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.

Oxygen use in Atacama large millimeter and submillimeter (ALMA) arrays in Chajnantor valley at 5050 m / Uso de oxígeno en Atacama large millimeter and submillimeter (ALMA) en el valle de Chajnantor a 5050 m

The Chilean workforce has over 200,000 people that are intermittently exposed to altitudes over 4000 m. In 2012, the Ministry of Health provided a technical guide for high altitude workers that included a series of actions to mitigate the effects of hypoxia. Previous studies have shown the positive effect of oxygen enrichment at high altitudes. The Atacama Large Millimeter / submillimeter Arrays (ALMA) radiotelescope operate at 5,050 m (Array Operation Site, AOS) and is the only place in the world where Pressure Swing Adsorption (PSA) and Liquid Oxygen technologies have been installed at a large scale. Here we discuss our experience using oxygen supplementation at ALMA, to prevent the malaise and/or risks associated with exposure at 5,050 m. Antenna operators experienced chronic intermittent hypobaric hypoxia (CIHH, shiftwork 8 days HA*6 days rest SL) over 4 years. Studies to define normal O2 saturation values were performed in OSF and AOS by continuous recording during the shift. The outcomes showed no differences between production procedures (PSA or Liquid oxygen) in regulating oxygen availability at AOS facilities. As a result, big-scale installations have difficulties reaching the appropriate oxygen concentration due to leaks in high mobility areas. In addition, the PSA plant requires adequation and maintenance to operate at a very high altitude.

La fuerza laboral chilena cuenta con más de 200.000 personas que están expuestas intermitentemente a altitudes superiores a los 4000 m. En 2012, el Ministerio de Salud entregó una guía técnica para trabajadores de altura que incluía una serie de acciones para mitigar los efectos de la hipoxia. Estudios anteriores han demostrado el efecto positivo del enriquecimiento de oxígeno en altitudes elevadas. El radiotelescopio Atacama Large Millimeter/submillimeter Arrays (ALMA) opera a 5.050 m (Array Operation Site, AOS) y es el único lugar en el mundo donde se han instalado tecnologías de adsorción por cambio de presión (PSA) y oxígeno líquido a gran escala. Aquí discutimos nuestra experiencia usando suplementos de oxígeno en ALMA, para prevenir el malestar y/o los riesgos asociados con la exposición a 5.050 m. Los operadores de antena experimentaron hipoxia hipobárica intermitente crónica (CIHH, trabajo por turnos 8 días HA*6 días descanso SL) durante 4 años. Se realizaron estudios para definir valores normales de saturación de O2 en OSF y AOS mediante registro continuo durante el turno. Los resultados no mostraron diferencias entre los procedimientos de producción (PSA u oxígeno líquido) en la regulación de la disponibilidad de oxígeno en las instalaciones de AOS. Como resultado, las instalaciones a gran escala tienen dificultades para alcanzar la concentración de oxígeno adecuada debido a fugas en áreas de alta movilidad. Además, la planta de PSA requiere de adecuación y mantenimiento para operar a gran altura.

Fisiología respiratoria hipoxemia / Hypoxemia

La hipoxemia ocurre producto de una inadecuada captación de oxígeno a nivel pulmonar y se manifiesta como presión arterial de oxígeno menor a 60 mmHg o saturación arterial de oxígeno menor de 90%. Los mecanismos fisiopatológicos por los cuales se puede producir hipoxemia son hipoventilación, alteración del equilibrio ventilación perfusión, shunt cardiaco, alteración de la difusión y disminución de la presión inspirada de oxígeno. La comprensión de estos mecanismos es fundamental para entender su presentación clínica en distintas enfermedades.

Hypoxemia is the name given to inadequate uptake in the lung and is defined as an arterial oxygen pressure less than 60 mmHg or arterial oxygen saturation less than 90%. The pathophysiological mechanisms that can produce hypoxemia are: hypoventilation, ventilation perfusion mismatch, cardiac shunt, diffusion impairment and decreased inspired oxygen pressure. Full comprehension of these mechanism facilitates the understanding of hypoxemia among different diseases.

Asociación e interacciones de la apnea obstructiva del sueño (AOS) y del síndrome de hipoventilación obesidad (SHO) / Metabolic associations of the obstructive sleep apnea (AOS) and hypoventilation obesity syndrome

La apnea obstructiva del sueño (AOS) y el síndrome hipoventilación-obesidad (SHO) son patologías que se encuentran estrechamente asociadas a la obesidad como principal factor de riesgo, hasta un 70% de los pacientes con AOS son obesos. Ambas patologías comparten procesos fisiopatológicos comunes, donde destaca la inflamación sistémica, lo que, sumado a la hipoxia crónica intermitente y la fragmentación del sueño característicos de la AOS, aumenta considerablemente el riesgo de presentar comorbilidades metabólicas como síndrome metabólico, alteraciones en el metabolismo de la glucosa (resistencia a la insulina y diabetes mellitus tipo 2), y hígado graso metabólico. En esta revisión narrativa, se describirán los mecanismos identificados en estas asociaciones, así como la prevalencia y la evidencia sobre el tratamiento de la AOS y del SHO

Obstructive sleep apnea (OSA) and obesity-hypoventilation syndrome (OHS) are pathologies that are closely associated with obesity as the main risk factor, up to 70% of patients with OSA are obese. Both pathologies share common pathophysiological processes, where systemic inflammation stands out, which, added to the intermittent chronic hypoxia and sleep fragmentation characteristic of OSA, considerably increases the risk of presenting metabolic comorbidities such as metabolic syndrome, alterations in the metabolism of the glucose (insulin resistance and type 2 diabetes mellitus), and metabolic fatty liver. In this narrative review, the mechanisms identified in these associations will be described, as well as the prevalence and evidence on the treatment of OSA and OHS

