Cysteinyl leukotriene blockade does not prevent acute mountain sickness.
BACKGROUND
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.


OBJECTIVE
We hypothesized that cysteinyl leukotrienes (CysLTs) may be involved in the pathogenesis of AMS, as these compounds are known to increase endothelial permeability.


METHODS
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.


RESULTS
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.


CONCLUSIONS
These results do not support a role for the CysLTs mediating the early development of AMS through the CysLT-1 receptor.
Muza
Stephen R
SR
Thermal and Mountain Medicine Division, U.S. Army Research Institute of Environmental Medicine, Natick, MA 01760-5007, USA. Stephen.muza@us.army.mil
Kaminsky
David
D
Fulco
Charles S
CS
Banderet
Louis E
LE
Cymerman
Allen
A
D000085:Acetates / Q000008:administration & dosage / Q000494:pharmacology*; D000284:Administration, Oral; D000328:Adult; D000532:Altitude Sickness / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control*; D000704:Analysis of Variance; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D003521:Cyclopropanes; D003545:Cysteine / Q000378:metabolism*; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D020024:Leukotriene Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D015289:Leukotrienes / Q000378:metabolism*; D008297:Male; D015995:Prevalence; D011804:Quinolines / Q000008:administration & dosage / Q000494:pharmacology*; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D013440:Sulfides; D016896:Treatment Outcome
D000085:Acetates; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D011804:Quinolines; D013440:Sulfides; C112381:cysteinyl-leukotriene; D003545:Cysteine; C093875:montelukast