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Pulmonary Edema by Ascending to High Altitudes
Pulmonary Edema by Ascending to High Altitudes* EMILIO MARTICORENA, M.D., FERNANDO
A.
TAPIA, M.D., JUAN
DYER,
M.D.,
JOSE SEVERINO, M.D., NATALIO BANCHERO, M.D., RAUL GAMBOA, M.D.,
HEYER
KRUGER, M.D. AND DANTE PENALOZA, M.D., F.C.C.P.
Lima, Peru
M
nendy at high altitudes who developed acute pulmonary edema upon their return to the mountains, after being at lower or sea levels for four to 75 days. Most of them had made short trips to lower levels previously without developing symptoms on returning to higher altitudes. Five had previously developed pulmonary edema on similar circumstances. Two residents of Jauja, 10,499 feet above sea level, had symptoms during their first trip to an altitude of 14,100 feet (4,300 meters) after being at sea level for 14 to 20 months. One patient was born in Lima (500 feet above sea level), but lived at 14,200 feet above sea level (Cerro de Pasco) most of her life; in the last two years, she had spent nine months each year at sea level and had developed pulmonary edema each time she returned. All patients were examined at the time of the acute episode except one who died at home without medical attention; the clinical data were obtained from the relatives and proved by post-mortem examinati~n. Most of the patients had a medical examination for routine check-up or other illness at different intervals prior to the acute episode. None had evidence of pulmonary or cardiac disease. Daily clinical observations were made until complete clearing of the pulmonary symptoms and signs; several patients were seen again from ten to 30 days after discharge from the hospital. Complete 12-lead electrocardiograms and roentgenograms of the chest were taken during the acute episode and daily until three days after clinical manifestations of the pulmonary edema had disappeared. In three patients, chest films five to six months before were available for comparison. Cardiothoracic ratio
ANY INSTANCES OF ACUTE PULMO-
nary edema after ascending to high altitudes have been reported in persons without cardiopulmonary disease. This phenomenon has been observed more frequently in young persons living at high altitudes upon returning to the mountains after a relatively short period at lower levels. 1~ Pulmonary edema has also been reported in mountain climbers.... The mechanisms of its production have not been clearly demonstrated; however, it is generally accepted that anoxia is the main causative factor. Very few hemodynamic data have been obtained during the acute episodes,"1' and post-mortem histologic studies have been reported only in non-acclimatized mountain climbers.' The present report includes clinical, roentgenologic, and electrocardiographic observations made during the acute episode and on recovery of pulmonary edema occurring on ascending to high altitudes. Cardiac catheterization was carried out in one case. Histologic studies performed in two patients revealed distinct features of this syndrome. Preliminary observations were reported previously.
1.
MATERIAL
This study includes observations in 36 persons (30 men and six women) from five to 37 years of age, most of them under 20, residents of altitudes 13,700 feet (4,200 meters) or more above sea level. There were 33 who were born and lived penna·From the Cardiovascular Laboratory, High Altitudes Research Institute, Peruvian University of Medical and Biological Sciences, and the Division of Medicine, Cerro de Pasco Corporation. This investigation was supported by U. S. Public Health Service Research Grants RG-8576, H7000, and H-6910 from the Division of General Medical Sciences and the National Heart Institute.
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274
EMILIO MARTICORENA,
1: Roentgenograms of a patient with high altitude pulmonary edema. (A) during acute phase: coarse mottling exudate in both lung fields; apices and bases uninvolved. (B) 24 hours later: rapid clearing of exudate; (C) 48 hours later: clear lung fields. FIGURE
et at.
DiseaSC50f the Ch'll
FIGURE 2: Chest films of another patient with severe clinical manifestations of pulmonary edema at high altitude. (A) during acute phase: pre· dominant confluent exudate in the left lung; car· diac borders masked; (B) 24 hours later: rapid resolution of exudate; (C) 48 hours later: com· plete clearing of exudate.
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and frontal area were calculated in the serial films. Only five patients were brought to lower levels for treatment. All but one were treated with humid O 2 given by mask or tent. Only one patient received intravenous digitalis the first 24 hours. In one patient, right cardiac catheterization was performed as soon as he was brought down to sea level. Laboratory studies included complete blood count and cell volume determinations. Post-mortem studies were available in two patients. CLINICAL OBSERVATIONS
The time of onset of pulmonary edema after the return to high altitudes varied from three to 48 hours; the majority of patients developed acute pulmonary edema during the first 24 hours. In four cases, it occurred while sleeping and in six immediately after an unusual or prolonged effort. Only one had symptoms of infection of the upper respiratory tract preceding the acute episode. The most frequent early symptoms were: headache, restlessness, increasing dyspnea, dry cough, palpitations, precordial discomfort and nausea. The manifestations of severe respiratory distress appeared in the course of a few hours after the initial symptoms except in one patient who complained of headache and tiredness for 48 hours preceding the respiratory picture. During the acute phase of pulmonary edema, the patients experienced marked dyspnea, wet cough with foamy pink or whitish sputum, cold perspiration, anxiety, occasional vomiting, chills, diffuse muscular and joints aching, thirst, weakness and sensory disturbances. They were markedly dyspneic, in the orthopneic position with cyanosis of the lips and nail beds in the severe cases; marked pallor of the face was observed in most of the patients. The skin was cold and clammy, the lungs were full of wet rales (fine, medium and coarse) and ronchi. Tachycardia and mild to moderate hypotension were present. Only one patient had blood pressure levels of 152/60
3: Chest films of a patient showing: (A) during acme of pulmonary edema: confluent coarse mottling predominantly in the right lung; apices and costo-diaphragmatic angles free; normal heart size; (B) 24 hours later: decreasing exudate; (C) 48 hours later: clear lung fields. FIGURE
EMILIO MARTICORENA, et ale during the attack. Most of the patients were afebrile and several had slight temperature elevation during the first 36 hours. Leukocytosis was present in most of the cases. Administration of humid oxygen produced a beneficial effect and rapid improvement of the clinical condition. Disappearance of the pulmonary congestive signs was observed in 24 to 48 hours. Progress examination four weeks later did not reveal residual symptoms or signs. Two patients died 38 and 53 hours after the onset of symptoms. The first developed acute pulmonary edema three hours after his arrival at Cerro de Pasco, and did not receive any medical attention. The second developed acute pulmonary edema ten hours after his arrival at the high altitude and after running for one hour. Administration of oxygen was inadequate; intraI II III oVR aVL oVF
Diseases of the Chest
venous strophantus and phlebotomy of 200 mI. of blood were of no beneficial effect. ROENTGENOLOGIC STUDIES Representative examples of the roentgenologic findings during the acute pulmonary edema are shown in Figs. 1, 2 and 3. The radiologic appearance was predominantly a coarse mottling exudate scattered in both lung fields, but more confluent and prominent in both parahilar regions and usually with the apices and bases uninvolved. In some cases, the exudate was predominant in one lung and in only one patient was it exclusively localized in the left lung. The radiologic appearance of pulmonary edema disappeared completely, usually within 48 to 72 hours. Clinical improvement preceded the complete clearing of radiologic signs. VI V4 V2 V3 V6 VS
4: Electrocardiograms recorded in one patient with high altitude pulmonary edema: (A) taken the fint day, when the pulmonary edema was severe; (B, C, D and E) recorded at 24-hour intervals, when the pulmonary edema was subsiding. Note in tracing A the positive displacement of the RS-T segment instead of the negative one which is often associated with right bundle branch block. In the following records this finding gradually disappean while the T waves become negative in the right precordial leads. In the last tracing the ischemic T -wave pattern decreases. FIOURE
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In all patients the pulmonary artery was prominent during the attack, decreasing in size upon recovery. The heart was nonnal in size and configuration with only minor or no decrease in overall size after clearing of pulmonary changes. In five patients, the cardiac borders were masked by the exudate and in two of them, it was not possible to outline the cardiac silhouette for measurement. ELECTROCARDIOGRAPHIC FINDINGS
Variations in the electrocardiogram during the pulmonary edema and on recovery are shown in Figs. 4, 5 and 6. The electrocardiographic pattern observed during the episode of respiratory distress was similar to that observed in acute cor pulmonale and other forms of acute right ventricular overloading.
