Treatment Of Acute Mountain Sickness Research Articles

Lactobacillus delbrueckii subsp. bulgaricus Alleviates Acute Injury in Hypoxic Mice.

Acute mountain sickness (AMS) is a common ailment in high-altitude areas caused by the body's inadequate adaptation to low-pressure, low-oxygen environments, leading to organ edema, oxidative stress, and impaired intestinal barrier function. The gastrointestinal tract, being the first to be affected by ischemia and hypoxia, is highly susceptible to injury. This study investigates the role of Lactobacillus delbrueckii subsp. bulgaricus in alleviating acute hypoxic-induced intestinal and tissue damage from the perspective of daily consumed lactic acid bacteria. An acute hypoxia mouse model was established to evaluate tissue injury, oxidative stress, inflammatory responses, and intestinal barrier function in various groups of mice. The results indicate that strain 4L3 significantly mitigated brain and lung edema caused by hypoxia, improved colonic tissue damage, and effectively increased the content of tight junction proteins in the ileum, reducing ileal permeability and alleviating mechanical barrier damage in the intestines due to acute hypoxia. Additionally, 4L3 helped to rebalance the intestinal microbiota. In summary, this study found that Lactobacillus delbrueckii subsp. bulgaricus strain 4L3 could alleviate acute intestinal damage caused by hypoxia, thereby reducing hypoxic stress. This suggests that probiotic lactic acid bacteria that exert beneficial effects in the intestines may alleviate acute injury under hypoxic conditions in mice, offering new insights for the prevention and treatment of AMS.

Gastrointestinal syndrome encountered during a train voyage to high altitudes: A 14-day survey of 69 passengers in China

BackgroundThe diagnosis and evaluation of the severity of acute mountain sickness (AMS) continue to be problematic due to a lack of consensus on the inclusion of symptoms in a scoring system. Recent investigations highlight the significance of gastrointestinal symptoms in identifying this condition. However, the specific gastrointestinal symptoms associated with AMS have not been thoroughly elucidated in previous studies, and the underlying risk factors remain inadequately comprehended. MethodsThis study aimed to investigate the characteristics, trends, and risk factors related to gastrointestinal symptoms encountered during train travel to high altitude. A total of 69 passengers, specifically all with medical backgrounds, were surveyed 6 times over a period of 14 days. ResultsThe daily incidence of abdominal discomfort was higher than non-gastrointestinal symptoms within 14 days. Gastrointestinal symptoms demonstrated a greater prevalence, longer duration, and increased risk compared to non-gastrointestinal symptoms, such as headaches. The symptoms of abdominal distension and bowel sound hyperaction were found to be prevalent and persistent among patients diagnosed with AMS, exhibiting a high incidence rate. Gender, age, body mass index (BMI), smoking habits, and alcohol consumption were identified as risk factors associated with the occurrence and duration of gastrointestinal symptoms. ConclusionThis study suggests that gastrointestinal symptoms are more common and persistent when traveling to the plateau by train. These symptoms should be taken into consideration in the further diagnosis and prevention of AMS. Therefore, this study provides a significant theoretical foundation for the prevention and treatment of AMS.

WITHDRAWN: Wilderness Medical Society Clinical Practice Guidelines for the Prevention, Diagnosis, and Treatment of Acute Altitude Illness: 2024 Update

To provide guidance to clinicians about best practices, the Wilderness Medical Society (WMS) convened an expert panel to develop evidence-based guidelines for prevention, diagnosis, and treatment of acute mountain sickness, high altitude cerebral edema, and high altitude pulmonary edema. Recommendations are graded based on the quality of supporting evidence and the balance between the benefits and risks/burdens according to criteria put forth by the American College of Chest Physicians. The guidelines also provide suggested approaches for managing each form of acute altitude illness that incorporate these recommendations as well as recommendations on how to approach high altitude travel following COVID-19 infection. This is an updated version of the original WMS Consensus Guidelines for the Prevention and Treatment of Acute Altitude Illness published in Wilderness & Environmental Medicine in 2010 and the subsequently updated WMS Practice Guidelines for the Prevention and Treatment of Acute Altitude Illness published in 2014 and 2019.

