Mal agudo de montaña: pasado, presente y futuro / Acute mountain sickness: past, present and future

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

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

Phytochemistry and Biological Activities of Werneria and Xenophyllum species / Fitoquímica y actividades biológicas de especies de Werneria y Xenophyllum

Plants of the genera Werneria (Asteraceae) and Xenophyllum (genus extracted from Werneria) are used in traditional medicine of Latin America for the treatment of mountain sickness, hypertension and gastrointestinal disorders. Only a small number of species of these genera have been studied, leading to the isolation of compounds belonging to the classes of benzofurans, chromenes, acetophenones, coumarates, diterpenes and pyrrolizidine alkaloids. Some of the plant extracts and/or compounds have shown antimicrobial, anti-HIV, hypotensive and photoprotective activities.

Las plantas de los géneros Werneria (Asteraceae) y Xenophyllum (género extraido de Werneria) son usadas en la medicina tradicional de América Latina para el tratamiento del mal de montaña, hipertensión y desórdenes gastrointestinales. Solo un pequeño número de especies de estos géneros ha sido investigado, lográndose aislar compuestos que pertenecen a las clases de benzofuranos, cromenos, acetofenonas, cumaratos, diterpenos y alcaloides pirrolizidínicos. Algunos de los extractos y/o compuestos de dichas plantas han mostrado actividades antimicrobianas, anti-HIV, hipotensoras y fotoprotectoras.

Acetazolamida como tratamiento del mal agudo de montaña / Acetazolamide for the treatment of acute mountain sickness

INTRODUCCIÓN El mal agudo de montaña es la patología más prevalente relacionada con la exposición aguda a la altura, secundaria a los efectos de la hipoxia hipobárica en nuestro organismo. La acetazolamida se ha utilizado tradicionalmente para su prevención y tratamiento, sin embargo, aún existe controversia respecto al grado de utilidad que tiene este medicamento como monoterapia. MÉTODOS Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un meta análisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES Identificamos una revisión sistemática que incluyó dos estudios primarios, ambos correspondientes a ensayos aleatorizados. Concluimos que no es posible establecer con claridad si el tratamiento con acetazolamida disminuye los síntomas del mal agudo de montaña ni si aumenta el riesgo de efectos adversos, debido a que la certeza de la evidencia existente ha sido evaluada como muy baja.

INTRODUCTION Acute mountain sickness is the most prevalent illness related to acute exposure to high altitude, secondary to the hypobaric hypoxia effects in our body. Acetazolamide has been traditionally used for its prevention and treatment, however, there is still controversy regarding the degree of usefulness of this medication as monotherapy. METHODS We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS We identified a systematic review that included two primary studies, both corresponding to randomized trials. We conclude that it is not possible to establish clearly whether treatment with acetazolamide reduces the symptoms of acute mountain disease or increases the risk of adverse effects, because the certainty of the existing evidence has been evaluated as very low.

Edema pulmonar de altura: Modelo de estudio de la fisiopatología del edema pulmonar y de la hipertensión pulmonar hipóxica en humanos / High altitude pulmonary edema. An experiment of Nature to study the underlying mechanisms of hypoxic pulmonary hypertension and pulmonary edema in humans

La altura, fascinante laboratorio natural de investigación médica, provee resultados con importantes implicancias para la comprensión de enfermedades que afectan a millones de personas que viven en ella, asi como para el tratamiento de enfermedades ligadas a la hipoxemia en pacientes que viven en baja altitud. El edema pulmonar de altura (EPA) es una entidad que pone en peligro la vida y que ocurre en sujetos predispuestos pero sanos. Esto permite estudiar los mecanismos subyacentes del edema pulmonar en humanos, sin la presencia de factores que presten a la confusión como enfermedades concomitantes. El EPA resulta de la conjunción de dos defectos mayores: acumulación de líquido en el espacio alveolar debido a una hipertensión pulmonar hipóxica exagerada, y alteración en la eliminación del mismo por un defecto en el transporte transepitelial alveolar de sodio. En esta revisión, describimos brevemente las características clínicas y revisaremos este novedoso concepto. Proveemos evidencia experimental de como la síntesis alterada de óxido nítrico y/o la disminución de su biodisponibilidad representan el defecto central que predispone a la vasoconstricción pulmonar hipóxica exagerada y a la acumulación de líquido en el espacio alveolar. Mostramos que la hipertensión pulmonar hipóxica exagerada, per se, no es suficiente para producir un EPA, y que una alteración en la eliminación del fluido del espacio alveolar representa un segundo mecanismo fisiopatológico importante. Finalmente, describimos cómo los nuevos aportes obtenidos de los estudios del EPA pueden ser trasladados al manejo de otros estados patológicos ligados a la hipoxemia.

