Severe Acute Mountain Sickness Research Articles

Effect of progressive normobaric hypoxia on dynamic cerebral autoregulation.

What is the central question of this study? Acute hypoxia reduces dynamic cerebral autoregulation (dCA); however, it is unclear what level of hypoxia is necessary to exert this effect. We sought to investigate whether dCA would be reduced during progressive periods of normobaric hypoxia using a duplex Doppler ultrasound technique to evaluate the volumetric blood flow. What is the main finding and its importance? We showed that dCA decreased linearly as inspired O2 decreased from 21 to 12%. Additionally, symptoms of acute mountain sickness were related to changes in dCA. Our results may provide a sensitive and clinically relevant test to evaluate the risk of acute mountain sickness. Cerebral blood flow is maintained at relatively constant levels over a wide range of perfusion pressures via cerebral autoregulation (CA). Although acute hypoxia reduces dynamic CA, it is unclear what level of hypoxia is necessary to exert this effect. We evaluated dynamic CA during progressive normobaric hypoxia (∼1 h at each of 21, 18, 15 and 12% O2 ) using duplex ultrasonography to measure volumetric changes in common carotid artery blood flow of 11 healthy young men. Dynamic CA was evaluated by the thigh-cuff method and represented as the rate of regulation of vascular conductance. On a separate occasion, symptoms of acute mountain sickness were evaluated during 6h of prolonged hypoxia (fractional inspired O2 of 14.1%) using the Lake Louise Questionnaire. Repeated-measures ANOVA with linear trend analysis indicated that dynamic CA decreased progressively as fractional inspired O2 was reduced (P<0.001). Spearman rank order analysis revealed that symptoms of acute mountain sickness were related to changes in the rate of regulation of vascular conductance from 21 to 15% (r=-0.869, P=0.006) and from 21 to 12% O2 (r=-0.648, P=0.040), respectively. These results suggest that dynamic CA worsens with progressive hypoxia and that reductions in dynamic CA during moderate to severe hypoxia (<15% O2 ) may be related to the severity of acute mountain sickness.

Seven Passive 1-h Hypoxia Exposures Do Not Prevent AMS in Susceptible Individuals.

The present study evaluated the effects of a preacclimatization program comprising seven passive 1-h exposures to 4500-m normobaric hypoxia on the prevalence and severity of acute mountain sickness (AMS) during a subsequent exposure to real high altitude in persons susceptible to AMS. The project was designed as a randomized controlled trial including 32 healthy female and male participants with known susceptibility to AMS symptoms. After baseline measurements, participants were randomly assigned to the hypoxia or the control group to receive the preacclimatization program (seven passive 1-h exposures within 7 d to normobaric hypoxia or sham hypoxia). After completing preacclimatization, participants were transported (bus, cog railway) to real high altitude (3650 m, Mönchsjoch Hut, Switzerland) and stayed there for 45 h (two nights). Symptoms of AMS and physiological responses were determined repeatedly. AMS incidence and severity did not significantly differ between groups during the high-altitude exposure. In total, 59% of the hypoxia and 67% of the control group suffered from AMS at one or more time points during the high-altitude exposure. Hypoxic and hypercapnic ventilatory responses were not affected by the preacclimatization program. Resting ventilation at high altitude tended to be higher (P = 0.06) in the hypoxia group compared with the control group. No significant between-group differences were detected for heart rate variability, arterial oxygen saturation, and hematological and ventilatory parameters during the high-altitude exposure. Preacclimatization using seven passive 1-h exposures to normobaric hypoxia corresponding to 4500 m did not prevent AMS development during a subsequent high-altitude exposure in AMS-susceptible persons.

Benzolamide improves oxygenation and reduces acute mountain sickness during a high-altitude trek and has fewer side effects than acetazolamide at sea level.

