Chronic mountain sickness, optimal hemoglobin, and heart disease

For the male inhabitants of La Paz, Bolivia (3200-4100 m), and other high altitude regions in America and Asia, chronic mountain sickness (CMS) is a major health problem. Since CMS was first described by Carlos Monge in the Peruvian Andes in 1925, numerous research papers have been devoted to this topic, but many unanswered questions still exist with respect to the beginning of the disease and its cause(s). The experience with CMS has shown that an excessively high hemoglobin concentration is not favorable for high altitude acclimatization, and the hypothesis of theoretically "optimal" hematocrit and "optimal" hemoglobin has been made. The calculated optimal hemoglobin concentration of 14.7 g/dL for resting men in the Andes is discussed as theoretical and not applicable in real life. The most frequent congenital and acquired heart diseases are discussed, such as patent ductus, atrial septum defect, ventricle septum defect among congenital heart diseases and the still very frequent rheumatic valve cardiopathies and Chagas disease as acquired cardiopathies. Among the typical acquired heart diseases of the high altitude dweller, special attention is given to chronic cor pulmonale as a consequence of severe CMS with pulmonary hypertension.     

氧输送量及其代偿因素与急性高原病的关系研究

目的 研究全身和大脑氧输送量(DO2)及其代偿因素在急性低氧适应过程中的变化以及与急性高原病(AMS)的关系.方法 选取世居平原、乘飞机进藏的青年男性147人作为受试对象,入藏后48h内填写制式AMS流行病学观察表,于进藏前1周、入藏后48h内进行心率(HR)、血压(Bp)、血氧饱和度(SaO2)、心输出量(CO)、每搏输出量(SV)及大脑中动脉流速(MCAv)测量,严格按照路易斯湖评分系统(LLS)进行诊断并做作统计学分析.结果 147名受试对象中58.5％(86人)发生AMS.低氧暴露后,SaO2降低10％,与AMS评分呈负相关;全身DO2提高19％、CO提高32.5％、HR升高31.7％,且AMS者明显高于非AMS者,SV无显著性改变;MCAv加快10％,且AMS者具有更快的MCAv;由于SaO2降低10％与MCAv加快相匹配,使得大脑氧输送量(DO2C)无改变;平均动脉压(MBP)增加,大脑中动脉阻力单位(RMCA)明显降低,且AMS者降得更低.以DO2的关键代偿因素HR、MCAv作为AMS的客观评估指标,联合HR≥85次/min与MCAv≥ 66cm/s,其诊断的阳性预测值为82.4％,特异性为90.2％.结论 DO2及其代偿因素在急性低氧暴露后的调节适应过程中具有重要作用,其中HR、MCAv可能与AMS的发生机制有关且可间接反映对机体氧债的补偿水平,对AMS具有较好的评估能力,可作为AMS诊断的客观辅助指标.     

Acute mountain sickness: controversies and advances

This review discusses the impact of recent publications on pathophysiologic concepts and on practical aspects of acute mountain sickness (AMS). Magnetic resonance imaging studies do not provide evidence of total brain volume increase nor edema within the first 6 to 10 h of exposure to hypoxia despite symptoms of AMS. After 16 to 32 h at about 4500 m, brain volume increases by 0.8% to 2.7%, but morphological changes do not clearly correlate with symptoms of AMS, and lumbar cerebrospinal fluid pressure was unchanged from normoxic values in individuals with AMS. These data do not support the prevailing hypothesis that AMS is caused by cerebral edema and increased intracranial pressure. Direct measurement of increased oxygen radicals in hypoxia and a first study reducing AMS when lowering oxygen radicals by antioxidants suggest that oxidative stress is involved in the pathophysiology of AMS. Placebo-controlled trials demonstrate that theophylline significantly attenuates periodic breathing without improving arterial oxygen saturation during sleep. Its effects on AMS are marginal and clearly inferior to acetazolamide. A most recent large trial with Ginkgo biloba clearly showed that this drug does not prevent AMS in a low-risk setting in which acetazolamide in a low dose of 2 x 125 mg was effective. Therefore, acetazolamide remains the drug of choice for prevention and the recommended dose remains 2 x 250 mg daily until a lower dose has been tested in a high-risk setting and larger clinical trials with antioxidants have been performed.     

