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1.
Physiol Rep ; 8(24): e14615, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33340275

RESUMO

Recent reports suggest that high-altitude residence may be beneficial in the novel coronavirus disease (COVID-19) implicating that traveling to high places or using hypoxic conditioning thus could be favorable as well. Physiological high-altitude characteristics and symptoms of altitude illnesses furthermore seem similar to several pathologies associated with COVID-19. As a consequence, high altitude and hypoxia research and related clinical practices are discussed for potential applications in COVID-19 prevention and treatment. We summarize the currently available evidence on the relationship between altitude/hypoxia conditions and COVID-19 epidemiology and pathophysiology. The potential for treatment strategies used for altitude illnesses is evaluated. Symptomatic overlaps in the pathophysiology of COVID-19 induced ARDS and high altitude illnesses (i.e., hypoxemia, dyspnea…) have been reported but are also common to other pathologies (i.e., heart failure, pulmonary embolism, COPD…). Most treatments of altitude illnesses have limited value and may even be detrimental in COVID-19. Some may be efficient, potentially the corticosteroid dexamethasone. Physiological adaptations to altitude/hypoxia can exert diverse effects, depending on the constitution of the target individual and the hypoxic dose. In healthy individuals, they may optimize oxygen supply and increase mitochondrial, antioxidant, and immune system function. It is highly debated if these physiological responses to hypoxia overlap in many instances with SARS-CoV-2 infection and may exert preventive effects under very specific conditions. The temporal overlap of SARS-CoV-2 infection and exposure to altitude/hypoxia may be detrimental. No evidence-based knowledge is presently available on whether and how altitude/hypoxia may prevent, treat or aggravate COVID-19. The reported lower incidence and mortality of COVID-19 in high-altitude places remain to be confirmed. High-altitude illnesses and COVID-19 pathologies exhibit clear pathophysiological differences. While potentially effective as a prophylactic measure, altitude/hypoxia is likely associated with elevated risks for patients with COVID-19. Altogether, the different points discussed in this review are of possibly some relevance for individuals who aim to reach high-altitude areas. However, due to the ever-changing state of understanding of COVID-19, all points discussed in this review may be out of date at the time of its publication.


Assuntos
Aclimatação , Doença da Altitude/fisiopatologia , Altitude , /fisiopatologia , Doença da Altitude/epidemiologia , Doença da Altitude/terapia , Animais , /terapia , Humanos , Prevalência , Prognóstico , Fatores de Proteção , Medição de Risco , Fatores de Risco
2.
Life Sci ; 266: 118873, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33309718

RESUMO

AIMS: Hypoxia-inducible factors (HIFs) play important roles in the pathogenesis of erythrocytosis in chronic mountain sickness (CMS). von Hippel-Lindau (VHL) is a key regulator of hypoxia that can direct the poly-ubiquitylation and degradation of HIFs. Epigenetic mechanisms are believed to contribute toward adaption to chronic hypoxia. Here, we investigated the contribution and mechanism of VHL methylation in rats with erythrocytosis in CMS. MAIN METHODS: The methylation status of VHL was measured via bisulfite sequencing PCR, while VHL, DNMT1, DNMT3α, and DNMT3ß expression were assessed using real-time reverse transcription PCR and western blotting. HIF-2α and EPO expression levels in bone marrow were determined via immunohistochemical staining, and erythroid hyperplasia in bone marrow sections were observed with hematoxylin and eosin staining. KEY FINDINGS: We found that chronic hypoxia triggered erythroid hyperplasia in the bone marrow and increased the quantity of peripheral red blood cells in CMS rats. Chronic hypoxia significantly induced methylation at the CpG site in the VHL promoter, decreased VHL expression, and increased HIF-2α and EPO expression. Chronic hypoxia increased DNMT3α and DNMT3ß expression, consistent with the decrease in VHL expression. The DNA methyltransferase inhibitor 5-azacytidine reduced chronic hypoxia-induced erythroid proliferation in the bone marrow of rats with CMS by suppressing VHL methylation and DNMTs expression. SIGNIFICANCE: Our study suggests that VHL methylation contributes toward excessive erythrocytosis in CMS by upregulating the HIF-2α/EPO pathway in the bone marrow of rats. We demonstrated that the DNMT inhibitor 5-azacytidine can attenuate erythroid hyperplasia in the bone marrow by demethylating the VHL promoter.


