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Acute mountain sickness (AMS) and high-altitude cerebral edema share common clinical characteristics, suggesting cerebral swelling may be an important factor in the pathophysiology of AMS. Hypoxia and hypocapnia associated with high altitude are known to exert strong effects on the control of the cerebral circulation, yet how these effects interact during acute hypoxia, and whether AMS-susceptible subjects may have a unique response, is still unclear. To test if self-identified AMS-susceptible individuals show altered brain swelling in response to acute hypoxia, we used quantitative arterial spin-labeling and volumetric MRI to measure cerebral blood flow and cerebrospinal fluid (CSF) volume changes during 40 min of acute hypoxia. We estimated changes in cerebral blood volume (CBV) (from changes in cerebral blood flow) and brain parenchyma swelling (from changes in CBV and CSF). Subjects with extensive high-altitude experience in two groups participated: self-identified AMS-susceptible (n = 6), who invariably experienced AMS at altitude, and self-identified AMS-resistant (n = 6), who almost never experienced symptoms. During 40-min hypoxia, intracranial CSF volume decreased significantly [-10.5 ml (SD 6.9), P < 0.001]. There were significant increases in CBV [+2.3 ml (SD 2.5), P < 0.005] and brain parenchyma volume [+8.2 ml (SD 6.4), P < 0.001]. However, there was no significant difference between self-identified AMS-susceptible and AMS-resistant groups for these acute-phase changes. In acute hypoxia, brain swelling occurs earlier than previously described, with significant shifts in intracranial CSF occurring as early as 40 min after exposure. These acute-phase changes are present in all individuals, irrespective of susceptibility to AMS.

Increased intracranial pressure is suspected in the pathogenesis of acute mountain sickness (AMS), but no studies have correlated it with the presence or severity of AMS. We sought to determine whether increased optic nerve sheath diameter, a surrogate measure of intracranial pressure, is associated with the presence and severity of AMS. We performed a cross-sectional study of travelers ascending through Pheriche, Nepal (4,240 m), from March 3 to May 14, 2006. AMS was assessed using the Lake Louise score. Optic nerve sheath diameter was measured by ultrasound. Ultrasound exams were performed and read by separate blinded observers. Two-hundred eighty seven subjects were enrolled. Ten of these underwent repeat examination. Mean optic nerve sheath diameter was 5.34 mm [95% confidence interval (CI) 5.18-5.51 mm] in the 69 subjects with AMS vs. 4.46 mm (95% CI 4.39-4.54 mm) in the 218 other subjects (P < 0.0001). There was also a positive association between optic nerve sheath diameter and total Lake Louise score (P for trend < 0.0001). In a multivariate logistic regression model of factors associated with AMS, optic nerve sheath diameter was strongly associated with AMS (odds ratio 6.3; 95% CI, 3.7-10.8; P < 0.001). In 10 subjects with repeat examinations, change in Lake Louise score had a strong positive correlation with change in optic nerve sheath diameter (R(2) = 0.84, P < 0.001). Optic nerve sheath diameter, a proxy for intracranial pressure, is associated with the presence and severity of AMS.

Objective: To determine the efficacy of 2 different sources of Ginkgo biloba extract (GBE) in reducing the incidence and severity of acute mountain sickness (AMS) following rapid ascent to high altitude., Methods: Two randomized, double-blind, placebo-controlled cohort studies were conducted in which participants were treated with GBE (240 mg x d(-1)) or placebo prior to and including the day of ascent from 1600 m to 4300 m (ascent in 2 hours by car). Acute mountain sickness was diagnosed if the Environmental Symptom Questionnaire III acute mountain sickness-cerebral (AMS-C) score was > or =0.7 and the Lake Louise Symptom (LLS) score was > or =3 and the participant reported a headache. Symptom severity was also determined by these scores., Results: Results were conflicting: Ginkgo biloba reduced the incidence and severity of AMS compared to placebo in the first but not the second study. In the first study, GBE reduced AMS incidence (7/21) vs placebo (13/19) (P = .027, number needed to treat = 3), and it also reduced severity (AMS-C = 0.77 +/- 0.26 vs 1.59 +/- 0.27, P = .029). In the second study, GBE did not reduce incidence or severity of AMS (GBE 4/15 vs placebo 10/22, P = .247; AMS-C = 0.48 +/- 0.13 vs 0.58 +/- 0.11, P = .272). The primary difference between the 2 studies was the source of GBE., Conclusions: The source and composition of GBE products may determine the effectiveness of GBE for prophylaxis of AMS.

Cognitive and neuropsychological functions have been impaired at high altitude and the effects depend on altitude and duration of stay. However, the neurobiological mechanism of this impairment is poorly understood especially exposure to different duration. Aim of the present study was to investigate the changes of behavior, biochemistry and morphology after exposure to different duration of hypobaric hypoxia. The rats were exposed continuously to a simulated high altitude of 6100m for 3, 7, 14 and 21 days in an animal decompression chamber. Spatial reference memory was tested by Morris water maze. The oxidative stress markers like free radicals, NO, lipid peroxidation, LDH activity and antioxidant systems like GSH, GSSG, GPx, GR, SOD were estimated from cortex, hippocampus and striatum. The morphological changes, neurodegeneration, DNA fragmentation and mode of cell death have also been studied. It was observed that the spatial reference memory was significantly affected after exposure to hypobaric hypoxia. Increased oxidative stress markers along with decreased effectiveness of antioxidant system were also observed in hypoxia-exposed animals. Further pyknotic, shrunken, tangle-like neurons were observed in all these regions after hypoxia and neurodegeneration, DNA fragmentation and apoptosis were also observed in all the three regions. But after 21 days of exposure, the spatial memory was improved along with improvement of antioxidant activities. Our result suggests that the apoptotic death may be involved in HA-induced memory impairment and after 7 days of exposure the effect was more pronounced but after 21 days of exposure recovery was observed.

Background and Purpose: At high altitudes barometric pressure is reduced and, thus, less oxygen is inhaled. Reduced oxygen concentration in brain tissue can lead to cerebral damage and neurological and cognitive deficits. The present study was designed to explore the effects of high-altitude exposure using a quantitative MRI technique, voxel-based morphometry., Methods: We studied nine world-class mountain climbers before (baseline) and after (follow-up) an extremely high-altitude ascent of Everest and K2. We investigated the effects of repeated extremely high-altitude exposures by comparing mountain climbers' scans at baseline with scans of 19 controls. In addition, we measured the effects of a single extremely high-altitude expedition by comparing mountain climbers' scans at baseline and follow-up., Results: A region of reduced white matter density/volume was found in the left pyramidal tract near the primary (BA 4) and supplementary (BA 6) motor cortex when mountain climbers at baseline were compared with controls. Further, when mountain climbers' scans before and after the expedition were compared, a region of reduced grey matter density/volume was found in the left angular gyrus (BA 39)., Conclusion: These findings suggest that extremely high-altitude exposures may cause subtle white and grey matter changes that mainly affect brain regions involved in motor activity.

