Sinus vein thrombosis following exposure to simulated high altitude

A relation exists between high altitude exposure and a hypercoagulable state, the nature of which is not entirely clear. This has been mostly reported in mountain climbers. We report a 19-yr-old female, working as a high-altitude chamber instructor, who presented with severe frontal headaches which persisted for a month following routine high altitude chamber training. The patient was in generally good health and was using oral contraceptives for 3 yr prior to the event. Due to the unremitting nature of the symptoms, the patient was admitted to a neurology department, and computerized tomography (CT) and magnetic resonance imaging (MRI) were performed. Sagittal and transverse sinus vein thrombosis were diagnosed and anticoagulant therapy was initiated (low molecular weight heparin followed by warfarin). Following treatment, a slow symptomatic improvement was observed, and the patient was discharged. On discharge, it was recommended she continue oral anticoagulant therapy (warfarin). A complete coagulation screening panel was performed, which was negative. Although the relation between high altitude exposure and a hypercoagulable state is well known, this is the first time a case of sinus vein thrombosis has been reported after high altitude chamber training. Careful history and closely monitored medical follow-up should be performed on all designated staff exposed to simulated altitude. Even though there is no conclusive evidence regarding it, we suggest, as a matter of caution, that women using oral contraceptives should consider their risks before deciding to undertake exposure to simulated altitude in chambers. Literature review and detailed recommendations for prevention are provided.     

Increased oxidative stress following acute and chronic high altitude exposure

The generation of reactive oxygen species is typically associated with hyperoxia and ischemia reperfusion. Recent evidence has suggested that increased oxidative stress may occur with hypoxia. We hypothesized that oxidative stress would be increased in subjects exposed to high altitude hypoxia. We studied 28 control subjects living in Lima, Peru (sea level), at baseline and following 48 h exposure to high altitude (4300 m). To assess the effects of chronic altitude exposure, we studied 25 adult males resident in Cerro de Pasco, Peru (altitude 4300 m). We also studied 27 subjects living in Cerro de Pasco who develop excessive erythrocytosis (hematocrit > 65%) and chronic mountain sickness. Acute high altitude exposure led to increased urinary F(2)-isoprostane, 8-iso PGF(2 alpha) (1.31 +/- 0.8 microg/g creatinine versus 2.15 +/- 1.1, p = 0.001) and plasma total glutathione (1.29 +/- 0.10 micromol versus 1.37 +/- 0.09, p = 0.002), with a trend to increased plasma thiobarbituric acid reactive substance (TBARS) (59.7 +/- 36 pmol/mg protein versus 63.8 +/- 27, p = NS). High altitude residents had significantly elevated levels of urinary 8-iso PGF(2 alpha) (1.3 +/- 0.8 microg/g creatinine versus 4.1 +/- 3.4, p = 0.007), plasma TBARS (59.7 +/- 36 pmol/mg protein versus 85 +/- 28, p = 0.008), and plasma total glutathione (1.29 +/- 0.10 micromol versus 1.55 +/- 0.19, p < 0.0001) compared to sea level. High altitude residents with excessive erythrocytosis had higher levels of oxidative stress compared to high altitude residents with normal hematological adaptation. In conclusion, oxidative stress is increased following both acute exposure to high altitude without exercise and with chronic residence at high altitude.     

Optic neuropathy following an altitude exposure

This case report describes a 20-yr-old man who presented with retro-orbital pain and blurred vision in his left eye 3 wk after an altitude exposure in a hypobaric chamber. He was found to have significant deficits in color vision and visual fields consistent with an optic neuropathy in his left eye. The patient was diagnosed with decompression sickness and treated with hyperbaric oxygen with a U.S. Navy Treatment Table VI. All signs and symptoms resolved with a single hyperbaric oxygen treatment but recurred. A head MRI revealed a left frontoethmoid sinus opacity. A concomitant sinusitis was diagnosed. The patient had full resolution of symptoms after a total of four hyperbaric oxygen treatments and antibiotic therapy at 6-wk follow-up. Although a para-infectious etiology for this patient's optic neuropathy cannot be excluded, his history of altitude exposure and significant, rapid response to hyperbaric oxygen treatment strongly implies decompression sickness in this case.     

Case report: myopic shift in a stable corneal graft following high altitude exposure.

Refractive changes in patients after radial keratotomy who are exposed to high altitudes have been reported previously. Hypoxic environments may cause corneal curvature changes in surgically altered corneas that result in refractive error shifts. We report a patient who experienced a partially reversible myopic shift in a previously stable corneal transplant after prolonged exposure to high altitude.     