Characterization of oxidative stress in animal model of neonatal hypoxia

Purpose To evaluate the oxidative stress in swine neonates submitted to hypoxia. Methods Ten large white piglets, healthy newborns, of both sexes, were divided into two groups and submitted to an experimental hypoxia protocol with reduced inspired oxygen fraction. The hypoxia group, composed of six animals, was submitted to oxygen reduction for 180 min. The animals in the control group, n = 4, were handled and evaluated simultaneously, but without oxygen reduction. Results 180 min after the start of the hypoxic insult, a significant difference was observed in the oximetry, and heart rate of the hypoxia group was compared to the control group (p<0.05). There was no significant difference in the oxidative stress analyses. Reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), lipid peroxidation (TBARS), protein carbonyl (PC), and myeloperoxidase (MPO) in the piglets’ brain tissue were analyzed. Conclusions Hypoxia causes adverse effects in swine neonates, although there is a natural physiological resistance of swine neonates to respond to this insult. Analyses of GSH, SOD, CAT, TBARS, MPO, and PC were tabulated and are presented as parameters for further studies to be carried out on an animal model of swine hypoxia.

Hipoxemia silenciosa y uso de oxímetro de pulso en el hogar para detección precoz de complicaciones por Covid-19: reporte de un caso y revisión de la literatura / Silent hypoxemia and use of pulse oximeter at home for early detection of complications from Covid-19: a case report and review of the literature

Silent hypoxemia is one of the clinical presentations caused by SARS-CoV-2. It is still considered a medical mystery, as there are inconsistencies between arterial oxygen saturation levels and respiratory symptoms; a clinical scenario that had not been seen before. Their main risk is that it delays medical assistance because they do not have breathing difficulties and, when they consult, the lung damage is quite advanced. The early detection of hypoxia can favor the premature diagnosis of COVID-19 pneumonia and start treatment without delay. The pulse oximeter is presented as a useful, inexpensive, and easy-to-use tool for monitoring oxygen saturation at home in mild illness and detecting silent hypoxemia. This work presents the case of a patient with COVID-19 who, thanks to the use of a pulse oximeter at home, was able to detect silent hypoxemia and favored the early diagnosis of SARS-CoV-2 pneumonia. (AU)

Enfermedad por coronavirus (COVID-19) en terapia intensiva: informe de un caso / Coronavirus disease (covid-19) in critical care: a case report

Una de las características de la afección pulmonar por enfermedad por coronavirus (COVID-19) es la disociación entre la gravedad de la hipoxemia y el mantenimiento de una mecánica respiratoria relativamente conservada. En este contexto se ha establecido una teoría en relación con dos fenotipos de pacientes con síndrome de distrés respiratorio del adulto (SDRA): un fenotipo Low, caracterizado por baja elastancia y baja reclutabilidad, y un fenotipo High, con características de alta elastancia y alta reclutabilidad. Presentamos el caso de un paciente que cursó internación en la Unidad de Terapia Intensiva de Adultos de nuestro hospital, con clínica, mecánica ventilatoria y patrón tomográfico compatible con el fenotipo Low de SDRA por COVID-19. (AU)

Dissociation between severity of hypoxemia and relative preserved respiratory mechanics is a characteristic observed in lung impairment due to coronavirus disease (COVID-19). Patients with COVID-19 that present adult respiratory distress syndrome (ARDS) are identified for one of two phenotypes according to a theory recently established. The Low phenotype is distinguished by low elastance and low recruitability; and the High phenotype, by high elastance and high recruitability. The case describes a patient admitted in the adult Intensive Care Unit of Hospital Italiano de Buenos Aires with observed symptoms, ventilatory mechanics and tomographic pattern that are compatible with Low phenotype of ARDS due to COVID-19. (AU)

El lado oculto de la hipoxemia / The dark side of hypoxemia

Acute respiratory distress syndrome (ARDS) is characterized by an increase in the intrapulmonary shunt (measured by the PaO2/FiO2 ratio) caused by bilateral alveolar-interstitial infiltrates which are not fully explained by fluid overload. However, there are some ARDS cases which present severe hypoxemia without clear lung infiltrates. An example of this, which has generated great controver- sy, is the infection caused by SARS-CoV-2. Understanding the pathophysiology of hypoxemia is absolutely crucial in order to establish the most appropriate therapeutic strategy for each patient. In the case of a severe hypoxemia (PaO/ FiO2 < 200 which represents a shunt greater than 30%) with a chest X-ray (or CT) without clear and extensive bilateral infiltrates, it is important to consider that the shunt can be caused due to vascular involvement. This shunt could be explained two ways: an increase in pulmonary vascular resistance (PVR), which generates a right-to-left shunt through the patent foramen ovale (PFO), or an alteration of the hypoxic pulmonary vasoconstriction reflex (HPV). The HPV reflex is activated in an attempt to redistribute the vascular flow to better ventilated areas. However, there are some situations (such as viral infections) that can alter this reflex and worsen the hypoxemia. The concomitant use of vasoactive drugs (such as inhaled nitric oxide) and vasopressors (such as dopa- mine or norepinephrine) has been proposed with the aim of reducing PVR and the flow through the PFO; or to redistribute the flow to better ventilated areas if an alteration of the RVP is suspected.

