Heart disease in the Argentine

Heart disease in the Argentine

American VOL. Heart FEBRUARY, 25 Original HEART Journal - No. 2 1943 Communications DISEASE IN THE ARGENTINE” PEDRO COSSIO,M.D. BUENOS AIRE...

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American VOL.

Heart FEBRUARY,

25

Original HEART

Journal

-

No. 2

1943

Communications

DISEASE

IN THE ARGENTINE”

PEDRO COSSIO,M.D. BUENOS AIRES, S. A.

T

HE important and useful activity developed by United States investigators during the last few years has had great influence on the progress of medical knowledge everywhere, and the repercussions thereof in the Argentine have been so great that, today, North American medical literature predominates above that from all other countries, quite contrary to the situation in the past. In respect to heart disease, this influence has been even more marked in my country, so much so, that the nomenclature and criteria for its diagnosis, as adopted by the American Heart Association, is used in every heart clinic, and the textbook written by the president, Paul D. White, has the greatest circulation and respect in the field of cardiology. As a consequence, for the last few years, 90 per cent of our physicians who have gone to study abroad have chosen the Unit,ed States; that is how I came to New York in 1936, and I had the good fortune to see for myself, and appreciate, that exceptionally clear-sighted man, Lewis A. Conner, whose name has been given to this special lecture on cardiovascular problems. Now I have come again to the United States to give the Conner Lecture on heart disease in the Argentine. This quite unexpected honor is deeply appreciat,ed by me, and should be interpreted as a generous act on the part of the American Heart Association to the investigators of heart disease in my country. This, indeed, is handsome proof of the human solidarity which binds us together more than ever in these days that challenge traditional American liberty. PUBLIC HEALTH

PROBLEMS

The Public Health Service of my country, on several occasions (Sussini and Cossio,l and Spangenberg2), has considered heart disease as one of the fundamental problems of public health. This is due not only *Lewis A. Conner Lecture, American N. J., June 5, 1942. Received for publication June 22, 1942.

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Population: 13,000,OOO. Population with heart disease : 260,000. Heart disease incidvncc : 2 pw cent.

The official statistics of mortality show that, heart, disease is the chief cawe of death. The average number of deaths today in my country is 161,223 per year, of which 26,068 are caused by heart disease, 24,909 by pulmonary disease esclusiw of tuberrulosis, 17.531 b?- disease of the gastrointestinal tract, 13,850 hp tuberculosis, 10,813 by cancer, 10,604 by disease of the nervous system, 8,921 by infectious diseases, excluding tuberculosis, and the remaining 49.987 by various other diseases. Thew incidences signif>- the following percentages in mortality : heart, disease. 16 per cent ; pulmonary discasc. excluding tuberculosis, 15 per cent : gastrointestinal disease, 11 per cowl ; tuberculosis. 9 per cent ; cancw, 7 per cent, ; nervous system discasc, 6 per cent, ; infections diseases. csclutling tl~beyqlosis. 5 JWl' cent, ;rnd otllct* discnscsi. 31 ~c’I‘ ?cnt (Tal)l(l TT).

Heart I >ancer

disease

Pulmonary tuberculosis Tubrrculosis

Other

causes

disease,

excluding

The predominance of heart disease in the mortality of my country is still greater if one takes into account only the deaths in the cities. For example, in Buenos Aires the deaths numbered 28,537 during 1940; 6,894 were from heart disease, 4,286 from cancer, 3,064 from nontuberculous pulmonary disease, 2,745 from tuberculosis, 2,485 from nervous system disease, 2,273 from gastrointestinal disease! 1,212 from infections diseases, excluding tuberculosis, and 5,565 from other causes. These incidences girt the following percentages: heart disease, 24 per cent; cancer, 15 per cent; pulmonary discasc, excepting t,uberculosis, 11 per cent; tuberculosis, 10 per cent; nervous system disease, 9 per cent; gastrointestinal disease, 8 per cent; infectious diseases, excluding tnberculosis, 4 per cent ; and several other causes, 19 per cent (Table II). number of death6 52.000

i 50 .ooo

1 ALL

OTHER

il

CAUSES

1

18.000 16.000 14.000 12.000 10.000 8.000

under Fig.