Hypobaric hypoxia has been reported to cause memory dysfunction. The possible molecular mechanism involved, however, remains to be explored. The role that glutamate and its receptors play in causing excitotoxicity in ischemia and neurodegenerative diseases indicates the possible occurrence of a similar phenomenon in hypobaric hypoxia. The present study aimed to elucidate the molecular events occurring at glutamatergic synapses in hypobaric hypoxia using Sprague-Dawley rats as a model system. The animals were exposed to an altitude of 7,600 m for different durations. Hypobaric hypoxia was found to cause oxidative stress, chromatin condensation, and neurodegeneration. A temporal change in the expression of the ionotropic receptors of glutamate was also observed. Expression of the N-methyl-D-aspartate (NMDA) receptor increased, and expression of glutamate receptor subunit 2 of the alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionate receptor decreased. We also observed increased activity of glutamate dehydrogenase, indicating greater synthesis and release of glutamate after 3 and 7 days of exposure. Administration of a selective NMDA antagonist during exposure was found to ameliorate neuronal degeneration, providing evidence for the occurrence of excitotoxicity in hypobaric hypoxia. Our study indicates that excitotoxicity occurs in hypobaric hypoxia. This study also indicates the appropriate period for drug administration during exposure to hypobaric hypoxia and establishes ionotropic receptors of glutamate as potential therapeutic targets for ameliorating high-altitude-induced cognitive dysfunction.

Introduction: High-altitude cerebral edema is a potentially fatal neurologic syndrome that develops in subjects exposed to high-altitude. It may appear associated to other forms of altitude illnesses as acute mountain sickness or high-altitude pulmonary edema. The exact pathophysiology of high-altitude cerebral edema is still unknown and there is not consensus about the primarily type of edema: vasogenic or cytotoxic. We present a patient who suffered high-altitude cerebral edema and the clinical, neuroimaging and ultrasonographic findings at first and during the follow up., Clinical Case: A 49 year old man, mountain climber, at altitude of 5,400 m presented altered mental status and ataxia with progressive neurologic deterioration, associated to pulmonary edema. After being introduced at hyperbaric chamber, patient was descended to hospital. The magnetic resonance imaging (MRI) revealed increased T2 signal in the white matter, especially in the splenium of the corpus callosum. Corticosteroids and acetazolamide were administered and patient was transferred to our hospital. Transcranial Doppler sonography (TCD-A) using acetazolamide showed an impaired cerebral vasoreactivity. Clinical improvement of the patient was fast. MRI performed 14 days after clinical onset showed partial resolution of corpus callosum lesion. MRI and TCD-A performed six months after were normal., Conclusions: TCD-A in our patient show a diminished cerebral vasoreactivity related to high-altitude cerebral edema. These findings suggest that impairment of cerebral autoregulation might play a role in high-altitude cerebral edema pathogenesis. Reversible clinical and neuroimaging changes indicate a predominant vasogenic edema.

Three groups of male rats were submitted to an intermittent hypobaric hypoxia (IHH) program for 22 days (4 h/day, 5 days/week) in a hypobaric chamber at a simulated altitude of 5000 m. Hearts were removed at the end of the program (H group) and 20 and 40 days later (P20 and P40 groups). A control group (C) was maintained at sea-level pressure. Transverse sections from myocardium were cut and histochemically stained in order to measure fiber morphometry and capillaries. We observed a progressive increase from C to H to P20 animals in capillary (4124 to 4733 to 4816 capillaries/mm(2)) and fiber densities (2844 to 3125 to 3284 fibers/mm(2)) associated with significant reductions in fiber area (273, 235, and 227 microm(2)), perimeter (69, 64, and 62 microm), and diffusion distances (18.2, 16.9, and 16.6 microm). The most significant differences between C and hypoxic groups were found when morphometrical and vascular fiber parameters were combined. The myocardium of the latter had more capillaries per fiber area and per fiber perimeter. These findings indicate that the IHH program elicits an adaptive response of rat myocardium to a more efficient O2 delivery to mitochondria of cardiac muscle cells. Capillarization and fiber morphometric changes showed marked differences over time. In all cases, P20 had higher capillarization parameters and fiber morphometry reductions than H, thus indicating that a delay of about 20 days exists after the hypoxic stimulus ceases to reach complete angiogenesis and fiber morphometry changes. However, P40 animals showed a recovery to basal values of the parameters related to fiber morphometry (area, perimeter, and diffusion distances), but maintained high capillarity values (capillary density, NCF, CCA, CCP).

Hypobaric hypoxia (HH), a predisposing environmental condition at high altitude (HA), encountered by many mountaineers, jeopardizes their normal physiology like motor coordination and cognitive functions. A large body of evidence shows that HH has deleterious effect on cognitive functions. Among them the hippocampal dependent memory deficit is well known. However, our current understanding of the mechanistic details of cognitive deficits at HA remains largely unclear and hence limits a solution for this problem. Therefore, the present study was designed to investigate the temporal component of the hippocampal pyramidal neuron damage in the rat brain subjected to chronic HH exposure. Three groups (sham HH, 3 days HH and 7 days HH) of rats were exposed to simulated HH equivalent to 6100 m in an animal decompression chamber for 3 or 7 days. Later, the hippocampal (CA1 and CA3) neurons were analysed for the cell morphology, neurodegeneration and DNA fragmentation. The CA1 and CA3 neurons showed HH induced neuronal pyknosis, cell shrinkage, and consequent inter-cellular vacuolization in the CA1 and CA3 areas. In addition, the total neuron (intact) numbers and mean surface area were decreased. The number of dead neurons increased significantly following exposure to HH for 3 or 7 days. The neurodegenerative (Fluoro jade B) and apoptotic (TUNEL) markers were more positive in CA1 and CA3 neurons. The magnitude of morphological changes, neurodegeneration and apoptosis was enhanced in 7 days HH group than 3 days HH group. Our studies indicate that CA3 neurons are more vulnerable to HH than CA1 neurons, and that may destabilize the neural circuits in the hippocampus and thus cause memory dysfunction.

