Phospholipase D regulates ferroptosis signal transduction in mouse spleen hypoxia response

High-altitude hypoxia exposure can lead to phospholipase D-mediated lipid metabolism disorder in spleen tissues and induce ferroptosis. Nonetheless, the key genes underlying hypoxia-induced splenic phospholipase D and the ferroptosis pathway remain unclear. This study aimed to establish a hypoxia animal model. Combined transcriptomic and proteomic analyses showed that 95 predicted target genes (proteins) were significantly differentially expressed under hypoxic conditions. Key genes in phospholipase D and ferroptosis pathways under hypoxic exposure were identified by combining Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis techniques. Gene set enrichment analysis (GSEA) showed that the differential gene sets of the phospholipase D and ferroptosis signaling pathways were upregulated in the high-altitude hypoxia group. The genes in the phospholipase D signalling pathway were verified, and the expression levels of KIT and DGKG were upregulated in spleen tissues under hypoxic exposure. Subsequently, the mRNA and protein expression levels of genes from the exogenous pathway such as TFRC, SLC40A1, SLC7A11, TRP53, and FTH1 and those from the endogenous pathway such as GPX4, HMOX1, and ALOX15 differentials in the ferroptosis signalling pathway were verified, and the results indicated significant differential expression. In summary, exposure to high-altitude hypoxia mediated phospholipid metabolism disturbance through the phospholipase D signalling pathway and further induced ferroptosis, leading to splenic injury.

New immunological aspects of peri-implantitis

ABSTRACT Objective: This study aimed to compare the levels of HIF1-α, VEGF, TNF-α, and IL-10 in the peri-implant crevicular fluid of patients with and without peri-implantitis. Methods: Forty patients, comprising 16 with and 24 without peri-implantitis were selected. Results: Patients with peri-implantitis exhibited significantly higher HIF-1α levels than those without peri-implantitis (p=0.0005). TNF-α revealed significant positive correlations with IL-10 (p=0.0008) and VEGF (p=0.0246), whereas HIF-1α and IL-10 levels (p=0.0041) demonstrated a negative and significative correlation in the peri-implantitis group. Conclusion: This study, for the first time demonstrates the balance of HIF-1α, TNFα, IL-10, and VEGF in peri-implantitis. It shows an elevated HIF-1α levels in patients with peri-implantitis, which could have stemmed from persistent inflammation- triggered hypoxia. Furthermore, the positive correlation between TNF-α and VEGF suggests intensified proinflammatory activity in peri-implantitis. Nevertheless, further studies are essential to understand these immune dynamics in peri-implantitis.

Acute physiological responses to "recovery intermittent hypoxia" in hiit / Respuestas agudas a la "hipoxia intermitente de recuperación" en el hiit / Respostas fisiológicas agudas à "hipóxia intermitente de recuperação" no hiit

ABSTRACT Introduction: Traditional intermittent hypoxia training improves sport performance after short periods of exposure, but acute exposure to intermittent hypoxia leads to decreased training intensity and technical quality. The solution to overcome these negative effects may be to perform efforts in normoxia and the intervals between efforts in hypoxia, maintaining the quality of training and the benefits of hypoxia. Objective: This study aimed to evaluate the acute physiological responses to hypoxia exposure during recovery between high intensity efforts. Materials and methods: Randomized, one-blind, placebo-controlled study. Sixteen men performed a graded exercise test to determine their maximal intensity and two sessions of high-intensity interval training. The training intervals could be in hypoxia (HRT), FIO2: 0.136 or normoxia (NRT), FIO2: 0.209. During the two-minute interval between the ten one-minute efforts, peripheral oxygen saturation (SpO2), heart rate (HR), blood lactate ([La]), blood glucose ([Glu]) were constantly measured. Results: There were differences in HR (TRN = 120 ± 14 bpm; TRH = 129 ± 13 bpm, p < 0.01) and SpO2 (TRN = 96.9 ± 1.0%; TRH = 86.2 ± 3.5%, p < 0.01). No differences in [La] and [Glu] TRN (4.4 ± 1.7 mmol.l-1; 3.9 ± 0.5 mmol.l-1) and TRH (5.2 ± 2.0 mmol.l-1; 4.0 ± 0.8 mmol.l-1, p = 0.17). Conclusion: The possibility of including hypoxia only in the recovery intervals as an additional stimulus to the training, without decreasing the quality of the training, was evidenced. Level of Evidence II; Randomized Clinical Trial of Minor Quality.

RESUMEN Introducción: El entrenamiento tradicional en hipoxia intermitente mejora el rendimiento deportivo tras cortos periodos de exposición, sin embargo, la exposición aguda a la hipoxia intermitente conduce a una disminución de la intensidad del entrenamiento y de la calidad técnica. La solución para superar estos efectos negativos puede ser realizar los esfuerzos en normoxia y los intervalos entre esfuerzos en hipoxia, manteniendo la calidad del entrenamiento y los beneficios de la hipoxia. Objetivo: Este estudio pretendía evaluar las respuestas fisiológicas agudas a la exposición a la hipoxia durante la recuperación entre esfuerzos de alta intensidad. Materiales y métodos: Estudio aleatorizado, a ciegas y controlado con placebo. Dieciséis hombres realizaron una prueba de ejercicio graduado para determinar su intensidad máxima y dos sesiones de entrenamiento por intervalos de alta intensidad. Los intervalos de entrenamiento podían ser en hipoxia (HRT), FIO2: 0,136 o normoxia (NRT), FIO2: 0,209. Durante el intervalo de dos minutos entre los diez esfuerzos de un minuto, se midieron constantemente la saturación periférica de oxígeno (SpO2), la frecuencia cardiaca (FC), el lactato en sangre ([La]) y la glucemia ([Glu]). Resultados: Hubo diferencias en la FC (TRN = 120 ± 14 lpm; TRH = 129 ± 13 lpm, p < 0,01) y la SpO2 (TRN = 96,9 ± 1,0%; TRH = 86,2 ± 3,5%, p < 0,01). No hubo diferencias en [La] y [Glu] TRN (4,4 ± 1,7 mmol.l-1; 3,9 ± 0,5 mmol.l-1) y TRH (5,2 ± 2,0 mmol.l-1; 4,0 ± 0,8 mmol.l-1, p = 0,17). Conclusión: Se evidenció la posibilidad de incluir hipoxia sólo en los intervalos de recuperación como estímulo adicional al entrenamiento sin disminuir la calidad del mismo. Nivel de Evidencia II; Ensayo Clínico Aleatorizado de Baja Calidad.