l.-Deaths

from

heart

disease compared decades, in the

with deaths Argentine.

from

all

other

causes,

by

The predominance of deaths from heart disease in the mortality of t.he cities over the mortality of the whole country shows that heart disease is more frequent in the cities than in the country districts. The greater incidence in the cities is due partly to the greater frequency of deaths from pneumonia and gastrointestinal disease in t,he country districts, and partly to its actually greater frequency in the cities; so that, today, the death rate from heart disease is 280 per 100,000 inhabitants, and, in the whole country, only 213 per 100,000 inhabitants. The mortalit,y from heart disease shows a significant difference according to age. More than one-half of the deaths, namely, 60 per cent, occur in people over 60 years of age, 24 per cent among those 40 to 60 years

Fig.

L-Deaths

from heart disease, cancer. Buenos Aires annually from

tuberculosis, 1920 to 1940

and lobar inclusive.

pneumonia

in

,280

280

,260

2io 240

.Pbo

220

,220 ,200

200

.180

180 160 140 120 100 80 60 40

I , . . .

1920 Fig. disease, annually

1 19$5

Z.-Deaths from heart disease, and infectious diseases (per from 1920 to 1940.

19%

1955

tuberculosis, cancer. pneumonia, hundred thousand inhabitants)

1940 gastrointestinal in Buenos Aires

is from ItcaVt discxscb it) I host: I)c:l\rcVll 10 ilIlt 60 ~Wrs UJ:ilg(‘, \VIl('I'l!ilS, in people ol’ 20 to 40 y(lars (II’ ;tg!‘ti. only 1 OII~ of’ 9 &laths is from hrarl disease, and among those under 20 yews oL’ age, 1 out of 60 is from heart disease (Fig. 1) . The predominance of heart disease in the mortality of my country Iw gradually become a fact rllnG~g the lasl 1’cw \-c;irs, first, by ils absolrttc increase, and, second, as a rcsnlt of lcsseninp of some of 1.11~~ other causes, especially infectious diseases, incl ucling p~mmonia and tuberculosis, as well as gastrointestinal diseases. In 1920, in Buenos Aires, 4,100 persons died from hear1 disease (Figs. 2 and 3), which is 254 out of every 100,000 inhabitants; now the deaths number 6,S94, which is 280 out of cvcry 100,000 inhabitants. In the same year, 1920, on the contrar!-, there were 314 deaths pel 100,000 from tuberculosis ; 213 per 100,000 from lung disease, excluding tuberculosis; 165 per 100,000 from gastrointestinal disease ; and 91 per 100,000 from other infectious diseases, whereas, today, there are 110 per 100,000 from t,uberculosis ; 120 per 100,000 from pulmonary disease, excluding tuberculosis ; 90 per 100,000 from gastrointestinal disease, and 5 per 100,000 from other infections diseases. It is not possible to know with any exactness t,he economic losses caused by heart disease, but, to give some idea, it is enough to say that 40 per cent of the pensions paid to invalids in t,he whole country are drawn by people with heart disease. The Civil Service Pension Board for the 300,000 government employees pays 6,000,OOO Argentine paper dollars annually for heart disease incapacity alone. The Railway Pension Board for the 140,000 employees paid, during the last 18 years, 32,000,OOO Argentine paper dollars for heart disease incapacity. It has been calculated that the pecuniary losses occasioned bg heart disease in my country are more than 100,000,000 Argentine paper dollars per year, including medical attention and virtual salaries. The causes of heart disease in the Argentine are the same as in other countries, but with different predominances occasioned by climate, habits, and other unknown factors. The city of Buenos Aires, with 2,500,OOO inhabitants and ways of living common to all big cities, is situated at south latitude 35O, with a t,emperate, but damp, climate. The causes of heart disease, according to clinical, radiologic, and electrocardiographic studies of 10,000 patients (4,000 private cases and 6,000 hospital cases, the last including more than 400 autopsies), are as follows: coronary insufficiency, 29.6 per cent ; infectious disease, 25.1 per cent; rheumatism, 18.2 per cent; syphilis, 7.7 per cent; arterial hypertension, 27.5 per cent (systemic, 23.7 per cent, pulmonary, 3.7 per cent 1 : thyrotoxicosis, 5.8 per cent; trauma, wounds, and other causes, 4.9 per cent; congenital anomalies, 2.4 per cent ; and unknown causes, 1.5 per cent (Table III).