High altitude constitutes an exciting natural laboratory for medical research. Over the past decade, it has become clear that the results of high-altitude research may have important implications not only for the understanding of diseases in the millions of people living permanently at high altitude, but also for the treatment of hypoxemia-related disease states in patients living at low altitude. High-altitude pulmonary edema (HAPE) is a life-threatening condition occurring in predisposed, but otherwise healthy subjects, and, therefore, allows to study underlying mechanisms of pulmonary edema in humans, in the absence of confounding factors. Over the past decade, evidence has accumulated that HAPE results from the conjunction of two major defects, augmented alveolar fluid flooding resulting from exaggerated hypoxic pulmonary hypertension, and impaired alveolar fluid clearance related to defective respiratory transepithelial sodium transport. Here, after a brief presentation of the clinical features of HAPE, we review this novel concept. We provide experimental evidence for the novel concept that impaired pulmonary endothelial and epithelial nitric oxide synthesis and/or bioavailability may represent the central underlying defect predisposing to exaggerated hypoxic pulmonary vasoconstriction and alveolar fluid flooding. We demonstrate that exaggerated pulmonary hypertension, while possibly a condition sine qua non, may not be sufficient to cause HAPE, and how defective alveolar fluid clearance may represent a second important pathogenic mechanism. Finally, we outline how this insight gained from studies in HAPE may be translated into the management of hypoxemia related disease states in general.

Acute mountain sickness score and hypoxemia

Hypoxemia is the immediate consequence of hyobaric hypoxia, which is the crucial starting mechanism of acute mountain sickness [AMS]. The AMS is generally a benign and self-limiting condition which can be prevented by gradual ascent. However, ascent rates recommended for prophylaxis of AMS are far slower than those attempted during military operations and by climbers. The current study was carried out to quantify the relationship between AMS and hypoxemia alongwith evaluating the benefits of acetazolamide-dexamethasone chemoprophylaxis during acute ascent. Twenty-four low lander male adults [age mean +/- SE 27.8 +/- 1.24 years] were selected. They were grouped in a double-blind fashion into four groups and each group [n = 6] received placebo [multivitamin] or acetazolamide [250 mg] or dexamethasone [4 mg] or a combined regimen of the two drugs twice daily for 5 days, commencing 24 hours before ascent. The volunteers reached the altitude of 4578 meters within a span of one day. Their AMS symptoms were recorded on modified environmental symptoms questionnaire [ESQ], after 24 and 72 hours of ascent. Arterial PO2, SO2 and PCO2 were measured by GEMSTAT blood-gas analyzer [Mallincrodt-USA]. The ESQ, AMS-C [cerebral] and AMS-R [respiratory] scores of combined therapy group were significantly lower as compared to the other groups on the symptom rating scale. The significant finding amongst the volunteers taking acetazolamide was mild to moderate diuresis whereas severity of headache was markedly less in dexamethasone group. The commonest feature of combined therapy was that none of the volunteers complained of headache, dysponea, irritability and more than mild disturbance of sleep. The ESQ scores of volunteers were inversely correlated to PaO2 and SaO2 after 24 hours of ascent to 4578 meters. The study concludes that severity of AMS is closely related to hypoxemia and combination therapy of acetazolamide-dexamethasone may be effective in preventing AMS