| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Swiss Cardiovascular Center Bern, University of Bern, 3010 Bern, Switzerland; 2 Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland; 3 Laboratory of Cardiovascular and Respiratory Physiology, Erasme University Hospital, 1070 Brussels, Belgium; and 4 Medical Intensive Care Unit of the Department of Internal Medicine, University Hospital Zürich, 8091 Zürich, Switzerland
 |
ABSTRACT |
|---|
 TOP
 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Exaggerated hypoxia-induced pulmonary hypertension is a hallmark of high-altitude pulmonary edema (HAPE) and plays a major role in its pathogenesis. Many studies of HAPE have estimated systolic pulmonary arterial pressure (SPAP) with Doppler echocardiography. Whereas at low altitude, Doppler echocardiographic estimation of SPAP correlates closely with its invasive measurement, no such evidence exists for estimations obtained at high altitude, where alterations of blood viscosity may invalidate the simplified Bernoulli equation. We measured SPAP by Doppler echocardiography and invasively in 14 mountaineers prone to HAPE and in 14 mountaineers resistant to this condition at 4,559 m. Mountaineers prone to HAPE had more pronounced pulmonary hypertension (57 ± 12 and 58 ± 10 mmHg for noninvasive and invasive determination, respectively; means ± SD) than subjects resistant to HAPE (37 ± 8 and 37 ± 6 mmHg, respectively), and the values measured in the two groups as a whole covered a wide range of pulmonary arterial pressures (30-83 mmHg). Spearman test showed a highly significant correlation (r = 0.89, P < 0.0001) between estimated and invasively measured SPAP values. The mean difference between invasively measured and Doppler-estimated SPAP was 0.5 ± 8 mmHg. At high altitude, estimation of SPAP by Doppler echocardiography is an accurate and reproducible method that correlates closely with its invasive measurement.
Doppler echocardiography; right heart catheterization; high-altitude pulmonary edema
| |
INTRODUCTION |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
HIGH-ALTITUDE PULMONARY EDEMA (HAPE) is a life-threatening condition occurring in predisposed subjects at altitudes above 2,500 m (7, 9-11). An exaggerated hypoxia-induced vasoconstriction of the pulmonary arterial vascular bed is a hallmark of HAPE and is thought to play a major role in its pathogenesis (7, 9-11). For obvious reasons, in almost all of the studies at high altitude, pulmonary arterial pressure has been estimated by Doppler echocardiography, and invasive measurements by right heart catheterization are scarce (1, 5, 6, 9). At low altitude, Doppler-derived gradients across the tricuspid valve are easily performed and correlate well with invasively measured pulmonary arterial pressures (2, 3, 12, 14). At high altitude, whole blood viscosity is altered (8), and whether these alterations are of sufficient magnitude to invalidate the simplified Bernoulli equation (which ignores viscous friction) (13) is unknown. We therefore performed at a high-altitude research laboratory (4,559 m) direct invasive and Doppler echocardiographic measurements of systolic pulmonary arterial pressure in HAPE-susceptible and HAPE-resistant mountaineers.
| |
METHODS |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Study design and subjects. Thirty otherwise-healthy mountaineers were recruited for the study, and twenty-eight were finally included. Among them, 14 [3 women and 11 men, mean (±SD) age 40 ± 3 yr] had previously developed at least one episode of clinically and radiographically documented HAPE (HAPE susceptible; HAPE-S group). The 14 other subjects (4 women and 10 men, mean age 30 ± 2 yr) were known to be resistant to HAPE (HAPE-R group; repeated alpine-style climbing to peaks above 4,000 m without symptoms of pulmonary edema). Two HAPE-S subjects who developed acute HAPE were not included in the study (because of insufficient quality of Doppler-derived gradients across the tricuspid valve in one case and because oxygen had been delivered between the echocardiographic and invasive determinations of pulmonary pressures in the other case). All subjects ascended in groups of two to four from 1,130 to 4,559 m within a period of 24 h. The ascent consisted of a transport by cable car to an altitude of 3,200 m; a 1.5-h climb to an altitude of 3,611 m, where the subjects stayed overnight; and, on the next day, a 4.5-h climb to the high-altitude research laboratory at Capanna Regina Margherita. The subjects then spent 2 days and 2 nights at this hut. Doppler echocardiographic estimations and invasive measurements of systolic pulmonary arterial pressure were performed after the first night spent at the Margherita hut or earlier if the subject had developed HAPE. Seven HAPE-S subjects had acute pulmonary edema at the time of the determinations of pulmonary arterial pressure. The experimental protocol was approved by the Institutional Review Boards on Human Investigation (University Hospitals, Lausanne and Zürich, Switzerland), and all subjects provided written informed consent before ascent.