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Sinus tachycardia was present in all cases (heart rate average 124, range 105150). The amplitude of the P waves did not exceed the 3 mm., but they were slightly peaked in most of the tracings, especially in leads II and VI. SAQRS was oriented to the right and fOlWard with a mean value of +123° (range +15 to ±1800). Tall R waves in aVR, Rs complexes in VsR and fairly deep S waves in V6 were frequently present. Slight positive displacement of the RS-T segment was noted in right precordial leads in several patients, and this occurred in spite of the presence of right bundle branch block observed in some cases. Abnonnal configuration of the T waves was seen in the same leads and in seven patients the T waves were rather tall and peaked in precordial as well as in limb leads. 0
A
c o FIGURE 5: Electrocardiograms taken at 24-hour intervals in another case with high altitude pulmonary edema. Serial tracings show changes related to acute right ventricular overloading, which gradually decreases.
EMILIO MARTICORENA,
et al.
Oi_of the Chest
A
B
c FIGURE 6: Electrocardiograms obtained in a 13-year-old boy, 24 houn, 48 hOl1n and four weeks after the onset of pulmonary edema. Right SAQRS deviation is a frequent findings in the natives of high altitude. The acute right ventricular overloading is reflected in the tint tracing by a positive displacement of the RS-T segment in right precordial leads. It disappears when the overloading decreases and the T waves become deeply negative, peaked and symmetrical. In the last tracing the ventricular repoIarization becomes normal. Peaked P waves seen in the tint two tracings become normal in the final record.
The P and QRS changes decreased in 24 to 48 hours in relation to the clinical and roentgenologic improvement. The positive displacement of the RS-T segment also disappeared in right precordial leads.
The T waves became more abnormal, some times flat or negative, peaked and symmetrical during the following two or three days. The disturbances of the ventricular repolarization disappeared later than the
FIGURE 7: Roentgenograms obtained in same patient as Fig. 4. (A) At high altitude when the pulmonary edema was "severe; (B) 22 houn later, during the right heart catheterization performed at sea level when the clinical manifestations were subsiding.
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FIOURE 8: Histologic section showing pulmonary edema and hyaline membranes (in dark black) in close contact with alveolar wall (PAS staining).
changes of the auricular and ventricular depolarization. After recovery the electrocardiogram was similar to those observed in normal persons living permanendy in similar high altitudes. 11." HEMODYNAMIC STUDIES
Right cardiac catheterization was performed in one case 40 hours after the onset of the pulmonary edema, when the clinical and roentgenologic manifestations were subsiding (Fig. 7). This study was performed as soon as he was brought down to sea level; at this time, the arterial oxygen saturation, the pulmonary artery and capillary pressures were normal. However, changes observed in the serial electrocardiograms of this patient suggest that pulmonary hypertension and acute right ventricular overloading were present previously (Fig. 4). HISTOLOGIC FINDINGS
Macroscopic and microscopic evidence of severe pulmonary edema was present in both cases with necropsy studies. There were extensive areas with hyaline membranes in close contact with the alveolar wall and also floating like tangled material in the edema fluid, more numerous in the lower and middle lobes (Fig. 8). Histochemical analysis of the hyaline membrane
revealed an identical composition to the hyaline membranes of the newborn. The alveolar septi were thickened due to marked capillary congestion. Focal areas of emphysema alternated with the areas of edema. The pulmonary veins showed marked congestion. In both cases recent vascular thrombi were found; in one, they were located in the small pulmonary arteries, in the other, at the septal capillaries. Both patients exhibited thickening of the muscular arteries, numerous preterminal arterioles and interseptal vessels with definite muscular media. These changes were more severe than those seen in high altitude acclimatized residentsl • and in one of them, the changes were similar to those observed in severe chronic pulmonary hypertension with occlusive changes, intimal sclerosis and muscular hyperplasia of small arteries and arterioles. In this case, small, localized areas of healed tuberculosis were observed in the left lung. Moderate to severe right ventricular hypertrophy was found in both patients. There was neither left atrial nor left ventricular dilatation and the left ventricular myocardium had no pathologic changes. DISCUSSION
Pulmonary edema of high altitude appears to be the result of hemodynamic
EMILIO MARTICORENA,
changes occurring primarily in the pulmonary vascular bed. Cardiac catheterization performed in three patients, one by Fred and his associates' and two by Hultgren and co-workers,' has confirmed the presence of pulmonary hypertension in these cases and has revealed normal left atrial pressure. This latter finding makes less probable the possibility that pulmonary edema of high altitude is due primarily to an increase of left ventricular diastolic pressure with or without myocardial failure. In addition, the roentgen examination did not reveal enlargement of the left cardiac chambers, and this also was observed in the two necropsied cases. Nonnal pulmonary capillary pressures in two patients with high altitude pulmonary edema have been reported by Hultgren. l1 This finding is in agreement with previous investigations perfonned in man suggesting that pulmonary hypertension induced by acute hypoxia is mainly due to vasoconstriction at precapillary leveI. 1I•1• If pulmonary capillary hypertension is not present in high altitude pulmonary edema, we would have to admit the presence of an increased capillary permeability; this possibility has not been demonstrated in experiments on acute hypoxia, but it cannot be entirely excluded in cases of high altitude pulmonary edema. The frequent finding of fibrin and hyaline membrane in the alveolar exudate in such cases may be an indication .of increased capillary permeability. Besides these changes probably taking place in the pulmonary capillaries, other factors may playa role in the mechanism of production of this type of pulmonary edema. It is known that cardiac output increases in response to experimental acute hypoxial '.1f and the magnitude of such increase is related to the degree of anoxemia. lf•I ' Hurtado and Aste-Salazar11 have demonstrated that the degree of anoxemia is more accentuated in newcomers than in residents of high altitude. While the cardiac output remains within normal limits in the high altitude resident,II it is prob-
et ale
Diseases of
the Chest
