earlypregnancy ; but comparatively little attention hasbeen paid to the quantitative aspects of the excre-tion of these substances. The figures published haveusually been derived from a composite of a seriesof patients. According to Zondek 2 the concentra-tion of gonadotropic substances rises rapidly in thefirst month of pregnancy, remains at a high levelfor several months, and declines gradually in the latermonths and rapidly after labour. The curves givenin Robson’s 3 and Frank’s 4 reviews are of this type.There has been some suggestion that the qualitativeAschheim-Zondek reaction could become negativein the later months of pregnancy. Hamburger 5followed one case at intervals throughout pregnancyand stated that there was a maximum at the thirdmonth followed by a slight fall. Smith and Smith 6

followed a series of cases through the early monthsof pregnancy and reported that there was a peak