Yin K, Hock C E, Tahamont M, Wong P Y
Department of Cell Biology, University of Medicine and Dentistry, New Jersey, School of Osteopathic Medicine, Stratford 08084, USA.
Shock. 1998 Jun;9(6):434-42. doi: 10.1097/00024382-199806000-00008.
The pathophysiology of experimental acute endotoxemia is a complex process involving both cardiovascular dysfunction and an inflammatory response. We have examined the correlation in hemodynamic changes and the pulmonary inflammatory response after lipopolysaccharide (LPS) administration with respect to time. Importantly, we have measured the lung and plasma levels of nitric oxide (NO) over time, as well as rapid generation of lung superoxide after LPS administration. In anesthetized rats given a bolus injection of LPS (10 mg/kg intravenously, from Salmonella enteritidis), mean arterial blood pressure dropped by 63-70% within 15 min, and cardiac output fell by 57-63% within 20 min compared with saline controls. Mean arterial blood pressure recovered slightly but was still 51, 30, and 25% less than that of saline controls 45, 105, and 165 min after LPS administration, respectively. Cardiac output remained depressed throughout the experimental period and was 35% lower than in saline controls 165 min after LPS treatment. There was a small increase in plasma nitrite/nitrate as an index of plasma NO production after 45 min and a 10-fold increase 165 min after LPS addition compared with controls, strongly suggesting that NO mediates the hypotension that occurs 165 min after LPS administration. Lung NO production increased twofold 105 min after LPS administration and remained higher than in saline controls. Histological sections showed that there was fluid accumulation and alveolar collapse in the lung 45 min after LPS, whereas after 165 min, there was extensive tissue damage and increased leukocyte accumulation compared with controls. These results suggest that there was no correlation between early (1 h) tissue damage and NO production. We found an increase in lung superoxide generation 15 min after injection of LPS that coincided with the alterations in cardiovascular function. These results suggest that early lung tissue damage and/or hemodynamic changes may be due to superoxide generation from the lung.
实验性急性内毒素血症的病理生理学是一个复杂的过程，涉及心血管功能障碍和炎症反应。我们研究了脂多糖（LPS）给药后血流动力学变化与肺部炎症反应随时间的相关性。重要的是，我们测量了随时间变化的肺和血浆中一氧化氮（NO）水平，以及LPS给药后肺中超氧化物的快速生成。在静脉注射LPS（10mg/kg，肠炎沙门氏菌）的麻醉大鼠中，与生理盐水对照组相比，平均动脉血压在15分钟内下降了63 - 70%，心输出量在20分钟内下降了57 - 63%。平均动脉血压略有恢复，但在LPS给药后45、105和165分钟时，分别仍比生理盐水对照组低51%、30%和25%。心输出量在整个实验期间一直处于较低水平，在LPS治疗后165分钟比生理盐水对照组低35%。与对照组相比，45分钟后作为血浆NO生成指标的血浆亚硝酸盐/硝酸盐略有增加，LPS添加后165分钟增加了10倍，强烈表明NO介导了LPS给药后165分钟出现的低血压。LPS给药后105分钟肺中NO生成增加了两倍，且仍高于生理盐水对照组。组织学切片显示，LPS给药后45分钟肺中有液体蓄积和肺泡塌陷，而165分钟后，与对照组相比有广泛的组织损伤和白细胞积聚增加。这些结果表明，早期（1小时）组织损伤与NO生成之间没有相关性。我们发现注射LPS后15分钟肺中超氧化物生成增加，这与心血管功能的改变同时发生。这些结果表明，早期肺组织损伤和/或血流动力学变化可能是由于肺中超氧化物的生成。