Chemical characteristics of Rhodiola Crenulata and its mechanism in acute mountain sickness using UHPLC-Q-TOF-MS/MS combined with network pharmacology analysis

Ethnopharmacological relevanceRhodiola crenulata (Hook.f. & Thomson) H.Ohba has a long history of clinical application for the prevention and treatment of acute mountain sickness (AMS) in traditional Chinese medicine. However, gaps in knowledge still exist in understanding the underlying mechanisms of Rhodiola crenulata against AMS. AimsTo address this problem, a comprehensive method was established by combining UHPLC-Q-TOF-MS/MS analysis and network pharmacology. Materials and methodsThe ingredients of Rhodiola crenulata were comprehensively analyzed using UHPLC-Q-TOF-MS/MS method. On this basis, a network pharmacology method incorporated target prediction, protein-protein interaction network, gene enrichment analysis and components-targets-pathways network was performed. Finally, the possible mechanisms were verified through molecular docking, in vitro and in vivo experiments. ResultsA total of 106 constituents of Rhodiola crenulata were charactered via UHPLC-Q-TOF-MS/MS. The 98 potentially active compounds out of 106 were screened and corresponded to 53 anti-AMS targets. Gene enrichment analysis revealed that hypoxia and inflammation related genes may be the central factors for Rhodiola crenulata to modulate AMS. Molecular docking revealed that TNF, VEGFA and HIF-1α had high affinities to Rhodiola crenulata compounds. Subsequently, Rhodiola crenulata extract was indicated to inhibit the protein expression level of TNF in hypoxia induced H9c2 cells. Lastly, Rhodiola crenulata extract was further verified to ameliorate heart injury and decreased the heart levels of TNF, VEGFA and HIF-1α in acute hypoxia-induced rats. ConclusionsThis study used UHPLC-Q-TOF-MS/MS analysis and a network pharmacology to provide an important reference for revealing the potential mechanism of Rhodiola crenulata in the prevention and treatment of AMS.

Altitude, Acute Mountain Sickness, and Acetazolamide: Recommendations for Rapid Ascent.

Toussaint, Claudia M., Robert W. Kenefick, Frank A. Petrassi, Stephen R. Muza, and Nisha Charkoudian. Altitude, acute mountain sickness, and acetazolamide: recommendations for rapid ascent. High Alt Med Biol. 22:5-13, 2021. Background: Sea level natives ascending rapidly to altitudes above 1,500 m often develop acute mountain sickness (AMS), including nausea, headaches, fatigue, and lightheadedness. Acetazolamide (AZ), a carbonic anhydrase inhibitor, is a commonly used medication for the prevention and treatment of AMS. However, there is continued debate about appropriate dosing, particularly when considering rapid and physically demanding ascents to elevations above 3,500 m by emergency medical and military personnel. Aims: Our goal in the present analysis was to evaluate and synthesize the current literature regarding the use of AZ to determine the most effective dosing for prophylaxis and treatment of AMS for rapid ascents to elevations >3,500 m. These circumstances are specifically relevant to military and emergency medical personnel who often need to ascend rapidly and perform physically demanding tasks upon arrival at altitude. Methods: We conducted a literature search from April 2018 to February 2020 using PubMed, Google Scholar, and Web of Science to identify randomized controlled trials that compared AZ with placebo or other treatment with the primary endpoint of AMS incidence and severity. We included only research articles/studies that focused on evaluation of AZ use during rapid ascent. Results: Four doses of AZ (125, 250, 500, and 750 mg daily) were identified as efficacious in decreasing the incidence and/or severity of AMS during rapid ascents, with evidence of enhanced effectiveness with higher doses. Conclusions: For military, emergency medical, or other activities involving rapid ascent to altitudes >3,500 m, doses 500-750 mg/day within 24 hours of altitude exposure appear to be the most effective for minimizing symptoms of AMS.

