leukotriene-e4 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

Elevated urine and blood leukotriene levels have been reported after ascent to high altitude in association with acute mountain sickness (AMS) and high-altitude pulmonary edema. Zileuton is an inhibitor of the enzyme 5-lipoxygenase that catalyzes conversion of arachidonic acid to leukotrienes. Study objectives and design: The objectives of this randomized, double-blind, placebo-controlled clinical trial were to determine whether zileuton (600 mg po qid) is effective prophylaxis for AMS, and to measure the effect of ascent to high altitude and zileuton on urinary leukotriene E(4) levels.. The study group consisted of volunteers from among climbers on the West Buttress of Mt. McKinley (Denali), Alaska. After baseline urine samples at sea level, subjects flew by airplane to 2,300 m, and then ascended to the 4,200-m camp in 5 to 10 days.. Using an enzyme immunoassay, urinary leukotriene E(4) was found to decrease after ascent to high altitude in both the zileuton and placebo groups. Urinary leukotriene E(4) in the zileuton group (n = 9) decreased from 67 +/- 35 pg/mg creatinine at sea level to 33 +/- 22 pg/mg creatinine at high altitude (p = 0.003) [mean +/- SD]. Urinary leukotriene E(4) in the placebo group (n = 9) decreased from 97 +/- 82 pg/mg creatinine at sea level to 44 +/- 21 pg/mg creatinine at high altitude (p = 0.045). One subject in the zileuton group and three subjects in the placebo group met Lake Louise criteria for AMS after arriving at 4,200 m (p = 0.257).. Elevated leukotrienes are not associated with ascent to high altitude. In subjects with AMS, urinary leukotrienes were not elevated, suggesting that leukotrienes may not be a component of the pathophysiology of AMS. The low incidence of AMS and the small sample size in this study prevented determination of whether zileuton is effective prophylaxis for AMS.

Topics: Acclimatization; Administration, Oral; Adult; Alaska; Altitude Sickness; Arachidonate 5-Lipoxygenase; Double-Blind Method; Drug Administration Schedule; Female; Humans; Hydroxyurea; Inflammation Mediators; Leukotriene E4; Lipoxygenase Inhibitors; Male; Middle Aged; Mountaineering; Oximetry; Premedication; Statistics as Topic; Treatment Outcome

To examine whether increased urinary cysteinyl-leukotriene E(4) (LTE(4)) excretion, which has been found to be elevated in patients presenting with high-altitude pulmonary edema (HAPE), precedes edema formation.. Prospective studies in a total of 12 subjects with susceptibility to HAPE.. In a chamber study, seven subjects susceptible to HAPE and five nonsusceptible control subjects were exposed for 24 h to an altitude of 450 m (control day), and exposed for 20 h to 4,000 m after slow decompression over 4 h. In a field study, prospective measurements at low and high altitude were performed in five subjects developing HAPE at 4,559 m.. Mountaineers with a radiographically documented history of HAPE and control subjects who did not develop HAPE with identical high-altitude exposure.. 24-h urine collections.. In the hypobaric chamber, none of the subjects developed HAPE. The 24-h urinary LTE(4) did not differ between HAPE susceptible and control subjects, nor between hypoxia and normoxic control day. In the field study, urinary LTE(4) was not increased in subjects with HAPE compared to values obtained prior to HAPE at high altitude and during 2 control days at low altitude.. These data do not provide evidence that cysteinyl-leukotriene-mediated inflammatory response is associated with HAPE susceptibility or the development of HAPE within the context of our studies.

Topics: Adult; Altitude Sickness; Disease Susceptibility; Humans; Leukotriene E4; Male; Middle Aged; Mountaineering; Prospective Studies; Pulmonary Edema; Reference Values

To determine whether urinary leukotriene E4 (uLTE4) levels increase upon exposure to high altitude, and also to ascertain the relationship between uLTE4 levels and symptoms of acute mountain sickness (AMS).. Prospective, unblinded, single-factor (altitude) experimental study.. US Army research laboratory facilities at sea level ([SL] 50 m), 1,830 m, and 4,300 m.. Eight healthy male subjects ranging in age from 19 to 24 years.. uLTE4 levels and symptoms of AMS were measured at just above SL (50 m), 3 1/2 days after being transported from SL to moderate altitude (MA) (1,830 m), and 1 1/2 days after ascent from 1,830 to 4,300 m (high altitude [HA]). Symptoms of AMS were assessed using standard indexes derived from the Environmental Symptoms Questionnaire weighted toward cerebral (AMS-C) and respiratory (AMS-R) manifestations. Oxygen saturation was measured noninvasively by pulse oximetry at SL and HA.. The mean (+/-SEM) uLTE4 levels (pg/mg creatinine) were 67.9 (+/-13.2) at SL; 82.3 (+/-5.5) at MA; and 134.8 (+/-19.4) at HA (p < 0.05 comparing HA with SL and MA).. We conclude that uLTE4 levels increase shortly after exposure to HA even after staging for 4 days at MA. Although this study does not clearly demonstrate a relationship between uLTE4 levels and symptoms of AMS, it supports the hypothesis that leukotrienes may be involved in the pathophysiologic state of AMS.

Topics: Adult; Altitude; Altitude Sickness; Humans; Hypoxia; Leukotriene E4; Male; Prospective Studies