Travel At High Altitude, a booklet that can be freely download by clicking this link - a guide to staying healthy in the mountains.

Altitude Symposium Wednesday 3rd December 2008 at Worcester College, Oxford.

Mountain Medicine and High Altitude, Physiology Course, December 5th-7th 2008

Important dates for 2008

Research proposals for Hidden Valley Expedition 2008

The International HAPE Database www.altitude.org/hape.htm

Medex Hidden Valley Expedition 2008 Blogsite

Booking Information for Medex Hidden Valley Expedition 2008

Medical Expeditions Science: 2003

Introduction

By Jim Milledge

This report gives some idea of the scope of the science attempted on the Expedition. In compiling it, from contribution from all the lead researchers, I was struck again by the incredible diversity of the projects undertaken. An enormous amount of hard work went into preparing and carrying through these projects by a large number of people. Apart from the names which appear in this report, there were many others without whose contribution the science would not have happened. It may be invidious to name some and not all but risking that I would like to pay tribute again to George Wormald who, though not able to come on the expedition, dealt with all the air freight, Denzil Broadhurst and Jim Duff who ran Base Camp so efficiently and much else. Annabel Nickol who, with help from Paul Richards, lead the science program and also the other members of Group 4 who set up Base Camp, especially the scientific infra-structure. Thanks are also due to Simon and Sally for organising the whole trip and getting us there and back. Ted Carter, Chief Technician at Queen Mary College who make his lab available and patiently helped us in innumerable ways during the data collection week-ends. Finally, of course, the science could not have been done without the active cooperation of all members who acted as (willing!) subjects.

As compared with the previous two Med Exp. Expeditions a much higher proportion of members were involved with research. This meant that the potential for tension between getting on with their own research and acting as subjects for others, was even greater than on previous expeditions. It is to everyone’s credit that in the event, both during the week-ends in London and during the time at Base Camp this potential threat did not become a problem.

Daily Data Collection

By David Collier

Work on altitude headache with Eli Silber found that only half of reported headaches during the K98 expedition were accompanied by positive AMS scores. The visual analogue scale information taken at the same time as self-reported headaches suggested that such headaches were also associated with impairment of other capacities. This implies that the Lake Louise score may miss a substantial fraction of altitude illness. Whilst this might not matter for a scoring system for AMS to be used to diagnose and treat significant illness, this is not ideal for a research tool.

Tom Martin and I derived a Visual Analogue Scale (VAS) score from the K98 data, which we think may be a more sensitive measure of altitude illness than the Lake Louise Score. This requires validation in a number of other settings, one of which was the Medical Expeditions Makalu 2003 trek. Further data will also be collected on the APEX 2003 trip to Chacaltaya.

The 57 members of the Expedition each had a data diary which they filled in each morning and evening of the trek. The data recorded included; location, altitude, barometric pressure, air temperature, SaO₂, pulse rate, symptoms of AMS both Lake Louise score and VAS, bowel movements and consistency and any medication taken. This vast amount of data has been entered into a large spreadsheet and the accuracy of entry is being checked. When this is complete the spreadsheet will be available to researchers who can then use it in the analysis of their own data.

I am very grateful to all members who diligently filled in their diaries and to the data collection officers in each group who ensured that this was done.

Hypoxic ventilatory response (HVR), acclimatisation to altitude and the ACE gene

Giorgos Tsianos, Jim Milledge, Annabel Nickol, Daniel Matisson, David Collier and Hugh Montgomery

Background There are two versions (or alleles) of the angiotensin converting enzyme, ACE, gene: an I form (insertion) and D form (deletion). Everyone has two alleles. Elite performance at high altitude and increased oxygen saturation levels in the blood during different ascent profiles is associated with the ACE I-allele.

Aims To see whether those people with the I gene have a greater increase in breathing when exposed to low oxygen levels. This might be apparent as a greater hypoxic ventilatory response (this is the amount by which breathing is increased as the oxygen level is lowered), or at altitude by higher oxygen saturations and lower carbon-dioxide levels.

Methods At sea level the hypoxic ventilatory response was measured. Gene studies were carried out to split the volunteers into two groups: those with two versions of the I gene (II) or one of each (ID), and those with two versions of the D gene (DD).

During the trek from 937m to 5000m resting oxygen saturations were measured twice daily. At Base Camp expiratory carbon dioxide levels and respiratory rate were measured each morning on the first 3 days.

