Autonomic cardiovascular function in high-altitude Andean natives with chronic mountain sickness.

We evaluated autonomic cardiovascular regulation in subjects with polycythemia and chronic mountain sickness (CMS) and tested the hypothesis that an increase in arterial oxygen saturation has a beneficial effect on arterial baroreflex sensitivity in these subjects. Ten Andean natives with a Hct >65% and 10 natives with a Hct <60%, all living permanently at an altitude of 4,300 m, were included in the study. Cardiovascular autonomic regulation was evaluated by spectral analysis of hemodynamic parameters, while subjects breathed spontaneously or frequency controlled at 0.1 and 0.25 Hz, respectively. The recordings were repeated after a 1-h administration of supplemental oxygen and after frequency-controlled breathing at 6 breaths/min for 1 h, respectively. Subjects with Hct >65% showed an increased incidence of CMS compared with subjects with Hct <60%. Spontaneous baroreflex sensitivity was significantly lower in subjects with high Hct compared with the control group. The effects of supplemental oxygen or modification of the breathing pattern on autonomic function were as follows: 1) heart rate decreased significantly after both maneuvers in both groups, and 2) spontaneous baroreflex sensitivity increased significantly in subjects with high Hct and did not differ from subjects with low Hct. Temporary slow-frequency breathing may provide a beneficial effect on the autonomic cardiovascular function in high-altitude natives with CMS.     

Atrial natriuretic peptide in acute mountain sickness

To test the hypothesis that elevated atrial natriuretic peptide (ANP) may be involved in altered fluid homeostasis at high altitude, we examined 25 mountaineers at an altitude of 550 m and 6, 18, and 42 h after arrival at an altitude of 4,559 m, which was climbed in 24 h starting from 3,220 m. In 14 subjects, symptoms of acute mountain sickness (AMS) were absent or mild (group A), whereas 11 subjects had severe AMS (group B). Fluid intake was similar in both groups. In group B, urine flow decreased from 61 +/- 8 (base line) to 36 +/- 3 (SE) ml/h (maximal decrease) (P less than 0.05) and sodium excretion from 7.9 +/- 0.9 to 4.6 +/- 0.7) mmol.l-1.h-1 (P less than 0.05); ANP increased from 31 +/- 4 to 87 +/- 26 pmol/l (P less than 0.001), plasma aldosterone from 191 +/- 27 to 283 +/- 55 pmol/l (P less than 0.01 compared with group A), and antidiuretic hormone (ADH) from 1.0 +/- 0.1 to 2.9 +/- 1.2 pmol/l (P = 0.08 compared with group A). These variables did not change significantly in group A, with the exception of a decrease in plasma aldosterone from 189 +/- 19 to 111 +/- 17 pmol/l (P less than 0.01). There were no measurable effects of elevated ANP on natriuresis, cortisol, or blood pressure. The reduced diuresis in AMS may be explained by increased plasma aldosterone and ADH overriding the expected renal action of ANP. The significance of elevated ANP in AMS remains to be established.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cerebral blood flow in acute mountain sickness

Changes in cerebral blood flow (CBF) were measured using the radioactive xenon technique and were related to the development of acute mountain sickness (AMS). In 12 subjects, ascending from 150 to 3,475 m, CBF was 24% increased at 24 h [45.1 to 55.9 initial slope index (ISI) units] and 4% increased at 6 days (47.1 ISI units). Four subjects had similar increases of CBF when ascending to 3,200 m 3 mo later, indicating the reproducibility of the measurements. In nine subjects, ascending from 3,200 to 4,785-5,430 m, CBF increased to 76.4 ISI units, 53% above estimated sea-level values. CBF and increases in CBF were similar in subjects with or without AMS. In six subjects, CBF was measured before and after therapeutic intervention. At 2 h CBF increased 22% (71.3 to 87.3 ISI units) above pretreatment values in three subjects given 1.5 g acetazolamide, while three subjects given placebo showed no change. Symptoms remained unaltered in all subjects during the 2 h of the study. Overall, the results indicated that increases in CBF were similar in subjects with or without AMS while acetazolamide-provoked increases of CBF in AMS subjects caused no acute change in symptoms. Alterations in CBF cannot be directly implicated in the pathogenesis of AMS.     

Successful treatment of acute mountain sickness with dexamethasone.

A double blind, randomised, placebo controlled trial of treatment with dexamethasone for acute mountain sickness was performed in the Capanna "Regina Margherita" at an altitude of 4559 m in the Alps Valais. After 12-16 hours of treatment (8 mg dexamethasone initially, followed by 4 mg every six hours) the mean acute mountain sickness score decreased significantly from 5.4 to 1.3, and eight of 17 patients became totally asymptomatic. Mean arterial oxygen saturation rose from 75.5% to 82.0%, and there was a small increase in standard spirometric measurements. In the placebo group none of these variables changed significantly. It is concluded that dexamethasone may be used as emergency treatment for acute mountain sickness to facilitate safe descent to a lower altitude.     