The present study applied T2- and diffusion-weighted magnetic resonance imaging to examine if mild cerebral edema and subsequent brain swelling are implicated in the pathophysiology of acute mountain sickness (AMS). Twenty-two subjects were examined in normoxia (21% O2), after 16 hours passive exposure to normobaric hypoxia (12% O2) corresponding to a simulated altitude of 4,500 m and after 6 hours recovery in normoxia. Clinical AMS was diagnosed in 50% of subjects during hypoxia and corresponding headache scores were markedly elevated (P<0.05 versus non-AMS). Hypoxia was associated with a mild increase in brain volume (+7.0+/-4.8 ml, P<0.05 versus pre-exposure baseline) that resolved during normoxic recovery. Hypoxia was also associated with an increased T2 relaxation time (T2rt) and a general trend toward an increased apparent diffusion coefficient (ADC). During the normoxic recovery, brain volume and T2rt recovered to pre-exposure baseline values, whereas a more marked reduction in ADC in the splenium of the corpus callosum (SCC) was observed (P<0.05). While changes in brain volume and T2rt were not selectively different in AMS, ADC values were consistently lower (P<0.05 versus non-AMS) and associated with the severity of neurologic symptoms. Acute mountain sickness was also characterized by an increased brain to intracranial volume ratio (P<0.05 versus non-AMS). These findings indicate that mild extracellular vasogenic edema contributes to the generalized brain swelling observed at high altitude, independent of AMS. In contrast, intracellular cytotoxic edema combined with an anatomic predisposition to a 'tight-fit' brain may prove of pathophysiologic significance, although the increase in brain volume in hypoxia was only about 0.5% of total brain volume.

More than 140 million people worldwide live >2500 m above sea level. Of them, 80 million live in Asia, and 35 million live in the Andean mountains. This latter region has its major population density living above 3500 m. The primary objective of the present study is to review the physiology, pathology, pathogenesis, and clinical features of the heart and pulmonary circulation in healthy highlanders and patients with chronic mountain sickness. A systematic review of worldwide literature was undertaken, beginning with the pioneering work done in the Andes several decades ago. Original articles were analyzed in most cases and English abstracts or translations of articles written in Chinese were reviewed. Pulmonary hypertension in healthy highlanders is related to a delayed postnatal remodeling of the distal pulmonary arterial branches. The magnitude of pulmonary hypertension increases with the altitude level and the degree of exercise. There is reversal of pulmonary hypertension after prolonged residence at sea level. Chronic mountain sickness develops when the capacity for altitude adaptation is lost. These patients have moderate to severe pulmonary hypertension with accentuated hypoxemia and exaggerated polycythemia. The clinical picture of chronic mountain sickness differs from subacute mountain sickness and resembles other chronic altitude diseases described in China and Kyrgyzstan. The heart and pulmonary circulation in healthy highlanders have distinct features in comparison with residents at sea level. Chronic mountain sickness is a public health problem in the Andean mountains and other mountainous regions around the world. Therefore, dissemination of preventive and therapeutic measures is essential.

Acute mountain sickness (AMS) can occur during climbs to high altitudes and may seriously disturb the behavioral and intellectual capacities of susceptible subjects. During a Himalayan expedition 32 mountaineers were examined with electroencephalography (EEG) and transcranial doppler sonography (TCD) to assess relative changes of middle cerebral artery velocity in relation to end-expiratory CO2 (EtCO2), peripheral saturation (SaO2), and symptoms of AMS. We tested the hypothesis that O2 desaturation and EtCO2 changes precede the development of AMS and result in brain dysfunction and compensatory mechanisms which can be measured by EEG and TCD, respectively. Contrary to our hypothesis, we found that subjects who later developed symptoms of AMS between 3,440 m and 5,050 m altitude exhibited an increase of slow cerebral activity in the right temporal region already at 3,440 m. Cerebral blood flow increased in these mountaineers in the right middle cerebral artery at 5,050 m. These findings indicate that regional brain dysfunction, which can be documented by EEG, heralds the appearance of clinical symptoms of AMS.

To investigate the consequences of inborn excessive erythrocytosis, we made use of our transgenic mouse line (tg6) that constitutively overexpresses erythropoietin (Epo) in a hypoxia-independent manner, thereby reaching hematocrit levels of up to 0.89. We detected expression of human Epo in the brain and, to a lesser extent, in the lung but not in the heart, kidney, or liver of tg6 mice. Although no acute cardiovascular complications are observed, tg6 animals have a reduced lifespan. Decreased swim performance was observed in 5-mo-old tg6 mice. At about 7 mo, several tg6 animals developed spastic contractions of the hindlimbs followed by paralysis. Morphological analysis by light and electron microscopy showed degenerative processes in liver and kidney characterized by increased vascular permeability, chronic progressive inflammation, hemosiderin deposition, and general vasodilatation. Moreover, most of the animals showed severe nerve fiber degeneration of the sciatic nerve, decreased number of neuromuscular junctions, and degeneration of skeletal muscle fibers. Most probably, the developing demyelinating neuropathy resulted in muscular degeneration demonstrated in the extensor digitorum longus muscle. Taken together, chronically increased Epo levels inducing excessive erythrocytosis leads to multiple organ degeneration and reduced life expectancy. This model allows investigation of the impact of excessive erythrocytosis in individuals suffering from polycythemia vera, chronic mountain sickness, or in subjects tempted to abuse Epo by means of gene doping.

Objective: Previous studies have questioned whether there is an improved cardiac function after high-altitude training. Accordingly, the present study was designed specifically to test whether this apparent blunted response of the whole heart to training can be accounted for by altered mechanical properties at the cellular level., Methods: Adult rats were trained for 5 weeks under normoxic (N, NT for sedentary and trained animals, respectively) or hypobaric hypoxic (H, HT) conditions. Cardiac morphology and function were evaluated by echocardiography. Calcium Ca2+ sensitivity of the contractile machinery was estimated in skinned cardiomyocytes isolated from the left ventricular (LV) sub-epicardium (Epi) and sub-endocardium (Endo) at short and long sarcomere lengths (SL)., Results: Cardiac remodelling was harmonious (increase in wall thickness with chamber dilatation) in NT rats and disharmonious (hypertrophy without chamber dilatation) in HT rats. Contrary to NT rats, HT rats did not exhibit enhancement in global cardiac performance evaluated by echocardiography. Stretch- dependent Ca2+ sensitization of the myofilaments (cellular index of the Frank-Starling mechanism) increased from Epi to Endo in N rats. Training in normoxic conditions further increased this stretch-dependent Ca2+ sensitization. Chronic hypoxia did not significantly affect myofibrilar Ca2+ sensitivity. In contrast, high-altitude training decreased Ca2+ sensitivity of the myofilaments at both SL, mostly in Endo cells, resulting in a loss of the transmural gradient of the stretch-dependent Ca2+ sensitization. Expression of myosin heavy chain isoforms was affected both by training and chronic hypoxia but did not correlate with mechanical data., Conclusions: Training at sea level increased the transmural gradient of stretch-dependent Ca2+ sensitization of the myofilaments, accounting for an improved Frank-Starling mechanism. High-altitude training depressed myofilament response to Ca2+, especially in the Endo layer. This led to a reduction in this transmural gradient that may contribute to the lack of improvement in LV function via the Frank-Starling mechanism.

