Voluntary Increase of Minute Ventilation for Prevention of Acute Mountain Sickness.

This study evaluated the feasibility and efficacy of voluntary sustained hyperventilation during rapid ascent to high altitude for the prevention of acute mountain sickness (AMS). Study subjects (n=32) were volunteer participants in a 2-day expedition to Mount Leoneras (4954 m), starting at 2800m (base camp at 4120 m). Subjects were randomized to either: 1) an intervention group using the voluntary hyperventilation (VH) technique targeting an end-tidal CO2 (ETCO2)<20 mmHg; or 2) a group using acetazolamide (AZ). During the expedition, respiratory rate (28±20 vs. 18±5 breaths/min, mean±SD, P<0.01) and SpO2 (95%±4% vs. 89%±5%, mean±SD, P<0.01) were higher, and ETCO2 (17±4 vs. 26±4 mmHg, mean±SD, P<0.01) was lower in the VH group compared to the AZ group - as repeatedly measured at equal fixed intervals during the ascent - showing the feasibility of the VH technique. Regarding efficacy, the incidence of 6 (40%) subjects registering an LLS score≥3 in the VH group was non-inferior to the 3 (18%) subjects in the acetazolamide group (P=0.16, power 28%). Voluntary increase in minute ventilation is a feasible technique, but - despite the underpowered non-inferiority in this small-scale proof-of-concept trial - it is not likely to be as effective as acetazolamide to prevent AMS.

Poor Knowledge of Acute Mountain Sickness in Latin American Medical Students.

INTRODUCTION: Acute altitude exposure is a common event in Latin America that can result in mild to severe altitude illness. Medical students from some Latin American countries receive little information on this topic. Our aim was to determine the knowledge and incidence of acute mountain sickness (AMS), as well as the methods used to prevent AMS among medical students attending the Pan-American Student Meeting in Cusco, Peru, a city at high altitude (3400 m). METHODS: We conducted a cross-sectional study on medical students attending a conference. Participants completed a questionnaire on the day of registration that collected demographic data and investigated students' knowledge of AMS, its prophylaxis, and their personal experience of symptoms. RESULTS: A total of 840 students attended the meeting. Two hundred eighty-eight returned surveys, 51 from high altitude locations. Respondent age was 23±3 y (mean±SD), and 72% were female. Thirty-two percent had basic knowledge about symptoms of AMS. Headache was recognized as a symptom by 79%. Knowledge of AMS prophylaxis was reported by 70%. Coca leaf products and dimenhydrinate were mentioned by 30 and 16%, respectively, whereas acetazolamide was recognized by only 10% of participants. AMS incidence was 42%. Prophylactic measures were adopted by 47% of the participants in our study. Thirty-six percent used dimenhydrinate and 27% used coca tea. Less than 1% used acetazolamide as recommended. CONCLUSIONS: We found poor knowledge of AMS and effective prophylaxis among medical students from several South American countries traveling to 3400 m.

Risk factors for acute mountain sickness in travellers to Cusco, Peru: coca leaves, obesity and sex.

BACKGROUND: Acute mountain sickness (AMS) may occur after rapid ascents to altitudes >2500 m. Cusco (3350 m) in Peru is a popular destination for altitude inexperienced travellers. This study aimed at evaluating the incidence and risk factors for AMS among a cohort of foreign Spanish language students in Cusco. METHODS: We performed a cohort study among young healthy foreign Spanish language students arriving to Cusco between 2012 and 2016. Consenting students answered an enrollment questionnaire on demographics, travel history and intended AMS preventive behaviour within 48 h of arrival. At 4-5 days after enrollment participants answered a second questionnaire about actual preventive behaviour before symptoms and the development of symptoms compatible with AMS during their first 48 h in Cusco. We used the 2018 Lake Louise Scoring System for AMS diagnosis. Participants with headache and a score ≥ 3 were considered to have AMS. RESULTS: We enrolled 142 language students, the median age was 21 years (interquartile range 20-25) and 57% were female. Participants decreased physical activity (38%), increased fluid intake (34%), drank coca leaf tea (34%), took acetazolamide (16%) and acclimatized at a lower altitude (6%) to prevent AMS. Thirty-nine percent had AMS. In the multivariate analysis, obesity [odds ratio (OR) 14.45 (2.33-89.6)] and female sex [OR 4.32 (1.81-10.28)] were associated with increased risk of AMS. Taking acetazolamide [OR 0.13 (0.03-0.56)] was associated with decreased AMS risk. Consumption of coca leaf tea was not associated with decreased risk of AMS. CONCLUSIONS: In our cohort, AMS affected two out of five travellers. Obesity and female sex were associated with increased risk. Drinking coca leaf tea for prevention did not decrease the risk of AMS. Acetazolamide prophylaxis was associated with decreased risk of AMS.

