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1.
Sensors (Basel) ; 21(4)2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33578839

RESUMO

Background: Finger pulse oximeters are widely used to monitor physiological responses to high-altitude exposure, the progress of acclimatization, and/or the potential development of high-altitude related diseases. Although there is increasing evidence for its invaluable support at high altitude, some controversy remains, largely due to differences in individual preconditions, evaluation purposes, measurement methods, the use of different devices, and the lacking ability to interpret data correctly. Therefore, this review is aimed at providing information on the functioning of pulse oximeters, appropriate measurement methods and published time courses of pulse oximetry data (peripheral oxygen saturation, (SpO2) and heart rate (HR), recorded at rest and submaximal exercise during exposure to various altitudes. Results: The presented findings from the literature review confirm rather large variations of pulse oximetry measures (SpO2 and HR) during acute exposure and acclimatization to high altitude, related to the varying conditions between studies mentioned above. It turned out that particularly SpO2 levels decrease with acute altitude/hypoxia exposure and partly recover during acclimatization, with an opposite trend of HR. Moreover, the development of acute mountain sickness (AMS) was consistently associated with lower SpO2 values compared to individuals free from AMS. Conclusions: The use of finger pulse oximetry at high altitude is considered as a valuable tool in the evaluation of individual acclimatization to high altitude but also to monitor AMS progression and treatment efficacy.


Assuntos
Doença da Altitude , Altitude , Aclimatação , Doença da Altitude/diagnóstico , Humanos , Masculino , Oximetria , Oxigênio
4.
Wilderness Environ Med ; 32(1): 88-91, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33516622

RESUMO

We report a case of prolonged motivational deficit as a sequela of high altitude cerebral edema (HACE), the most severe form of neuropsychiatric dysfunction arising from traveling to high altitude. Magnetic resonance imaging of the brain showed hyperintense lesions in the globi pallidi bilaterally on T2-weighted images. Single-photon emission computed tomography showed hypoperfusion in dorsolateral and orbital prefrontal cortices bilaterally and in the anterior cingulate cortex. This case suggests that a prolonged motivational deficit can occur in patients with HACE. The case may also suggest that HACE can cause network disturbances between the prefrontal cortex and the globi pallidi.


Assuntos
Doença da Altitude/complicações , Apatia , Edema Encefálico/complicações , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Humanos , Masculino
5.
Wilderness Environ Med ; 32(1): 36-40, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33431301

RESUMO

INTRODUCTION: A significant number of climbers on Mount Kilimanjaro are affected by altitude-related disorders. The aim of this study was to determine the main causes of morbidity and mortality in a representative cohort of climbers based on local hospital records. METHODS: We conducted a 2-y retrospective chart review of all patients presenting to the main referral hospital in the region after a climb on Mount Kilimanjaro, including all relevant records and referrals for postmortem studies. RESULTS: We identified 62 climbers who presented to the hospital: 47 inpatients and 15 outpatients. Fifty-six presented with high altitude illness, which included acute mountain sickness (n=8; 14%), high altitude pulmonary edema (HAPE) (n=30; 54%), high altitude cerebral edema (HACE) (n=7; 12%), and combined HAPE/HACE (n=11; 20%). The mean altitude of symptom onset ranged from 4600±750 m for HAPE to 5000±430 m for HAPE/HACE. The vast majority of inpatients (n=41; 87%) were improved on discharge. Twenty-one deceased climbers, most having died while climbing (n=17; 81%), underwent postmortem evaluation. Causes of death were HAPE (n=16; 76%), HAPE/HACE (n=3; 14%), trauma (1), and cardiopulmonary (1). CONCLUSIONS: HAPE was the main cause of death during climbing as well as for hospital admissions. The vast majority of climbers who presented to hospital made a full recovery.


