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Previous studies suggest that 5 days of prophylactic ginkgo decreases the incidence of acute mountain sickness (AMS) during gradual ascent. This trial was designed to determine if ginkgo is an effective prophylactic agent if begun 1 day prior to rapid ascent. In this double-blind, randomized, placebo-controlled trial, 26 participants residing at sea level received ginkgo (60 mg TID) or placebo starting 24 h before ascending Mauna Kea, Hawaii. Subjects were transported from sea level to the summit (4205 m) over 3 hours, including 1 hour at 2835 m. The Lake Louise Self-report Questionnaire constituted the primary outcome measure at baseline, 2835 m, and after 4 h at 4205 m. AMS was defined as a Lake Louise Self-report Score (LLSR) >/= 3 with headache. Subjects who developed severe AMS were promptly transported to lower altitude for the remainder of the study. The ginkgo (n = 12) and placebo (n = 14) groups were well matched (58% vs. 50% female; median age 28 yr, range 22-53 vs. 33 yr, range 21-53; 58% vs. 57% Caucasian). Two (17%) subjects on ginkgo and nine (64%) on placebo developed severe AMS and required descent for their safety (p = 0.021); all recovered without sequelae. Median LLSR at 4205 m was significantly lower for ginkgo versus placebo (4, range 1-8 vs. 5, range 2-9, p = 0.03). Ginkgo use did not reach statistical significance for lowering incidence of AMS compared with placebo (ginkgo 7/12, 58.3% vs. placebo 13/14, 92.9%, p = 0.07). Twenty-one of 26 (81%) subjects developed AMS overall. This is the first study to demonstrate that 1 day of pretreatment with ginkgo 60 mg TID may significantly reduce the severity of AMS prior to rapid ascent from sea level to 4205 m.

Endogenously produced nitric oxide plays a major role in lung physiology and pathology. Inhaled nitric oxide given exogenously has been studied extensively as a treatment for many lung diseases, and the results suggest that it may help improve oxygenation in some patients. Several issues need to be addressed, however, before it can be used in routine clinical practice.

Almost every second trekker or climber develops two to three symptoms of the high altitude illness after a rapid ascent (> 300 m/day) to an altitude above 4000 m. We distinguish two forms of high altitude illness, a cerebral form called acute mountain sickness and a pulmonary form called high altitude pulmonary edema. Essentially, acute mountain sickness is self-limiting and benign. Its symptoms are mild to moderate headache, loss of appetite, nausea, dizziness and insomnia. Nausea rarely progresses to vomiting, but if it does, this may anticipate a progression of the disease into the severe form of acute mountain sickness, called high altitude cerebral edema. Symptoms and signs of high altitude cerebral edema are severe headache, which is not relieved by acetaminophen, loss of movement coordination, ataxia and mental deterioration ending in coma. The mechanisms leading to acute mountain sickness are not very well understood; the loss of cerebral autoregulation and a vasogenic type of cerebral edema are being discussed. High altitude pulmonary edema presents in roughly twenty percent of the cases with mild symptoms of acute mountain sickness or even without any symptoms at all. Symptoms associated with high altitude pulmonary edema are incapacitating fatigue, chest tightness, dyspnoe at the minimal effort that advances to dyspnoe at rest and orthopnoe, and a dry non-productive cough that progresses to cough with pink frothy sputum due to hemoptysis. The hallmark of high altitude pulmonary edema is an exaggerated hypoxic pulmonary vasoconstriction. Successful prophylaxis and treatment of high altitude pulmonary edema using nifedipine, a pulmonary vasodilator, indicates that pulmonary hypertension is crucial for the development of high altitude pulmonary edema. The primary treatment of high altitude illness consists in improving hypoxemia and acclimatization. For prophylaxis a slow ascent at a rate of 300 m/day is recommended, if symptoms persist, acetazolamide at a dose of 500 mg/day is effective. Mild acute mountain sickness may also be treated with the same dose acetazolamide. Glucocorticoids are the first line treatment of the malignant form of acute mountain sickness. Nifedipine is effective only for the prophylaxis and treatment of high altitude pulmonary edema.