Relationships Between Ventilatory And Heart Rate Responses To Hypobaric Hypoxia: Influences Of Acetazolamide

Acetazolamide (AZ) is often used for prevention and/or treatment of acute mountain sickness (AMS), particularly during rapid ascent to altitudes > 3000 m. Although it is known that AZ augments ventilation (VE), it is unclear how this may affect chemoreflex relationships among ventilatory variables and control of heart rate (HR). PURPOSE: The purpose of the study was two-fold: 1), establish the effect of AZ and hypobaric hypoxia (HH) on VE and HR; and 2), estimate the effect of AZ on the chemoreflex relationship between VE and HR. METHODS: After completing familiarization testing at sea level (SL), 10 male volunteers (22 ± 3 yr; height: 176.0 ± 7.1 cm; weight: 77.5 ± 11.5 kg) completed two 30 hr HH exposures (~ 3500 m); one while taking AZ (500 mg/day) and one while taking a placebo, in a single-blind crossover design in random order. Ventilation and gas exchange, including HR, VE, and end-tidal partial pressure of carbon dioxide (PetCO2), were measured three times at rest, once at SL and then at ~2 and 24 hours into exposure to simulated altitude. A linear mixed model with a random intercept per subject was utilized to evaluate the influences of AZ and HH on HR, VE, and PetCO2. RESULTS: VE increased and PetCO2 decreased (p<0.05 for all) with both HH and AZ. HR increased with HH (p<0.001), but there was no further effect of AZ (p=0.15). HR was related to both VE (p=0.009) and PetCO2 (p<0.001) in all subjects. AZ shifted the relationships between HR, VE, and PetCO2, but there was no interaction between AZ and HH (p>0.10 for both). Overall, while AZ augmented VE it did not affect the slope of the relationship between HR and VE, but rather shifted the relationship to lower VE values. CONCLUSION: During exposure to HH, activation of the chemoreflex augments both ventilation and sympathetic outflow to the heart causing increased HR. Our present findings that VE tended to be lower for a given level of HR during AZ trials, suggest that AZ may have an influence to shift the relationship between these two chemoreflex-mediated events. Funded by USAMRMC; author views not official US Army or DOD policy.

Prospective Double-Blinded Randomized Field-Based Clinical Trial of Metoclopramide and Ibuprofen for the Treatment of High Altitude Headache and Acute Mountain Sickness

High altitude headache (HAH) and acute mountain sickness (AMS) are common pathologies at high altitudes. There are similarities between AMS and migraine headaches, with nausea being a common symptom. Several studies have shown ibuprofen can be effective for AMS prophylaxis, but few have addressed treatment. Metoclopramide is commonly administered for migraine headaches but has not been evaluated for HAH or AMS. We aimed to evaluate metoclopramide and ibuprofen for treatment of HAH and AMS. We performed a prospective, double-blinded, randomized, field-based clinical trial of metoclopramide and ibuprofen for the treatment of HAH and AMS in 47 adult subjects in the Mount Everest region of Nepal. Subjects received either 400 mg ibuprofen or 10 mg metoclopramide in a 1-time dose. Lake Louise Score (LLS) and visual analog scale of symptoms were measured before and at 30, 60, and 120 min after treatment. Subjects in both the metoclopramide and ibuprofen arms reported reduced headache severity and nausea compared to pretreatment values at 120 min. The ibuprofen group reported 22 mm reduction in headache and 6 mm reduction in nausea on a 100 mm visual analog scale at 120 min. The metoclopramide group reported 23 mm reduction in headache and 14 mm reduction in nausea. The ibuprofen group reported an average 3.5-point decrease on LLS, whereas the metoclopramide group reported an average 2.0-point decrease on LLS at 120 min. Metoclopramide and ibuprofen may be effective alternative treatment options in HAH and AMS, especially for those patients who additionally report nausea.

Significance of the proper acclimatization, use of the acetazolamide and dexamethasone in prevention of acute mountain sickness (AMS) – literature review

