Abstracts

1. HYPOXIA AND HYPERCAPNIA DURING RESPIRATION INTO ARTIFICIAL AIR POCKETS IN SNOW

SUMANN Günther, BRUGGER Hermann, SCHOBERSBERGER Wolfgang, MEISTER Roland, GUNGA Hanns-Christian, MAIR Peter, FALK Markus
Division for Gen. & Surgical Intensive Care Medicine, Innsbruck, Austria

Factors governing survival following complete burial under a snow avalanche are speed of extrication, presence of an air pocket and maintenance of a clear airway. We assessed the effect of breathing into an artificial air pocket in snow on changes in respiratory gases of avalanche victims.
We undertook a prospective randomized 2x2 cross-over study in 12 subjects. 28 tests were carried out in which they breathed into air pockets of different volumes (1l or 2l) within snow of different density. The volunteers were sitting in the open-air and were not buried.
The tests showed that during respiration into the air pockets oxygen saturation decreased significantly
within 4 min, dependent on snow density, and was inversely proportional to air pocket volume. End-tidal carbon dioxide rose significantly and a respiratory acidosis developed.
Although contributing factors of snow burial like the influence of snow pressure on chest and ventilation, hypothermia and stress were not assessed in this simulatory model, we were able to elucitate an important part of the pathophysiology of avalanche burial.

2. PREDICTED HYPOXIA IMAGE AND VO2max VALUE IN SKELETAL MUSCLE WORKING UNDER ACUTE HYPOXIA AT DIFFERENT LEVELS OF MUSCLE BLOOD FLOW

K.Lyabakh*, I. Mankovskaya** , M. Filippov**
*Institute of Cybernetics, **Institute of Physiology, Kiev, Ukraine (katya@public.icyb.kiev.ua)

The aim of the study was to investigate the influence of muscle blood flow F and oxygen partial pressure of arterial blood (PaO2), on VO2max and to predict the size, shape, and position of hypoxia zone in muscle fiber working under hypoxemia. The computer model of O2 delivery-consumption in muscle was used for calculation of tissue pO2 and VO2 distribution. VO2max, end capillary pO2 and graphic hypoxia images in tissue were investigated as a function of PaO2 and F (100< F < 600 ml/min/100g, 30<PaO2 < 100 mm Hg). The results showed that an increase of F leads to a rise of VO2max. Despite the lower VO2max in hypoxia, the venous blood had the lower pO2 in hypoxia than in normoxia. Muscle oxygen diffusion was found to be one of the most significant factors limiting VO2max during acute hypoxemia. This finding was supported by the calculated images of hypoxia in muscle fiber working at VO2max.

3. PHYSIOLOGICAL AND BIOCHEMICAL MECHANISMS OF HUMAN ADAPTATION TO HIGH ALTITUDE HYPOXIA

Mahnovsky Valentin
International Univ. Kyrgyzstan (vmak@iuk.kg)

The studies were conducted in acute phase of adaptation of young men with high- (HHR) and low- (LHR) hypoxic resistance at altitude of 3,600 m (Pamirs). Measurements of the arterial pressure, ECG, integral rheocardiography and oxyhaemometry were used for estimating the human functional state in mountain conditions. Spectrometric analysis was used for estimating carbohydrate, lipid and nitrous metabolism. It was shown that in LHR group Central Nervous System (CNS) depression took place that led to a decrease of compensatory cardiovascular reaction to the dosed Flack test, in particular to an inhibition of the cardiac activity, to deceleration of the blood flow rate, to a decrease of the cardiac output and peripheral resistance of the blood vessels, and to predominant cardiac type of blood circulation’s self-regulation. The HHR have a compensatory reaction which reveals itself in an increase of the cardiac activity, in the ventricle contraction and in vasoconstriction of the blood vessels. At the same time an excitability of the parasymphatetic innervating centers decreased and the new, more “economical” level of the CNS functioning was established. It was shown that the HHR adaptive process is connected with a compensation of the biochemical energy by means of anaerobic glycolysis stimulation which is accompanied by increase of glucose utilization without lactate accumulation, but for the LHR it is connected with a predominance of gluconeogenesis reactions. Also in the LHR group a significant increase of blood cholesterol and signs of blood uremia were recorded. The HHR adaptation is accompanied with small changes in quantity of blood cholesterol and nitrous metabolism products.

4. WHO REACHES THE SUMMIT OF ACONCAGUA ?

SCHNEIDER Michael‡ , PINTO Hernán*, GONZÁLEZ Gabriela*, CHIOCCONI Ramón*, MOHR Yanina*, LEAL Conxita**, MAGGIORINI Marco†, BÄRTSCH Peter‡, PESCE Carlos*
*Deptartamento Medicina de Montaña, Centro APTUS de Medicina Deportiva, Buenos Aires; **Institut d'Estudis de Medicina de Muntanya, Barcelona, Departments of Internal Medicine, University Hospitals of †Zürich and ‡Heidelberg

919 mountaineers were interviewed on returning from Aconcagua to establish factors associated with reaching the summit. Complete data-sets were obtained from 705 subjects. Susceptibility to AMS was assessed by scoring symptoms on previous exposures, mountaineering activity by previous max. altitude and days spent above 3000 m per year, pre-acclimatization by days above 3000 m in the last 4 weeks. Factor analysis revealed 3 groups with the following characteristics:

Parameter
Group 1
Group 2
Group 3
p
total number of subjects
254
268
183
summit reached
90%
76%
14%
<0,001
max. altitude reached previously
6659
6246
5051
<0,001
days above 3000m/year
44
17
13
<0,001
days above 3000m last 4 weeks
2,7
1,0
0,7
<0,001
score of AMS history
2,0
5,3
2,7
<0,001
AMS on Aconcagua
4%
72%
37%
<0,001
took acetazolamide
8%
31%
9%
<0,001
took analgesics
23%
48%
38%
<0,001
summit was not the object
0%
0%
19%
<0,001

Age, BMI, gender and hours of training are not significantly different between groups. Each variable in the table correlates significantly with reaching the summit in regression models. Thus previous mountain experience, pre-acclimatization and low susceptibility for AMS are associated with reaching the summit of Aconcagua.

5. PRELIMINARY STUDY: EFFECTS OF EXTREME ALTITUDE ON ERYTHROPOIETIN AND ERYTHROPOIESIS

Janelle Grainger*, Chris Howe, Graham Trout, Rymantas Kazlauskas
Australian Sports Drug Testing Laboratory. (*janelle.grainger@agal.gov.au)

We evaluated the effects of extreme altitude on erythropoietin (EPO) and erythropoiesis. Three subjects (two experienced mountain guides and one novice climber) underwent climbing expeditions in the Himalaya mountain ranges for periods between 3 and 5 weeks. Blood and urine samples were collected for analysis before and after the expeditions. The novice reported a viral illness on return. Haematological parameters of the two guides remained within laboratory reference ranges. The novice climber had prolonged elevation of haematocrit, percentage reticulocytes and soluble transferrin receptor after returning to sea level, suggesting a sustained acceleration of erythropoiesis. Urinary EPO glycoforms, analysed by isoelectric focussing and Western blotting, altered markedly only in the novice climber, to less acidic isoforms, although the pattern differed qualitatively from that seen in recombinant EPO. This pattern is associated with increased receptor binding but decreased serum half-life in vivo. These findings suggest that EPO glycosilation, and therefore bioactivity is modulated as a response to hypoxic stimulus. Further study may confirm the relationship between this modulation, maximum altitude, time at altitude and other stressors.

