Dept. Internal Medicine VII / Sports Medicine

A Century of Researchat the Capanna Regina Margherita
Peter Bärtschwww.klinikum.uni-heidelberg.de/sportmedizinInternational Reseach Institution
recognised by Nat. Acad. Sci. US•••

N. Zuntz, Berlin
J. Barcroft, Cambridge
A. Durig, Vienna
A. Cogo, High Alt. Med Biol 1: 137-147, 2000

Zuntz, N. et al. Höhenklima und Bergwanderungen, Deutsches Verlagshaus Bong & Co., Berlin 1906

Aereas of Research• ventilation and gas exchange• blood• systemic circulation• nutrition• metabolism• muscle strength• mountain sicknessRegistration of Thorax Movements

Periodic Breathing at High Altitude

Sleep Studies% peridoc breathing

10090CRMOE II

807060504030201004559m
not sicksick

Eichenberger; AJRCCM 1996

4572m

6100m
not sick7620m

Anholm; Am Rev Respir Dis 1992

AltitudeLancet ii: 639-641, 1988

O2-Sättigung(%) ABK-C Score

Klinischer Score

CO2 hilft nicht gegen akute Bergkrankheit

Bärtsch et al.,Lancet ii: 772 - 775, 1990

O2

CO2Atemluft

Old Hut: Kreuzer Expedition 1963

Katecholamine im Urin
während einer Monte-Rosa-Expedition
9080

Noradrenalin

70

Adrenalin

60504030201000m

3000 m

3650 m4560 m0m

Cunningham WL et al., JAP 20:607-610, 1965

1978 - 1980

Flight to Capanna Regina Margherita (4559 m)

Symptoms of Acute Mountain Sickness (AMS)„Usual“ Symptoms

Warning Symptoms• headache• headache resistant to analgesics• loss of appetite/nausea• vomiting• insomnia• ataxia• dizzines• apathy / somnolence• peripheral oedema• neglect, dissimulation

Prevalence of AMS at CRM
60prevalence %50n = 209

403020100nosymptoms

1-2
symptoms>2
symptoms
Maggiorini; BMJ 301 1990

High altitude pulmonary edema (HAPE)

25 year-old healthy mountaineer

High altitude pulmonary edema (HAPE)• Setting:- rapid ascent above 3000 - 4000 m• Symptoms: - often preceded by AMS- dyspnea, decreased exercise performance,cough- orthopnea, gurgling, pink frothy sputum- ataxia, decreased consciousness• Prognosis: - rapid complete resolution after descent- high mortality without treatment• Incidence: - variable, individual susceptibility

Prevalence of HAPE in theCapanna Margherita (4559 m)

ascentprevalence

overall2 - 5 days

< 0,2 %

without a history of HAPE

22 hours

6%

with a history of HAPE

22 hours

60 %Bärtsch, Lancet 390:571, 2002

Research at the Margherita Hut since 1983
Affiliations of first and last authors• Austria:

Innsbruck• Belgium:

Brussels• Denmark:Copenhagen• Germany:

Heidelberg, Munich• Italy:

Milano, Ferrara, Padova• Switzerland:Bern, Geneva, Lausanne, Zurich• USA:

Seattle, San DiegoScientific Publications of Research Performed atthe Margeritha Hut from 1983 to 2005
• 71 original research papers in Medline• 40 papers published in leading journals of:General Medicine

Specialized Area

Physiology

NEJM 3
JAMA 1
Lancet 7 (3 RL)
BMJ
4Circulation
AJCCMRadiology

431J Physiol 1
AJP
3JAP
12TotalTotal

8Total1517

Examples of Research Performed at theCapanna Regina Margherita

1. High Altitude Pulmonary Edema- Prevention and Treatment- Pathophysiology
2. Environmental Physics

Pulmonary Artery Pressure
at an Altitude of 4559 m70

PAP (mmHg)

605040

HAPE

30Non-HAPE20100490 m

day1day 2day 3

Nifedipine for treatment of HAPE

Oelz, Lancet ii:1241-44, 1989

Study Design4559 m4559 m3611 m

3230 m
Tag 1Tag 2

Tag 3

Tag 41190 m
15.00

24.00

24.00

24.00

Pulmonary Vasodilators Prevent HAPE

Nifedipine 3x20 mg
Radiographic endpoint: HAPE
Nifedipine

1 of 10 (= 10%)

