EPAS1 and VEGFA gene variants are related to the symptoms of acute mountain sickness in Chinese Han population: a cross-sectional study.

BACKGROUND: More people ascend to high altitude (HA) for various activities, and some individuals are susceptible to HA illness after rapidly ascending from plains. Acute mountain sickness (AMS) is a general complaint that affects activities of daily living at HA. Although genomic association analyses suggest that single nucleotide polymorphisms (SNPs) are involved in the genesis of AMS, no major gene variants associated with AMS-related symptoms have been identified. METHODS: In this cross-sectional study, 604 young, healthy Chinese Han men were recruited in June and July of 2012 in Chengdu, and rapidly taken to above 3700 m by plane. Basic demographic parameters were collected at sea level, and heart rate, pulse oxygen saturation (SpO2), systolic and diastolic blood pressure and AMS-related symptoms were determined within 18-24 h after arriving in Lhasa. AMS patients were identified according to the latest Lake Louise scoring system (LLSS). Potential associations between variant genotypes and AMS/AMS-related symptoms were identified by logistic regression after adjusting for potential confounders (age, body mass index and smoking status). RESULTS: In total, 320 subjects (53.0%) were diagnosed with AMS, with no cases of high-altitude pulmonary edema or high-altitude cerebral edema. SpO2 was significantly lower in the AMS group than that in the non-AMS group (P = 0.003). Four SNPs in hypoxia-inducible factor-related genes were found to be associated with AMS before multiple hypothesis testing correction. The rs6756667 (EPAS1) was associated with mild gastrointestinal symptoms (P = 0.013), while rs3025039 (VEGFA) was related to mild headache (P = 0.0007). The combination of rs6756667 GG and rs3025039 CT/TT further increased the risk of developing AMS (OR = 2.70, P < 0.001). CONCLUSIONS: Under the latest LLSS, we find that EPAS1 and VEGFA gene variants are related to AMS susceptibility through different AMS-related symptoms in the Chinese Han population; this tool might be useful for screening susceptible populations and predicting clinical symptoms leading to AMS before an individual reaches HA. TRIAL REGISTRATION: Chinese Clinical Trial Registration, ChiCTR-RCS-12002232 . Registered 31 May 2012.

Pre-degenerated peripheral nerves co-cultured with bone marrow-derived cells: a new technique for harvesting high-purity Schwann cells.

Schwann cells play an important role in the peripheral nervous system, especially in nerve repair following injury, so artificial nerve regeneration requires an effective technique for obtaining purified Schwann cells. In vivo and in vitro pre-degeneration of peripheral nerves have been shown to obtain high-purity Schwann cells. We believed that in vitro pre-degeneration was simple and controllable, and available for the clinic. Thus, we co-cultured the crushed sciatic nerves with bone marrow-derived cells in vitro. Results demonstrated that, 3 hours after injury, a large number of mononuclear cells moved to the crushed nerves and a large number of bone marrow-derived cells infiltrated the nerve segments. These changes promoted the degradation of the nerve segments, and the dedifferentiation and proliferation of Schwann cells. Neural cell adhesion molecule and glial fibrillary acidic protein expression were detected in the crushed nerves. Schwann cell yield was 9.08 ± 2.01 × 104/mg. The purity of primary cultured Schwann cells was 88.4 ± 5.79%. These indicate a successful new method for obtaining Schwann cells of high purity and yield from adult crushed sciatic nerve using bone marrow-derived cells.

A specific objective supplemental factor in evaluating acute mountain sickness: ΔHR in combination with SaO2.

BACKGROUND: So far, there have been no measurements confirmed useful in diagnosing acute mountain sickness (AMS). The aim of this study was to determine the role of heart rate (HR) difference (ΔHR) and oxygen saturation ( SaO2) as objective risk factors in aiding the diagnosis of AMS. METHODS: A total of 1,019 participants were assigned to either the acute exposure group (AEG): from 500 m to 3,700 m by flight within 2.5 h (n = 752); or the pre-acclimatization group (PAG): ascended to 4,400 m from 3,650 m within three hours by car after adapting 33 days at 3,650 m (n = 267). The questionnaires or measurements of resting SaO2 (oxygen saturation) and HR were completed between 18 and 24 h before departure and after arrival. RESULTS: Incidence of AMS was 61.3 % (461) in AEG, with 46.1 % (347) mild cases and 15.2 % (114) severe cases. In PAG, the incidence was 38.9 % (104), with 30.7 % (82) mild cases and 8.2 % (22) severe cases. The AMS subjects showed a significant increase in HR and a decrease in SaO2 levels compared with the non-AMS subjects in both groups. ΔHR and post-exposure SaO2 were significantly correlated with the Lake Louise Score (LLS) in both groups. Stepwise logistic regression analysis revealed the ΔHR >25 and SaO2 < 88 % in AEG as well as ΔHR >15 and SaO2 < 86 % in PAG to be independent risk factors of AMS. Combining these two measurements could specifically indicate participants with AMS, which showed a positive predictive value of 89 % and specificity of 97 % in AEG as well as 85 % and 98 % in PAG. CONCLUSION: ΔHR or SaO2, as objective measurements, correlate with AMS. Combination of these two measurements may be useful as an additional specific and objective factor to further confirm the diagnosis of AMS.