Acute mountain sickness (AMS) is an ilness, that occurs in non-acclimatized individuals after rapid ascent to high altitude, typically above 2,500 metres (8,000 ft). The main causes of the AMS are: reduced air pressure and lower oxygen levels at high altitudes. The early symptoms of AMS are non-specific such as: headache, anorexia, nausea, vomiting, fatigue, dizziness, and sleep disturbance, but not all need to be present at one time. It is very important to recognise the early symptoms of AMS and to start the treatment, because untreated AMS can progress to the life‐threatening: high altitude cerebral edema (HACE) and high altitude pulmonary edema (HAPE). Treatment of AMS consists of stabilization of the patient conditon, descent to lower altitude, oxygen therapy and administering acetazolamide and dexamethasone. The aim of this study was to evaluate the significance of the proper acclimatization, use of the acetazolamide and dexamethasone in prevention of acute mountain sickness (AMS).Proper acclimatization, use of the acetazolamide and dexamethasone are highly effective in prevention of occurrence and reducing the symptoms of acute mountain sickness (AMS). Pharmacological prophylaxis is not necessary in low-risk situations but should be considered in addition to gradual ascent for use in moderate- to high-risk situations Acetazolamide should be strongly considered in climbers and travelers at moderate or high risk of AMS with ascent to high altitude. Dexamethasone can be used as an alternative in individuals with a history of intolerance of or allergic reaction to acetazolamide. In rare circumstances (eg, military or rescue teams that must ascend rapidly to and perform physical work at &gt;3500 m), consideration can be given to concurrent use of acetazolamide and dexamethasone.

Systematically investigating the pharmacological mechanism of Dazhu Hongjingtian in the prevention and treatment of acute mountain sickness by integrating UPLC/Q-TOF-MS/MS analysis and network pharmacology

Members of the genus Rhodiola L. have been widely used in Tibetan medicines for preventing and treating acute mountain sickness (AMS) for a long time. However, the pharmacological mechanisms of these medicines in treating AMS remain unclear. To address this problem, an integrative method combining ultra-performance liquid chromatography coupled with a quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS/MS)analysis and network pharmacology was employed. First, the chemical profiles of Dazhu Hongjingtian (DZ, a Chinese medicine preparation composed of R. kirilowii (Regel) Maxim) were identified or tentatively characterized. Second, the targets of DZ were predicted using the SwissTargetPrediction and STITCH databases; the targets of AMS were also collected from the Drugbank and TTD databases. Then, networks between targets and compounds or diseases were constructed by Cytoscape 3.6.1. Third, GO and pathway enrichment analyses were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID). As a result, 40 ingredients of 53 compounds in DZ might be biologically active. These activities were related to the regulatory effects of the ingredients on 68 significant signaling pathways, such as the inflammation pathway, apoptosis pathway, HIF-1 signaling pathway, and others, by targeting 33 proteins, including PTGS2 and PTGS1, ALOX5 and ALOX15, BCL2 and BCL2L1, the protein kinase C (PKC) family and HIF1A, among others.

Understanding molecular mechanisms of Rhodiola rosea for the treatment of acute mountain sickness through computational approaches (a STROBE-compliant article).

Rhodiola rosea has been used in the treatment of acute mountain sickness (AMS) for a long time, but the mechanism of its action is not still completely clear. In this paper, the therapeutic mechanism of R rosea for AMS was investigated by analysis of the relationship between R rosea compositions and hypoxia-inducible factor 1 (HIF-1) degradation pathway.System biology and network biology, computational approaches were used to explore the molecular mechanisms of traditional Chinese medicine (TCM).Our results showed that chemical compositions of R rosea could inhibit the targets of HIF-1 degradation pathway in multi-composition/multi-target ways.We conclude that the 18 components with more than 2 targets and 5 targets (arrest-defective-1 [ARD1], forkhead transcription factor [FOXO4], osteosarcoma-9 [OS-9], prolyl hydroxylase 2 [PHD2], human double minute 2 [Hdm2]) deserve to be noticed, and PHD2, receptor for activated C-kinase1 (RACK1) and spermidine/spermine-N1-acetyltransferase-1 (SSAT1) may be the targets of active ingredients of rhodionin, rhodiosin, and rhodiolatuntoside, respectively.

Prospective Double-Blinded Randomized Field-Based Clinical Trial of Metoclopramide and Ibuprofen for the Treatment of Acute Mountain Sickness

Prospective Double-Blinded Randomized Field-Based Clinical Trial of Metoclopramide and Ibuprofen for the Treatment of Acute Mountain Sickness

Systemic pro-inflammatory response facilitates the development of cerebral edema during short hypoxia.

