Effects of cyclooxygenase inhibitors on the alterations in lung mechanics caused by endotoxemia in the unanesthetized sheep.
Effects of cyclooxygenase inhibitors on the alterations in lung mechanics caused by endotoxemia in the unanesthetized sheep.
复制标题
环氧合酶抑制剂对未麻醉羊内毒素血症引起的肺力学改变的影响。
DOI：
10.1172/jci110985
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发表时间：
1983
期刊：
影响因子：
--
通讯作者：
Brigham,KL
中科院分区：
文献类型：
--
作者：
Snapper,JR;Hutchison,AA;Ogletree,ML;Brigham,KL
研究人员在 12 只长期使用仪器、未麻醉的绵羊身上研究了大肠杆菌内毒素对肺力学、血流动力学、气体交换以及肺液体和溶质交换的影响。通过研究用甲氯芬那酸钠和布洛芬抑制环氧合酶之前和之后的绵羊，研究了花生四烯酸代谢的环氧合酶产物作为内毒素诱导的肺力学改变的介质的可能作用。以随机顺序对绵羊进行了三次研究：（a）单独输注甲氯芬那酸钠（或布洛芬）； (b) 单独的大肠杆菌内毒素； (c) 甲氯芬那酯（或布洛芬）和内毒素。单独使用甲氯芬那酯对任何测量的变量都没有影响。仅内毒素就会引起肺力学的早期显着变化：穿过肺部的气流阻力 (RL) 增加 10 倍，动态肺顺应性 (Cdyn) 下降 80%，功能残气量 (FRC) 下降超过 30%。内毒素血症后肺泡与动脉的氧差 (delta AaPO2) 显着增加。当有足够的甲氯芬那酯抑制肺淋巴中血栓素-B2和6-酮前列腺素F1α的积累时，内毒素不会导致RL增加，Cdyn下降不到40%，FRC仅下降6%。甲氯芬那酯可显着减轻内毒素血症引起的低氧血症和早期肺动脉高压，但对晚期肺液体和溶质交换的增加没有影响。布洛芬与甲氯芬那酯具有相似的效果。我们的结论是，内毒素血症后观察到的肺动脉高压和肺力学变化可能至少部分是由缩窄前列腺素或血栓素介导的，并且可以通过阻止这些介质的内源性合成来改善气体交换。
The effects of Escherichia coli endotoxin on lung mechanics, hemodynamics, gas exchange, and lung fluid and solute exchange were studied in 12 chronically instrumented unanesthetized sheep. A possible role for cyclooxygenase products of arachidonate metabolism as mediators of the endotoxin-induced alterations in lung mechanics was investigated by studying sheep before and after cyclooxygenase inhibition with sodium meclofenamate and ibuprofen. Sheep were studied three times in random order: (a) sodium meclofenamate (or ibuprofen) infusion alone; (b) E. coli endotoxin alone; and (c) meclofenamate (or ibuprofen) and endotoxin. Meclofenamate alone had no effect on any of the variables measured. Endotoxin alone caused early marked changes in lung mechanics: resistance to airflow across the lungs (RL) increased 10-fold, dynamic lung compliance (Cdyn) decreased 80% and functional residual capacity (FRC) decreased by greater than 30%. The alveolar-to-arterial oxygen difference (delta AaPO2) increased markedly following endotoxemia. In the presence of sufficient meclofenamate to inhibit accumulation of thromboxane-B2 and 6-keto-prostaglandin F1 alpha in lung lymph, endotoxin caused no increase in RL, Cdyn decreased by less than 40%, and FRC decreased by only 6%. Meclofenamate significantly attenuated the hypoxemia and early pulmonary hypertension caused by endotoxemia but had no effect on the late increases in lung fluid and solute exchange. Ibuprofen had similar effects to those observed with meclofenamate. We conclude that both the pulmonary hypertension and changes in lung mechanics observed after endotoxemia may be mediated, at least in part, by constrictor prostaglandins or thromboxanes and that gas exchange may be improved by preventing endogenous synthesis of these mediators.