RESUMO Introdução: O treinamento de hipóxia intermitente tradicional melhora o desempenho esportivo após curtos períodos de exposição, porém a exposição aguda à hipóxia intermitente leva à diminuição da intensidade do treinamento e da qualidade técnica. A solução para superar esses efeitos negativos pode ser realizar esforços em normóxia e os intervalos entre os esforços em hipóxia, mantendo a qualidade do treinamento e os benefícios da hipóxia. Objetivo: Este estudo teve como objetivo avaliar as respostas fisiológicas agudas à exposição de hipóxia durante a recuperação entre esforços de alta intensidade. Materiais e métodos: Estudo aleatório e one-blinded, com efeito placebo controlado. Dezesseis homens realizaram um teste de exercício graduado para determinar sua intensidade máxima e duas sessões de treinamento intervalado de alta intensidade. Os intervalos de treinamento podem ser em hipóxia (TRH), FIO2: 0,136 ou normóxia (TRN), FIO2: 0,209. Durante os dois minutos de intervalo entre os dez esforços de um minuto, foram medidos constantemente a saturação periférica de oxigênio (SpO2), frequência cardíaca (FC), lactato sanguíneo ([La]), glicemia ([Glu]). Resultados: Houve diferenças na FC (TRN = 120 ± 14 bpm; TRH = 129 ± 13 bpm, p <0,01) e SpO2 (TRN = 96,9 ± 1,0%; TRH = 86,2 ± 3,5%, p <0,01). Sem diferenças em [La] e [Glu] TRN (4,4 ± 1,7 mmol.l-1; 3,9 ± 0,5 mmol.l-1) e TRH (5,2 ± 2,0 mmol.l-1; 4,0 ± 0,8 mmol.l-1, p = 0,17). Conclusão: Evidenciou-se a possibilidade de incluir a hipóxia apenas nos intervalos de recuperação como um estímulo adicional ao treinamento, sem diminuir a qualidade do treinamento. Nível de Evidência II; Estudo Clínico Randomizado de Menor Qualidade.

Cobalt Chloride as a Hypoxia Mimicking Agent Induced HIF-1α and mTOR Expressions of Human Umbilical Cord Mesenchymal Stem Cells

ABSTRACT Objective: To assess the effects of cobalt chloride (CoCl2) as a hypoxia mimicking agent on human umbilical cord mesenchymal stem cells (hUCMSCs) expression of HIF-1α and mTOR for use in regenerative dentistry. Material and Methods: Human umbilical cord mesenchymal stem cells were isolated and then cultured. The characteristics of stemness were screened and confirmed by flow cytometry. The experiment was conducted on hypoxia (H) and normoxia (N) groups. Each group was divided and incubated into 24-, 48-, and 72-hours observations. Hypoxic treatment was performed using 100 µM CoCl2 on 5th passage cells in a conventional incubator (37°C; 5CO2). Then, immunofluorescence of HIF-1α and mTOR was done. Data was analyzed statistically using One-way ANOVA and Tukey's HSD. Results: Significant differences were found between normoxic and hypoxic groups on HIF-1α (p=0.015) and mTOR (p=0.000) expressions. The highest HIF-1α expression was found at 48 hours in the hypoxia group, while for mTOR at 24 hours in the hypoxia group. Conclusion: Hypoxia using cobalt chloride was able to increase human umbilical cord mesenchymal stem cells expression of HIF-1α and mTOR.

Effects of GW501516 on the injury of pulmonary artery endothelial cells induced by hypoxia and its mechanism / 中国药房

OBJECTIVE To investigate the effects of the peroxisome proliferator-activated receptors δ （PPARδ） agonist GW501516 on the injury of pulmonary artery endothelial cells （PAECs） induced by hypoxia and its mechanism. METHODS The cytotoxic effects of GW501516 were observed by detecting the relative survival rate of PAECs； the protein expression of PPARδ was determined by Western blot assay. The cellular model of PAECs injury was established under hypoxic conditions； using antioxidant N-acetylcysteine （NAC） as positive control， the effects of GW501516 on cell injury and reactive oxygen species （ROS） production were investigated by detecting cell apoptotic rate， cell viability， lactate dehydrogenase （LDH） activity and ROS levels. Using nuclear factor erythroid 2-related factor 2（Nrf2） activator dimethyl fumarate （DMF） as positive control， PAECs were incubated with GW501516 and/or Nrf2 inhibitor ML385 under hypoxic conditions； the mechanism of GW501516 on PAECs injury induced by hypoxia was investigated by detecting cell injury （cell apoptosis， cell viability， LDH activity）， the levels of superoxide dismutase （SOD）， glutathione peroxidase （GPx）， catalase （CAT）， malondialdehyde （MDA） and ROS， the expressions of Nrf2， heme oxygenase-1 （HO-1） and cleaved-caspase-3 （C-caspase-3） protein. RESULTS The results demonstrated that hypoxia inhibited the protein expression of PPARδ （P＜0.05）， while GW501516 promoted the protein expression of PPARδ in hypoxia- exposed PAECs without obvious cytotoxic effects. GW501516 inhibited the apoptosis of PAECs， improved cell viability， and reduced LDH activity and ROS levels. GW501516 could up-regulate the protein expression of HO-1 in PAECs and the levels of SOD， GPx and CAT， while down-regulated the levels of MDA and ROS by activating the Nrf2 pathway （P＜0.05）； but Nrf2 inhibitor ML385 could reverse the above effects of GW501516 （P＜0.05）. GW501516 exerted similar effects to Nrf2 activator DMF in down-regulating the expression of C-caspase-3 and inhibiting the injury of PAECs under conditions of hypoxia （P＜0.05）. Moreover， Nrf2 inhibitor ML385 reversed the 163.com inhibition effects of GW501516 on PAECs injury （P＜0.05）. CONCLUSIONS GW501516 can relieve the hypoxia-induced injury of PAECs via the inhibition of oxidative stress， the mechanism of which may be associated with activating Nrf2.

Relationship between prehospital clinical status intracranial pressure and outcomes in pediatric patients with severe head trauma

Introduction: The prehospital phase of the management of pediatric severe traumatic brain injury may have a direct influence on the results. Objective: To evaluate the influence of prehospital variables on intracranial pressure and the results in pediatric patients with severe TBI. Method: A descriptive study of 41 pediatric patients who were admitted to the medical emergency department and later admitted to the pediatric intensive care unit due to severe head trauma was carried out between January 2003 and December 2018. Results: children aged 5-17 years predominate, and the highest number of cases were received between 0-3h at the neurotrauma center. Of the 41 cases, 27 arrived with a non-expedited airway and hypoxia was verified upon arrival by pulse oximetry. A correlation was observed between arterial hypotension on admission and elevated intracranial pressure in 9 of 15 children (60%) and in the deceased (40%). Discussion: Clinical conditions, oxygenation, arterial hypotension, and treatment in the prehospital phase may influence the state of intracranial pressure and other intracranial variables in pediatric patients with severe head injury.

