Effect of Cysteninyl Leukotriene Blockade on the Development of Acute Mountain Sickness
Abstract
Acute Mountain Sickness (AMS) may be a manifestation of hypoxia-induced cerebral edema resulting, in part, from increased capillary permeability. Leukotrienes (LTB4, LTC4) may be involved in the pathogenesis of AMS, as these compounds are known to increase endothelial permeability. To test the hypothesis that cysteinyl leukotrienes (LTC4) are involved in the development of AMS, we orally administered a cysteinyl leukotriene receptor blocker (montelukast) prior to and during exposure to high altitude (4300 m) in a hypobaric chamber. We assessed whether blocking cysteinyl leukotriene receptors decreases the prevalence and/or severity of AMS and associated physiological and cognitive responses. Eleven lowlanders (9 men, 2 women) were exposed twice, 2 weeks apart to 4300 m for 24 hours. Each subject received 10 mg montelukast 25 and 1 h prior to ascent. AMS symptoms were assessed using the Environmental Symptoms Questionnaire (ESQ) and the Lake Louise AMS Scoring System (LL) after 11 and 22 h altitude exposure. Urinary LTE4 (uLTE4) was assayed as an integrated measure 0 cysteinyl leukotriene production. After 11 h exposure, AMS prevalence and symptom severity by LL was lower (p<0.05) during montelukast administration compared to placebo during the first 12 h, but not different after 22 h exposure. The LL identified more subjects with AMS than the ESQ, but the scores between the two assessments were highly correlated (r=0.78 to 0.98). Urinary LTE4 was not significant elevated after 24 h exposure, nor did uLTE4 levels correlate with AMS severity. However, uLTE4 tended to be higher (p"'0.06) during montelukast treatment compared to placebo. Compared to placebo, montelukast administration was not associated with any significant differences in resting SaO2, PETO2, PETCO2, 24h urine volume, TBhW or changes in cognitive performance at sea level or high altitude. However, cognitive performance did recover after only 12 hours of altitude exposure.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2001
- Accession Number
- ADA391503
Entities
People
- Charles S. Fulco
- David Kaminsky
- Larry A. Sonna
- Louis E. Banderet
- Stephen R. Muza
Organizations
- United States Army Research Institute of Environmental Medicine