RESUMO
Medical personnel need practical guidelines on how to construct high altitude ascents to induce altitude acclimatization and avoid acute mountain sickness (AMS) following the first night of sleep at high altitude. Using multiple logistic regression and a comprehensive database, we developed a quantitative prediction model using ascent profile as the independent variable and altitude acclimatization status as the dependent variable from 188 volunteers (147 men, 41 women) who underwent various ascent profiles to 4 km. The accumulated altitude exposure (AAE), a new metric of hypoxic dose, was defined as the ascent profile and was calculated by multiplying the altitude elevation (km) by the number of days (d) at that altitude prior to ascent to 4 km. Altitude acclimatization status was defined as the likely presence or absence of AMS after ~24 h of exposure at 4 km. AMS was assessed using the Cerebral Factor Score (AMS-C) from the Environmental Symptoms Questionnaire and deemed present if AMS-C was ≥0.7. Other predictor variables included in the model were age and body mass index (BMI). Sex, race, and smoking status were considered in model development but eliminated due to inadequate numbers in each of the ascent profiles. The AAE (km·d) significantly (P < 0.0001) predicted AMS in the model. For every 1 km·d increase in AAE, the odds of getting sick decreased by 41.3%. Equivalently, for every 1 km·d decrease in AAE, the odds of getting sick increased by 70.4%. Age and BMI were not significant predictors. The model demonstrated excellent discrimination (AUC = 0.83 (95% CI = 0.79-0.91) and calibration (Hosmer-Lemeshow = 0.11). The model provides a priori estimates of altitude acclimatization status resulting from the use of various rapid, staged, and graded ascent profiles.
Assuntos
Aclimatação/fisiologia , Doença da Altitude/diagnóstico , Hipóxia/fisiopatologia , Adolescente , Adulto , Idoso , Altitude , Doença da Altitude/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Medição de Risco , Fatores de Tempo , Adulto JovemRESUMO
PURPOSE: Despite decades of research, no predictive models of acute mountain sickness (AMS) exist, which identify the time course of AMS severity and prevalence following rapid ascent to various altitudes. METHODS: Using general linear and logistic mixed models and a comprehensive database, we analyzed 1292 AMS cerebral factor scores in 308 unacclimatized men and women who spent between 4 and 48 h at altitudes ranging from 1659 to 4501 m under experimentally controlled conditions (low and high activity). Covariates included in the analysis were altitude, time at altitude, activity level, age, body mass index, race, sex, and smoking status. RESULTS: AMS severity increased (P < 0.05) nearly twofold (i.e., 179%) for every 1000-m increase in altitude at 20 h of exposure, peaked between 18 and 22 h of exposure, and returned to initial levels by 48 h of exposure regardless of sex or activity level. Peak AMS severity scores were 38% higher (P < 0.05) in men compared with women at 20 h of exposure. High active men and women (>50% of maximal oxygen uptake for >45 min at altitude) demonstrated a 72% increase (P < 0.05) in the odds (odds ratio, 1.72; confidence interval, 1.03-3.08) of AMS compared with low active men and women. There was also a tendency (P = 0.10) for men to demonstrate greater odds of AMS (odds ratio, 1.65; confidence interval, 0.84-3.25) compared with women. Age, body mass index, race, and smoking status were not significantly associated with AMS. CONCLUSIONS: These models provide the first quantitative estimates of AMS risk over a wide range of altitudes and time points and suggest that in addition to altitude and time at altitude, high activity increases the risk of developing AMS. In addition, men demonstrated increased severity but not prevalence of AMS.
Assuntos
Doença da Altitude/etiologia , Modelos Biológicos , Aclimatação/fisiologia , Doença Aguda , Adolescente , Adulto , Doença da Altitude/fisiopatologia , Intervalos de Confiança , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Medição de Risco , Fatores Sexuais , Fatores de Tempo , Adulto JovemRESUMO
Staged ascent (SA), temporary residence at moderate altitude en route to high altitude, reduces the incidence and severity of noncardiopulmonary altitude illness such as acute mountain sickness. To date, the impact of SA on pulmonary arterial pressure (PAP) is unknown. We tested the hypothesis that SA would attenuate the PAP increase that occurs during rapid, direct ascent (DA). Transthoracic echocardiography was used to estimate mean PAP in 10 healthy males at sea level (SL, P(B) approximately 760 torr), after DA to simulated high altitude (hypobaric chamber, P(B) approximately 460 torr), and at 2 times points (90 min and 4 days) during exposure to terrestrial high altitude (P(B) approximately 460 torr) after SA (7 days, moderate altitude, P(B) approximately 548 torr). Alveolar oxygen pressure (Pao(2)) and arterial oxygenation saturation (Sao(2)) were measured at each time point. Compared to mean PAP at SL (mean +/- SD, 14 +/- 3 mmHg), mean PAP increased after DA to 37 +/- 8 mmHg (Delta = 24 +/- 10 mmHg, p < 0.001) and was negatively correlated with both Pao(2) (r(2) = 0.57, p = 0.011) and Sao(2) (r(2) = 0.64, p = 0.005). In comparison, estimated mean PAP after SA increased to only 25 +/- 4 mmHg (Delta = 11 +/- 6 mmHg, p < 0.001), remained unchanged after 4 days of high altitude residence (24 +/- 5 mmHg, p = not significant, or NS), and did not correlate with either parameter of oxygenation. SA significantly attenuated the PAP increase associated with continuous direct ascent to high altitude and appeared to uncouple PAP from both alveolar hypoxia and arterial hypoxemia.
