Circulatory dynamics during high altitude pulmonary edema

doi:10.1016/0002-9149(69)90517-7

The American Journal of Cardiology

Volume 23, Issue 3, March 1969, Pages 369-378

https://doi.org/10.1016/0002-9149(69)90517-7 Get rights and content

Abstract

Cardiac catheterization studies have been carried out in 2 young male subjects who experienced acute pulmonary edema after a brief sojourn at sea level, when they returned to their native town located at 14,200 feet above sea level. The investigation was performed at this altitude during the acute episode and was repeated after complete recovery. Further studies were made in 1 subject after prolonged residence at sea level.

Severe hypoxemia, a marked degree of pulmonary hypertension and increased pulmonary vascular resistance were found during the acute pulmonary edema. These findings were associated with low cardiac output and pulmonary wedge pressure. The degree of pulmonary hypertension was significantly reduced after inhalation of 100 per cent oxygen. Following recovery, physiologic observations were similar to those seen in healthy residents well acclimatized to high altitudes. The data obtained suggest the presence of arteriolar constriction at the precapillary level due to severe hypoxia.

Several factors may explain the severe hypoxemia observed in patients with high altitude pulmonary edema. Exercise and sleeping may decrease significantly the arterial oxygen saturation at high altitudes. Pulmonary edema occurred during exercise in our first case, and during sleep in the second. However, special susceptibility appears to be present in humans who develop pulmonary edema after rapid exposure to high altitudes. The role of a sudden rise of pulmonary artery pressure in producing pulmonary edema without elevation of pulmonary wedge pressure is not clear.

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Cited by (77)