Doppler echocardiography.
Echocardiographic recordings were obtained with a real-time, phased
array sector scanner (model Sonos 2500 or 5000; Hewlett-Packard, Andover, MA) with an integrated color Doppler system and a transducer containing crystal sets for imaging (2.5 MHz) and for continuous-wave Doppler recording (1.9 MHz). The recordings were stored on S-VHS videotape for analysis by an investigator (the study
echocardiographer), who was unaware of the subject's clinical history.
The recordings were analyzed two times (analyses 1 and
2), at least 3 mo apart, by the study echocardiographer. All
reported values represent the mean of at least three measurements.
After tricuspid regurgitation had been localized with Doppler color
flow imaging, the peak flow velocity of the transtricuspid jet
(VTR) was measured with the use of
continuous-wave Doppler (Fig. 1),
and the pressure gradient between the right ventricle and the
right atrium was calculated by use of the modified Bernoulli equation:
PRV-RA = 4(VTR)2, where P is pressure
difference, RV is right ventricle, and RA is right atrium
(4). Systolic pulmonary arterial pressure was estimated by
adding the clinically determined mean jugular venous pressure
(14) to the pressure gradient between the right ventricle
and atrium.
|
Right heart catheterization. Right heart catheterization was performed immediately after Doppler echocardiography with the use of a standard thermodilution balloon-tipped pulmonary arterial catheter (131H-7F Baxter) inserted via an internal jugular vein. To enhance safety of the procedure, the internal jugular vein was first located by use of an ultrasound Doppler device (SonoGuide2; Darbomed, Fehraltdorf, Switzerland). After localization of the vein and local anesthesia (lidocaine 1%), the vein was cannulated with a sheath (Arrow, Erding, Germany) by use of the Seldinger technique. Thereafter, the pulmonary arterial catheter was floated under constant-pressure wave monitoring into the pulmonary artery for the measurements of right atrial and pulmonary arterial pressure. A small polyethylene catheter (Vygon, Ecouen, France) was inserted into a radial artery or a femoral artery to measure systemic arterial pressure. Pulmonary and systemic arterial pressures were measured with the use of transducers (Homedica, Cham, Switzerland) connected to a hemodynamic and electrocardiographic monitoring system (Sirecust 404; Siemens, Erlangen, Germany). The pressure transducers were zero-referenced at midchest, and vascular pressures were measured at end expiration. The vascular pressure signals were sampled at 200 Hz by use of an analog-to-digital converter (RTI 800, Analog Device) and stored on a personal computer (Fig. 1). For pulmonary arterial pressure measurements, the subjects were asked to stop breathing at the end of a normal tidal volume for a period of 8 s. Heart rate was determined by a continuously monitored electrocardiogram. Cardiac output (Q) was measured by thermodilution with the use of of injections of 10 ml of 5% cold dextrose in water (8-10°C) and a computer (Vigilance, Baxter, Switzerland) and was calculated as the mean of three to five determinations.
Statistics. Statistical analysis was performed with the help of the Statistical Analysis System software package (version 6.12; SAS Institute, Cary, NC). The unpaired Student's t-test was used for the comparisons between the HAPE-S and HAPE-R groups. A paired t-test was used for the comparisons between invasively measured and Doppler echocardiographically estimated parameters. Spearman correlation and Bland-Altman analysis were performed. P value < 0.05 was considered statistically significant. Values are means ± SD.
| |
RESULTS |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Heart rate (82 ± 11 vs. 79 ± 11 beats/min) and
systemic blood pressure (141/76 ± 18/10 vs. 132/78 ± 9/8)
did not significantly differ between the HAPE-S and the HAPE-R
subjects. Pulmonary vascular resistance index and invasively measured
or Doppler echocardiographically estimated systolic pulmonary arterial
pressures, as expected, were significantly higher in HAPE-S than in
HAPE-R subjects (Table 1, Fig.