Assuntos
Doença da Altitude/fisiopatologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Metilação de DNA , Eritropoetina/metabolismo , Hipóxia/fisiopatologia , Policitemia/patologia , Proteína Supressora de Tumor Von Hippel-Lindau/metabolismo , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Doença Crônica , Modelos Animais de Doenças , Eritropoetina/genética , Regulação da Expressão Gênica , Masculino , Policitemia/genética , Policitemia/metabolismo , Ratos , Ratos Sprague-Dawley , Proteína Supressora de Tumor Von Hippel-Lindau/genética
3.
Rev. med. cine ; 16(4): 261-277, dic. 2020. ilus
Artigo em Espanhol | IBECS | ID: ibc-199492

RESUMO

Este artículo sirve para iniciarse en las bases docentes de la actual fisiología de la aviación, cuyo origen se remonta al comienzo de la Segunda Guerra Mundial. Bombarderos en picado (1941) de Michael Curtiz es un excelente material docente para ayudar en la comprensión de las distintas causas del síncope de los pilotos en las alturas, permitiendo la reflexión y la búsqueda de soluciones o alternativas a través de experimentos que permiten la recuperación de la homeostasis corporal. Su material audiovisual comparte escenas reales del ejército americano que permiten acceder a estos descubrimientos y al avance del estado actual de la moderna fisiología aeroespacial


This article serves to begin in the teaching bases of the current aviation physiology, whose origin dates back to the beginning of World War II. Dive Bomber (1941) by Michael Curtiz is an excellent teaching material to help in the understanding of the different causes of the pilots’ syncope at heights, allowing thinking and the search for solutions or alternatives through experiments that allow the recovery of the body homeostasis. His audiovisual material shares real scenes of the United States Army that allow access to these discoveries and the progress of the current state of modern aerospace physiology


Assuntos
Humanos , Filmes Cinematográficos , Pilotos , Medicina Aeroespacial , Medicina nas Artes , Síncope/fisiopatologia , Articulação Atlantoccipital/lesões , Atlas Cervical/lesões , Processo Odontoide/lesões , Doença da Altitude/fisiopatologia , Aptidão Física/fisiologia
4.
PLoS One ; 15(8): e0236919, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32845910

RESUMO

Mount Everest is an extreme environment for humans. Nevertheless, hundreds of mountaineers attempt to summit Everest each year. In a previous study we analyzed interview data for all climbers (2,211) making their first attempt on Everest during 1990-2005. Probabilities of summiting were similar for men and women, declined progressively for climbers about 40 and older, but were elevated for climbers with experience climbing in Nepal. Probabilities of dying were also similar for men and women, increased for climbers about 60 and older (especially for the few that had summited), and were independent of experience. Since 2005, many more climbers (3,620) have attempted Everest. Here our primary goal is to quantify recent patterns of success and death and to evaluate changes over time. Also, we investigate whether patterns relate to key socio-demographic covariates (age, sex, host country, prior experience). Recent climbers were more diverse both in gender (women = 14.6% vs. 9.1% for 1990-2005) and in age (climbers ≥ 40 = 54.1% vs. 38.7%). Strikingly, recent climbers of both sexes were almost twice as likely to summit-and slightly less likely to die-than were comparable climbers in the previous survey. Temporal shifts may reflect improved weather forecasting, installation of fixed ropes on much of the route, and accumulative logistic equipment and experience. We add two new analyses. The probability of dying from illness or non-traumas (e.g., high-altitude illness, hypothermia), relative to dying from falling or from 'objective hazards' (avalanche, rock or ice fall), increased marginally with age. Recent crowding during summit bids was four-fold greater than in the prior sample, but surprisingly crowding has no evident effect on success or death during summit bids. Our results inform prospective climbers as to their current odds of success and of death, as well as inform governments of Nepal and China of the safety consequences and economic impacts of periodically debated restrictions based on climber age and experience.