Ibuprofen versus acetazolamide for prevention of acute mountain sickness. / Ibuprofeno comparado con acetazolamida para prevención de mal agudo de montaña.

INTRODUCTION: Acute mountain sickness is a common condition occurring in healthy subjects that undergo rapid ascent without prior acclimatization, as low as 2500 meters above sea level. The classic preventive agent has been acetazolamide, although in the last decade there has been evidence favoring ibuprofen. However, it is unclear which method is more efficient. METHODS: We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis) and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified two systematic reviews that included only one primary study, which is a randomized trial. We concluded it is not possible to establish whether ibuprofen is better or worse than acetazolamide because the certainty of evidence has been evaluated as very low.

INTRODUCCIÓN: El mal agudo de montaña es una condición frecuente en individuos sanos, sin aclimatación que se exponen a alturas desde 2500 metros sobre el nivel del mar. Clásicamente se ha utilizado acetazolamida para prevenirlo, pero en los últimos años ha surgido evidencia a favor de ibuprofeno. Sin embargo, no está claro cuál de estos tratamientos es más efectivo. MÉTODOS: Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos dos revisiones sistemáticas que en conjunto incluyeron un estudio primario, el cual corresponde a un ensayo aleatorizado. Concluimos que no es posible establecer con claridad si ibuprofeno es mejor o peor que acetazolamida debido a que la certeza de evidencia existente ha sido evaluada como muy baja.

Ibuprofeno comparado con acetazolamida para prevención de mal agudo de montaña / Ibuprofen versus acetazolamide for prevention of acute mountain sickness

INTRODUCCIÓN: El mal agudo de montaña es una condición frecuente en individuos sanos, sin aclimatación que se exponen a alturas desde 2500 metros sobre el nivel del mar. Clásicamente se ha utilizado acetazolamida para prevenirlo, pero en los últimos años ha surgido evidencia a favor de ibuprofeno. Sin embargo, no está claro cuál de estos tratamientos es más efectivo. MÉTODOS: Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos dos revisiones sistemáticas que en conjunto incluyeron un estudio primario, el cual corresponde a un ensayo aleatorizado. Concluimos que no es posible establecer con claridad si ibuprofeno es mejor o peor que acetazolamida debido a que la certeza de evidencia existente ha sido evaluada como muy baja.

INTRODUCTION: Acute mountain sickness is a common condition occurring in healthy subjects that undergo rapid ascent without prior acclimatization, as low as 2500 meters above sea level. The classic preventive agent has been acetazolamide, although in the last decade there has been evidence favoring ibuprofen. However, it is unclear which method is more efficient. METHODS: We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis) and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified two systematic reviews that included only one primary study, which is a randomized trial. We concluded it is not possible to establish whether ibuprofen is better or worse than acetazolamide because the certainty of evidence has been evaluated as very low.

Determining the Operating Costs of a Medical Surveillance Program for Copper Miners Exposed to High Altitude-Induced Chronic Intermittent Hypoxia in Chile Using a Combination of Microcosting and Time-Driven Activity-Based Costing.