BackgroundHigh-altitude cerebral edema (HACE) is the severe type of acute mountain sickness (AMS) and life threatening. A subclinical inflammation has been speculated, but the exact mechanisms underlying the HACE are not fully understood.MethodsHuman volunteers ascended to high altitude (3860 m, 2 days), and rats were exposed to hypoxia in a hypobaric chamber (5000 m, 2 days). Human acute mountain sickness was evaluated by the Lake Louise Score (LLS), and plasma corticotrophin-releasing hormone (CRH) and cytokines TNF-α, IL-1β, and IL-6 were measured in rats and humans. Subsequently, rats were pre-treated with lipopolysaccharide (LPS, intraperitoneal (ip) 4 mg/kg, 11 h) to induce inflammation prior to 1 h hypoxia (7000 m elevation). TNF-α, IL-1β, IL-6, nitric oxide (NO), CRH, and aquaporin-4 (AQP4) and their gene expression, Evans blue, Na+-K+-ATPase activity, p65 translocation, and cell swelling were measured in brain by ELISA, Western blotting, Q-PCR, RT-PCR, immunohistochemistry, and transmission electron micrography. MAPKs, NF-κB pathway, and water permeability of primary astrocytes were demonstrated. All measurements were performed with or without LPS challenge. The release of NO, TNF-α, and IL-6 in cultured primary microglia by CRH stimulation with or without PDTC (NF-κB inhibitor) or CP154,526 (CRHR1 antagonist) were measured.ResultsHypobaric hypoxia enhanced plasma TNF-α, IL-1β, and IL-6 and CRH levels in human and rats, which positively correlated with AMS. A single LPS injection (ip, 4 mg/kg, 12 h) into rats increased TNF-α and IL-1β levels in the serum and cortex, and AQP4 and AQP4 mRNA expression in cortex and astrocytes, and astrocyte water permeability but did not cause brain edema. However, LPS treatment 11 h prior to 1 h hypoxia (elevation, 7000 m) challenge caused cerebral edema, which was associated with activation of NF-κB and MAPKs, hypoxia-reduced Na+-K+-ATPase activity and blood-brain barrier (BBB) disruption. Both LPS and CRH stimulated TNF-α, IL-6, and NO release in cultured rat microglia via NF-κB and cAMP/PKA.ConclusionsPreexisting systemic inflammation plus a short severe hypoxia elicits cerebral edema through upregulated AQP4 and water permeability by TLR4 and CRH/CRHR1 signaling. This study revealed that both infection and hypoxia can cause inflammatory response in the brain. Systemic inflammation can facilitate onset of hypoxic cerebral edema through interaction of astrocyte and microglia by activation of TLR4 and CRH/CRHR1 signaling. Anti-inflammatory agents and CRHR1 antagonist may be useful for prevention and treatment of AMS and HACE.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-016-0528-4) contains supplementary material, which is available to authorized users.

310 Prospective Double-Blinded Randomized Field-Based Clinical Trial of Metoclopramide and Ibuprofen for the Treatment of Acute Mountain Sickness

310 Prospective Double-Blinded Randomized Field-Based Clinical Trial of Metoclopramide and Ibuprofen for the Treatment of Acute Mountain Sickness

Wilderness Medical Society Practice Guidelines for the Prevention and Treatment of Acute Altitude Illness: 2014 Update

To provide guidance to clinicians about best practices, the Wilderness Medical Society convened an expert panel to develop evidence-based guidelines for prevention and treatment of acute mountain sickness, high altitude cerebral edema, and high altitude pulmonary edema. These guidelines present the main prophylactic and therapeutic modalities for each disorder and provide recommendations about their role in disease management. Recommendations are graded based on the quality of supporting evidence and balance between the benefits and risks/burdens according to criteria put forth by the American College of Chest Physicians. The guidelines also provide suggested approaches to prevention and management of each disorder that incorporate these recommendations. This is an updated version of the original WMS Consensus Guidelines for the Prevention and Treatment of Acute Altitude Illness published in Wilderness & Environmental Medicine 2010;21(2):146-155.