6. CHARACTERISTICS OF HIGH ALTITUDE HEADACHE

Schneider Michael, Bernasch Dirke, Weymann Jörn, Bärtsch Peter
Department of Internal Medicine, Universitiy of Heidelberg

To characterize high altitude headache we obtained questionnaires from 1213 mountaineers 2- 6 hours after arrival at 4559m. The history of migraine was assessed by the Kieler Headache Questionnaire and acute mountain sickness (AMS) by the AMS-C-Score of the Environmental Symptom Questionnaire. 589 (49%) subjects had headache and 133 (11%) a history of migraine. Factors-analysis identified 2 types of headache with the following characteristics:

 
Type 1
Type 2
p
Number of subjects
417
172
one-sided
0%
58%
<0,001
both-sided
100%
42%
<0,001
pulsating
20%
53%
<0,001
reduction of activity
21%
53%
<0,001
nausea
7%
26%
<0,001
photophobia
18%
47%
<0,001
sonophobia
11%
41%
<0,001
fulfilling criterions of migraine
0%
65%
<0,001
AMS-C-Score evening
0,48(±0,4)
0,78(±0,6)
<0,001
history of migraine
8%
26%
<0,001

The frequency of AMS (defined as AMS-CŽ0.7) and the mean AMS-C scores were not significantly different between mountaineers with and without a history of migraine at low altitude. These data demonstrate that: 1.) a history of migraine at low altitude is not strongly associated AMS and 2.) that headache in severe AMS is often migraine like and that this type of headache occurs in 75% of mountaineers independent of a history of migraine at low altitude.

7. ANALGESIA WITH ALMOTRIPTAN AGAINST NAPROXENO, FOR THE TREATMENT OF HEADACHE FOR AMS

Angel Poudereux de Andrés*, Nanci Goikoetxea Salgueiro**
*UCI, **Serv. Medicina Interna. Hospital General de Soria

In the Spring of 2000, during an expedition to the Satopanth (7075 m) a comparative study was carried out on the efficacy of Naproxeno and Almotriptan, used to combat headaches that make their appearance during the height acclimation period, affecting the participants in this type of expedition.
The study covered a period of 19 days at heights over 3500 m, during which the maximum height reached was 5700 m. The number of participants was 9, (8 men, 1 woman), none of which had antecedents of frequent headaches. Ages ranged between 27 and 51.
Each participant was given a card on which he or she recorded the intensity level of headache (scored subjectively between 1 and 3) and the degree of relief (scored subjectively between 1 and 5) two hours after administration of the medicine (A or B, respectively) and the presence or absence of accompanying symptoms, i.e nausea, dizziness...).
42 cases of headaches were recorded, of which only 25 were treated. 11 were treated with A (Naproxeno), while 14 were treated with B (Almotriptan). For technical reasons, many other cases of headache were not registered in the study.
Despite the small size of the sample, the results of the study clearly demonstrate (pŹ 0,001), significant higher efficacy of Naproxeno over Almotripan for the treatment of this type of headache.

8. NORMAL BMPR-2 GENE IN INDIVIDUALS SUSCEPTIBLE TO HIGH ALTITUDE PULMONARY EDEMA (HAPE-S)

Dehnert C.*, Miltenberger-Miltenyi G.**, Grünig E.†, Bärtsch P.*, Janssen B.**
*Dept. of Sports Medicine, **Dept. of Human Genetics and †Dept. of Cardiology, University Hospital Heidelberg, Germany

High pulmonary artery pressure (PAP) is essential for the development of HAPE. HAPE-S have both enhanced pulmonary vasoconstrictor response (PVR) to hypoxia and elevated PAP during normoxic exercise. We demonstrated a similar PVR to hypoxia and normoxic exercise in members of families with primary pulmonary hypertension (PPH) who share the risk haplotype with the index patient. Recent data show mutations in the BMPR-2 gene in PPH patients. Therefore we investigated whether mutations in the BMPR-2 gene also play a role in the development of HAPE. DNA of 11 patients (age 54±9 y) with well documented history of HAPE (median 2, range2-4 episodes of HAPE) and increased PAP response to exercise and hypoxia was screened for BMPR-2 mutations by the denatured high performance liquid chromatography method. Compared to HAPE-resistant controls (n=12, age 56±8 y) systolic PAP in HAPE-S was elevated during normoxic exercise (56±14 vs. 50±10 mmHg; p=0.14) and after 2 h at FiO2=0.12 (52±9 vs. 40±7 mmHg; p<0.01). The exon-wise analysis of the BMPR-2 gene did not show any mutations in HAPE-S. Our results suggest that the genetic background is different between HAPE and PPH but we can not exclude other possible candidate genes, eventually also located on chromosome 2, playing a role in the manifestation of HAPE.

9. PREVENTION OF ACUTE MOUNTAIN SICKNESS BY ACETAZOLAMIDE IN NEPALI PORTERS: A DOUBLE BLIND CONTROLLED TRIAL

Hillenbrand P, Pahari A, Soon Y, Subedi D, Bajacharya R, Gurung P, Lal B, Marahatta R, Pradhan Rai D, Sharma S, Wright A, Bradwell A, and BMRES
Tribhuvan University Teaching Hospital, Kathmandu and Birmingham Medical Research Expeditionary Society

Acetazolamide can prevent acute mountain sickness (AMS), but there have been no controlled trials of this drug in mountain porters, some of whom die of AMS every year. We therefore performed a randomised, double blind controlled trial of Diamox (acetazolamide) 250mg daily vs placebo. Nepali doctors stationed at Namche Bazar (altitude 3440m, in the Everest region) enrolled 401 porters, (297 lowlanders, 108 highlanders). Porters were given seven days' supply of trial medication and assessed at three trekking posts, the highest at Lobuje (4930m). Many were partially acclimatised on reaching Namche Bazar, thereafter the rate of ascent (mean 5.31 days), SD 0.966) allowed further acclimatisation.
Only 183/401 (45.63%) porters completed the trial and AMS occurred in only 17/183 (9.29%), 16 lowlanders and 1 highlander. Of these, 10 took acetazolamide (mean AMS score 4.10, SD 0.916) and 7 placebo (mean score 3.43, mean 0.593); the difference between these groups was not statistically significant. The low AMS incidence and lack of benefit from acetazolamide probably resulted from acclimatisation to altitude.