[The change of left ventricular function upon acute high altitude exposure and its relationship with acute mountain sickness].

OBJECTIVE: To investigate the changes of the cardiac hemodynamics after acute high altitude exposure in healthy young males and the relationship with acute mountain sickness(AMS). METHODS: Left ventricular function and oxyhemoglobin saturation (SaO2), heart rate (HR), blood pressure (BP) were measured in 218 healthy young males before and after high altitude exposure within 24 h respectively. According to the lake louise score criteria, the subjects were divided into two groups: acute mountain sickness group (AMS group) and non acute mountain sickness group (non-AMS group). RESULTS: HR, diastolic blood pressure (DBP), mean arterial pressure (MAP), left ventricular ejection fraction (LVEF), stroke volume (SV), stroke index (SI) cardiac output (CO), cardiac index (CI) were significantly increased upon acute high altitude exposure (P < 0.05). Whereas SaO2 and end-systolic volume (ESV) were significantly decreased (P < 0.05). In addition, HR, systolic blood pressure (SBP) and MAP in AMS group were significantly higher than those in non-AMS group (P < 0.05). But stroke index (SI) and end-diastolic volume (EDV) in AMS group were significantly lower than those in non-AMS group (P < 0.05). CONCLUSION: Cardiac function in healthy young males upon acute high altitude exposure was enhanced. EDV, HR and SI might become the indexes of predicting the acute mountain sickness in the future.

Sleep quality changes in insomniacs and non-insomniacs after acute altitude exposure and its relationship with acute mountain sickness.

OBJECTIVE: We aimed to observe the changes in subjective sleep quality among insomniacs and non-insomniacs after acute ascending to 3,700 m and its possible relationship with acute mountain sickness (AMS). METHODS: A total of 600 adult men were recruited. Subjects' subjective sleep quality was evaluated by the Athens Insomnia Scale. AMS was assessed using the Lake Louise scoring system. Arterial oxygen saturation was measured. RESULTS: Despite insomnia resolution in only a few subjects, the prevalence of insomnia among insomniacs remained stable at 90% after rapid ascent to 3,700 m. However, among non-insomniacs, the prevalence of insomnia sharply increased to 32.13% in the first day of altitude exposure and progressively reduced to 4.26% by the 60th day of altitude stay. Moreover, the prevalences of insomnia symptoms decreased more markedly from day 1 to day 60 at 3,700 m among non-insomniacs than among insomniacs. At 3,700 m, the prevalence of AMS among insomniacs was 79.01%, 60.49%, and 32.10% on the first, third, and seventh days, respectively, which was significantly higher than that among non-insomniacs. Multivariate regression revealed that elevated Athens Insomnia Scale scores are an independent risk factor for AMS (adjusted odds ratio 1.388, 95% confidence interval: 1.314-1.464, P<0.001), whereas high arterial oxygen saturation and long duration of altitude exposure are protective factors against AMS. CONCLUSION: Our results suggest that the effect of high-altitude exposure on subjective sleep quality is more marked, but disappears more quickly, among non-insomniacs than among insomniacs, whereas AMS is especially common among insomniacs. Moreover, poor subjective sleep quality is a risk factor for AMS.

Age as a risk factor for acute mountain sickness upon rapid ascent to 3,700 m among young adult Chinese men.

BACKGROUND: The aim of this study was to explore the relationship between age and acute mountain sickness (AMS) when subjects are exposed suddenly to high altitude. METHODS: A total of 856 young adult men were recruited. Before and after acute altitude exposure, the Athens Insomnia Scale score (AISS) was used to evaluate the subjective sleep quality of subjects. AMS was assessed using the Lake Louise scoring system. Heart rate (HR) and arterial oxygen saturation (SaO2) were measured. RESULTS: Results showed that, at 500 m, AISS and insomnia prevalence were higher in older individuals. After acute exposure to altitude, the HR, AISS, and insomnia prevalence increased sharply, and the increase in older individuals was more marked. The opposite trend was observed for SaO2. At 3,700 m, the prevalence of AMS increased with age, as did severe AMS, and AMS symptoms (except gastrointestinal symptoms). Multivariate logistic regression analysis showed that age was a risk factor for AMS (adjusted odds ratio [OR] 1.07, 95% confidence interval [CI] 1.01-1.13, P<0.05), as well as AISS (adjusted OR 1.39, 95% CI 1.28-1.51, P<0.001). CONCLUSION: The present study is the first to demonstrate that older age is an independent risk factor for AMS upon rapid ascent to high altitude among young adult Chinese men, and pre-existing poor subjective sleep quality may be a contributor to increased AMS prevalence in older subjects.