Prediction of acute mountain sickness by monitoring arterial oxygen saturation during ascent

Acute mountain sickness (AMS) is a common problem while ascending at high altitude. AMS may progress rapidly to fatal results if the acclimatization process fails or symptoms are neglected and the ascent continues. Extensively reduced arterial oxygen saturation at rest (R-Spo?) has been proposed as an indicator of inadequate acclimatization and impending AMS. We hypothesized that climbers less likely to develop AMS on further ascent would have higher Spo? immediately after exercise (Ex-Spo?) at high altitudes than their counterparts and that these postexercise measurements would provide additional value for resting measurements to plan safe ascent. The study was conducted during eight expeditions with 83 ascents. We measured R-Spo? and Ex-Spo? after moderate daily exercise [50?m walking, target heart rate (HR) 150?bpm] at altitudes of 2400 to 5300?m during ascent. The Lake Louise Questionnaire was used in the diagnosis of AMS. Ex-Spo? was lower at all altitudes among those climbers suffering from AMS during the expeditions than among those climbers who did not get AMS at any altitude during the expeditions. Reduced R-Spo? and Ex-Spo? measured at altitudes of 3500 and 4300?m seem to predict impending AMS at altitudes of 4300?m (p?相似文献   

Nrf2基因单核苷酸多态性与急性高原病相关性研究

目的：探讨中国汉族人群中Nrf2基因多态性与急性高原病（ AMS）易感性的关系。方法采用巢式病例研究方法,以603名急进3700 m高原的中国汉族青年男性为研究对象,根据路易斯湖评分系统（ LLSS）分为病例组（n＝369）和对照组（n＝234）,采用Sequenom Mass Array 质谱阵列技术检测两组人群Nrf2基因位点rs10497511和rs2364722的基因多态性。结果病例组与对照组中rs10497511和rs2364722位点分别检测出T、C和A、G等位基因;两位点等位基因频率在两组间差异无统计学意义（P＞0．05）。进一步对2个位点的基因型共显性模型、显性模型和隐性模型分析也未提示差异有统计学意义（P＞0．05）。结论 Nrf2基因rs10497511和rs2364722位点多态性与中国汉族男性人群AMS发病可能无相关性。     

急进高原环境对血管内皮功能的影响及其与急性高原病的关系

目的 观察人群急进高原后血管内皮功能相关指标的变化,并探讨其与急性高原病(AMS)的关系.方法 在平原地区招募32名受试者,以汽车方式急进高原(海拔3900m).进入高原第5天根据路易斯湖量表评分,将受试者分为AMS+组(n=14)和AMS-组(n=18).ELISA法检测人群血清一氧化氮(NO)、内皮素-1(ET-1)、血管内皮生长因子(VEGF)、血管内皮钙黏蛋白(VE-cadherin)、丙二醛(MDA)及超氧化物歧化酶(SOD)等指标的变化.采用Pearson相关法分析上述指标与AMS的关系.结果 急进高原后第5天时32名受试者中AMS的发生率为43.8％.与平原相比,受试者急进高原后血清NO、SOD水平明显降低(P＜0.05,P＜0.01),ET-1和MDA水平明显升高(P＜0.05).与AMS-人群比较,AMS+人群NO、VEGF和VE-cadherin、SOD水平均明显降低(P＜0.05,P＜0.01),ET-1水平明显升高(P＜0.01).相关性分析显示,急性高原暴露第5天人群血清NO、VEGF、VE-cadherin、SOD水平与AMS呈显著负相关,ET-1水平与AMS呈显著正相关.结论 急进高海拔环境可能导致血管内皮功能受损,血管内皮功能相关指标的变化可能为AMS的预警及诊断提供参考.     

Pulse oximetry in the diagnosis of acute mountain sickness

Acute mountain sickness (AMS) is a common condition in individuals who travel to altitudes over 2000 m. While AMS is an important public health problem, no measurements can reliably support or predict the diagnosis with any degree of confidence. We therefore set out to study whether pulse oximetry data are associated with AMS. We studied 169 subjects who had recently arrived by foot at 3080 m. Subjects completed a demographic survey, which collected data on ascent profiles and AMS symptoms. Resting arterial oxygen saturation and pulse rate were then measured using finger pulse oximetry. Forty-six subjects (27%) had AMS, using the Lake Louise score. Only pulse rate was significantly associated with the presence of AMS (OR: 1.4; 95% CI, 1.1 to 1.9; p < 0.05, backwards stepwise logistical regression). A trend showed worse AMS diagnoses were associated with higher mean pulse rates (p < 0.05, ANOVA linear weighted analysis). While some previous studies have shown an association between decreased oxygen saturation and acute mountain sickness at altitude, our results did not demonstrate such an association. The utility of pulse oximetry remains limited in the diagnosis of AMS. We recommend further study to determine the possible utility of pulse rate in the diagnosis and prediction of AMS.     

