Gust R, Kozlowski J, Stephenson A H, Schuster D P
Pulmonary and Critical Care Division, Washington University School of Medicine, St. Louis, Missouri, USA.
Am J Respir Crit Care Med. 1998 Jun;157(6 Pt 1):1919-26. doi: 10.1164/ajrccm.157.6.9704110.
We evaluated the effects of low-dose endotoxin (15 microg/kg) on the pulmonary and systemic responses to oleic acid (OA)-induced acute lung injury in dogs. Animals given endotoxin alone (n = 5) showed a modest decrease in arterial blood pressure, but no effects on pulmonary hemodynamics, blood gases, cardiac output, or lung water accumulation. Animals (n = 6) given only OA (0.08 ml/kg) showed the expected development of mild-moderate pulmonary hypertension, a comparable reduction in arterial blood pressure, hypoxemia, increased lung water concentration, and an altered intrapulmonary perfusion pattern, as assessed by positron emission tomography. Animals (n = 7) given the same dose of endotoxin, followed 30 min later by the same dose of OA, developed a similar increase in lung water concentration as the group given OA alone, but failed to develop pulmonary hypertension or to redistribute pulmonary blood flow away from the edematous lung regions. In addition, arterial blood pressure fell significantly more than in the other groups. These responses were associated with a 30-fold increase in circulating prostacyclin (assayed as 6-keto prostaglandin F1 alpha [PGF1alpha]). The effects on systemic blood pressure, intrapulmonary blood flow redistribution, and eicosanoid production were eliminated by pretreating (n = 5) animals with meclofenamate (2 mg/kg). The results are consistent with a "priming" effect of low-dose endotoxin on the pulmonary endothelium, with exaggerated prostacyclin production in response to a subsequent lung injury. This interaction leads to altered intrapulmonary hemodynamics that exacerbate the development of hypoxemia, and to significant decreases in systemic blood pressure. To the extent that the lung is the most likely source of the increased prostacyclin production, the synergistic effects of low-dose endotoxin and lung injury may produce a kind of "lung shock."
我们评估了低剂量内毒素（15微克/千克）对犬油酸（OA）诱导的急性肺损伤的肺和全身反应的影响。单独给予内毒素的动物（n = 5）动脉血压有适度下降，但对肺血流动力学、血气、心输出量或肺水积聚无影响。仅给予OA（0.08毫升/千克）的动物（n = 6）出现了预期的轻度至中度肺动脉高压，动脉血压有类似程度的降低，低氧血症，肺水浓度增加，以及正电子发射断层扫描评估的肺内灌注模式改变。给予相同剂量内毒素，30分钟后再给予相同剂量OA的动物（n = 7），肺水浓度的增加与仅给予OA的组相似，但未出现肺动脉高压，也未使肺血流从水肿肺区重新分布。此外，动脉血压下降幅度明显大于其他组。这些反应与循环前列环素增加30倍有关（以6-酮前列腺素F1α[PGF1α]测定）。用甲氯芬那酸（2毫克/千克）预处理动物（n = 5）可消除对全身血压、肺内血流重新分布和类花生酸产生的影响。结果与低剂量内毒素对肺内皮的“预激”作用一致，即对随后的肺损伤会过度产生前列环素。这种相互作用导致肺内血流动力学改变，加重低氧血症的发展，并使全身血压显著降低。就肺最有可能是前列环素产生增加的来源而言，低剂量内毒素和肺损伤的协同作用可能产生一种“肺休克”。