10. TREKKERS’ AWARENESS OF ACUTE MOUNTAIN SICKNESS (AMS) AND ACETAZOLAMIDE

Subedi D, Marahatta R, Sharma S, Hillenbrand P, Soon Y, and BMRES
Tribhuvan University Teaching Hospital, Kathmandu, Nepal and Birmingham Medical Research Expeditionary Society

Trekkers descending from Namche Bazar (altitude 3440 m), at the end of their Himalayan trek were questioned about Acute Mountain Sickness (AMS) symptoms, using the Lake Louise Questionnaire. They were also asked whether acetazolamide masked AMS and whether they had attended lectures on AMS. 150 trekkers participated; AMS occurred in (38.7%), mean score 4.83 (SD 1.94). Females reported significantly more AMS than males (42.3%v36.7%,P=0.0014). Of the 59 trekkers would had AMS, only 57.6% thought they had suffered AMS; 35.6% attributed their symptoms to other causes and 6.8% were unsure. Acetazolamide (“Diamox”) was taken for AMS prevention by 18% and for treatment by 10.7%; the rest, (71.3%) did not take acetazolamide. When asked whether acetazolamide masked AMS, 16.7% believed that it did, 40% did not and 39.3% did not know. Lectures on AMS were attended by 47.4% of trekkers but 20% of these still thought acetazolamide masked AMS. AMS is common in trekkers but often unrecognised and the role of acetazolamide is often misunderstood. There is a need for better education of trekkers.

11. A NOVEL CONTINUOUS POSITIVE AIRWAYS PRESSURE (CPAP) DEVICE FOR USE AT HIGH ALTITUDE

Peter R. Davis*, Jorian Kippax*, Geoffrey M. Shaw*, David R. Murdoch*, Jennifer L. Goodhall**
*Christchurch Hospital, Christchurch, New Zealand, **St Bartholomews & The Royal London Hospital, London, United Kingdom

Continuous positive airways pressure (CPAP) is used to treat cardiogenic pulmonary oedema and acute lung injury, and has been advocated as a means of treating high altitude pulmonary oedema (HAPE). Until now, logistical and technical constraints have prevented the evaluation of CPAP in the high-altitude environment. One of us (GS), in association with the medical device company Lifevent®, has developed a unique portable CPAP device using very low gas flows. This device was evaluated in 14 subjects after rapid ascent to 3205 m on Aoraki/Mt Cook. One of the subjects developed HAPE within 8 hours of arrival.
This is the first report of CPAP use in the wilderness environment. CPAP was effectively delivered without loss of mask pressure, or re-breathing, with flow rates at times approximating minute ventilation. Peripheral oxygen saturation (SpO2) was significantly increased at CPAP of 5,10 and 15 cm H2O, while respiratory rate decreased. At ambient pressure SpO2 = 89.9% (95% confidence interval 87.8% to 92.0%), vs. 94.1% at 5 cmH2O (95% confidence interval 92.9% to 95.3%, p = 0.0012). The subject with HAPE improved dramatically with CPAP. There was no reduction in apparent cardiac output with increases in CPAP. This device may offer a practical, drug-free solution for treating high altitude illness.

12. MAGNESIUM IN THE TREATMENT OF ACUTE MOUNTAIN SICKNESS: A RANDOMIZED, DOUBLE BLIND, PLACEBO-CONTROLLED TRIAL

L. Dumont*, C. Lysakowski*, B. Kayser**, M.R. Tramèr*, C. Mardirosoff†, J.D. Junod*, E. Tassonyi*
*Division of Anesthesiology, Department APSIC, Geneva University Hospitals, and **UDREM, Geneva University Medical School, Switzerland. †Department of Anesthesiology, Clinique de Savoie, Annemasse, France

The pathophysiology of acute mountain sickness (AMS) probably involves hypoxia induced cerebral edema from an increased cerebral blood flow in presence of cytotoxic components. The latter may include N-Methyl-D-Aspartate (NMDA) receptor stimulation mediated calcium influx into neurons that leads to cellular swelling. Magnesium is a physiologic NMDA receptor blocker. The aim of this study was to test the efficacy of intravenous magnesium in the treatment of established AMS. In the Capanna Margherita (4,559 m), 25 volunteer subjects with overt AMS (AMS score > 6 with ataxia) were randomized to a 30 min intravenous magnesium sulfate infusion (4 g, 16 mmol) or placebo.
Treatment success was defined as > 50% reduction in the Lake Louise score within 1h. Although 11 of 12 subjects with established AMS who received intravenous magnesium had reduced AMS scores after one hour, only three were treatment successes (25%) compared with none of 13 subjects receiving placebo (P = 0.1). With magnesium, mean AMS score had decreased from 11.6±1.7 to 9.9±3.5 (P = 0.01); with placebo infusion, AMS scores remained unchanged. With intravenous magnesium, more subjects had a transient flush (75% versus 8%, P = 0.001). In subjects with established AMS, intravenous magnesium somewhat reduces symptom severity, but this effect is not clinically relevant. Even though magnesium is not useful for treating AMS a potential role of magnesium in the pathophysiology of AMS cannot be ruled out.

13. THE RELATIONSHIP BETWEEN OXYGEN SATURATION AND ACUTE MOUNTAIN SICKNESS IN INDIVIDUALS ASCENDING TO 3080M

Terry O’Connor, Gerald Dubowitz, Philip Bickler
Dept Anesthesia, UCSF, San Francisco, USA

Pulse oximetry (SpO2) is an increasingly utilized tool in the diagnosis of altitude related illness such as acute mountain sickness (AMS). While some evidence suggests SpO2 helps to predict susceptibility, we have inadequate data on the relationship of SpO2 to the presence of AMS. Additionally there is little data describing normal values for SpO2 at altitude. We therefore set out to observe AMS and SpO2 in healthy volunteers who ascended by foot to 3080m (Mt Rainier, USA) from 1640m. A questionnaire-based survey was used to study 89 subjects (20 female 69male). Co-synchronous resting pulse and saturation data were obtained using a finger pulse oximeter after arrival to 3080m. Using the Lake Louise Score, 16% of subjects had AMS at 3080m. Mean SpO2 was 90% ± 4%. No correlation was seen between the presence of AMS and the SpO2 (Chi Square = 0.55). We conclude that while pulse oximetry is a useful and readily available physiological tool, the SpO2 does not correlate with AMS as defined by the Lake Louise Score.

14. HEART RATE CORRELATES WITH ACUTE MOUNTAIN SICKNESS IN SUBJECTS AT 3080M

Terry O’Connor, Gerald Dubowitz, Philip Bickler
Dept Anesthesia, UCSF, San Francisco

In spite of many studies of acute mountain sickness (AMS), there are little data on physiological variables that correlate with the presence or susceptibility to AMS. We therefore set out to study the relationship between heart rate and AMS in resting subjects at 3080m.
We observed 191 (33 female, 158 male) recently arrived volunteers at 3080m on Mt Rainier (Washington, USA) according to their own ascent profile. Each completed a questionnaire-based survey; co-synchronous resting pulse data were obtained using a finger pulse oximeter.
AMS was observed in 16% of subjects (Lake Louise Score). Mean resting pulse rate over a 30sec period was 90bpm ± 14. Using a Chi Square test, AMS score and pulse were highly correlated (Chi Square 0.013), suggesting subjects with a higher pulse rate were more likely to have AMS. There was no significant difference between males and females.
We conclude that pulse rate offers a simple test, which correlates to the symptoms of AMS. It may prove to be a useful objective tool facilitating AMS diagnosis at moderate altitudes.

