OBJECTIVE:Altitude-related and exercise-related elevations in blood pressure (BP) increase the likelihood of developing pulmonary hypertension and high-altitude illness during high-altitude sojourn. This study examined the antihypertensive effect and potential exercise benefit of the angiotensin II receptor antagonist losartan when taken at altitude.METHODS:Twenty participants, paired for age and ACE genotype status, completed a double-blinded, randomised study, where participants took either losartan (100 mg/day) or placebo for 21 days prior to arrival at 5035 m (Whymper Hut, Mt Chimborazo, Ecuador). Participants completed a maximal exercise test on a supine cycle ergometer at sea level (4 weeks prior) and within 48 hours of arrival to 5035 m (10-day ascent). Power output, beat-to-beat BP, oxygen saturation (SpO2) and heart rate (HR) were recorded during exercise, with resting BP collected from daily medicals during ascent. Before and immediately following exercise at 5035 m, extravascular lung water prevalence was assessed with ultrasound (quantified via B-line count).RESULTS:At altitude, peak power was reduced relative to sea level (p<0.01) in both groups (losartan vs placebo: down 100±29 vs 91±28 W, p=0.55), while SpO2 (70±6 vs 70±5%, p=0.96) and HR (146±21 vs 149±24 bpm, p=0.78) were similar between groups at peak power, as was the increase in systolic BP from rest to peak power (up 80±37 vs 69±33 mm Hg, p=0.56). Exercise increased B-line count (p<0.05), but not differently between groups (up 5±5 vs 8±10, p=0.44).CONCLUSION:Losartan had no observable effect on resting or exercising BP, exercise-induced symptomology of pulmonary hypertension or performance at 5035 m.

IntroductionProteinuria increases at altitude and with exercise, potentially as a result of hypoxia. Using urinary alpha-1 acid glycoprotein (α1-AGP) levels as a sensitive marker of proteinuria, we examined the impact of relative hypoxia due to high altitude and blood pressure-lowering medication on post-exercise proteinuria.MethodsTwenty individuals were pair-matched for sex, age and ACE genotype. They completed maximal exercise tests once at sea level and twice at altitude (5035 m). Losartan (100 mg/day; angiotensin-receptor blocker) and placebo were randomly assigned within each pair 21 days before ascent. The first altitude exercise test was completed within 24–48 hours of arrival (each pair within ~1 hour). Acetazolamide (125 mg two times per day) was administrated immediately after this test for 48 hours until the second altitude exercise test.ResultsWith placebo, post-exercise α1-AGP levels were similar at sea level and altitude. Odds ratio (OR) for increased resting α1-AGP at altitude versus sea level was greater without losartan (2.16 times greater). At altitude, OR for reduced post-exercise α1-AGP (58% lower) was higher with losartan than placebo (2.25 times greater, p=0.059) despite similar pulse oximetry (SpO2) (p=0.95) between groups. Acetazolamide reduced post-exercise proteinuria by approximately threefold (9.3±9.7 vs 3.6±6.0 μg/min; p=0.025) although changes were not correlated (r=−0.10) with significant improvements in SpO2 (69.1%±4.5% vs 75.8%±3.8%; p=0.001).DiscussionProfound systemic hypoxia imposed by altitude does not result in greater post-exercise proteinuria than sea level. Losartan and acetazolamide may attenuate post-exercise proteinuria, however further research is warranted.

Ataxia at altitude is reviewed in relation to acute mountain sickness (AMS). The cause of ataxia occurring at altitude is unknown but may be hypoxia affecting basal ganglia and hindbrain activity. Ataxia is an important sign of high altitude cerebral edema (HACE) but is less well-established as a clinical feature of AMS. Assessment of ataxia is part of the Environmental Systems and the Lake Louise questionnaires, together with a heel-to-toe measurement. More precise measures of ataxia include the Sharpened Romberg Test (SRT) and the use of unstable platforms. Isolated ataxia at altitude may not be related to AMS or HACE. Age affects ataxia and careful baseline measurements are essential in older subjects before results at high altitude can be interpreted. Testing for ataxia needs to be standardized with sufficient learning time. Ataxia should be distinguished from weakness or fatigue occurring at altitude. Specialized tests have not been shown to be clinically important. Our results above 5000 m showed that an abnormal SRT may be specific for AMS but with relatively poor sensitivity. Wobble board results have not correlated with AMS scores consistently. Other authors using an unstable platform in a chamber and static posturography during 3 days of exposure to 4559 m also found no relationship with AMS scores. Ataxia is a common and important clinical feature of HACE but is unhelpful in the assessment of mild or even moderate AMS in the absence of an altered mental state. The simple heel-to-toe test remains a useful part of the assessment of more severe AMS bordering on HACE.