Acetazolamide is the standard carbonic anhydrase (CA) inhibitor used for acute mountain sickness (AMS), however some of its undesirable effects are related to intracellular penetrance into many tissues, including across the blood–brain barrier. Benzolamide is a much more hydrophilic inhibitor, which nonetheless retains a strong renal action to engender a metabolic acidosis and ventilatory stimulus that improves oxygenation at high altitude and reduces AMS. We tested the effectiveness of benzolamide versus placebo in a first field study of the drug as prophylaxis for AMS during an ascent to the Everest Base Camp (5340 m). In two other studies performed at sea level to test side effect differences between acetazolamide and benzolamide, we assessed physiological actions and psychomotor side effects of two doses of acetazolamide (250 and 1000 mg) in one group of healthy subjects and in another group compared acetazolamide (500 mg), benzolamide (200 mg) and lorazepam (2 mg) as an active comparator for central nervous system (CNS) effects. At high altitude, benzolamide‐treated subjects maintained better arterial oxygenation at all altitudes (3–6% higher at all altitudes above 4200 m) than placebo‐treated subjects and reduced AMS severity by roughly 50%. We found benzolamide had fewer side effects, some of which are symptoms of AMS, than any of the acetazolamide doses in Studies 1 and 2, but equal physiological effects on renal function. The psychomotor side effects of acetazolamide were dose dependent. We conclude that benzolamide is very effective for AMS prophylaxis. With its lesser CNS effects, benzolamide may be superior to acetazolamide, in part, because some of the side effects of acetazolamide may contribute to and be mistaken for AMS.

Prevalence of acute mountain sickness on Mount Fuji: A pilot study.

Few studies have investigated climbing-related acute mountain sickness (AMS) on Mt Fuji. Although several studies of AMS have been conducted elsewhere, Mt Fuji is unique because there are many mountain lodges between the fifth station (a common starting point for climbers at an altitude of 2305 m) and the summit (3776 m), and many climbers commonly sleep overnight at mountain lodges during their ascents. This study surveyed the prevalence of AMS among climbers on Mt Fuji to determine which factors, if any, were related to the risk of developing AMS. This study collected data from 345 participants who climbed Mt Fuji in August 2013, including information regarding age, sex, climbing experience and whether the climber stayed at a mountain lodge (n = 239). AMS was surveyed using the Lake Louise Score (LLS) questionnaire. The item on perceived sleep quality was excluded for those who did not stay at a mountain lodge (n = 106). The overall prevalence of AMS was 29.5% (≥ 3 LLS with headache). According to a univariate analysis, AMS was not associated with sex (male vs female), age group (20-29, 30-39, 40-49 or >50 years) or stay at a mountain lodge (single day vs overnight stay). Conversely, prior experience climbing Mt Fuji (no prior attempts vs one or more prior attempts) was related to the risk of AMS. In addition, there was a significant deviation in the number of participants reporting poor sleep, and total sleep time was significantly shorter in participants with AMS. These preliminary findings suggest that no single factor can explain the risk for developing AMS while climbing Mt Fuji. In addition, impaired perceived sleep quality was associated with the severity of AMS in climbers who stayed overnight at a mountain lodge.

A Preliminary Genome-Wide Association Study of Acute Mountain Sickness Susceptibility in a Group of Nepalese Pilgrims Ascending to 4380 m.

There is significant interindividual variation in acute mountain sickness (AMS) susceptibility in humans. To identify genes related to AMS susceptibility, we used a genome-wide association study (GWAS) to simultaneously test associations between genetic variants dispersed throughout the genome and the presence and severity of AMS. DNA samples were collected from subjects who ascended rapidly to Gosainkunda, Nepal (4380 m), as part of the 2005, 2010, and 2012 Janai Purnima festivals. The Lake Louise Score was used to measure AMS severity. The primary analysis was based on 99 male subjects (43 with AMS; 56 without AMS). Genotyping for the GWAS was performed using Infinium Human Core Exome Bead Chips (542,556 single-nucleotide polymorphisms were assayed), and validation genotyping was performed with pyrosequencing in two additional cohorts (n = 101 for each). In total, 270,389 single nucleotide polymorphisms (SNPs) passed quality control, and 4 SNPs (one intronic, three nonsynonymous) in the FAM149A gene were associated with AMS severity after correcting for multiple hypothesis testing (p = 1.8E-7); however, in the validation cohorts, FAM149A was not associated with the presence or severity of AMS. No other genes were associated with AMS susceptibility at the genome-wide level. Due to the large influence of environmental factors (i.e., ascent rate and altitude attained) and the difficulties associated with the AMS phenotype (i.e., low repeatability, nonspecific symptoms, potentially independent ailments), we suggest that future studies addressing the variation in the acute human hypoxia response should focus on objective responses to acute hypoxia instead of AMS.