Assuntos
Doença da Altitude/epidemiologia , Edema Encefálico/etiologia , Montanhismo , Edema Pulmonar/etiologia , Ferimentos e Lesões/epidemiologia , Adolescente , Adulto , Idoso , Altitude , Doença da Altitude/mortalidade , Edema Encefálico/mortalidade , Coleta de Dados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Edema Pulmonar/mortalidade , Estudos Retrospectivos , Tanzânia/epidemiologia , Ferimentos e Lesões/mortalidade , Ferimentos e Lesões/patologia , Adulto Jovem
6.
Life Sci ; 270: 119012, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33422543

RESUMO

AIMS: Memantine is a non-competitive antagonist of glutamatergic NMDA receptor that is mainly used in the treatment of Alzheimer's disease. The excitatory toxicity mediated by glutamate via glutamatergic receptor signals is considered to be one of the mechanisms mediating neuronal injury and cognitive impairment after exposure to a hypoxic environment at a high altitude. Therefore, in this study, we hypothesized that inhibiting glutamate signaling using memantine could alleviate neuronal injury and cognitive impairment in rats exposed to chronic hypoxia. MAIN METHODS: we made animal models in the natural environment of the Qinghai-Tibet Plateau at an altitude of 4300 m, and used animal behavior, morphology, molecular biology and other methods to evaluate the impact of chronic hypoxia exposure on cognitive function and the neuroprotective effect of Memantine. KEY FINDINGS: Our results showed that the expression of NMDA receptors increased, while the expression of AMPA receptors decreased, after 4 weeks of chronic hypoxia exposure. Concomitantly, apoptotic neuronal cell death in the hippocampus and frontal cortex was significantly increased, along with levels of oxidative stress, whereas innate ability to inhibit free radicals decreased. Moreover, after 8 weeks of hypoxia exposure, learning, memory, and space exploration abilities were significantly decreased. Notably, after treatment with memantine, apoptotic neuronal cell death, oxidative stress, and free radical levels decreased, and the cognitive function of the animals improved. SIGNIFICANCE: Present study shows that chronic hypoxia can produce the excitatory toxicity leading to neural injury and cognitive impairment that can be suppressed with memantine treatment by inhibiting excitatory toxicity.


Assuntos
Doença da Altitude/metabolismo , Disfunção Cognitiva/tratamento farmacológico , Memantina/farmacologia , Altitude , Doença da Altitude/tratamento farmacológico , Doença de Alzheimer/tratamento farmacológico , Animais , Morte Celular/efeitos dos fármacos , Cognição/efeitos dos fármacos , Modelos Animais de Doenças , Antagonistas de Aminoácidos Excitatórios/farmacologia , Ácido Glutâmico/metabolismo , Hipocampo/metabolismo , Hipóxia/metabolismo , Masculino , Memantina/metabolismo , Memória/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Neurotoxinas/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/metabolismo
7.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(1): 50-56, 2021 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-33474889

RESUMO

Historically, the Cambrian explosion was a major life evolution event caused by changes of natural environmental oxygen concentration. The use of oxygen was part of the basic survival instinct of higher life, which evolved a complex regulation system in response to variant levels of oxygen concentration. Hypoxia is one of the typical environmental characteristics in plateau areas. After long-term natural selection in hypoxic conditions, numerous species living in plateau areas have evolved unique mechanisms adapted to hypoxia. Recent studies have found that there are some similarities in adaptation to hypoxia between the animals in highland and different types of human solid tumor cells. Herein, we will summarize recent findings about the hypoxia adaptation evolution in high-altitude animals and the characteristics of hypoxic solid tumors, especially the reactive oxygen species responses in hypoxic solid tumors. We believe that deciphering the underlying molecular mechanisms involved in hypoxia adaptation in highland will facilitate the identification of new genes or biomarkers critical for research on hypoxic solid tumors in the future.