1). Systolic pulmonary arterial pressure was 58 ± 10 mmHg in
HAPE-S but only 37 ± 6 mmHg in HAPE-R subjects (P < 0.0001). When all subjects were analyzed together, the mean
difference between invasively measured and Doppler
echocardiographically estimated systolic pulmonary arterial pressures
was 
0.5 ± 8 mmHg (Fig. 2). Figure
3 shows that there was a strong
relationship (r = 0.89, P < 0.0001)
between invasively and echocardiographically obtained measurements of
systolic pulmonary arterial pressure. The intraobserver variability
between the first and the second Doppler analyses was very small. The
r values for the correlation coefficients between invasively
measured pulmonary arterial pressure and the first and second Doppler
echocardiographic measurements were 0.89 (P < 0.0001)
and 0.85 (P < 0.0001), respectively; the r
value for the correlation coefficient between the first and the second
Doppler measurements was 0.92 (P < 0.0001).
|
|
|
| |
DISCUSSION |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
The present results show, for the first time at high altitude, that Doppler echocardiographically estimated systolic pulmonary arterial pressure correlates very well with its invasive measurement in both HAPE-susceptible mountaineers and subjects resistant to such edema. These findings indicate that Doppler echocardiography is an accurate and reproducible method for estimating pulmonary arterial pressure at high altitude, the most important predictor of an augmented susceptibility to HAPE. They also indicate that despite alterations of blood viscosity at high altitude (8), the simplified Bernoulli equation, which ignores viscous friction, remains valid.
Measured peak velocity of tricuspid regurgitation jet was used to estimate pulmonary arterial pressure in this study, because this technique is easy to perform and correlates well with invasive measurements at low altitude (2, 3, 12, 14). At lowland, reported r values for correlation coefficients between Doppler-estimated and invasively measured systolic pulmonary arterial pressures vary between 0.95 and 0.97 (2, 3, 12, 14). None of these reports, however, included a Bland-Altman analysis. Although Doppler estimates of pulmonary pressure are operator dependent (2-4, 7, 12, 14), the slightly smaller r values in the present field study may be related, at least in part, to the difficulties of examining severely dyspneic and tachypneic subjects, with seven of them suffering full-blown HAPE. Moreover, the fact that echocardiography and right heart catheterization were performed sequentially may also have contributed to slightly larger differences between the estimated and invasively measured pressures than those observed in studies at low altitude using strictly simultaneous measurements. Nevertheless, our data indicate that at high altitude, provided sufficient individual echogenicity, a broad spectrum of systolic pulmonary arterial pressures can be reliably estimated by the Doppler-derived transtricuspid pressure gradient. In conclusion, Doppler echocardiography represents an accurate and reproducible method for estimating pulmonary arterial pressure at high altitude.
| |
ACKNOWLEDGEMENTS |
|---|
We are indebted to our subjects; to the Sezione Varallo del Club Alpino Italiano for providing the locations in the Capanna Regina Margherita; to our mountain guides Andrea Enzio, Osvaldo Antonietti, and Bruno Brand for leading our subjects safely to the hut; to Hewlett-Packard for providing the echocardiographic equipment; and to the Swiss Army for transporting part of the material.
| |
FOOTNOTES |
|---|
This work was supported, in part, by grants from the Swiss National Science Foundation, the International Olympic Committee, the Fondazione Dottor PierLuigi Crivelli, the Hamasil Foundation, the Placide Nicod Foundation, the Olga Mayenfisch Foundation, and the Hermann Kurz Foundation, Zürich, Switzerland.
Parts of this work were presented at the 71st Scientific Sessions of the American Heart Association, Dallas, Texas, November 1998, and at the 11th International Hypoxia Symposium, Jasper, Alberta, Canada, February 1999.
Address for reprint requests and other correspondence: Y. Allemann, Swiss Cardiovascular Center Bern, Div. of Cardiology, Univ. Hospital, 3010 Bern, Switzerland (E-mail: Yves.Allemann{at}insel.ch).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 14 March 2000; accepted in final form 9 May 2000.
| |
REFERENCES |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
1.
Antezana, G,
Leguia G,
and
Guzman A.
Hemodynamic study of high altitude pulmonary edema (12,000 ft).
In: High Altitude Physiology and Medicine, edited by Brendel W,
and Zink R.. New York: Springer Verlag, 1982, p. 232-241.
2.
Berger, M,
Haimowitz A,
Van Tosh A,
Berdoff RL,
and
Goldberg EE.
Quantitative assessment of pulmonary hypertension in patients with tricuspid regurgitation using continuous wave Doppler ultrasound.
J Am Coll Cardiol
6:
359-365,
1985[Abstract].
3.
Currie, PJ,
Seward JB,
Chan KL,
Fyfe DA,
Hagler DJ,
Mair DD,
Reeder GS,
Nishimura RA,
and
Tajik AJ.
Continuous wave Doppler determination of right ventricular pressure: a simultaneous Doppler-catheterization study in 127 patients.
J Am Coll Cardiol
6:
750-756,
1985[Abstract].
4.
Hatle, L,
Brubakk A,
Tromsdal A,
and
Angelsen B.
