5-脂氧合酶抑制剂对登高后急性高原病及尿白三烯E4的影响。

Grissom Colin K, Richer Lori D, Elstad Mark R

Pulmonary Division, LDS Hospital, Eighth Ave and C St, Salt Lake City, UT 84143, USA.

Chest. 2005 Feb;127(2):565-70. doi: 10.1378/chest.127.2.565.

BACKGROUND

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.

SETTING AND PARTICIPANTS

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.

MEASUREMENTS AND RESULTS

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).

CONCLUSIONS

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.

背景

据报道，在攀登至高原后，尿液和血液中的白三烯水平会升高，这与急性高原病（AMS）和高原肺水肿有关。齐留通是一种5-脂氧合酶抑制剂，该酶催化花生四烯酸转化为白三烯。研究目的和设计：这项随机、双盲、安慰剂对照临床试验的目的是确定齐留通（600毫克口服，每日四次）对AMS是否有有效的预防作用，并测量攀登至高原和齐留通对尿白三烯E4水平的影响。

设置和参与者

研究组由阿拉斯加麦金利山（迪纳利峰）西支脉的登山者中的志愿者组成。在海平面采集基线尿液样本后，受试者乘坐飞机抵达2300米处，然后在5至10天内攀登至4200米的营地。

测量和结果

使用酶免疫分析法发现，在齐留通组和安慰剂组中，攀登至高原后尿白三烯E4均降低。齐留通组（n = 9）的尿白三烯E4从海平面时的67±35皮克/毫克肌酐降至高原时的33±22皮克/毫克肌酐（p = 0.003）[均值±标准差]。安慰剂组（n = 9）的尿白三烯E4从海平面时的97±82皮克/毫克肌酐降至高原时的44±21皮克/毫克肌酐（p = 0.045）。到达4200米后，齐留通组有1名受试者和安慰剂组有3名受试者符合AMS的路易斯湖标准（p = 0.257）。