Time-dependent cardiovascular and inflammatory changes in acute endotoxemia.
Time-dependent cardiovascular and inflammatory changes in acute endotoxemia.
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急性内毒素血症中时间依赖性心血管和炎症变化。
DOI：
10.1097/00024382-199806000-00008
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Wong,PY
中科院分区：
文献类型：
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作者：
Yin,K;Hock,CE;Tahamont,M;Wong,PY
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，我们已经测量了肺和血浆一氧化氮（NO）水平随时间的变化，以及快速生成的肺超氧化物后，LPS管理。与生理盐水对照组相比，静脉注射LPS（10 mg/kg，来自沙门氏菌）的麻醉大鼠，平均动脉血压在15分钟内下降63-70%，心输出量在20分钟内下降57-63%。平均动脉血压略有恢复，但仍分别为51，30和25%，低于生理盐水对照组45，105和165分钟后，LPS管理。心输出量在整个实验期间保持抑制，并且在LPS处理后165分钟比盐水对照低35%。有一个小的增加，血浆亚硝酸盐/硝酸盐作为血浆NO生产的指标45分钟后，165分钟后增加10倍，LPS添加与对照组相比，强烈表明，NO介导的低血压发生后165分钟LPS管理。肺NO的产生增加了两倍105分钟后，LPS管理，并保持高于生理盐水对照组。组织学切片显示，LPS后45分钟，肺中有液体积聚和肺泡萎陷，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产生之间没有相关性。我们发现，肺超氧化物生成增加15分钟后，注射LPS，符合心血管功能的改变。这些结果表明，早期肺组织损伤和/或血液动力学变化可能是由于从肺产生超氧化物。
The pathophysiology of experimental acute endotoxemia is a complex process involving both cardiovascular dysfunction and an inflammatory response. We have examined the correlation in hemody-namic 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.