High Altitude Illness

High-altitude illnesses include acute mountain sickness (AMS), high-altitude cerebral edema (HACE), and high-altitude pulmonary edema (HAPE). Gradual ascent provides the optimal means of avoiding high-altitude illness; thus, public education regarding gradual ascent plays an important role in reducing the morbidity and mortality of serious altitude illness. This review summarizes the primary types of acute altitude sickness, acclimatization to high altitude, assessment and stabilization, diagnosis, treatment and disposition, prophylaxis, and outcomes for patients with high-altitude illness. Figures show physiologic changes leading to acclimatization to high altitude, HAPE physiology, the ‘bar-code sign’ indicating the presence of pneumothorax, the ‘waves on a beach’ sign indicating the absence of pneumothorax, images of lungs with and without edema on ultrasonography, a chest x-ray of HAPE, and a photograph of a portable hyperbaric treatment bag. Tables list rules to avoid serious altitude illness; initial assessment of the new patient with potential high-altitude illness; differential diagnosis, diagnostic criteria, and treatments for AMS, HACE, and HAPE; the Lake Louise score for establishing AMS severity; and prophylaxis for cerebral forms of altitude illness. Videos show the use of a high-frequency linear array probe to assess pneumothorax. This review contains 8 highly rendered figures, 14 tables, 3 videos, and 68 references.

Hypoxia, Hypobaria, and Exercise Duration Affect Acute Mountain Sickness

This study simultaneously quantified the effects of normobaric hypoxia (NH), hypobaric hypoxia (HH), exercise duration, and exposure time on acute mountain sickness severity (AMS-C). Thirty-six subjects (27.7 ± 7.8 yr) participated in a partial repeated measures study, completing two of six conditions: normobaric normoxia (NN: 300 m/984 ft equivalent), NH or HH (Po2 = 91 mmHg; 4400 m/14,436 ft equivalent), combined with moderate intensity cycling for 10 or 60 min. Subjects completed the Environmental Symptoms Questionnaire and oxygen saturation (Spo₂) was measured before, 1.5 h, 4 h, and 6.5 h into an 8-h exposure, and 1.5 h post-exposure. We fit multiple linear regression models with cluster adjusted standard errors on the exposure times using NH, HH, and long exercise as indicator variables, and AMS-C as the outcome variable. The Spo₂and pre-exposure AMS-C score were used as covariates. NH and HH led to substantial and progressively increasing AMS-C, but NN did not. The effect of HH on AMS-C was significantly different from NH, with AMS-C in HH being 1.6 times higher than in NH. HH led to significantly increasing AMS-C, regardless of the exercise duration, while NH only did so in combination with longer exercise. Increases in AMS-C were each independently related to NH, HH, and long duration exercise, with HH affecting AMS-C more severely. This suggests that hypobaria may affect AMS development above the level induced by hypoxia alone. This further suggests that NH and HH may not be interchangeable for studying AMS and that exercise duration may impact physiological responses.

Remote ischemic preconditioning for prevention of high-altitude diseases: fact or fiction?

