Castiello A, Paterson J F, Shelley S A, Haller E M, Balis J U
Department of Pathology, University of South Florida Health Science Center, Tampa, USA.
Shock. 1994 Dec;2(6):427-32. doi: 10.1097/00024382-199412000-00007.
Although prolonged Gram-negative sepsis with high permeability alveolar edema, a well documented cause of adult respiratory distress syndrome, has been shown to result in surfactant alterations, the effects of acute endotoxemia on the lung surfactant system are largely unknown. In this study, lethal endotoxemia (> 80% mortality at 24 h) resulting in severe, rapid leukopenia with progressive thrombocytopenia was achieved through intraperitoneal injection of adult Fischer 344 rats with 3.5 mg of Escherichia coli endotoxin/kg. After assessment of pulmonary mechanics under general anesthesia, endotoxin-injected rats and appropriate controls were killed at 4, 8, and 12 h for morphological and biochemical analyses. Morphometric estimation of surfactant membrane subtypes in bronchoalveolar lavage fluid revealed prominent alterations including significant decrease (45%) in tubular myelin 12 h post-endotoxin, with a threefold increase in lamellar body-like forms at 8 and 12 h. Acute endotoxicosis resulted in decrease of total dynamic compliance, whereas pulmonary resistance remained unchanged. These changes were associated with margination of polymorphonuclear leukocytes in lung microcirculation, multifocal septal edema, and decrease in lamellar body lysozyme specific activity at 12 h. Alveolar edema, as determined by measurement of total protein in cell-free bronchoalveolar lavage fluid, was absent in both controls and endotoxin-injected rats. The results indicate that bloodborne lung injury induced by lethal endotoxicosis initiates acute perturbation of secreted surfactant membranes with pulmonary dysfunction in the absence of high protein alveolar edema.
尽管长期革兰氏阴性菌败血症伴有高渗透性肺泡水肿（这是成人呼吸窘迫综合征的一个充分记录的病因）已被证明会导致表面活性剂改变，但急性内毒素血症对肺表面活性剂系统的影响在很大程度上尚不清楚。在本研究中，通过给成年Fischer 344大鼠腹腔注射3.5 mg大肠杆菌内毒素/kg，实现了致死性内毒素血症（24小时死亡率>80%），导致严重、快速的白细胞减少并伴有进行性血小板减少。在全身麻醉下评估肺力学后，在4、8和12小时处死注射内毒素的大鼠和适当的对照组，进行形态学和生化分析。对支气管肺泡灌洗液中表面活性剂膜亚型的形态计量学估计显示出显著改变，包括内毒素注射后12小时管状髓磷脂显著减少（45%），而在8小时和12小时层状体样形式增加了三倍。急性内毒素中毒导致总动态顺应性降低，而肺阻力保持不变。这些变化与肺微循环中多形核白细胞的边缘化、多灶性间隔水肿以及12小时时层状体溶菌酶比活性降低有关。通过测量无细胞支气管肺泡灌洗液中的总蛋白来确定的肺泡水肿，在对照组和注射内毒素的大鼠中均未出现。结果表明，致死性内毒素中毒引起的血源性肺损伤在不存在高蛋白肺泡水肿的情况下引发分泌性表面活性剂膜的急性紊乱并伴有肺功能障碍。