15. PULMONARY ARTERY PRESSURE CHANGES DURING ASCENT TO HIGH ALTITUDE MEASURED BY ECHOCARDIOGRAPHY

Gerald Dubowitz, Philip Bickler
Department of Anesthesia, UCSF, San Francisco, USA

Hypoxia causes an increase in pulmonary artery systolic pressure (PASP). While this has been documented in normal subjects at high altitude, the evolution of these changes during acclimatization and ascent remains unclear. We set out to observe changes in PASP measured non-invasively using echocardiography in six volunteers during a 3 day ascent to 4317m. Data from 1227m, 3075m, 3779m and 4317m were compared to baseline sea level measurements. Mean PASP of 35mmHg at 3779m was significantly increased, as was 34mmHg at 4317m compared to sea level (mean = 21mmHg, P<0.05). The mean PASP increase to 25mmHg at 3075m was not significant compared to sea level.
This data suggests that significant changes in PASP occur during exposure to 3779m and higher. We were unable to establish whether exposure to moderate altitudes prevents PASP rise at higher altitudes. Further controlled studies are needed to establish whether time at altitude affects the magnitude of PASP rise and the relationship of this to disease states such as acute mountain sickness and high altitude pulmonary edema.

16. ACUTE MOUNTAIN SICKNESS ON ACONCAGUA (6962 m)

PESCE Carlos*, PINTO Hernán*, GONZÁLEZ Gabriela*, CHIOCCONI Ramón*, MOHR Yanina*, LEAL Conxita**, MAGGIORINI Marco†, SCHNEIDER Michael‡, BÄRTSCH Peter‡
*Departamento Medicina de Montaña, Centro APTUS de Medicina Deportiva, Buenos Aires; **Institut d'Estudis de Medicina de Muntanya, Barcelona, Departments of Internal Medicine, University Hospitals of †Zürich and ‡Heidelberg

To assess factors associated with acute mountain sickness (AMS) information was obtained by questionnaires at Laguna de los Horcones (2900 m) from 919 mountaineers returning from climbing on Aconcagua between January 3 and 31, 2001. AMS is defined as a score > 4 of the Lake Louise self report questionnaire, which was filled out retrospectively for the day when subjects had felt worst. AMS prevalence was 39%. No history of AMS, a higher altitude reached on previous exposures, more days spent above 3000 m per year and in the preceding months were associated with a lower AMS prevalence in a bivariate analysis while there were no effects for age, gender, BMI, use of oral contraceptives, smoking tobacco and training hours. Ascent rate was negatively correlated with AMS (r = -0.11, p = 0.01). Not being susceptible to AMS had the biggest effect in multivariate analysis, reducing the relative risk (RR) by 2.7 (95%-CI: 2.1 to 3.4). Previous climbing above 6000m and spending more then 10 days per year and 5 days in the last 2 months above 3000 m taken together resulted in a further reduction of RR by 2.1(95%-CI:1.3 to 3.4) Our data show that the best predictors of AMS on Aconcagua are susceptibility, previous mountaineering activity and pre-acclimatization. Ascent rate may be slightly slowed down as a consequence of AMS in the setting of staged ascent.

17. CHARACTERISTICS OF MOUNTAINEERS ASCENDING ACONCAGUA (6962 m)

PESCE Carlos*, PINTO Hernán*, GONZÁLEZ Gabriela*, CHIOCCONI Ramón*, MOHR Yanina*, LEAL Conxita**, MAGGIORINI Marco†, SCHNEIDER Michael‡, BÄRTSCH Peter‡
*Departamento Medicina de Montaña, Centro APTUS de Medicina Deportiva, Buenos Aires; **Institut d'Estudis de Medicina de Muntanya, Barcelona, Departments of Internal Medicine, University Hospitals of †Zürich and ‡Heidelberg

To describe the population ascending Monte Aconcagua information by questionnaires was obtained from 919 returning mountaineers between January 3 and 31, 2001, at Laguna de los Horcones (2900 m). AMS is defined as a score >4 of the Lake Louise self report questionnaire, which was filled out in retrospect for the day when subjects had felt worst. Climbers came from Europe: 54%, South America:27%, North America:14%, Asia and Oceania: 5%. 15 % were women. Further characteristics are: Age (years): <30:27%; 30-39:39%; 40-49:22%, and Ž 50:13%. BMI (kg/m 2 ) <20:8%; 21-23: 57%; 24-26:22%; >26:13%. Training (h/week):0–4:29%; >10:41%. Days spent above 3000 m per year: 0-4:28% and >20:28%. Previous highest altitude (m): =4000:8%; 4001-6000:44%; 6001-7000:41%; >7000, 7%. 36% took analgesics, 16% acetazolamide, 3% sleeping pills and 1% corticosteroids. 51% abstained from any drugs. The summit was reached by 60%. The prevalence of AMS (individuals taking acetazolamide and corticosteroids excluded) was 39 % (95% CI: 35-43%). Conclusions: There is a large variability regarding previous mountaineering experience, a low percentage of women, and a rather high success rate on Aconcagua. The prevalence of AMS is comparable to data reported in the literature for studies using similar definitions of AMS.

18. HIGH ALTITUDE INCREASES SERUM MIF

Linda E. KEYES*, Ian CLARK**, Gig LEADBETTER†, Kirsten MAAKESTAD‡, Sheryl OLSON°, Peter H HACKETT°
*University of Colorado Health Sciences Center, **Australian National Unversity, †Mesa State College, ‡University of Missouri, °Colorado Springs, Colorado

Macrophage migration inhibitory factor (MIF) is an endogenous glucocorticoid regulator. MIF counter-regulates the actions of endogenous cortisol, is induced by hypoxia and is important in inflammatory responses such as sepsis. We asked whether MIF was increased on acute exposure to high altitude and whether higher levels were associated with the occurrence of AMS. Methods: 38 healthy subjects ascended rapidly to 4300m. Half the subjects took gingko biloba 120mg orally as AMS prophylaxis and half took placebo. AMS was measured by the Lake Louise score (LLS) and the Environmental Sickness Questionnaire – C score (ESQ-c). Serum was drawn for MIF analysis before and after ascent. Serum MIF was analyzed by ELISA. Results: MIF increased in all subjects (1.26±0.14 vs. 2.3±0.31 ng/ml p<.01). Treatment with Gingko had no effect on MIF levels before or after ascent (1.39±0.25 vs 1.08±0.17 ng/ml, placebo vs. gingko before, p=NS and 2.59±0.47 vs 2.05±0.42 ng/ml after, p=NS). There was no correlation between MIF levels and the severity of AMS by LLS or ESQ-c.
Conclusions: Acute high altitude exposure increases serum MIF. Gingko biloba does not prevent AMS by altering MIF levels. Further studies are needed to elucidate the role of MIF in adaptation to high altitude exposure.