Assuntos
Doença da Altitude , Altitude , Aclimatação , Animais , Humanos , Hipóxia , Oxigênio , Seleção Genética
8.
Wilderness Environ Med ; 32(1): 114-120, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33339717

RESUMO

This Lessons from History article about the naming of the extreme altitude "Death Zone" explores the historical mountaineering and medical literature relevant to the topic. Swiss alpinist and radiologist Edouard Wyss-Dunant (1897-1983) authored several reports and books about expeditions to arctic regions, deserts, and the Himalaya. Encouraged by the success of a Swiss expedition to the Garhwal Himalaya in 1947, Wyss-Dunant joined his fellow climbers from Geneva on a 1949 expedition to several peaks in the Kanchenjunga region. Wyss-Dunant was then invited to lead the spring 1952 Swiss Everest expedition. Despite this being the first Swiss attempt on Everest and on an untried route, Raymond Lambert and Tenzing Norgay nearly summitted Everest from the Nepal side. Wyss-Dunant earned mountaineering immortality by coining the phrase the Death Zone during the expedition's foray into the upper regions of Everest. Wyss-Dunant went on to become a president of the Swiss Alpine Club and the International Climbing and Mountaineering Federation. His writings and that of others provide an evocative supporting narrative to illustrate some of the problems of living (or dying) at extreme altitude.


Assuntos
Doença da Altitude/mortalidade , Altitude , Expedições/história , Montanhismo/história , História do Século XX , Humanos , Nepal
9.
J Intensive Care Med ; 36(1): 3-8, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32909898

RESUMO

Coronavirus Disease 2019 (COVID-19) has had a devastating impact on the ability of highly trained healthcare providers to render sufficient care, due to both the significant demand on resources and the unique nature of this disease that make it resistant to traditional therapies. This review sought to determine the potential role of phosphodiesterase-5 inhibitors (PDE-5) in the management of COVID-19 by extrapolating relevant data and clinical studies from other related disease states, including acute respiratory distress syndrome, acute lung injury, and high altitude pulmonary edema. Following a literature search, 4 reports were analyzed and included in this review. While the heterogenicity of data and the small number of trials included limit the interpretation and applicability, it was consistently demonstrated that PDE-5 inhibitors lowered pulmonary arterial pressures. The overall benefit of these agents is seemingly dependent upon the etiology of the respiratory failure, which warrants expanded clinical investigation for COVID-19.


Assuntos
Doença da Altitude/tratamento farmacológico , Hipertensão Pulmonar/tratamento farmacológico , Inibidores da Fosfodiesterase 5/farmacologia , /tratamento farmacológico , /tratamento farmacológico , Humanos , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/metabolismo
10.
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
11.
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
12.
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
13.
Medicine (Baltimore) ; 99(46): e23233, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33181710

RESUMO

BACKGROUND: Acute mountain sickness (AMS) is the effect when people accessing high altitude in a short period of time. As a cyclooxygenase (COX) inhibitor, ibuprofen could alleviate the symptoms of AMS. However, whether it can prevent AMS or not is still controversial. It is necessary to perform a meta-analysis to evaluate the role of ibuprofen in AMS prophylaxis. METHODS: PubMed, EMBASE, Medline, ISI Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI) will be searched for the relevant published studies that explored the value of ibuprofen in AMS prophylaxis from inception to October 2020. The data will be independently extracted by 2 researchers. Risk of bias will be evaluated based on Cochrane risk of bias assessment tool. Heterogeneity among the included studies will be evaluated by χ and I values. The meta-analysis was conducted by RevMan software version 5.3. RESULTS: This study will evaluate the role of ibuprofen in AMS prophylaxis. CONCLUSION: This study will summarize the current evidence of ibuprofen in AMS prophylaxis, which could further guide the recommendation in prevention of AMS.Open Science Framework (OSF) registration number: October 8, 2020. osf.io/n3mjt.