High-altitude headache and acute mountain sickness

IntroductionHeadache is the most common complication associated with exposure to high altitude, and can appear as an isolated high-altitude headache (HAH) or in conjunction with acute mountain sickness (AMS). The purpose of this article is to review several aspects related to diagnosis and treatment of HAH. DevelopmentHAH occurs in 80% of all individuals at altitudes higher than 3000m. The second edition of ICHD-II includes HAH in the chapter entitled “Headaches attributed to disorder of homeostasis”. Hypoxia elicits a neurohumoral and haemodynamic response that may provoke increased capillary pressure and oedema. Hypoxia-induced cerebral vasodilation is a probable cause of HAH. The main symptom of AMS is headache, frequently accompanied by sleep disorders, fatigue, dizziness and instability, nausea and anorexia. Some degree of individual susceptibility and considerable inter-individual variability seem to be present in AMS. High-altitude cerebral oedema is the most severe form of AMS, and may occur above 2500m. Brain MRI studies have found variable degrees of oedema in subcortical white matter and the splenium of the corpus callosum. HAH can be treated with paracetamol or ibuprofen. Pharmacological treatment of AMS is intended to increase ventilatory drive with drugs such as acetazolamide, and reduce inflammation and cytokine release by means of steroids. ConclusionsSymptom escalation seems to be present along the continuum containing HAH, AMS, and high-altitude cerebral oedema.

Anuric Acute Kidney Injury Induced by Acute Mountain Sickness Prophylaxis With Acetazolamide.

Acetazolamide (ACZ) is a sulfonamide derivative that inhibits carbonic anhydrase and is the mainstay for prevention and treatment of acute mountain sickness (AMS). Acute kidney injury (AKI) is not well recognized as a complication of ACZ ingestion, especially when low doses are used for short periods of time. We report a case of a healthy, middle-aged man who developed severe AKI after the ingestion of ACZ for AMS prophylaxis. The patient presented with bilateral flank pain and anuric AKI without radiographic signs of obstructive uropathy. All blood and urine testing to determine the cause of AKI were negative or normal. The patient required 2 sessions of hemodialysis due to worsening metabolic derangements, which included severe anion gap metabolic acidosis and hyperphosphatemia. Renal function returned to baseline after 96 hours of supportive care. The pathogenesis of AKI in our patient was attributed to ACZ-induced sulfonamide crystalluria causing intratubular obstruction and retrograde urine flow, but not intraureteric precipitation or obstructive uropathy. This classic presentation of anuric AKI and renal colic has been previously described with higher doses of ACZ for prolonged periods of time but never with low doses for AMS prophylaxis such as in our patient (total dose of 1250 mg within 48 hours). Our case highlights the risk of adverse renal outcomes following ACZ ingestion, even in previously healthy individuals, and suggests that increased fluid intake may be advisable for travelers taking ACZ prophylaxis.

Bioavailability, tissue distribution, and excretion characteristics of the novel carbonic anhydrase inhibitor tolsultazolamide in rats

Tolsultazolamide, a novel carbonic anhydrase inhibitor, is designed for the prophylaxis and treatment of acute mountain sickness. The aim of this study was to investigate the pharmacokinetics, tissue distribution, and excretion characteristics of tolsultazolamide and the sex difference in pharmacokinetics in rats. For pharmacokinetic study, rats were intravenously injected tolsultazolamide at 1 and 2 mg/kg or orally administered tolsultazolamide at 20, 40, or 80 mg/kg) in a pharmacokinetic study. The concentrations of tolsultazolamide in plasma were determined with high-performance liquid chromatography, with a liquid-liquid extraction. For tissue distribution study, tolsultazolamide (80 mg/kg) was orally administered to overnight fasted rats (six per group and three per sex). Samples were collected from the brain, heart, lung, liver, spleen, muscle, kidney, stomach, fat, intestines, pancreas and sexual gland. For excretion study, tolsultazolamide (40 mg/kg) was orally administered to 6 rats (three per sex). The urine, feces, and bile samples were collected at 24, 48, and 72 h. After its intravenous administration, tolsultazolamide was rapidly eliminated from the plasma, with T1/2 of about 60-90 min. The AUC0-t and the initial concentration (C0) values were proportional to the intravenous doses. After its oral administration, tolsultazolamide showed dose-independent pharmacokinetic characteristics, with Tmax and T1/2 of approximately 2 h and 5-7 h, respectively, and good oral absolute bioavailability of about 60%. Tolsultazolamide was distributed widely in various tissues. The highest tolsultazolamide levels were detected in the stomach, intestine, spleen, lung, and kidney. Total excretion of unchanged tolsultazolamide in the urine, feces, and bile was less than 2%. The Cmax and AUC of tolsultazolamide were significantly higher in female rats than those in male rats. Clearance and volume of distribution were greater in male rats than those in female rats. The oral absolute bioavailability was also significantly different between female rats (about 83%) and male rats (about 37%). Tolsultazolamide was well absorbed and widely distributed in the rat, and very little of the unchanged form was excreted. Sex had a significant effect on the pharmacokinetics of tolsultazolamide.