ably increased during the initial period of exposure to high altitudes. A further increase in cardiac output induced by exertion may take place in some cases. The development of pulmonary edema occurring in some patients while sleeping could be explained by an additional increment in cardiac output in these circumstances; this may be related ot the postural changeSl and to the fall in arterial O 2 saturation on supine position and particularly during sleeping as observed at high altitudes by Hurtado. a Another factor which probably participates in the production of high altitude pulmonary edema is an increase of pulmomonary blood volume. Studies on the effect of acute hypoxia upon the pulmonary blood volume are contradictory. Recent studies in man by Fritts and co-workers" indicate that acute hypoxia does not produce any increase of blood volume in the lungs. However, all the climatic conditions present on ascending to high altitudes, e.g., a low temperature, are not reproduced in experiments on acute hypoxia. Marked pallor and coldness are usually observed on persons ascending to high altitude, suggesting the presence of peripheral vasoconstriction. According to Sarnoff's observations," the peripheral vasoconstriction may produce displacement of blood into the pulmonary circulation; therefore, it is possible that an increase in the pulmonary blood volume may occur preceding the high altitude pulmonary edema. The higher incidence of this type of pulmonary edema in high altitude natives returning to their place of residence after a short stay at sea level may be explained in a way by a partial loss of their adaptation mechanisms, and by the fact that the total blood volume, characteristically increased in these subjects, does not decrease during the first weeks of residence at sea level because the lesser production of red cells is compensated by a proportionate increase in plasma volume.1I An association of the several factors already mentioned is likely to occur in pro-
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PULMONARY EDEMA BY ASCENDING TO HIGH ALTITUDES
ducing the high altitude pulmonary edema. Besides, a certain unknown individual predisposition may be present. It is probable that the disturbances occurring in the pulmonary circulation in these cases, are only a magnification of the hemodynamic changes occurring in every person ascending to high altitudes. Electrocardiographic changes related to acute or subacute right ventricular overloading have been observed during the first days of residence at high altitudes in persons who do not develop pulmonary edema.- They are similar, but of lesser degree than those observed in persons developing pulmonary edema, and suggest a certain degree of pulmonary hypertension. Similar changes in the electrocardiogram have been observed in high altitude residents when they lose their acclimatization and develop chronic mountain sickness; in such cases, cardiac catheterization reveals an increase of the pulmonary artery pressures to levels higher than in the acclimatized resident.'" For a better understanding of the mechanisms producing the high altitude pulmonary edema, we feel further hemodynamic studies are necessary in cases with this condition, as well as in people who do not develop pulmonary edema after ascending to high altitudes. SUMMARY
Acute pulmonary edema was observed in 36 young healthy persons after ascending to altitudes 13,700 feet or more above sea level. Most of them were born and living permanently at high altitudes and developed pulmonary edema on returning to the mountains after a relatively short stay at lower or sea levels. The clinical manifestations were usually severe and rapidly progressive disappearing in 24 to 48 hours with oxygen administration. The predominant roentgenologic appearance was a coarse mottling exudate, more confluent in both parahilar regions. The heart size remained normal. The electrocardiogram showed acute right ventricular overloading and primary disturbances
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of repolarization probably related to right ventricular myocardial ischemia. Cardiac catheterization perfonned in one patient during the recovery period at sea level, revealed nonna! pressures in the pulmonary artery and capillary bed. Necropsies perfonned in two patients showed severe pulmonary edema, extensive areas with hyaline membrane, thrombosis of distal arteries and septal capillaries and multiple preterminal arterioles. The left atrium and ventricle were nonnal and there was a moderate right ventricular hypertrophy usually found in the high altitude resident. Pulmonary edema of high altitude appears to be the result of a magnification of the hemodynamic changes occurring during a rapid exposure to an environment of hypoxia and low temperature. These changes would be an increase in cardiac output and pulmonary blood volume, pulmonary vasoconstriction at pre-capillary level with secondary pulmonary hypertension, and increased pulmonary capillary permeability. ACItNOWLEOOMENT: The authon acknowledge the facilities given by Dr. Kurt Hellriegel, Chief Medical Division, Cerro de Pasco Corporation, Peru. RESUMEN
Se observ6 edema pulmonar agudo en 26 personas despues de ascender a alturas de 13,700 pies 0 mayores. La mayorfa de elIas habfan nacido y vivido a elevadas altitudes y el edema se present6 al regresar a las montaiias despues de corta permanencia a altitudes mas bajas 0 al mvel del mar. . Las manifestaciones clfnicas fueron habitualmente graves y rapidamente progresivas, desapareciendo en 24 a 48 horas con la administraci6n de oxfgeno. EI aspecto radiol6gico predominante fue de exudado en forma de moteado grueso mas confluente en ambas regiones parahiliares. EI tamaiio del coraz6n permaneci6 normal. EI ECG mostr6 sobrecarga ventricular derecha aguda y trastomos primarios de repolarizaci6n probablemente en relaci6n con isquemia miocardica ventricular derecha. EI cateterismo cardiac llevado a cabo en un enfermo durante el perlodo de recuperaci6n al mvel del mar revel6 presiones normales en la arteria pulmonar y en el lecho capilar. Las necropsias en dos pacientes mostraron grave edema pulmonar, areas extensas con membrana hialina, trombosis de las arterias distales y de los capitares septales y
EMILIO MARTICORENA,
multiples arteriolas preterminales. La auricula izquierda y el ventrlculo estaban normales y hubo una moderada hipertrofia ventricular derecha que es la habitualmente encontrada en el residente de la gran altitude EI edema pulmonar de la gran altitud parece resultar de un incremento de los cambios hen1.odinamicos que ocurren cuando hay una rapida exposici6n a un ambiente de hipoxia y baja temperatura. Estos cambios consistirfan en un aumento del gasto cardiaco y del volumen de la sangre pulmonar, vasoconstricci6n pulmonar al nivel precapilar con hipertensi6n pulmonar secundaria y aumento de la permeabilidad capilar pulmonar. RESUME
On a pu constater chez 26 individus jeunes et sains, un oedeme pulmonaire aigu, apres ascension a des altitudes de 4.000 m. et plus au-dessus du niveau de la mer. La plupart d'entre eux etaient nes et vivaient de fa~on permanente a des altitudes elevees, et furent atteints d'oedeme pulmonaire lors du retour dans les montagnes aplU un sejour relativement court a des altitudes plus basses ou au niveau de la mer.
Les manifestations cliniques furent generalement graves et rapidement progressives, dispairaissant en 24 a 48 h. apres administration d'oxygene. L'apparence radiologique predominante fut celie d'un exsudat grossierement nodulaire, plus dense dans les regions parahilaires. La taille du coeur resta normaIe. L'electrocardiogramrrie montra un ventricule droit travaillant en surcharge et des perturbations primaires de repolarisation, liees probablement a une ischemie myocardique du ventricule droit. Le catheterisme cardiaque pratique sur un malade pendant la periode de guerison au niveau de la mer, revela des pressions normales dans l'artere pulmonaire et Ie lit capillaire. Des autopsies pratiquees chez deux malades montrerent un oedeme pulmonaire grave, des zones extensives avec membrane hyaline, une thrombose des arteres distales et des capillaires des parois et des multiples arterioles preterminales. L'oreillette et Ie ventricule gauches etaient normttux, et il y avait une hypertrophie moderee du ventricule droit banale chez les individus residant en haute altitude. L'oedeme pulmonaire de haute altitude semble
etre Ie resultat d'une augmentation des altera-
tions hemodynamiques survenant pendant une exposition rapide a un milieu de faible oxygenation et a basse temperature. ees modifications determineraient une surchage du debit cardiaque et du volume sanguin pulmonaire, une vasoconstriction pulmonaire au niveau pre-capillaire avec hypertension pulmonaire secondaire et augmentation de la permeabilite capillaire pulmonaire.