Un síndrome de distrés respiratorio agudo (SDRA) se caracteriza por un incremento del intrapulmonar (medido por el cociente PaO2/FiO2) causado por una afectación alveolo-intersticial bilateral no explicada por sobrecarga hídrica. Sin embargo, hay casos de SDRA que presentan una marcada hipoxemia sin claros infiltrados pulmonares. Un ejemplo de este caso, que ha generado gran controversia, es la infección por SARS-CoV-2. El entendimiento de la fisiopato- logía de la hipoxemia es absolutamente clave para establecer la estrategia terapéutica más adecuada en cada paciente. Ante una hipoxemia grave (PaO2/FiO2 < 200 que representa un superior al 30%) y con una radiografía de tórax (o con TAC) sin claros y extensos infiltrados bilaterales, el podría deberse a una afectación vascular. Esto podría explicarse por dos causas: un aumento de las resistencias vasculares pulmonares (RVP), que genera un derecha- izquierda a través del foramen oval permeable (FOP) o una alteración del reflejo de vasoconstricción pulmonar hipóxico (VPH). El reflejo de VPH se activa en un intento por redistribuir el flujo vascular hacia las zonas mejor ventiladas. Sin embargo, existen situaciones (como infecciones víricas) que pueden alterar dicho reflejo y agravar la hipoxemia. Se ha propuesto el uso concomitante de fármacos vasoactivos (como el óxido nítrico inhalado) y vasopresores (como do- pamina o noradrenalina) con el objetivo de disminuir las RVP y el flujo a través del FOP; o para redistribuir el flujo a zonas mejor ventiladas si se sospecha una alteración del RVP.

Avaliação do ventrículo esquerdo em pacientes com DPOC e hipoxemia noturna / Evaluation of the left ventricle in patients with COPD and nocturnal hypoxemia

RESUMO Objetivo Verificar a associação entre massa e espessura do ventrículo esquerdo (VE) e presença de hipoxemia noturna significativa em pacientes portadores de DPOC com hipoxemia diurna leve. Métodos Estudo transversal realizado em pacientes ambulatoriais, clinicamente estáveis, portadores de DPOC e hipoxemia leve (saturação de oxigênio ≥ 90 a ≤ 94%, identificados por oximetria não invasiva) em um centro clínico especializado no atendimento de doenças respiratórias em Goiânia (GO). Todos foram submetidos a avaliação clínica, espirometria, polissonografia, ecocardiografia, gasometria arterial, teste de caminhada de 6 minutos e radiografia de tórax. Resultados Foram avaliados 64 pacientes com DPOC e hipoxemia noturna. Pacientes com hipoxemia noturna significativa apresentaram parâmetros ecocardiográficos associados a mais quantidade de musculatura do VE quando comparados a pacientes com hipoxemia noturna leve. A relação entre volume/massa do VE foi significativamente menor no grupo com hipoxemia noturna significativa (0,64 ± 0,13 versus 0,72 ± 0,12; p = 0,04) e a espessura diastólica do septo interventricular e a espessura diastólica da parede posterior do VE foram significativamente maiores nesse grupo (9,7 ± 0,92 versus 9,1 ± 0,90; p = 0,03) (9,7 ± 1,0 versus 8,9 ± 1,0; p = 0,01). O tempo de sono REM com saturação abaixo de 85% prediz significativamente a espessura do septo (ajuste para índice de massa corporal [IMC], idade e pressão arterial média; r2 = 0,20; p = 0,046). Conclusão Em indivíduos portadores de DPOC e hipoxemia noturna significativa, foi observada associação entre hipoxemia severa no sono REM e parâmetros ecocardiográficos que indicam aumento da massa do VE. Tal fato sugere que esse subgrupo de indivíduos pode se beneficiar de uma avaliação ecocardiográfica do VE.

ABSTRACT Objective To verify association between left ventricular (LV) mass and thickness and the presence of significant nocturnal hypoxemia in patients with COPD with mild diurnal hypoxemia. Methods A cross-sectional study carried out in clinically stable outpatients with COPD and mild hypoxemia (oxygen saturation ≥90 to ≤94%, identified by noninvasive oximetry) in a clinic specialized in the treatment of respiratory diseases in Goiânia-GO. All patients were submitted to clinical evaluation, spirometry, polysomnography, echocardiography, arterial blood gas analysis, 6-minute walk test and chest X-ray. Results Patients with significant nocturnal hypoxemia had echocardiographic parameters associated with increase of LV musculature when compared to patients with mild nocturnal hypoxemia. The LV volume/mass ratio was significantly lower in the group with significant nocturnal hypoxemia (ratio 0.64 ± 0.13 versus 0.72 ± 0.12, p = 0.04), the thickness diastolic diameter of the interventricular septum and the diastolic thickness of the LV posterior wall were significantly higher in this group (9.7 ± 0.92 versus 9.1 ± 0.90 p = 0.03), (9.7 ± 1.0 versus 8.9 ± 1.0, p = 0.01. The time in REM sleep with saturation below 85% significantly predicted septum thickness (adjustment for BMI, age and mean blood pressure, r2 = 0.20; p = 0.046). Conclusion We observed association between severe REM sleep hypoxemia and echocardiographic parameters indicating increased LV mass in individuals with COPD and significant nocturnal hypoxemia. This suggests that this subgroup of individuals may benefit from an echocardiographic evaluation of the left ventricle.

Effects of ketoprofen in spermatogenesis of mice exposed to continuos hypobaric hypoxia / Efecto del ketoprofeno en la espermatogénesis de ratones expuestos a hipoxia hipobárica continua

Hypoxia hypobaric (HH) can cause alterations at testicular level, with temperature increase, intrascrotal alteration and deterioration of spermatogenesis. Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ketoprofen have anti-angiogenic properties, and can decrease testicular abnormalities. The objective of the study was to evaluate the effect of ketoprofen on spermatogenesis of mice exposed to continuous hypobaric hypoxia. 78 Mus musculus CF-1 male mice 3 to 4 months old were used and subjected to HH in chamber at 4200 m. They were divided into 13 groups (G) of 6 animals: 10 with HH cycles (1, 2, 3, 4 and 8, lasting 8.3 days each cycle, two groups each) and 3 in normoxia (Nx). Intraperitoneal ketoprofen 25 mg/kg was administered every 4 days. Euthanasia of these animals was performed at the end of each cycle and in the case the Nx groups at the end of cycles 1, 4 and 8. Percentage of microhematocrit and reticulocytes were measured in blood smears and a morphometric and histopathological analysis of the height of the epithelium, the tubular diameter and the diameter of the tubular lumen was made. It was shown that hematocrit increases continuously up to 8 cycles, while reticulocytes increase up to 3 cycles. Continuous HH decreases the tubular diameter in a sustained manner and proportional to HH cycles, and the height increased only in the groups subjected to 8 cycles. The groups treated with ketoprofen saw a decrease in angiogenesis, presenting some degree of protection at the testicular level.

