(Circulation. 2001;103:2078.)
© 2001 American Heart Association, Inc.
Clinical Investigation and Reports |
High-Altitude Pulmonary Edema Is Initially Caused by an Increase in Capillary Pressure
From the Medical Intensive Care Unit of the Department of Internal Medicine (M.M., I.G.), the Division of Nuclear Medicine (F.P.) and the Department of Radiology (M.H.), UniversitätsSpital, Zürich, and the Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne (C.S., M.L., U.S.), Switzerland; and the Departments of Intensive Care and Physiology (S.P., C.M., R.N.), Erasme University Hospital, Brussels, Belgium.
Correspondence to Professor Dr. med. M. Maggiorini, Medizinische Intensivstation, UniversitätsSpital Zürich, Rämistrasse 100, CH-8091 Zürich, Switzerland. E-mail klinmax{at}usz.unizh.ch
Background—High-altitude pulmonary edema (HAPE) is characterized by severe pulmonary hypertension and bronchoalveolar lavage fluid changes indicative of inflammation. It is not known, however, whether the primary event is an increase in pressure or an increase in permeability of the pulmonary capillaries.
Methods and Results—We studied pulmonary hemodynamics, including capillary pressure determined by the occlusion method, and capillary permeability evaluated by the pulmonary transvascular escape of 67Ga-labeled transferrin, in 16 subjects with a previous HAPE and in 14 control subjects, first at low altitude (490 m) and then within the first 48 hours of ascent to a high-altitude laboratory (4559 m). The HAPE-susceptible subjects, compared with the control subjects, had an enhanced pulmonary vasoreactivity to inspiratory hypoxia at low altitude and higher mean pulmonary artery pressures (37±2 versus 26±1 mm Hg, P<0.001) and pulmonary capillary pressures (19±1 versus 13±1 mm Hg, P<0.001) at high altitude. Nine of the susceptible subjects developed HAPE. All of them had a pulmonary capillary pressure >19 mm Hg (range 20 to 26 mm Hg), whereas all 7 susceptible subjects without HAPE had a pulmonary capillary pressure <19 mm Hg (range 14 to 18 mm Hg). The pulmonary transcapillary escape of radiolabeled transferrin increased slightly from low to high altitude in the HAPE-susceptible subjects but remained within the limits of normal and did not differ significantly from the control subjects.
Conclusions—HAPE is initially caused by an increase in pulmonary capillary pressure.
Key Words: edema • lung • capillaries
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|
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|
|
|
|
|
|
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|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
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|
|
|
|
|
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|
|
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|
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|
|
|
|
|
|
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|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
P. Hackett and D. Rennie High-Altitude Pulmonary Edema JAMA, May 1, 2002; 287(17): 2275 - 2278. [Full Text] [PDF]
|
|
|
|
 |
|
 A. G. Durmowicz Pulmonary Edema in 6 Children With Down Syndrome During Travel to Moderate Altitudes Pediatrics, August 1, 2001; 108(2): 443 - 447. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|