Objective: This exploratory study assessed a potential relationship between elevated carboxyhemoglobin (COHb) levels and acute mountain sickness (AMS) at 4300 m on Denali. Additional analysis assessed the relationship among COHb levels, AMS, and climber characteristics and behaviors., Methods: Participants were screened for AMS with the Lake Louise Self-Report questionnaire and answered questions focusing on AMS symptoms, prevention, and previous altitude illness. Levels of COHb were measured by serum cooximetry. Additional questions assessed stove practices, climbing practices, and climber behaviors. Nonparametric statistical analyses were performed to examine potential relationships among COHb levels, AMS symptoms, and climber behaviors., Results: A total of 146 climbers participated in the study. Eighteen climbers (12.5%) were positive for carbon monoxide (CO) exposure and 20 (13.7%) met criteria for AMS. No significant relationship was observed between positive CO exposure and positive criteria for AMS. Climbers descending the mountain were 3.6 times more likely to meet the study criteria for positive CO exposure compared with those ascending the mountain (P = .42). In addition, COHb levels were significantly higher for those descending the mountain (P = .012) and for those taking prophylactic medications (P = .010). Climbers meeting positive criteria for AMS operated their stoves significantly longer (P = .047)., Conclusions: No significant relationship between AMS symptoms and CO exposure was observed. This may have been affected by the low percentage of climbers reporting AMS symptoms, as well as limited power. Descending climbers had a 3.6 times increased risk of CO exposure compared with ascending climbers and had significantly higher COHb scores. Increased hours of stove operation was significantly linked to climbers who also met criteria for AMS.

Objective: This study aimed to determine the efficacy, tolerability, and practicality of acetazolamide for the prevention of acute mountain sickness (AMS) in Nepali trekking porters early in the trekking season., Methods: This study was a randomized, double-blind controlled trial with 400 male Nepali porters in the Mount Everest region of Nepal, trekking from Namche Bazaar (3440 m) to Lobuche (4930 m), the study endpoint. Participants were randomized to receive 250 mg acetazolamide daily or placebo, and AMS symptom scores (Lake Louise) were compared in highlanders vs lowlanders., Results: Only 109 (27.2%) of the 400 porters completed the trial (28 highlanders, 81 lowlanders). The rest either dropped out (275/400 porters, 68.8%) or were excluded (16/400 porters, 4%). Acute mountain sickness occurred in 13 (11.9%) of 109 porters; all were lowlanders; 7 were taking acetazolamide, 6 taking placebo. Birthplace, acclimatization in the week before the trial, ascent rate, and rest days were the most important variables affecting the incidence of AMS. No highlanders, but 13 (16.1%) of 81 lowlanders had AMS (P = .016). Acclimatization in the pretrial week reduced AMS incidence (P = .013), as did a slower ascent rate (P = .0126), but rest days were the most potent prophylactic variable (P = .0001). Side effects were more frequent in porters taking acetazolamide than in the placebo group (P = .0001), but there were no serious side effects., Conclusions: Acetazolamide was tolerable, but impractical for the routine prevention of AMS in Nepali porters. A good trekking schedule and adequate acclimatization remain the most effective preventive measures. This study identified lowland porters as a high-risk group for developing AMS.

Purpose: There are only anecdotal and small reports on brain systematic magnetic resonance imaging (MRI) studies in mountain climbers. The purpose of our work is to study the risk of brain lesions in mountain climbers by means of conventional MRI and magnetic resonance spectroscopy (MRS)., Methods: We recruited 35 climbers consecutively (12 were professional and 23 were amateur) in 4 expeditions without supplementary oxygen: 12 professionals and one amateur went up to Mt. Everest (8848 m), 8 amateurs to Mt. Aconcagua (6959 m), 7 amateurs to Mont Blanc (4810 m), and 7 amateurs to Mt. Kilimanjaro (5895 m). The mean age was 33.8 years (range: 22-46). All of them underwent general medical examination, standard blood tests, and MRI of the brain after the expeditions. MRI also was carried out in a control group of 20 healthy subjects. Single-voxel MR spectroscopy was carried out in 14 amateur subjects after the expeditions and in 10 healthy controls. As outcome measures, we evaluated changes in the hematocrit value, presence of cerebral lesions on MRI, as well as atrophy and dilatation of Virchow-Robin spaces, and differences in the metabolite ratios obtained from brain MRS in comparison with controls., Results: Only 1 in 13 of the Everest climbers had a normal MRI; the amateur showed frontal subcortical lesions, and the remainder had cortical atrophy and enlargement of Virchow-Robin spaces but no lesions. Among the remaining amateurs, 13 showed symptoms of high-altitude illness, 5 had subcortical irreversible lesions, and 10 had innumerable widened Virchow-Robin spaces. Conversely, we did not see any lesion in the control group. We found no significant differences in the metabolite ratios between climbers and controls., Conclusions: We conclude that there is enough evidence of brain damage after high altitude climbing; the amateur climbers seem to be at higher risk of suffering brain damage than professional climbers.

High altitude retinopathy (HAR) was first described in 1969 as engorgement of retinal veins with occasional papilloedema and vitreous hemorrhage. Since then various studies have attempted to define the incidence, etiology and significance of this phenomenon, usually with small numbers of subjects. Recently studies on relatively large groups of subjects in Nepal, Bolivia and Tibet have confirmed that the retinal vasculature becomes engorged and tortuous in all lowlanders ascending above 2500m. Sometimes this leads to hemorrhages, cotton wool spots and papilloedema, which is the pathological state better known as high altitude retinopathy. These studies have also shown a significant change in both corneal thickness and intraocular pressure at altitude. The retinal blood vessels are the only directly observable vascular system in the human body and also supply some of the most oxygen-demanding tissue, the photoreceptors of the retina. New techniques are being applied in both hypobaric chamber and field expeditions to observe changes in retinal function during conditions of hypobaric hypoxia. This work allows better advice to be given to lowlanders traveling to altitude either if they have pre-existing ocular conditions or if they suffer from visual problems whilst at altitude. This especially applies to the effect of altitude on refractive eye surgery and results of recent studies will be discussed so that physicians can advise their patients using the latest evidence. Retinal hypoxia at sea level accounts for the developed world's largest cause of blindness, diabetic retinopathy. The investigation of retinal response to hypobaric hypoxia in healthy subjects may open new avenues for treatment of this debilitating disease.