Introducción: La fase prehospitalaria del manejo del traumatismo craneoencefálico grave pediátrico puede tener una influencia directa en los resultados. Objetivo: Evaluar la influencia de variables prehospitalarias sobre la presión intracraneal y los resultados en pacientes pediátricos con TCE grave. Metodología: Se realizó un estudio descriptivo de 41 pacientes pediátricos que ingresaron al servicio de urgencias médicas y posteriormente ingresaron a la unidad de cuidados intensivos pediátricos por traumatismo craneoencefálico severo entre enero de 2003 y diciembre de 2018. Resultados: predominan los niños de 5 a 17 años, y el mayor número de casos se recibieron entre las 0-3h en el centro de neurotrauma. De los 41 casos, 27 llegaron con vía aérea no acelerada y se verificó hipoxia al llegar mediante oximetría de pulso. Se observó correlación entre hipotensión arterial al ingreso y presión intracraneal elevada en 9 de 15 niños (60%) y en los fallecidos (40%). Discusión: Las condiciones clínicas, la oxigenación, la hipotensión arterial y el tratamiento en la fase prehospitalaria pueden influir en el estado de la presión intracraneal y otras variables intracraneales en pacientes pediátricos con traumatismo craneoencefálico grave.

Encefalopatia hipoxica isquemica neonatal avances y nuevos tratamientos basados en las bases patofisiologicas de la injuria / Neonatal hypoxic ischemic encephalopathy: Progress and new treatments according to the pathophysiological basis of the injury

Resumen La encefalopatía hipóxica isquémica del neonato (EIH) es un tipo de injuria causada por la falta de oxí geno en el cerebro durante el periodo neonatal. Es un síndrome clínico claramente reconocible en recién na cidos a término y prematuros debido a asfixia fetal en el momento del nacimiento. Se estima que EHI ocurre a una frecuencia de1 a 3 por cada 1000 nacimientos vivos al año en países desarrollados. En países de bajo o mediano ingreso, la incidencia es hasta 10-20 veces más alta, equivalente a 1-8 nacidos vivos por cada 1000. El impacto social y económico ha sido estimado en cerca de 50.2 millones de dólares por año de vida ajustados a discapacidad. Así mismo, se estima que 7 es el número necesario de pacientes a tratar con hipotermia corporal terapéutica (HCT) para evitar un caso de muerte o minusvalía severa. La etiología es multifactorial e incluye factores prenatales, perinatales o post natales. El diagnóstico se basa en la incapacidad para respirar en el momento del nacimiento requirien do ventilación asistida, Apgar menos de 5 a los 5 y 10 minutos, alteración del estado normal de conciencia, reflejos neonatales y de tono muscular. Este artículo revisa los avances y estrategias terapéuticas estableci das y emergentes basadas en las fases pato-fisiológicas de este proceso.

Abstract Neonatal hypoxic ischemic encephalopathy (HIE) is a type of injury caused by lack of oxygen in the brain during the neonatal period. It is a clinical syndrome clearly rec ognizable in term and premature newborns secondary to asphyxia at the time of delivery. HIE is estimated to occur at a frequency of 1-3 for each 1000 alive newborns per year in developed countries. In countries of low or medium income, the incidence is up to 10-20 times higher, equivalent to 1-8 alive newborns per each 1000. The social and economic impact has been estimated near US$ 50.2 million per year of life adjusted to disability. At the same time, it is estimated in 7, the number of patients needed to treat with corporal cooling therapy (CCT) to prevent one case of death or se vere disability. The etiology is multifactorial and includes prenatal, perinatal and postnatal factors. The diagnosis is based in the inability to support spontaneous breath at the time of delivery requiring assisted ventilation, Apgar less than 5 at 5 and 10 minutes, altered level of consciousness, neonatal reflexes and muscle tone. This article is a review of the stablished and emergent therapeutic strategies based on the pathophysiological disease process.

Síndromes clínicos en la infección aguda y crónica de la COVID-19 en población nativa y residente de altura durante la primera y segunda ola

Objetivo: Clasificar los síntomas de la infección aguda y crónica de la COVID-19 en síndromes clínicos, en un grupo poblacional que vive en altura, durante la primera y segunda ola. Materiales y métodos: Estudio prospectivo y longitudinal. Se aplicó un cuestionario virtual a personas infectadas por el SARS-CoV-2 durante la primera y segunda ola, en el periodo marzo del 2020 a diciembre del 2021. Las medidas de tendencia central se expresaron en promedios y porcentajes, con un intervalo de confianza del 95 %. La prueba de ji al cuadrado asoció variables y consideró un valor p ≤ 0,05. Se utilizó el paquete estadístico SPSS 22. Resultados: Participaron 87 mujeres y 63 varones, con una edad promedio de 44,12 (±14,56) años. El 48,70 % se contagiaron en la primera ola y 51,30 %, en la segunda. Los 59 síntomas identificados se agruparon en 19 síndromes correspondientes a la fase aguda y 18 correspondientes a la fase crónica. Los síndromes más frecuentes en la fase aguda fueron el tóxico-infeccioso agudo incompleto, con 79,30 %; el de disfunción del gusto y olfato, con 60,70 %, y el ansioso-depresivo, con 56,79 %. La fase crónica se denominó síndrome pos-COVID-19 y fue subdividida en tres fases, la posaguda, la crónica y la de transportador prolongado. En las fases posaguda y crónica aparecen el síndrome de agotamiento muscular y el doloroso, que persisten hasta la fase de transportador prolongado, en donde los síntomas residuales se consideran secuelas. El síndrome pos-COVID-19 se presentó en 64,55 % de los participantes. Conclusiones: Este estudio ha demostrado una frecuencia mayor de síntomas dependientes de la invasión del virus al sistema nervioso central y periférico tanto en la fase aguda como en el síndrome pos-COVID-19. Es posible que la hipoxia hipobárica al prolongar la inflamación y estimular el estrés oxidativo determine un síndrome pos-COVID-19 más prolongado, y que este tenga mayor repercusión en el sistema nervioso.