Cefalea de elevada altitud y mal de altura

IntroductionHeadache is the most common complication associated with exposure to high altitude, and can appear as an isolated high-altitude headache (HAH) or in conjunction with acute mountain sickness (AMS). The purpose of this article is to review several aspects related to diagnosis and treatment of HAH. DevelopmentHAH occurs in 80% of all individuals at altitudes higher than 3000 meters. The second edition of ICHD-II includes HAH in the chapter entitled “Headaches attributed to disorder of homeostasis”. Hypoxia elicits a neurohumoral and haemodynamic response that may provoke increased capillary pressure and oedema. Hypoxia-induced cerebral vasodilation is a probable cause of HAH. The main symptom of AMS is headache, frequently accompanied by sleep disorders, fatigue, dizziness and instability, nausea and anorexia. Some degree of individual susceptibility and considerable inter-individual variability seem to be present in AMS. High-altitude cerebral oedema is the most severe form of AMS, and may occur above 2500 meters. Brain MRI studies have found variable degrees of oedema in subcortical white matter and the splenium of the corpus callosum. HAH can be treated with paracetamol or ibuprofen. Pharmacological treatment of AMS is intended to increase ventilatory drive with drugs such as acetazolamide, and reduce inflammation and cytokine release by means of steroids. ConclusionsSymptom escalation seems to be present along the continuum containing HAH, AMS, and high-altitude cerebral oedema.

Effects of non‐steroid anti‐inflammatory drugs on the human hypoxic ventilatory response and acclimatization

Recent studies show that inflammation contributes to respiratory chemoreflex plasticity during chronic hypoxia. Ibuprofen (a non‐steroidal anti‐inflammatory drug, NSAID) prevents the normal time‐dependent increase in the hypoxic ventilatory response (HVR) in chronically hypoxic rats (Respir. Physiol. Neurobiol. 178: 381–386, 2011). We hypothesized that inflammatory pathways contribute to ventilatory acclimatization to hypoxia in humans also. To test this, we measured the isocapnic HVR in 5 subjects at sea level and at high altitude (3,800m) using a randomized, double‐blind, repeated measures protocol. Ibuprofen or placebo was administered (400mg TID) over 48 hours at sea level and over 48 hours at 3,800m. We measured HVR at 24 and 48 hours of treatment at sea level and 3,800m. Results showed no significant difference in the HVR between placebo and ibuprofen treatments at sea level. A significant increase in the HVR at altitude occurred with placebo, indicating normal ventilatory acclimatization. However, ibuprofen blocked the increase in HVR at altitude, showing significantly less HVR increase with ibuprofen versus placebo. The results may have implications for the treatment of acute mountain sickness at high altitude with NSAIDs. Supported by UC White Mt. Res. St., NIH RO1 HL‐ 081823 &amp; 1P01 HL 098053.

Acute mountain sickness, two cases and their treatment in the field

The number of lowland dwellers traveling at high altitudes has greatly increased in recent decades. Business travelers flying to La Paz or Lhasa are at risk of altitude illnesses, similarly to miners and soldiers transported to high altitudes. Traveling to high altitude requires adaptation and if this process fails due to too rapid an ascent rate or susceptibility of the climber, acute mountain sickness (AMS) may result. Doctors and nurses in travel clinics, health centers and occupational health care clinics may face patients asking advice on how to plan their trips or manage AMS, or the health care personnel may take part in a travel to high altitude environment. Two patients, aged 29 and 47 years, who fulfilled the criteria for AMS were studied. The clinical findings and treatment in the field are described including the review of the current recommendations for prevention and treatment of AMS. Both patients developed a severe AMS due to too rapid ascent and their denial of the symptoms. Prevention is the safest and the most efficient method in the care concerning AMS. Realizing the risk of mountain sickness, active inquiry about the symptoms and correctly timed reaction to them, in other words interrupting the ascent or descending, help to reduce and even to prevent the development of serious problems.