Preconditioning refers to exposure to brief episodes of potentially adverse stimuli and protects against injury during subsequent exposures. This was first described in the heart, where episodes of ischemia/reperfusion render the myocardium resistant to subsequent ischemic injury, which is likely caused by reactive oxygen species (ROS) and proinflammatory processes. Protection of the heart was also found when preconditioning was performed in an organ different from the target, which is called remote ischemic preconditioning (RIPC). The mechanisms causing protection seem to include stimulation of nitric oxide (NO) synthase, increase in antioxidant enzymes, and downregulation of proinflammatory cytokines. These pathways are also thought to play a role in high-altitude diseases: high-altitude pulmonary edema (HAPE) is associated with decreased bioavailability of NO and increased generation of ROS, whereas mechanisms causing acute mountain sickness (AMS) and high-altitude cerebral edema (HACE) seem to involve cytotoxic effects by ROS and inflammation. Based on these apparent similarities between ischemic damage and AMS, HACE, and HAPE, it is reasonable to assume that RIPC might be protective and improve altitude tolerance. In studies addressing high-altitude/hypoxia tolerance, RIPC has been shown to decrease pulmonary arterial systolic pressure in normobaric hypoxia (13% O2) and at high altitude (4,342 m). Our own results indicate that RIPC transiently decreases the severity of AMS at 12% O2. Thus preliminary studies show some benefit, but clearly, further experiments to establish the efficacy and potential mechanism of RIPC are needed.

Study Looking at End Expiratory Pressure for Altitude Illness Decrease (SLEEP-AID).

Lipman, Grant S., Nicholas C. Kanaan, Caleb Phillips, Dave Pomeranz, Patrick Cain, Kristin Fontes, Becky Higbee, Carolyn Meyer, Michael Shaheen, Sean Wentworth, and Diane Walsh. Study Looking at End Expiratory Pressure for Altitude Illness Decrease (SLEEP-AID). High Alt Med Biol 16:154-161, 2015.--Acute mountain sickness (AMS) affects 25%-70% of the tens of millions of high altitude travelers annually, with hypoxia and nocturnal desaturations as major contributing factors. This is the first double blind randomized placebo controlled trial to assess expiratory positive airway pressure (EPAP) for AMS prevention and nocturnal hypoxic events. Healthy adult participants trekking in the Khumbu region of the Himalayas were randomized to a single-use EPAP nasal strip, or a visually identical sham device (placebo) prior to first night sleeping between 4371-4530 m (14,340-14,800 ft). The primary outcome was AMS incidence, measured by Lake Louise Questionnaire (LLQ), with secondary outcomes of AMS severity (by LLQ) and physiologic sleep indices measured by continuous sleep monitor. Intent-to-treat analysis included 219 participants with comparable demographic characteristics, of which 115 received EPAP and 104 placebo. There was no decrease in AMS with EPAP intervention (14% EPAP vs. 17% placebo; p=0.65; risk difference (-)3.15%, 95% CI (-)12.85%-6.56%). While overall AMS severity was not different between groups, EPAP reported decreased incidence of headache (64% vs. 76%; p<0.05, OR 0.51, 95% CI 0.27-0.95) and dizziness (81% vs. 98%; p<0.03, OR 0.29, 95% CI 0.09-0.78). During sleep, EPAP resulted in significant improvements in average peripheral oxygenation (Spo(2)) (80% versus 78%; p<0.01, mean difference=2, 95% CI 0.58-3.63) and a reduced percentage of time below 80% Spo(2) (31% vs. 46%; p<0.03, median difference=16, 95% CI 2.22-28.18). This lightweight and inexpensive EPAP device did not prevent acute mountain sickness, but did reduce the subgroup incidence of headache and dizziness while improving average nighttime peripheral oxygenation.

KAJIAN RISIKO CEDERA DAN MASALAH UMUM PENDAKI MAHASISWA UNIVERSITAS UDAYANA

There are many tourist activities that can be promoted in rural spaces, including the active experience of nature through outdoor sports, either challenging or, rather, calm and contemplative in nature and hiking is one of the most popular forms of enjoying an active nature experience. High‐altitude illness may be divided into the acute syndromes that affect lowland or highland residents ascending to altitudes greater than those to which they are accustomed and the chronic conditions that affect individual resident at high altitude for long periods. The acute adult syndromes of high altitude are acute mountain sickness, high‐ altitude pulmonary oedema (HAPE) and high‐altitude cerebral oedema. Hypoxia is the main factor for theacute high‐altitude illnesses. The incidence and severity of acute mountain sickness, HAPE and high‐altitude cerebral oedema are related to the speed of ascent and the maximum height gained.