Objective: To classify into clinical syndromes the symptoms of acute and chronic COVID-19 infection among a highaltitude population during the first and second waves. Materials and methods: A prospective and longitudinal study. An online questionnaire was administered to people infected with SARS-CoV-2 during the first and second waves from March 2020 to December 2021. The measures of central tendency were expressed as means and percentages with a 95 % confidence interval. The chi-square test associated the variables and considered a p value ≤ 0.05. IBM SPSS Statistics statistical software V22 was used. Results: A total of 87 women and 63 men with an average age of 44.12 (± 14.56) years participated in the research, out of whom 48.70 % and 51.30 % were infected in the first and second waves, respectively. The 59 reported symptoms were grouped into 19 syndromes for the acute phase and 18 for the chronic phase. The most frequent syndromes in the acute phase were incomplete acute toxic infectious disorders (79.30 %), taste and smell disorders (60.70 %) and anxiety and depressive disorders (56.79 %). Chronic COVID was called post-COVID-19 syndrome and was subdivided into three phases: post-acute, chronic and long-haul. In the post-acute and chronic phases, muscle fatigue and weakness as well as pain and aches appeared, persisting until the long-haul phase, where lingering symptoms were considered sequelae. Post-COVID-19 syndrome occurred in 64.55 % of the participants. Conclusions: This study has shown an increased frequency of symptoms affecting the central and peripheral nervous system in both the acute phase and post-COVID-19 syndrome. It is possible that hypobaric hypoxia, by prolonging inflammation and stimulating oxidative stress, may lead to a longer post-COVID-19 syndrome, with a greater impact on the nervous system.

Factor inducible por hipoxia en cáncer

El oxígeno y dióxido de carbono son vitales en la respiración, sus variaciones fuera del rango fisiológico son una amenaza para la supervivencia de las células. La hipoxia es una condición común en la mayoría de los tumores malignos, la cual promueve angiogénesis y vascularización disfuncional, mayor proliferación celular y la adquisición de un fenotipo de transición epitelial a mesenquimatoso, que contribuye con la metástasis; asimismo, altera el metabolismo de las células cancerosas y genera resistencia a la terapia, ya que induce a la inactividad celular. Por tanto, la hipoxia es un factor negativo, asociado a resultados adversos en la mayoría de los tratamientos de los distintos tipos de cáncer. El factor inducible por hipoxia (HIF) es el factor de transcripción relacionado con la hipoxia en cáncer, que produce la activación de más de una centena de genes reguladores de la actividad celular, que generan funciones cruciales para el desarrollo del cáncer. El objetivo principal de la presente revisión es puntualizar la importancia de la hipoxia en la génesis del cáncer, conocer las principales moléculas que interactúan en la expresión del HIF, explicar los mecanismos moleculares de las vías involucradas en la inducción del HIF, las consecuencias celulares por su alteración y las potenciales terapias dirigidas contra este factor. Se consultaron PubMed, Scopus y SciELO, del año 1990 hasta el año 2022, y se buscaron las referencias bibliográficas en relación con las palabras clave asociadas al factor inducible por hipoxia y cáncer. En conclusión, la sobreexpresión de HIF-1α en biopsias tumorales se asocia con una mayor mortalidad de pacientes en cánceres humanos. Los posibles genes diana regulados por HIF-1α que pueden desempeñar un papel en la progresión tumoral están empezando a descubrirse. A pesar de que se han estudiado cientos de compuestos en relación con el HIF en cáncer, en la actualidad existen pocos inhibidores del HIF aprobados en el mercado mundial; asimismo, muchos estudios clínicos, en sus distintas fases en desarrollo, no muestran resultados alentadores. Probablemente, en el futuro, cuando se tenga una mejor comprensión de la estructura, funcionamiento molecular y biológico de este factor, se desarrollarán fármacos más específicos para la inhibición del HIF.

Oxygen and carbon dioxide are essential for breathing; variations in these gases outside of the normal range are a threat to cell survival. Hypoxia is a common condition that occurs in most malignant tumors, increases angiogenesis and defective vascularization, promotes cell proliferation and acquires an epithelial-mesenchymal transition phenotype, which causes metastasis. It also affects cancer cell metabolism and makes patients resistant to treatment by causing cell quiescence. As a result, hypoxia is a detrimental component that is linked to unfavorable outcomes in most cancer treatments. Through the activation of more than a hundred genes that control cell activity, which produce key functions for cancer development, the transcription factor known as hypoxia-inducible factor (HIF) is linked to hypoxia in cancer. This review's main goals are to highlight the role of hypoxia in the development of cancer, identify the key molecules that interact to promote HIF expression, explain the molecular mechanisms of the pathways that lead to HIF induction, describe the cellular effects of HIF alteration, and discuss potential HIF-targeted therapies. Articles from 1990 to 2022 were reviewed in PubMed, Scopus and SciELO databases. Keywords related to cancer and HIF were searched in bibliographical references. In conclusion, HIF-1α overexpression in tumor biopsies is associated with increased patient mortality in human cancers. Potential HIF-1α-regulated target genes that may play a role in tumor progression are starting to be identified. Although hundreds of chemicals have been studied in relation to HIF in cancer, there are currently few approved HIF inhibitors available on the global market; moreover, many clinical trials, in their various stages of development, do not show encouraging results. It is likely that in the future, when there is a better understanding of the structure, molecular and biological functioning of this factor, more specific drugs for HIF inhibition will be developed.

Necrosis laminar cortical cerebral como manifestación de estatus epiléptico inducido por consumo crónico de alcohol

Introducción: la necrosis laminar cortical es un término radiológico que describe la presencia de lesiones hiperdensas de localización cerebral, las cuales siguen una distribución giriforme y se observan con mayor sensibilidad en los estudios de resonancia magnética cerebral (RM). Esta condición patológica, que afecta a la corteza del cerebro, suele ser secundaria a una depleción de sus fuentes energéticas como consecuencia de hipoxia cerebral, alteraciones metabólicas, hipoglicemia, falla renal o hepática, intoxicaciones o infecciones. Presentación del caso: se reporta el caso de un hombre de 23 años, con antecedente de consumo crónico de alcohol, quien ingresó al servicio de urgencias de nuestra institución con un estado epiléptico. El estudio de resonancia magnética cerebral demostró la presencia de una necrosis laminar cortical con posterior déficit neurocognitivo y funcional. Conclusión: si se consideran las secuelas neurológicas potenciales asociadas a un estado epiléptico, relacionadas con necrosis laminar cortical cerebral, es necesario hacer un diagnóstico etiológico precoz, así como una atención terapéutica temprana a los pacientes.

