Little Tina, Butler Bruce D
Baromedical Laboratory, Department of Anesthesiology, The University of Texas Medical School, Houston, TX 77030, USA.
Aviat Space Environ Med. 2008 Feb;79(2):87-93. doi: 10.3357/asem.2118.2008.
Venous bubbles resulting from experimental decompression sickness (DCS) may cause an inflammatory-like reaction with activation of granulocytes and release of metabolites from arachidonic acid. The release of cyclooxygenase and lipoxygenase pathway mediated metabolites, namely thromboxane B2 (TXB2) and leukotriene E4 (LTE4) likely contribute to this overall DCS response. In the present study we examined the effect on DCS outcome of several agents affecting both pathways.
Indomethacin and acetylsalicylic acid were administered to study the cyclooxygenase pathway mediators, Zafirlukast and Zileuton to study inhibition of the lipoxygenase pathway, and isoproterenol for its beta-agonist effects. The agents were administered to randomly selected Sprague-Dawley rats prior to compression to 683 kPa for 60 min. Following 60 min recovery post-decompression, DCS evaluation included: gross symptoms; pulmonary edema; bronchoalveolar lavage and pleural fluid protein; white blood cell and differential cell counts; and urine, bronchoalveolar lavage, and plasma TXB2 and LTE4 analysis.
The results indicate that both Zafirlukast and Zileuton reduced the reported DCS symptoms, pulmonary edema, pleural and bronchoalveolar lavage protein levels, white blood cell counts in the pleural and bronchoalveolar lavage, and leukotriene levels in the bronchoalveolar lavage vs. that of vehicle-treated rats exposed to compression/decompression. The effect of these agents on pleural and bronchial alveolar protein levels demonstrated protective effects on microvascular permeability. Acetylsalicylic acid and indomethacin treatment had less effect on reducing inflammatory-induced changes.
The effect of inflammatory-like responses to DCS can be altered with pharmacological intervention given prior to compression.
实验性减压病（DCS）产生的静脉气泡可能引发类似炎症的反应，导致粒细胞活化并释放花生四烯酸代谢产物。环氧合酶和脂氧合酶途径介导的代谢产物，即血栓素B2（TXB2）和白三烯E4（LTE4）的释放可能促成了整体的DCS反应。在本研究中，我们考察了几种影响这两条途径的药物对DCS结果的影响。
给予吲哚美辛和乙酰水杨酸以研究环氧合酶途径介质，给予扎鲁司特和齐留通以研究脂氧合酶途径的抑制作用，并给予异丙肾上腺素以观察其β-激动剂效应。在将随机选择的斯普拉格-道利大鼠压缩至683 kPa持续60分钟之前给予这些药物。减压后恢复60分钟后，DCS评估包括：总体症状；肺水肿；支气管肺泡灌洗和胸腔积液蛋白；白细胞和分类细胞计数；以及尿液、支气管肺泡灌洗和血浆TXB2及LTE4分析。
结果表明，与接受压缩/减压的赋形剂处理大鼠相比，扎鲁司特和齐留通均减轻了报告的DCS症状、肺水肿、胸腔和支气管肺泡灌洗蛋白水平、胸腔和支气管肺泡灌洗中的白细胞计数以及支气管肺泡灌洗中的白三烯水平。这些药物对胸腔和支气管肺泡蛋白水平的影响表明对微血管通透性具有保护作用。乙酰水杨酸和吲哚美辛治疗在减轻炎症诱导的变化方面效果较差。
在压缩前给予药物干预可改变对DCS的类似炎症反应的影响。