et aLe
Diseases of the Chest ZUSAMMENFASSUNG
Ein akutes Lungenoedem wurde bei 26 jungen gesunden Personen beobachtet nach Aufstieg auf Hohen von 13700 Fuj3 oder mehr iiber Meereshohe. Die meisten von ihnen waren geboren und lebten andauemd in gro13en Hohen, und es kam bei ihnen zu einem Lungenoedem nach Ruckkehr in das Gebirge nach einer relativ kurzen Aufenthaltsdauer in geringen oder Meereshohen. Die klinischen Manifestation en bestanden gewohnlich in schweren und rasch fortschreitenden Krankheitserscheinungen, die innerhalb 24 bis 48 Stunden nach Sauerstoff-Behandlung verschwanden. Die vorherrschenden rontgenologischen Befunde bestanden in einer grobkornigen exsudativen Tiipfelung, die in beiden parahiliren Regionen zur Konfluenz neigte. Die Herzgroj3e blieb normal. Das Elektrokardiogramm zeigte eine akte 'Oberlastung des rechten Ventrikels und primire Storungen in der Depolarisation, wahrscheinlich in Zusammenhang mit einer Myocardischimie des rechten Ventrikels. Eine bei einem Patienten wihrend der Erholungsphase auf Meereshohe vorgenommene Herzkatheterisierung ergab normale Druckwerte in der Lungenarterie und dem Kapillarbett. An 2 Patienten vorgenommene Sektionen zeigten schweres Lungenoedem, ausgedehnte Bezirke mit hyalinen Membranen, Thrombose von distalen Arterien und septalen Kapillaren und multiplen priterminalen Arteriolen. Linker Vorhof und Ventrikel waren normal, und es bestand eine massige Hypertrophie des rechten Ventrikels, wie man sie gewohnlich bei Bewohnern groJ3erer Hohen findet. Das Lungenoedem in groJ3er Hohe scheint das Ergebnis einer EIWeiterung hamodynamischer Veranderungen zu sein, die wihrend einer schenlien Exposition gegeniiber einer Umgebung mit Hypoxamie und niedriger Temperatur auftreten. Diese Veranderungen beinhalten eine Zunahme des Herzminutenvolumens und des pulmonalen Blutvolumens, p u Im 0 n a Ie r Gefaj3konstriktion auch im prikapillaren Bereich mit sekundarer pulmonaler Hypertension und erhohter pulmonaler kapillarer Permeabilitiit. REFERENCES
2 3
4
5
HURTADO, A.: "Aspectos Fisiol6gicos de la Vida en la Altura," Imp. Edit. Rimac S. A., Lima, 1937. LUNDBERO, E.: "Edema Agudo del Pulm6n en el Soroche," Conferencia Asociacion Medica de Yauli, Oroya, 1952. LIZARRAOA, L.: "Soroche Agudo: Edema Agudo del Pulm6n," An. Fac. Med., Lima, 38:244, 1955. BARDALES, A.: "Edema Agudo por Soroche Grave," Rev. Peruana Cardiol., 6: 115, 1957. ALZAMORA-CASTRO. V., GAJUUDO-LECCA, C. AND BATTILANA, G.: "Pulmonary Edema of High Altitude," Am. ]. Cardiol., 7: 769, 1961.
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PULMONARY EDEMA BY ASCENDING TO HIGH ALTITUDES
6 HULTGREN, H. N., SPICKARD, W. B., HELLRIEGEL, K. AND HOUSTON, C. S.: "High Altitude Pulmonary Edema," M.d., 40:289, 1961. 7 HOUSTON, C. S.: "Acute Pulmonary Edema of High Altitude," N.w Engl. I. M.d., 263: 478, 1960. 8 FRED, H. L., SCHMIDT, A. M., BATES, T. AND
HECHT, H. H.: "Acute Pulmonary Edema of Altitude," Circulation, 25: 929, 1962. 9 HULTGREN, H. N., SPICKARD, W. AND LOPEZ, C.: "Further Studies of High Altitude Pulmonary Edema," Brit. Heart I., 24:95, 1962. 10 PENALOZA, D.: "Pulmonary Edema at High Altitude," Panel Discussion (1962 Aspen Conference), in: Progress in R.s.arch in Emphy-
sema and Chronic Bronchitis: Normal and Abnormal Pulmonary Circulation, S. Karger, Basel, 1963.
11 HULTGREN, H. N.: "Pulmonary Edema at High Altitude," Panel Discussion (1962 Aspen Conference), in: Progress in R.search in Emph,s.ma and Chronic Bronchitis: Normal and Abnormal Pulmonary Circulation, S. Karger, Basel, 1963. 12 PENALOZA, D., GAMBOA, R., DYER, J., ECHE-
VA1UUA, M. AND MARTICORENA, E.: "The Influence of High Altitudes on the Electrical Activity of the Heart. I. Electrocardiographic and Vectorcardiographic Observations in the Newborn, Infants and Children," Am. Heart I., 59: Ill, 1960. 13 PENALOZA" D., GAMBOA, R., MARTICORENA, E., ECHEVARRIA, M., DYER, J. AND GUTIERREZ, E. : "The Influence of High Altitudes on the Electrical Activity of the Heart. Electrocardiographic and Vectorcardiographic Observations in Adolescence and Adulthood," Am. Heart I.,
61: 101, 1961. 14 AtuAs-STELLA, J. AND SALDANA, M.: "The Muscular Pulmonary Arteries in People Native to High Altitudes," M edicina Thoracalis, 19:
484, 1962. 15 MOTLEY, H. L., COURNAND, A., WERltO, L.,
HIMMELSTEIN, A. AND DRESDALE, D.: "The Influence of Short Periods of Induced Acute Anoxia upon Pulmonary Artery Pressures in Man," Am. /. Physiol., 150:315, 1947. 16 FRITTS, H. W. AND COURNAND, A.: "Physiological Factors Regulating Pressure, Flow and Distribution of Blood in the Pulmonary Circulation," In: Pulmonary Circulation, p. 62; Ed.
ADAMS, W. R. AND VEITR, I., Grune and Stratton, New York, 1959. 17 FISHMAN, A. P., FRITTS, H. W. AND COURNAND, A.: "Effects of Acute Hypoxia and Exercise on the Pulmonary Circulation," Cir-
culation, 22: 204, 1960. 18 LEWIS, B. M. AND GoRLIN, R.: "Effeco of
Hypoxia on Pulmonary Circulation of the Dog," Am. I. Physiol., 170:574, 1952. 19 HURTADO, A. AND ASTE-SALAZAIl, H.: "Arterial Blood Gases and Acid-Base Balance at Sea Level and at High Altitudes," /. Appl. Physiol.,
1: 304, 1948. 20 PENALOZA, D.,
SIIIB, F., BANeHERo, N., CRUZ, J. AND MARTICORENA, E.: "Pulmonary Hypertension in Healthy Men Born and Living at High Altitudes," Jfm. /. Cardiol., 11: 150,
1963. 21 REEVES, J. T., GROVER, R. F., BLOUNT, S. G., JR. AND FILLEY, G. F.: "Cardiac Output Response to Standing and Treadmill Walking,"
/. Appl. Ph,siol., 16: 283, 1961.
22 HURTADO, A.: Unpubliahed Observations. 23 FRITTS, H. W., ODBLL, J. E., HAJuus, P., BRAUNWALD, E. W. AND FISHMAN, A. P.:
"Effects of Acute Hypoxia on the Volume of Blood in the Thorax," Circulation, 22: 216,
1960. 24 SARNOFF, S. AND SARNOPF, L. C.: "Neurohemodynamics of Pulmonary Edema. II. The
Role of Sympathetic Pathways in the Elevation of Pulmonary and Systemic Vascular Pressures Following the Intracisternal Injection of Fibrin," Circulation, 6:51, 1952. 25 REYNAFARJE, C., LoZANO, R. AND VALDIVIEZO, J. : "The Polycythemia of High Altitudes : Iron Metabolism and Related Aspects," Blood,
14:433, 1959. 26 PENALOZA, D., ECHEVAlUUA, M., MARTICORENA,
E. AND GAMBOA, R. : "Early Electrocardiographic Changes Produced by Ascending to High .~ltitudes," Am. Heart I., 56: 493, 1958. 27 PENALOZA, D., SIME, F., BANCHERO, N. AND GAMBOA, R. : "Pulmonary Hypertension in Healthy Man Born and Living at High Altitudes," M.dicina Thoracalis, 19:449, 1962.
For reprints, please write Dr. Dante Penaloza, High Altitude Research Institute, P. O. Box 1116, Lima, Peru.
INTRAVENOUS ISOPROTERENOL AND EPINEPHRINE Intravenous administration of dllute solutions of Isoproterenol and epInephrine has proved effective In the prevention of ventricular tachycardia and fibrillation In patients with Stokes-Adams disease. Given In this way, the drugs have quIck, transIent actions that permit moment-to-moment control. This therapeutIc approach may seem paradOXic In view of the well-known action of these drugs In IncreasIng ventricular Irritablllty. In addition to this action, however, and crucial to the therapeutic value of this technlc, the drugs accelerate the basic Idlo-
ventricular pacemakers, and thereby suppress ectopIc actIVity in complete heart block. Aggravation of Irrltabillty, either before acceleration becomes adequate or from excessive doses, may be alarming at times. It Is Important to have an external countershock defibrillator In readiness for ventricular fibrillation. LlNENTHAL, A. J. AND ZoLL, P. M.: ··Prevention of Ventricular Tachycardia and Fibrillation by Intravenous Isoproterenol and Epinephrine," Cir,.lMiotl, 27:5, 1963.