Outcome Preliminary results show that there is no difference in hypoxic ventilatory response at sea level between the two groups, and no difference in expiratory carbon dioxide at Base Camp. The oxygen saturations will be examined soon. It seems that even though the I-allele of the ACE gene has been associated with an increased hypoxic ventilatory response during exercise in low oxygen levels, as well as increased blood oxygen saturation levels during rapid ascent profiles, this may not be the case during well planned, slow, and staged ascents to high altitude. The latter precautions could allow mountaineers to acclimatise better to the decreased oxygen pressures at altitude, protect them from the dangers of high altitude illnesses, and so contribute to an enhanced performance in such environmental conditions despite any genetic predisposition to the ACE I/D polymorphism.

Gastrointestinal perfusion at high altitude whilst resting and exercising

Stuart McCorkell, Daniel Martin, Mike Grocott

This project was conducted by the Baruntse expedition group. We hypothesised that during hypoxia at high altitude, particularly when this was exacerbated by exercise, the blood flow to the gut would be impaired because blood supply would be directed elsewhere (heart, brain, muscles) to preserve oxygen delivery to "vital organs". To test the hypothesis we studied 6 healthy volunteers at Chamlang Base Camp (5000m) at rest and then using a stepped exercise protocol (stepping on and off large stone block) whilst measuring the carbon dioxide concentration in the stomach using a gastric tonometer. The gastric tonometer measures an increase in intra-gastric PCO₂ when blood flow to the stomach is impaired. This is probably due to a combination of increased CO₂ production related to anaerobic metabolism (resultant on decreased tissue perfusion) and decreased clearance of CO₂ with reduced blood flow.

Preliminary analysis of the results showed significant hypoxia with exercise and suggest that some subjects had the predicted rise in intra-gastric CO₂ during exercise but others did not. In some cases the intragastric CO₂ was less than end-tidal CO₂ which is physiologically improbable. Our experiment was limited by the lack of availability of blood gas measurements for technical reasons. These results may indicate technical problems with the use of the tonometer at high altitude (we had to conduct major repairs at base camp and were not able to recalibrate the instrument after this) or may be related to air swallowing occurring at the high levels of ventilation necessary to sustain the exercise protocol.

Arterial oxygen saturation and heart rate at high altitude during the trek

Chris Wolff

Aims To study changes in Oxygen saturation (SaO₂) and heart rate during ascent at altitude.

Methods I have plotted some data acquired during the trek that shows what happens to oxygen saturations (SaO₂) on ascent and the reciprocal relationship found with heart rate. The group 2 values from morning and evening data collection sessions were averaged; immediately prior to and following ascent for rest day sessions at low and moderately high altitude. The low altitude ascent was from Salpha Phedi (1250 m; mean SaO₂ 95.4%) to Guraise (2800 m; height change 1550 m). Barometric pressures (PB), were 459 mm Hg and 385 mm Hg); acclimatization was for 36 hrs.

Outcome SaO₂ rose from the initial mean value of 90.9% to 93% by the morning after arrival (around 12 hrs). There was no further rise in the remaining 24 hrs. This differed from the second group 2 acclimatization at Tagnag (at 4300 m; PB 456), illustrated in the left panel of the figure.

Fig 1. (left) Data from Group 2 members ascending from Kothe to Tagnag

Fig 2. (centre) Same data, (filled symbols only) plotted as heart rate V SaO₂ to show reciprocal relationship of hear rate to SaO₂.

Fig 3. (right) Heart rate and SaO₂ in one subject climbing from Kothe to Tagnag showing the same relationship.

The ascent was from a higher level (Kothe at 3620 m; PB 498 mm Hg; mean SaO₂ 90.7%) and was around twice the recommended (300 m) increment (> 700 m). There was barely any improvement in SaO₂ from the arrival value (84.9 %) for over 24 hours (85.2%). Eventually SaO₂ reached 88.1% (at 60 hrs.) and may still have been rising.

The middle panel shows that there was a highly significant reciprocal relationship between acclimatization mean heart rate (HR) and SaO₂. HR is known to correlate well with cardiac output (Q); so this is compatible with whole body oxygen delivery (DaO₂ = Q x SaO₂ x Hb x a constant) being kept constant (as seen with cerebral DaO₂).