BACKGROUND: Copper mining installations in Chile use a large number of workers who do their jobs at high altitudes, exposing them to the conditions of chronic intermittent hypobaric hypoxia. The Chilean Safety Association implements the surveillance program. OBJECTIVE: This organization, under the sponsorship of the Chilean Superintendency of Social Security, was interested in determining the costs involved in this program to support its decision-making processes and to improve its performance. METHODS: Direct operating costs of the Hypoxia Medical Surveillance Program were determined through on-site surveys applied to the organization's local agencies in charge. The microcosting method was used, quantifying personnel costs, consumables, and equipment and overhead costs. Time-driven activity-based costing was partially adapted for the allocation of personnel and equipment costs. Costs concerning activities, groups of activities and items, and average cost per exposed worker were determined. RESULTS: The annual costs of the program were $127 299.58. The highest costs corresponded to the assessment activities, which were $89 192.13, representing 60.06% of the total. The labor factor costs were $77 568.50, which represents 60.93% of the total. The average cost per worker in the program is $21.17. CONCLUSIONS: The partial adaptation of the time-driven activity-based costing method in combination with the microcosting method provides a suitable solution to determine the total costs of running a healthcare program of this kind. The information generated by this study will aid in the decision-making and management processes of the Hypoxia Medical Surveillance Program.

Interventions for preventing high altitude illness: Part 1. Commonly-used classes of drugs.

BACKGROUND: High altitude illness (HAI) is a term used to describe a group of cerebral and pulmonary syndromes that can occur during travel to elevations above 2500 metres (8202 feet). Acute hypoxia, acute mountain sickness (AMS), high altitude cerebral oedema (HACE) and high altitude pulmonary oedema (HAPE) are reported as potential medical problems associated with high altitude. In this review, the first in a series of three about preventive strategies for HAI, we assess the effectiveness of six of the most recommended classes of pharmacological interventions. OBJECTIVES: To assess the clinical effectiveness and adverse events of commonly-used pharmacological interventions for preventing acute HAI. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (OVID), Embase (OVID), LILACS and trial registries in January 2017. We adapted the MEDLINE strategy for searching the other databases. We used a combination of thesaurus-based and free-text terms to search. SELECTION CRITERIA: We included randomized-controlled and cross-over trials conducted in any setting where commonly-used classes of drugs were used to prevent acute HAI. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as expected by Cochrane. MAIN RESULTS: We included 64 studies (78 references) and 4547 participants in this review, and classified 12 additional studies as ongoing. A further 12 studies await classification, as we were unable to obtain the full texts. Most of the studies were conducted in high altitude mountain areas, while the rest used low pressure (hypobaric) chambers to simulate altitude exposure. Twenty-four trials provided the intervention between three and five days prior to the ascent, and 23 trials, between one and two days beforehand. Most of the included studies reached a final altitude of between 4001 and 5000 metres above sea level. Risks of bias were unclear for several domains, and a considerable number of studies did not report adverse events of the evaluated interventions. We found 26 comparisons, 15 of them comparing commonly-used drugs versus placebo. We report results for the three most important comparisons: Acetazolamide versus placebo (28 parallel studies; 2345 participants)The risk of AMS was reduced with acetazolamide (risk ratio (RR) 0.47, 95% confidence interval (CI) 0.39 to 0.56; I2 = 0%; 16 studies; 2301 participants; moderate quality of evidence). No events of HAPE were reported and only one event of HACE (RR 0.32, 95% CI 0.01 to 7.48; 6 parallel studies; 1126 participants; moderate quality of evidence). Few studies reported side effects for this comparison, and they showed an increase in the risk of paraesthesia with the intake of acetazolamide (RR 5.53, 95% CI 2.81 to 10.88, I2 = 60%; 5 studies, 789 participants; low quality of evidence). Budenoside versus placebo (2 parallel studies; 132 participants)Data on budenoside showed a reduction in the incidence of AMS compared with placebo (RR 0.37, 95% CI 0.23 to 0.61; I2 = 0%; 2 studies, 132 participants; low quality of evidence). Studies included did not report events of HAPE or HACE, and they did not find side effects (low quality of evidence). Dexamethasone versus placebo (7 parallel studies; 205 participants)For dexamethasone, the data did not show benefits at any dosage (RR 0.60, 95% CI 0.36 to 1.00; I2 = 39%; 4 trials, 176 participants; low quality of evidence). Included studies did not report events of HAPE or HACE, and we rated the evidence about adverse events as of very low quality. AUTHORS' CONCLUSIONS: Our assessment of the most commonly-used pharmacological interventions suggests that acetazolamide is an effective pharmacological agent to prevent acute HAI in dosages of 250 to 750 mg/day. This information is based on evidence of moderate quality. Acetazolamide is associated with an increased risk of paraesthesia, although there are few reports about other adverse events from the available evidence. The clinical benefits and harms of other pharmacological interventions such as ibuprofen, budenoside and dexamethasone are unclear. Large multicentre studies are needed for most of the pharmacological agents evaluated in this review, to evaluate their effectiveness and safety.

