Berg John T, Ramanathan S, Swenson Erik R
Department of Pharmacology, University of Hawaii, Honolulu, HI 96822, USA.
Wilderness Environ Med. 2004 Spring;15(1):32-7. doi: 10.1580/1080-6032(2004)015[0032:iohpvp]2.0.co;2.
Rapid ascent to high altitude causes hypoxic pulmonary vasoconstriction (HPV) and leads to high-altitude pulmonary edema (HAPE) in susceptible humans. Vasodilating agents lessen HAPE (as evidenced by radiographic and gas exchange measurements), but data establishing their effectiveness on alveolar protein content and hemorrhage are lacking. This study was designed to assess whether preventing HPV reduces the alveolar-capillary barrier leak characteristic of HAPE.
Rats were pretreated with saline (control group) or acetazolamide (20 mg/kg) or nickel chloride (60 mg/kg) (experimental groups) to prevent HPV and were exposed to high altitude (0.5 atm for 24 hours) in a hypobaric chamber. High-altitude pulmonary edema was then assessed by gravimetric analysis of heart and lung tissue, a visual score of lung hemorrhage, and measurement of protein content in bronchoalveolar lavage fluid.
Saline-treated rats developed a mild protein leak indicative of early HAPE that was prevented by inhibition of HPV: protein in bronchoalevolar lavage fluid of saline-treated rats, 21.6 +/- 3.2 mg/dL (mean +/- SEM); HPV-inhibited rats, 12.6 +/- 0.7 mg/dL; air-exposed rats, 13.4 +/- 1.4 mg/ dL (P < .05 saline vs other groups, analysis of variance [ANOVA]). The lungs of saline-treated rats were also mildly hemorrhagic (3.4 +/- 0.9 on a scale of 1-9, where 1 is normal), and the lungs of HPV-inhibited rats appeared normal (1.2 +/- 0.1) (P = .032). Finally, right ventricle weight (adjusted for initial body weight) increased in saline-treated rats: saline-treated, 0.64 +/- 0.02; HPV-inhibited, 0.56 +/- 0.02; air-exposed, 0.59 +/- 0.02 (P < .05, saline vs HPV-inhibited group).
The results demonstrate that treatment with NiCl2 or acetazolamide prevents HAPE in rats and are consistent with a role for elevated pulmonary artery pressure in the pathogenesis of HAPE.
快速上升到高海拔地区会导致低氧性肺血管收缩（HPV），并在易感人群中引发高原肺水肿（HAPE）。血管扩张剂可减轻HAPE（影像学和气体交换测量结果证明），但缺乏关于其对肺泡蛋白含量和出血有效性的确切数据。本研究旨在评估预防HPV是否能减少HAPE特有的肺泡-毛细血管屏障渗漏。
大鼠分别用生理盐水（对照组）、乙酰唑胺（20mg/kg）或氯化镍（60mg/kg）进行预处理（实验组）以预防HPV，然后在低压舱中暴露于高海拔环境（0.5个大气压，持续24小时）。随后通过对心脏和肺组织进行重量分析、对肺出血进行视觉评分以及测量支气管肺泡灌洗液中的蛋白含量来评估高原肺水肿情况。
生理盐水处理的大鼠出现了轻度蛋白渗漏，这表明早期HAPE通过抑制HPV得以预防：生理盐水处理的大鼠支气管肺泡灌洗液中的蛋白含量为21.6±3.2mg/dL（平均值±标准误）；HPV受抑制的大鼠为12.6±0.7mg/dL；暴露于空气的大鼠为13.4±1.4mg/dL（方差分析[ANOVA]，生理盐水组与其他组相比，P<.05）。生理盐水处理的大鼠肺部也有轻度出血（在1-9分的评分中为3.4±0.9，1分为正常），而HPV受抑制的大鼠肺部看起来正常（1.2±0.1）（P = 0.032）。最后，生理盐水处理的大鼠右心室重量（根据初始体重调整）增加：生理盐水处理组为0.64±0.02；HPV受抑制组为0.56±0.02；暴露于空气组为0.59±0.02（生理盐水组与HPV受抑制组相比，P<.05）。
结果表明，用氯化镍或乙酰唑胺治疗可预防大鼠发生HAPE，这与肺动脉压力升高在HAPE发病机制中的作用一致。