Editorial commentary: The heart at high altitude
2023, Trends in Cardiovascular Medicine
Brain Natriuretic Peptide Levels and the Occurrence of Subclinical Pulmonary Edema in Healthy Lowlanders at High Altitude
2015, Canadian Journal of Cardiology
Citation Excerpt :
This finding is in concordance with our previous ultrasound investigation in the Himalayan Khumbu3 and confirms the high incidence of silent HA interstitial edema among newcomers4 and experienced climbers,5 reinforcing the theory of EVLF as part of a normal physiological response to hypobaric hypoxia. Complex interactions between pulmonary vascular reactivity, fluid retention, vascular permeability, and LV diastolic filling properties, modulated by individual genetic background, still need to be investigated to elucidate this phenomenon.5-9 Regarding the BNP response observed throughout the ascension (ie, stable levels until post-summit increase and decrease), our findings somewhat deviate from those of Woods et al., who described increased BNP levels at rest and after exercise at 4270 m.12,13 Not irreconcilable with the present study, they observed the highest levels in those with severe AMS and exaggerated PASP, and no increase in 4 subjects.
High altitude (HA) pulmonary edema (PE) results from complex and misunderstood interactions between adaptation mechanisms. We assessed the occurrence of subclinical PE and brain natriuretic peptide (BNP) levels among nonacclimatized individuals during an expedition on Mount Elbrus (5642 m).
Seven subjects underwent assessment of vital signs, Lake Louise Score, ultrasound lung comets using handheld echography and circulating BNP using capillary testing at different stages of ascension, in addition to baseline echocardiography. Friedman tests were used to compare serial measurements.
Heart rate, Lake Louise Score (P < 0.0001) and blood pressure (P = 0.037) increased during ascension; oxygen saturation decreased (P < 0.0001). BNP increased (40.7 ± 16.8 vs 19.7 ± 3.04 pg/mL; P < 0.01) after the summit, as did ultrasound lung comet count throughout ascension (P < 0.0001), but both parameters were not correlated (r = 0.36; P = 0.42). Post-summit peak BNP correlated with baseline left ventricular mass index (r = −0.79; P = 0.033).
This study confirms the high incidence of subclinical PE during subacute exposure to hypobaric hypoxia and enhancement of this phenomenon after exertion. Although not correlated with the degree of PE, BNP levels increased after sustained effort at HA, but not at rest. Further investigation is needed to determine the mechanisms underlying the BNP response at HA and its usefulness as a monitoring tool during expeditions.
L’œdème pulmonaire (OP) de haute altitude (HA) résulte d’interactions complexes et méconnues entre les mécanismes d’adaptation. Nous avons évalué l’apparition d’OP subclinique et les concentrations du peptide natriurétique de type B (BNP : brain natriuretic peptide) chez les individus non acclimatés durant une expédition au Mont Elbouz (5642 m).
Sept sujets ont subi l’évaluation des signes vitaux, le score de Lake Louise, les queues de comète en échographie pulmonaire à l’aide de l’échographie manuelle et le BNP circulant à l’aide du test capillaire à différentes étapes de l’ascension, en plus de l’échocardiographie initiale. Les tests de Friedman ont été utilisés pour comparer les mesures sérielles.
La fréquence cardiaque, le score de Lake Louise (P < 0,0001) et la pression artérielle (P = 0,037) ont augmenté au cours de l’ascension; la saturation en oxygène a diminué (P < 0,0001). Le BNP a augmenté (40,7 ± 16,8 vs 19,7 ± 3,04 pg/ml; P < 0,01) après le sommet, comme l’a été le comptage des queues de comète à l’échographie pulmonaire tout au long de l’ascension (P < 0,0001), mais les deux paramètres ne corrélaient pas (r = 0,36; P = 0,42). Les concentrations maximales du BNP après le sommet corrélaient avec l’indice de masse ventriculaire gauche initial (r = −0,79; P = 0,033).
L’étude confirme l’incidence élevée de l’OP subclinique durant l’exposition subaiguë à l’hypoxie hypobare et l’amélioration de ce phénomène après l’effort. Bien qu’elles n’aient pas corrélé avec le degré d’OP, les concentrations du BNP ont augmenté après l’effort soutenu en HA, mais non au repos. D’autres études sont nécessaires pour déterminer les mécanismes qui sous-tendent la réponse du BNP à la HA et son utilité comme outil de surveillance durant les expéditions.
Echocardiographic Assessment of Cardiac Performance in Response to High Altitude and Development of Subclinical Pulmonary Edema in Healthy Climbers
2013, Canadian Journal of Cardiology
Citation Excerpt :
According to Allemann et al., who introduced the concept of compensated diastolic dysfunction, overt diastolic dysfunction is prevented by augmented atrial contraction in healty individuals.17 From a conceptual point of view, HAPE is recognized as a noncardiogenic pulmonary edema, consistent with our findings.1-3,5-7 With increased PAP and afterload, the right ventricle is submitted to a considerable burden of physiologic demand at high altitude.
Data regarding the effect of high altitude on heart function are sparse and conflicting. We aimed to assess the right and left ventricular responses to altitude-induced hypoxia and the occurrence of subclinical pulmonary edema.
Echocardiography was performed according to protocol on 14 subjects participating in an expedition in Nepal, at 3 altitude levels: Montreal (30 m), Namche Bazaar (3450 m), and Chukkung (4730 m). Systematic lung ultrasound was performed to detect ultrasound lung comets.
Pulmonary artery systolic pressure increased in all subjects between Montreal and Chukkung (mean 27.4 ± 5.4 mm Hg vs 39.3 ± 7.7 mm Hg; P < 0.001). Right ventricular (RV) myocardial performance index (MPI) increased significantly (0.32 ± 0.08 at 30 m vs 0.41 ± 0.10 at 4730 m; P = 0.046). A trend toward deteriorated RV free wall longitudinal strain was observed between Montreal and Chukkung (−25.9 [5.3%] vs −21.9 [6.4%]; P = 0.092). The left ventricular early diastolic inflow velocity/atrial mitral inflow velocity and early diastolic inflow velocity/mean of the maximal early diastolic mitral annulus tissue doppler velocities ratios remained unchanged. At 4730 m, ultrasound lung comets were seen in all subjects except 1. None had clinical criteria for high-altitude pulmonary edema (HAPE). All altered parameters normalized after return to sea level.