19. MAGNESIUM IN THE PREVENTION OF ACUTE MOUNTAIN SICKNESS: A RANDOMIZED, DOUBLE BLIND, PLACEBO-CONTROLLED TRIAL

L. Dumont*, C. Lysakowski*, B. Kayser**, M.R. Tramèr*, C. Mardirosoff†, J.D. Junod*, E. Tassonyi*
*Division of Anesthesiology, Department APSIC, Geneva University Hospitals; **UDREM Geneva University Medical School, Switzerland; †Department of Anesthesiology, Clinique de Savoie, Annemasse, France

The pathophysiology of acute mountain sickness (AMS) probably involves hypoxia induced cerebraledema from an increased cerebral blood flow in presence of cytotoxic components. The latter may include N-Methyl-D-Aspartate (NMDA) receptor stimulation mediated calcium influx into neurons that leads to cellular swelling. Magnesium is a physiologic NMDA receptor blocker. Uncontrolled observations suggest that oral magnesium may prevent acute mountain sickness. The aim of this study was to test this hypothesis with a randomized, double blind, placebo-controlled trial.
Methods
Seventy volunteers were randomly allocated to oral magnesium-citrate 400 mg (16.5 mmol) or placebo. Treatment taken every 8hours for 72 hours, from the beginning of the ascent to the end of a stay at altitude. Ascent from 1,130 m to 4,559 m lasted 24±2 hours and the following 48 hours were spent at 4,559 m. AMS was assessed 12-hourly using the Lake Louise score.
Results
There were 9 dropouts. With magnesium, 12/30 subjects (40%) were prevention failures (score at any time point =6 and/or ataxia) compared with 11/31 (36%) with placebo (RR 1.13, 95%CI 0.59 to 2.15). Onset time, incidence and severity of AMS was similar in both groups. 50 of all subjects (82%) had a score > 3 at any time-point during the study period; 32 (52%) had a score > 6. With magnesium, significantly more subjects had diarrhea (32% vs 12%).
Conclusions
In a setting of unacclimatized subjects rapidly ascending to high altitude a high oral intake of magnesium does not prevent nor attenuate nor delay AMS.

20. MIDAZOLAM IMPROVES SLEEP AND DOES NOT EXACERBATE ACUTE MOUNTAIN
SICKNESS DURING RAPID ASCENT TO 4559m

Stefano ANASTASI, Paolo ERBA, Oliver SENN, Konrad E. BLOCH, Marco MAGGIORINI
Intensive Care Medicine and Pulmonary Division, University Hospital Zurich, Switzerland

To investigate whether the intake of 15mg midazolam may precipitate acute mountain sickness (AMS) during the ascent to 4559m within 24 hours. Forty-six healthy mountaineers were randomly assigned to receive midazolam (M) or placebo (P) for two consecutive nights (3650m and 4559m). AMS score, sleep quality (0 = excellent, 3 = very poor) and efficiency, breathing patterns and peripheral SO2 were measured. The results (mean±SEM) obtained at 4559m are in the table.

  Placebo Midazolam P value
Subjective sleep quality 1.74 ± 0.14 1.17 ± 0.17 0.02
Sleep efficiency (% time a sleep) 76 ± 3 84 ± 2 0.04
Apnea index (Apneas/h sleep) 78 ± 16 54 ± 12 0.24
SaO2 < 70% (% time in bed) 52 ± 9 37 ± 8 0.19
AMS-c score 0.60 ± 0.12 0.31 ± 0.08 0.06

In conclusion midazolam at the dose of 15mg improves sleep quality and does not enhance the development of AMS in healthy mountaineers during rapid ascent to high altitude.

21. CHARACTERISTICS OF NOCTURNAL BREATHING PATTERNS AT HIGH ALTITUDE IN PEOPLE DEVELOPING ACUTE MOUNTAIN SICKNESS

Paolo Erba, Stefano Anastasi, Oliver Senn, Marco Maggiorini, Konrad E. Bloch
Intensive Care Medicine and Pulmonary Division, University Hospital Zurich, Switzerland

To investigate whether acute mountain sickness (AMS) after rapid ascent to high altitude is associated
with sleep and breathing disturbances during night. In 25 healthy mountaineers during the first night at 4559m we recorded sleep efficiency, breathing patterns and pulse oximetry (SpO2). AMS (score >4) was defined using Lake Louise criteria. Values are medians (quartiles).

  Controls (n=11) AMS (n=14)
AMS score (morning) 3 (2 to 4) 7 (7 to 9) *
Sleep efficiency (%) 86 (80 to 89) 70 (60 to 81) *
Respiratory rate (min -1 ) 17 (16 to 20) 19 (14 to 22)
Tidal volume (L) 0.36 (0.31 to 0.40) 0.46 (0.36 to 0.60)*
Ventilation (L/min) 5.8 (5.2 to 6.3) 9.1 (6.3 to 10.5)*
Apnea/Hypopnea Index (h -1 ) 41 (13 to 93) 92 (34 to 134)
SpO2 (%) 74 (68 to 78) 60 (53 to 73)*

* p<0.05 vs controls

We conclude that subjects with AMS, compared to controls, have a lower SpO2, this despite increased but unstable ventilation, which may reduce sleep efficiency.

22. POSITIVE ASSOCIATION OF THE ENDOTHELIAL NITRIC OXIDE SYNTHASE GENE POLYMORPHISMS WITH HIGH-ALTITUDE PULMONARY EDEMA

Yunden Droma, Masayuki Hanaoka, Masao Ota*, Yoshihiko Katsuyama**, Tomonobu Koizumi, Keisaku Fujimoto, Toshio Kobayashi, Keishi Kubo
Departments of Internal Medicine, *Legal Medicine and **Pharmacy, Shinshu University School of Medicine, Matsumoto, Japan

In order to elucidate the genetic background of the defective nitric oxide (NO) synthesis in the lung of high-altitude pulmonary edema (HAPE), we examined the Glu298Asp variant and 27-basepair (bp) variable numbers of tandem repeats (VNTR) polymorphisms of the endothelial NO synthase (eNOS) gene using polymerase chain reaction followed by restriction fragment length polymorphism.in 41 HAPE-susceptible subjects (HAPE-s) and 51 healthy climbers (control group) of a Japanese population. The Asp.allelic frequency of the Glu298Asp variant was 51.2% in HAPE-s and 15.7% in controls, which was significantly different between the two groups (P=0.000266). The eNOS4a allelic frequency of 27-bp VNTR was 41.5% in HAPE-s, significantly higher than that of 11.8% in controls (P=0.001067). The frequency of combining both the Asp and eNOS4a alleles was 26.8% in HAPE-s, but none of the controls were genotyped the two polymorphisms simultaneously, with more powerful significant difference between the two groups (P=0.0000587). Both polymorphisms of the eNOS gene were significantly associated with HAPE. A genetic background may underlie the impaired NO synthesis in the pulmonary circulation of HAPE-s. These polymorphisms could be as genetic markers for predicting the susceptibility to HAPE.

23. RESPIRATORY CHANGES RELATED TO EPITHELIAL ION TRANSPORT AT ALTITUDE

Mason NP*, Petersen M*, Imanow B**, Matveykine O**, Gautier MT*, Sarybaev A**, Aldashev A**, Mélot C*, Naeije R*
*Dept. of Physiology, Free University of Brussels, Belgium **National Centre for Cardiology and Internal Medicine, Bishkek, Kyrgyzstan

Methods: Nasal potential difference (NPD); lung water (LW) measured by electrical impedance tomography; cough threshold (CT) to inhaled citric acid; forced vital capacity (FVC) and pulmonary artery pressure (PAP) estimated by Doppler echocardiography were measured at 700m (BL) and during 2 weeks at 3800m (HA) in the Tien Shan mountains in 20 healthy volunteers.