Prevalence of acute mountain sickness in the Swiss Alps.

OBJECTIVE--To assess the prevalence of symptoms and signs of acute mountain sickness of the Swiss Alps. DESIGN--A study using an interview and clinical examination in a representative population of mountaineers. Positive symptoms and signs were assigned scores to quantify the severity of acute mountain sickness. SETTING--Four huts in the Swiss Alps at 2850 m, 3050 m, 3650 m, and 4559 m. SUBJECTS--466 Climbers, mostly recreational: 47 at 2850 m, 128 at 3050 m, 82 at 3650, and 209 at 4559 m. RESULTS--In all, 117 of the subjects were entirely free of symptoms and clinical signs of acute mountain sickness; 191 had one or two symptoms and signs; and 158 had more than two. Those with more than two symptoms and signs were defined as suffering from acute mountain sickness. At 4559 m 11 climbers presented with high altitude pulmonary oedema or cerebral oedema, or both. Men and women were equally affected. The prevalence of acute mountain sickness correlated with altitude: it was 9% at 2850 m, 13% at 3050 m, 34% at 3650 m, and 53% at 4559 m. The most frequent symptoms and signs were insomnia, headache, peripheral oedema, and scanty pulmonary rales. Severe headache, vomiting, dizziness, tachypnoea, and pronounced pulmonary rales were associated with other symptoms and signs and therefore characteristic of acute mountain sickness. CONCLUSION--Acute mountain sickness is not an uncommon disease at moderately high altitude--that is, above 2800 m. Severe headache, vomiting, dizziness, tachypnoea, and pronounced pulmonary rales indicate severe acute mountain sickness, and subjects who suffer these should immediately descend to lower altitudes.     

Early fluid retention and severe acute mountain sickness.

Field studies of acute mountain sickness (AMS) usually include variations in exercise, diet, and environmental conditions over days and development of clinically apparent edemas. The purpose of this study was to clarify fluid status in persons developing AMS vs. those remaining without symptoms during simulated altitude with controlled fluid intake, diet, temperature, and without exercise. Ninety-nine exposures of 51 men and women to reduced barometric pressure (426 mmHg = 16,000 ft. = 4,880 m) were carried out for 8-12 h. AMS was evaluated by Lake Louise (LL) and AMS-C scores near the end of exposure. Serial measurements included fluid balance, electrolyte excretions, and plasma concentrations, regulating hormones, and free water clearance. Comparison between 16 subjects with the lowest AMS scores near the end of exposure ("non-AMS": mean LL = 1.0, range = 0-2.5) and 16 others with the highest AMS scores ("AMS": mean LL = 7.4, range = 5-11) demonstrated significant fluid retention in AMS beginning within the first 3 h, resulting from reduced urine flow. Plasma Na+ decreased significantly after 6 h, indicating dilution throughout the total body water. Excretion of Na+ and K+ trended downward with time in both groups, being lower in AMS after 6 h, and the urine Na+-to-K+ ratio was significantly higher for AMS after 6 h. Renal compensation for respiratory alkalosis, plasma renin activity, aldosterone, and atrial natriuretic peptide were not different between groups, with the latter tending to rise and aldosterone falling with time of exposure. Antidiuretic hormone fell in non-AMS and rose in AMS within 90 min of exposure and continued to rise in AMS, closely associated with severity of symptoms and fluid retention.     

Current prevention and management of acute mountain sickness.

Acute mountain sickness was known to the Chinese in ancient times, as they traversed mountain passes between the Great Headache and Little Headache mountains into present-day Afghanistan. The Jesuit priest, Father Joseph Acosta, lived in Peru during the sixteenth century; he described both this syndrome and deaths which occurred in the high Andes. The incidence of high-altitude illness will rise as previously remote sites become more accessible to trekkers and skiers. Prevention and treatment are important concerns for those physicians who wish to advise their more adventuresome patients properly. This article incorporates a selected review of pertinent investigations, in the English-language literature over the past five years, into material previously presented at travel symposia for clinicians managing the prophylaxis and treatment of acute mountain sickness.     