Background: Hypoxemia is the immediate consequence of hyobaric hypoxia, which is the crucial starting mechanism of acute mountain sickness (AMS). The AMS is generally a benign and self-limiting condition which can be prevented by gradual ascent. However, ascent rates recommended for prophylaxis of AMS are far slower than those attempted during military operations and by climbers., Objective: The current study was carried out to quantify the relationship between AMS and hypoxemia alongwith evaluating the benefits of acetazolamide-dexamethasone chemoprophylaxis during acute ascent., Subjects and Methods: Twenty-four low lander male adults (age mean +/- SE 27.8 +/- 1.24 years) were selected. They were grouped in a double-blind fashion into four groups and each group (n = 6) received placebo (multivitamin) or acetazolamide (250 mg) or dexamethasone (4 mg) or a combined regimen of the two drugs twice daily for 5 days, commencing 24 hours before ascent. The volunteers reached the altitude of 4578 meters within a span of one day. Their AMS symptoms were recorded on modified environmental symptoms questionnaire (ESQ), after 24 and 72 hours of ascent. Arterial PO2, SO2 and PCO2 were measured by GEMSTAT blood-gas analyzer (Mallincrodt-USA)., Results: The ESQ, AMS-C (cerebral) and AMS-R (respiratory) scores of combined therapy group were significantly lower as compared to the other groups on the symptom rating scale. The significant finding amongst the volunteers taking acetazolamide was mild to moderate diuresis whereas severity of headache was markedly less in dexamethasone group. The commonest feature of combined therapy was that none of the volunteers complained of headache, dysponea, irritability and more than mild disturbance of sleep. The ESQ scores of volunteers were inversely correlated to PaO2 and SaO2 after 24 hours of ascent to 4578 meters., Conclusion: The study concludes that severity of AMS is closely related to hypoxemia and combination therapy of acetazolamide-dexamethasone may be effective in preventing AMS.

Inhibition of carbonic anhydrase in general or specific inhibition of one the different isoenzymes results in a significant metabolic acidosis due to renal bicarbonate loss. The increase of arterial pCO2 stimulates central and peripheral chemoreceptors and enhances ventilation. The inhibition of carbonic anhydrase as a respiratory stimulant is an accepted measure for the prevention of acute mountain sickness, has been used for a restricted number of subjects with sleep-disordered breathing or chronic hypoxaemic lung disease. The few indications and the narrow therapeutic index restrict the use of carbonic anhydrase blockers as stimulants for ventilation.

Objective: To observe the preventive and therapeutic effects of gangliosides on acute altitude hypoxic brain damage., Method: Fifteen Wistar rats, weighed 180-220 g, were randomly divided into 3 groups, hypoxia group A, hypoxia group B and normoxia group. The rats in hypoxia group A were exposed to a simulated altitude of 7000 m for 5 hours and the rats in hypoxia group B were exposed to hypoxia after intraperitoneal administration of mixed gangliosides (100 mg/kg/d) for 3 days., Result: Gangliosides could ameliorate the severity of damage in neuronal bodies, cellular skeletons and synapses, especially in synapses., Conclusion: It is suggested that gangliosides are effective in preventing and treating hypoxic brain damages by decreasing the accumulation of intracellular Ca2+, and stabilizing CaM and CaM PKII activity during acute hypoxia.

A randomized two-part study was conducted in order to determine the efficacy of theophylline in the treatment of acute mountain sickness during fast ascent to altitudes >2,500 m. Fourteen healthy male subjects participated in a randomized single-blind placebo-controlled crossover study carried out in a decompression chamber (simulated altitude 4,500 m). A second randomized single-blind, placebo-controlled study was conducted at a high-altitude research laboratory (3,454 m) and included 21 healthy male subjects. The study medication was either 375 mg oral slow-release theophylline (250 mg if <70 kg) or a matched placebo tablet taken twice daily. The acute mountain sickness score (AMSS) was assessed three times a day, beginning 18 h prior to altitude exposure and continuing for 18 h after altitude exposure. In addition, measurements of respiratory frequency, pulse rate, oxygen saturation and arterial blood gas levels were performed. Acute mountain sickness was significantly reduced by theophylline during the decompression chamber study (mean+/-SD 1.2+/-0.9) with placebo versus 3.6+/-0.8 with theophylline; p=0.03). During the high-altitude study, subjects with theophylline showed a significantly lower AMSS on arrival and after 18 h at altitude (0.6 versus 2.3, p=0.03). Oxygenation was improved in both parts of the study. In conclusion, oral slow-release theophylline improves acute mountain sickness.

Today we distinguish cerebral (acute mountain sickness AMS, high altitude cerebral edema HACE) and pulmonal (high altitude pulmonary edema HAPE) altitude disorders. Incidence, predisposition and risk factors of all kinds of altitude sickness vary both individually and geographically. For practical reasons the leading symptoms are essential: altitude headache, ataxia and sudden loss of strength. Depending on the severity of symptoms the main emergency measures are: rest, descent or evacuation, warmth. Additional therapeutical measures can be helpful if a sudden evacuation to lower altitudes is delayed: oxygen, portable hyperbaric chamber, ibuprofen/naproxen, nifedipine, dexamethasone. Acetazolamide should not be used as an emergency therapy any more.