Coca: High Altitude Remedy of the Ancient Incas.

The use of coca leaf for medicinal purposes is a centuries-old tradition of the native peoples of South America. Coca products are thought by many laypersons to provide risk-free benefits to users participating in strenuous activities at high altitude. Physiologic studies of coca have increased understanding of its possible mechanism of action as well as its potential impact on high altitude activities. This present work explores the role of coca throughout the history of the Andean peoples and explores whether this ancient remedy has a place in modern medicine. A focused summary of research articles with particular relevance to the field of wilderness medicine is also included to better provide the reader with lessons not only from history but also from another culture.

A strategy for reducing neonatal mortality at high altitude using oxygen conditioning.

Neonatal mortality increases with altitude. For example, in Peru the incidence of neonatal mortality in the highlands has been shown to be about double that at lower altitudes. An important factor is the low inspired PO2 of newborn babies. Typically, expectant mothers at high altitude will travel to low altitude to have their babies if possible, but often this is not feasible because of economic factors. The procedure described here raises the oxygen concentration in the air of rooms where neonates are being housed and, in effect, this means that both the mother and baby are at a much lower altitude. Oxygen conditioning is similar to air conditioning except that the oxygen concentration of the air is increased rather than the temperature being reduced. The procedure is now used at high altitude in many hotels, dormitories and telescope facilities, and has been shown to be feasible and effective.

Oxigenación cerebral en habitantes de gran altura con y sin hipertensión pulmonar de altura / Cerebral oxygenation in high altitude inhabitants with and without high altitude pulmonary hypertension

La Hipertensión pulmonar de gran altura (HAPH),una enfermedad crónica relacionada con laaltura, que causa hipoxemia y un deterioro enel rendimiento del ejercicio. Se ha evaluadola hipótesis que, la limitación hemodinámicae hipoxemia en pacientes con (HAPH), estánasociados con un deterioro en la oxigenación deltejido cerebral (CTO), comparados con habitantes...

Serious altitude illness in travelers who visited a pre-travel clinic.

BACKGROUND: Few data are available on the incidence and predictors of serious altitude illness in travelers who visit pre-travel clinics. Travel health consultants advise on measures to be taken in case of serious altitude illness but it is not clear if travelers adhere to these recommendations. METHODS: Visitors to six travel clinics who planned to travel to an altitude of ≥3,000 m were asked to complete a diary from the first day at 2,000 m until 3 days after reaching the maximum sleeping altitude. Serious altitude illness was defined as having symptoms of serious acute mountain sickness (AMS score ≥ 6) and/or cerebral edema and/or pulmonary edema. RESULTS: The incidence of serious altitude illness in the 401 included participants of whom 90% reached ≥4,000 m, was 35%; 23% had symptoms of serious AMS, 25% symptoms of cerebral edema, and 13% symptoms of pulmonary edema. Independent predictors were young age, the occurrence of dark urine, travel in South America or Africa, and lack of acclimatization between 1,000 and 2,500 m. Acetazolamide was brought along by 77% of the responders of whom 41% took at least one dose. Of those with serious altitude illness, 57% had taken at least one dose of acetazolamide, 20% descended below 2,500 m on the same day or the next, and 11% consulted a physician. CONCLUSIONS: Serious altitude illness was a very frequent problem in travelers who visited pre-travel clinics. Young age, dark urine, travel in South America or Africa, and lack of acclimatization nights at moderate altitude were independent predictors. Furthermore, we found that seriously ill travelers seldom followed the advice to descend and to visit a physician.