Assuntos
Adaptação Fisiológica/fisiologia , Doença da Altitude/fisiopatologia , Montanhismo/fisiologia , Consumo de Oxigênio/fisiologia , Artéria Pulmonar/fisiologia , Adulto , Doença da Altitude/sangue , Ambiente Controlado , Hemodinâmica/fisiologia , Humanos , Masculino , Experimentação Humana não Terapêutica , Alvéolos Pulmonares/fisiologia , Troca Gasosa Pulmonar/fisiologia , Valores de Referência , Adulto JovemRESUMO
PURPOSE: This study tested the hypothesis that antioxidant supplementation would attenuate plasma cytokine (IL-6, tumor necrosis factor (TNF)-alpha), and C-reactive protein (CRP) concentrations at rest and in response to exercise at 4300-m elevation. METHODS: A total of 17 recreationally trained men were matched and assigned to an antioxidant (N = 9) or placebo (N = 8) group in a double-blinded fashion. At sea level (SL), energy expenditure was controlled and subjects were weight stable. Then, 3 wk before and throughout high altitude (HA), an antioxidant supplement (10,000 IU beta-carotene, 200 IU alpha-tocopherol acetate, 250 mg ascorbic acid, 50 microg selenium, 15 mg zinc) or placebo was given twice daily. At HA, energy expenditure increased approximately 750 kcal.d(-1) and energy intake decreased approximately 550 kcal.d, resulting in a caloric deficit of approximately 1200-1500 kcal.d(-1). At SL and HA day 1 (HA1) and day HA13, subjects exercised at 55% of VO2peak until they expended approximately 1500 kcal. Blood samples were taken at rest, end of exercise, and 2, 4, and 20 h after exercise. RESULTS: No differences were seen between groups in plasma IL-6, CRP, or TNF-alpha at rest or in response to exercise. For both groups, plasma IL-6 concentration was significantly higher at the end of exercise, 2, 4, and 20 h after exercise at HA1 compared with SL and HA13. Plasma CRP concentration was significantly elevated 20 h postexercise for both groups on HA1 compared to SL and HA13. TNF-alpha did not differ at rest or in response to exercise. CONCLUSION: Plasma IL-6 and CRP concentrations were elevated following exercise at high altitude on day 1, and antioxidant supplementation did not attenuate the rise in plasma IL-6 and CRP concentrations associated with hypoxia, exercise, and caloric deficit.
Assuntos
Altitude , Antioxidantes/administração & dosagem , Proteína C-Reativa/metabolismo , Exercício Físico/fisiologia , Interleucina-6/sangue , Fator de Necrose Tumoral alfa/metabolismo , Adulto , Análise de Variância , Composição Corporal , Catecolaminas/sangue , Método Duplo-Cego , Ingestão de Energia , Metabolismo Energético , Humanos , Masculino , Estudos Prospectivos , Inquéritos e QuestionáriosRESUMO
INTRODUCTION: Hypobaric hypoxia and heightened metabolic rate increase free radical production. PURPOSE: We tested the hypothesis that antioxidant supplementation would reduce oxidative stress associated with increased energy expenditure (negative energy balance) at high altitude (HA 4300 m). METHODS: For 12 d at sea level (SL), 18 active men were fed a weight-stabilizing diet. Testing included fasting blood and 24-h urine samples to assess antioxidant status [plasma alpha-tocopherol, beta-carotene, lipid hydroperoxides (LPO), and urinary 8-hydroxydeoxyguanosine (8-OHdG)] and a prolonged submaximal (55% Vo2peak) oxidative stress index test (OSI) to evaluate exercise-induced oxidative stress (plasma LPO, whole blood reduced and oxidized glutathione, glutathione peroxidase, and urinary 8-OHdG). Subjects were then matched and randomly assigned to either a placebo or antioxidant supplement group for a double-blinded trial. Supplementation (20,000 IU of beta-carotene, 400 IU alpha-tocopherol acetate, 500 mg ascorbic acid, 100 microg selenium, and 30 mg zinc, or placebo) was begun 3 wk prior to and throughout a 14-d HA intervention. At HA, subjects' daily energy intake and expenditure were adjusted to achieve a caloric deficit of approximately 1400 kcal. Fasting blood and 24-h urine samples were collected throughout HA and the OSI test was repeated on HA day 1 and day 13. RESULTS: Resting LPO concentrations increased and urinary 8-OHdG concentrations decreased over HA with no effect of supplementation. Prolonged submaximal exercise was not associated with increased concentrations of oxidative stress markers at SL or HA. CONCLUSIONS: Antioxidant supplementation did not significantly affect markers of oxidative stress associated with increased energy expenditure at HA.