La hipoxia hipobárica (HH) puede provocar alteraciones a nivel testicular, con aumento de la temperatura, alteración intraescrotal y deterioro de la espermatogénesis. Los antiinflamatorios no esteroidales (AINEs) como el ketoprofeno tienen propiedades antiangiogénicas, pudiendo disminuir las alteraciones testiculares. El objetivo de estudio fue evaluar el efecto del ketoprofeno en la espermatogénesis de ratones expuestos a hipoxia hipobárica continua. Se utilizaron 78 ratones macho Mus musculus CF-1 de 3 a 4 meses de edad y se sometieron a HH en cámara a 4200 m. Se dividieron en 13 grupos (G) de 6 animales: 10 con ciclos de HH (1, 2, 3, 4 y 8, con duración de 8,3 días cada ciclo, dos grupos cada uno) y 3 en normoxia (Nx). Se administró ketoprofeno intraperitoneal 25 mg/kg cada 4 días. La eutanasia de estos animales se realizó al final de cada ciclo y en el caso los grupos Nx al final de los ciclos 1, 4 y 8. Se midió porcentaje de microhematocrito y reticulocitos en frotis de sangre y se hizo un análisis morfométrico e histopatológico de la altura del epitelio, el diámetro tubular y el diámetro de la luz tubular. Se evidenció que el hematocrito aumenta de manera continua hasta los 8 ciclos, en cambio los reticulocitos aumentan hasta los 3 ciclos. La HH continua disminuye el diámetro tubular de forma sostenida y proporcional a los ciclos de HH, y la altura aumentó sólo en los grupos sometidos a 8 ciclos. Los grupos tratados con ketoprofeno se vio una disminución de la angiogénesis, presentando algún grado de protección a nivel testicular.

Entrenamiento de fuerza y resistencia en hipoxia: efecto en la hipertrofia muscular / The training of strength-resistance in hypoxia: effect on muscle hypertrophy

Resumen El entrenamiento en altitud y el entrenamiento en hipoxia simulada producen adaptaciones fisiológicas y bioquímicas en el músculo esquelético como la capacidad oxidativa, así como modificaciones de la actividad mitocondrial, en el metabolismo aerobio y en el contenido demioglobina. El propósito de esta revisión fue analizar las adaptaciones del músculo esquelético en respuesta a la exposición temporal a la hipoxia combinada con ejercicios de fuerza y resistencia. Según los hallazgos de numerosos autores, las adaptaciones estructurales del músculo son similares en la hipoxia y en la 'normoxia', con excepción de un aumento en el volumen muscular y en el área de la sección transversal de la fibra muscular, que son mayores en la hipoxia. En conclusión, la sinergia del entrenamiento de fuerza y resistencia y la hipoxia normobárica produce mejores y mayores adaptaciones, ganancias y cambios fisiológicos beneficiosos en el tejido muscular, lo cual genera cambios fenotípicos favorables, como la hipertrofia del músculo esquelético.

Abstract Altitude and simulated-hypoxia training produces different physiological and/or biochemical adaptations in the skeletal muscle. These are: oxidative capacity, mitochondrial activity modifications, aerobic metabolism changes and myoglobin content. The purpose of this review was to analyze the adaptations of skeletal muscle in response to the combination of strength-resistance exercise and hypoxia. In general terms, the structural adaptations of the muscle are similar in hypoxia and normoxia except that hypoxia training produces an increase of the volume and cross-sectional area of the muscle fiber. In conclusion, the synergic effect of the combination of strength resistance training with normobaric hypoxia produces better and greater adaptations and beneficial physiological changes of the muscle tissue, which shows favorable phenotypic changes in skeletal muscle hypertrophy.

Impact of adherence to long-term oxygen therapy on patients with COPD and exertional hypoxemia followed for one year / Impacto da adesão à oxigenoterapia de longa duração em pacientes com DPOC e hipoxemia decorrente do esforço acompanhados durante um ano

ABSTRACT Objective: To determine the impact of adherence to long-term oxygen therapy (LTOT) on quality of life, dyspnea, and exercise capacity in patients with COPD and exertional hypoxemia followed for one year. Methods: Patients experiencing severe hypoxemia during a six-minute walk test (6MWT) performed while breathing room air but not at rest were included in the study. At baseline and after one year of follow-up, all patients were assessed for comorbidities, body composition, SpO2, and dyspnea, as well as for anxiety and depression, having also undergone spirometry, arterial blood gas analysis, and the 6MWT with supplemental oxygen. The Saint George's Respiratory Questionnaire (SGRQ) was used in order to assess quality of life, and the Body mass index, airflow Obstruction, Dyspnea, and Exercise capacity (BODE) index was calculated. The frequency of exacerbations and the mortality rate were noted. Treatment nonadherence was defined as LTOT use for < 12 h per day or no LTOT use during exercise. Results: A total of 60 patients with COPD and exertional hypoxemia were included in the study. Of those, 10 died and 11 experienced severe hypoxemia during follow-up, 39 patients therefore being included in the final analysis. Of those, only 18 (46.1%) were adherent to LTOT, showing better SGRQ scores, higher SpO2 values, and lower PaCO2 values than did nonadherent patients. In all patients, SaO2, the six-minute walk distance, and the BODE index worsened after one year. There were no differences between the proportions of adherence to LTOT at 3 and 12 months of follow-up. Conclusions: Quality of life appears to be lower in patients with COPD and exertional hypoxemia who do not adhere to LTOT than in those who do. In addition, LTOT appears to have a beneficial effect on COPD symptoms (as assessed by SGRQ scores). (Brazilian Registry of Clinical Trials - ReBEC; identification number RBR-9b4v63 [http://www.ensaiosclinicos.gov.br])