模拟高原环境大鼠AQP5表达和肺动脉压变化

目的：通过模拟海拔4000m高原环境,观察大鼠肺动脉压（PAP）和肺组织水通道蛋白5（aquaporins 5,AQP5）表达变化,探讨高原肺水肿的产生机制。方法：低压氧舱减压至海拔4000m,在缺氧、缺氧复合寒冷和缺氧复合寒冷运动条件下,用心导管检测PAP变化,用免疫组化和Western blot检测肺组织AQP5表达变化。结果：与平原对照组及平原寒冷组比较,缺氧、缺氧复合寒冷、缺氧复合寒冷运动引起大鼠PAP明显升高（P〈0．01～0．05）;与两个平原组比较,AQP5在缺氧及缺氧复合寒冷运动条件下表达均增高,但均无统计学意义。模拟高原缺氧24～72h内,在缺氧复合寒冷运动条件下AQP5表达呈增高的趋势,48h达到高峰,72h较前下降;免疫组化结果显示,缺氧复合寒冷运动组较平原对照组肺间质增厚、肿大,AQP5表达明显增多。结论：高原缺氧复合寒冷运动时,AQP5表达增加,且与肺含水量和HAPE发病时相呈一致性趋势,提示AQP5可能对肺泡型肺水肿发生起代偿作用,其机制有待进一步研究。     

Gene expression in chronic high altitude diseases

Chronic mountain sickness (CMS) and high altitude pulmonary hypertension (HAPH) have been well described in different mountainous regions of the world as chronic high altitude (HA) diseases. This review briefly summarizes the available data from some genes known to be regulated by hypoxia-inducible factor 1 (HIF-1) and/or by hypoxia that have been studied in populations from these regions suffering from CMS and/or HAPH. Excessive erythrocytosis, caused by a lower oxygen saturation and hypoxic ventilatory response and/or ventilatory inefficiency, is the outstanding sign of CMS, and right ventricular enlargement, pulmonary hypertension, and remodeling of pulmonary arterioles are hallmarks of HAPH. Familial character and heritability studies have suggested that genetic factors could make a contribution to the pathogenesis of CMS and HAPH. Even though some alleles are more prevalent (G allele of eNOS polymorphism Glu298Asp in Sherpas and ACE I allele in HAPH Kyrgyz) or less prevalent (ACE D allele in HA Andeans) in the different high altitude populations, published data to date are insufficient for a rigorous test of any hypothesis regarding the implications of these gene polymorphims in CMS or HAPH.     

Irreversible subcortical dementia following high altitude illness

In this report, we present the cases of two 63-year-old women who developed high altitude cerebral edema complicated by the occurrence of permanent neuropsychiatric sequelae. They shared a similar clinical course, in that both developed disturbance of consciousness shortly after their arrival at Cuzco, Peru (3500 m), and both developed persistent neuropsychiatric symptoms after resolution of the acute illness. Interestingly, in case 2 there was a 1-month lucid interval between remission of high altitude illness and occurrence of the irreversible neuropsychiatric sequelae. Brain computerized tomography in case 1 and brain magnetic resonance imaging in case 2 disclosed lesions in the globus pallidus bilaterally, suggesting that the neuropsychiatric symptoms in these patients were manifestations of subcortical dementia. The development of high altitude illness was considered to be attributable to mild restrictive lung impairment in case 1 and to a deficient ventilatory response to hypoxia in case 2. It must therefore be borne in mind that irreversible subcortical dementia may be associated with high altitude cerebral edema.     

Dental fractures on acute exposure to high altitude

There is little in the literature on dental restoration breakage in the aviation environment since reports of problems in combat aviators in War World II. We report two cases of dental fractures during acute exposure to a hypobaric environment. Case 1 was a young officer who suffered an amalgam restoration breakage during a 25,000-ft decompression chamber simulation. Case 2 occurred in an experienced aviator who had a tooth cusp fracture in a molar with a defective amalgam restoration during an unpressurized helicopter flight to 18,000 ft. In both cases, after removing the defective fillings, deep secondary caries were found; both teeth were successfully restored. Because hard-tissue tooth fracture during a high-altitude flight is a rare event, few flight surgeons or dentists are familiar with this phenomenon. We recommend regular dental examinations with careful assessment of previous dental restorations in aircrew subject to decompression.     