Network analysis reveals distinct clinical syndromes underlying acute mountain sickness.

Acute mountain sickness (AMS) is a common problem among visitors at high altitude, and may progress to life-threatening pulmonary and cerebral oedema in a minority of cases. International consensus defines AMS as a constellation of subjective, non-specific symptoms. Specifically, headache, sleep disturbance, fatigue and dizziness are given equal diagnostic weighting. Different pathophysiological mechanisms are now thought to underlie headache and sleep disturbance during acute exposure to high altitude. Hence, these symptoms may not belong together as a single syndrome. Using a novel visual analogue scale (VAS), we sought to undertake a systematic exploration of the symptomatology of AMS using an unbiased, data-driven approach originally designed for analysis of gene expression. Symptom scores were collected from 292 subjects during 1110 subject-days at altitudes between 3650 m and 5200 m on Apex expeditions to Bolivia and Kilimanjaro. Three distinct patterns of symptoms were consistently identified. Although fatigue is a ubiquitous finding, sleep disturbance and headache are each commonly reported without the other. The commonest pattern of symptoms was sleep disturbance and fatigue, with little or no headache. In subjects reporting severe headache, 40% did not report sleep disturbance. Sleep disturbance correlates poorly with other symptoms of AMS (Mean Spearman correlation 0.25). These results challenge the accepted paradigm that AMS is a single disease process and describe at least two distinct syndromes following acute ascent to high altitude. This approach to analysing symptom patterns has potential utility in other clinical syndromes.

Role of maca (Lepidium meyenii) consumption on serum interleukin-6 levels and health status in populations living in the Peruvian Central Andes over 4000 m of altitude.

Lepidium meyenii (Maca) is a plant that grows at over 4,000 m above sea level in the central Peruvian Andes. The hypocotyls of this plant are traditionally consumed for their nutritional and medicinal properties. The aim of this study was to determine the health status based on a health related quality of life (HRQL) questionnaire (SF-20) and serum levels of interleukin 6 (IL-6) in subjects that are maca consumers. For this, a cross-sectional study was designed to be performed in 50 subjects from Junin (4,100 m): 27 subjects were maca consumers and 23 were non-consumers. The SF-20 survey is used to obtain a summary measure of health status. The stand up from a chair and sit down (SUCSD) test (to assess lower-extremity function), hemoglobin measurement, blood pressure, sexual hormone levels, serum IL-6 levels and the score of chronic mountain sickness (CMS) were evaluated. Testosterone/estradiol ratio (P <0.05), IL-6 (P < 0.05) and CMS score were lower, whereas the health status score was higher, in maca consumers when compared to non-consumers (P < 0.01). A greater proportion of maca consumers successfully completed the SUCSD test compared to non-consumers (P < 0.01), showing a significant association with lower values of serum IL-6 (P < 0.05). In conclusion, consumption of maca was associated with low serum IL-6 levels and in turn with better health status scores in the SF-20 survey and low chronic mountain sickness scores.

Acute mountain sickness impact among travelers to Cusco, Peru.

BACKGROUND: Increasing numbers of travelers are visiting high altitude locations in the Andes. The epidemiology of acute mountain sickness (AMS) among tourists to high altitude in South America is not well understood. METHODS: A cross-sectional study to evaluate the epidemiology, pre-travel preparation, and impact of AMS among travelers to Cusco, Peru (3,400 m) was performed at Cusco's International Airport during June 2010. Foreign travelers, 18 years or older, staying 15 days or less, departing Cusco were invited to participate. Demographic, itinerary, and behavioral data were collected. The Lake Louise Clinical score (LLCS) was used to assess AMS symptoms. RESULTS: In total, 991 travelers participated, median age 32 years (interquartile range 25-49), 55.5% female, 86.7% tourists, mostly from the United States (48.2%) and England (8.1%). Most (76.7%) flew from sea level to Cusco and 30.5% visited high altitude in the previous 2 months. Only 29.1% received AMS advice from a physician, 19% recalled advice on acetazolamide. Coca leaf products (62.8%) were used more often than acetazolamide (16.6%) for prevention. AMS was reported by 48.5% and 17.1% had severe AMS. One in five travelers with AMS altered their travel plans. Travelers older than 60 years, with recent high altitude exposure, who visited lower cities in their itinerary, or used acetazolamide were less likely to have AMS. Using coca leaf products was associated with increased AMS frequency. CONCLUSIONS: AMS was common and adversely impacted plans of one in five travelers. Acetazolamide was associated with decreased AMS but was prescribed infrequently. Other preventive measures were not associated with a decrease in AMS in this population. Pre-travel preparation was suboptimal.

