Olson N C, Brown T T, Anderson D L
J Appl Physiol (1985). 1985 Jan;58(1):274-84. doi: 10.1152/jappl.1985.58.1.274.
We studied the porcine pulmonary response to endotoxemia before and after administration of nonsteroidal antiinflammatory drugs (NSAID, i.e., indomethacin or flunixin meglumine) or dexamethasone (DEX). Escherichia coli endotoxin was infused intravenously into anesthetized 10- to 12-wk old pigs for 4.5 h. In endotoxemic pigs, the phase 1 (i.e., 0-2 h) increases in pulmonary arterial pressure, pulmonary vascular resistance (PVR), and alveolar-arterial O2 gradient and the decreases in cardiac index (CI) and lung dynamic compliance (Cdyn) were blocked by NSAID. Thus phase 1 changes were cyclooxygenase dependent. Furthermore, these effects were blocked or greatly attenuated by DEX. During phase 2 of endotoxemia (i.e., 2-4.5 h), the increased PVR and decreased CI and Cdyn were not blocked by NSAID but were attenuated by DEX, suggesting the presence of cyclooxygenase-independent metabolites. Both NSAID and DEX blocked the endotoxin-induced increases in lung water, bronchoalveolar lavage (BAL) neutrophil, and BAL albumin content. The fall in plasma proteins persisted in NSAID but not DEX-treated pigs. We conclude that endotoxemia in the pig causes severe acute respiratory failure largely mediated by cyclooxygenase and possibly lipoxygenase products of arachidonic acid metabolism.
我们研究了非甾体抗炎药（NSAID，即吲哚美辛或氟尼辛葡甲胺）或地塞米松（DEX）给药前后猪对内毒素血症的肺反应。将大肠杆菌内毒素静脉注入10至12周龄的麻醉猪体内，持续4.5小时。在内毒素血症猪中，肺动脉压、肺血管阻力（PVR）和肺泡-动脉氧梯度在第1阶段（即0至2小时）的升高以及心脏指数（CI）和肺动态顺应性（Cdyn）的降低被NSAID阻断。因此，第1阶段的变化是依赖环氧化酶的。此外，这些作用被DEX阻断或大大减弱。在内毒素血症的第2阶段（即2至4.5小时），PVR升高以及CI和Cdyn降低未被NSAID阻断，但被DEX减弱，这表明存在不依赖环氧化酶的代谢产物。NSAID和DEX均阻断了内毒素诱导的肺水、支气管肺泡灌洗（BAL）中性粒细胞和BAL白蛋白含量的增加。血浆蛋白的下降在NSAID处理的猪中持续存在，但在DEX处理的猪中不存在。我们得出结论，猪的内毒素血症会导致严重的急性呼吸衰竭，这在很大程度上是由花生四烯酸代谢的环氧化酶和可能的脂氧化酶产物介导的。