Intravenous Infusion of Nitroglycerine Leads to Increased Permeability on Dynamic Contrast-Enhanced MR Imaging in Pig Brains.

It has been suggested that off-label use of transdermal nitroglycerine patches to prevent frostbite may lead to severe acute mountain sickness and ataxia. The aim of this study was to investigate the effect of nitroglycerine on brain vascular permeability by using dynamic contrast-enhanced MR imaging in a swine model. Eight Danish Landrace-Yorkshire-Danish Landrace pigs of approximately 20-25 kg were scanned with a dynamic contrast-enhanced MR perfusion protocol with and without nitroglycerine intravenous infusion. Compartmental analysis was performed on the basis of the Tofts model, and voxel-based quantitative values of the volume transfer constants from the vascular to the extracellular space were determined. The scan with nitroglycerine infusion resulted in significantly higher volume transfer constant values than values derived from the first scan without nitroglycerine infusion. Increased volume transfer constant values were observed in 6 of 8 animals. Infusion of nitroglycerine increases the vascular permeability of the swine brain on the basis of the transfer constant estimated from dynamic contrast-enhanced MR imaging.

Symptom progression in acute mountain sickness during a 12-hour exposure to normobaric hypoxia equivalent to 4500 m.

The diagnosis and quantification of severity of acute mountain sickness (AMS) continue to be problematic. What symptoms should be included in a score and how to weigh any given symptom in the total score remain matter of debate. Seventy seven healthy male (n=43) and female (n=34) volunteers, aged between 18 and 42 years, were exposed to normobaric hypoxia (Fio2=12.6%≙4500 m) for 12 hours. Symptoms of AMS according to the Lake Louise Scoring system (LLS) were recorded before and after 30 min, 3, 6, 9, and 12 hours in hypoxia. AMS scores continued to increase steeply during the entire hypoxia exposure in subjects suffering from AMS (LLS>2). Headache was the predominant symptom and the severity of nausea progressed faster in subjects who left the hypoxia room prematurely (severely affected by AMS) compared to those moderately affected (LLS>2 but completing the 12-h hypoxia exposure). Whereas headache scores up to 6 hours in hypoxia were not correlated with other AMS symptoms, nausea was correlated with dizziness and fatigue (r=0.45 and 0.56, p<0.01). Cluster analysis identified three different distributions of symptom severity compatible with being very likely free of AMS (cluster 1), compatible with very likely suffering from AMS (cluster 3), and compatible with ambiguous allocation (cluster 2). In conclusion, our findings confirm that headache plus one or more of the symptoms nausea, dizziness, and fatigue of at least mild to moderate severity are required for diagnosis of AMS. The inter-relationship between nausea, dizziness, and fatigue, however, raises the question whether each of these symptoms should be given equal diagnostic weighting. The time course of symptom progression within the first hours at altitude may provide clinically important information on the severity of subsequent AMS development and will support the decision to start therapeutic intervention.

Correlation between blood pressure changes and AMS, sleeping quality and exercise upon high-altitude exposure in young Chinese men.

