Exaggerated systemic oxidative-inflammatory-nitrosative stress in chronic mountain sickness is associated with cognitive decline and depression.

KEY POINTS: Chronic mountain sickness (CMS) is a maladaptation syndrome encountered at high altitude (HA) characterised by severe hypoxaemia that carries a higher risk of stroke and migraine and is associated with increased morbidity and mortality. We examined if exaggerated oxidative-inflammatory-nitrosative stress (OXINOS) and corresponding decrease in vascular nitric oxide bioavailability in patients with CMS (CMS+) is associated with impaired cerebrovascular function and adverse neurological outcome. Systemic OXINOS was markedly elevated in CMS+ compared to healthy HA (CMS-) and low-altitude controls. OXINOS was associated with blunted cerebral perfusion and vasoreactivity to hypercapnia, impaired cognition and, in CMS+, symptoms of depression. These findings are the first to suggest that a physiological continuum exists for hypoxaemia-induced systemic OXINOS in HA dwellers that when excessive is associated with accelerated cognitive decline and depression, helping identify those in need of more specialist neurological assessment and targeted support. ABSTRACT: Chronic mountain sickness (CMS) is a maladaptation syndrome encountered at high altitude (HA) characterised by severe hypoxaemia that carries a higher risk of stroke and migraine and is associated with increased morbidity and mortality. The present cross-sectional study examined to what extent exaggerated systemic oxidative-inflammatory-nitrosative stress (OXINOS), defined by an increase in free radical formation and corresponding decrease in vascular nitric oxide (NO) bioavailability, is associated with impaired cerebrovascular function, accelerated cognitive decline and depression in CMS. Venous blood was obtained from healthy male lowlanders (80 m, n = 17), and age- and gender-matched HA dwellers born and bred in La Paz, Bolivia (3600 m) with (CMS+, n = 23) and without (CMS-, n = 14) CMS. We sampled blood for oxidative (electron paramagnetic resonance spectroscopy, HPLC), nitrosative (ozone-based chemiluminescence) and inflammatory (fluorescence) biomarkers. We employed transcranial Doppler ultrasound to measure cerebral blood flow (CBF) and reactivity. We utilised psychometric tests and validated questionnaires to assess cognition and depression. Highlanders exhibited elevated systemic OXINOS (P < 0.05 vs. lowlanders) that was especially exaggerated in the more hypoxaemic CMS+ patients (P < 0.05 vs. CMS-). OXINOS was associated with blunted cerebral perfusion and vasoreactivity to hypercapnia, impaired cognition and, in CMS+, symptoms of depression. Collectively, these findings are the first to suggest that a physiological continuum exists for hypoxaemia-induced OXINOS in HA dwellers that when excessive is associated with accelerated cognitive decline and depression, helping identify those in need of specialist neurological assessment and support.

[Six minute walk test in young native high altitude residents]. / Prueba de caminata de 6 minutos en residentes nativos de gran altitud.

Background: The 6-minute walk test is widely used and evaluates the functional capacity to perform sub-maximal exercise, its behavior in healthy young native hight-altitude resident is unknown. Objective: To describe the behavior of the 6-minute walk test in healthy young native hight-altitude resident. Material and methods: Analytical cross-sectional design. Consecutive subjects born and residents of the cities of La Paz and El Alto (Bolivia), both genders, without cardiopulmonary disease or physical limitation were studied. Their altitude, hematological, demographic and simple spirometry variables were informed. The differences were calculated with the t-test for independent or dependent groups according to the type of comparison. A p < 0.05 was considered significant. Results: 110 subjects were studied, at an altitude of 3673 ± 250 meters above sea level, age 24 ± 5 years old, 67 (60.90%) were women. The hemoglobin was 15.20 ± 2.46 g/dL. Prior to the test in 37 (33.63%) subjects the partial oxygen saturation was < 92% (90.92 ± 0.92%), its correlation whit meters walked, r = - 0.244, p < 0.010. Total meters walked: 581 ± 35 (627.3 ± 52.88 sea level); with the reference equations from Enright PL: 542 ± 75 and Osses AR: 459 ± 104, both obtained at < 1000 meters above sea level. Vital signs were whitin normal limits. Conclusion: Sub-maximal exercise capacity estimated with the six-minute walk test at high altitude is lower than that reported at sea level.Reference equations underestimated the meters walked at high altitude.