Results: On ascent to HA, NPD hyperpolarized from -13.7 ± 1.6 to -17.5 ± 1.5 mV (mean ± SEM, p<0.05); LW increased and FVC and CT decreased (all p<0.05). There was only a mild increase in PAP (12 ± 1 to 20 ± 1 mmHg), which would be insufficient to cause increased capillary filtration. All changes were most prominent during the first 2 days at HA, and thereafter tended to return to normal. The amiloride-inhibitable portion of NPD did not change.

Conclusion: These results suggest that altitude causes a subclinical increase in LW accounting for decreased FVC and CT, potentially explained by increased respiratory epithelial anion secretion.

24. DEXAMETHASONE PREVENTS THE MICROCIRCULATORY INFLAMMATORY RESPONSE TO SYSTEMIC HYPOXIA

Norberto C. Gonzalez, Dawn Steiner, John G. Wood
Department of Molecular and Integrative Physiology, University of Kansas Medical Center, USA

Dexamethasone is effective in the treatment of AMS, suggesting an inflammatory component in this condition. We have shown that systemic hypoxia produces an inflammatory response characterized by increases in reactive oxygen species (ROS) generation, leukocyte-endothelial adhesive interactions, and vascular permeability in various microcirculatory beds of rats. The objective of this study was to determine if dexamethasone prevents these responses. The mesenteric microcirculation of rats was studied using intravital microscopy. Hypoxia (FiO2 = 0.10) increased the number of leukocytes adhering to venules (leukocytes / 100µm) from 0.5 ± 0.2 in normoxia to 10.7 ± 0.7 after 10 min of hypoxia (p<0.05) . This was accompanied by a 61 ± 10 % increase (p<0.05) in the fluorescence intensity of dihydrorhodamine (DHR), an ROS probe. Pretreatment with dexamethasone (2 mg/kg subcutaneously 24 h before hypoxia) completely blocked the increase in leukocyte adherence and in DHR fluorescence.

These results indicate that dexamethasone prevents the inflammatory response to hypoxia in the mesenteric microcirculation and suggest that its effect on AMS may be due to its anti-inflammatory properties.

25. LACK OF ASSOCIATION OF HIGH ALTITUDE PULMONARY EDEMA AND POLYMORPHISMS OF THE NO PATHWAY

Peter Bärtsch*, Walter Emil Haefeli**, Christiane Gasse**, Michael Hoffmann†, Jörn Weymann*, Simon Gibbs‡, Johanna Weiss**
*Division of Sports Medicine and **Clinical Pharmacology, Dept. Internal Medicine, University Hospital Heidelberg, Germany; †Division of Clinical Chemistry, Albert-Ludwigs-University, Freiburg, Germany; ‡National Heart and Lung Institute and Medicine and Hammersmith Hospital, London, UK

Recent findings suggest that low NO levels in pulmonary vessels contributes to the enhanced hypoxic pulmonary vascular response in individuals susceptible to high altitude pulmonary edema (HAPE). Therefore we hypothesized that nitric oxide synthase (NOS)-3 gene polymorphisms like G894T or CA-repeats in intron 13 associated with a decreased synthesis of NO may contribute to susceptibility to HAPE, while the C242T polymorphism in the p22phox gene (important component of the NAD(P)H oxidase) may be associated with decelerated degradation of NO and thus resistance to HAPE. Therefore we assessed these genotypes in 51 mountaineers susceptible and in 52 mountaineers not susceptible to HAPE. The frequency of the TT genotype of G894T polymorphism was 14% in HAPE-susceptible and 8% in HAPE-resistant individuals, the frequency of the T-allele was 37% vs. 30%, the frequency of CA-repeats Ž 38 was 10% vs. 8%. The frequency of the TT-genotype of p22phox C242T polymorphism was 10% vs. 10%, and for the T-allele 33% vs. 36%. None of the differences in the frequencies proved to be significant.

We conclude that there is no evidence for a major role of the examined gene polymorphisms in the pathophysiology accounting for susceptibility to HAPE.

26. ACUTE MOUNTAIN SICKNESS (AMS) PRESENTING TO THE KUMTOR MINE SITE, KYRGYZ REPUBLIC (CIRCA 4000 M)

Ashyrbaev A, Nakahara S, Wakai S
University of Tokyo, Department of International Community Health 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan, 113-0033

The AMS incidence rate (IR) among general visitors to high altitude is substantial. This cross sectional study estimates AMS IR among shift workers and explores a role of occupational factors for AMS. Convenience sampling was used. Respondents were regarded as AMS (-) and AMS (+). A score of ±3 points (by Lake Louise score) was a threshold for AMS. For statistical analysis SPSS for Windows 10.0 (1999) was used. Total 200 workers (79% M, 21% F). Mean age and BMI of them 36.6±8.37 and 24.8±3.33 respectively. 46% workers live at sea level, 54% of them live at an altitude of 1700 m. The mean work duration was 3.9±1.51 years. Physical workers are represented 59.5%, office workers 40.5%. Smokers 41.5% and non-smokers 58.5% AMS IR was 25%. Physical workers are more likely to develop AMS (Odds Ratio 0.48; 95% confidence interval, 0.24-0.96). There was relationship between chronic diseases and AMS (Odds Ratio 2.24; 95% confidence interval, 1.09-4.58).

No associations between age, gender, BMI, altitude of residence, previous experience of work at high altitude, years of work at the mine site with AMS was found.

27. ACUTE MOUNTAIN SICKNESS AND ACETAZOLAMIDE: WHAT DO TREKKERS KNOW?

Major R, Ainsworth H, Wright D and BMRES
University of Birmingham Medical School, United Kingdom

Ascending trekkers were interviewed after spending one night at Namche Bazaar (3440m) in Nepal. Questionnaires were used to record Acute Mountain Sickness (AMS) scores (Lake Louise), use of Acetazolamide (AZ) and subject demographics. There were 89 subjects, 55 (62%) male and 34 (38%) female. Ages ranged from 18 to 60 years, with most being 21-30. The majority (73%) were travelling independently but 27% were on commercial treks. Only 11 (12%) were taking AZ but 28 (31%) had AMS scores of three or more. Independent travellers were less likely (p<0.05) to have any knowledge about prophylactic use of AZ in AMS. Trekkers with knowledge of AZ use were more likely to be carrying AZ for emergencies (p<0.01). More than a third of young independent trekkers had significant AMS, which was not reduced by prior knowledge about or use of AZ. Commercial treks provide information and emergency AZ but this does not reduce the incidence of AMS. We found no individual factor associated with reduced incidence of AMS.

28. SUBLINGUAL GLYCERYL TRINITRATE-INDUCED HEADACHE AS A PREDICTOR FOR INCIPIENT ACUTE MOUNTAIN SICKNESS

Dr Roger CN McMorrow, Dr Nigel D Hart
Medex, 148 Finaghy Road South, Belfast, BT10 0DG, N. Ireland

The most common symptom associated with Acute Mountain Sickness (AMS) is headache. The headache may be caused by meningeal irritation as a result of blood vessel dilatation. Glyceryl trinitrate is known to dilate cerebral vasculature and causes headaches similar in quality to the headache associated with AMS.
This study evaluated the relationship between GTN- induced headache and AMS scores. Nine subjects were studied at sea level and on every day of ascent to the summit of Kilimanjaro (5896m). Each day, sublingual GTN was administered and headache score shift between pre and post dose was rated by the subjects. Subjects also rated their daily AMS score. The data was analysed using the Fisher test. A positive correlation (p=0.003) was demonstrated between GTN induced- headache score shift and shifts in AMS score observed on further ascent of between 400-1000m in the next 24hour period. The likelihood of a large AMS shift carries a relative risk of 5.42 for a large headache score shift. Sublingual GTN may be useful as a predictor for incipient AMS. Further studies may be useful to test this hypothesis.