A.
TAPIA, M.D., JUAN
DYER,
M.D.,
JOSE SEVERINO, M.D., NATALIO BANCHERO, M.D., RAUL GAMBOA, M.D.,
HEYER
KRUGER, M.D. AND DANTE PENALOZA, M.D., F.C.C.P.
Lima, Peru
M
nendy at high altitudes who developed acute pulmonary edema upon their return to the mountains, after being at lower or sea levels for four to 75 days. Most of them had made short trips to lower levels previously without developing symptoms on returning to higher altitudes. Five had previously developed pulmonary edema on similar circumstances. Two residents of Jauja, 10,499 feet above sea level, had symptoms during their first trip to an altitude of 14,100 feet (4,300 meters) after being at sea level for 14 to 20 months. One patient was born in Lima (500 feet above sea level), but lived at 14,200 feet above sea level (Cerro de Pasco) most of her life; in the last two years, she had spent nine months each year at sea level and had developed pulmonary edema each time she returned. All patients were examined at the time of the acute episode except one who died at home without medical attention; the clinical data were obtained from the relatives and proved by post-mortem examinati~n. Most of the patients had a medical examination for routine check-up or other illness at different intervals prior to the acute episode. None had evidence of pulmonary or cardiac disease. Daily clinical observations were made until complete clearing of the pulmonary symptoms and signs; several patients were seen again from ten to 30 days after discharge from the hospital. Complete 12-lead electrocardiograms and roentgenograms of the chest were taken during the acute episode and daily until three days after clinical manifestations of the pulmonary edema had disappeared. In three patients, chest films five to six months before were available for comparison. Cardiothoracic ratio
ANY INSTANCES OF ACUTE PULMO-
nary edema after ascending to high altitudes have been reported in persons without cardiopulmonary disease. This phenomenon has been observed more frequently in young persons living at high altitudes upon returning to the mountains after a relatively short period at lower levels. 1~ Pulmonary edema has also been reported in mountain climbers.... The mechanisms of its production have not been clearly demonstrated; however, it is generally accepted that anoxia is the main causative factor. Very few hemodynamic data have been obtained during the acute episodes,"1' and post-mortem histologic studies have been reported only in non-acclimatized mountain climbers.' The present report includes clinical, roentgenologic, and electrocardiographic observations made during the acute episode and on recovery of pulmonary edema occurring on ascending to high altitudes. Cardiac catheterization was carried out in one case. Histologic studies performed in two patients revealed distinct features of this syndrome. Preliminary observations were reported previously.
1.
MATERIAL
This study includes observations in 36 persons (30 men and six women) from five to 37 years of age, most of them under 20, residents of altitudes 13,700 feet (4,200 meters) or more above sea level. There were 33 who were born and lived penna·From the Cardiovascular Laboratory, High Altitudes Research Institute, Peruvian University of Medical and Biological Sciences, and the Division of Medicine, Cerro de Pasco Corporation. This investigation was supported by U. S. Public Health Service Research Grants RG-8576, H7000, and H-6910 from the Division of General Medical Sciences and the National Heart Institute.
273
274
EMILIO MARTICORENA,
1: Roentgenograms of a patient with high altitude pulmonary edema. (A) during acute phase: coarse mottling exudate in both lung fields; apices and bases uninvolved. (B) 24 hours later: rapid clearing of exudate; (C) 48 hours later: clear lung fields. FIGURE
et at.
DiseaSC50f the Ch'll
FIGURE 2: Chest films of another patient with severe clinical manifestations of pulmonary edema at high altitude. (A) during acute phase: pre· dominant confluent exudate in the left lung; car· diac borders masked; (B) 24 hours later: rapid resolution of exudate; (C) 48 hours later: com· plete clearing of exudate.
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275
and frontal area were calculated in the serial films. Only five patients were brought to lower levels for treatment. All but one were treated with humid O 2 given by mask or tent. Only one patient received intravenous digitalis the first 24 hours. In one patient, right cardiac catheterization was performed as soon as he was brought down to sea level. Laboratory studies included complete blood count and cell volume determinations. Post-mortem studies were available in two patients. CLINICAL OBSERVATIONS
The time of onset of pulmonary edema after the return to high altitudes varied from three to 48 hours; the majority of patients developed acute pulmonary edema during the first 24 hours. In four cases, it occurred while sleeping and in six immediately after an unusual or prolonged effort. Only one had symptoms of infection of the upper respiratory tract preceding the acute episode. The most frequent early symptoms were: headache, restlessness, increasing dyspnea, dry cough, palpitations, precordial discomfort and nausea. The manifestations of severe respiratory distress appeared in the course of a few hours after the initial symptoms except in one patient who complained of headache and tiredness for 48 hours preceding the respiratory picture. During the acute phase of pulmonary edema, the patients experienced marked dyspnea, wet cough with foamy pink or whitish sputum, cold perspiration, anxiety, occasional vomiting, chills, diffuse muscular and joints aching, thirst, weakness and sensory disturbances. They were markedly dyspneic, in the orthopneic position with cyanosis of the lips and nail beds in the severe cases; marked pallor of the face was observed in most of the patients. The skin was cold and clammy, the lungs were full of wet rales (fine, medium and coarse) and ronchi. Tachycardia and mild to moderate hypotension were present. Only one patient had blood pressure levels of 152/60
3: Chest films of a patient showing: (A) during acme of pulmonary edema: confluent coarse mottling predominantly in the right lung; apices and costo-diaphragmatic angles free; normal heart size; (B) 24 hours later: decreasing exudate; (C) 48 hours later: clear lung fields. FIGURE
EMILIO MARTICORENA, et ale during the attack. Most of the patients were afebrile and several had slight temperature elevation during the first 36 hours. Leukocytosis was present in most of the cases. Administration of humid oxygen produced a beneficial effect and rapid improvement of the clinical condition. Disappearance of the pulmonary congestive signs was observed in 24 to 48 hours. Progress examination four weeks later did not reveal residual symptoms or signs. Two patients died 38 and 53 hours after the onset of symptoms. The first developed acute pulmonary edema three hours after his arrival at Cerro de Pasco, and did not receive any medical attention. The second developed acute pulmonary edema ten hours after his arrival at the high altitude and after running for one hour. Administration of oxygen was inadequate; intraI II III oVR aVL oVF
Diseases of the Chest
venous strophantus and phlebotomy of 200 mI. of blood were of no beneficial effect. ROENTGENOLOGIC STUDIES Representative examples of the roentgenologic findings during the acute pulmonary edema are shown in Figs. 1, 2 and 3. The radiologic appearance was predominantly a coarse mottling exudate scattered in both lung fields, but more confluent and prominent in both parahilar regions and usually with the apices and bases uninvolved. In some cases, the exudate was predominant in one lung and in only one patient was it exclusively localized in the left lung. The radiologic appearance of pulmonary edema disappeared completely, usually within 48 to 72 hours. Clinical improvement preceded the complete clearing of radiologic signs. VI V4 V2 V3 V6 VS
4: Electrocardiograms recorded in one patient with high altitude pulmonary edema: (A) taken the fint day, when the pulmonary edema was severe; (B, C, D and E) recorded at 24-hour intervals, when the pulmonary edema was subsiding. Note in tracing A the positive displacement of the RS-T segment instead of the negative one which is often associated with right bundle branch block. In the following records this finding gradually disappean while the T waves become negative in the right precordial leads. In the last tracing the ischemic T -wave pattern decreases. FIOURE
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In all patients the pulmonary artery was prominent during the attack, decreasing in size upon recovery. The heart was nonnal in size and configuration with only minor or no decrease in overall size after clearing of pulmonary changes. In five patients, the cardiac borders were masked by the exudate and in two of them, it was not possible to outline the cardiac silhouette for measurement. ELECTROCARDIOGRAPHIC FINDINGS
Variations in the electrocardiogram during the pulmonary edema and on recovery are shown in Figs. 4, 5 and 6. The electrocardiographic pattern observed during the episode of respiratory distress was similar to that observed in acute cor pulmonale and other forms of acute right ventricular overloading.