Assuntos
Envelhecimento/fisiologia , Mortalidade , Montanhismo/fisiologia , Montanhismo/estatística & dados numéricos , Caracteres Sexuais , Adulto , Doença da Altitude/fisiopatologia , Desempenho Atlético , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos
5.
Ann Am Thorac Soc ; 17(8): 918-921, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32735170

RESUMO

Amid efforts to care for the large number of patients with coronavirus disease (COVID-19), there has been considerable speculation about whether the lung injury seen in these patients is different than acute respiratory distress syndrome from other causes. One idea that has garnered considerable attention, particularly on social media and in free open-access medicine, is the notion that lung injury due to COVID-19 is more similar to high-altitude pulmonary edema (HAPE). Drawing on this concept, it has also been proposed that treatments typically employed in the management of HAPE and other forms of acute altitude illness-pulmonary vasodilators and acetazolamide-should be considered for COVID-19. Despite some similarities in clinical features between the two entities, such as hypoxemia, radiographic opacities, and altered lung compliance, the pathophysiological mechanisms of HAPE and lung injury due to COVID-19 are fundamentally different, and the entities cannot be viewed as equivalent. Although of high utility in the management of HAPE and acute mountain sickness, systemically delivered pulmonary vasodilators and acetazolamide should not be used in the treatment of COVID-19, as they carry the risk of multiple adverse consequences, including worsened ventilation-perfusion matching, impaired carbon dioxide transport, systemic hypotension, and increased work of breathing.


Assuntos
Doença da Altitude , Infecções por Coronavirus , Hipertensão Pulmonar , Pandemias , Pneumonia Viral , Acetazolamida/farmacologia , Doença da Altitude/fisiopatologia , Doença da Altitude/terapia , Betacoronavirus/isolamento & purificação , Inibidores da Anidrase Carbônica/farmacologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/terapia , Humanos , Hipertensão Pulmonar/fisiopatologia , Hipertensão Pulmonar/terapia , Lesão Pulmonar/etiologia , Lesão Pulmonar/fisiopatologia , Lesão Pulmonar/terapia , Nifedipino/farmacologia , Pneumonia Viral/fisiopatologia , Pneumonia Viral/terapia , /fisiopatologia , Vasodilatadores/farmacologia
6.
Respir Physiol Neurobiol ; 279: 103476, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32522574

RESUMO

A very recent epidemiological study provides preliminary evidence that living in habitats located at 2500 m above sea level (masl) might protect from the development of severe respiratory symptoms following infection with the novel SARS-CoV-2 virus. This epidemiological finding raises the question of whether physiological mechanisms underlying the acclimatization to high altitude identifies therapeutic targets for the effective treatment of severe acute respiratory syndrome pivotal to the reduction of global mortality during the COVID-19 pandemic. This article compares the symptoms of acute mountain sickness (AMS) with those of SARS-CoV-2 infection and explores overlapping patho-physiological mechanisms of the respiratory system including impaired oxygen transport, pulmonary gas exchange and brainstem circuits controlling respiration. In this context, we also discuss the potential impact of SARS-CoV-2 infection on oxygen sensing in the carotid body. Finally, since erythropoietin (EPO) is an effective prophylactic treatment for AMS, this article reviews the potential benefits of implementing FDA-approved erythropoietin-based (EPO) drug therapies to counteract a variety of acute respiratory and non-respiratory (e.g. excessive inflammation of vascular beds) symptoms of SARS-CoV-2 infection.


Assuntos
Aclimatação/fisiologia , Doença da Altitude/fisiopatologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/fisiopatologia , Eritropoetina/farmacologia , Hipóxia/fisiopatologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/fisiopatologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/metabolismo , Humanos , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/metabolismo
7.
Am J Physiol Heart Circ Physiol ; 319(1): H203-H212, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32502374