Comparing questionnaires for the assessment of acute mountain sickness

Exposure to high altitude in nonacclimatized subjects may lead to acute mountain sickness (AMS). AMS is a syndrome characterized by headache accompanied by one or more other symptoms, such as light-headedness, dizziness, loss of appetite, nausea, vomiting, fatigue, lassitude, and trouble sleeping. Assessing the presence and degree of AMS can be done using self-administered questionnaires like the Lake Louise Questionnaire (LLQ) and the Environmental Symptoms Questionnaire-III (ESQ-III). We compared LLQ and ESQ-III in 266 trekkers of different nationalities trekking over a 5400-m-high pass to assess if the two questionnaires identify the same population as suffering from AMS and to see whether using English questionnaires poses problems for nonnative English-speaking persons. The use of English questionnaires by nonnative English speakers influenced the outcome for some nationalities. For criterion scores yielding similar prevalence of AMS, ESQ-III labeled 20% of cases differently (AMS or no AMS) when compared to LLQ. Correlations between similar individual questions of ESQ-III and LLQ were variable, and there was considerable scatter between ESQ-III and LLQ scores. In conclusion, English questionnaires may pose problems in some international settings, and ESQ-III and LLQ may identify different populations as suffering from AMS.     

Dexamethasone for prevention and treatment of acute mountain sickness

We wished to determine in a field study the effectiveness of dexamethasone for prevention and treatment of acute mountain sickness (AMS). Prevention Trial: We transported 15 subjects from sea level to 4,400 m (PB = 400 mm Hg) on Denali (Mt. McKinley) by means of a 1-h helicopter flight. In a randomized, double-blind fashion we gave eight subjects a placebo and seven subjects 2 mg dexamethasone orally every 6 h, starting 1 h before take-off. The entire placebo group and five of the dexamethasone group developed AMS within 5 h, and became progressively more ill until 12 h when the trial was terminated. We concluded that 2 mg of dexamethasone every 6 h did not prevent AMS in active soldiers rapidly transported to high altitude. Treatment Trial: We treated 11 of those with moderate to severe AMS (symptom score 4.5 +/- 0.7, range 3 to 11) with 4 mg of dexamethasone every 6 h orally or intramuscularly for 24 h. All were markedly improved at 12 h (symptom score 1.0 +/- 0.3, p less than 0.001, range 0 to 3), but symptoms increased after the drug was discontinued at 24 h (symptom score = 2.4 +/- 0.5). We conclude that dexamethasone in a dosage of 4 mg PO or IM every 6 h is an effective treatment for AMS, but that illness may recur with abrupt discontinuation of the drug.     

慢性高原病的脑磁共振弥散张量成像研究

目的：应用3.0T磁共振弥散张量成像（diffusion tensor imaging,DTI）技术,评价慢性高原病患者脑白质的各向异性分数（fractional anisotrophy,FA）。方法：本研究共包括9例慢性高原病患者和10例正常志愿者,行常规MRI扫描及DTI扫描,测定DTI图像上不同脑白质区的FA值,并比较两组FA值的差异。结果：两组常规MR检查未见明确差异,DTI示慢性高原病组双侧额叶及海马旁白质、胼胝体膝部FA值较正常志愿者组降低,差异具有统计学意义（P〈0.05）。结论：慢性高原病患者部分脑白质区FA值下降,提示脑白质纤维束完整性受损。     

Acute mountain sickness: influence of susceptibility,preexposure, and ascent rate

PURPOSE: We examined the interaction of various established risk factors for acute mountain sickness (AMS) in a setting relevant for mountaineering and trekking. METHODS: Questionnaires were obtained from 827 mountaineers on the day of arrival at the Capanna Margherita (4559 m) and on the next morning. Susceptibility to AMS was assessed by type and frequency of symptoms during previous exposures. AMS was defined as an AMS-C score >/= 0.7 (environmental symptom questionnaire) on the morning after arrival at 4559 m. Preexposure was defined as having spent more than 4 d above 3000 m during the 2 months preceding the climb to the Capanna Margherita. Slow ascent was defined as ascending in more than 3 d. A risk model was developed by multiple logistic regression and prospectively validated on independent data. RESULTS: In susceptible individuals, the prevalence of AMS was 58% with rapid ascent and no preexposure, 29% with preexposure only, 33% with slow ascent only, and 7% with both preexposure and slow ascent. The corresponding values for nonsusceptible individuals were 31%, 16%, 11%, and 4%. The overall odds ratio for developing AMS in susceptible versus nonsusceptible individuals was 2.9 (95% confidence interval, 2.1-4.1). Age, gender, training, body mass index, alcohol intake, and cigarette smoking had no significant effect in bivariate analyses or in multivariate logistic regressions. CONCLUSION: Individual susceptibility, rate of ascent, and preexposure are the major, independent determinants for prevalence of AMS.     