Background: Research has focused mainly on the relationship of zinc and copper contents and physical stresses like running, cycling, etc. It has also been reported that other forms of stresses change the concentration of these trace elements in humans. However,there are no reports on the effects of high altitude induced hypoxic stress on the plasma levels of these metals. Since hypoxia is one of the important stresses, we considered it appropriate to observe the changes in the levels of zinc and copper concentrations and in certain related zinc and copper enzymes and hormones in the plasma of human volunteers on acute induction to high altitude. From these findings, we intended to ascertain whether supplementation of these trace elements would be required for optimal health under such conditions., Hypothesis: On acute induction to hypoxia, contents of these trace elements may change as the requirements of stressed organs and tissue may increase. Hence, further supplementation may be beneficial under hypoxic stress for better adaptability., Method: Volunteers were divided into two groups: with and without zinc and copper salt supplementation. Blood samples were collected at sea level and on induction to acute hypoxia on days 3 and 10. Trace mineral contents and their related enzyme (alkaline phosphatase) and hormone (ceruloplasmin) levels were determined in plasma samples., Results: Plasma zinc contents were significantly reduced upon induction to high altitude in the non-supplemented group, but not in the zinc-supplemented group. Alkaline phosphatase activity increased significantly upon induction to the high altitude stress. The enzyme activity remained elevated up to day 10 of the stress. Plasma copper contents and ceruloplasmin activity did not change upon induction to high altitude., Conclusion: Under hypoxic stress, circulating levels of zinc and alkaline phosphatase in plasma changed appreciably as plasma zinc was transported into the organs and tissues. However, circulating levels of copper and ceruloplasmin in plasma did not change, indicating no extra supplementation of copper is required under hypoxic stress.

Headache is known to be the predominant symptom in acute mountain sickness which is also frequently accompanied by nausea, vomiting and insomnia. Nowadays, every year millions of skiers and mountaineers are attracted to mountains all over the world. At altitudes between 2500 m and 5000 m about 20% to 90% of those who are not adapted to high altitude will experience high altitude headache (HAH). It is well documented that HAH can be best prevented by observance of the golden rule: not to go too high too fast. Although many mountaineers are aware of this rule, its observance is complicated by unknown individual susceptibility, the location of mountain huts, the use of cable cars, limited holiday time, unfavorable weather or avalanche conditions. Therefore, there is a widespread use of drugs for the treatment and prevention of HAH. In the past, the increase in cerebral blood flow during acute hypoxia was thought to be the main cause of HAH. More recent findings, however, have caused this hypothesis to be reduced in importance and have supported the pathogenetic consequence of sensitization of intracranial pain-sensitive structures. The effectiveness of cyclooxygenase inhibition for the treatment and prevention of HAH suggests that especially prostaglandins may be an important mediator between hypoxia and HAH. Besides oxygen, acetazolamide, dexamethasone and especially inhibitors of prostaglandin synthesis such as ibuprofen and naproxen are approved for the treatment of HAH. Acetazolamide, dexamethasone, and aspirin were also found to prevent HAH. The most beneficial effects however, may be achieved by the combined application of acetazolamide and aspirin. This combination increases oxygenation and reduces prostaglandin synthesis.

At an altitude of about 3000 m even healthy people suffer from hypoxemia due to the low oxygen partial pressure. As a physiological countermeasure the oxygen partial pressure is increased. In the present study the following procedures are looked into: 1. Pressurized breathing, 2. Oxygen bulus breathing. It was found out that both procedures are appropriate to increase the oxygen partial pressure efficiently. However, bolus breathing is more effective, since an almost 100% hemoglobin saturation may be achieved even with small bolus volumes when the subject is at rest or under little physical strain. Pressurized breathing seems to be an appropriate emergency measure when a sudden pressure loss occurs in an aircraft for a short while provided that the subject is familiar with the breathing technique.

Objective: To evaluate the clinical effects and mechanism of anticholinergics in treating high altitude pulmonary edema (HAPE)., Methods: 582 patients with HAPE (in 4700-5260 m) were divided into 2 groups: one group (393 patients) was treated with anticholinergic (Group A), and the other 189 cases were treated with a general therapy without anticholinergic (Grorp B)., Results: Compared with Group B, the average admitted days were reduced, the symptom, physical and X-ray signs disappeared more quickly (P < 0.001), the cure rate was raised clearly (P < 0.05) in Group A and the abnormal changes of hemodynamics had been adjusted (P < 0.05, P < 0.01)., Conclusions: Anticholinergic used for HAPE has a rapid and exact curative effect, a slight side effect, and a shorten course of treatment.