RESUMO

High-altitude (>2,500 m) residence increases the incidence of intrauterine growth restriction (IUGR) due, in part, to reduced uterine artery blood flow and impaired myometrial artery (MA) vasodilator response. A role for the AMP-activated protein kinase (AMPK) pathway in protecting against hypoxia-associated IUGR is suggested by genomic and transcriptomic studies in humans and functional studies in mice. AMPK is a hypoxia-sensitive metabolic sensor with vasodilatory properties. Here we hypothesized that AMPK-dependent vasodilation was increased in MAs from high versus low-altitude (<1,700 m) Colorado women with appropriate for gestational age (AGA) pregnancies and reduced in IUGR pregnancies regardless of altitude. Vasoreactivity studies showed that, in AGA pregnancies, MAs from high-altitude women were more sensitive to vasodilation by activation of AMPK with A769662 due chiefly to increased endothelial nitric oxide production, whereas MA responses to AMPK activation in the low-altitude women were endothelium independent. MAs from IUGR compared with AGA pregnancies had blunted vasodilator responses to acetylcholine at high altitude. We concluded that 1) blunted vasodilator responses in IUGR pregnancies confirm the importance of MA vasodilation for normal fetal growth and 2) the increased sensitivity to AMPK activation in AGA pregnancies at high altitude suggests that AMPK activation helped maintain MA vasodilation and fetal growth. These results highlight a novel mechanism for vasodilation of MAs under conditions of chronic hypoxia and suggest that AMPK activation could provide a therapy for increasing uteroplacental blood flow and improving fetal growth in IUGR pregnancies.NEW & NOTEWORTHY Intrauterine growth restriction (IUGR) impairs infant well- being and increases susceptibility to later-in-life diseases for mother and child. Our study reveals a novel role for AMPK in vasodilating the myometrial artery (MA) from women residing at high altitude (>2,500 m) with appropriate for gestational age pregnancies but not in IUGR pregnancies at any altitude.


Assuntos
Doença da Altitude/metabolismo , Artérias/metabolismo , Retardo do Crescimento Fetal/metabolismo , Miométrio/irrigação sanguínea , Proteínas Quinases/metabolismo , Vasodilatação , Adulto , Doença da Altitude/fisiopatologia , Artérias/efeitos dos fármacos , Artérias/fisiopatologia , Feminino , Retardo do Crescimento Fetal/fisiopatologia , Humanos , Óxido Nítrico/metabolismo , Gravidez , Pironas/farmacologia , Tiofenos/farmacologia
9.
Am J Physiol Regul Integr Comp Physiol ; 319(1): R114-R122, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32432914

RESUMO

Exercise-heat acclimation (EHA) induces adaptations that improve tolerance to heat exposure. Whether adaptations from EHA can also alter responses to hypobaric hypoxia (HH) conditions remains unclear. This study assessed whether EHA can alter time-trial performance and/or incidence of acute mountain sickness (AMS) during HH exposure. Thirteen sea-level (SL) resident men [SL peak oxygen consumption (V̇o2peak) 3.19 ± 0.43 L/min] completed steady-state exercise, followed by a 15-min cycle time trial and assessment of AMS before (HH1; 3,500 m) and after (HH2) an 8-day EHA protocol [120 min; 5 km/h; 2% incline; 40°C and 40% relative humidity (RH)]. EHA induced lower heart rate (HR) and core temperature and plasma volume expansion. Time-trial performance was not different between HH1 and HH2 after 2 h (106.3 ± 23.8 vs. 101.4 ± 23.0 kJ, P = 0.71) or 24 h (107.3 ± 23.4 vs. 106.3 ± 20.8 kJ, P > 0.9). From HH1 to HH2, HR and oxygen saturation, at the end of steady-state exercise and time-trial tests at 2 h and 24 h, were not different (P > 0.05). Three of 13 volunteers developed AMS during HH1 but not during HH2, whereas a fourth volunteer only developed AMS during HH2. Heat shock protein 70 was not different from HH1 to HH2 at SL [1.9 ± 0.7 vs. 1.8 ± 0.6 normalized integrated intensities (NII), P = 0.97] or after 23 h (1.8 ± 0.4 vs. 1.7 ± 0.5 NII, P = 0.78) at HH. Our results indicate that this EHA protocol had little to no effect-neither beneficial nor detrimental-on exercise performance in HH. EHA may reduce AMS in those who initially developed AMS; however, studies at higher elevations, having higher incidence rates, are needed to confirm our findings.