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This incidence is modified by age. Arann and Krcutzcr,‘i in stutl).ing 1,500 children with organic heart tliseasc, fount1 rlicumatism in 60 per cent, congenital anomalies in 2S per cent, and several other causes in 12 per cent ; that is to say, of 10 children, 6 had rheumatism, 3 congenital anomalies, and 1 heart disease of another kind. Between the ages of 20 and 40 years, rheumatism remained the chief cause in 4 out of 10 casc~s. After 40, the most important cause is coronary disease and arterial hypertension in the following proportions: in every 10 cases there arc’ 4 of coronary disease, 3 of hypertension, and 3 of other diseases. Aftci the age of 60, this proportion is greater, i.e., 6 of coronary disease, 3 111 hypertension, and 1 of other ‘diseases (Cossio and CampanaY) .

CORWBA

Fig.

,

4.

There is also a difference between private and hospital patients, depending upon their respective economic capacities. In private practice, rheumatism is slightly less frequent than among hospital patients, i.e., in the first, 17 per cent, and, in the second, 19 per cent, but, on the contrary, in private practice coronary disease, including angina pectoris, is much more common than among hospital patients ; coronary disease among private patients represents 35.9 per cent, and, in the hospital group, 23.3 per cent.

It 11X3 is iln

disease

IWCIl

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in the ArgcIItiIich

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consumption of meat per perso is 107 kg. and the incidence of coronar) disease is only 29.6, whereas. in the? ITnited States, the yearly cons~~mpi ion of meat per prrsoII is 66 kg. ((~Iomez”), and the inc4dence of coronar> disease is 3i.7 per cent (White and Jones”). 111 other

cities

of IIIy couIItq

(I*‘ig.

4) the imidenc’e

of the

C~RUSCS

of heart disease is similar to that, in Buenos Aires, but with some diiferenccs according to the clima1.e and the degree of commodit,ics available. In Rosario, with its 500,000 Ijeople, and more or less the same climate but quieter living, Gonzalez Sabathi?’ found less coronary arter! (‘astro Auh011e”’ tlisrase among 4,500 private ant1 hospital paticrits. I’ound more rheumatism among 3,594 patients in the city of Mendoza, On the contrary, which has a population of 83,000 hut, a colder winter. in Cordoha, with 273,000 inhabitants and a much warmer and driet climate, Maldonado Allende’O fonncl very much less rheumatism, i.e., only II per rent, hut more syphilis, i.e., 17 per cent.. RIlCDI(‘:\I,