We describe a case report of a subject suffering high-altitude cerebral and pulmonary edema successfully treated with low flow rates of supplemental oxygen administered with a breathing system designed to conserve oxygen supplies at high altitude.

Circulating endothelial progenitor cells (EPCs) are believed to contribute to vascular homeostasis; unfortunately, the response of EPCs in physiological conditions remains largely unknown. Herein we report our observations of a 44-year-old healthy subject after a trek in the Himalayas that support high-altitude hypoxia and exercise oxygen demands are strong stimuli for clonogenic endothelial cell activation and activity, as shown by the increase in the number of mature EPCs and in the endothelial colony-forming unit capacity. Both of these effects were completely reverted at sea level, 45 days after the subject's trek., (2005 Wiley-Liss, Inc.)

Objective: To investigate the protective effects of oxygen therapy on gut barrier function of rabbits after hemorrhagic shock at high altitude., Methods: Fifteen rabbits were exposed to a simulated 4000 m high altitude in a hypobaric chamber, and they were randomly divided into two groups of treatment and control. Then hemorrhagic shock was induced through bleeding to mean artery pressure 40 mmHg (1 mmHg=0.133 kPa). After 1 hour, the rabbits were resuscitated with infusion of total volume of shed blood and balanced saline equivalent to 1.5 times of the shed blood. In addition, the animals of the treatment group were given oxygen therapy., Results: After 4 hours treatment, the mean arterial pressure of the treatment group was increased significantly in comparison with the control group, and the concentrations of plasma lactate in the former were significantly decreased after treatment for 4 hours and 8 hours. The plasma lipopolysaccharide levels in the treatment group were significantly lower than those in the control after treatment, and the histologic evidence of damage to the intestinal mucosa of the rabbits in the treatment group was less marked than that in the control group (P<0.05 or P<0.01)., Conclusion: Hemorrhagic shock at high altitude may cause disruption of the intestinal mucosa barrier and oxygen therapy could afford protection to the intestinal mucosa barrier in such circumstance.

As part of an emergency medical system protocol, national park service rangers certified at the level of an emergency medical technician-basic (EMT-B) are taught to recognize and treat high-altitude pulmonary edema and high-altitude cerebral edema. In Sequoia and Kings Canyon National Parks, this is done with the assistance of physician on-line medical control as a backup. High-altitude pulmonary edema and high-altitude cerebral edema are both potentially fatal altitude illnesses that can be particularly problematic in the backcountry, where evacuation may be delayed. We report a case of high-altitude pulmonary edema and high-altitude cerebral edema occurring at moderate altitude that was successfully treated by park rangers with the Gamow Bag.

Objective: To perform a pilot study exploring the prevalence of acute mountain sickness (AMS) in adolescents on ascent to altitude and evaluating whether this age group is capable of self-assessment of AMS using the Lake Louise scoring system., Methods: Twelve teenagers aged 15 to 18 years old (5 girls) traveled for 21 days between 2400 and 5500 m. Each member of the expedition completed a Lake Louise self-assessment questionnaire on a daily basis. Group leaders (nonmedical) were informed about any subject with a score of 3 or more. Appropriate treatments were then initiated. Detailed analysis of data was undertaken on return to the UK., Results: There was 100% completion of 252 questionnaires. Eleven of the 12 subjects (91.7%) had symptom scores greater than or equal to 3, consistent with a diagnosis of AMS, on at least one day (range, 0-8). Symptoms of AMS were more common in the female group members (P = .041)., Conclusions: AMS is a common problem among adolescents. There are increasing numbers of adolescents traveling to high altitudes, and there appears to be a lack of information about the prevalence of AMS in this age group. Motivated adolescents seemed capable of self-monitoring for AMS using the Lake Louise questionnaire. Combined with an appropriate ascent profile and support, we feel this approach may contribute to safety in the mountains and merits further study.

Free radical-mediated changes in vascular permeability and subsequent inflammatory response may be a contributory pathogenetic cofactor responsible for the development of neurological sequelae associated with acute mountain sickness (AMS). To investigate this, 49 subjects were examined at sea level and serially after rapid ascent to 4,559 m. Although the venous concentration of total creatine phosphokinase activity was measured in all subjects, a complementary examination of lipid peroxidation (F(2)-isoprostanes), inflammatory (TNF-alpha, IL-1beta, IL-2, IL-6, IL-8, C-reactive protein), and cerebrovascular tissue damage (neuron-specific enolase) biomarkers was confined to a subcohort of 24 subjects. A selective increase (P < 0.05) in total creatine phosphokinase was observed in subjects diagnosed with AMS at high altitude (n = 25) compared with apparently healthy controls (n = 24). However, despite a marked increase in IL-6 and C-reactive protein attributable primarily to subjects developing high-altitude pulmonary edema, subcohort analyses demonstrated no selective differences in F(2)-isoprostanes, neuron-specific enolase, or remaining proinflammatory cytokines due to AMS (n = 14). The present findings are the first to demonstrate that free radical-mediated neuronal damage of sufficient degree to be detected in the peripheral circulation does not occur and is, therefore, unlikely to be an important, initiating event that is critical for the development of AMS. The pathophysiological significance of increased sarcolemmal membrane permeability and inflammatory response, either as a cause or epiphenomenon of AMS and/or high-altitude pulmonary edema, remains to be elucidated.

Acute mountain sickness and high altitude cerebral edema are specific pathologies of high altitude exposure. The usual symptoms of acute mountain sickness are headache, nausea, vomiting, insomnia, lassitude, dizziness and ataxia. High altitude cerebral oedema is a severe state of acute mountain sickness with, in addition, alteration of mental status and consciousness. The pathophysiology of these 2 diseases are essentially due to an increase of intracranial pressure directly dependent of an increase of cerebral volume. Molecular and cellular mechanisms underlying acute mountain sickness and high altitude cerebral oedema are still poorly understood. The regulation of cerebral blood flow by nitric oxide seems to play a major role.