Subclinical HAPE is frequent in healthy lowlander climbers. This is the first study to document a trend towards decreased RV free wall strain and MPI increment at high altitude. Whether rising RV MPI is a physiologic adaptive mechanism to hypoxia or a pathologic response identifying HAPE-susceptible subjects needs further study.
Les données concernant l'effet de la haute altitude sur le fonctionnement du cœur sont rares et contradictoires. Nous avions pour but d'évaluer les réponses du ventricule gauche et du ventricule droit à l'hypoxie de l'altitude et la survenue de l'œdème pulmonaire subclinique.
L'échocardiographie a été réalisée selon le protocole auprès de 14 sujets participant à une expédition au Népal, et ce, à 3 différentes altitudes : Montréal (30 m), Namche Bazaar (3 450 m) et Chukkung (4 730 m). Une échographie pulmonaire systématique a été réalisée pour détecter les « queues de comètes » à l'échographie pulmonaire.
La pression systolique de l'artère pulmonaire a augmenté chez tous les sujets entre Montréal et Chukkung (moyenne de 27,4 ± 5,4 mm Hg vs 39,3 ± 7,7 mm Hg; P < 0,001). L'indice de performance myocardique (IPM) du ventricule droit (VD) a augmenté de façon significative (0,32 ± 0,08 à 30 m vs 0,41 ± 0,10 à 4 730 m; P = 0,046). Une tendance à la détérioration de la déformation longitudinale de la paroi libre du VD a été observée entre Montréal et Chukkung (−25,9 [5,3 %] vs −21,9 [6,4 %]; P = 0,092). La vitesse du flux diastolique précoce du ventricule gauche et la vitesse du flux mitral, ainsi que la vitesse du flux diastolique précoce et la moyenne des ratios des vitesses diastoliques précoces maximales au Doppler tissulaire de l'anneau mitral sont demeurées inchangées. À 4 730 m, des « queues de comètes » à l'échographie pulmonaire ont été observées chez tous les sujets sauf 1. Aucun d'entre eux n'a montré les critères cliniques de l'œdème pulmonaire de haute altitude (OPHA). Tous les paramètres altérés sont revenus à la normale lors du retour au niveau de la mer.
L'OPHA subclinique est fréquent chez les grimpeurs de basse altitude en santé. C'est la première étude à documenter la tendance à la diminution de la déformation de la paroi libre du VD et à l'augmentation de l'IPM à haute altitude. Que l'augmentation de l'IPM du VD soit un mécanisme physiologique d'adaptation à l'hypoxie ou une réponse pathologique repérant les sujets susceptibles de souffrir d'un OPHA, d'autres études sont nécessaires.
Effects of high-altitude exposure on the pulmonary circulation
2012, Revista Espanola de Cardiologia
High-altitude pulmonary edema is associated with coagulation and fibrinolytic abnormalities
2012, American Journal of the Medical Sciences
High-altitude pulmonary edema (HAPE) can develop in unacclimatized persons after acute ascent to high altitude and is associated with fibrinolytic and coagulation abnormalities. The authors investigated whether fibrinolytic and coagulation abnormalities were associated with the severity of HAPE.
Sixty-one patients who developed HAPE after acute ascent to altitudes above 3600 m were recruited. Twenty unacclimatized controls who acutely ascended to the same altitude and 20 acclimatized inhabitants served as controls. Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) levels were measured using chromogenic substrate assays. Plasma fibrinogen concentration was determined by the sodium sulphite fractionation method. The concentrations of fibrin/fibrinogen degradation products (FDP) and D-dimer were measured by enzyme linked immunosorbent assay.
The plasma concentrations of D-dimer, fibrinogen, FDP and t-PA and PAI-1 were significantly higher in patients with HAPE than controls. In addition, these abnormalities were correlated with the severity of HAPE. The plasma concentrations of D-dimer and fibrinogen recovered to normal upon recovery from HAPE while t-PA, PAI-1 and FDP levels in HAPE patients still remained significantly increased over those of unacclimatized controls.
The development of HAPE is associated with abnormalities in the fibrinolysis and coagulation system, and these abnormalities correlate with the severity of HAPE.
Prevention and treatment of high-altitude pulmonary edema
2010, Progress in Cardiovascular Diseases
We distinguish two forms of high altitude illness, a cerebral form called acute mountain sickness and a pulmonary form called high-altitude pulmonary edema (HAPE). Individual susceptibility is the most important determinant for the occurrence of HAPE. The hallmark of HAPE is an excessively elevated pulmonary artery pressure (mean pressure 36-51 mm Hg), caused by an inhomogeneous hypoxic pulmonary vasoconstriction which leads to an elevated pulmonary capillary pressure and protein content as well as red blood cell-rich edema fluid. Furthermore, decreased fluid clearance from the alveoli may contribute to this noncardiogenic pulmonary edema. Immediate descent or supplemental oxygen and nifedipine or sildenafil are recommended until descent is possible. Susceptible individuals can prevent HAPE by slow ascent, average gain of altitude not exceeding 300 m/d above an altitude of 2500 m. If progressive high altitude acclimatization would not be possible, prophylaxis with nifedipine or tadalafil for long sojourns at high altitude or dexamethasone for a short stay of less then 5 days should be recommended.

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^☆: This work was supported by U. S. Public Health Service Research Grant HE-06910 and U. S. Army Research Grant DA-HC19-67-G-0025.

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Clinical studyCirculatory dynamics during high altitude pulmonary edema☆

Abstract

Edema agudo por soroche grave

Rev. Peruana cardiol.

Pulmonary edema of high altitude

Am. J. Cardiol.

High altitude pulmonary edema

Medicine

High-altitude pulmonary edema

Lancet

Acute pulmonary edema of high altitude

New England J. Med.

Acute pulmonary edema of altitude

Circulation

Pulmonary edema at high altitude (Panel discussion)

Med. thorac.

Aspectos Fisiológicos de la Vida en la Altura

Edema agudo del pulmón en el soroche

Soroche agudo: Edema agudo del pulmón

An. Fac. med. Lima

Further studies of high altitude pulmonary edema

Brit. Heart J.

Pulmonary edema by ascending to high altitudes

Dis. Chest

Physiologic studies of pulmonary edema at high altitude

Circulation

Pulmonary hypertension in healthy men born and living at high altitudes

Am. J. Cardiol.

Pulmonary circulation in acclimatized man at high altitude

J. Appl. Physiol.

Clinical study
Circulatory dynamics during high altitude pulmonary edema☆