BackgroundExcessive elevation of arterial blood pressure (BP) at high altitude can be detrimental to our health due to acute mountain sickness (AMS) or some AMS symptoms. This prospective and observational study aimed to elucidate blood pressure changes induced by exposure to high-altitude hypoxia and the relationships of these changes with AMS prevalence, AMS severity, sleep quality and exercise condition in healthy young men.MethodsA prospective observational study was performed in 931 male young adults exposed to high altitude at 3,700 m (Lhasa) from low altitude (LA, 500 m). Blood pressure measurement and AMS symptom questionnaires were performed at LA and on day 1, 3, 5, and 7 of exposure to high altitude. Lake Louise criteria were used to diagnose AMS. Likewise, the Athens Insomnia Scale (AIS) and the Epworth Sleepiness Scale (ESS) were filled out at LA and on day 1, 3, and 7 of exposure to high altitude.ResultsAfter acute exposure to 3,700 m, diastolic blood pressure (DBP) and mean arterial blood pressure (MABP) rose gradually and continually (P < 0.05). Analysis showed a relationship with AMS for only MABP (P < 0.05) but not for SBP and DBP (P > 0.05). Poor sleeping quality was generally associated with higher SBP or DBP at high altitude, although inconsistent results were obtained at different time (P < 0.05). SBP and Pulse BP increased noticeably after high-altitude exercise (P < 0.05).ConclusionsOur data demonstrate notable blood pressure changes under exposure to different high-altitude conditions: 1) BP increased over time. 2) Higher BP generally accompanied poor sleeping quality and higher incidence of AMS. 3) SBP and Pulse BP were higher after high-altitude exercise. Therefore, we should put more effort into monitoring BP after exposure to high altitude in order to guard against excessive increases in BP.

Cerebrovascular compliance is not associated with acute mountain sickness following staged ascent to 4300 m (708.3)

We hypothesized that a reduction in cerebrovascular compliance (∆V), due to cerebral edema, would be associated with acute mountain sickness (AMS) following staged ascent to 4300 m. Forty‐five unacclimatized men and women (mean±SD; 24±5 yr) were exposed to 48 h at a staging altitude at or above 2500 m followed by 24 h at 4300 m. AMS was assessed using the Environmental Symptoms Questionnaire. Near‐infrared spectroscopy was used to assess ∆V within the right frontal lobe via calculation of change in relative total hemoglobin concentration from resting baseline to peak value during a valsalva maneuver to a fixed pressure. Hemoglobin and hematocrit were measured to calculate changes in plasma volume (PV). All assessments were completed at rest in the morning at sea level (SL) and after 24 hours at 4300 m (HA). AMS severity increased (P&lt;0.001) from SL (0.07±0.15) to HA (0.44±0.43). ∆V also increased (P&lt;0.001) from SL (3.08±0.35) to HA (4.60±0.49). PV decreased (P&lt;0.001) from SL to HA (‐17.3±7.1%). No relationship was found between the change in ∆V from SL to HA and the change in AMS severity (r=0.04;p=0.78), but the change in ∆V was significantly associated with the % change in PV (r=0.34;p=0.01). We conclude that ∆V was not related to AMS, potentially caused by cerebral edema, but rather hemoconcentration following staged ascent to 4300 m. Funding: USAMRMC. Authors’ views not official US Army or DOD policy.Grant Funding Source: Supported by USAMRMC

Acute Mountain Sickness Is Not Repeatable Across Two 12-Hour Normobaric Hypoxia Exposures

The purposes of this experiment were to determine the repeatability of acute mountain sickness (AMS), AMS symptoms, and physiological responses across 2 identical hypoxic exposures. Subjects (n = 25) spent 3 nights at simulated altitude in a normobaric hypoxia chamber: twice at a partial pressure of inspired oxygen (PIO2) of 90mmHg (4000 m equivalent; "hypoxia") and once at a PIO2 of 132 mmHg (1000 m equivalent; "sham") with 14 or more days between exposures. The following variables were measured at hours 0 and 12 of each exposure: AMS severity (ie, Lake Louise score [LLS]), AMS incidence (LLS ≥3), heart rate, oxygen saturation, blood pressure, and the fraction of exhaled nitric oxide. Oxygen saturation and heart rate were also measured while subjects slept. The incidence of AMS was not statistically different between the 2 exposures (84% vs 56%, P > .05), but the severity of AMS (ie, LLS) was significantly lower on the second hypoxic exposure (mean [SD], 3.1 [1.8]) relative to the first hypoxic exposure (4.8 [2.3]; P < .001). Headache was the only AMS symptom to have a significantly greater severity on both hypoxic exposures (relative to the sham exposure, P < .05). Physiological variables were moderately to strongly repeatable (intraclass correlation range 0.39 to 0.86) but were not associated with AMS susceptibility (P > .05). The LLS was not repeatable across 2 identical hypoxic exposures. Increased familiarity with the environment (not acclimation) could explain the reduced AMS severity on the second hypoxic exposure. Headache was the most reliable AMS symptom.