Introducción: la prueba de caminata de 6 minutos es de amplio uso y evalúa la capacidad funcional para realizar ejercicio submáximo, se desconoce su comportamiento en residentes jovenes sanos nativos de gran altitud. Objetivo: describir el comportamiento de la prueba de caminata de 6 minutos en residentes jovenes sanos nativos de gran altitud. Material y métodos: estudio de diseño transversal análitico. Se estudiaron sujetos consecutivos nacidos y residentes de las ciudades de La Paz y El Alto (Bolivia), de ambos géneros, sin enfermedad cardiopulmonar o limitación fisica. Se acotaron variables de altitud, hematológicas, demográficas y espirometria simple. Las diferencias fueron calculadas con la prueba t para grupos independientes o dependientes según la comparación. Una p < 0.05 fue considerada significativa. Resultados: se estudiaron 110 sujetos, altitud de 3673 ± 250 metros sobre el nivel del mar, edad 24 ± 5 años, 67 (60.90%) fueron mujeres. La hemoglobina 15.20 ± 2.46 g/dL, previo a la prueba, en 37 (33.63%) sujetos, la saturación parcial de oxigeno estuvo < 92% (90.92 ± 0.92%), su correlación con metros caminados r = - 0.244, p < 0.010. Metros caminados totales: 581 ± 35 (627.3 ± 52.88 nivel del mar); con las fórmulas de referencia de Enright PL: 542 ± 75, y de Osses AR: 459 ± 104, ambas obtenidas a < 1000 msnm. Los signos vitales estuvieron dentro de limites normales. Conclusión: la capacidad de realizar ejercicio submáximo estimada con la prueba de caminata de 6 minutos en la gran altitud es menor que la referida a nivel del mar. Las formulas de referencia infraestimaron los metros caminados en la gran altitud.

Elevation of Pulmonary Artery Pressure in Newborns from High-Altitude Pregnancies Complicated by Preeclampsia.

We hypothesized that fetal exposure to the oxidative stress induced by the combined challenge of preeclampsia (PE) and high altitude would induce a significant impairment in the development of pulmonary circulation. We conducted a prospective study in La Paz (Bolivia, mean altitude 3625 m) in which newborns from singleton pregnancies with and without PE were compared (PE group n = 69, control n = 70). We conducted an echocardiographic study in these infants at the median age of two days. The percentage of cesarean deliveries and small for gestational age (SGA) infants was significantly higher in the PE group. Heart rate, respiratory rate, and oxygen saturation did not vary significantly between groups. Estimated pulmonary arterial pressure and pulmonary vascular resistance were 30% higher in newborns exposed to PE and high altitude compared with those exposed only to high altitude. We also detected signs of right ventricular hypertrophy in infants subjected to both exposures. In conclusion, this study provides evidence that the combination of PE and pregnancy at high altitude induces subclinical alterations in the pulmonary circulation of the newborn. Follow-up of this cohort may provide us with valuable information on the potential increased susceptibility to developing pulmonary hypertension or other pulmonary and cardiovascular disorders.

[Chronic exposure to altitude. Clinical characteristics and diagnosis]. / Exposición crónica a la altura. Características clínicas y diagnóstico

Chronic exposure to altitude has been associated with hypobaric hypoxia in its inhabitants. Two entities have been associated with it, high altitude pulmonary hypertension and chronic mountain sickness. Its physiological and pulmonary circulation characteristics are described, as well as its clinical profile and diagnosis.

La exposición crónica a la altitud se ha asociado a hipoxia hipobárica en quienes la experimentan. Dos entidades se han asociado a la hipoxia hipobárica: la hipertensión pulmonar de la alta altitud y el mal de montaña crónico. Se describen sus características fisiológicas y de la circulación pulmonar, así como su perfil clínico y el diagnóstico.