The right hand chart represents SaO₂ and heart rate at a high metabolic rate, recorded on Piotr at 10-minute intervals by Mireille during a fast climb during the Kothe/Tagnag ascent. The two points with x in the middle were recorded during recovery. This HR v SaO₂ relationship is highly significant and inverse, as in the acclimatization studies. Again this suggests an evening out of DaO₂.

These anecdotal plots illustrate: 1. The initial maximum fall in SaO₂ after each ascent. 2. The slow SaO₂ rise for the higher altitude following a large ascent (delayed acclimatization). 3. The reciprocal relationship of heart rate and SaO₂ for each of two very different metabolic rates. This is consistent with relative DaO₂ constancy for a particular metabolic rate.

Oxygen delivery in sub maximal exercise at sea level and at altitude after slow acclimatization

Chris Wolff, Doug Thake, Dan Matisson, Lisa Handcock, Alex Truesdell, David Collier and Jim Milledge

Aims To study the oxygen delivery system at rest and exercise at sea level and altitude and to determine if, at altitude, there is evidence of “steal” of blood flow. We hoped to study about 10 subjects.

The first two subjects analysed showed linear increases in cardiac output both at rest and at Chamlang base camp (5000 m approx.). In both there was a greater resting output at BC than at sea level with the altitude line, for cardiac output versus watts, above and parallel to the sea level line (see figure, left and middle graphs). The watts values are approximate so the result is a tentative one awaiting calculation of oxygen consumption. It seems likely that the increase in cardiac output (CO) above the resting value at sea level provides all the required oxygen delivery to the exercising muscle (DO_2M; Wolff, 2002). The excess cardiac output per Watt is the same at altitude but with a lower oxygen concentration (CaO₂ = SaO₂ x Hb x 1.34). There would be enough oxygen delivery per Watt if Hb had increased enough to compensate for the lowering of SaO₂, i.e. if SaO₂ x Hb for altitude was the same as at sea level.

For these two subjects, oxygen delivery (DO₂) can be seen to be the same at altitude as at sea level at these low work rates. However, for the third subject (right hand graphs) delivery is less at altitude than at sea level, a lower slope of the DO₂ / work line. This suggests a degree of ”steal” of blood flow by the working muscles from other vascular beds in this subject. Partial analysis of a further five subjects indicate that they show similarly reduced DO₂ at altitude.

REFERENCE: Wolff, C.B. (2003) Cardiac output, oxygen consumption and muscle oxygen delivery in sub maximal exercise - Normal and low O₂ states. Oxygen Transport to Tissue XXIII, Ed. Wilson D. et al., Kluwer Academic/Plenum Publishers,

Non-invasive assessment of cardiac function during acclimatisation to high altitude

Gerald Dubowitz

Background Echocardiography is a simple technique in which function of the heart and blood flow through it may be examined non-invasively. In utero there is a connection between the right and left chambers of the heart through the foramen ovale. This lets the blood by-pass the lungs, which serve no purpose for gas, exchange since this is occurring via the placenta. During birth the foramen ovale closes in most people so that blood flows through the lungs. In a minority it remains open, known as a ‘patent foramen ovale’ or PFO. It was speculated that ascent to high altitude might increase the prevalence of PFO by raising the pressure of arterial blood flowing to the lungs.

Aims The aim of this study was to evaluate whether in some people ascent to altitude leads to the presence of a PFO that was not apparent at sea level, and to determine whether people with a PFO do worse at altitude.

Methods Echocardiography was carried out at sea level and at Base Camp. A couple of mL of the volunteer’s blood was withdrawn from a cannula, mixed with bubbles and then reinjected. The bubbles show up on the echo, so revealing the presence of any abnormal connection between the right and left chambers of the heart such as a PFO.

Results and preliminary conclusions 32 studies were conducted at sea level and 50 at Base Camp. A number of people had a PFO at altitude that had not been apparent at sea level. It would seem that the presence of a PFO does not correlate with acute mountain sickness or cardiac function per se. Further studies would be helpful to see if there are other implications of a PFO at altitude on performance.

It was incidentally observed that a small subset of trekkers who took prophylactic acetazolamide had lower pulmonary arterial pressures.

Heart rate variability at high altitude

Paul Richards, Mireille Baart, Mark Dayer, Annabel Nickol and Mary Morrell

Background Heart rate variability (HRV), which refers to the beat-to-beat alterations in heart rate, is a useful tool for studying autonomic function. HRV-analysis can provide information about the relative balance between the activities of the parasympathetic and sympathetic nervous systems.