Objective: The major therapeutic effect of dexamethasone on persons affected by high-altitude illness may be upon vascular leakiness with a consequent decrease in cerebral edema. We set out to determine if dexamethasone ameliorates the cognitive/psychomotor effects of acute exposure to high altitude on asymptomatic subjects., Methods: Six adult subjects were tested at baseline (2500 m) with standard, computerized cognitive and psychomotor tests. Over the next 4 days, subjects were acclimatized to an altitude of 3700 m. On the fifth day, subjects ascended to 4800 m where predexamethasone testing was administered. No subject had symptoms of frank altitude illness at 4800 m. To limit acclimatization, subjects descended to 3700 m within 4 hours. The first 4-mg dose of oral dexamethasone was given in the evening of day 5. A second 4-mg dose of dexamethasone was given the following morning, and subjects reascended to 4800 m where postdexamethasone testing was performed., Results: All cognitive and psychomotor tests showed improved reaction times in subjects who were given dexamethasone. Mean reaction time (+/- SD) for shape recognition went from 1.20 +/- 0.36 seconds at 2500 m to 1.40 +/- 0.37 seconds at 4800 m. After dexamethasone administration, mean shape recognition time declined to 1.26 +/- 0.32 seconds (P = .052)., Conclusion: These data show a trend toward decreased cognitive deficits in subjects pretreated with dexamethasone. One possibility for this trend is that cognitive deficits in otherwise asymptomatic subjects exposed to high altitude are caused by subclinical cerebral edema.

This study investigates changes of adenylyl cyclase activity in the heart of young and adult Wistar rats exposed to experimental conditions simulating high altitude hypoxia as a model for interpretation of some adaptive changes of adenylyl cyclase observed in human. The exposure of rats to intermittent high altitude (IHA) hypoxia (5000 m) showed significant adaptive changes. The right ventricular weight and the ratio of right/left ventricular weights of adult rats exposed to IHA were significantly increased when compared to appropriate controls; adaptive changes of cardiac adenylyl cyclase being dependent on the age of the animals. The isoprenaline-stimulated activity was higher in the left than in the right ventricle, and in both ventricles it was higher in young rats than in adult rats. When compared to controls, isoprenaline stimulation was decreased in the right ventricles of adapted young rats and, by contrast, it was increased in the left ventricles of adapted adult rats. This decrease and increase of adenylyl cyclase activity evoked by isoprenaline was paralleled by forskolin-induced adenylyl cyclase activity in these experimental groups. It seems therefore that the changes in the pattern of total adenylyl cyclase activity observed under IHA hypoxia may at least be partially explained by the changes of beta-adrenergic receptor susceptibility following IHA hypoxia.

The present study examined the effects of high-altitude exposure on the pineal gland, the main source of production of melatonin. It was surmised that hypoxia experienced at high altitude, caused by decreased oxygen tension in the ambient air, might lead to some structural alterations in the pineal gland and, hence, affect its melatonin production. Adult Wistar rats were exposed to an altitude of 8,000 m for 2 hr in an altitude chamber and then sacrificed at various time intervals after the exposure. Normal rats kept at ground level were used as controls. Blood samples were collected at various time intervals for measurement of plasma melatonin level, and the pineal glands from both groups were processed for electron microscopy and immunohistochemistry. The plasma melatonin level showed a steady increase following altitude exposure peaking at 7 days and returned to control levels thereafter. Between 1 and 4 days after altitude exposure, the mitochondrial number and lipid droplets in the pinealocytes appeared to be reduced compared with those in control rats. At 7 days, however, the mitochondrial numbers and lipid droplets were noticeably increased. At the same time interval, the expression of complement type 3 receptors and major histocompatibility class II antigens as detected with the antibodies OX-42 and OX-6, respectively, in macrophages/microglia was up-regulated compared with that in the control rats and those killed at earlier times. This was attributed to the increased serum melatonin after the altitude exposure. By 14 and 21 days, the ultrastructure of pinealocytes and immunoreactivity of macrophages/microglia were comparable with those in the control rats. We conclude from this study that an altitude exposure in rats leads to an increase in melatonin production, which returned to control levels with passage of time., (Copyright 2002 Wiley-Liss, Inc.)

Objective: To investigate the changes of antioxidative capacity and endothelial function among patients with high altitude pulmonary edema (HAPE)., Methods: The serum levels of SOD, MDA, GSH, NO, NOS and ET-1 were measured before and after treatment among 34 cases of patients with HAPE, and 20 local healthy volunteers served as control., Results: The serum levels of SOD, GSH, NO and NOS were lower in patient-group before treatment than after treatment and those in control-group significantly (P < 0.01), while the concentration of MDA and ET-1 were higher in patient-group before treatment than after treatment and those in the control-group significantly (P < 0.01). The serum levels of SOD, MDA, GSH, NO, NOS and ET-1 were not different between patient-group after treatment and the control-group (P > 0.05)., Conclusion: The results indicated that changes of SOD, MDA, GSH, NO, NOS and ET-1 may participate in the course of HAPE.

High altitude retinal hemorrhages are commonly seen at altitudes above 4270 m. While these hemorrhages are generally asymptomatic, macular involvement may result in permanent visual acuity deficit. We present the case of a 29-year-old male recreational skier who traveled to a ski resort at 2930 m, ascended to 3470 m, and developed acute mountain sickness, high altitude pulmonary edema, and bilateral retinal hemorrhages. A funduscopic examination to determine if macular retinal hemorrhage is present may be performed by clinicians in the final assessment of patients following altitude illness.

In order to characterize the pathological features of high altitude pulmonary edema (HAPE) occurring at moderate altitude in Japan, we performed routine hematoxylin and eosin (HE) staining in lung materials from HAPE autopsied cases. We also undertook advanced immunohistochemical staining for observation of type II pneumocytes, pulmonary surfactant (PS), and mast cells in the lung of HAPE cases to examine the biological changes within the lung parenchyma. The pathological findings of HAPE were characterized by alveolar edema, congestion of pulmonary vessels, alveolar hyaline membranes, alveolar hemorrhage, and multithrombi and fibrin clots, but maintained alveolar structure. The immunostaining results showed that the type II pneumocytes were cellular fusion, deformity, and exfoliation from the walls of alveoli; the PS not only lined the alveolar surface, but was also patchily distributed within alveoli; and the number of mast cells were increased (9.0 +/- 0.9 cells/mm(2)) compared to that in controls (1.1 +/- 0.4 cells/mm(2)) (p < 0.01). We conclude that the pathological features of HAPE at moderate altitude in Japan are similar to others reported worldwide, and that the type II pneumocytes, PS, and mast cells may contribute to some extent to pathophysiological parts in the development and progression of HAPE.