RESUMO Objetivo: Determinar o impacto da adesão à oxigenoterapia de longa duração (OLD) na qualidade de vida, dispneia e capacidade de exercício em pacientes com DPOC e hipoxemia decorrente do esforço acompanhados durante um ano. Métodos: Foram incluídos no estudo pacientes que apresentaram hipoxemia grave durante um teste de caminhada de seis minutos (TC6) realizado enquanto respiravam ar ambiente, mas não em repouso. No início e após um ano de acompanhamento, todos os pacientes foram avaliados quanto a comorbidades, composição corporal, SpO2 e dispneia, bem como quanto a ansiedade e depressão, além de terem sido submetidos a espirometria, gasometria arterial e TC6 com oxigênio suplementar. O Saint George's Respiratory Questionnaire (SGRQ) foi usado para avaliar a qualidade de vida, e o índice Body mass index, airflow Obstruction, Dyspnea, and Exercise capacity (BODE; índice de massa corporal, obstrução do fluxo aéreo, dispneia e capacidade de exercício) foi calculado. A frequência de exacerbações e a taxa de mortalidade foram registradas. Usar OLD durante < 12 h por dia ou não usar OLD durante o exercício caracterizaram não adesão ao tratamento. Resultados: Foram incluídos no estudo 60 pacientes com DPOC e hipoxemia decorrente do esforço. Destes, 10 morreram e 11 apresentaram hipoxemia grave durante o acompanhamento; portanto, foram incluídos na análise final 39 pacientes. Destes, apenas 18 (46,1%) aderiram à OLD, apresentando melhor pontuação no SGRQ, maior SpO2 e menor PaCO2 do que os pacientes que não aderiram à OLD. Em todos os pacientes, a SaO2, a distância percorrida no TC6 e o índice BODE pioraram após um ano. Não houve diferenças entre as proporções de adesão à OLD aos 3 e 12 meses de acompanhamento. Conclusões: A qualidade de vida parece ser menor em pacientes com DPOC e hipoxemia decorrente do esforço que não aderem à OLD do que naqueles que o fazem. Além disso, a OLD parece ter efeito benéfico nos sintomas da DPOC (avaliados pela pontuação obtida no SGRQ). (Registro Brasileiro de Ensaios Clínicos - ReBEC; número de identificação RBR- 9b4v63 [http://www.ensaiosclinicos.gov.br])

Effects of vagotomy on cardiovascular and heart rate variability alterations following chronic normobaric hypoxia in adult rabbits

BACKGROUND: chronic hypoxia increases basal ventilation and pulmonary vascular resistance, with variable changes in arterial blood pressure and heart rate, but it's impact on heart rate variability and autonomic regulation have been less well examined. We studied changes in arterial blood pressure, heart rate and heart rate variability (HRV) in rabbits subjected to chronic normobaric hypoxia (CNH; PB ~ 719 mmHg; FIO2 ~ 9.2%) for 14 days and assess the effect of autonomic control by acute bilateral vagal denervation. RESULTS: exposure to CNH stalled animal weight gain and increased the hematocrit, without affecting heart rate or arterial blood pressure. Nevertheless, Poincaré plots of the electrocardiographic R-R intervals showed a reduced distribution parallel to the line of identity, which interpreted as reduced long-term HRV. In the frequency domain, CNH reduced the very-low- (< 0.2 Hz) and high-frequency components (> 0.8 Hz) of the R-R spectrograms and produced a prominent component in the low-frequency component (0.2-0.5 Hz) of the power spectrum. In control and CNH exposed rabbits, bilateral vagotomy had no apparent effect on the short- and long-term HRV in the Poincaré plots. However, bilateral vagotomy differentially affected higher-frequency components (> 0.8 Hz); reducing it in control animals without modifying it in CNH-exposed rabbits. CONCLUSIONS: These results suggest that CNH exposure shifts the autonomic balance of heart rate towards a sympathetic predominance without modifying resting heart rate or arterial blood pressure.

Sleep-disordered breathing in patients with COPD and mild hypoxemia: prevalence and predictive variables / Prevalência e variáveis preditivas de distúrbios respiratórios do sono em pacientes com DPOC e hipoxemia leve

ABSTRACT Objective: To infer the prevalence and variables predictive of isolated nocturnal hypoxemia and obstructive sleep apnea (OSA) in patients with COPD and mild hypoxemia. Methods: This was a cross-sectional study involving clinically stable COPD outpatients with mild hypoxemia (oxygen saturation = 90-94%) at a clinical center specializing in respiratory diseases, located in the city of Goiânia, Brazil. The patients underwent clinical evaluation, spirometry, polysomnography, echocardiography, arterial blood gas analysis, six-minute walk test assessment, and chest X-ray. Results: The sample included 64 patients with COPD and mild hypoxemia; 39 (61%) were diagnosed with sleep-disordered breathing (OSA, in 14; and isolated nocturnal hypoxemia, in 25). Correlation analysis showed that PaO2 correlated moderately with mean sleep oxygen saturation (r = 0.45; p = 0.0002), mean rapid eye movement (REM) sleep oxygen saturation (r = 0.43; p = 0.001), and mean non-REM sleep oxygen saturation (r = 0.42; p = 0.001). A cut-off point of PaO2 ≤ 70 mmHg in the arterial blood gas analysis was significantly associated with sleep-disordered breathing (OR = 4.59; 95% CI: 1.54-13.67; p = 0.01). The model showed that, for identifying sleep-disordered breathing, the cut-off point had a specificity of 73.9% (95% CI: 51.6-89.8%), a sensitivity of 63.4% (95% CI: 46.9-77.9%), a positive predictive value of 81.3% (95% CI: 67.7-90.0%), and a negative predictive value of 53.1% (95% CI: 41.4-64.4%), with an area under the ROC curve of 0.69 (95% CI: 0.57-0.80), correctly classifying the observations in 67.2% of the cases. Conclusions: In our sample of patients with COPD and mild hypoxemia, the prevalence of sleep-disordered breathing was high (61%), suggesting that such patients would benefit from sleep studies.