Postexercise peripheral oxygen saturation after completion of the 6-minute walk test predicts successfully reaching the summit of Aconcagua.

OBJECTIVE: The 6-minute walk test (6MWT) is a single measurement of functional status in patients with cardiovascular disease. It has not been studied at high altitude. We investigate the screening value of 6-minute walk distance (6MWD) and postexercise vital sign (VS) measurements as predictors of successfully reaching the summit or development of acute mountain sickness (AMS) on Aconcagua (6962 m). METHODS: Prospective observational cohort in Aconcagua Provincial Park, Argentina. Adults climbing the normal route who registered with base camp physicians were included. There were no exclusion criteria. VSs were measured before (resting) and after (postexercise) completion of 6MWT while volunteers acclimatized at Plaza de Mulas base camp (4365 m). Volunteers proceeded towards the summit at their own pace and upon descent returned a questionnaire with maximum altitude reached and Lake Louise AMS Self-report Score (LLSelf). RESULTS: One hundred twenty-four volunteers completed the 6MWT. Sixty-four volunteers (51.6%) completed questionnaires; 56% summited. Median LLSelf was 4 (IQR: 3.0-6.5). There was no association between any resting or postexercise VS measurements and AMS. However, mean postexercise SpO(2) was 80.8% in summiters and 76.4% in nonsummiters, a difference of -4.4% (95% CI: -6.7 to -2.0, p = 0.0005). Postexercise SpO(2) < 75% had 97.2% sensitivity and negative likelihood ratio of 0.086 in predicting the outcome of successfully reaching the summit: only one climber with SpO(2) < 75% successfully reached the summit. CONCLUSIONS: This study provides the first published data on 6MWD recorded in the field at high altitude. Postexercise SpO(2) < 75% may be a useful screening test for predicting the outcome of successfully reaching the summit of Aconcagua.

Oxidative stress in rat testis and epididymis under intermittent hypobaric hypoxia: protective role of ascorbate supplementation.

Hypobaric hypoxia (HH), an environmental condition of high altitude encountered by mountaineers, miners, and observatory, rural health, border patrol, and rural education workers, jeopardizes normal physiologic functions in humans. The present study was conducted to evaluate the effects of intermittent HH (IHH; equivalent to 4600 m above mean sea level) on oxidative stress and the protective role of dietary ascorbic acid on rat testis and epididymis. Ten-week-old male Wistar rats were assigned to 1 of 6 groups: 1) normobaric (Nx), 2) Nx + physiologic solution (Nx + PS), 3) Nx + ascorbic acid (Nx + AA), 4) IHH, 5) IHH + PS, or 6) IHH + AA. Animals subjected to IHH were exposed for 96 hours followed by normobaric conditions for 96 hours for a total of 32 days. The control groups (2 and 5) were injected with doses of PS, and the treated groups (3 and 6) were injected with doses of AA (10 mg x kg(-1) body weight) at an interval of 96 hours. Rats were sacrificed on day 32 after initiation of the protocol. The testis and epididymis were collected to determine the activity and expression of glutathione reductase and the levels of lipid peroxide formation. An epididymal sperm count was also performed in each animal. The results of this study revealed that IHH induced lipid peroxidation, a reduction in glutathione reductase activity in testis and epididymis, and a significant decrease in epididymal sperm count. Treatment with AA prevented these changes. In conclusion, AA was capable of decreasing oxidative stress in testis and epididymis under IHH. This protection by AA of the IHH-induced lipid peroxidation can be explained in part by the preservation of glutathione reductase activity in these organs.