We applied a novel MR imaging technique to investigate the effect of acute mountain sickness on cerebral tissue water. Nine volunteers were exposed to hypobaric hypoxia corresponding to 4572 m altitude for 32 h. Such an exposure may cause acute mountain sickness. We imaged the brains of the volunteers before and at 32 h of hypobaric exposure with two different MRI techniques with subsequent data processing. (1) Brain volumes were calculated from 3D MRI data sets by applying a computerized brain segmentation algorithm. For this specific purpose a novel adaptive 3D segmentation program was used with an automatic correction algorithm for RF field inhomogeneity. (2) T(2) decay rates were analyzed in the white matter. The results demonstrated that a significant brain swelling of 36.2 +/- 19.6 ml (2.77 +/- 1.47%, n = 9, P < 0.001) developed after the 32-h hypobaric hypoxia exposure with a maximal observed volume increase of 5.8% (71.3 ml). These volume changes were significant only for the gray matter structures in contrast to the unremarkable changes seen in the white matter. The same study repeated 3 weeks later in 6 of 9 original subjects demonstrated that the brains recovered and returned approximately to the initially determined sea-level brain volume while hypobaric hypoxia exposure once again led to a significant new brain swelling (24.1 +/- 12.1 ml, 1.92 +/- 0.96%, n = 6, P < 0.005). On the contrary, the T(2) mapping technique did not reveal any significant effect of hypobaria on white matter. We present here a technique which is able to detect reversible brain volume changes as they may occur in patients with diffuse brain edema or increased cerebral blood volume, and which may represent a useful noninvasive tool for future evaluations of antiedematous drugs., (Copyright 2001 Academic Press.)

This study examined the effects of high altitude exposure on neurons in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus in adult and neonatal rats. In adult control rats, occasional Fos-like immunoreactive neurons were localized in both the hypothalamic nuclei. A marked increase in Fos positive cells was induced at 1-4 h following altitude exposure but it was reduced to levels comparable to the controls at 24 h. The expression of neuronal nitric oxide synthase (nNOS) immunoreactivity in the PVN and SON followed a similar temporal pattern. The nNOS immunoreactivity, which was constitutively expressed in the hypothalamic neurons in the control rats, was noticeably augmented at 1-4 h, but it was comparable to the controls at 24 h following altitude exposure. In postnatal rats, Fos expression was not detected in the hypothalamic neurons of the controls. Induction of Fos expression was observed in some neurons at 1-4 h following altitude exposure but it was diminished at 24 h. There was no noticeable change in nNOS expression in both the control and altitude exposed postnatal rats; in both instances, it was barely detectable. It is concluded that both the PVN and SON of the adult rats are activated at high altitude exposure and that they may be involved in the regulation of neuroendocrine, cardiovascular and respiratory functions in hypobaric hypoxia. This study has also shown the differential response of the hypothalamus neurons between the two age groups to the hypoxic insult. Our results suggest that the adult neurons are probably more sensitive to the reduced oxygen levels in hypobaric hypoxia, as reflected by the upregulated NOS expression in this age group but not in the postnatal rats.

Aim and Methods: Contents of glutamate (Glu), asparate (Asp) and expression of prepro-somatostatin mRNA (PPS-mRNA) in rat hypothalamus were measured by using imitated altitude hypoxia rat model, amino acid analyzer and in situ hybridization technique., Results: After rats were subjected to altitude hypoxia, contents of Glu and Asp in hypothalamus and PPS-mRNA expression in periventricular nucleus (PeVN), paraventricular nucleus (PaVN) and arcuate nucleus (ArcN) were increased significantly. Ketamine, a NMDA receptor antagonist, could decrease the number of PPS-mRNA neurons in rat hypothalamus evoked by altitude hypoxia, but had no effect on Glu and Asp contents evoled by altitude hypoxia., Conclusion: It is suggested that somatostatin maybe paticipate in altitude hypoxia reaction, Glu can enhance PPS-mRNA expression through NMDA receptor.

Objective: To characterise the clinical features and nerve biopsy findings in patients with chronic mountain sickness (CMS) living in the Peruvian Andes, with particular attention to the occurrence of the "burning feet-burning hands" syndrome., Methods: Symptoms and signs were documented clinically in 10 patients with CMS and compared with those in five healthy subjects all living at 4338 metres altitude. Sural nerve biopsies were obtained from three patients with CMS. The nerve fibre population and endoneurial microvessels were analyzed morphometrically., Results: All patients with CMS experienced burning and tingling paraesthesiae in the distal parts of their limbs. Similar but milder symptoms confined to the feet occurred in four of five controls. Three patients with CMS had a mild sensory neuropathy on examination, controls were clinically normal. Nerve biopsies showed a mild demyelinating neuropathy in all three with a reduction in the unmyelinated axon population in one. The endoneurial blood vessels showed a reduced thickness in the basal laminal zone compared with control values but were otherwise normal., Conclusions: Apart from well recognised symptoms and signs of CMS, the study has shown that such patients may also exhibit a mild sensory neuropathy. Its relation to the burning feet-burning hands syndrome, which was not confined to the patients but was also found in controls at altitude, is uncertain. The time course and pattern of the centrifugal resolution of the burning paraesthesiae complex on low altitude sojourn of high altitude natives raises the possibility that a mechanism involving altered axonal transport may be involved. The reduced thickness of the basal laminal zone of microvessels implies that adaptive structural changes to hypobaric hypoxia may also occur in peripheral nerve and are similar to those reported in other tissues of high altitude natives.

A case of high altitude pulmonary oedema (HAPE) in a climber who made a rapid ascent on Mt McKinley (Denali), Alaska is described. The bronchoalveolar lavage (BAL) fluid contained increased numbers of red blood cells and an abundance of haemosiderin laden macrophages consistent with alveolar haemorrhage. The timing of this finding indicates that alveolar haemorrhage began early during the ascent, well before the onset of symptoms. Although evidence of alveolar haemorrhage has been reported at necropsy in individuals dying of HAPE, previous reports have not shown the same abundance of haemosiderin laden macrophages in the BAL fluid. These findings suggest that alveolar haemorrhage is an early event in HAPE.