Introduction: Cortical laminar necrosis (CLN) is radiologically defined as high-intensity cortical lesions on T1-weighted MRI images that follow a gyral distribution in the brain. Histopathologically, this pathological condition is characterized by necrosis of the cortex involving neurons, glial cells, and blood vessels. It is usually triggered by hypoxia, metabolic alterations, drugs, intoxications, or infections. Case description: We report the case of a 23-year-old man with a history of chronic alcohol abuse who was admitted to our institution with status epilepticus. The brain magnetic resonance imaging performed on this patient showed cortical laminar necrosis associated with subsequent neurocognitive deficits. Conclusion: Due to the potential neurological sequelae secondary to status epilepticus in relation to cortical laminar necrosis as permanent brain damage, it is necessary to provide early diagnosis and treatment for these patients.

Expression of protein phosphatase 4 in different tissues under hypoxia

Relevant research data shows that there is a certain degree of energy metabolism imbalance in highland residents. Protein phosphatase 4 (PP4) has been found as a new factor in the regulation of sugar and lipid metabolism. Here, we investigate the differential expression of PP4 at a simulated altitude of 4,500 m in the heart, lung, and brain tissues of rats. A hypoxic plateau rat model was established using an animal decompression chamber. A blood routine test was performed by an animal blood cell analyzer on rats cultured for different hypoxia periods at 4,500 m above sea level. Quantitative polymerase chain reaction (qPCR) and western blot were used to detect the changes of protein phosphatase 4 catalytic subunit (PP4C) gene and protein in heart, lung, and brain tissues. The PP4C gene with the highest expression level found in rats slowly entering the high altitude area (20 m-2200 m-7 d-4500 m-3 d) was about twice as high as the low elevation group (20 m above sea level). The simulated high-altitude hypoxia induced an increase of PP4C expression level in all tissues, and the expression in the lung tissue was twice as expressed as heart and brain tissue at high altitude (P < 0.05). These results suggest that the PP4 phosphatase complex is ubiquitously expressed in rat tissues and likely involved in adaptation to or disease associated with high-altitude hypoxia.

The Role of MMP-9 in Regulating Degradation of the Splenic Microvascular Basement Membrane Induced by High Altitude Hypoxia / Rol de la MMP-9 en la Regulación de la Degradación de la Membrana Basal Microvascular Esplénica Inducida por Hipoxia de Altura

SUMMARY: To investigate changes of MMP-9 in the rat spleen and hypoxia-induced microvascular basement membrane under high altitude hypoxia. Thirty male specific pathogen-free Sprague Dawley rats were randomly divided into control and hypoxia groups, with 15 rats in each group. The rats in the control group were placed in Dingxi City, Gansu Province (2080 m above sea level) for 30 days. Rats in the hypoxia group were raised in a hypoxic environment in Maduo County, Qinghai Province (4300 m above sea level), for 30 days to establish a hypoxic rat model. Routine blood tests, MMP-9 mRNA, MMP-9 protein, and the spleen microvascular basement membrane were detected. (1) Compared with the control group, the red blood cell count, hemoglobin, and hematocrit levels of the rats in the hypoxia group were all increased; thus, a hypoxia model was successfully established. (2) Compared with the control group, the expression of MMP-9 mRNA and protein was significantly higher in the spleen of rats in the hypoxic group, and the difference was statistically significant (P <0.05). (3) Compared with the control group, the blood vessel basement membrane in the spleen of the hypoxia group was degraded. Under natural low air pressure and high altitude conditions, the expression of MMP-9 in rat spleen tissue increases and participates in the degradation of the microvascular basement membrane.

El objetivo de este trabajo fue investigar los cambios de la MMP-9 en el bazo de la rata y la membrana basal microvascular inducida bajo hipoxia a gran altura. Treinta ratas macho Sprague Dawley, libres de patógenos específicos, se dividieron aleatoriamente en dos grupos de 15 ratas cada uno, un grupo control y un grupo hipoxia. Durante 30 días las ratas del grupo control estuvieron en la ciudad de Dingxi, provincia de Gansu (2080 m sobre el nivel del mar). Las ratas del grupo de hipoxia se criaron en un entorno hipóxico en el condado de Maduo, provincia de Qinghai (4300 m sobre el nivel del mar), durante 30 días para establecer un modelo de rata hipóxica. Se realizaron análisis de sangre de rutina, ARNm de MMP-9, proteína MMP-9 y de la membrana basal microvascular del bazo. En comparación con el grupo control, el recuento de glóbulos rojos, la hemoglobina y los niveles de hematocrito de las ratas del grupo de hipoxia aumentaron; por lo tanto, se estableció con éxito un modelo de hipoxia. En comparación con el grupo control, la expresión de ARNm y proteína de MMP-9 fue significativamente mayor en el bazo de las ratas del grupo hipóxico, siendo la diferencia estadísticamente significativa (P <0,05). En comparación con el grupo control, la membrana basal de los vasos sanguíneos estaba degradada en el bazo del grupo hipoxia. En condiciones naturales de baja presión atmosférica y gran altitud, la expresión de MMP-9 en el tejido del bazo de la rata aumenta y participa en la degradación de la membrana basal microvascular.

Importance of assessing biomarkers and physiological parameters of anemia-induced tissue hypoxia in the perioperative period

Abstract Anemia is associated with increased risk of Acute Kidney Injury (AKI), stroke and mortality in perioperative patients. We sought to understand the mechanism(s) by assessing the integrative physiological responses to anemia (kidney, brain), the degrees of anemia-induced tissue hypoxia, and associated biomarkers and physiological parameters. Experimental measurements demonstrate a linear relationship between blood Oxygen Content (CaO2) and renal microvascular PO2 (y = 0.30x + 6.9, r2= 0.75), demonstrating that renal hypoxia is proportional to the degree of anemia. This defines the kidney as a potential oxygen sensor during anemia. Further evidence of renal oxygen sensing is demonstrated by proportional increase in serum Erythropoietin (EPO) during anemia (y = 93.806*10−0.02, r2= 0.82). This data implicates systemic EPO levels as a biomarker of anemia-induced renal tissue hypoxia. By contrast, cerebral Oxygen Delivery (DO2) is defended by a profound proportional increase in Cerebral Blood Flow (CBF), minimizing tissue hypoxia in the brain, until more severe levels of anemia occur. We hypothesize that the kidney experiences profound early anemia-induced tissue hypoxia which contributes to adaptive mechanisms to preserve cerebral perfusion. At severe levels of anemia, renal hypoxia intensifies, and cerebral hypoxia occurs, possibly contributing to the mechanism(s) of AKI and stroke when adaptive mechanisms to preserve organ perfusion are overwhelmed. Clinical methods to detect renal tissue hypoxia (an early warning signal) and cerebral hypoxia (a later consequence of severe anemia) may inform clinical practice and support the assessment of clinical biomarkers (i.e., EPO) and physiological parameters (i.e., urinary PO2) of anemia-induced tissue hypoxia. This information may direct targeted treatment strategies to prevent adverse outcomes associated with anemia.