Endocrine aspects of high altitude acclimatization and acute mountain sickness

The acute acclimatization to high altitude is underpinned by a diuresis (and to a lesser extent a natriuresis) that facilitates a reduction in plasma volume. This allows a haemoconcentration to occur that increases the oxygen carrying capacity of a given volume of blood, a vital effect in the presence of a reduced partial pressure of oxygen. This critical acclimatization process is orchestrated by the endocrine system. This review will present the key evidence regarding the changes in several important hormones that affect this process.     

Reappraisal of acetazolamide for the prevention of acute mountain sickness: a systematic review and meta-analysis

Acetazolamide is used to prevent acute mountain sickness (AMS). We assessed efficacy and harm of acetazolamide for the prevention of AMS, and tested for dose-responsiveness. We systematically searched electronic databases (until April 2011) for randomized trials comparing acetazolamide with placebo for the prevention of AMS. For each dose, risk ratios were aggregated using a Mantel-Haenszel fixed effect model. Numbers needed to treat (NNT) to benefit one subject with each dose were calculated for different baseline risks. Modes of ascent were taken as proxies of baseline risks. Twenty-four trials were included; 1011 subjects received acetazolamide 250, 500, or 750?mg day?1; 854 received placebo. When climbing, median speed of ascent was 14?m/h, average AMS rate in controls was 34%, and NNT to prevent AMS with acetazolamide 250, 500, and 750?mg/day compared with placebo was 6.5, 5.9, and 5.3. When ascending by transport and subsequent climbing (speed of ascent 133?m/h) or by transport alone (491?m/h), average AMS rate in controls was 60%, and NNT with acetazolamide 250, 500, and 750?mg/day was 3.7, 3.3, and 3.0. In hypobaric chambers, median speed of ascent was 4438?m/h, average AMS rate in controls was 86%, and NNT with acetazolamide 250, 500, and 750?mg/day was 2.6, 2.3, and 2.1. The risk of paresthesia was increased with all doses. The risk of polyuria and taste disturbance was increased with 500 and 750?mg/day. The degree of efficacy of acetazolamide for the prevention of AMS is limited when the baseline risk is low, and there is some evidence of dose-responsiveness.     

A review of the relationship between patent foramen ovale and type II decompression sickness.

The significance of patent foramen ovale (PFO) in the pathophysiology of Type II decompression sickness (DCS) remains controversial. PFOs are common, occurring in approximately one quarter of the normal population, thus making right-to-left shunting of venous gas emboli (VGE) a theoretical concern in both hyper- and hypobaric situations. Despite this high prevalence of PFO in the general population, and the relatively common occurrence of venous gas bubbles in diving and altitude exposures, the incidence of Type II DCS in diving or with altitude is remarkably low. Although the literature supports a relationship between the presence and size of PFO and cryptogenic stroke, and an increased relative risk of Type II DCS with a PFO in divers, the absolute increase in risk accrued is small. Hence, the value of screening is also controversial. This paper presents a summary of the literature on PFOs and DCS in animals, and in human altitude and diving, focusing on the latter; as well the analogous literature on cryptogenic stroke. The results of an examination of the literature on detection of, screening for, and treatment of PFOs is also presented.     

Amelioration of the symptoms of acute mountain sickness by staging and acetazolamide.

Treatment by 4 d of residence at 1600 m plus the administration of 500 mg acetazolamide b.i.d. for the last 2 d at 1600 m and the first 2 d at 4300 m was compared with no treatment prior to ascent to 4300 m for prophylaxis of acute mountain sickness. The treatment successfully prevented almost all symptoms of acute mountain sickness. It had no effect on the diminished capacity for maximal or prolonged heavy physical work. The treatment produced a relative acidosis and a comparatively greater arterial oxygen tension at 4300 m.     

守备时间对守备人员心理健康的影响

目的：了解高山、海岛人员的心理健康水平和守备时间与心理健康的关系。方法：从649名守备人员中按比例随机抽取86名人员为研究组，用SCL－90量表进行测量，结果与中国常模组比较，并对守备6个月以下者（短时间组）与6个月以上者（长时间组）进行比较。结果：86名高山、海岛人员躯体化症状显著高于常模组（P＜0．01），人际关系敏感显著低于对照组（P＜0．001）；长时期组的总分、总均分、阳性项目数、躯体化症状、人际关系敏感、焦虑，敌对、偏执、精神病性和其它因子的标准分显著高于短时间组（P＜0．05－0．01）。结论：高山、海岛人员的心理健康水平较常模低，长时间组的心理健康水平明显低于短时间组，环境因素是导致这个结果的主要原因。