29. RESPUESTA AL ESTIMULO ANDROGENICO DE LAS GLÁNDULAS COAGULANTES EN RATAS EXPUESTAS A LA ALTURA (MOROCOCHA 4,540 m)

E. Mujica Alban, J. Aliaga Arauco, M. Ortiz Sanchez, R.J Huaman Olarte
Instituto Nacional de Biología Andina. Facultad de Medicina. Universidad Nacional Mayor San Marcos. Lima Perú

Las glándulas coagulantes de la rata al igual que la vesícula seminal en el hombre producen fructosa bajo estimulo androgénico. En trabajos previos hemos reportado que la exposición aguda a la altura, tanto en ratas como en humanos produce un aumento de testosterona sérica.
El presente trabajo se realizó con el objeto de conocer si las glándulas coagulantes de ratas expuestas a la altura responden al estimulo androgénico de forma similar que al nivel del mar. 50 ratas macho nacidas en Lima(150m) fueron llevadas a Morococha (4,540 m) y divididas en dos grupos: 25 sin tratamiento y 25 recibieron Sulpiride (Dogmatil-Spedrog) a fin de disminuir los valores de testosterona sérica. 50 ratas fueron trabajadas en Lima (control) en grupos similares. Se analizó testosterona por RIA y fructosa por el método de Roe modificado por Foreman. Los resultados indicaron que en la altura la respuestas al estimulo androgénico es la misma que al nivel del mar.

30. 3% CARBON DIOXIDE INCREASES CEREBRAL OXYGEN DELIVERY WHEN BREATHING HYPOXIC GAS MIXTURES

Imray CHE, Wright AW, Chan C, Bradwell AR, and the Birmingham Medical Research and Expeditionary Society

Oxygen delivery to tissues is critical in determining performance and illness at all altitudes. 17 subjects (3 female, age 22-56) were studied at 50m. Once a steady state had been achieved, supplementary CO2 was then added to the 12% oxygen. Minute volume (MV) was measured. Pulse oximetry (SpO2) and end tidal CO2 (PetCO2) were measured using a Propac Encore Monitor; regional cerebral oxygenation (rSO2) was measured using a Critikon 2020 monitor; middle cerebral artery velocity (MCAV) was assessed using a Logidop 3 machine. Oxygen delivery (DO2) was calculated (MCAV X SpO2). Baseline studies were followed by 1 minute of voluntary forced hyperventilation (FHV).

Results:

 
PetCO2
SpO2
rSO2
MCAV
DO2
MV
Baseline
39 (3.1)
97.6 (1.2)
69.7 (2.8)
53.1 (8.1)
5182
12% oxygen
36.0 (3.5)*
79 (3.1)*
63.7 (3.1)*
58.9 (10.3)
4653*
7.8 (1.9)*
O2/CO2
46.2 (6.3)**
93.6 (5.6)**
69.0 (3.0)**
62.4 (8.5)**
5840**
11.0 (5.1)

Statistics: Paired t test * p<0.05 vs Baseline, ** p<0.05 vs 12% oxygen

Conclusion: 12% oxygen results in a fall in SpO2, PetCO2, DO2 and cerebral rSO2. The oxygen/carbon dioxide mix increased DO2 to above baseline levels.

31. 3% CARBON DIOXIDE INCREASES CEREBRAL OXYGEN DELIVERY AT 150m & 3549m

Imray CHE, Walsh S, Clarke T, Hoar H, Harvey TC, Chan CWM, Forster PJG, and BMRES

The role of supplementary carbon dioxide at altitude has yet to be determined. The effect on oxygen delivery to the brain was calculated based upon previously collected data. 12 subjects were studied at 150m and a month later at 3459m. Air, 3%CO2, 35%O2, and 3%CO2/35% O2 were used. Pulse oximetry (SpO2) was measured using a Propac Encore Monitor; regional cerebral oxygenation (rSO2) was measured using a Critikon 2020 monitor; middle cerebral artery velocity (MCAV) was assessed using a Logidop 3 machine. Oxygen delivery (DO2) was calculated (MCAV X SpO2).

Results:

 
SpO2 %
MCAV
RSO2
DO2
150m Air
97.5(1.5)
58.8 (14.2)
69.9 (2.6)
5773
3549m Air
91.3(3.0)
63.1 (18.6)
65.6 (2.8)
5761
150m CO2
98.5(1.0)*
68.1 (13.3)*
70.6 (2.5)*
6707*
3549m CO2
93.3(3.0)*
68.6 (19.2)*
66.7 (3.2)*
6414*
150m O2
99.3(0.7)*
54.0 (16.5)*
70.3 (2.6)*
5362
3549m O2
99.6(0.8)*
58.1 (16.5)*
68.8 (2.9)*
5786
150m Mix
99.5(0.2)*
64.8 (13.4)*
71.0 (2.6)*
6447*
3549m Mix
100(0.0)*
62.0 (20.8)
70.2 (3.8)*
6200*

Statistics: Paired t test * p<0.05 vs Baseline

Conclusion
DO2 remains constant on air. Supplementary 3% CO2 and the mix increases oxygen delivery at both altitudes.

32. CEREBRAL OXYGEN DELIVERY FALLS WITH VOLUNTARY FORCED HYPERVENTILATION AT ALTITUDE

Imray CHE, Hoar H, Beazeley M, Wright AD, Bradwell AR, Chan C, and BMRES

Hyperventilation profoundly affects PeCO2, and in turn cerebral blood flow. This study aimed to further investigate effects on cerebral oxygen delivery at altitude. 8 subjects were studied at 0m, 2400m and 5050m. Pulse oximetry (SpO2) and end tidal CO2 (PetCO2) were measured using a Propac Encore Monitor; regional cerebral oxygenation (rSO2) was measured using a Critikon 2020 monitor; middle cerebral artery velocity (MCAV) was assessed using a Logidop 3 machine. Oxygen delivery (DO2) was calculated (MCAV X SpO2). Baseline studies were followed by 1 minute of voluntary forced hyperventilation (FHV).

Results:

 
0m
0m FHV
2400m
2400m FHV
5050m
5050m FHV
SpO2 %
98.7 (1.5)
99.5 (1.7)*
94.6 (1.5)
99.7 (0.5)*
73.6 (4.9)
95.5 (0.9)*
PetCO2
37.4 (1.9)
21.9 (2.8)*
36.4 (2.8)
19.4 (1.8)*
29.4 (1.8)
7.0 (2.6)*
MCAV cm/s
54.5 (10.2)
37.2 (16.1)*
55.9 (14.8)
25.1 (9.6)*
61.8 (12.4)
19.6 (11.3)*
rSO2 %
69.2(2.7)
67.2(3.1)*
68.5(2.1)
68.3(2.1)
62.1(1.6)
66.9(1.34)*
DO2
5379
3701*
5228
2492*
4548
1824*

Statistics: Paired t test/ANOVA * p<0.005 FHV vs Baseline at 0m, 2400m, 5050m.