Coagulation and fibrinolysis in acute mountain sickness and beginning pulmonary edema

To examine whether intravascular coagulation and/or decreased fibrinolysis precedes high-altitude pulmonary edema (HAPE) we examined 25 male mountaineers (median age 40 yr) at low altitude (550 m) and after 6, 18, and 42 h at an altitude of 4,559 m, which was climbed in 24 h. In 14 subjects, 2 of whom showed radiological evidence of HAPE after 42 h, symptoms of acute mountain sickness (AMS) were mild or absent. Eleven subjects suffered from AMS, six of whom developed radiologically documented HAPE after 18 or 42 h. In the absence of AMS there were no significant changes at high altitude, with the exception of a decrease in bleeding time from 246 +/- 18 to 212 +/- 13 (SE) (P less than 0.05). In AMS, partial thromboplastine time decreased from 34.2 +/- 0.8 to 31.1 +/- 0.5 s (P less than 0.001) and factor VIII procoagulant activity and von Willebrand factor antigen were increased by 57 +/- 12 and 70 +/- 13%, respectively (P less than 0.001), whereas there were no significant changes in beta-thromboglobulin (BTG), fibrinopeptide A (FPA), and fibrin fragment B beta 15-42. In subjects with HAPE, BTG, FPA, and B beta 15-42 were normal before and in beginning HAPE. Preceding HAPE, euglobulin clot lysis time declined at high compared with low altitude from 289 +/- 48 to 201 +/- 42 min without venous occlusion (VO) and from 107 +/- 36 to 86 +/- 31 min after VO (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Blood rheology in acute mountain sickness and high-altitude pulmonary edema.

The role of blood rheology in the pathogenesis of acute mountain sickness and high-altitude pulmonary edema was investigated. Twenty-three volunteers, 12 with a history of high-altitude pulmonary edema, were studied at low altitude (490 m) and at 2 h and 18 h after arrival at 4,559 m. Eight subjects remained healthy, seven developed acute mountain sickness, and eight developed high-altitude pulmonary edema. Hematocrit, whole blood viscosity, plasma viscosity, erythrocyte aggregation, and erythrocyte deformability (filtration) were measured. Plasma viscosity and erythrocyte deformability remained unaffected. The hematocrit level was lower 2 h after the arrival at high altitude and higher after 18 h compared with low altitude. The whole blood viscosity changed accordingly. The erythrocyte aggregation was about doubled 18 h after the arrival compared with low-altitude values, which reflects the acute phase reaction. There were, however, no significant differences in any rheological parameters between healthy individuals and subjects with acute mountain sickness or high-altitude pulmonary edema, either before or during the illness. We conclude that rheological abnormalities can be excluded as an initiating event in the development of acute mountain sickness and high-altitude pulmonary edema.     

定量蛋白质组学在急性高原病研究中的应用进展

急性高原病(acute mountain sickness,AMS)是人体急性暴露于高原低压低氧环境后出现多系统生理紊乱的临床综合征。定量蛋白质组学技术可以系统定量并描述机体蛋白质组成和动态变化规律,近年来在多种疾病的预防、诊断、治疗和发生机制等方面研究应用广泛。本文系统综述了定量蛋白质组学技术及其在AMS的预防、诊断、治疗和急进高原习服机制研究中的应用进展,以期为AMS的发病机制、提前干预、临床治疗和AMS的蛋白质组学研究提供参考。     

Exercise exacerbates acute mountain sickness at simulated high altitude.

We hypothesized that exercise would cause greater severity and incidence of acute mountain sickness (AMS) in the early hours of exposure to altitude. After passive ascent to simulated high altitude in a decompression chamber [barometric pressure = 429 Torr, approximately 4,800 m (J. B. West, J. Appl. Physiol. 81: 1850-1854, 1996)], seven men exercised (Ex) at 50% of their altitude-specific maximal workload four times for 30 min in the first 6 h of a 10-h exposure. On another day they completed the same protocol but were sedentary (Sed). Measurements included an AMS symptom score, resting minute ventilation (VE), pulmonary function, arterial oxygen saturation (Sa(O(2))), fluid input, and urine volume. Symptoms of AMS were worse in Ex than Sed, with peak AMS scores of 4.4 +/- 1.0 and 1.3 +/- 0.4 in Ex and Sed, respectively (P < 0.01); but resting VE and Sa(O(2)) were not different between trials. However, Sa(O(2)) during the exercise bouts in Ex was at 76.3 +/- 1.7%, lower than during either Sed or at rest in Ex (81.4 +/- 1.8 and 82.2 +/- 2.6%, respectively, P < 0.01). Fluid intake-urine volume shifted to slightly positive values in Ex at 3-6 h (P = 0.06). The mechanism(s) responsible for the rise in severity and incidence of AMS in Ex may be sought in the observed exercise-induced exaggeration of arterial hypoxemia, in the minor fluid shift, or in a combination of these factors.     

Hypothalamic-pituitary-adrenal axis following glucocorticoid prophylaxis against acute mountain sickness.