Assuntos
Aclimatação , Pressão do Ar , Exercício Físico/fisiologia , Temperatura Alta , Hipóxia/fisiopatologia , Adolescente , Altitude , Doença da Altitude/fisiopatologia , Limiar Anaeróbio , Proteínas de Choque Térmico HSP70/metabolismo , Frequência Cardíaca , Humanos , Umidade , Masculino , Desempenho Físico Funcional , Mecânica Respiratória , Adulto Jovem
10.
DNA Cell Biol ; 39(4): 548-554, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32155344

RESUMO

The Qing-Tibet Plateau is characterized by low oxygen pressure, which is an important biomedical and ecological stressor. However, the variation in gene expression during periods of stay on the plateau has not been well studied. We recruited eight volunteers to stay on the plateau for 3, 7, and 30 days. Human Clariom D arrays were used to measure transcriptome changes in the mRNA expression profiles in these volunteers' blood. Analysis of variance (ANOVA) indicated that 699 genes were significantly differentially expressed in response to entering the plateau during hypoxic exposure. The genes with changes in transcript abundance were involved in the terms phosphoprotein, acetylation, protein binding, and protein transport. Furthermore, numerous genes involved in hematopoietic functions, including erythropoiesis and immunoregulation, were differentially expressed in response to hypoxia. This phenomenon may be one of reasons why the majority of people entering the plateau do not have excessive erythrocyte proliferation and are susceptible to infection.


Assuntos
Aclimatação/genética , Doença da Altitude/genética , Doença da Altitude/fisiopatologia , Hipóxia/fisiopatologia , Leucócitos/fisiologia , Altitude , Eritrócitos/citologia , Eritropoese/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/genética , Humanos , Leucopoese/genética , Masculino , Oxigênio , Tibet
12.
Wilderness Environ Med ; 31(2): 157-164, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32205041

RESUMO

INTRODUCTION: A history of preexisting hypertension is common in people participating in mountain activities; however, the relationship between blood pressure (BP), preexisting hypertension, and acute mountain sickness (AMS) is not well studied. We sought to determine these relationships among trekkers in the Everest region of Nepal. METHODS: This was a prospective observational cohort study of a convenience sample of adult, nonpregnant volunteers trekking in the Everest Base Camp region in Nepal. We recorded Lake Louise Scores for AMS and measured BP at 2860 m, 3400 m, and 4300 m. The primary outcome was AMS. RESULTS: A total of 672 trekkers (including 60 with history of preexisting hypertension) were enrolled at 2860 m. We retained 529 at 3400 m and 363 at 4300 m. At 3400 m, 11% of participants had AMS, and 13% had AMS at 4300 m. We found no relationship between AMS and measured BP values (P>0.05), nor was there any relation of BP to AMS severity as measured by higher Lake Louise Scores (P>0.05). Preexisting hypertension (odds ratio [OR] 0.16; 95% CI 0.025-0.57), male sex (OR 0.59; 95% CI 0.37-0.96), and increased SpO2 (OR 0.93; 95% CI 0.87-0.98) were associated with reduced rates of AMS in multivariate analyses adjusting for known risk factors for AMS. CONCLUSIONS: AMS is common in trekkers in Nepal, even at 3400 m. There is no relationship between measured BP and AMS. However, a medical history of hypertension may be associated with a lower risk of AMS. More work is needed to confirm this novel finding.


Assuntos
Doença da Altitude/epidemiologia , Altitude , Hipertensão/complicações , Montanhismo , Doença Aguda/epidemiologia , Adulto , Idoso , Doença da Altitude/etiologia , Doença da Altitude/fisiopatologia , Pressão Sanguínea , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nepal/epidemiologia , Prevalência , Estudos Prospectivos , Fatores de Risco
13.
Sci Rep ; 10(1): 5414, 2020 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-32214168