Smoking is associated with the incidence of AMS: a large-sample cohort study.

BACKGROUND: In recent years, the number of people visiting high altitudes has increased. After rapidly ascending to a high altitude, some of these individuals, who reside on plains or other areas of low altitude, have suffered from acute mountain sickness (AMS). Smoking interferes with the body's oxygen metabolism, but research about the relationship between smoking and AMS has yielded controversial results. METHODS: We collected demographic data, conducted a smoking history and performed physical examinations on 2000 potential study participants, at sea level. Blood pressure (BP) and pulse oxygen saturation (SpO2) were measured for only some of the patients due to time and manpower limitations. We ultimately recruited 520 smokers and 450 nonsmokers according to the inclusion and exclusion criteria of our study. Following acute high-altitude exposure, we examined their Lake Louise Symptom (LLS) scores, BP, HR and SpO2; however, cerebral blood flow (CBF) was measured for only some of the subjects due to limited time, manpower and equipment. RESULTS: Both the incidence of AMS and Lake Louise Symptom (LLS) scores were lower in smokers than in nonsmokers. Comparing AMS-related symptoms between nonsmokers and smokers, the incidence and severity of headaches and the incidence of sleep difficulties were lower in smokers than in nonsmokers. The incidences of both cough and mental status change were higher in smokers than in nonsmokers; blood pressure, HR and cerebral blood flow velocity were lower in smokers than in nonsmokers. CONCLUSION: Our findings suggest that the incidence of AMS is lower in the smoking group, possibly related to a retardation of cerebral blood flow and a relief of AMS-related symptoms, such as headache.

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

BACKGROUND: Excessive 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. METHODS: A 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. RESULTS: After 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). CONCLUSIONS: Our 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.

Risk factors for high-altitude headache upon acute high-altitude exposure at 3700 m in young Chinese men: a cohort study.

BACKGROUND: This prospective and observational study aimed to identify demographic, physiological and psychological risk factors associated with high-altitude headache (HAH) upon acute high-altitude exposure. METHODS: Eight hundred fifty subjects ascended by plane to 3700 m above Chengdu (500 m) over a period of two hours. Structured Case Report Form (CRF) questionnaires were used to record demographic information, physiological examinations, psychological scale, and symptoms including headache and insomnia a week before ascending and within 24 hours after arrival at 3700 m. Binary logistic regression models were used to analyze the risk factors for HAH. RESULTS: The incidence of HAH was 73.3%. Age (p =0.011), physical labor intensity (PLI) (p =0.044), primary headache history (p <0.001), insomnia (p <0.001), arterial oxygen saturation (SaO2) (p =0.001), heart rate (HR) (p =0.002), the Self-Rating Anxiety Scale (SAS) (p <0.001), and the Epworth Sleepiness Scale (ESS) (p <0.001) were significantly different between HAH and non-HAH groups. Logistic regression models identified primary headache history, insomnia, low SaO2, high HR and SAS as independent risk factors for HAH. CONCLUSIONS: Insomnia, primary headache history, low SaO2, high HR, and high SAS score are the risk factors for HAH. Our findings will provide novel avenues for the study, prevention and treatment of HAH.

Anxiety correlates with somatic symptoms and sleep status at high altitudes.

High altitude exposure results in many physical and psychological discomforts, with anxiety and sleep disturbances being the most common ones. This cross-sectional study was performed to explore the relationship between anxiety, somatic symptoms, and sleep status at high altitude. A sample of 426 young males between 18 and 24 years old ascended from low-level land to 3600 m, where they acclimated for 40 days, before ascending to 4400 m. Questionnaires including the Louise Lake Score (LLS, for diagnosis of acute mountain sickness [AMS]), the Self-rating Anxiety Scale (SAS), the Epworth Sleepiness Scale (ESS), and the Athens Insomnia Scale (AIS) were administered immediately before departure from 3600 m (40th day) and the day after arrival at 4400 m (20 days after the first data collection). Physiological parameters were also measured. We observed that 49 of 426 and 51 of 329 people were diagnosed with anxiety according to SAS at 3600 and 4400 m, respectively. Physical symptoms were more severe in subjects with anxiety, and the severity of anxiety was significantly positively correlated to the severity of insomnia and increased heart rate (HR). Overall, these data indicate that after 40 days acclimatization in 3600 m, anxious persons have more severe somatic symptoms. When ascending to higher altitudes, these individuals are more likely to develop AMS, show more severe symptoms, and are prone to insomnia and more serious daytime sleepiness. Insomnia and elevated HR are indicators of anxiety severity.