We would like to report on the 1-day altitude medicine research meeting held at the Birmingham Medical Institute, Birmingham, UK on December 4, 2009. The meeting provided an opportunity for researchers from several different high altitude research groups in the United Kingdom to present their findings and share experiences from recent laboratory and field work. In addition, the meeting aimed to welcome newcomers, foster collaboration, and encourage more individuals to get involved in altitude research. Data presented in the meeting drew from several recent expeditions and chamber studies, demonstrating how active these UK groups currently are. Recent projects included the University of Bangor trip to the European Alps, the BMRES hypoxic chamber studies in Glamorgan and field studies in Northern Chile, University of Oxford chamber and field studies, University of Edinburgh research at Kilimanjaro, and Caudwell Xtreme Everest expeditions to Cho Oyu and Everest. The first of the morning's sessions concentrated on molecular studies on oxidative and nitrosative stress. Professor Martin Feelisch (University of Warwick) began the meeting with a summary of the role of nitric oxide in the body's response to hypoxia. Professor Damian Bailey (University of Glamorgan) presented an overview of current evidence for the production of free radicals in hypoxia and demonstrated that radical production correlates with impaired cerebral autoregulation. He presented the hypothesis that blood-brain barrier function becomes dysregulated in hypoxia, and may be a contributory factor to the development of high altitude cerebral edema (HACE). Nicky Kolfshoten (Caudwell Xtreme Everest) presented a study that examined the potential correlation between headache score and head size (a proxy measure of intracranial volume) in trekkers ascending to Everest base camp, and Andrew Sutherland (University of Oxford) gave an update on optic nerve sheath diameter and correlation with acute mountain sickness (AMS) scores. These studies prompted a vigorous debate about whether AMS and HACE are the result of raised intracerebral volume or intracranial pressure. Included in a session on training and acclimatization were presentations on studies into weight loss and gastrointestinal function at altitude. Data from Xtreme Everest, presented by Maryam Khoshravi, investigated weight loss on two separate Himalayan expeditions to Cho Oyo and Everest, and an intrinsic genetic basis for high altitude weight loss was proposed. This was complemented by a BMRES study investigating the mechanism of high altitude gastrointestinal dysfunction, which measured gut blood flow in response to food ingestion. The day highlighted the volume of current work investigating pulmonary hypertension at altitude, especially at the University of Oxford Department of Physiology, Anatomy and Genetics: Mari Herigstad presented data from a chamber study looking at the effect of hypoxia on the ability of the pulmonary vasculature to dilate on exercise, and Nick Talbot described his work on the effect of iron supplementation and depletion on pulmonary hypertension. Cameron Holloway (University of Oxford) presented some fascinating results that may shed light on mechanisms of cardiac function at altitude, of which we eagerly await full publication. Attendees were also reminded of the high altitude pulmonary edema (HAPE) database (www.hape.org.uk) which now has more than 600 possible cases of HAPE registered, and people are encouraged to look at the website, and publicize it when traveling at altitude. Between sessions there was time available to view the posters, providing a valuable opportunity for some of the younger members of the research groups to present and discuss their work. The prize for best poster was jointly awarded to Karl New and Sarah Major. The Research award was won by Cameron Holloway, and Maryam Khoshravi was given the Young Investigator award. In addition, a hotly contested photographic competition ran throughout the day, which was won by Paul Firth and Hannah Collins. During the afternoon David Hillebrandt gave an update on the Diploma in Mountain Medicine (University of Leicester), which now has more than 100 graduates from all corners of the globe. Paul Firth (Harvard University) concluded the meeting with a fascinating talk that discussed findings from his extensive research into the causes of deaths on Mount Everest, a difficult and important subject. The day brought into focus the interesting work that is currently going on in UK altitude research. It also highlighted some of the controversial “hot topics”, such as the etiology of HACE and application of new techniques, including cardiac magnetic resonance spectroscopy, portable duplex Doppler ultrasound, and magnetic resonance angiography, to illuminate the path towards improved understanding of high altitude pathophysiology.

OBJECTIVE:To test the hypothesis that acclimatization to high altitude results in an improvement of the ventilatory threshold (VT).METHODS:Eight lowlanders underwent cardiopulmonary exercise testing with a cycle ergometer to determine VT and peak oxygen uptake (Vo2peak) in Coventry, United Kingdom (altitude: 80 m), on arrival in leh, india (altitude: 3500 m), and after 12 days of acclimatization that included a 5-day high altitude trek up to 4770 m.RESULTS:Vo2peak fell on arrival at 3500 m and remained depressed at 12 days. VT was depressed on arrival at high altitude and was further depressed at 12 days. VT as a proportion of the Vo2peak was decreased on arrival at high altitude, and after acclimatization, this relationship was further decreased.CONCLUSIONS:Individuals who are sedentary or not participating in regular physical training appear to require a longer period of acclimatization than trained athletes. With the increasing numbers participating in high-altitude trekking and charity climbs of peaks, such as Mt. Kilimanjaro, this information has clinically significant practical implications for those leading or acting as medical advisors.