高原环境暴露的脑MRI研究进展

高原低氧低压环境会引起人脑病理生理变化。MRI检查可以无创探查脑结构和功能变化。结构MRI包括常规MRI、基于体素的形态学分析（VBM）、基于表面的形态学测量（SBM）和扩散张量成像（DTI）;功能MRI主要包括血氧水平依赖（BOLD）脑功能成像和灌注加权成像（PWI）。与常规MRI相比,其他几种新的MRI技术具有能对病变定量和高敏感度的特点,有利于高原疾病的早期防治。就高原环境暴露下的脑结构和功能MRI研究进行综述。     

Heart rate variability in rats acclimatized to high altitude

The aims of this study were to relate heart morphology and functions changes to heart rate variability (HRV) components after acclimatization to high altitude and to define whether preadaptation to hypoxia could modulate HRV responses to acute hypoxic stress. Doppler-echocardiographic studies of the left ventricle were performed in female Wistar rats before, during, and after a 10-week exposure to moderate hypobaric hypoxia (CH rats, approximately 4000 m simulated) or normoxia (N rats, approximately 55 m). Right ventricular morphology and function and pulmonary artery pressure were evaluated using heart catheterization. Spectral analysis of HRV was studied after exposure in conscious unrestrained rats in normoxia and during acute hypoxic stress. Necropsy right ventricular hypertrophy and intraventricular and pulmonary artery hypertension were found in CH rats compared with N rats. Echocardiographic left ventricular morphology and functions were similar between the groups after exposures. Compared to the control group, CH rats had similar heart rates and HRV components when measured in normoxia. During acute hypoxic stress, HRV decreased in all rats, but less in CH rats. These results support the hypothesis that long-term mild hypoxia may moderate sympathetic activation induced by acute hypoxia and that right ventricular hypertrophy cannot be the direct cause of such a shift in sympathovagal nerve interaction during acute hypoxic stress.     

睡眠剥夺对模拟高原环境下高原肺水肿形成的影响

目的探讨睡眠剥夺对模拟高原环境下高原肺水肿（high altitude pulmonary edema,HAPE）形成的影响,为防治HAPE提供理论依据。方法雄性SD大鼠,随机分成4组,即平原对照组、高原对照组、高原剥夺组、平原剥夺组,睡眠剥夺采用小平台水环境法建立,高原环境用5000 m低压氧舱模拟。通过测定大鼠肺湿/干比值、肺含水比值、动脉血气来评定肺水肿的程度,并通过大鼠肺组织石蜡切片观察各组病变。结果高原剥夺组的肺湿/干比值及肺含水量比值显著高于其余3组（P〈0.01）。高原剥夺组可见肺间质增厚、肿大,大量多核细胞,肺泡腔变小,肺泡内无液体渗出,其他组病理切片未见上述变化。结论高原环境下睡眠剥夺可促发急性HAPE的形成可能与交感神经活性增强有关。     

呼吸不同浓度氧气对兔高空暴露的防护作用

目的 观察兔暴露于高空时呼吸不同浓度氧气后的生理变化和组织超微结构改变,探讨分子筛氧源在高空的防护效果。方法 将20只兔随机分为呼吸空气组(A)、呼吸63％富氧气体组(B)、呼吸83％富氧气体组(C)和呼吸纯氧组(D)。各组兔在低压舱内上升到11000m,停留30min,记录心脏区气泡、心电图和客观反应,观察心和脑组织超微结构的变化,肾组织促红细胞生成素(EPO)的表达。结果 空气组心脏区气泡数量明显增加,多数兔出现心律失常;富氧浓度组和纯氧组偶见气泡;随着吸人气氧浓度的增加,脑、心组织超微结构缺氧改变减轻,肾EPOmRNA表达的阳性率降低。结论 呼吸含氧浓度大于80％的富氧气体对高空暴露的机体有明显的防护作用。     

高原地区大鼠烫伤延迟复苏后Peyer氏结中Bax表达及其意义

目的：探讨不同海拔高度大鼠烫伤延迟复苏后回肠Peyer氏结淋巴细胞凋亡和Bax基因表达的意义。方法：Wistar大鼠132只,分别在海拔1517m和3848m随机分为延迟复苏组（DFR）、即时复苏组（IFR）和假伤组（SG）,建立TBSA 30％Ⅲ度烫伤模型,分别于伤后6、12、24、48和72h取材。采用TUNEL、免疫组化与图象分析技术,观察Peyer氏结中淋巴细胞凋亡率及Bax表达。结果：淋巴细胞凋亡率在各海拔高度DFR组和IFR组均高于SG组,随海拔高度上升凋亡率有所上升;DFR组凋亡率高于同海拔IFR组,海拔3848m各实验组分别高于海拔1517m（P〈0．05）;Bax表达强度变化平行于淋巴细胞凋亡率变化,但在伤后6h和72h海拔3848m各实验组分别高于海拔1517m（P〈0．05）。结论：高原地区烫伤延迟复苏后Bax表达增高可能是Peyer氏结T淋巴细胞凋亡增加的重要原因之一。     