We carried out a randomized, double-blind trial at 3800 m altitude to test whether a small degree of room oxygen enrichment at night improves sleep quality, and performance and well-being the following day. Eighteen sea-level residents drove from sea level to 3800 m in one day, and then slept one night in ambient air, and another night in 24% oxygen, the order being randomized. With oxygen enrichment the subjects had fewer apneas (P < 0.01) and spent less time in periodic breathing with apneas (P < 0.01) than when they slept in ambient air. Subjective assessments of sleep quality were also significantly improved. There was a lower acute mountain sickness score during the morning after oxygen-enriched sleep (P < 0.01) and a greater increase in arterial oxygen saturation from evening to morning (P < 0.05). The larger increases in arterial oxygen saturation from evening to morning suggest that the control of breathing may have been altered. Installing an oxygen-enriched room at high altitude is relatively simple and inexpensive, and shows promise for improving well-being of both commuters and residents.

Objective: To investigate the therapeutic effect of low-concentration of nitroic oxide (NO) inhalation in high-altitude pulmonary edema., Method: Sixty-five male patients with high-altitude pulmonary edema were randomized into three groups. Patients in the conventional therapy group received oxygen, intravenous furosemide, aminophylline and dexamethasone; patients in the nifedipine group received oral nifedipine (10 mg, tid) in addition to conventional therapy; and patients in the NO group received NO (10 ppm) inhalation for 30 min, in addition to oral nifedipine. The time for which pulmonary rales on auscultation and shadows on chest radiograph lasted, and the course of disease, were compared., Result: In the NO group, pulmonary rales disappeared in 0.4 +/- 0.3 d, shadows on chest radiograph disappeared in 0.6 +/- 0.2 d, and the course of disease was 1.8 +/- 0.7 d, all of which were significantly different from those of the nifedipine group (2.4 +/- 1.4 d, 4.1 +/- 1.7 d, 6.8 +/- 1.8 d, respectively) and the conventional therapy group (3.7 +/- 1.2 d, 5.5 +/- 1.8 d, 9.6 +/- 3.1 d, respectively)., Conclusion: Low-concentration NO inhalation on the basis of conventional and nifedipine therapies was very effective in the treatment of high-altitude pulmonary edema, which deserves further and larger scale investigation.

We have developed an anesthetized microswine model of hypoxemic hypothermia and rewarming for testing prophylaxes and treatments. The respiratory stimulant almitrine bismesylate (ALM) was considered as a potential field expedient therapy for hypoxemic hypothermia. Preliminary experiments demonstrated that five consecutive 100 micrograms.kg-1 ALM intravenous (i.v.) doses given to normothermic microswine 3-4 min apart increased minute ventilation from an average of 3.4 L.min-1 to 4.5 L.min-1 (n = 2). However, when either a single i.v. ALM dose of 150 micrograms.kg-1 (n = 1) or three consecutive 100 micrograms.kg-1 i.v. doses given 15 min apart (n = 1) to hypoxemic hypothermic microswine with a mean esophageal temperature (Tes) = 28.8 degrees C, and a mean arterial O2 partial pressure (PaO2) = 49 mmHg, the hypoxemia was potentiated (mean PaO2 = 32 mmHg) and respiratory arrest ensued. Other experiments using continuous ALM i.v. infusion (1.0 microgram.kg-1.min-1) in hypoxemic hypothermic microswine (n = 6, Tes = 30.6 +/- 0.5, PaO2 = 55.4 +/- 12.9) did not demonstrate significant (p < or = 0.05) cardiorespiratory differences (ventilation, heart rate, blood pressure, blood gases) when compared to hypoxemic hypothermic controls (n = 6, Tes = 30.7 +/- 0.5, PaO2 = 53.3 +/- 13.6). These results suggest that high dose i.v. bolus administration of ALM is not indicated as a potential field expedient therapy for hypoxemic hypothermia, while further work is required to assess the potential efficacy of other continuous low dose i.v. infusion regimens.