RESUMO Objetivo: Inferir a prevalência e as variáveis preditivas de hipoxemia noturna e apneia obstrutiva do sono (AOS) em pacientes portadores de DPOC com hipoxemia leve. Métodos: Estudo transversal realizado em pacientes ambulatoriais, clinicamente estáveis, portadores de DPOC e hipoxemia leve (saturação de oxigênio = 90-94%) em um centro clínico especializado no atendimento de doenças respiratórias em Goiânia (GO). Os pacientes foram submetidos à avaliação clínica, espirometria, polissonografia, ecocardiografia, gasometria arterial, teste de caminhada de seis minutos e radiografia de tórax. Resultados: Foram avaliados 64 pacientes com DPOC e hipoxemia leve, e 39 (61%) apresentaram distúrbios respiratórios do sono (14 com AOS e 25 com hipoxemia noturna isolada). A análise de correlação mostrou moderada correlação da PaO2 com saturação média do sono (r = 0,45; p = 0,0002), saturação média do sono rapid eye movement (REM; r = 0,43; p = 0,001) e saturação média do sono não-REM (r = 0,42; p = 0,001). Um ponto de corte de PaO2 ≤ 70 mmHg (OR = 4,59; IC95%: 1,54-13,67; p = 0,01) na gasometria arterial foi significativamente associada com distúrbios respiratórios do sono. O modelo mostrou que, para identificar distúrbios respiratórios do sono, o ponto de corte teve uma especificidade de 73,9% (IC95%: 51,6-89,8%), uma sensibilidade de 63,4% (IC95%: 46,9-77,9%) e valores preditivos positivo e negativo de 81,3% (IC95%: 67,7-90,0%) e 53,1% (IC95%: 41,4-64,4%), respectivamente. A área sob a curva ROC foi de 0,69 (IC95%: 0,57-0,80), e a proporção de observações corretamente classificadas foi de 67,2% dos casos. Conclusões: A elevada prevalência de distúrbios respiratórios do sono em portadores de DPOC e hipoxemia leve nesta amostra (61%) sugere que esses pacientes podem se beneficiar da realização de estudos do sono.

Significance of Hypoxia-related microRNA for Estimating the Cause of Mechanical Asphyxia Death / 法医学杂志

Under hypoxia condition, microRNA （miRNA） can interact with transcription factors for regulating the cell metabolism, angiogenesis, erythropoiesis, cellular proliferation, differentiation and apoptosis. The biological processes above may play an important role in mechanical asphyxia death. This article reviews the regulating function of miRNA under hypoxia condition and the influence of hypoxia to biosynthesis of miRNA, which may provide some new ideas to the research of miRNA on determining the cause of mechanical asphyxia death in the field of forensic medicine.

Importance of SERCA2a on early isolated diastolic dysfunction induced by supravalvular aortic stenosis in rats

Cardiac remodeling is defined as changes in shape and function of the heart in response to aggression (pressure overload). The sarcoplasmic reticulum calcium ATPase cardiac isoform 2a (SERCA2a) is a known factor that influences function. A wide spectrum of studies report a decrease in SERCA2a in heart failure, but none evaluate it's the role in early isolated diastolic dysfunction in supravalvular aortic stenosis (AoS). Our hypothesis was that SERCA2a participates in such dysfunction. Thirty-day-old male Wistar rats (60-80 g) were divided into AoS and Sham groups, which were submitted to surgery with or without aorta clipping, respectively. After 6 weeks, the animals were submitted to echocardiogram and functional analysis by isolated papillary muscle (IPM) in basal condition, hypoxia, and SERCA2a blockage with cyclopiazonic acid at calcium concentrations of 0.5, 1.5, and 2.5 mM. Western-blot analyses were used for SERCA2a and phospholamban detection. Data analysis was carried out with Student's t-test and ANOVA. AoS enhanced left atrium and E and A wave ratio, with preserved ejection fraction. Basal condition in IPM showed similar increases in developed tension (DT) and resting tension (RT) in AoS, and hypoxia was similar between groups. After cyclopiazonic acid blockage, final DT was equally decreased and RT was similar between groups, but the speed of relaxation was decreased in the AoS group. Western-blot was uniform in all evaluations. The hypothesis was confirmed, since functional parameters regarding SERCA2a were changed in the AoS group.

Effect of high altitude hypoxia on the postnatal development of rat testis: histological and histometric study / Efecto de la hipoxia a gran altitud en el desarrollo postnatal en testículos de rata: estudio histológico e histométrico

The study was carried out at two different altitudes in the southern region of Saudi Arabia: Abha, 2,800 meters above sea level, the high altitude (HA) area and Jazan, 40 meters above sea level the low altitude (LA) area. Following exposure to high altitude, and up to the third week of postnatal development, some of the seminiferous tubules showed detachment from the basal lamina, spaces of different sizes within the epithelial layer with vacuoles in the center and Pyknotic nuclei were noted in the spermatogonia and primordial germ cells. Rounded spermatids were seen in the lumen only on day 35 of hypoxic group, no spermatozoa were recognized until day 45 of postnatal development. On day 45 hypoxic rat testes revealed various types of atrophy and degeneration in the seminiferous tubules and in the interstitial tissue, there was detachment of the basal laminae of the tubules and a profound decrease in cellularity. Significant decrease in epithelial height was noticed in these animals (P <0.05). Also, the diameter of the tubules showed slight decrease with concomitant increase in interstitial spaces in all hypoxic rats.