La importancia de la determinación de la deuda de oxígeno en el perioperatorio / The importance of oxygen debt determination in the perioperative period

Resumen: El fenómeno de la deuda de oxígeno (dO2) descrito hace varias décadas en el contexto del ejercicio físico se ha incorporado progresivamente al terreno de la medicina. En particular se ha utilizado durante los cambios hemodinámicos producidos por la cirugía y la anestesia en los pacientes de alto riesgo. La dO2 se definió como el aumento en la cantidad de oxígeno consumida por el organismo inmediatamente después de realizar un ejercicio físico hasta que el consumo se normaliza nuevamente. En el perioperatorio se llega a producir cuando se presenta un desbalance entre la oferta (DO2) y la demanda de oxígeno (VO2) que lleva a hipoxia tisular. El grado de la dO2 tisular se ha relacionado directamente con la falla de órganos múltiples y morbimortalidad perioperatoria. A pesar de los avances en la medicina, aún no es posible prevenir o disminuir la dO2 con la administración de líquidos o con el uso de agentes vasoactivos. Por lo que un retardo o manejo inadecuado de la hemodinámica perioperatoria producirá hipoperfusión e hipoxia tisular afectando los resultados de la cirugía. El conocimiento y la valoración de la dO2 es esencial durante la anestesia del paciente de alto riesgo. Para lograr este objetivo se requiere del uso de índices adecuados que permitan detectar y cuantificar la hipoperfusión tisular y el desbalance entre la DO2 y la VO2. En esta revisión se presentan los conceptos fundamentales de la dO2, su mecanismo, detección y cuantificación; además de las intervenciones para evitarla o disminuirla y las recomendaciones para los anestesiólogos con el fin de asegurar mejores resultados en los pacientes quirúrgicos de alto riesgo.

Abstract: The phenomenon of oxygen debt (dO2) described several decades ago in the context of physical exercise has been incorporated into medicine, particularly during the hemodynamic changes produced by surgery and anesthesia in high-risk patients. dO2 is defined as the increase in the amount of oxygen consumed by the body immediately after physical exercise until O2 consumption returns to normal. In the perioperative period, an imbalance between oxygen supply (DO2) and demand (VO2) could generate dO2. The degree of tissue dO2 has been directly related to multiple organ failure and perioperative morbimortality. Despite advances in medicine, it is not yet possible to prevent or lower the dO2 with fluid administration or vasoactive agents. Delay or inadequate management of hemodynamics could produce tissue hypoperfusion and hypoxia, affecting surgery outcomes. Knowledge and assessing dO2 during perioperative are essential during anesthesia for high-risk patients. Adequate indices are required to detect and quantify tissue hypoperfusion and the imbalance between DO2 and VO2 during anesthesia. This review presents the mechanism, detection, and quantification of dO2. In addition to interventions to avoid or reduce dO2 and recommendations for anesthesiologists to ensure better results in high-risk surgical patients.

Concentraciones de oxígeno intermitentes tienen impacto en el desarrollo postnatal temprano de ratas Sprague-Dawley: efectos en CA1 del hipocampo / Intermittent oxygen concentrations have an impact on the early postnatal development of Sprague-Dawley rats: effects on hippocampal CA1

El periodo postnatal temprano se caracteriza por rápido crecimiento cerebral, posiblemente relacionado con variaciones del oxígeno tisular. Esto ha motivado el estudio de protocolos que suministran diferentes concentraciones de oxígeno intermitentes, para observar sus efectos morfológicos y cerebrales. Se utilizaron 52 crías de ratas Sprague Dawley, distribuidas en igual número a cuatro grupos experimentales, Control (C, 21 %O2), Hipoxia Intermitente (HI, 11 %O2), Hiperoxia Intermitente (HOI, 30 %O2) e Hipoxia Hiperoxia Intermitente (HHI, 11 % -30 %O2). Los protocolos consideraron 5 ciclos de 5 minutos de dosificación, durante 50 minutos diarios. Se realizó en una cámara semihermética entre los días 5 al 11 postnatales. Las evaluaciones de crecimiento corporal y cuantificación neuronal, se realizaron en las crías macho, en el día 28 postnatal. El peso corporal en el grupo hipoxia intermitente mostró diferencias significativas respecto al grupo hiperoxia intermitente (HI vs HOI, p<0,01) y al grupo hipoxia-hiperoxia Intermitente (HI vs HHI, p< 0,001). La talla corporal disminuyó en el grupo hipoxia-hiperoxia intermitente con diferencias significativas respecto del grupo control (C vs HHI, p<0,05) y respecto del grupo hipoxia intermitente (HHI vs HI, p< 0,01). El conteo neuronal en el área CA1 del hipocampo aumentó en el grupo hipoxia intermitente con diferencias significativas respecto a los grupos control (C vs HI; p<0,05), al grupo hiperoxia intermitente (HI vs HOI; p<0,001) y al grupo hipoxia-hiperoxia intermitente (HI vs HHI; p<0,001). Finalmente, el grupo hipoxia- hiperoxia Intermitente disminuyó significativamente en la cantidad de neuronas en comparación al grupo hiperoxia intermitente (HHI vs HOI; p<0,001). La hipoxia intermitente mostró resultados beneficiosos en el crecimiento corporal y cantidad de neuronas en el área CA1 del hipocampo, en contraste, la hipoxia hiperoxia intermitente experimentó resultados adversos con disminución de estas variables, en el periodo postnatal temprano de la rata.

SUMMARY: The early postnatal period is characterized by rapid brain growth, possibly related to variations in tissue oxygen. This has motivated the study of protocols that supply different intermittent oxygen concentrations, to observe their morphological and cerebral effects. Fifty-two pups Sprague-Dawley rats were distributed in equal numbers into four experimental groups, Control (C, 21 %O), Intermittent Hypoxia (HI, 11 %O), Intermittent Hyperoxia (HOI, 30 %O2) and Intermittent Hypoxia Hyperoxia (HHI, 11 % - 30 %O2). The protocols considered 5 cycles of 5 min of dosing, for 50 min diary. It was performed in a semi- hermetic chamber between 5 to 11postnatal days. The evaluations of body growth and neuronal quantification were analyzed in male pups, on postnatal day 28. Body weight in the intermittent hypoxia group showed significant differences compared to the intermittent hyperoxia group (HI vs HOI, p<0.01) and the intermittent hypoxia- hyperoxia group (HI vs HHI, p<0.001). Body size decreased in the Intermittent hypoxia-hyperoxia group with significant differences compared to the control group (C vs HHI, p<0.05) and with respect to the intermittent hypoxia group (HHI vs HI, p<0.01). The neuronal count in the area CA1 of the hippocampus increased in the intermittent hypoxia group with significant differences compared to the control groups (C vs HI; p<0.05), to the intermittent hyperoxia group (HI vs HOI; p< 0.001) and the intermittent hypoxia-hyperoxia group (HI vs HHI; p<0.001). Finally, the intermittent hypoxia- hyperoxia group decreased significantly in the number of neurons compared with the intermittent hyperoxia group (HHI vs HOI; p<0.001). Intermittent hypoxia showed beneficial results in body growth and the number of neurons in the CA1 area of the hippocampus, in contrast, intermittent hypoxia-hyperoxia experienced adverse results with a decrease in these variables, in the early postnatal period of the rat.