Conclusion. At 5050m SpO2, PetCO2, rSO2, and DO2 fell, whilst MCAV rose compared to 0m. FHV reduced PetCO2 and increased SpO2 at all altitudes. At 0m, the reduction in MCAV overrode the small increase in SpO2, resulting in a drop in cerebral oxygenation and DO2; however at 5050m the increase in SpO2 was so great that despite the reduction in MCAV there is an increase in rSO2 and there was a fall in DO2.

33. ENHANCEMENT OF CEREBRAL AUTOREGULATION IN NEWCOMERS TO HIGH ALTITUDE

Christian Mélot*, Jacques Berré*, Bakyt Egimnazarov†, Oleg Pak†, Akpay Sarybayev†, Nicholas Mason**, Robert Naeije**
*Department of Intensive Care, Erasme University Hospital, Brussels, Belgium. **Department of physiology, Free University of Brussels, Belgium. †National Centre for Cardiology and Internal Medicine, Bishkek, Kyrgyzstan.

Cerebral autoregulation (CA) is the capacity of the brain to maintain constant blood supply within a wide range of mean arterial blood pressure values. CA is generally thought to be altered in newcomers to high altitude suffering from high altitude cerebral edema, a severe form of acute mountain sickness.
Twenty young males volunteers were evaluated at low altitude (Bishkek, 760 m), at days 1, 2, 5, 10 and 15 at high altitude (Kum–Tor, 3800 m), and at day 1 after return to low altitude. We evaluated dynamic CA by computing the autoregulation index (ARI) by analyzing the change in cerebral blood flow velocity measured by transcranial Doppler during hypotension induced by reperfusion of the lower limbs after 3 minutes of acute ischemia. None of the subjects suffered from acute mountain sickness. ARI increased within the first days at high altitude and reached a maximal value (+ 30 %) at day 5 compared to low altitude value (from 3.9+0.3 to 5.1+0.3, p < 0.005, mean+SE). This increase at day 5 was partially attenuated after correction of hypocapnia (4.8+0.4) but not after correction of hypoxemia (5.1+0.2).

In conclusion: CA seems to be enhanced in newcomers to high altitude in the absence of acute mountain sickness. This increase in CA results partially from hypocapnia due to hyperventilation.

34. 6-HYDROXYDOPAMINE-INDUCED LOCUS COERULEUS LESIONS ALTER THE HYPOXIC VENTILATORY RESPONSE IN CONSCIOUS RATS

Christophe SOULAGE*, David PERRIN*, Jean Marie COTTET-EMARD**, Jean Marc PEQUIGNOT*
*UMR CNRS 5123 - Physiologie des Régulations; **Laboratoire de Physiologie de l’Environnement. Université Claude Bernard; LYON, France

Upon exposure to hypoxia, the initial and most important response is an increase in alveolar ventilation.
There is now growing evidence that the medullary catecholaminergic groups (A1C1, A2C2, A5, A6) participate in the ventilatory response to hypoxia. The present study was designed to assess the involvement of the A6 noradrenergic cell group, located in the locus coeruleus (LC), for the establishment of the ventilatory response to short-term hypoxia. The breathing response to acute hypoxia (10% O2) was measured in awake rats 15 days after an unilateral lesion of LC with 6-hydroxydopamine. The 6-hydroxydopamine infused “in situ” caused a major loss of noradrenergic neurons and noradrenalin content in the A6 area. Whereas basal resting ventilation is unaffected by the lesion, tidal volume component of the hypoxic ventilatory response is blunted (-67%) and the respiratory “roll-off” is reversed. We concluded that i) LC noradrenergic neurons are not essential for breathing modulation under normoxia, ii) under hypoxia, tidal volume is controlled by central nervous mechanisms, iii) noradrenergic neurons of the LC are involved in this regulation.

35. POSSIBLE DISSOCIATION BETWEEN ATTENTION AND MEMORY IMPAIRMENTS RELATED TO MODERATE HIGH ALTITUDE

Javier Virués Ortega, David Segui Durán, Gualberto Buela-Casal
Department of Personality, Assessment and Treatment. University of Granada (Spain)

A multiple baseline design (lowland1-altitude1-lowland2-altitude2) were used with five young climbers (22.4 years) without previous experience in mountains higher than 3500 m. They carried out two ascents to peaks higher than 4500 m resting a week after the first climbing. They stayed six days higher than 4000ms the first time and four days in the second case. All the days in which the research took place the subjects completed the digit span subtest of the Weschler scale and a time estimation test for short periods three times a day. The digit span was considered a short-tern memory (STM) measure while the time estimation test was considered an attention measure. There was no significant difference between the two baseline phases (lowland1-lowland2) neither between the two experimental phases (altitude1-altitude2). There were no effects in time estimation test average or standard deviation for the different conditions. A slight but significant effect was found in the memory task (7.82+/- 1.53 vs. 5.87 +/- 1.82; p<0.05). The results show that the stay during moderate periods at altitudes near 4000 m produce slight impairment in STM whereas the attention related to time estimation tasks remains unaffected.

36. PILOT STUDY: MATRIX OF CORRELATION OF PHYSIOLOGICAL AND PERCEPTIVE VARIABLES RELATED TO MODERATE HIGH ALTITUDE

Javier Virués Ortega*, Gualberto Buela-Casal*, Sergio Herrera López**
*Department of Personality Assessment and Treatment. University of Granada (Spain). **Unidad de Salud Mental Infanto-Juvenil. Princesa de España Hospital of Jaén (Spain)

Two groups of young climbers (n1=4 y n2=5) ascended independently the Mont Blanc (4808 m.). They spent four and three days respectively till the return to lowland. From the day before the ascent till the day after the descent the following variables were monitored three times a day. Blood Pressure (diastolic, systolic and average: DBP, SBP, ABP), Peripheral Temperature (PT), Heart Rate (HT) and the rest time before the recording (DESC) as physiological variables. The somnolence measured by the Stanford Somnolence Scale (SSS), time estimation measured by the Time Estimation Test (MET and DTET) as perceptive variables and the altitude (MS) recorded by GPS Garmin 12 or by map as environmental variable. The correlation matrix obtained is presented. The results show significant association between PT and MS (r= 0,72; p<0,01), DESC and SBP (r=0,62; p<0,05), SSS and PT (r=-0,63; p<0,05) and between SSS and DESC (r=0,62; p<0,05). There were no significant relations with the time estimation measures. Should be noted the strong association found between altitude and peripheral temperature and how the peripheral temperature is also related with the perceived somnolence.

Table 1. Correlation matrix of physiologic and perspective variables.

MS
DBP
SBP
ABP
HR
PT
DESC
SSS
MET
DTET
 
0,66*
0,30
0,24
0,60
0,72**
-0,30
-0,28
-0,10
0,26
MS
   
0,03
0,76**
0,20
0,44
-0,27
-0,36
-0,07
0,41
DBP
     
0,67*
0,19
0,59
0,62*
-0,26
0,34
0,09
SBP
       
-0,40
-0,39
0,07
0,04
0,26
0,25
ABP
         
0,73**
-0,30
-0,13