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In 1930, Padilla and I organized, in the Physical 1)iagnostic Institute of the Medical School of Buenos Aires, the first postgraduate course on heart disease, which consisted of lectures and bedside teaching. Xincc then, other similar courses hare been conducted in the Institute of Physiology and in the Ramos Mejia Hospital, also at Buenos Aires. During the last few years a postgraduate course in heart disease has been held in the Institute of Physiology of the Medical School of Cordoba. The result of these activities is Ihat today there are in my country forty specialists in heart disease, all members of the Argentine Cardiological Society, which holds six meetings yearly in the chief hospitals of Buenos Aires. The Argentine JIetrrt .Jlourxcd, already in its ninth year, is the official organ of this society. In some of the hospitals o-EBuenos Aires there are “cardiac clinics ” and, in the others, ’ ’ heart stations or laboratories ’ ’ in charge of specialists in heart disease, with all the equipment necessary to make a complete diagnosis. In addition, each cardiac clinic has its own social service. The clinics have accomnlodatiol~s for inpatients and outpatients, the stations only for outpatients. Some cities in the interior, such as Rosario, Cordoba, Tucum&n, and Mendoza, also have their own cardiac clinics or heart stations, which are organized like those in the city of Buenos Aires. One of the cardiac clinics, for example, which is in my personal charge In at, the Medical School Hospital, has fort,y beds for cardiac patients. addition to the regular diagnostic equipment, we have instruments for research work, such as apparatus for optical graphic and electrical

c0ss10

:

HEART

DISEASE

IN

THE

ARGENTINE

153

registration of heart sounds and arterial and jugular pulse, and for the estimation of cardiac output, blood and alveolar gases, blood volume, and so forth. Recently the Medical School received an important donation to endow an institution dedicated exclusively to cardiovascular investigation. Likewise, the public health service has a department, also in my charge, for making the medical examinations that are necessary for the cmployces who are pensioned off for heart disease. This department also functions in the periodic health examinations of Government employees as a preventive measure against incapacity through heart disease. RESEARCH

CONTRIBUTIOiYS

The first original contribution in the Argentine was the syndrome happily called by Ayerza,ll in 1901, “cardiacos negros,” meaning black cardiacs, consisting of hypercyanosis, dyspnea, and overstrain of the right ventricle, with edema. In the beginning there was some confusion about this syndrome ; it was thought to have a specific cause, and was called primary sclerosis or syphilis of the pulmonary artery ( Arrillagal* ) , hyperplasia of the marrow (Escudero13), and so on. Later, intensive studies have shown that the initial lesion is a chronic bronchopneumonia caused by a common infection, exceptionally by syphilis or tuberculosis, with or without pulmonary arterial sclerosis and obliteration of the smaller arteries and arterioles ; this is followed by overstrain of the right ventricle, with myocardial failure, which is today called chronic car pulmonale, but with the particular characteristic that cyanosis predominates because of a disturbance in the gaseous interchange in the lungs brought about by lessenin, D of the tension of the alveolar oxygen, i.e., so-called alveolar hypoventilation, caused by loss of the pulmonary elasticity and an increase of the pulmonary dead space (Ayerza, Solari, and Berconsky, I4 Cossio and Berconskp,‘” and Capdehourat16). Several other contributions have been made, but only a few will be mentioned. In 1917, Hardoy and Houmay17 proved, by experiments and clinical observations, the value of giving 1 or 2 mg. of epinephrine by parenteral administration in the Adams-Stokes syndrome with auriculoventricular block. In .1921, Guglielmeti, Arrillaga, and Waldorpls showed the effect of quinidine on the heart by experiments on dogs. After a brief phase of stimulation, with increased heart rate, a second phase of depression followed, with decreased heart rate, and lessening of the excitability of the myocardium set in, preventing or abolishing experimental fibrillation of the auricles. In 1924, Padillal” published a book on electrocardiography which was epoch-making in South America. Completely illustrated by his own