Aims It is known that high altitude has an effect on the nervous system. The aim of this study is to investigate the effect of high altitude on parasympathetic and sympathetic balance using HRV-analysis.

At high altitude many people suffer from periodic breathing. It is known that at sea level HRV is related to periodic breathing during sleep in patients with congestive heart failure. The second aim of this experiment is to investigate if there is a relationship between HRV and periodic breathing at high altitude.

If we observe any difference in parasympathetic and sympathetic balance at high altitude the hypothesis is that this is due to sympathetic stimulation by the stress of hypoxia. Another aim of the study is then to investigate if this hypoxic stress is just general altitude hypoxia or if it is also influenced by the additional hypoxic insult of periodic breathing desaturations during sleep.

Preliminary results Six male subjects participated in the study. At sea level and at altitude (5000m) overnight ECG-recordings were taken. The ECG-recordings still need to be analysed for HRV after which we can draw our conclusions. We are developing methods to analysis the ECG-recordings for accurate HRV (it is not as simple as we first thought!) after which we can draw our conclusions.

Glyeroltrinitrate headache as a predictor of acute altitude sickness, and its effect on brain blood flow

Neil Richardson, Oliver Kemp, Anja Kuttler, Roger McMorrow, Nigel Hart, Chris Imray

Background There is evidence that the brain swells at altitude, and it might be the case that people who cannot accommodate this swelling are more susceptible to getting acute mountain sickness (AMS). In other words, people more susceptible to AMS have a brain that fits tightly into the skull. Headache is a very important symptom of AMS and feels very similar to headaches caused by GTN, a drug that causes blood vessels to widen. We thought that GTN might be a good predictor of who was more likely to get AMS. We believed that GTN would do this by causing an increase in the volume of blood in the skull, that, when combined with brain swelling from altitude, cause greater stimulation of the nerves in the head leading to a more severe headache.

Aims (1) To see if there was a relationship between the severity of the headache caused by GTN and the symptoms of AMS as we ascended in altitude. If there was a relationship between headache with GTN and AMS, we needed to know whether the actions of GTN on blood flow were the same at sea level and altitude. If they were, we could assume that the difference in headache was due to the brain swelling at altitude, therefore our second aim was (2) To see if GTN had similar actions on changes in blood flow to the brain at altitude and sea level.

Methods We asked people who were on the Medex Makalu 2003 expedition to take GTN the evening before they ascended more than 300 m in height whilst trekking to base camp. We measured people’s headache by asking them to mark a cross on a line 10cm long between two statements, ‘No Headache’ at one end and ‘Worst Headache’ at the other end. We then compared this to how bad their AMS symptoms were the next day once they had ascended to a greater altitude. Once at base camp we gave the subjects GTN and measured changes in the amount of oxygenated and deoxygenated blood flowing to the head. We also measured blood pressure, heart rate and other factors. We compared these values to ones already attained at sea level.

Results and Conclusions There was no correlation between headache severity and AMS. This could be due to a number of reasons including the gradual ascent profile. This gradual ascent profile meant there were very few cases of AMS amongst the expedition.

There was little change in the effect of GTN on oxygenated and deoxygenated blood flowing to the brain at altitude compared to sea level. Other effects of GTN on blood pressure etc were all similar at altitude and sea level. This meant that the effects of GTN were conserved at altitude. However, as GTN was a poor predictor of who got AMS, it was of little consequence. However, one very interesting result was that the amount of oxygenated blood flowing to the head at base camp (just over 5000 m) suggested that the brain was lacking oxygen. It was previously believed that the blood flow to the head increased to compensate fully for the lack of oxygen in the blood at that altitude but our data disagrees with that. This data is in agreement with recent work by Chris Wolff and Chris Imray.

Sleep disruption at high altitude and its influence on next day vigilance and cognition

Annabel Nickol, Paul Richards, Philippa Seal, Juliette Leverment, Tracey Hughes, Mike Skinner, Gerald Dubowitz, John Stradling, Jim Milledge and Mary Morrell

Background The low oxygen levels of high altitude can lead to periodic breathing and poor sleep quality at high altitude. Patients who have disturbed sleep due to breathing disorders (e.g. in obstructive sleep apnoea) have reduced ability to concentrate or vigilance, and impairments in some areas of cognition. Gerald Dubowitz has previously shown that a sleeping tablet, Temazepam, improves sleep quality at altitude. Some people have been concerned that if the sleeping tablet has not worn off by the next morning, it might impair mental performance.