Antiviral cell resistance of blood monocytes and lymphocytes was studied in 29 healthy human subjects subjected to acute altitude hypoxia (AAH) in climatic chamber TABAI, and 39 healthy males during rapid ascent from the sea level up to 3250 m. The antiviral resistance of immune cells was found to be suppressed by AAH. Double blind method was used to compare effects of placebo, dexamethasone and olifen (approved by the Pharmacology Committee of the Russian Ministry of Health as an antihypoxic preparation) on the antiviral resistance of cells during AAH. Unlike dexamethasone, from the onset of AAH olifen prevented decline of the antiviral resistance of cells; olifen successfully remedied disorders resulted from stay in AAH.

Method: We recruited 44 subjects to participate in a study of the preventive effect of Ginko biloba extract (EGb 761) on acute mountain sickness (AMS) and vasomotor changes of the extremities during a Himalayan expedition. After giving their written informed consent, the subjects were randomized to two groups. One group received 160 mg of EGb 761 per day in two divided doses and the other group received placebo. Assessment was based on the course of the Environmental Symptom Questionnaire (ESQ) score and the cold gradient measured by photoplethysmography., Results: The prophylactic efficacy of treatment with EGb 761 was clearly demonstrated in this study. In terms of factor 1 (AMS-Cerebral), no subject in the EGb 761 group developed acute mountain sickness versus 40.9% of subjects in the placebo group; this difference was very significant (p < or = 1.4 x 10(-3)). In terms of factor 2 (AMS-Respiratory), 3 subjects (13.6%) in the EGb 761 group developed acute mountain sickness versus 18 (81.8%) in the placebo group; this difference was very significant (p = 1.2 x 10(-5))., Conclusion: Due to its multiple pharmacological actions, EGb 761 provides an interesting response to the prevention of mountain sickness for moderate altitude (5400 m) with gradual exposure. It also decreased vasomotor disorders of the extremities, as demonstrated by plethysmography (p < 10(-8)) and a specific questionnaire (p < 10(-9)).

In simulating acute hypoxic hypoxia with the participation of male volunteers, the authors investigated the antihypoxic and antioxidative activity of metabolic drugs (jakton, amtizole succinate, nootropil, probucol, and a mixture which consists of jakton, amtizole succinate, and probucol). The pharmaceuticals were shown to have heterodirectional effects on lipid peroxidative processes. Drugs having a pronounced antioxidative activity (such as probucol and the mixture) promotes oxygen utilization during hypoxia and posthypoxic reoxygenation chiefly by the oxygenase pathway. This rearrangement of oxygen utilization processes caused an increase in human high-altitude resistance. The use of the above drugs is a promising trend in the development of an adaptative response to hypoxia in persons engaged in hazardous jobs.

The fundi of 14 climbers were monitored on ascent to 6000 metres over a 15 day period in the Nepal Himalaya. A total of 4 climbers experienced symptomless haemorrhages. These haemorrhages were not secondary to changes in haemoglobin concentration, nor did they appear correlated to the use of acetazolamide. The risk of developing retinal haemorrhage was, however, significantly greater in the better acclimatized individuals. Possible reasons for this relationship are discussed.

The primary physiologic disturbance at high altitude is hypoxemia, which leads to a cascade of secondary changes in each step of the oxygen-transport chain. The author, in this review, focuses on the alterations in ventilatory control and alveolar-capillary gas exchange at high altitude and discusses the clinical pulmonary complications associated with these alterations, as well as their prevention and management.

Acute altitude illnesses include acute mountain sickness (AMS), a benign condition involving headache, nausea, vomiting, irritability, insomnia, dizziness, lethargy, and peripheral edema, and potentially lethal high-altitude cerebral edema and pulmonary edema (HAPE). Recent evidence is summarized that AMS is related to cerebral edema secondary at least in part to hypoxic cerebral vasodilation and elevated cerebral capillary hydrostatic pressure. This results in reduced brain compliance with compression of intracranial structures in the absence of altered global brain metabolism. It is postulated that these primary intracranial events elevate peripheral sympathetic activity that acts neurogenically in the lung possibly in concert with pulmonary capillary stress failure to cause HAPE and in the kidney to promote salt and water retention. The adrenergic responses are likely modulated by striking increases of aldosterone, vasopressin and atrial natriuretic peptide. The effects of exercise on altitude-induced illness and various therapeutic regimens (acetazolamide, CO2 breathing, dexamethasone, and alpha adrenergic inhibitors) are discussed in light of this hypothesis.