cases, it was an cshanstivc ant1 so~~lltl stud!- on this illll~orlan[, 1~1c~lhot1 of examination, which was quite unknown to us at that timr. Since 1928, Padilla and Ctwsio?” have used cluinidine sulfate intravenously in doses of 0.50 to 1.5 (:m. in a 5 per dent solution witliollt harming their paCents. This has been given t,o pat icnts with paroxysmal tachpcardia of ventricular 01’ supraventricul;lr origin, paroxysmal auricular fibrillation, and flut,ter ., eood results have been obtained even in cases in which this medication had been ineffective by mouth. In 1929, Padilla and Cossio?’ made an exhaustive clinical and anatotlric* study of coronary arterial occlusion, in which they pointed out 111~ill)portance of alterations in auriculorcntricular and ventricular condnctioa, and of ventricular tachycardia in cases of infarction of the inter\-cntricular septum. In addition, they demonstrated for t,he first time the: absence of the coronary S-T segment and of the coronary T wave in myocardial infarction with bundle branch block. Battro,“? almost at the same time, made similar studies on coronary occlusion, and, some years later, Martinezz3 did the same. In 1931, Martini and JoselevichZ4 made an extensive clinical and anatomic study of the right vent,ricnlar failure which is caused by displacement of the interventricular sept,um (syndrome of Bernheim) . They emphasized that the absence of lun, v congestion is a differential point; such cong&ion is charaetcristic o-f right ventricular failure secondary to left ventrknlar failure, which is alwags accompanied h) pulmonary congestion of various degrees. From 1931 until t,he present, timct, the graphic registration of heart sounds has hecn thr object of special at,tention. Kraun Menbntlrz and Orjas2;’ have recorded the ihircl physiologic heart sound in 12 per certi- of 100 tnctliral students, and the prqvstolic auricular sound in 15 per cent. With my collaboratorP I have identified a systolic and a protodiastolic sound in auriculoventricnlar block. The syst,olic sound is present when auricular contraction coincides with the middle of ventricular systole, and t,he protodiastolic sound occurs when auricular contraction coincides Ivith rapid ventricular inflow, producing the summation phenomenon. We2’ have given cvidcncc of the alternation of heart sounds in rasps of pulsus alternans. The alternation of the first sound and of the gallop rhythm is always concordant, whereas the alternation of the second sound map be concordant or discordant in such a way t,hat the heart beat which produces the larger pulse wavy has a loud first sound, pronounced gallop rhythm, and a loud or a faint sccontl sound. P have proved that. often there is a third, protodinstolic sonncl in acfivc rhcumniic hrart disease ~~*ilh mitral rcgurgritntion, ant1 also ih;ll Ihc flln(4 ionnl milral murmur of rheumatic cardit,is occurs only in the early and middle phases of ventricular systole.

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GOIlZaleZ SabathiP proved that, when thcrc is physiologic lWlU~)li(~iti.ion of lhc second heart sountl, 111~c~los~~rcoi’ lhc aort.ic valve precedes that of the pulntoniwy valve, which is contrary lo all classical medical knowledge.

P’ have shown that, with aLlricnlo~ontricular nodal rhythm, the first heart sound is louder and reduplicated. This enables us to distinguish parosysmal tachycardia of auriculoventricular nodal origin. In 1934, Gonzalez Sabathii? called our attention to engorgement, of t,he left external jugular vein as a sign of lengthening and widening of 1hc: aortic arch, with pressure on the left innominate vein. In 1935, Moia”” stated for the first, time that the T wave of the precordial lead in normal children can be negative. In 1937! I”” called attention to, and named, the “bronchial dance”; this curious phenomenon, a to-and-fro movement of the bronchi on the right side, is easily seen on the fluoroscopic screen in the presence of unusual enlargement of the left auricle, with mitral regurgitation. Also in 1937, Battro, Braun Menilndez, and OriaP showed that electrocardiographic patterns of bundle branch block are not always found with abnormal asynchronism in ventricular contraction. In 1939, Enquin and Aguirre”” were able to visualize the whole left auricle and all of the thoracic aorta by ultrapenetrating radiography, giving evidence of its usefulness in the diagnosis of heart disease. In 1940, Arana and Kreutzer,S” in a study of 600 children with diphtheria, found that the electrocardiographic changes are sometimes reversible, and, at other times, irreversible, which should be remembered in order to avoid a mistake in diagnosis. two types of In 1941, Vedoya and Gonzalez Videla 37 differentiated sinoauricular block : one with occasional dropped beats and progressive lengthening of sinoauricular conduction, with heart beats in groups similar to the Wenckebach periods of auricnloventricular block; and the other, with occasional dropped beats but without the progressive lengthening of sinoauricular conduction. Also in 1941, Cossio, de1 Castillo, de la Balze, and Iteforzo”s demonstrated reversible heart enlargement in cases of nontoxic goiter after This enlargement is apparently due to overstrain of the thyroidectomy. right ventricle caused by an arteriov,enous fistula in the thyroid gland and the neighboring vascular bed. Finally, since 1937, arterial hypertension caused by clamping the renal arteries of dogs has been the subject of a great deal of study. In 1937, Houssap and FascioloS9 gave a clear demonstration that the ischemic kidney of hypertensive dogs liberates a pressor substance into the blood. Grafting such kidneys into the necks of recently nephrectomized dogs caused a rise in the blood pressure of the recipient dog. Later, Houssay and Taquini40 showed t,hat the titrated plasma of the