277
Sinus tachycardia was present in all cases (heart rate average 124, range 105150). The amplitude of the P waves did not exceed the 3 mm., but they were slightly peaked in most of the tracings, especially in leads II and VI. SAQRS was oriented to the right and fOlWard with a mean value of +123° (range +15 to ±1800). Tall R waves in aVR, Rs complexes in VsR and fairly deep S waves in V6 were frequently present. Slight positive displacement of the RS-T segment was noted in right precordial leads in several patients, and this occurred in spite of the presence of right bundle branch block observed in some cases. Abnonnal configuration of the T waves was seen in the same leads and in seven patients the T waves were rather tall and peaked in precordial as well as in limb leads. 0
A
c o FIGURE 5: Electrocardiograms taken at 24-hour intervals in another case with high altitude pulmonary edema. Serial tracings show changes related to acute right ventricular overloading, which gradually decreases.
EMILIO MARTICORENA,
et al.
Oi_of the Chest
A
B
c FIGURE 6: Electrocardiograms obtained in a 13-year-old boy, 24 houn, 48 hOl1n and four weeks after the onset of pulmonary edema. Right SAQRS deviation is a frequent findings in the natives of high altitude. The acute right ventricular overloading is reflected in the tint tracing by a positive displacement of the RS-T segment in right precordial leads. It disappears when the overloading decreases and the T waves become deeply negative, peaked and symmetrical. In the last tracing the ventricular repoIarization becomes normal. Peaked P waves seen in the tint two tracings become normal in the final record.
The P and QRS changes decreased in 24 to 48 hours in relation to the clinical and roentgenologic improvement. The positive displacement of the RS-T segment also disappeared in right precordial leads.
The T waves became more abnormal, some times flat or negative, peaked and symmetrical during the following two or three days. The disturbances of the ventricular repolarization disappeared later than the
FIGURE 7: Roentgenograms obtained in same patient as Fig. 4. (A) At high altitude when the pulmonary edema was "severe; (B) 22 houn later, during the right heart catheterization performed at sea level when the clinical manifestations were subsiding.
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PULMONARY EDEMA BY ASCENDING TO HIGH ALTITUDES
279
FIOURE 8: Histologic section showing pulmonary edema and hyaline membranes (in dark black) in close contact with alveolar wall (PAS staining).
changes of the auricular and ventricular depolarization. After recovery the electrocardiogram was similar to those observed in normal persons living permanendy in similar high altitudes. 11." HEMODYNAMIC STUDIES
Right cardiac catheterization was performed in one case 40 hours after the onset of the pulmonary edema, when the clinical and roentgenologic manifestations were subsiding (Fig. 7). This study was performed as soon as he was brought down to sea level; at this time, the arterial oxygen saturation, the pulmonary artery and capillary pressures were normal. However, changes observed in the serial electrocardiograms of this patient suggest that pulmonary hypertension and acute right ventricular overloading were present previously (Fig. 4). HISTOLOGIC FINDINGS
Macroscopic and microscopic evidence of severe pulmonary edema was present in both cases with necropsy studies. There were extensive areas with hyaline membranes in close contact with the alveolar wall and also floating like tangled material in the edema fluid, more numerous in the lower and middle lobes (Fig. 8). Histochemical analysis of the hyaline membrane
revealed an identical composition to the hyaline membranes of the newborn. The alveolar septi were thickened due to marked capillary congestion. Focal areas of emphysema alternated with the areas of edema. The pulmonary veins showed marked congestion. In both cases recent vascular thrombi were found; in one, they were located in the small pulmonary arteries, in the other, at the septal capillaries. Both patients exhibited thickening of the muscular arteries, numerous preterminal arterioles and interseptal vessels with definite muscular media. These changes were more severe than those seen in high altitude acclimatized residentsl • and in one of them, the changes were similar to those observed in severe chronic pulmonary hypertension with occlusive changes, intimal sclerosis and muscular hyperplasia of small arteries and arterioles. In this case, small, localized areas of healed tuberculosis were observed in the left lung. Moderate to severe right ventricular hypertrophy was found in both patients. There was neither left atrial nor left ventricular dilatation and the left ventricular myocardium had no pathologic changes. DISCUSSION
Pulmonary edema of high altitude appears to be the result of hemodynamic
EMILIO MARTICORENA,
changes occurring primarily in the pulmonary vascular bed. Cardiac catheterization performed in three patients, one by Fred and his associates' and two by Hultgren and co-workers,' has confirmed the presence of pulmonary hypertension in these cases and has revealed normal left atrial pressure. This latter finding makes less probable the possibility that pulmonary edema of high altitude is due primarily to an increase of left ventricular diastolic pressure with or without myocardial failure. In addition, the roentgen examination did not reveal enlargement of the left cardiac chambers, and this also was observed in the two necropsied cases. Nonnal pulmonary capillary pressures in two patients with high altitude pulmonary edema have been reported by Hultgren. l1 This finding is in agreement with previous investigations perfonned in man suggesting that pulmonary hypertension induced by acute hypoxia is mainly due to vasoconstriction at precapillary leveI. 1I•1• If pulmonary capillary hypertension is not present in high altitude pulmonary edema, we would have to admit the presence of an increased capillary permeability; this possibility has not been demonstrated in experiments on acute hypoxia, but it cannot be entirely excluded in cases of high altitude pulmonary edema. The frequent finding of fibrin and hyaline membrane in the alveolar exudate in such cases may be an indication .of increased capillary permeability. Besides these changes probably taking place in the pulmonary capillaries, other factors may playa role in the mechanism of production of this type of pulmonary edema. It is known that cardiac output increases in response to experimental acute hypoxial '.1f and the magnitude of such increase is related to the degree of anoxemia. lf•I ' Hurtado and Aste-Salazar11 have demonstrated that the degree of anoxemia is more accentuated in newcomers than in residents of high altitude. While the cardiac output remains within normal limits in the high altitude resident,II it is prob-
et ale
Diseases of
the Chest
