Leukotriene receptor blockade does not prevent acute mountain sickness induced by normobaric hypoxia.
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.
Luks
Andrew M
AM
Pulmonary and Critical Care Division, Department of Medicine, University of Washington, Seattle, Washington 98195-6522, USA. aluks@u.washington.edu
Henderson
William R
WR
Swenson
Erik R
ER
D000064:Acclimatization / Q000187:drug effects; D000085:Acetates / Q000008:administration & dosage*; D000284:Administration, Oral; D000328:Adult; D000532:Altitude Sickness / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control*; D001273:Atmosphere Exposure Chambers; D018592:Cross-Over Studies; D003521:Cyclopropanes; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000150:complications; D020024:Leukotriene Antagonists / Q000008:administration & dosage*; D017999:Leukotriene E4 / Q000652:urine; D008297:Male; D011292:Premedication; D011804:Quinolines / Q000008:administration & dosage*; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D013440:Sulfides
D000085:Acetates; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; D011804:Quinolines; D013440:Sulfides; D017999:Leukotriene E4; C093875:montelukast