Uso de cánula nasal de alto flujo artesanal como oxigenoterapia en insuficiencia respiratoria por COVID-19 / Use of artisanal high flow nasal cannula as oxygen therapy in respiratory failure due to COVID-19

Los riesgos asociados a la neumonía por (SARS-CoV-2) es la generación de insuficiencia respiratoria secundaria que en algunos casos desencadenara al tan temido síndrome de distres respiratorio (SDRA); Informes sobre atención clínica, indican que tiene una incidencia (SDRA) de 3-10 % con necesidad de Asistencia Respiratoria Mecánica (ARM) en pacientes hospitalizados; por lo que dispositivos de oxigenación no invasivos siguen siendo una opción atractiva, de forma inicial. Caso clínico: mujer de 47 años con insuficiencia respiratoria secundario a neumonía por COVID-19, por la gravedad se indica su ingreso a terapia intensiva, pero por razones de falta de unidad es manejada en unidad respiratoria, con el uso de dispositivos de oxigenación de armado ARTESAL, de manera exitosa, con la utilización de CNAF-artesanal, se pretende mejorar el trabajo respiratorio, índices de oxigenación, mientras se da tratamiento a la infección por el COVID-19; el objetivo del presente caso es reportar el presente caso con evolución favorable a la literatura disponible. Discusión: El uso de terapia de oxigenación con dispositivo de Cánula Nasal de Alto Flujo, aún no ha sido normatizado en pacientes con COVID-19, pero existe evidencia clínica sobre los efectos beneficiosos en la insuficiencia respiratoria en neonatos mas no en adultos. Conclusión: El uso temprano de la CNAF-artesanal en la insuficiencia respiratoria resulta muy atractivo, más aún con dispositivo de confección artesanal, da una opción más al paciente fuera de UTI, pudiendo apoyar en evitar la intubación y su ingreso a ventilación mecánica.

The risks associated with pneumonia (SARS-CoV-2) is the generation of secondary respiratory failure that in some cases will trigger the much feared respiratory distress syndrome (ARDS); Reports on clinical care indicate that it has an incidence (ARDS) of 3-10% with the need for Mechanical Respiratory Assistance (ARM) in hospitalized patients; so non-invasive oxygenation devices remain an attractive option, initially. Clinical case: a 47-year-old woman with respiratory failure secondary to covid-19 pneumonia. Due to the severity, her admission to intensive care is indicated, but for reasons of lack of unity, she is managed in a common room, with the use of high-pressure oxygenation devices. ARTISAL assembly, successfully, with the use of CNAF-artisanal, is intended to improve the work of breathing, and oxygenation indices, while treating the infection by COVID-19; The objective of this case is to report the present case with a favorable evolution based on the available literature. Discussion: The use of oxygenation therapy with a High Flow Nasal Cannula device has not yet been standardized in patients with COVID-19, but there is clinical evidence on the beneficial effects in respiratory failure in neonates but not in adults. Conclusion: The early use of the artisan HFNC in respiratory failure is very attractive, even more so with an artisanal device, it gives the patient another option outside the ICU, being able to help avoid intubation and admission to mechanical ventilation.

Exaggerated pulmonary hypertension and right ventricular dysfunction in high-altitude dwellers with patent foramen ovale.

BACKGROUND: There is considerable interindividual variability in pulmonary artery pressure among high-altitude (HA) dwellers, but the underlying mechanism is not known. At low altitude, a patent foramen ovale (PFO) is present in about 25% of the general population. Its prevalence is increased in clinical conditions associated with pulmonary hypertension and arterial hypoxemia, and it is thought to aggravate these problems. METHODS: We searched for a PFO (transesophageal echocardiography) in healthy HA dwellers (n = 22) and patients with chronic mountain sickness (n = 35) at 3,600 m above sea level and studied its effects (transthoracic echocardiography) on right ventricular (RV) function, pulmonary artery pressure, and vascular resistance at rest and during mild exercise (50 W), an intervention designed to further increase pulmonary artery pressure. RESULTS: The prevalence of PFO (32%) was similar to that reported in low-altitude populations and was not different in participants with and without chronic mountain sickness. Its presence was associated with RV enlargement at rest and an exaggerated increase in right-ventricular-to-right-atrial pressure gradient (25 ± 7 mm Hg vs 15 ± 9 mm Hg, P < .001) and a blunted increase in fractional area change of the right ventricle (3% [-1%, 5%] vs 7% [3%, 16%], P = .008) during mild exercise. CONCLUSIONS: These findings show, we believe for the first time, that although the prevalence of PFO is not increased in HA dwellers, its presence appears to facilitate pulmonary vasoconstriction and RV dysfunction during a mild physical effort frequently associated with daily activity. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01182792; URL: www.clinicaltrials.gov.