The pituitary-adrenocortical and adrenomedullary response to high altitude (HA) stress was studied following daily single dose administration of prednisolone as a prophylaxis against altitude-induced acute mountain sickness (AMS). Forty healthy men, randomly divided into two groups of twenty, received placebo or prednisolone 20 mg once a day at 08.00 h for two days prior to induction to HA and during an initial three days stay at an altitude of 3450 m. The AMS score and circulatory levels of ACTH, cortisol, epinephrine and norepinephrine were measured at sea level (SL) and during residency at HA. The sensitivity of the hypothalamic-pituitary-adrenal axis in subjects receiving prednisolone therapy was evaluated at SL and on day four of stay at HA. Administration of prednisolone significantly (p < 0.01) decreased the severity of AMS in all the subjects. The steroid dose used did not inhibit endogenous secretion of ACTH, cortisol, epinephrine or norepinephrine, as HA response to adrenocortical and adrenomedullary hormones was identical in placebo and prednisolone treated subjects. The integrity of the hypothalamic-pituitary-adrenal axis was maintained well in subjects receiving low dose prednisolone therapy. These observations suggest that short-term administration of prednisolone is able to curtail AMS without causing suppression of the hypothalamic-pituitary-adrenal axis.     

Plasma cytokine profiling to predict susceptibility to acute mountain sickness

Extensive studies have been performed on acute mountain sickness (AMS), but biomarkers predicting AMS are lacking. Presently, the mainstay methods to identify AMS biomarkers include proteomic and genetic methods at high altitudes or in hypoxic simulated chambers. In the present study, we compared plasma cytokine profiles between AMS-susceptible individuals and AMS-resistant individuals at low altitude by cytokine array analysis. In total, 75 differentially expressed cytokines were identified between AMS-susceptible individuals and AMS-resistant individuals, most involved in inflammation. A quantifiable human custom cytokine antibody array was then used to further test results of cytokine array analysis. Compared to AMS-resistant individuals, the level of insulin-like growth factor binding protein 6 (IGFBP-6) was significantly lower in AMS-susceptible individuals (37,318.99 ± 23,493.11 pg/mL and 25,665.38 ± 25,691.29 pg/mL, respectively; P = 0.04). Conversely, the levels of serum amyloid A1 (SAA1), dickkopf WNT signaling pathway inhibitor 4 (Dkk4), and interleukin 17 receptor A (IL-17RA) were significantly higher in AMS-susceptible individuals than in AMS-resistant individuals (SAA1: 4,069.69 ± 2,502.93 pg/mL vs. 2,994.98 ± 2,295.91 pg/mL, P = 0.05; Dkk4: 2,090.00 ± 2,094.89 pg/mL vs. 1,049.88 ± 1,690.93 pg/mL, P = 0.07; IL-17RA: 11.52 ± 8.33 pg/mL vs. 8.67 ± 6.22 pg/mL, P = 0.08). Although further in-depth research is required to examine the possible role of these cytokines in the development of AMS, these four cytokines may be of use in predicting AMS-susceptibility in a low-altitude environment.     

高原致适应剂新复方党参片预防急性高原反应的效果

目的:观察高原致适应剂新复方党参片对急性高原反应(AMS)的预防效果。方法:世居平原者驻守海拔1400m3个月的45名青年男性官兵,随机分为新复方党参片组(30人)和对照组(15人),采用单盲试验方法,于行军前5d开始分别口服新复方党参片和安慰剂片,乘车行军3d,于3700m习服4d,直至进驻高原(海拔5200m)第3天后停药,共服药15d。进驻高原后第1、3、5天,依国家军用标准GJB1098-91急性高原反应的诊断和处理原则,随访记录受试者的AMS症状,然后分度评分,检测受试者的心率(HR)、血氧饱和度(SaO2)。进驻高原后第6天,检测用力肺活量(FVC)、1秒用力呼气量(FEV1.0)、FEV1.0/FVC,一秒率(FEV1%)、最大呼气中期流速(FEF25%～75%)、呼气峰流速(PEF)、最大通气量(MVV)、左右手交叉敲击动作频率总次数(Ttis)、错误次数(Etis)、正确次数(Ctis)、平均时间(Atime)和数字记忆能力试验错误记忆次数总和(Sum)。结果:与对照组比较,进驻高原后第1、3、5d,新复方党参片组AMS症状显著减轻(P0.01);新复方党参片组与对照组的AMS程度分度分布不同(P0.01),新复方党参片组中症状较轻的(基本无反应、轻度反应)占比重较大,而对照组中症状较重的(中度反应、重度反应)占比重较大;新复方党参片组AMS发生率明显降低;与对照组比较,新复方党参片组的FVC、FEV1.0、FEF25%～75%、PEF、MVV升高有统计学意义(P0.05,P0.01),FEV1%差异无统计学意义;与对照组比较,新复方党参片组的Ttis、Ctis增加(P0.05,P0.01),Atime减少(P0.05),Etis和Sum差异无统计学意义。结论:新复方党参片能减轻AMS的程度,减轻AMS的症状,降低AMS发生率;并能显著改善受试者的肺通气功能和手指运动能力。