Significant health hazards to the traveller arise from altitude, heat, cold and water. Altitude-induced illness encompasses the benign but common syndrome of acute mountain sickness and also life-threatening pulmonary and cerebral oedema; inadequate acclimatization and rapid ascent are important precipitating factors in each case. Prophylaxis and up to date choices of treatment are discussed in the context of underlying physiological changes. Heat illnesses include exhaustion and heat stroke; they result from increased core temperature and/or physiological responses including peripheral vasodilation and sweating. Preventive measures include acclimatization, ample water without added salt, and matching dress and exercise to the environment. Cold environments pose risk of hypothermia and local cold injury which include frostbite and non-freezing cold injury; as frostnip is only diagnosed after treatment, it is a category of limited usefulness. Prevention of each disorder requires correct clothing and equipment and good training. Other hazards include immersion, and flying too soon after diving.

Climbing in the Alps and trekking in the Andes or in the Himalayas became more and more popular in the last years. This is the reason why more and more tourists develop symptoms of acute mountain sickness (AMS) at an altitude higher than 2500 m a.s.l. To avoid an unpleasant stay at altitude, an accurate acclimatization is necessary. This can be achieved by a slow ascent at a climbing rate of 300 to 600 m in one day. If that is not possible, climbers should spend at least nine or more nights at an altitude higher than 2500 m a.s.l. in the last 30 days before ascent. This would improve performance at high altitude and significantly decrease symptoms of AMS. If acclimatization for one or another reason may not be possible or if somebody is still susceptible to AMS, pharmacological prophylaxis and treatment can be used. Drug of first choice for AMS prophylaxis is acetazolamide, a carboanhydrase inhibitor who increases ventilation. Acetazolamide has been used in a dosage of 250 to 500 mg 12 to 24 h. before ascent. If climbers have a history of high-altitude pulmonary edema (HAPE), nifedipine, a potent vasodilator which decreases pulmonary artery pressure, is the drug of the first choice and should be taken in a dosage of 3 x 20 mg, beginning one day before climbing and continuing during climbing. Prophylactic administration of nifedipine has no effect on symptoms of AMS in subjects who are not susceptible to HAPE.(ABSTRACT TRUNCATED AT 250 WORDS)

Sleep and respiration data from two French medical high altitude expeditions (Annapurna 4,800 m and Mt Sajama 6,542 m) are presented. Difficulties in maintaining sleep and a SWS decrease were found with periodic breathing (PB) during both non-REM and REM sleep. Extent of PB varied considerably among subjects and was not correlated to the number of arousals but to the intercurrent wakefulness duration. There was a positive correlation between the time spent in PB and the individual hypoxic ventilatory drive. The relation between PB, nocturnal desaturation, and mountain sickness intensity are discussed. Acclimatization decreased the latency toward PB and improved sleep. Hypnotic benzodiazepine intake (loprazolam 1 mg) did not worsen either SWS depression or apneas and allowed normal sleep reappearance after acclimatization.

High altitude pulmonary edema (HAPE) is characterized by marked pulmonary hypertension. Treatment of 6 subjects suffering from radiographically documented HAPE with the calcium channel blocker nifedipine, lowered pulmonary artery pressure and resulted in clinical improvement, better oxygenation, reduction of alveolar-arterial oxygen gradient and a progressive clearing of alveolar edema on chest x-ray. This amelioration occurred despite continued exercise at an altitude above 4000 m and without supplementary oxygen. Prophylactic application of nifedipine slow release preparation, 20 mg every 8 hours, prevented HAPE in 9 out of 10 subjects with a history of radiographically documented HAPE upon rapid ascent and subsequent stay to an altitude of 4559 m. Seven of 11 comparable subjects who received placebo developed pulmonary edema at 4559 m. As compared with the subjects who received placebo, those who received nifedipine had a significantly lower mean systolic pulmonary artery pressure, alveolar-arterial pressure gradient of oxygen and symptom score of acute mountain sickness at 4559 m. Thus nifedipine offers a potential emergency treatment of HAPE when descent or evacuation is impossible and oxygen is not available. Prophylactic administration of nifedipine prevents HAPE in susceptible subjects. High pulmonary artery pressure has an important role in the pathogenesis of HAPE.

High altitude pulmonary edema is characterized hemodynamically by a markedly restricted pulmonary vascular bed. Pulmonary vascular resistance is six to eight times higher than control values at altitude, and mean pulmonary pressure is generally elevated two to four-fold over control values. We wished to compare the effect of various vasodilators on the hemodynamics of HAPE, both to gauge their potential effectiveness in treatment of HAPE, and also to gain clues as to the mechanism of the altered pulmonary circulation. In a series of field experiments using a total of 16 subjects with HAPE and 10 well controls, we measured pulmonary hemodynamics by non-invasive Doppler echocardiography. The per cent reduction in pulmonary vascular resistance and mean pulmonary artery pressure, respectively, were 46 and 33 for oxygen, 30 and 29 for nifedipine, 29 and 25 with hydralazine, 57 and 42 with phentolamine, and 72 and 52 when oxygen and phentolamine were combined. All the vasodilators improved gas exchange, suggesting a link between edema formation and pulmonary vasoconstriction. A number of vasodilators may be useful in the treatment of HAPE; the superiority of an alpha adrenergic blocker may implicate the sympathetic nervous system in the pathophysiology of high altitude pulmonary edema.