Comparison between selective head cooling and whole-body cooling in neonatal therapeutic hypothermia / Comparação entre resfriamento seletivo da cabeça e resfriamento de corpo inteiro na hipotermia terapêutica neonatal

INTRODUCTION: Experimental evidence, as well as improved clinical studies of the reduction of brain injury and, improves the neurological outcome, in newborns with hypoxic-ischemic encephalopathy (HIE) occurring in therapeutic hypothermia (TH). OBJECTIVE: To verify the potential of hypothermic hypoxic-ischemic encephalopathy (HIE) therapy in neonatal asphyxia, based on literature data, comparing the benefits between selective head cooling (SHC) and whole-body cooling (WBC), see that the use of TH as a standard treatment in newborns with moderate or severe HIE has been adopted. METHODS: A search was performed in the PubMed and SciELO databases of human studies, using the keywords "Therapeutic Hypothermia", "Induced Hypothermia", and "Hypoxic-Ischemic Encephalopathy", "Selective cooling of the head", "Total body cooling" and its variables. RESULTS: Eleven articles were selected to compose the review, after detailed reading. There is a consensus, that the reduction of the risk of death or disability at 18 months of life in neonates with moderate to severe HIE, occurs to TH through the techniques of WBC or SHC. It was found in the studies that there is no difference in terms of adverse effects between the two methods. As for radiological changes, such as hypoxic-ischemic injuries and the incidence of seizures after cooling, they are more frequent with SHC. CONCLUSION: Both WBC and SHC demonstrated neuroprotective properties, although WBC provides a broader area of brain protection. However, no significant differences were found between the methods in terms of adverse effects and beneficial short or long-term results.

INTRODUÇÃO: Evidências experimentais, assim como estudos clínicos, sugerem a redução da lesão cerebral e melhora do desfecho neurológico, em recém-nascidos com encefalopatia isquêmica hipóxica (EHI) submetidos à hipotermia terapêutica (HT). OBJETIVO: Verificar a potencialidade da terapia hipotérmica de encefalopatia hipóxico-isquêmica (EHI) na asfixia neonatal, com base em dados da literatura, comparando os benefícios entre o resfriamento seletivo da cabeça (RSC) e o resfriamento de corpo inteiro (RCI), visto que o uso de hipotermia terapêutica (HT) como tratamento padrão em recém-nascidos com EHI moderada ou grave tem sido amplamente adotada. MÉTODOS: Foi realizada uma busca nas bases de dados PubMed e SciELO de estudos em humanos, utilizando-se as palavras-chave "Therapeutic Hypothermia", "Induced Hypothermia", "Hypoxic-Ischemic Encephalopathy", "selective head cooling", "whole body cooling" e suas respectivas variáveis. RESULTADOS: Foram selecionados 11 artigos para compor a revisão, após leitura detalhada. É consenso, a redução do risco de morte ou incapacidade aos 18 meses de vida nos neonatos com EHI moderado a grave, submetidos à HT através das técnicas de RCI ou RSC. Constatou-se diante dos estudos que não há diferença em termos de efeitos adversos entre os dois métodos. Quanto às alterações radiológicas, as lesões hipóxico-isquêmicas e incidência de convulsões após o resfriamento são mais frequentes com o RSC. CONCLUSÃO: Tanto RCI quanto o RSC demonstraram propriedades neuroprotetoras, embora o RCI proporcione uma área de proteção cerebral mais ampla. No entanto, não foram constatadas diferenças significativas entre os métodos quanto a efeitos adversos e a resultados benéficos em curto e longo prazo.

Efectos psiquiátricos de la hipoxia normobárica intermitente. Un Estudio prospectivo

Introducción: La hipoxia intermitente consiste en la administración de aire reducido en oxígeno por episodios, para lograr hipoxia en sangre, alternados con intervalos de normoxia. Tiene uso terapéutico en varias patologías médicas, pero sus efectos psiquiátricos no han sido estudiados. Se han descrito efectos neurogénicos y en modelos animales puede ayudar a prevenir depresión y ansiedad en respuesta al estrés. Objetivo: Determinar la existencia de efectos psiquiátricos de la hipoxia normobárica intermitente en seres humanos. Método: Estudio prospectivo descriptivo. Se incluyeron pacientes mayores de 18 años, que tuvieran programado un plan de hipoxia normobárica intermitente en la clínica Hipoxykine. Se utilizó una ficha de registro y la escala breve de síntomas (BSI) que fue realizada al inicio, mitad (segunda semana) y finalizado el tratamiento (cuarta semana). Resultados: Se incluyeron 22 participantes (50% mujeres) con una mediana de edad de 46 años. Hubo una reducción del índice global de gravedad del BSI estadísticamente significativo (p <0.05) al comparar tanto la primera como la segunda medición respecto a la final. Respecto al análisis según género, esta diferencia fue estadísticamente significativa (p <0.05) en hombres. Conclusiones: La hipoxia normobárica intermitente no produce ni empeora síntomas psiquiátricos y podría tener potencial terapéutico. Se requieren nuevos estudios prospectivos.