RESUMO

Previous investigations have indicated that environmental and genetic factors collectively contribute to the development of acute mountain sickness (AMS), but whether the EDN1 gene is involved in AMS remains to be elucidated. A total of 356 healthy male soldiers who had not traveled to high altitudes in the previous 12 months were enrolled in our study. All participants were taken by plane from 500 m (Chengdu in Sichuan Province) to a 3700 m highland (Lhasa) within 2 hours. Clinical data were collected within 24 hours, and pulmonary function parameters were completed simultaneously. Genotypes were obtained by using iMLDR genotyping assays. A total of 237 soldiers (66.57%) presented AMS symptoms, including headache, dizziness, gastrointestinal upset and fatigue. Soldiers with AMS showed an increase in heart rate (HR), plasma tryptophan and serotonin, and a decrease in SaO2, FEV1, PEF, FVC, V75, V50, V25 and MMF (all P < 0.01). Notably, allele T in single nucleotide polymorphism (SNP) rs2070699 showed a positive correlation with the occurrence of AMS. A general linear regression analysis showed that rs2060799, Mean Arterial Pressure (MAP), SaO2, FVC, tryptophan and serotonin were independent predictors for the occurrence of AMS. Importantly, the area under the curve (AUC) values for tryptophan (0.998), serotonin (0.912) and FVC (0.86) had diagnostic specificity and sensitivity. Our results demonstrated that AMS is accompanied by changes in lung function parameters, increased plasma tryptophan and serotonin levels, and that the EDN1 polymorphism is a potential risk factor for AMS.


Assuntos
Doença da Altitude/genética , Endotelina-1/genética , Doença Aguda , Adulto , Altitude , Doença da Altitude/fisiopatologia , Área Sob a Curva , Pressão Arterial/genética , Frequência Cardíaca/genética , Humanos , Pulmão/fisiologia , Masculino , Oxigênio/metabolismo , Fatores de Risco , Adulto Jovem
14.
J. health med. sci. (Print) ; 6(1): 9-16, ene.-mar. 2020.
Artigo em Espanhol | LILACS | ID: biblio-1096527

RESUMO

Evidencias en textos históricos Chinos de los años 403 AC y de la Conquista Española en 1590, muestran de las condiciones singulares que afectaban tanto a hombres como a animales al ascender por sectores montañosos por sobre 4000 m., y que ahora reconocemos como mal agudo de montaña. Ya desde el siglo XIX, se ha reconocido que es la falta de oxígeno (hipoxia) el factor determinante de la respuesta aclimatatoria como de la desaclimatización a la hipoxia de altura. El objetivo de la actual revisión fue una puesta al día de definiciones, factores que inciden en una mayor incidencia de mal agudo de montaña, mecanismo fisiológico propuesto, el desarrollo de estrategias farmacológicas para la prevención y/o tratamiento y por último, se ha revisado respecto de las distintas estrategias que se han desarrollado para la evaluación de la susceptibilidad individual, conocido comúnmente como test de hipoxia.


Some Chinese historical text from 403 BC and the Spanish Conquest in 1590 indicates unique conditions that affected both men and animals when climbing mountainous areas over 4000 m. and that is currently known as Acute Mountain Sickness (MAM). Since the XIX century, the lack of oxygen (hypoxia), has been recognized as the main factor of the acclimatization and declimatization to the high altitude hypoxia. The aim of the current revision is an update of definitions, factors that contribute the Acute Mountain Sickness, the proposed physiological mechanism, the development of pharmacological strategies for the prevention and/or treatment, and finally, we reviewed the different strategies developed for the individual susceptibility assessment, generally known as hypoxia test.


Assuntos
Humanos , Doença da Altitude/fisiopatologia , Doença da Altitude/tratamento farmacológico , Doença da Altitude/epidemiologia , Fatores de Risco , Suscetibilidade a Doenças , Doença da Altitude/etiologia
15.
Am J Med ; 133(10): e584-e588, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32081656

RESUMO

PURPOSE: Acute mountain sickness commonly occurs following ascent to high altitude and is aggravated following sleep. Cephalad fluid shifts have been implicated. We hypothesized that sleeping with the upper body elevated by 30º reduces the risk of acute mountain sickness. METHODS: In a pragmatic, randomized, observer-blinded field study at 4554 meters altitude, we investigated 134 adults aged 18-70 years with a Lake Louise score between 3 and 12 points on the evening of their arrival at the altitude. The individuals were exposed to sleeping on an inflatable cushion elevating the upper body by 30º or on a sham pillow in a horizontal position. The primary endpoint was the change in the Acute Mountain Sickness-Cerebral (AMS-C) score in the morning after sleeping at an altitude of 4554 meters compared with the evening before. Sleep efficiency was the secondary endpoint. RESULTS: Among 219 eligible mountaineers, 134 fulfilled the inclusion criteria and were randomized. The AMS-C score increased by 0.250 ± 0.575 in the control group and by 0.121 ± 0.679 in the intervention group (difference 0.105; 95% confidence interval, -0.098-0.308; P = .308). Oxygen saturation in the morning was 79% ± 6% in the intervention group and 78% ± 6% in the control group (P = .863). Sleep efficiency did not differ between groups (P = .115). CONCLUSIONS: Sleeping with the upper body elevated by 30° does not lead to relevant reductions in acute mountain sickness symptoms or hypoxemia at high altitude.