Assuntos
Doença da Altitude/prevenção & controle , Protocolos Clínicos , Ibuprofeno/uso terapêutico , Profilaxia Pré-Exposição/normas , Doença da Altitude/tratamento farmacológico , Humanos , Ibuprofeno/farmacologia , Metanálise como Assunto , Profilaxia Pré-Exposição/métodos , Revisões Sistemáticas como Assunto
14.
Nat Commun ; 11(1): 4928, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004791

RESUMO

High-altitude adaptation of Tibetans represents a remarkable case of natural selection during recent human evolution. Previous genome-wide scans found many non-coding variants under selection, suggesting a pressing need to understand the functional role of non-coding regulatory elements (REs). Here, we generate time courses of paired ATAC-seq and RNA-seq data on cultured HUVECs under hypoxic and normoxic conditions. We further develop a variant interpretation methodology (vPECA) to identify active selected REs (ASREs) and associated regulatory network. We discover three causal SNPs of EPAS1, the key adaptive gene for Tibetans. These SNPs decrease the accessibility of ASREs with weakened binding strength of relevant TFs, and cooperatively down-regulate EPAS1 expression. We further construct the downstream network of EPAS1, elucidating its roles in hypoxic response and angiogenesis. Collectively, we provide a systematic approach to interpret phenotype-associated noncoding variants in proper cell types and relevant dynamic conditions, to model their impact on gene regulation.


Assuntos
Aclimatação/genética , Cromatina/metabolismo , Grupos Étnicos/genética , Redes Reguladoras de Genes , Modelos Genéticos , Altitude , Doença da Altitude/etnologia , Doença da Altitude/genética , Doença da Altitude/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Hipóxia Celular/genética , Células Cultivadas , Cromatina/genética , Sequenciamento de Cromatina por Imunoprecipitação , Resistência à Doença/genética , Feminino , Regulação da Expressão Gênica , Células Endoteliais da Veia Umbilical Humana , Humanos , Hipóxia/genética , Hipóxia/metabolismo , Oxigênio/metabolismo , Polimorfismo de Nucleotídeo Único , Gravidez , Cultura Primária de Células , RNA-Seq , Elementos Reguladores de Transcrição/genética , Seleção Genética , Tibet/etnologia , Fatores de Transcrição/metabolismo , Sequenciamento Completo do Genoma
15.
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
16.
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
17.
Am J Physiol Lung Cell Mol Physiol ; 319(2): L360-L368, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32692577

RESUMO

Hypobaric hypoxia poses stress to sojourners traveling to high-altitude. A cascade of physiological changes occurs to cope with or adapt to hypobaric hypoxia. However, an insufficient physiological response to the hypoxic condition resulting from imbalanced vascular homeostasis pathways results in high-altitude pulmonary edema (HAPE). The present study aims to identify the implication of miRNAs associating with HAPE and adaptation. We analyzed the expression of 1,113 miRNAs in HAPE-patients (HAPE-p), HAPE-free controls (HAPE-f), and highland natives (HLs). Based on miRNA profiling and in silico analyses, miR-124-3p emerged relevantly. We observed a significant overexpression of miR-124-3p in HAPE-p. In silico analyses revealed a direct interaction of miR-124-3p with vascular homeostasis and hypoxia-associated genes NOS3 (endothelial nitric oxide synthase), Apelin, and ETS1 (V-Ets avian erythroblastosis virus E2 oncogene homolog 1). Moreover, the transcript and biolevel expression of these genes were significantly decreased in HAPE-p when compared with HAPE-f or HLs. Our in vitro analysis in human umbilical vein endothelial cells demonstrated a significant knockdown of these genes both at transcript and protein levels following miR-124-3p overexpression. Conclusively, our results showed that miR-124-3p might play a plausible role in HAPE pathophysiology by inhibiting the expression of NOS3, Apelin, and ETS1.


Assuntos
Doença da Altitude/sangue , Doença da Altitude/metabolismo , Hipertensão Pulmonar/sangue , Hipertensão Pulmonar/metabolismo , Hipóxia/sangue , Hipóxia/metabolismo , MicroRNAs/sangue , Edema Pulmonar/sangue , Edema Pulmonar/metabolismo , Adaptação Fisiológica/fisiologia , Adulto , Altitude , Apelina/metabolismo , Linhagem Celular , Feminino , Células HEK293 , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Óxido Nítrico Sintase Tipo III/metabolismo , Proteína Proto-Oncogênica c-ets-1/metabolismo , Adulto Jovem
18.
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
19.
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
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