Effect of endotoxin pretreatment on the pulmonary vascular response to hypoxia in O2-exposed lambs.
Effect of endotoxin pretreatment on the pulmonary vascular response to hypoxia in O2-exposed lambs.
复制标题
内毒素预处理对 O2 暴露羔羊肺血管缺氧反应的影响。
DOI：
10.1152/jappl.1988.65.4.1586
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
France,ML
中科院分区：
文献类型：
--
作者：
Hazinski,TA;Kennedy,KA;France,ML
我们最近报道，内毒素输注O2暴露前显着减少或延迟肺水肿的形成和呼吸衰竭的发生，减少O2暴露的氧化应激。尽管内毒素治疗的这些有益作用，肺微血管通透性最终增加，但死后肺含水量低于预期。在某些物种中，长时间的O2呼吸会减弱或消除肺收缩肌对肺泡缺氧的反应，这种反应的丧失可能会进一步导致水肿的形成。为了确定在内毒素处理、O2暴露的羔羊中观察到的肺水肿减轻是否与缺氧性肺血管收缩（HPV）的保留有关，我们在等碳缺氧8分钟之前和之后测量了肺血管阻力（吸入O2分数0.12）在每天的O2暴露期间。在6个对照组羔羊，升压反应缺氧被取消后72小时，在O2，和羔羊发展呼吸衰竭后不久。在六个内毒素处理的羔羊，HPV保存长达144小时的O2暴露。在两个对照O2暴露的羔羊，其中HPV被废除，输注血管紧张素或前列腺素H2类似物增加肺血管阻力大于75%。我们的结论是，在羔羊1）高氧废除肺血管反应缺氧，2）内毒素预处理减少急性O2诱导的肺损伤和保存肺收缩反应缺氧，和3）在O2暴露过程中的HPV的损失可能是氧化剂介导的损伤缺氧反应本身的结果，而不是弥漫性损害的血管收缩效应机制的结果。
We recently reported that endotoxin infusion before O2 exposure significantly reduced or delayed the onset of pulmonary edema formation and respiratory failure by reducing the oxidant stress of O2 exposure. Despite these beneficial effects of endotoxin treatment, lung microvascular permeability eventually increased, but postmortem lung water content was less than expected. Prolonged O2 breathing blunts or abolishes the pulmonary constrictor response to alveolar hypoxia in some species, and it is possible that the loss of this response could contribute further to edema formation. To determine whether the reduction in lung edema observed in endotoxin-treated, O2-exposed lambs was linked to the preservation of hypoxic pulmonary vasoconstriction (HPV), we measured pulmonary vascular resistance before and after 8 min of isocarbic hypoxia (inspired O2 fraction 0.12) during each day of O2 exposure. In six control lambs, the pressor response to hypoxia was abolished after 72 h in O2, and the lambs developed respiratory failure shortly thereafter. In six endotoxin-treated lambs, HPV was preserved for as long as 144 h of O2 exposure. In two control O2-exposed lambs in whom HPV was abolished, the infusion of either angiotensin or prostaglandin H2 analogue increased pulmonary vascular resistance by greater than 75%. We conclude that in lambs 1) hyperoxia abolishes the pulmonary vascular response to hypoxia, 2) endotoxin pretreatment reduces acute O2-induced lung injury and preserves the pulmonary constrictor response to hypoxia, and 3) the loss of HPV during O2 exposure may be the result of oxidant-mediated injury to the hypoxia response itself and not the result of diffuse damage to the vasoconstrictor effector mechanism.