Assuntos
Doença da Altitude/terapia , Cefaleia/terapia , Hipóxia/terapia , Náusea/fisiopatologia , Posicionamento do Paciente/métodos , Sono , Doença Aguda , Adulto , Doença da Altitude/fisiopatologia , Feminino , Deslocamentos de Líquidos Corporais , Cefaleia/fisiopatologia , Frequência Cardíaca , Humanos , Hipóxia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Montanhismo , Oximetria
16.
Eur J Appl Physiol ; 120(3): 675-686, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32034478

RESUMO

PURPOSE: We examined the effects of hypoxaemia on dynamic cerebral autoregulation (dCA) in lowlanders and Sherpa highlanders. We hypothesized that dCA in lowlanders would be reduced to a greater extent in the common carotid artery (CCA) compared to the internal carotid artery (ICA) during acute hypoxia at sea level and at high altitude, whereas Sherpa highlanders would have preserved dCA upon ascent to high altitude. METHODS: dCA was calculated as the change in cerebrovascular conductance during transient hypotension induced via dual thigh-cuff release. Data were collected in 13 healthy lowlanders in normobaric normoxia and hypoxia (FIO2 = 0.11) at sea-level (344 m), and the day after arrival at 3440 m and 5050 m. In addition, 10 healthy Sherpa highlanders were tested at Kathmandu (~ 1400 m), and the day after arrival at 3440 m and 5050 m. RESULTS: The main findings were that: (1) in lowlanders, dCA in the CCA and ICA were both reduced by ~ 35% during normobaric hypoxia exposure at sea-level (P = 0.06 and P = 0.04, respectively); (2) CCA and ICA dCA were both similarly attenuated by ~ 40% at 5050 m in lowlanders, but not 3440 m, compared to sea-level (both P = 0.04); and (3) in Sherpa, high altitude had no impact on CCA dCA (P = 0.275), indicating intact cerebral autoregulation. CONCLUSION: Herein, we provide novel evidence that dCA, assessed via Duplex ultrasound, was attenuated in lowlanders with exposure to normobaric and hypobaric hypoxia, whereas it is potentially preserved in the Sherpa. The clinical implications of attenuated dCA in lowlanders, and the adaptive significance of this response in the Sherpa highlanders, remains to be elucidated.


Assuntos
Altitude , Circulação Cerebrovascular , Homeostase , Adaptação Fisiológica , Adulto , Doença da Altitude/fisiopatologia , Feminino , Humanos , Masculino , Adulto Jovem
17.
PLoS One ; 15(1): e0228267, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31995608

RESUMO

PURPOSE: To investigate changes in intraocular pressure (IOP) and axial length (AL) on the ascent to high altitude from Beijing to Lhasa. PATIENTS AND METHODS: Twenty volunteers (17 men, 3 women) who had been sent to work in Lhasa, Tibet for more than 6 months were enrolled. One of their journeys from Beijing to Lhasa was chosen as the time for the examination. IOP, AL, corneal curvature (K), and blood pressure (BP) were measured in Beijing (altitude 43 m) and Lhasa (altitude 3658 m). Their first examination was conducted at least 1 day before arriving in Lhasa and the second examination after they had stayed in Lhasa for 7 days. The data from the highland and lowland examinations were analyzed with a paired-sample T test and Pearson's correlation coefficient was calculated for the association between IOP and average BP. RESULTS: The mean IOP was 12.65±2.34 mmHg in Beijing and 14.85±3.1 mmHg in Lhasa. The mean AL was 24.61±1.50mm in Beijing, and 24.98±1.45 mm in Lhasa. The IOP and AL showed a significant elevation in highland compared with lowland (P<0.05). The mean K was 43.58±2.25 D in Beijing and 43.56±2.21 D in Lhasa and no significant difference was found in this study (P>0.05). A positive correlation between variance of IOP and ACD was found (r = 0.475, P<0.05) and no correlation between IOP and average BP was noted. CONCLUSIONS: High altitude may lead to a small but significant change in IOP and axial length. However, the shape of the corneal surface was not influenced by the hypobaric and hypoxic conditions.