Aims (1) To see whether people with marked sleep disruption at altitude had impaired vigilance and cognition the next day. (2) To see whether Temazepam led to an improvement in sleep disruption, vigilance and cognition compared to a Placebo tablet. (3) To see whether sleep disruption, vigilance and cognition improved following acclimatisation.

Methods Simple sleep studies were carried out which involved wearing a pulse oximeter on one finger to measure blood oxygen saturations and heart rate, and an actigraph to measure wrist movement on the other wrist. These measures help to indicate whether the volunteer is awake or asleep, and the character of their breathing. The day after each sleep study a test of vigilance was carried out. This was purposefully very boring, as volunteers were asked to lift their finger off a sensor every time a light came on at set intervals for 40 minutes. Tests of cognitive function were also carried out as is described later. The sleep study, vigilance and cognitive function tests were carried out on two consecutive nights just after arrival at Base Camp, and again after acclimatisation to altitude.

Preliminary results and conclusions We studied 32 people on arrival at Base Camp with Temazepam and Placebo, and 21 people after acclimatisation to altitude. Preliminary results show that vigilance is pretty good at altitude despite sleep disruption. This might be because we had the luxury of a good long sleep on most nights. Reassuringly, Temazepam does not seem to impair mental performance. Unexpectedly many people still had periodic breathing even after a week’s acclimatisation at Base Camp.

The actigraphic assessment of quality of sleep during ascent to high altitude

Michael Schupp

Aim: To assess the change in quality of sleep and sleep pattern during ascent from Tumlingtar (500m) to Chamlang base camp (5200m) over 3 weeks.

Methods: A total of 21 subjects were supplied with a wristwatch size accelerometer called Actiwatch which records movement of the dominant hand. It is an objective measure of quality of sleep and has been validated in shift workers, patients with chronic pain and people exposed to environmental noise such as residents near airports. This was accompanied by a sleep diary recording total bed time total sleep time and number of awakenings and 2 questions about the quality of sleep in the previous night in form of a visual analogue score.

Results: 19 out of 21 recordings were useful for analysis. 2 recordings had to be excluded due to equipment failure of the watch. Preliminary evaluation of the results show a significant rise in night activity above about 3000m with increasing numbers of awakenings during the night. Final analysis will be done once I get my hands on the sleep diaries, which are essential to define the sleep and bedtime periods prior to analysis of the actiwatch trace.

There seems to be a slight curse attached to the watch since a disproportionate number of subjects involved in the study developed serious complications such as HAPE and severe respiratory tract infections during the trip. I hope the subjects concerned won’t hold this against me!

Typical actiwatch trace at high altitude:

Eden Trace recording at different altitudes during ascent to Chamlang base camp (5200m)

Michael Schupp

Aim: To detect the night-time changes in breathing pattern, oxygen saturation and heart rate during a trek from Tumlingtar (500m) to Chamlang base camp (5200m).

Methods: 5 “volunteers” including myself were recruited to undergo 4 night-time recordings each at low altitude, intermediate altitude and at base camp. This not very popular project involved being wired up to 5 different detectors connected to a small recording unit prior to going to bed. These detectors consisted of 2 expansion belts around the chest and abdomen, a pulse oximeter on one finger, a snoring detector on the side of the neck and most popular of all a small cannula in the nose and mouth to detect airflow during expiration. The recording units needed recharging via solar power after each night which was the limiting factor to the number of recordings taken. Since the application of the detectors is slightly tricky and crucial to a good recording it had to be done by myself every time. This was not so bad at lower altitudes but rather unpleasant at higher altitudes and involved crawling into my victims tents, convincing them to get at least partially out of their sleeping bags and attach the monitors which took about 15min each. It usually involved the use of all my charm and elaborate persuasion to prevent the subjects from chickening out in the last minute. In the end I exploited the general graving for nice food by promising to invite everybody involved to a 4-course meal cooked by myself back in England.

Photo: Michael Schupp with Actiwatch and sleep monitor

Results: 3 subjects completed the entire series for which I am eternally grateful and 2 subjects failed to do the recording at base camp due to a severe chest infection (which subsequently spread to about everybody else in our group). The highest recording was taken on myself at high camp on Mera Peak, which was by far the worst night of the entire trip due to the altitude and a ferocious snow storm (see picture).