In 1939, B~~IIII hlt~11611tl~~~ :tllcl l~';ls~it)ld showtv 1 that wut.c ischemia ol’ the kidne\-s ~~rotluct~l the SU~IC’ (+fw~s. mcl, wit II I~~loi~* and R111fioz,~~ discovered in this Mood the h,vpcrtcnsin. that is responsihlc for the pressor and vasoconstrictor proprrties of the venous blood of ischemic kidnqys. It was found that this substanw is formed hy the enzymatic action of rcnin on a l~lootl globulin culled liyperterisinogen. Another enzyme, hylxrtensinasc, which is present in blood and l.issws, destroys hppcrtensin. The ischcmic kidneys secrete rcnin into the blood, and hypertensin is formed subsequently in the blood by the actioli 01 wllin on hypertensinogen (Leloir, Muiiox, I:raun Mrn&xlez, :ITI(~ b’asciolo*“) . Renin has hren found in the renal WI~OIN blood and in the general blood of hypertensive dogs (11~11 ‘Ore and Braun Men61ldez’~). The experiments of Hnidohro and Brnun RIen6ndcx4” haw shown that renin is secret,ed, cvcn hy normal kiclncp, whene\-clr t hc blood prcss~e falls. The kidnq- thus seems lo play its par1 in the normal rcglrlaf ion 01 art.crial blood presssnrr. SUlJStiJl~C~C,

