montelukast and Altitude-Sickness

Previous research has demonstrated that blood and urine concentrations of various leukotrienes are elevated with acute hypoxic exposure. Some of these studies have suggested that leukotrienes may be mediators in the pathogenesis of acute mountain sickness (AMS). We conducted a randomized, double-blind study to determine if AMS symptoms correlated with the increase in leukotriene synthesis and if prophylactic leukotriene receptor blockade would prevent the development of AMS in a simulated high altitude exposure. Three male and five female subjects completed two normobaric hypoxia chamber exposures (average F(IO2) 12.4 +/- 0.09%), receiving montelukast 10 mg daily for 4 days prior to one session and placebo for 4 days prior to the other session. There were no differences in Lake Louise AMS scores, time spent in the chamber, average oxygen saturation, and average heart rate during the montelukast and placebo sessions. Headache scores were higher during treatment with montelukast than during treatment with placebo. Compared to preexposure values, urinary leukotriene E4 concentrations were unchanged during the hypoxic chamber exposure following treatment with placebo or montelukast. Urinary leukotriene E4 excretion during the hypoxic exposure did not differ between the two sessions. A 4-day course of leukotriene receptor blockade does not prevent symptoms of AMS. These results suggest that leukotrienes do not play a causal role in the pathophysiology of AMS.

Topics: Acclimatization; Acetates; Administration, Oral; Adult; Altitude Sickness; Atmosphere Exposure Chambers; Cross-Over Studies; Cyclopropanes; Double-Blind Method; Female; Humans; Hypoxia; Leukotriene Antagonists; Leukotriene E4; Male; Premedication; Quinolines; Severity of Illness Index; Statistics, Nonparametric; Sulfides

Acute Mountain Sickness (AMS) is a multi-system disorder that is characterized by headache, anorexia, nausea, vomiting, insomnia, lassitude, and malaise. The syndrome is common in unacclimatized low altitude residents who rapidly ascend to terrestrial elevations exceeding 2,500 m. AMS may be a manifestation of hypoxia-induced cerebral edema resulting, in part, from increased capillary permeability.. We hypothesized that cysteinyl leukotrienes (CysLTs) may be involved in the pathogenesis of AMS, as these compounds are known to increase endothelial permeability.. To test this hypothesis, we orally administered a CysLTs type-1 receptor antagonist (montelukast) to 11 subjects prior to and during exposure to high altitude (4,300 m) in a hypobaric chamber in a randomized, placebo-controlled, crossover design. We measured the resulting prevalence and/or severity of AMS, plasma CysLTs levels and urinary CysLTE4, and associated physiological responses.. At 12 h exposure, AMS prevalence and symptom severity was lower (p = 0.002) during montelukast administration compared with placebo, but not different at 22 h exposure. Plasma CysLTs and urinary LTE4 levels were not significantly elevated at 22 h exposure, nor did these CysLTs levels correlate with AMS severity. Compared with placebo, montelukast administration was not associated with any significant differences in physiologic measures at sea level or high altitude.. These results do not support a role for the CysLTs mediating the early development of AMS through the CysLT-1 receptor.

Topics: Acetates; Administration, Oral; Adult; Altitude Sickness; Analysis of Variance; Chromatography, High Pressure Liquid; Cross-Over Studies; Cyclopropanes; Cysteine; Double-Blind Method; Enzyme-Linked Immunosorbent Assay; Female; Humans; Leukotriene Antagonists; Leukotrienes; Male; Prevalence; Quinolines; Severity of Illness Index; Statistics, Nonparametric; Sulfides; Treatment Outcome