高原低氧环境下大鼠血浆抗利尿激素水平变化研究

目的：研究高原低氧环境下大鼠血浆抗利尿激素（PAVP）水平变化，探讨其与急性高原病的关系。方法：将50只雄性SD大鼠随机分为5组．分别为24h、48h、72h、1w及1个月（A、B、C、D、E）组，同时设立对照组（西宁地区，海拔2260m），将5个实验组由西宁地区带至青海大学可可西里高原医学研究基地（海拔4600m），在不同时间点处死取材，应用放射免疫法检测PAVP的浓度，并与对照组比较。结果：PAVP浓度在初入高原后呈下降趋势，在48h达到最低，后逐渐回升，至1w时已经接近对照组水平，1个月时达到最高水平。结论：高原慢性低氧环境下，PAVP的浓度随着缺氧时间的延长而变化，此可能与机体缺氧程度及高原低氧习服过程有关。     

Ginkgo biloba extract prevents high altitude pulmonary edema in rats

Ginkgo biloba reduces the severity of acute mountain sickness in humans, but protection against high altitude pulmonary edema (HAPE) has not been reported. This study was conducted to determine if G. biloba would prevent early HAPE in rats. Six rats (ginkgo group) received G. biloba (200 mg/kg body weight in drinking water and an equal amount in peanut butter) for 2 days before and during high altitude exposure (380 mmHg pressure for 24 h). Six other rats (control group) received water and peanut butter alone. Protein concentrations in bronchoalveolar lavage fluid (BALF) were increased in control rats (19.8 +/- 2.6 mg/dL) compared to ginkgo rats (11.6 +/- 0.9 mg/dL; p = 0.014), demonstrating that untreated (control) rats developed mild HAPE following high altitude exposure. For comparison, BALF protein concentrations in sea-level rats (air group) given peanut butter were 12.6 +/- 0.8 mg/dL (n = 6). Although pleural effusions did not develop in any rats, the protein concentrations of pleural fluid were also increased in control rats (4.9 +/- 0.16 g/dL) compared to ginkgo rats (4.0 +/- 0.13; p = 0.001); air group: 3.5 +/- 0.08 g/dL. There were no differences in wet/dry lung weight ratios between groups, but wet left lung weights/preexposure body weight were increased in control rats (1.26 +/- 0.02 g/kg) compared to the ginkgo group (1.17 +/- 0.01 g/kg; p = 0.002); air group: 1.11 +/- 0.03 g/kg. In conclusion, the data show that G. biloba prevents the development of early HAPE in rats.     

Changes in glycolytic intermediates in rat erythrocytes during exposure to simulated high altitude

Regulatory mechanisms of erythrocyte glycolysis and 2,3-diphosphoglycerate (2,3DPG) metabolism under hypoxia were studied in rats exposed to a simulated altitude of 18,000 ft (5,486 m) for 5 d. Changes in erythrocyte glycolytic intermediates were determined by enzymatic analysis. Marked alterations of glycolytic intermediates were found during 1 d of exposure which were quite different from those observed during exposure for 2, 3, and 5 d. Alterations of intermediates seem to be highly correlated with blood pH changes; however, pH alone cannot explain the overall changes in intermediates. Results suggested that overall intermediate changes are the results of the combined effect of alterations of cellular pH and hemoglobin desaturation. Increased 2,3DPG at initial stages of exposure (within 1 d) may be caused mainly by the increased cellular pH; sustained elevation of 2,3DPG at later stages could be attributed to the relief of product inhibition of diphosphoglycerate mutase by deoxygenation.     

Changes in the serum LDH isoenzymes in monkey during chronic exposure to simulated high altitude

When the monkey was exposed to a simulated high altitude of 18,000 ft (5,486 m) for 30 d, the serum LDH activity was increased to its maximum in 1 week. After the monkey returned to sea level, the enzyme activity showed a rapid recovery. On the basis of electrophoretic analysis of LDH isoenzymes, the percentages of LDH-1 and LDH-2 were decreased during the first 2-3 weeks of hypoxic exposure whereas those of LDH-3, LDH-4 and LDH-5 were increased. After 2 or 3 weeks of hypoxic exposure, LDH-3, LDH-4, and LDH-5 become predominant, indicating that the isoenzyme pattern shifted to an anaerobic form from an aerobic form. These results clearly showed that relative proportions of the five isoenzymes were significantly altered by chronic hypoxia of high altitude and that the elevation of total serum LDH activity induced by hypoxia came predominantly from rapid accumulation of M type LDH isoenzymes in serum.