The equipment worked well in the low temperatures and the data is still awaiting analysis with the help of somebody experienced with the analysis software. However it is clear to see that episodes of periodic breathing and desaturation increased significantly at Tagnag (4300m) and above which certainly contributed to more frequent awakenings and a poorer quality of sleep.

The figure shows a typical record during sleep and shows periodic breathing. The top trace represents the nasal airflow. The next 2 traces show the chest and abdominal extension during inspiration and expiration. The 4^th trace is the oxygen saturation, which drops to about 70% at the end of apnoea.

Cognitive function at high altitude

Jennifer Leland and Greg Harris

Aims This study aimed to investigate decrements in cognitive performance at moderate and high altitude compared to sea level and to compare different methods of assessing cognitive functioning at altitude (paper and pencil tests vs. computerised assessment). The data will also be compared to that of the sleep team to evaluate if there is an association between cognitive performance and nocturnal periodicity of breathing.

Background Temporary impairments in cognitive functioning have been found at high altitude. Cognitive impairments have often led to accidents due to improper evaluation of danger or other poor judgement. Cognitive decrements appear to follow a specific time course after exposure to altitude with initial impairments in performance followed by a progressive return to baseline. This supports the hypothesis that there are different stages of adaptation to altitude, which, in turn, depend on factors associated with respiratory function. Unfortunately, however, many of the previous studies on human cognitive functioning at altitude can be criticised on methodological grounds, such as the absence of baseline data at sea level, small sample sizesor poorly normed tests.

Methods We hope we have overcome some of the problems discussed above by using previously well-validated tests. The (manual) neuropsychological tests used assessed cognitive functions which have previously been shown to be sensitive to the effects of altitude hypoxia and sleep apnoea; visual and verbal memory, planning and mental flexibility, motor speed and verbal expression. These were: Auditory-Verbal Learning Test (AVLT), Controlled Oral Word Association (COWA), Digit Symbol Substitution Test (DSST), Trail Making Test (TMT): Parts A and B, and the immediate and delayed Visual Memory task from the Wechsler Memory Scale. The computerised cognitive test battery (CogState) includes measures of sustained and divided attention, learning and memory, problem solving and decision-making. Alternative forms of each task were randomised across days and subjects.

Results Baseline and data at altitude on Day 1, Day 2 (pre-acclimatisation) and (Day 5-6 post-acclimatisation) for all tests (paper and pencil and computerised) on more than 20 subjects, baseline and pre-acclimatisation data collected for (approx.) 12 further subjects was collected.

Preliminary analysis of the computerised data indicates that there is a ‘failure to learn’ rather than a decrease in performance on arrival at altitude.

Effect of the parasympathetic nervous system on resting bronchial tone at altitude

Kate Wilson, Michelle White, Lisa Handcock and Martin Miller

Background This is a follow-up study to the enormously successful (and hugely unpopular) ‘histamine study’ of the K98 expedition. There we showed that the airways are narrowed at altitude compared to sea level (an increased resting bronchial tone).

Aim This narrowing could be due to a number of factors. On the 2003 expedition we looked at one of these, the parasympathetic nervous system to see if it's influence on the lungs is altered at altitude.

Methods 40 people volunteered to be studied and had their lung function measured before and after breathing ipatropium bromide (a drug which should enlarge the airways by blocking the parasympathetic nerves). We studied as many people as possible on arrival at base camp and some a week later.

Results Of the original subjects 35 were studied pre, and 28 post-acclimatisation. We had a lot of interest and cooperation from everyone (thank-you for that), and got some good spirometry flow loops. These are being analysed by Martin Miller in Birmingham and we hope to have some definite results to present at the ODG meeting in October.

Changes in respiratory ion transport at altitude

Nick Mason, Ali Mynett, Emma Lam, James Anholm Katja Ruh and Alex Horsley,

Ascent to high altitude results in changes in the lungs, which suggest the presence of oedema, an abnormal accumulation of fluid, around the air spaces in the lung known as alveoli. Traditionally it was thought that the formation and clearance of this oedema fluid depended on the pressure in the blood vessels around the alveoli. However, over the last 10 years it has become apparent that active sodium and chloride transport, by a system of channels and pumps in the walls of the cells surrounding the alveoli, plays an important role as well in the control of the oedema fluid and that a lack of oxygen can effect how this transport system works. Because sodium and chloride ions are charged particles, their transport across a membrane generates a potential (voltage) difference and with sensitive equipment it is possible to measure the changes in ion transport by measuring the changes in potential difference. Although this is not possible in the alveoli, the nose conveniently contains tissue with similar transport properties and the potential difference can be measured by means of a very small tube inserted 4 to 5 cm into one nostril and connected by an electrode to a voltmeter. A second electrode connected to a small drip in the arm completes the measuring circuit. By perfusing the nose with very low concentrations of different substances it is possible to stimulate or block different parts of the transport system.

