Dstl Porton Down, Salisbury, UK.
Inhal Toxicol. 2010 Dec;22(14):1135-43. doi: 10.3109/08958378.2010.527398. Epub 2010 Nov 18.
Inhalation of sulfur mustard (HD) vapor can cause life-threatening lung injury for which there is no specific treatment. A reproducible, characterized in vivo model is required to investigate novel therapies targeting HD-induced lung injury.
Anesthetized, spontaneously breathing large white pigs (~50 kg) were exposed directly to the lung to HD vapor at 60, 100, or 150 µg/kg, or to air, for ~10 min, and monitored for 6 h. Cardiovascular and respiratory parameters were recorded. Blood and bronchoalveolar lavage fluid (BALF) were collected to allow blood gas analysis, hematology, and to assay for lung inflammatory cells and mediators. Urine was collected and analyzed for HD metabolites. Histopathology samples were taken postmortem (PM).
Air-exposed animals maintained normal lung physiology whilst lying supine and spontaneously breathing. There was a statistically significant increase in shunt fraction across all three HD-exposed groups when compared with air controls at 3-6 h post-exposure. Animals were increasingly hypoxemic with respiratory acidosis. The monosulfoxide β-lyase metabolite of HD (1-methylsulfinyl-2-[2(methylthio)ethylsulfonyl)ethane], MSMTESE), was detected in urine from 2 h post-exposure. Pathological examination revealed necrosis and erosion of the tracheal epithelium in medium and high HD-exposed groups.
These findings are consistent with those seen in the early stages of acute lung injury (ALI).
吸入芥子气（HD）蒸气会导致危及生命的肺部损伤，而目前尚无针对这种损伤的特定治疗方法。因此，需要建立一种可重现的、具有特征的体内模型，以研究针对 HD 诱导的肺损伤的新疗法。
使用麻醉、自主呼吸的大白猪（~50kg），将其肺部直接暴露于 60、100 或 150μg/kg 的 HD 蒸气中，持续约 10min，并监测 6h。记录心血管和呼吸参数。采集血液和支气管肺泡灌洗液（BALF），进行血气分析、血液学检查，并测定肺内炎症细胞和介质。收集尿液，分析 HD 代谢物。死后采集组织病理学样本。
暴露于空气中的动物在仰卧位自主呼吸时保持正常的肺生理功能。与空气对照组相比，所有 3 个 HD 暴露组在暴露后 3-6h 的分流量均有统计学意义的增加。动物出现进行性低氧血症伴呼吸性酸中毒。HD 的单砜β-裂合酶代谢物（1-甲基亚磺酰基-2-[2（甲基巯基）乙基砜基]乙烷，MSMTESE）在暴露后 2h 的尿液中被检测到。病理检查显示中、高 HD 暴露组的气管上皮出现坏死和侵蚀。
这些发现与急性肺损伤（ALI）早期的表现一致。