REFERENCES

M., and Cossio, P.: Hol. ()lic. sari. panam. 17: ili!), 1038. 1. Sussini, 2. Spangenberg, J.: Bol. Ofic. sari. pauam. 21: 1, 1942. J. M., and Ruchelli. A. P.: 3. Macera, 1,:~s car(liopatias ‘1~ nuestro media escolar, Buenos Aires, 1940. C., (larrtin, R., and Seguw, A.: Jornatlw IIC la Asixtencia Social 4. Bocalandro, de1 Cardiaco, Buenos Aires, 27th to Nth, 1941, p. 130. 5. Rodriguez, CT. : Jornadas (1~ 1:~ .\sistewi:r Social (lrl (“ardiavo, Buenos -Gres. 27th to 30th, 1941, p. 194. 6. Personal communication. P., and Campana, M.: Hal. sari. Dep. nac. hix:. 7. Cossio, (1.: Personal communication. sI . Gomez, P. Il., and Jones, T.: Am. Heart .I. 3: :Kb”. 19°K !I. White, 10. Personal communication. 11. Ayerza, A. : Ewlerosis srcuntlaria (Ie la arteria pulmonar p su cuadro clinic0 Cardiacos negros, tesis de b’. Arrillaga, pwdrin,l .-\. Ayerza, Buenos Aires, 1912. I”. -\rrillagd, F’.: La artcritis pulmcmor y su cuallro vlini,w, Uuenas Aires, 1929. I’.: Semana m6d. 1: 907, 1926. 13. Ercudero f,., Solari, I,., and Brrconsk?;, I.: Krr. ,\sov. m&d. argent. Sac. Med. 14. Ayerza, Int. 6: 31, 1930. Henlana mGd. 2: Dli, 193” -. 13. Cossio, P., and Berconsky, I.: T,a cianosis dt* 10s cardiacas negrcw de Byerza, Buenos 16. C!apdehourat, IX.: Aires, 193-L. P. J., and Houssav, IS. A.: Rev. Asoc. u&d. argent. 27: 4fiJ, 1917. Ii. Hardoy, J., Arrillaga, @., and Waldorp, C.: Rev. Asoe. m6d. argent. 34: 18. Guglielmeti, 454 1921. T.: E>lectroeardiografia, Buenos Aires, 1924. 19. Padill;, ‘II). Padilla, T., and Co&o, P.: Bull. rt m6m. Sac. m6d. (1. 116~. de Paris. “1 T.. ant1 Cossio, P.: OclusiSn coronaria brusca j- lenta, Buenos .%ires, - . Padilla. 1936. .,., de oclusibn :oronilria, Buenos Aires, 1930. --. Battro, A. : Sindrome La angina de pechu, Buenos Aires, 1933. 23. Martinez, G.: L:I estenosis destrll-vc,ntric.ular (Sindrome de 24. Martini. T.. and .Joselevich. M.: Bernheim), Buenos Aire;, 1931. :! .j . Braun MenBndez, E., and Arias, 0.: Rev. argent. de cardiol. 1: 101, 1934-3.X 26. Cossio, P., and Braun Menbndez, E.: Rev. argent. de cardiol. 2: 1, 1935-36. Cossio, P., and Lasealea, M.: Rev. nrgent. de cardiol. 1: SXG, 1934.

c0ss10 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 14.

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Co&o, P., Lascalea, M., and Fongi, E.: Arch. Int. Med. 58: 812, 1936. Cossio, P.: Rev. argent. de cardiol. 5: 242, 193839. Gonzalez Sabathie, L.: Rev. argent. de cardiol. 5: 25, 193839. Cossio, P.: Rev. argent. de cardiol. 5: 242, 1938-39. Gonzalez Sabathie, L.: Rev. argent. de cardiol. 1: 2tii, 3934-35. Moia, B.: Rev. argent. de cardiol. 2: 26, 193536. Cossio, P.: Bull. et mAm. Soe. med. d. hop. de Paris 53: 21.5, 1937. Battro, A., Braun Menendez, E., and Orias, 0.: Rev. argent. de cardiol. 3: 325. 1936-37. Enquin, B., and Aguirre, P.: Rev. argent. de cardiol. 6: 83, 193940. Arana, R., and Kreutzer, R.: El electrocardiograma en la difteria, Buenos Aires, 1941. Vedoya, R., and Gonzalez Videla, J.: Rev. argent. de cardiol. 7: 2ii, 1940-41. Cossio, P.. Del Castillo. E.. Reforzo. Membrives J.. and De I,a Balze, I”.: Medic&a 1: 338. 1941. ’ Houssay, B. A., and Fasciolo, J. C.: Rev. Sot. srgent. de lriol. 13: 284, 193T. Houssav, B. A., and Taquini. A. C.: Rev. Sot. argent. de l)iol. 14: .?, 19:38. Braun ‘ivkenendkz, E., and Fascinlo, J. (1.: Rev. So?. argent. de biol: 15: 161, 1939. Braun Menendez, E., Fasciolo, .J. C., Leloir, 1,. F., and hluiloz, .J. RI.: Rev. Sot. argent. de biol. 15: 420, 1939. Leloir, L. F., MuAoz, J. M., Braun filenPndez, E., ant1 Fawiolo, J. C.: Rev. Sot. argent. de biol. 16: 75, 3940. Dell’Oro, R., and Braun MenPndez. E.: Rev. Sot. argent. de biol. 18: 1942 and

Braun

MenEndez,

E.:

To be published.