ably increased during the initial period of exposure to high altitudes. A further increase in cardiac output induced by exertion may take place in some cases. The development of pulmonary edema occurring in some patients while sleeping could be explained by an additional increment in cardiac output in these circumstances; this may be related ot the postural changeSl and to the fall in arterial O 2 saturation on supine position and particularly during sleeping as observed at high altitudes by Hurtado. a Another factor which probably participates in the production of high altitude pulmonary edema is an increase of pulmomonary blood volume. Studies on the effect of acute hypoxia upon the pulmonary blood volume are contradictory. Recent studies in man by Fritts and co-workers" indicate that acute hypoxia does not produce any increase of blood volume in the lungs. However, all the climatic conditions present on ascending to high altitudes, e.g., a low temperature, are not reproduced in experiments on acute hypoxia. Marked pallor and coldness are usually observed on persons ascending to high altitude, suggesting the presence of peripheral vasoconstriction. According to Sarnoff's observations," the peripheral vasoconstriction may produce displacement of blood into the pulmonary circulation; therefore, it is possible that an increase in the pulmonary blood volume may occur preceding the high altitude pulmonary edema. The higher incidence of this type of pulmonary edema in high altitude natives returning to their place of residence after a short stay at sea level may be explained in a way by a partial loss of their adaptation mechanisms, and by the fact that the total blood volume, characteristically increased in these subjects, does not decrease during the first weeks of residence at sea level because the lesser production of red cells is compensated by a proportionate increase in plasma volume.1I An association of the several factors already mentioned is likely to occur in pro-
Volume 45, No. March 1964
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PULMONARY EDEMA BY ASCENDING TO HIGH ALTITUDES
ducing the high altitude pulmonary edema. Besides, a certain unknown individual predisposition may be present. It is probable that the disturbances occurring in the pulmonary circulation in these cases, are only a magnification of the hemodynamic changes occurring in every person ascending to high altitudes. Electrocardiographic changes related to acute or subacute right ventricular overloading have been observed during the first days of residence at high altitudes in persons who do not develop pulmonary edema.- They are similar, but of lesser degree than those observed in persons developing pulmonary edema, and suggest a certain degree of pulmonary hypertension. Similar changes in the electrocardiogram have been observed in high altitude residents when they lose their acclimatization and develop chronic mountain sickness; in such cases, cardiac catheterization reveals an increase of the pulmonary artery pressures to levels higher than in the acclimatized resident.'" For a better understanding of the mechanisms producing the high altitude pulmonary edema, we feel further hemodynamic studies are necessary in cases with this condition, as well as in people who do not develop pulmonary edema after ascending to high altitudes. SUMMARY
Acute pulmonary edema was observed in 36 young healthy persons after ascending to altitudes 13,700 feet or more above sea level. Most of them were born and living permanently at high altitudes and developed pulmonary edema on returning to the mountains after a relatively short stay at lower or sea levels. The clinical manifestations were usually severe and rapidly progressive disappearing in 24 to 48 hours with oxygen administration. The predominant roentgenologic appearance was a coarse mottling exudate, more confluent in both parahilar regions. The heart size remained normal. The electrocardiogram showed acute right ventricular overloading and primary disturbances
281
of repolarization probably related to right ventricular myocardial ischemia. Cardiac catheterization perfonned in one patient during the recovery period at sea level, revealed nonna! pressures in the pulmonary artery and capillary bed. Necropsies perfonned in two patients showed severe pulmonary edema, extensive areas with hyaline membrane, thrombosis of distal arteries and septal capillaries and multiple preterminal arterioles. The left atrium and ventricle were nonnal and there was a moderate right ventricular hypertrophy usually found in the high altitude resident. Pulmonary edema of high altitude appears to be the result of a magnification of the hemodynamic changes occurring during a rapid exposure to an environment of hypoxia and low temperature. These changes would be an increase in cardiac output and pulmonary blood volume, pulmonary vasoconstriction at pre-capillary level with secondary pulmonary hypertension, and increased pulmonary capillary permeability. ACItNOWLEOOMENT: The authon acknowledge the facilities given by Dr. Kurt Hellriegel, Chief Medical Division, Cerro de Pasco Corporation, Peru. RESUMEN
Se observ6 edema pulmonar agudo en 26 personas despues de ascender a alturas de 13,700 pies 0 mayores. La mayorfa de elIas habfan nacido y vivido a elevadas altitudes y el edema se present6 al regresar a las montaiias despues de corta permanencia a altitudes mas bajas 0 al mvel del mar. . Las manifestaciones clfnicas fueron habitualmente graves y rapidamente progresivas, desapareciendo en 24 a 48 horas con la administraci6n de oxfgeno. EI aspecto radiol6gico predominante fue de exudado en forma de moteado grueso mas confluente en ambas regiones parahiliares. EI tamaiio del coraz6n permaneci6 normal. EI ECG mostr6 sobrecarga ventricular derecha aguda y trastomos primarios de repolarizaci6n probablemente en relaci6n con isquemia miocardica ventricular derecha. EI cateterismo cardiac llevado a cabo en un enfermo durante el perlodo de recuperaci6n al mvel del mar revel6 presiones normales en la arteria pulmonar y en el lecho capilar. Las necropsias en dos pacientes mostraron grave edema pulmonar, areas extensas con membrana hialina, trombosis de las arterias distales y de los capitares septales y
EMILIO MARTICORENA,
multiples arteriolas preterminales. La auricula izquierda y el ventrlculo estaban normales y hubo una moderada hipertrofia ventricular derecha que es la habitualmente encontrada en el residente de la gran altitude EI edema pulmonar de la gran altitud parece resultar de un incremento de los cambios hen1.odinamicos que ocurren cuando hay una rapida exposici6n a un ambiente de hipoxia y baja temperatura. Estos cambios consistirfan en un aumento del gasto cardiaco y del volumen de la sangre pulmonar, vasoconstricci6n pulmonar al nivel precapilar con hipertensi6n pulmonar secundaria y aumento de la permeabilidad capilar pulmonar. RESUME
On a pu constater chez 26 individus jeunes et sains, un oedeme pulmonaire aigu, apres ascension a des altitudes de 4.000 m. et plus au-dessus du niveau de la mer. La plupart d'entre eux etaient nes et vivaient de fa~on permanente a des altitudes elevees, et furent atteints d'oedeme pulmonaire lors du retour dans les montagnes aplU un sejour relativement court a des altitudes plus basses ou au niveau de la mer.
Les manifestations cliniques furent generalement graves et rapidement progressives, dispairaissant en 24 a 48 h. apres administration d'oxygene. L'apparence radiologique predominante fut celie d'un exsudat grossierement nodulaire, plus dense dans les regions parahilaires. La taille du coeur resta normaIe. L'electrocardiogramrrie montra un ventricule droit travaillant en surcharge et des perturbations primaires de repolarisation, liees probablement a une ischemie myocardique du ventricule droit. Le catheterisme cardiaque pratique sur un malade pendant la periode de guerison au niveau de la mer, revela des pressions normales dans l'artere pulmonaire et Ie lit capillaire. Des autopsies pratiquees chez deux malades montrerent un oedeme pulmonaire grave, des zones extensives avec membrane hyaline, une thrombose des arteres distales et des capillaires des parois et des multiples arterioles preterminales. L'oreillette et Ie ventricule gauches etaient normttux, et il y avait une hypertrophie moderee du ventricule droit banale chez les individus residant en haute altitude. L'oedeme pulmonaire de haute altitude semble
etre Ie resultat d'une augmentation des altera-
tions hemodynamiques survenant pendant une exposition rapide a un milieu de faible oxygenation et a basse temperature. ees modifications determineraient une surchage du debit cardiaque et du volume sanguin pulmonaire, une vasoconstriction pulmonaire au niveau pre-capillaire avec hypertension pulmonaire secondaire et augmentation de la permeabilite capillaire pulmonaire.