Placebo7 of 11 (= 64%)
Bärtsch, N Engl J Med 1991

Pulmonary Vasodilators Prevent HAPE

[mmHg]

PAP

70p < 0,001

Radiographic endpoint: HAPE

60504030

1 of 8 (= 13%)

Placebo7 of 9 (= 78%)

Maggiorini et al., HAMB 200420100TadalafilPlaceboTadalafil
2 x 10 mg(Abstract)

Examples of Research Performed at theCapanna Regina Margherita
1. High Altitude Pulmonary Edema● Prevention and treatment● Pathophysiology:- Type of leak
- Cause of exaggerated hypoxic
vasoconstriction
2. Environmental physics

Measurement of pressure in lung capillaries

Measurement of effective pulmonary capillarypressure at 4559 m80

Ppa

70

T 0, occlusionpressure (mmHg)

60
50

T 200

T 20004030Pc', 150 msec
20Ppao10001000

2000

3000

4000

time (msec)

5000

6000

7000

8000

Pressure in Pulmonary Vessels at 4559 m*50[mmHg]

4030*20100MEAN PAPControls (n=14)

Capillary Pressure

HAPE-S without HAPE (n=7)

Wedge Pressure

HAPE-S with HAPE (n=9)

Maggorini et al., Circulation 103:2078-2083, 2001

Bronchoalveolar Lavage at 4559 m

Bronchoalveolar Lavage at 4559 m

Swenson, JAMA 287: 2228-2235, 2002

Conclusion from these studies

Early HAPE is a non cardiogenic hydrostatic pulmonary
edema characterized by:• a leak of red cells and plasma proteins• without neutrophil recruitment• without inflammatory or chemotactic mediators

Examples of Research Performed at theCapanna Regina Margherita
1. High Altitude Pulmonary Edema● Prevention and treatment● Pathophysiology:- Type of leak
- Cause of exaggerated hypoxic
vasoconstriction
2. Environmental physics

Effect of NO inhalation (40ppm) in HAPE

*6060

4040202020

AaDO2 (mmHg)

20*15151010550Air

NOHAPEAirNO
non HAPE

PAP (mmHg)

80

AaDO2 (mmHg)

PAP (mmHg)

800Scherer et al; NEJM 1996

Perfusion scans in an individual with HAPE
in the left middel and lower lungfield

before NO

during NO (40 ppm)
Scherrer, New Engl J Med 334:624-629, 1996

Exhaled Nitric Oxide
HAPE-R

HAPE

HAPE at 4559m[pmol/sec][pmol/sec]

707060605050

HAPE- at 100m
HAPE-S(FiO2 = 0.12)n=2440n=1040n=13n=103030

202012243640[h]Duplain et al, AJRCCM 162: 221-224, 2000

Normoxia

Hypoxia2hHypoxia
4hBusch et al, AJRCCM 163: 368-373, 2001

Nitrate and nitrite in BAL fluidControls (n=6)

HAPE susceptible (n=9)

5*43*210490 m4559 m

Mean ± SE, * p<0.05 vs. 490 m

490 m4559 m 4559 m
before HAPE
with HAPE

Swenson, JAMA 2002*Colle Gnifetti (4500 m)

Courtesy of Dietmar WagenbachInstitute of Environmental Physics
University of Heidelberg

Courtesy of Dietmar WagenbachInstitute of Environmental Physics
University of Heidelberg

Courtesy of Dietmar WagenbachInstitute of Environmental Physics
University of Heidelberg

D. Wagenbach, Institute of Environmental Physics, Heidelberg

Long term change of Sulphateseen at Colle Gnifetti

Onset of industrial era

D. Wagenbach, Institute of Environmental Physics, Heidelberg

Rezente Azidität
6sauer0

alkalischAzidität [µeq/l]

3-3-6

2000

1950

1900

1850

1800

D. Wagenbach, Institute of Environmental Physics, Heidelberg

D. Wagenbach, Institute ofEnvironmental Physics,Heidelberg

1893 - 2005