From earlier work at altitude, as well as studies in a low-pressure chamber, we knew that changes in the ion transport system occurred rapidly on ascent to altitude, but had little idea of how the system behaves at altitudes above 4500m or what happens with acclimatisation. Our long-suffering volunteers underwent baseline tests in London, which were repeated when they arrived at Chamlang Base Camp at 5000m, after up to 17 days trekking. None of our subjects were suffering from significant acute mountain sickness. Initial analysis of the results from Nepal shows that, unlike in our previous studies, the nasal potential difference measurements were unchanged at Chamlang Base Camp compared to sea level. This surprising result suggests that changes in ion transport normalise in acclimatised subjects and so cannot be responsible for the development or potentiation of lung oedema, nor does the ion transport system increase its activity in an attempt to clear the excess fluid. These findings are another important piece in the jigsaw of understanding how the ion transport system and the control of lung oedema works at altitude.

We have submitted our provisional results as an abstract to the British Thoracic Society Winter Meeting.

Beau Lines at High Altitude

Fionn Bellis and Craig Brooks

Background Beau’s lines are transverse grooves across the nails. They occur when there has been interference with growth at nail matrix. Hypoxia, or lack of oxygen, can cause such growth deficits. There has been one published case report on the incidence of Beau’s lines at altitude, but many personal reports that their prevalence is high in those who have spent time at high altitude.

Aims To conduct a prospective study of the incidence of Beau’s lines in the members of Medical Expedition members travelling to Chamlang Base Camp 2003.

Methods 2-4 weeks after returning from Kathmandu volunteers were e-mailed to ask whether they had developed Beau’s lines. When information from the data books is available, relationships between the development of Beau’s lines and oxygen saturation and altitude will be examined.

Preliminary results Everyone on the trip consented to enrolment in the study (60 people). The prevalence of Beau’s lines so far is low, perhaps reflecting the gradual ascent profile of the trek groups.

The ACE gene and weight loss at altitude

Stephan Saunders, Matt Litchfield, Sarah Trippick, Sandra Green, Don Paterson, Hugh Montgomery and David Collier

Background This project was investigating the ACE gene. This is a gene that has been associated with endurance athletes and high altitude mountaineers although no mechanism for this association has been discovered.

Aims We were investigating how ACE genotype was associated with weight loss during the expedition since maintaining your weight could give an advantage at high altitude. The project used skin-folds and other simple body measurements to work out how much fat and muscle our subjects had in London, at Base Camp and back in Kathmandu. We convinced 44 wonderful people to take part and are immensely grateful to them all.

Outcomes We are still busy analysing the data but hope to have some answers soon. In the mean time Matt and Stephan are thinking of another project that will persuade women to come and undress for us despite surrounding snow. Awards for the strongest arms will be presented in Old Dungeon Gyll...

The effects of altitude and acclimatisation on retinal function

Dan Morris, Mike Donald, Jill Inglis, Ian Manovel and Rupert Bourne

Background High altitude retinopathy occurs when there are small bleeds at the back of the eye in response to the lack of oxygen in the air at altitude. Usually you are not aware of these bleeds and they clear up spontaneously.

Aims To see whether people with a high haematocrit (‘thicker’ blood) are more prone to bleeds at the back of the eye.

Preliminary results On this expedition we took pictures of everyone's eyes with a special digital camera and found that 18 out of 52 people (35%) had bleeds at base camp or back in Kathmandu after climbing Mera Peak. We also stabbed everyone's finger for blood (twice for those who were unwilling to donate!) and are currently analysing this and other data to find out who is most likely to suffer from this problem and why it happens. We also took up some sophisticated equipment to test colour vision and blood flow to the eye but this did not work, proving that in this harsh environment the simpler the test, the more likely it is to succeed! Many thanks to everyone who volunteered to be part of this study.

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