El estudio se llevó a cabo en dos sitios de altitud diferentes en la región sur de Arabia Saudita: en Abha, a 2.800 metros sobre el nivel del mar, la zona de gran altitud (GA) y en Jazan, a 40 metros sobre el nivel del mar, la zona de baja altitud. Después de la exposición a GA, y hasta la tercera semana del desarrollo postnatal, se observaron espermatogonias y células germinales primordiales en algunos túbulos seminíferos, un desprendimiento de la lámina basal, espacios de diferentes tamaños dentro de la capa epitelial, con vacuolas en el centro y núcleos picnóticos. Se encontraron espermátidas redondeadas a nivel del lumen en el día 35 de la hipoxia, y no se observaron espermatozoides hasta el día 45 del desarrollo postnatal. En el día 45, los testículos de las ratas hipóxicas revelaron varios tipos de atrofia y degeneración en los túbulos seminíferos y el tejido intersticial; no hubo separación de las láminas basales de los túbulos y se registró una profunda disminución de la celularidad. Además, se observó una disminución significativa en la altura del epitelio de estos animales (P <0,05). El diámetro de los túbulos mostró una ligera disminución con el aumento concomitante en los espacios intersticiales en todas las ratas hipóxicas.

Emissões otoacústicas em recém-nascidos com hipóxia perinatal leve e moderada / Otoacoustic emissions in newborns with mild and moderate perinatal hypoxia

RESUMO Introdução Atualmente, somente a hipóxia neonatal grave (evidenciada pelo valor do Apgar) é considerada risco para a deficiência auditiva. A hipóxia é uma das causas mais comuns de lesão e morte celular. Nos casos de hipóxia leve ou moderada, embora menor, a privação da oxigenação está presente e, dessa forma, algum dano ao sistema auditivo pode ocorrer. Objetivo Investigar as amplitudes das emissões otoacústicas em recém-nascidos a termo sem risco para deficiência auditiva que apresentaram hipóxia leve ou moderada. Métodos Foram selecionados 37 recém-nascidos de ambos os sexos, divididos em dois grupos: 25 do grupo controle, formado por recém-nascidos sem hipóxia, e 12 do grupo estudo, formado por recém-nascidos com hipóxia leve ou moderada. Resultados Foram pesquisadas as EOAT e EOAPD em ambos os grupos e comparados os seus resultados. Nas EOAPD foram encontradas diferenças estatísticas entre as amplitudes nas frequências 1.000, 2.800, 4.000 e 6.000 Hz. Nas EOAT foram encontradas diferenças estatísticas nas bandas de frequência de 1.000, 1.400, 2.000, 2.800 e 4.000 Hz, sendo as EOA do grupo estudo menores que as do grupo controle. Conclusão Embora a ocorrência de hipóxia neonatal leve e moderada não seja considerada risco para perda auditiva, a mínima privação do oxigênio durante o momento de hipóxia neonatal parece interferir no funcionamento das células ciliadas externas e, consequentemente, no nível de respostas das emissões otoacústicas. Dessa forma, faz-se necessário o acompanhamento longitudinal desses lactentes, a fim de identificar o possível impacto desses resultados na aquisição de linguagem e, futuramente, no desempenho escolar.

ABSTRACT Introduction Severe neonatal hypoxia (as evidenced by the Apgar value) is currently considered the only risk for hearing loss. Hypoxia is one of the most common causes of injury and cell death. The deprivation of oxygen in mild or moderate cases of hypoxia, although smaller, occurs and could cause damage to the auditory system. Objective To investigate the amplitude of otoacoustic emissions in neonates at term with mild to moderate hypoxia and no risk for hearing loss. Methods We evaluated 37 newborns, divided into two groups: a control group of 25 newborns without hypoxia and a study group of 12 newborns with mild to moderate hypoxia. TEOAE and DPOAE were investigated in both groups. Results The differences between groups were statistically significant in the amplitude of DPOAE at the frequencies of 1000, 2800, 4000 and 6000 Hz. In TEOAE, statistically significant differences were found in all tested frequency bands. OAE of the study group were lower than those in the control group. Conclusion Although the occurrence of mild and moderate neonatal hypoxia is not considered a risk factor for hearing loss, deprivation of minimum oxygen during neonatal hypoxia seems to interfere in the functioning of the outer hair cells and, consequently, alter the response level of otoacoustic emissions. Thus, hese children need longitudinal follow-up in order to identify the possible impact of these results on language acquisition and future academic performance.

Prevalence of lung structure abnormalities in patients with acromegaly and their relationship with gas exchange: cross-sectional analytical study with a control group / Prevalência de alterações na estrutura pulmonar em pacientes com acromegalia e sua relação com a troca gasosa: estudo transversal analítico com grupo controle

CONTEXT AND OBJECTIVE: Different functional respiratory alterations have been described in acromegaly, but their relationship with pulmonary tissue abnormalities is unknown. The objective of this study was to observe possible changes in lung structure and explain their relationship with gas exchange abnormalities. DESIGN AND SETTING: Cross-sectional analytical study with a control group, conducted at a university hospital. METHODS: The study included 36 patients with acromegaly and 24 controls who were all assessed through high-resolution computed tomography of the thorax (CT). Arterial blood gas, effort oximetry and serum growth hormone (GH) and insulin-like growth factor I (IGF-1) were also assessed in the patients with acromegaly. RESULTS: The abnormalities found in the CT scan were not statistically different between the acromegaly and control groups: mild cylindrical bronchiectasis (P = 0.59), linear opacity (P = 0.29), nodular opacity (P = 0.28), increased attenuation (frosted glass; P = 0.48) and decreased attenuation (emphysema; P = 0.32). Radiographic abnormalities were not associated with serum GH and IGF-1. Hypoxemia was present in seven patients; however, in six of them, the hypoxemia could be explained by underlying clinical conditions other than acromegaly: chronic obstructive pulmonary disease in two, obesity in two, bronchial infection in one and asthma in one. CONCLUSION: No changes in lung structure were detected through thorax tomography in comparison with the control subjects. The functional respiratory alterations found were largely explained by alternative diagnoses or had subclinical manifestations, without any plausible relationship with lung structural factors.