Noninvasive assessment of pressure drop in mitral stenosis by Doppler ultrasound.
Br Heart J
40:
131-140,
1978
5.
Hultgren, HN.
High altitude pulmonary edema: hemodynamic aspects.
Int J Sports Med
18:
20-25,
1997[Web of Science][Medline].
6.
Hultgren, HN,
Lopez CE,
Lundberg E,
and
Miller H.
Physiologic studies of pulmonary edema at high altitude.
Circulation
XXIX:
393-408,
1964.
7.
Oelz, O,
Maggiorini M,
Ritter M,
Waber U,
Jenni R,
Vock P,
and
Bartsch P.
Nifedipine for high altitude pulmonary oedema.
Lancet
2:
1241-1244,
1989[Web of Science][Medline].
8.
Reinhart, WH,
Kayser B,
Singh A,
Waber U,
Oelz O,
and
Bartsch P.
Blood rheology in acute mountain sickness and high-altitude pulmonary edema.
J Appl Physiol
71:
934-938,
1991
9.
Roy, SB,
Guleria JS,
Khanna PK,
Manchanda SC,
Pande JN,
and
Subba PS.
Haemodynamic studies in high altitude pulmonary oedema.
Br Heart J
31:
52-58,
1969
10.
Sartori, C,
Trueb L,
and
Scherrer U.
High-altitude pulmonary edema. Mechanisms and management.
Cardiologia
42:
559-567,
1997[Medline].
11.
Scherrer, U,
Vollenweider L,
Delabays A,
Savcic M,
Eichenberger U,
Kleger GR,
Fikrle A,
Ballmer PE,
Nicod P,
and
Bartsch P.
Inhaled nitric oxide for high-altitude pulmonary edema.
N Engl J Med
334:
624-629,
1996
12.
Stevenson, JG.
Comparison of several noninvasive methods for estimation of pulmonary artery pressure.
J Am Soc Echocardiogr
2:
157-171,
1989[Medline].
13.
Weyman, AE.
Principles of flow.
In: Principles and Practice of Echocardiography (2nd ed.), edited by Febiger L.. Philadelphia, PA: Lea & Febiger, 1994, p. 184-200.
14.
Yock, PG,
and
Popp RL.
Noninvasive estimation of right ventricular systolic pressure by Doppler ultrasound in patients with tricuspid regurgitation.
Circulation
70:
657-662,
1984
This article has been cited by other articles:
|
|
 |
|
  J.K. Baillie, A.A.R. Thompson, J.B. Irving, M.G.D. Bates, A.I. Sutherland, W. MacNee, S.R.J. Maxwell, and D.J. Webb Oral antioxidant supplementation does not prevent acute mountain sickness: double blind, randomized placebo-controlled trial QJM, May 1, 2009; 102(5): 341 - 348. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Faoro, S. Boldingh, M. Moreels, S. Martinez, M. Lamotte, P. Unger, S. Brimioulle, S. Huez, and R. Naeije Bosentan Decreases Pulmonary Vascular Resistance and Improves Exercise Capacity in Acute Hypoxia Chest, May 1, 2009; 135(5): 1215 - 1222. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Maignan, M. Rivera-Ch, C. Privat, F. Leon-Velarde, J.-P. Richalet, and I. Pham Pulmonary Pressure and Cardiac Function in Chronic Mountain Sickness Patients Chest, February 1, 2009; 135(2): 499 - 504. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Stuber, C. Sartori, C. S. Salmon, D. Hutter, S. Thalmann, P. Turini, P.-Y. Jayet, M. Schwab, C. Sartori-Cucchia, M. Villena, et al. Respiratory Nitric Oxide and Pulmonary Artery Pressure in Children of Aymara and European Ancestry at High Altitude Chest, November 1, 2008; 134(5): 996 - 1000. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-P. Richalet, M. Rivera-Ch, M. Maignan, C. Privat, I. Pham, J.-L. Macarlupu, O. Petitjean, and F. Leon-Velarde Acetazolamide for Monge's Disease: Efficiency and Tolerance of 6-Month Treatment Am. J. Respir. Crit. Care Med., June 15, 2008; 177(12): 1370 - 1376. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. A. Kaufmann, A. M. Bernheim, S. Kiencke, M. Fischler, J. Sklenar, H. Mairbaurl, M. Maggiorini, and H. P. Brunner-La Rocca Evidence supportive of impaired myocardial blood flow reserve at high altitude in subjects developing high-altitude pulmonary edema Am J Physiol Heart Circ Physiol, April 1, 2008; 294(4): H1651 - H1657. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Liu, G. M. Balanos, M. Fatemian, T. G. Smith, K. L. Dorrington, and P. A. Robbins Effects of hydralazine on the pulmonary vasculature and respiratory control in humans Exp Physiol, January 1, 2008; 93(1): 104 - 114. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Chin, R. N. Channick, N. H. Kim, and L. J. Rubin Central Venous Blood Oxygen Saturation Monitoring in Patients With Chronic Pulmonary Arterial Hypertension Treated With Continuous IV Epoprostenol: Correlation With Measurements of Hemodynamics and Plasma Brain Natriuretic Peptide Levels Chest, September 1, 2007; 132(3): 786 - 792. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Bernheim, S. Kiencke, M. Fischler, L. Dorschner, J. Debrunner, H. Mairbaurl, M. Maggiorini, and H. P. Brunner-La Rocca Acute Changes in Pulmonary Artery Pressures Due to Exercise and Exposure to High Altitude Do Not Cause Left Ventricular Diastolic Dysfunction Chest, August 1, 2007; 132(2): 380 - 387. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. K. Kojonazarov, B. Z. Imanov, T. A. Amatov, M. M. Mirrakhimov, R. Naeije, M. R. Wilkins, and A. A. Aldashev Noninvasive and invasive evaluation of pulmonary arterial pressure in highlanders Eur. Respir. J., February 1, 2007; 29(2): 352 - 356. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Allemann, D. Hutter, E. Lipp, C. Sartori, H. Duplain, M. Egli, S. Cook, U. Scherrer, and C. Seiler Patent Foramen Ovale and High-Altitude Pulmonary Edema JAMA, December 27, 2006; 296(24): 2954 - 2958. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. D. Hoit, N. D. Dalton, S. C. Erzurum, D. Laskowski, K. P. Strohl, and C. M. Beall Nitric oxide and cardiopulmonary hemodynamics in Tibetan highlanders J Appl Physiol, November 1, 2005; 99(5): 1796 - 1801. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Dehnert, E. Grunig, D. Mereles, N. von Lennep, and P. Bartsch Identification of individuals susceptible to high-altitude pulmonary oedema at low altitude Eur. Respir. J., March 1, 2005; 25(3): 545 - 551. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. P. Talbot, G. M. Balanos, K. L. Dorrington, and P. A. Robbins Two temporal components within the human pulmonary vascular response to ~2 h of isocapnic hypoxia J Appl Physiol, March 1, 2005; 98(3): 1125 - 1139. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. A. Ghofrani, F. Reichenberger, M. G. Kohstall, E. H. Mrosek, T. Seeger, H. Olschewski, W. Seeger, and F. Grimminger Sildenafil Increased Exercise Capacity during Hypoxia at Low Altitudes and at Mount Everest Base Camp: A Randomized, Double-Blind, Placebo-Controlled Crossover Trial Ann Intern Med, August 3, 2004; 141(3): 169 - 177. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Allemann, M. Rotter, D. Hutter, E. Lipp, C. Sartori, U. Scherrer, and C. Seiler Impact of acute hypoxic pulmonary hypertension on LV diastolic function in healthy mountaineers at high altitude Am J Physiol Heart Circ Physiol, March 1, 2004; 286(3): H856 - H862. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. P. Mason, M. Petersen, C. Melot, B. Imanow, O. Matveykine, M.-T. Gautier, A. Sarybaev, A. Aldashev, M. M. Mirrakhimov, B. H. Brown, et al. Serial changes in nasal potential difference and lung electrical impedance tomography at high altitude J Appl Physiol, May 1, 2003; 94(5): 2043 - 2050. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. L.M. Cruden, D. E. Newby, D. J. Webb, P. Bartsch, H. Mairbaurl, B. Basnyat, P. Prodhan, N. N. Noviski, T. B. Kinane, E. R. Swenson, et al. Salmeterol for the Prevention of High-Altitude Pulmonary Edema N. Engl. J. Med., October 17, 2002; 347(16): 1282 - 1285. [Full Text] [PDF]
|
|
|
|
|
|
C. Sartori, Y. Allemann, H. Duplain, M. Lepori, M. Egli, E. Lipp, D. Hutter, P. Turini, O. Hugli, S. Cook, et al. Salmeterol for the Prevention of High-Altitude Pulmonary Edema N. Engl. J. Med., May 23, 2002; 346(21): 1631 - 1636. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
, HAPE-susceptible subjects who developed HAPE;
, HAPE-susceptible subjects who did not develop HAPE;
, subjects resistant to HAPE.