Attenuation of S-cone function at high altitude assessed by electroretinography

As impaired S-cone function has been reported psychophysically this study assessed S-cone function during high altitude exposure using electroretinography (ERG) and investigated a possible association with severity of acute mountain sickness (AMS). This work is related to the Tübingen High Altitude Ophthalmology (THAO) study. Standard ERG equipment was used (Diagnosys LLC, Cambridge, UK) with special protocol settings to extract S-cone function. Twelve subjects were analyzed in the current study and examinations were performed in Tübingen, Germany (341m) as baseline and thereafter at the Capanna Margherita, Italy (4559m) at high altitude. Results were compared using a paired t-test. Correlations between ERG measurements and oxygen saturation (SpO2), heart rate (HR) and scores of acute mountain sickness (AMS-C and LL) were calculated using Pearson's correlation coefficients. Amplitudes of S-cone b-waves decreased significantly at high altitude (p=0.02). No significant changes were observed for implicit times of b-waves (p=0.63), a-waves (p=0.75) or for a-wave amplitudes (p=0.78). The incidence of AMS was 50% at high altitude according to AMS-C and LL scores (AMS-C⩾0.7 and LL⩾5). Heart rate increased to 84±10min(-1) and SpO2 decreased to 71.9±5.7% at high altitude. No significant correlation was found between S-cone ERG parameters and SpO2, HR, AMS-C and LL. For the first time our study defines a significant impairment of S-cone function at high altitude time using objective state of the art examination methods. No correlation between the functional impairment of S-cones and levels of AMS was detected.

Pupillary light reaction during high altitude exposure.

PurposeThis study aimed to quantify the pupillary light reaction during high altitude exposure using the state of the art Compact Integrated Pupillograph (CIP) and to investigate a potential correlation of altered pupil reaction with severity of acute mountain sickness (AMS). This work is related to the Tübingen High Altitude Ophthalmology (THAO) study.MethodsParameters of pupil dynamics (initial diameter, amplitude, relative amplitude, latency, constriction velocity) were quantified in 14 healthy volunteers at baseline (341 m) and high altitude (4559 m) over several days using the CIP. Scores of AMS, peripheral oxygen saturation and heart rate were assessed for respective correlations with pupil dynamics. For statistical analysis JMP was used and data are shown in terms of intra-individual normalized values (value during exposure/value at baseline) and the 95% confidence interval for each time point.ResultsDuring high altitude exposure the initial diameter size was significantly reduced (p<0.05). In contrast, the amplitude, the relative amplitude and the contraction velocity of the light reaction were significantly increased (p<0.05) on all days measured at high altitude. The latency did not show any significant differences at high altitude compared to baseline recordings. Changes in pupil parameters did not correlate with scores of AMS.ConclusionsKey parameters of the pupillary light reaction are significantly altered at high altitude. We hypothesize that high altitude hypoxia itself as well as known side effects of high altitude exposure such as fatigue or exhaustion after ascent may account for an altered pupillogram. Interestingly, none of these changes are related to AMS.

AltitudeOmics: cerebral autoregulation during ascent, acclimatization, and re-exposure to high altitude and its relation with acute mountain sickness

Cerebral autoregulation (CA) acts to maintain brain blood flow despite fluctuations in perfusion pressure. Acute hypoxia is thought to impair CA, but it is unclear if CA is affected by acclimatization or related to the development of acute mountain sickness (AMS). We assessed changes in CA using transfer function analysis of spontaneous fluctuations in radial artery blood pressure (indwelling catheter) and resulting changes in middle cerebral artery blood flow velocity (transcranial Doppler) in 21 active individuals at sea level upon arrival at 5,260 m (ALT1), after 16 days of acclimatization (ALT16), and upon re-exposure to 5,260 m after 7 days at 1,525 m (POST7). The Lake Louise Questionnaire was used to evaluate AMS symptom severity. CA was impaired upon arrival at ALT1 (P < 0.001) and did not change with acclimatization at ALT16 or upon re-exposure at POST7. CA was not associated with AMS symptoms (all R < 0.50, P > 0.05). These findings suggest that alterations in CA are an intrinsic consequence of hypoxia and are not directly related to the occurrence or severity of AMS.