et aLe
Diseases of the Chest ZUSAMMENFASSUNG
Ein akutes Lungenoedem wurde bei 26 jungen gesunden Personen beobachtet nach Aufstieg auf Hohen von 13700 Fuj3 oder mehr iiber Meereshohe. Die meisten von ihnen waren geboren und lebten andauemd in gro13en Hohen, und es kam bei ihnen zu einem Lungenoedem nach Ruckkehr in das Gebirge nach einer relativ kurzen Aufenthaltsdauer in geringen oder Meereshohen. Die klinischen Manifestation en bestanden gewohnlich in schweren und rasch fortschreitenden Krankheitserscheinungen, die innerhalb 24 bis 48 Stunden nach Sauerstoff-Behandlung verschwanden. Die vorherrschenden rontgenologischen Befunde bestanden in einer grobkornigen exsudativen Tiipfelung, die in beiden parahiliren Regionen zur Konfluenz neigte. Die Herzgroj3e blieb normal. Das Elektrokardiogramm zeigte eine akte 'Oberlastung des rechten Ventrikels und primire Storungen in der Depolarisation, wahrscheinlich in Zusammenhang mit einer Myocardischimie des rechten Ventrikels. Eine bei einem Patienten wihrend der Erholungsphase auf Meereshohe vorgenommene Herzkatheterisierung ergab normale Druckwerte in der Lungenarterie und dem Kapillarbett. An 2 Patienten vorgenommene Sektionen zeigten schweres Lungenoedem, ausgedehnte Bezirke mit hyalinen Membranen, Thrombose von distalen Arterien und septalen Kapillaren und multiplen priterminalen Arteriolen. Linker Vorhof und Ventrikel waren normal, und es bestand eine massige Hypertrophie des rechten Ventrikels, wie man sie gewohnlich bei Bewohnern groJ3erer Hohen findet. Das Lungenoedem in groJ3er Hohe scheint das Ergebnis einer EIWeiterung hamodynamischer Veranderungen zu sein, die wihrend einer schenlien Exposition gegeniiber einer Umgebung mit Hypoxamie und niedriger Temperatur auftreten. Diese Veranderungen beinhalten eine Zunahme des Herzminutenvolumens und des pulmonalen Blutvolumens, p u Im 0 n a Ie r Gefaj3konstriktion auch im prikapillaren Bereich mit sekundarer pulmonaler Hypertension und erhohter pulmonaler kapillarer Permeabilitiit. REFERENCES
2 3
4
5
HURTADO, A.: "Aspectos Fisiol6gicos de la Vida en la Altura," Imp. Edit. Rimac S. A., Lima, 1937. LUNDBERO, E.: "Edema Agudo del Pulm6n en el Soroche," Conferencia Asociacion Medica de Yauli, Oroya, 1952. LIZARRAOA, L.: "Soroche Agudo: Edema Agudo del Pulm6n," An. Fac. Med., Lima, 38:244, 1955. BARDALES, A.: "Edema Agudo por Soroche Grave," Rev. Peruana Cardiol., 6: 115, 1957. ALZAMORA-CASTRO. V., GAJUUDO-LECCA, C. AND BATTILANA, G.: "Pulmonary Edema of High Altitude," Am. ]. Cardiol., 7: 769, 1961.
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PULMONARY EDEMA BY ASCENDING TO HIGH ALTITUDES
6 HULTGREN, H. N., SPICKARD, W. B., HELLRIEGEL, K. AND HOUSTON, C. S.: "High Altitude Pulmonary Edema," M.d., 40:289, 1961. 7 HOUSTON, C. S.: "Acute Pulmonary Edema of High Altitude," N.w Engl. I. M.d., 263: 478, 1960. 8 FRED, H. L., SCHMIDT, A. M., BATES, T. AND
HECHT, H. H.: "Acute Pulmonary Edema of Altitude," Circulation, 25: 929, 1962. 9 HULTGREN, H. N., SPICKARD, W. AND LOPEZ, C.: "Further Studies of High Altitude Pulmonary Edema," Brit. Heart I., 24:95, 1962. 10 PENALOZA, D.: "Pulmonary Edema at High Altitude," Panel Discussion (1962 Aspen Conference), in: Progress in R.s.arch in Emphy-
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11 HULTGREN, H. N.: "Pulmonary Edema at High Altitude," Panel Discussion (1962 Aspen Conference), in: Progress in R.search in Emph,s.ma and Chronic Bronchitis: Normal and Abnormal Pulmonary Circulation, S. Karger, Basel, 1963. 12 PENALOZA, D., GAMBOA, R., DYER, J., ECHE-
VA1UUA, M. AND MARTICORENA, E.: "The Influence of High Altitudes on the Electrical Activity of the Heart. I. Electrocardiographic and Vectorcardiographic Observations in the Newborn, Infants and Children," Am. Heart I., 59: Ill, 1960. 13 PENALOZA" D., GAMBOA, R., MARTICORENA, E., ECHEVARRIA, M., DYER, J. AND GUTIERREZ, E. : "The Influence of High Altitudes on the Electrical Activity of the Heart. Electrocardiographic and Vectorcardiographic Observations in Adolescence and Adulthood," Am. Heart I.,
61: 101, 1961. 14 AtuAs-STELLA, J. AND SALDANA, M.: "The Muscular Pulmonary Arteries in People Native to High Altitudes," M edicina Thoracalis, 19:
484, 1962. 15 MOTLEY, H. L., COURNAND, A., WERltO, L.,
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ADAMS, W. R. AND VEITR, I., Grune and Stratton, New York, 1959. 17 FISHMAN, A. P., FRITTS, H. W. AND COURNAND, A.: "Effects of Acute Hypoxia and Exercise on the Pulmonary Circulation," Cir-
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Hypoxia on Pulmonary Circulation of the Dog," Am. I. Physiol., 170:574, 1952. 19 HURTADO, A. AND ASTE-SALAZAIl, H.: "Arterial Blood Gases and Acid-Base Balance at Sea Level and at High Altitudes," /. Appl. Physiol.,
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SIIIB, F., BANeHERo, N., CRUZ, J. AND MARTICORENA, E.: "Pulmonary Hypertension in Healthy Men Born and Living at High Altitudes," Jfm. /. Cardiol., 11: 150,
1963. 21 REEVES, J. T., GROVER, R. F., BLOUNT, S. G., JR. AND FILLEY, G. F.: "Cardiac Output Response to Standing and Treadmill Walking,"
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22 HURTADO, A.: Unpubliahed Observations. 23 FRITTS, H. W., ODBLL, J. E., HAJuus, P., BRAUNWALD, E. W. AND FISHMAN, A. P.:
"Effects of Acute Hypoxia on the Volume of Blood in the Thorax," Circulation, 22: 216,
1960. 24 SARNOFF, S. AND SARNOPF, L. C.: "Neurohemodynamics of Pulmonary Edema. II. The
Role of Sympathetic Pathways in the Elevation of Pulmonary and Systemic Vascular Pressures Following the Intracisternal Injection of Fibrin," Circulation, 6:51, 1952. 25 REYNAFARJE, C., LoZANO, R. AND VALDIVIEZO, J. : "The Polycythemia of High Altitudes : Iron Metabolism and Related Aspects," Blood,
14:433, 1959. 26 PENALOZA, D., ECHEVAlUUA, M., MARTICORENA,
E. AND GAMBOA, R. : "Early Electrocardiographic Changes Produced by Ascending to High .~ltitudes," Am. Heart I., 56: 493, 1958. 27 PENALOZA, D., SIME, F., BANCHERO, N. AND GAMBOA, R. : "Pulmonary Hypertension in Healthy Man Born and Living at High Altitudes," M.dicina Thoracalis, 19:449, 1962.
For reprints, please write Dr. Dante Penaloza, High Altitude Research Institute, P. O. Box 1116, Lima, Peru.
INTRAVENOUS ISOPROTERENOL AND EPINEPHRINE Intravenous administration of dllute solutions of Isoproterenol and epInephrine has proved effective In the prevention of ventricular tachycardia and fibrillation In patients with Stokes-Adams disease. Given In this way, the drugs have quIck, transIent actions that permit moment-to-moment control. This therapeutIc approach may seem paradOXic In view of the well-known action of these drugs In IncreasIng ventricular Irritablllty. In addition to this action, however, and crucial to the therapeutic value of this technlc, the drugs accelerate the basic Idlo-
ventricular pacemakers, and thereby suppress ectopIc actIVity in complete heart block. Aggravation of Irrltabillty, either before acceleration becomes adequate or from excessive doses, may be alarming at times. It Is Important to have an external countershock defibrillator In readiness for ventricular fibrillation. LlNENTHAL, A. J. AND ZoLL, P. M.: ··Prevention of Ventricular Tachycardia and Fibrillation by Intravenous Isoproterenol and Epinephrine," Cir,.lMiotl, 27:5, 1963.