Objective: To determine the efficacy of acetazolamide in the treatment of patients with acute mountain sickness and the effect of the drug on pulmonary gas exchange in acute mountain sickness., Design: A randomized, double-blind, placebo-controlled trial., Setting: The Denali Medical Research Project high-altitude research station (4200 m) on Mt. McKinley, Alaska., Participants: Twelve climbers attempting an ascent of Mt. McKinley (summit, 6150 m) who presented to the medical research station with acute mountain sickness., Intervention: Climbers were randomly assigned to receive acetazolamide, 250 mg orally, or placebo at 0 (baseline) and 8 hours after inclusion in the study., Main Outcome Measures: An assessment of acute mountain sickness using a symptom score and pulmonary gas exchange measurements was done at baseline and at 24 hours., Main Results: After 24 hours, five of six climbers treated with acetazolamide were healthy, whereas all climbers who received placebo still had acute mountain sickness (P = 0.015). Arterial blood gas specimens were obtained from three of the six acetazolamide recipients and all of the placebo recipients. The alveolar to arterial oxygen pressure difference (PAO2-PaO2 difference) decreased slightly over 24 hours in the acetazolamide group (-0.8 +/- 1.2 mm Hg) but increased in the placebo group (+3.3 +/- 2.3 mm Hg) (P = 0.024). Acetazolamide improved PaO2 over 24 hours (+2.9 +/- 0.8 mm Hg) when compared with placebo (-1.3 +/- 2.8 mm Hg) (P = 0.045)., Conclusion: In established cases of acute mountain sickness, treatment with acetazolamide relieves symptoms, improves arterial oxygenation, and prevents further impairment of pulmonary gas exchange.

Acetazolamide treatment ameliorates the symptoms of AMS; however, the mechanism by which this occurs is unclear. To examine the effects of acetazolamide on oxygenation, CO2 responsiveness and ventilatory pattern during acute exposure to HA, we studied two groups of subjects at SL and following rapid (less than 8 h) transport to HA. Acetazolamide or placebo tablets were given to groups 1 and 2, respectively, in a double-blind manner after baseline SL measurements; treatment was continued during HA exposure. There was no difference in the ventilatory pattern at HA, between the two groups. While the Ve achieved in response to CO2 at HA vs SL was much greater in each group the percent change from baseline at HA versus that at SL was not significantly different. The beneficial effects of acetazolamide in AMS are associated with a higher level of ventilation at HA and better oxygenation: CO2 chemosensitivity is not affected by acetazolamide at HA.

The efficacy of carbonic anhydrase (CA) inhibitors in amelioration of periodic breathing during sleep at high altitude is not fully understood. Although CA is present in a number of tissues, we hypothesized that selective renal CA inhibition without physiologically important inhibition of other tissue CA, may be sufficient alone by its generation of a mild metabolic acidosis to stimulate ventilation and prevent periodic breathing. We studied benzolamide (3 mg/kg), a selective inhibitor of renal CA, in 4 climbers on ventilation and ventilatory responses at sea level and on arterial O2 saturation (SaO2%) and periodic breathing during sleep at altitude. At sea level, ventilation increased and PaO2 rose accompanied by a mild metabolic acidosis. The isocapnic hypoxic ventilatory response was unchanged but the hyperoxic hypercapnic ventilatory response rose 40%. At high altitude (4400 m), daytime SaO2% improved from 81 to 85 and venous plasma HCO3- fell from 18.9 to 14.8 mM. During sleep, mean SaO2% rose from 76 to 80 and periodic breathing decreased 75%. We conclude that metabolic acidosis occurring with all CA inhibitors is one of the major stimulant actions of these drugs on ventilation while awake and during sleep at high altitude.

Acute mountain sickness has long been recognized as a potentially life-threatening condition afflicting otherwise healthy individuals who ascend rapidly to high altitude, where the partial pressure of oxygen in the air is reduced. The symptoms of acute mountain sickness are probably a consequence of disturbances in fluid balance brought about by severe tissue hypoxia. Acute mountain sickness can be prevented by an adequately slow ascent, which is the best method, but for those with limited time there are several drug therapies that provide a relatively good protection. John Coote describes these treatments and their possible mechanisms of pharmacological action.