CONTEXTO E OBJETIVO: Diferentes alterações funcionais respiratórias são descritas na acromegalia. Sua relação com anormalidades do tecido pulmonar é desconhecida. O objetivo foi observar possíveis alterações da estrutura pulmonar e explicar sua relação com anormalidades da troca gasosa. TIPO DE ESTUDO E LOCAL: Estudo transversal, analítico, com grupo de controle, realizado em um hospital universitário. MÉTODOS: Incluíram-se 36 pacientes com acromegalia e 24 controles que foram avaliados com tomografia computadorizada de alta resolução de tórax (TC); os acromegálicos também foram avaliados com gasometria arterial, oximetria de esforço e dosagens de hormônio de crescimento (GH) e fator de crescimento semelhante à insulina (IGF-1). RESULTADOS: As alterações encontradas na TC não foram estatisticamente diferentes entre os grupos acromegálico e de controle: bronquiectasia cilíndrica leve (P = 0,59), opacidades lineares (P = 0,29), opacidades nodulares (P = 0,28), aumento da atenuação (vidro fosco) (P = 0,48) e redução da atenuação (enfisema; P = 0,32). As alterações radiológicas não se relacionaram com as dosagens de GH e IGF-1. Hipoxemia estava presente em sete pacientes; contudo, em seis deles a hipoxemia poderia ser explicada por condição clínica subjacente diversa da acromegalia: doença pulmonar obstrutiva crônica em dois, obesidade em dois, infecção brônquica em um e asma em um. CONCLUSÕES: Não foram observadas alterações da estrutura pulmonar por tomografia de tórax, quando comparadas ao grupo de controle; as alterações funcionais respiratórias encontradas são explicáveis em grande parte por diagnósticos alternativos, ou se manifestam de forma subclínica, não apresentando relação plausível com o aspecto da estrutura pulmonar.

Uncoupling protein-2 mRNA expression in mice subjected to intermittent hypoxia / Expressão do mRNA da uncoupling protein-2 em camundongos submetidos à hipóxia intermitente

Objective: To investigate the effect of intermittent hypoxia-a model of obstructive sleep apnea (OSA)-on pancreatic expression of uncoupling protein-2 (UCP2), as well as on glycemic and lipid profiles, in C57BL mice. Methods: For 8 h/day over a 35-day period, male C57BL mice were exposed to intermittent hypoxia (hypoxia group) or to a sham procedure (normoxia group). The intermittent hypoxia condition involved exposing mice to an atmosphere of 92% N and 8% CO2 for 30 s, progressively reducing the fraction of inspired oxygen to 8 ± 1%, after which they were exposed to room air for 30 s and the cycle was repeated (480 cycles over the 8-h experimental period). Pancreases were dissected to isolate the islets. Real-time PCR was performed with TaqMan assays. Results: Expression of UCP2 mRNA in pancreatic islets was 20% higher in the normoxia group than in the hypoxia group (p = 0.11). Fasting serum insulin was higher in the hypoxia group than in the normoxia group (p = 0.01). The homeostasis model assessment of insulin resistance indicated that, in comparison with the control mice, the mice exposed to intermittent hypoxia showed 15% lower insulin resistance (p = 0.09) and 21% higher pancreatic β-cell function (p = 0.01). Immunohistochemical staining of the islets showed no significant differences between the two groups in terms of the area or intensity of α- and β-cell staining for insulin and glucagon. Conclusions: To our knowledge, this is the first report of the effect of intermittent hypoxia on UCP2 expression. Our findings suggest that UCP2 regulates insulin production in OSA. Further study of the role that UCP2 plays in the glycemic control of OSA patients is warranted. .

Objetivo: Investigar o efeito da hipóxia intermitente com um modelo de apneia obstrutiva do sono (AOS) sobre a expressão de uncoupling protein-2 (UCP2), assim como sobre perfis glicêmicos e lipídicos, em camundongos C57BL. Métodos: Camundongos C57BL machos foram expostos a hipóxia intermitente ou hipóxia simulada (grupo controle) 8 h/dia durante 35 dias. A condição de hipóxia intermitente envolveu a exposição dos camundongos a uma atmosfera de 92% de N e 8% de CO2 por 30 s, com redução progressiva de fração de O2 inspirado até 8 ± 1%, seguida por exposição a ar ambiente por 30 s e repetições do ciclo (480 ciclos no período experimental de 8 h). Os pâncreas foram dissecados para isolar as ilhotas. Foi realizada PCR em tempo real utilizando o método TaqMan. Resultados: A expressão do mRNA da UCP2 nas ilhotas pancreáticas foi 20% maior no grupo controle que no grupo hipóxia (p = 0,11). A insulina sérica de jejum foi maior no grupo hipóxia do que no grupo controle (p = 0,01). O modelo de avaliação da homeostase de resistência à insulina indicou que, em comparação com os camundongos controle, aqueles expostos à hipóxia intermitente apresentaram 15% menor resistência à insulina (p = 0,09) e 21% maior função das células beta (p = 0,01). A coloração das ilhotas pancreáticas por imuno-histoquímica não mostrou diferenças significativas entre os grupos em termos da área ou da intensidade das células alfa e beta, marcadas por insulina e glucagon. Conclusões: Segundo nosso conhecimento, esta é a primeira descrição do efeito da hipóxia intermitente sobre a expressão da UCP2. Nossos achados sugerem que UCP2 regula a produção de insulina na AOS. Futuras investigações sobre o papel da UCP2 no controle glicêmico em pacientes com AOS são justificadas. .