Assuntos
Doença da Altitude/prevenção & controle , Doença da Altitude/fisiopatologia , Antioxidantes/farmacologia , Exercício Físico/fisiologia , Estresse Oxidativo , Adulto , Antioxidantes/uso terapêutico , Dano ao DNA , Dieta , Método Duplo-Cego , Humanos , Peroxidação de Lipídeos , Masculino , PlacebosRESUMO
BACKGROUND: Acute Mountain Sickness (AMS) is a multi-system disorder that is characterized by headache, anorexia, nausea, vomiting, insomnia, lassitude, and malaise. The syndrome is common in unacclimatized low altitude residents who rapidly ascend to terrestrial elevations exceeding 2,500 m. AMS may be a manifestation of hypoxia-induced cerebral edema resulting, in part, from increased capillary permeability. HYPOTHESIS: We hypothesized that cysteinyl leukotrienes (CysLTs) may be involved in the pathogenesis of AMS, as these compounds are known to increase endothelial permeability. METHODS: To test this hypothesis, we orally administered a CysLTs type-1 receptor antagonist (montelukast) to 11 subjects prior to and during exposure to high altitude (4,300 m) in a hypobaric chamber in a randomized, placebo-controlled, crossover design. We measured the resulting prevalence and/or severity of AMS, plasma CysLTs levels and urinary CysLTE4, and associated physiological responses. RESULTS: At 12 h exposure, AMS prevalence and symptom severity was lower (p = 0.002) during montelukast administration compared with placebo, but not different at 22 h exposure. Plasma CysLTs and urinary LTE4 levels were not significantly elevated at 22 h exposure, nor did these CysLTs levels correlate with AMS severity. Compared with placebo, montelukast administration was not associated with any significant differences in physiologic measures at sea level or high altitude. CONCLUSIONS: These results do not support a role for the CysLTs mediating the early development of AMS through the CysLT-1 receptor.
Assuntos
Acetatos/farmacologia , Doença da Altitude/metabolismo , Doença da Altitude/prevenção & controle , Cisteína/metabolismo , Antagonistas de Leucotrienos/farmacologia , Leucotrienos/metabolismo , Quinolinas/farmacologia , Acetatos/administração & dosagem , Administração Oral , Adulto , Doença da Altitude/fisiopatologia , Análise de Variância , Cromatografia Líquida de Alta Pressão , Estudos Cross-Over , Ciclopropanos , Método Duplo-Cego , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Antagonistas de Leucotrienos/administração & dosagem , Masculino , Prevalência , Quinolinas/administração & dosagem , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Sulfetos , Resultado do TratamentoRESUMO
PURPOSE: The purpose of this study was to determine whether substrate oxidation during submaximal exercise in women is affected by an acute exposure to 4300-m altitude and menstrual cycle phase. METHODS: Eight female lowlanders (mean +/- SD; 33 +/- 3 yr, 58 +/- 6 kg, 163 +/- 8 cm) completed a peak oxygen uptake (VO2peak) and submaximal exercise to exhaustion (EXH) test at 70% of their altitude-specific VO2peak at sea level (SL) and during an acute altitude (AA) exposure to 4300 m in a hypobaric chamber (446 mm Hg) in their early-follicular and midluteal menstrual cycle phase. The respiratory exchange ratio (RER) was calculated from oxygen uptake and carbon dioxide output measurements made during the EXH tests, and used to estimate the percent contribution of fat and carbohydrate to energy metabolism. Blood samples were taken at rest and every 15 min during the EXH tests. Blood samples were evaluated for glucose, lactate, glycerol, free fatty acids, insulin, growth hormone, cortisol, glucagon, epinephrine, norepinephrine, estradiol, and progesterone concentrations. RESULTS: Despite increased (P < 0.05) estradiol and progesterone levels in the midluteal phase, substrate oxidation, energy substrates, and metabolic hormones were not affected by cycle phase at SL or AA. However, free fatty acids and cortisol were increased (P < 0.05) whereas RER was decreased (P < 0.05) during exercise upon AA exposure compared with SL in both cycle phases. CONCLUSIONS: These data suggest that substrate oxidation is altered in women during exercise at AA compared with SL but is not affected by cycle phase. Whether increased fat or protein oxidation accounts for the lower RER values during the AA exposure cannot be determined from this study but warrants further investigation.