Introduction: Intermittent normobaric hypoxia consists of the administration of air reduced in oxygen by episodes, to achieve hypoxia in blood alternated with intervals of normoxia. It has a role in brain development and neuroprotection. However, in the literature there are only studies in animal models. Objective: To determine the existence of psychiatric effects of intermittent normobaric hypoxia in humans. Method: Prospective descriptive study. We included patients over 18 years of age who had an intermittent normobaric hypoxia plan scheduled at the Hipoxykine clinic. A record sheet and the brief symptom inventory (BSI) were carried out at the beginning, middle (second week) and end of treatment (fourth week). Results: We included 22 participants (50% women) with a median age of 46 years. There was a reduction in the overall severity index of the statistically significant (p <0.05) when comparing both the first and second measurements with respect to the final. Regarding the analysis according to gender, this difference was statistically significant (p <0.05) in men. Conclusions: Intermittent normobaric hypoxia does not produce or worsen psychiatric symptoms. It could have therapeutic potential. Further prospective studies are required.

iPSCs ameliorate hypoxia-induced autophagy and atrophy in C2C12 myotubes via the AMPK/ULK1 pathway

Background Duchenne muscular dystrophy (DMD) is an X-linked lethal genetic disorder for which there is no effective treatment. Previous studies have shown that stem cell transplantation into mdx mice can promote muscle regeneration and improve muscle function, however, the specific molecular mechanisms remain unclear. DMD suffers varying degrees of hypoxic damage during disease progression. This study aimed to investigate whether induced pluripotent stem cells (iPSCs) have protective effects against hypoxia-induced skeletal muscle injury. Results In this study, we co-cultured iPSCs with C2C12 myoblasts using a Transwell nested system and placed them in a DG250 anaerobic workstation for oxygen deprivation for 24 h. We found that iPSCs reduced the levels of lactate dehydrogenase and reactive oxygen species and downregulated the mRNA and protein levels of BAX/BCL2 and LC3II/ LC3I in hypoxia-induced C2C12 myoblasts. Meanwhile, iPSCs decreased the mRNA and protein levels of atrogin-1 and MuRF-1 and increased myotube width. Furthermore, iPSCs downregulated the phosphorylation of AMPKA and ULK1 in C2C12 myotubes exposed to hypoxic damage. Conclusions Our study showed that iPSCs enhanced the resistance of C2C12 myoblasts to hypoxia and inhibited apoptosis and autophagy in the presence of oxidative stress. Further, iPSCs improved hypoxia-induced autophagy and atrophy of C2C12 myotubes through the AMPK/ULK1 pathway. This study may provide a new theoretical basis for the treatment of muscular dystrophy in stem cells.

Transcriptomics Provides Novel Insights into the Regulatory Mechanism of IncRNA HIF1 A-AS1 on Vascular Smooth Muscle Cells

ABSTRACT Introduction: Thoracic aortic aneurysm is a potentially fatal disease with a strong genetic contribution. The dysfunction of vascular smooth muscle cells (VSMCs) contributes to the formation of this aneurysm. Although previous studies suggested that long non-coding ribonucleic acid (RNA) hypoxia inducible factor 1 α-antisense RNA 1 (HIF1A-AS1) exerted a vital role in the progression and pathogenesis of thoracic aortic aneurysm, we managed to find a new regulatory mechanism of HIF1A-AS1 in VSMCs via transcriptomics. Methods: Cell viability was detected by the cell counting kit-8 assay. Cell apoptosis was assessed by Annexin V-fluorescein isothiocyanate/propidium iodide double staining. Transwell migration assay and wound healing assay were performed to check the migration ability of HIF1A-AS1 on VSMCs. The NextSeq XTen system (Illumina) was used to collect RNA sequencing data. Lastly, reverse transcription-quantitative polymerase chain reaction confirmed the veracity and reliability of RNA-sequencing results. Results: We observed that overexpressing HIF1A-AS1 successfully promoted apoptosis, significantly altered cell cycle distribution, and greatly attenuated migration in VSMCs, further highlighting the robust promoting effects of HIF1A-AS1 to thoracic aortic aneurysm. Moreover, transcriptomics was implemented to uncover its underlying mechanism. A total of 175 differently expressed genes were identified, with some of them enriched in apoptosis, migration, and cell cycle-related pathways. Intriguingly, some differently expressed genes were noted in vascular development or coagulation function pathways. Conclusion: We suggest that HIF1A-AS1 mediated the progression of thoracic aortic aneurysm by not only regulating the function of VSMCs, but also altering vascular development or coagulation function.

Fisiología respiratoria. Neumología de altura: saturación de oxígeno, edema pulmonar y pruebas de función pulmonar / Respiratory physiology - High -altitude pneumology: oxygen saturation, pulmonary edema and pulmonary function tests

En las alturas, sobre todo a 2500 metros sobre el nivel del mar, la cantidad absoluta de oxígeno va decreciendo y por lo tanto la cantidad disponible para el intercambio gaseoso disminuye, produciéndose una vasoconstricción hipóxica pulmonar (VHP). La VHP asociada a la hipoxia hipobárica de la altura produce un aumento de la presión pulmonar que es mayor en los lactantes y a mayores alturas. No hay valores únicos de saturación de oxígeno (SatO2) en la altura, porque ésta va disminuyendo según el mayor nivel de altura, aumenta con la edad, y la brecha entre la vigilia y sueño es grande (sobre todo en los primeros meses de vida). El 25% de los niños sanos que viven en altura tienen valores de SatO2 significativamente menores que el 75% restante. Los valores normales de los índices de apnea/hipopnea son distintos a los de nivel del mar. El edema pulmonar de las alturas es una patología frecuente, que se produce por un incremento desproporcionado en la VHP reflejando una hiperactividad del lecho vascular pulmonar ante la exposición aguda a la hipoxia hipobárica. Tiene cuatro fenotipos, es infrecuente en menores de 5 años y rara vez es mortal, la sospecha clínica y el manejo oportuno con oxigeno es la clave. Finalmente, en la altura los valores normales de la función pulmonar de la espirometría, oscilometría de impulso y capacidad de difusión son distintos que a nivel del mar.

At high altitude, especially > 2,500 meters above sea level, the absolute amount of oxygen decreases and therefore the amount available for gas exchange decreases, producing hypoxic pulmonary vasoconstriction (VHP). VHP associated with high-altitude hypobaric hypoxia produces an increase in pulmonary pressure that is greater in infants and at higher altitudes. There are no single values of oxygen saturation (SatO2) at altitude, because it decreases with the highest level of altitude, increases with age, and the gap between wakefulness and sleep is large (especially in the first months of life). Around 25% of healthy children living at altitude have SatO2 values significantly lower than the remaining 75%. The normal values of the apnea/hypopnea indices are different from those at sea level. High altitude pulmonary edema is a frequent pathology that is produced by a disproportionate increase in VHP reflecting hyperactivity of the pulmonary vascular bed in the face of acute exposure to hypobaric hypoxia, it has four phenotypes, it is uncommon in children under 5 years of age, and it is rarely fatal, the clinical suspicion and timely management with oxygen is the key. Finally, at high altitude, the normal values of lung function from spirometry, impulse oscillometry, and diffusing capacity are different from those at sea level.