The effects of exercise at high altitude on high-sensitivity cardiac troponin release and associated biventricular cardiac function

It has been consistently shown that heavy exercise leads to cardiac troponin (cTn) release and variable changes in post exercise cardiac function. This relationship has not been explored at increasing or significant high altitude (HA). This study assessed the effects of exercise at progressively increasing HA on high-sensitivity (hs)-cTnT levels and their relationship to biventricular cardiac function and severity of acute mountain sickness (AMS). Transthoracic echocardiograms, hs-cTnT levels and AMS scores were measured at rest at 1,300m then repeated post exercise and 12h later after progressive trekking to 3,440, 4,270m and at 5,150m (after trekking to 5,643m) on 19 healthy subjects (age 35.4±years, 52.6% males). There was a detectable increase (>5ng/L) in post exercise hs-cTnT with exercise at HA which became significant at 5,150m (5.84% at 3,440m, 5.2% at 4,270m and 56.3% at 5,150m; p=0.0005). Compared with baseline, HA to 5,150m led to a significant rise in post exercise Lake Louis AMS scores (p<0.001) pulmonary artery systolic pressure (PASP) (23.7±3.8 vs 37.9±11.7mmHg: p<0.001), cardiac output (5.2±1.2 vs 7.5±1.3l/min; p<0.001) and a fall in SpO2 (96.1±vs 77.4±12.0%; p<0.001). There was no change in stroke volume (p=0.10) or estimated filling pressures (E/E') of the left (p=0.50) and right ventricles (p=0.4). On multivariate analysis increasing cardiac output (p=0.02) and PASP (p=0.04) and decreasing SpO2 (p=0.01) were the only independent predictors of increasing cTnT levels (overall R (2)=0.23, p<0.0001). Moderate intensity exercise at significant HA influences the post exercise increase in hs-cTnT without overt deleterious effects on cardiac function.

Rhodiola crenulata extract for prevention of acute mountain sickness: a randomized, double-blind, placebo-controlled, crossover trial

BackgroundRhodiola crenulata (R. crenulata) is widely used to prevent acute mountain sickness in the Himalayan areas and in Tibet, but no scientific studies have previously examined its effectiveness. We conducted a randomized, double-blind, placebo-controlled crossover study to investigate its efficacy in acute mountain sickness prevention.MethodsHealthy adult volunteers were randomized to 2 treatment sequences, receiving either 800 mg R. crenulata extract or placebo daily for 7 days before ascent and 2 days during mountaineering, before crossing over to the alternate treatment after a 3-month wash-out period. Participants ascended rapidly from 250 m to 3421 m on two separate occasions: December 2010 and April 2011. The primary outcome measure was the incidence of acute mountain sickness, as defined by a Lake Louise score ≥ 3, with headache and at least one of the symptoms of nausea or vomiting, fatigue, dizziness, or difficulty sleeping.ResultsOne hundred and two participants completed the trial. There were no demographic differences between individuals taking Rhodiola-placebo and those taking placebo-Rhodiola. No significant differences in the incidence of acute mountain sickness were found between R. crenulata extract and placebo groups (all 60.8%; adjusted odds ratio (AOR) = 1.02, 95% confidence interval (CI) = 0.69–1.52). The incidence of severe acute mountain sickness in Rhodiola extract vs. placebo groups was 35.3% vs. 29.4% (AOR = 1.42, 95% CI = 0.90–2.25).ConclusionsR. crenulata extract was not effective in reducing the incidence or severity of acute mountain sickness as compared to placebo.Trial registrationClinicalTrials.gov NCT01536288.