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.

This study examined the effects of dexamethasone and exposure to high terrestrial altitude on cognitive performance, affect, and personality. Cognitive performance was evaluated by five cognitive tasks, affect was evaluated by the Clyde Mood Scale and the Multiple Affect Adjective Check List, and personality was examined using the Minnesota Multiphasic Personality Inventory. Sixteen healthy young men received either dexamethasone (4 mg every 6 h) (n = 7) or placebo (n = 9) for 34 h prior to and 52 h after ascent to 4,300 m. Subjects treated with dexamethasone correctly performed more computer interaction and addition problems than did placebo-treated subjects. They also were less sleepy, dizzy, depressed, and anxious than placebo-treated subjects at altitude. No adverse effects on cognitive performance, affect, or personality were noted after dexamethasone was discontinued on the third day at altitude. Results indicate that dexamethasone at the present dose positively influences cognitive performance and mood states at altitude, but has no residual effect on personality.

A possible contribution of exercise to the fluid retention associated with acute mountain sickness (AMS) was investigated in 17 mountaineers who underwent an exercise test for 30 min on a bicycle ergometer with a constant work load of 148 +/- 9 (SE) W at low altitude (LA) and with 103 +/- 6 W 4-7 h after arrival at 4,559 m or high altitude (HA). Mean heart rates during exercise at both altitudes and during active ascent to HA were similar. Exercise-induced changes at LA did not differ significantly between the eight subjects who stayed well and the nine subjects who developed AMS during a 3-day sojourn at 4,559 m. At HA, O2 saturation before (71 +/- 2 vs. 83 +/- 2%, P less than 0.01) and during exercise (67 +/- 2 vs. 72 +/- 1%, P less than 0.025) was lower and exercise-induced increase of plasma aldosterone (617 +/- 116 vs. 233 +/- 42 pmol/l, P less than 0.025) and plasma antidiuretic hormone (23.8 +/- 14.4 vs. 3.4 +/- 1.8 pmol/l, P less than 0.05) was greater in the AMS group, whereas exercise-induced rise of plasma atrial natriuretic factor and changes of hematocrit, potassium, and osmolality in plasma were similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Sodium nitroprusside (NP) alone Was given to the 39 cases with acute high-altitude pulmonary edema (AHPE). 33 of them (84.6%) fully recovered and 6 (15.38%) obviously improved in 72 hours. The total efficacy was 100%. There was obvious improvement in the cardiac pumping and contractile function as well as total peripheral resistance. The mean pulmonary artery pressure (MPAP) decreased from 52.22 +/- 7.51mmHg to 25.13 +/- 10.36mmHg in 3 to 5 hours after the first dose. Strophanthin K was given to another 11 cases with AHPE, But none fully recovered or obviously improved. During the 72 hours of treatment, 4 improved slightly, 4 showed no therapeutic effect and 3 became worse. The heart rate was reduced obviously and cardiac contractile function strengthened while the cardiac pumping function and total peripheral resistance had no change. Vasodilator therapy is a new method for AHPE treatment and this study shows that the NP is an ideal drug in treating AHPE and that dilation of the small pulmonary arteries by NP may explain its efficacy.

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.

Acute mountain sickness is a pathologic reaction as a result of bad adaptation to high altitudes (greater than 2.500 meters). The main symptoms are headache, nausea, vomits, and insomnia. When severe it can produce oliguria, retinal hemorrhage, ataxia and sometimes coma. Its etiology is not well known. It is considered that the first producer factor of the disease is tissular hypoxia secondary to low partial oxygen pressure existing in areas of high sea level. The treatment consists of descent and the use of dexametasone and acetazolamide.

A US Marine Corps Battalion Landing Team (BLT) of 638 men was deployed on a winter training exercise to an altitude of 2,065 to 2,620 m. Nine marines (1.4%) presented to the medical officers with incapacitating symptoms consistent with acute mountains sickness. Seven were treated with acetazolamide and experienced relief of their symptoms within 24 hours. The incidence of nonspecific complaints associated with acute mountain sickness at altitude was found to be significantly greater than the incidence at sea level of those same complaints in the same BLT performing a similar winter training exercise (0.16%). Blacks who had been raised in low-altitude regions were the most commonly afflicted. Prophylaxis with acetazolamide for subsequent altitude exposure can be recommended for those individuals identified as susceptible. Acute mountain sickness is not uncommon at intermediate altitudes.