Assuntos
Aclimatação , Altitude , Córnea/anatomia & histologia , Pressão Intraocular , Aclimatação/fisiologia , Adulto , Doença da Altitude/fisiopatologia , Câmara Anterior/anatomia & histologia , Câmara Anterior/fisiologia , Pequim , Pressão Sanguínea/fisiologia , Córnea/fisiologia , Feminino , Humanos , Pressão Intraocular/fisiologia , Masculino , Tibet , Fatores de Tempo , Corpo Vítreo/anatomia & histologia , Corpo Vítreo/fisiologia
18.
J Pharm Biomed Anal ; 179: 113028, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31835126

RESUMO

Members of the genus Rhodiola L. have been widely used in Tibetan medicines for preventing and treating acute mountain sickness (AMS) for a long time. However, the pharmacological mechanisms of these medicines in treating AMS remain unclear. To address this problem, an integrative method combining ultra-performance liquid chromatography coupled with a quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS/MS)analysis and network pharmacology was employed. First, the chemical profiles of Dazhu Hongjingtian (DZ, a Chinese medicine preparation composed of R. kirilowii (Regel) Maxim) were identified or tentatively characterized. Second, the targets of DZ were predicted using the SwissTargetPrediction and STITCH databases; the targets of AMS were also collected from the Drugbank and TTD databases. Then, networks between targets and compounds or diseases were constructed by Cytoscape 3.6.1. Third, GO and pathway enrichment analyses were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID). As a result, 40 ingredients of 53 compounds in DZ might be biologically active. These activities were related to the regulatory effects of the ingredients on 68 significant signaling pathways, such as the inflammation pathway, apoptosis pathway, HIF-1 signaling pathway, and others, by targeting 33 proteins, including PTGS2 and PTGS1, ALOX5 and ALOX15, BCL2 and BCL2L1, the protein kinase C (PKC) family and HIF1A, among others.


Assuntos
Doença da Altitude/tratamento farmacológico , Medicamentos de Ervas Chinesas/química , Rhodiola/química , Doença da Altitude/fisiopatologia , Cromatografia Líquida de Alta Pressão/métodos , Bases de Dados Factuais , Medicamentos de Ervas Chinesas/farmacologia , Espectrometria de Massas em Tandem/métodos
19.
Sci Rep ; 9(1): 19334, 2019 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-31852992

RESUMO

In chronic mountain sickness (CMS) patients, the structure of the brain, memory and cognition are often irreversibly damaged by chronic hypoxia due to red blood cell overcompensation, elevated haemoglobin and blood stasis. In this study, we aimed to evaluate this damage using diffusion tensor imaging (DTI) and to study the correlations among the fractional anisotropy (FA),the apparent diffusion coefficient (ADC) value, the severity index of CMS and the simple Mental State Examination (MMSE) score in CMS patients. A total of 17 patients with CMS and 15 healthy controls were recruited for conventional brain magnetic resonance imaging (MRI) and DTI scans, and ADC images were reconstructed along with FA and FA colour maps. The FA and ADC values of the selected regions of interest (ROIs) were measured and compared. The FA and ADC values were also compared with the haemoglobin (Hb) and MMSE scores. CMS patients are prone to intracranial ischaemia, infarction and haemorrhage. Multiple structural changes occur in the brain of CMS patients, and these changes are related to the severity of the disease and cognitive function variation. The white matter fibre bundles of CMS patients showed no obvious damage, except in the ischaemic site.


Assuntos
Doença da Altitude/diagnóstico por imagem , Doença da Altitude/fisiopatologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Cognição , Imagem de Tensor de Difusão , Adulto , Doença da Altitude/patologia , Anisotropia , Estudos de Casos e Controles , Doença Crônica , Tontura/diagnóstico por imagem , Cefaleia/diagnóstico por imagem , Humanos , Masculino
20.
Physiol Rep ; 7(20): e14263, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31660703

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 Jovem
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