High altitude has various effects on human beings. Altitude-related illnesses are a frequent cause of morbidity and occasional mortality in travelers to high altitudes throughout the world. The mountaineers all around the world are familiar with this condition, which is called acute mountain sickness (AMS). The primary altitude illnesses are AMS, high-altitude pulmonary edema and high-altitude cerebral edema. Altitude has potential undesired ophthalmological effects. The pathogenesis of these syndromes remains unclear despite considerable research in this field. Most of these problems are primarily preventable with an adequate level of information before and during travel. Further studies are needed to reveal the exact relationship between high altitude and ophthalmological findings. In this article, ophthalmological effects of high altitude, likely to be encountered by mountaineers as well as other enthusiasts of high altitude sports are reviewed. Emphasis on aviation and aerospace medicine is briefly given under related SUB&#95;TITLEs., (Copyright 2000 S. Karger AG, Basel.)

Autopsy findings in 10 cases of high-altitude pulmonary edema have been collected from published articles and personal observations. All cases were males with a mean age of 37 years (22-62). The altitude of occurrence was from 8400 to 17 500 feet. The mean combined lung weight in nine cases was 1682 g (1200-3000 g). Cerebral edema was present in five of eight cases. The most frequency pulmonary findings in addition to diffuse edema consisted of leukocyte infiltrates, alveolar hemorrhages, thrombi in small pulmonary arteries, and alveolar hyaline membranes. Pulmonary infarction was present in only one case. Right ventricular dilatation was commonly present. The left ventricle was normal. No significant coronary disease was present.

Hilltop (H) strain Sprague-Dawley rats are more susceptible to chronic mountain sickness than are the Madison (M) strain rats. It is unclear what role pulmonary vascular remodeling, polycythemia, and hypoxia-induced vasoconstriction play in mediating the more severe pulmonary hypertension that develops in the H rats during chronic hypoxia. It is also unclear whether the increased sensitivity of the H rats to chronic mountain sickness is specific for a hypoxia effect or, instead, reflects a general propensity toward the development of pulmonary hypertension. Monocrotaline (MCT) causes pulmonary vascular remodeling and pulmonary hypertension. We hypothesized that the difference in the pulmonary vascular response to chronic hypoxia between H and M rats reflects an increased sensitivity of the H rats to any pulmonary hypertensive stimuli. Consequently, we expected the two strains to also differ in their susceptibility to MCT-induced pulmonary hypertension. Pulmonary arterial pressures in conscious H and M rats were measured 3 wk after a single dose of MCT, exposure to a simulated high altitude of 18,000 ft (barometric pressure = 380 mmHg), and administration of a single dose of saline as a placebo. The H rats had significantly higher pulmonary arterial pressures and right ventricular weights after MCT and chronic hypoxia than did the M rats. The H rats also had more pulmonary vascular remodeling, i.e., greater wall thickness as a percentage of vessel diameter, after MCT and chronic hypoxia than did the M rats. The H rats had significantly lower arterial PO2 than did the M rats after MCT, but the degree of hypoxemia was mild [arterial PO2 of 72.5 +/- 0.8 (SE) Torr for H rats vs. 77.4 +/- 0.8 Torr for M rats after MCT]. The H rats had lower arterial PCO2 and larger minute ventilation values than did the M rats after MCT. These ventilatory differences suggest that MCT caused more severe pulmonary vascular damage in the H rats than in the M rats. These data support the hypothesis that the H rats have a general propensity to develop pulmonary hypertension and suggest that differences in pulmonary vascular remodeling account for the increased susceptibility of H rats, compared with M rats, to both MCT and chronic hypoxia-induced pulmonary hypertension.

1. The potential risk of brain damage when low-landers attempt to climb the highest summits is a well-known fact. However, very little is known about what occurs to Himalayan natives, perfectly adapted to high altitude, when performing the same type of activity. 2. Taking into account their long-life climbing experience at extreme altitudes, we examined seven of the most recognized Sherpas with the aim of performing a comprehensive neurological evaluation based on medical history, physical examination and magnetic resonance brain imaging. We compared them with one group of 21 lowland elite climbers who had ascended to altitudes of over 8000 m, and another control group of 21 healthy individuals who had never been exposed to high altitude. 3. While all of the lowland climbers presented psychoneurological symptoms during or after the expeditions, and 13 of them (61%) showed magnetic resonance abnormalities (signs of mild cortical atrophy and/or periventricular high-intensity signal areas in the white matter), only one Sherpa (14%) showed similar changes in the scans, presenting neurological symptoms at extreme altitude. The neurological examination was normal in all three groups, and no neuroimaging abnormalities were detected in the control group. 4. The significant differences, in both clinical and neuroimaging terms, suggest that Sherpa highlanders have better brain protection when exposed to extreme altitude. Although the key to protection against cerebral hypoxia cannot be established, it is possible that an increase in the usually short period of acclimatization could minimize brain damage in those low-landers who attempt the highest summits without supplementary oxygen.

The pathogenesis of high-altitude pulmonary oedema (HAPE) is disputed. Recent reports show a strong correlation between the occurrence of HAPE and pulmonary artery pressure, and it is known that the oedema is of the high-permeability type. We have, therefore, proposed that HAPE is caused by ultrastructural damage to pulmonary capillaries as a result of stress failure of their walls. However, no satisfactory electron microscopy studies are available in patients with HAPE, and animal models are difficult to find. Madison strain Sprague-Dawley rats show a brisk pulmonary pressure response to acute hypoxia and are susceptible to HAPE. We exposed 13 Madison rats to a pressure of 294 torr for up to 12.5 h, or 4 rats to 236 torr for up to 8 h. Pulmonary arterial or right ventricular systolic pressures measured with a catheter increased from 30.5 +/- 0.5 (SEM) in controls (n = 4) to 48 +/- 2 torr (n = 11). The lungs were fixed for electron microscopy with intravascular glutaraldehyde. Frothy bloodstained fluid was seen in the trachea of three animals. Ultrastructural examination showed evidence of stress failure of pulmonary capillaries, including disruption of the capillary endothelial layer, or all layers of the wall, swelling of the alveolar epithelial layer, red blood cells (RBCs) and oedematous fluid in the alveolar wall interstitium, proteinaceous fluid and RBCs in the alveolar spaces, and fluid-filled protrusions of the endothelium into the capillary lumen.(ABSTRACT TRUNCATED AT 250 WORDS)

Semen characteristics and testicular morphology of rhesus monkeys were studied on exposure to a simulated high altitude of 4411 m for 21 days. There was a partially reversible decrease in the semen volume, sperm count and sperm motility, as well as an elevation of pH and fructose concentration. These changes were associated with degeneration of the germinal epithelium and spermatogenic arrest at the end of third week of exposure which had not recovered even 3 weeks after the exposure.