期刊
CRITICAL CARE MEDICINE
卷 30, 期 4, 页码 868-873出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/00003246-200204000-00026
关键词
nitric oxide; nitric oxide synthase; myeloperoxidase; F2-isoprostanes; bronchoalveolar lavage; acute lung injury; inhaled nitric oxide; sepsis; mouse; inflammation
Objective: Although inhaled nitric oxide transiently improves oxygenation in patients with acute lung injury, it has not affected clinical outcomes. As well, the effects of inhaled nitric oxide on the pathophysiologic features of acute lung injury have not been well defined. Therefore, we assessed the effects of inhaled nitric oxide on the degree of pulmonary inflammation and injury in a mouse model of sepsis-induced acute lung injury. Design: Randomized, controlled animal study. Setting. Research laboratory of an academic institution. Subjects: Male C57BI/6 mice. Interventions. Sepsis was induced by cecal ligation and perforation. At the time of surgery, septic and naive mice were randomized to exposure to either 40 ppm inhaled nitric oxide or room air for 24 hrs before they were killed. Measurements and Main Results: Sepsis-induced acute lung injury was characterized by increased pulmonary myeloperoxidase (68 +/- 13 vs. 13 +/- 3 mU/mg protein in naive mice, p < .01), pulmonary 8-isoprostane content (627 +/- 51 vs. 88 +/- 20 pg/mg protein in naive mice, p < .01), and protein in bronchoalveolar lavage fluid (p < .05). Inhaled nitric oxide exposure in septic mice completely abrogated the septic increases in myeloperoxidase activity (p < .05) and pulmonary 8-isoprostane content (p < .05) but had no effect on bronchoalveolar lavage protein. The induction of sepsis also was associated with an increase in pulmonary inducible NO synthase activity (2.8 +/- 0.5 vs. 0.4 +/- 0.1 pmol(.)min(-1.)mg(-1) protein in naive mice, p < .05), and inhaled nitric oxide attenuated this increase in pulmonary inducible NO synthase activity (p < .05). Conclusions: Exposure to inhaled nitric oxide early in the course of sepsis-induced acute lung injury is associated with reduced pulmonary leukocyte infiltration and less oxidative injury. Decreased lung inflammation and injury with inhaled nitric oxide is associated with decreased pulmonary inducible NO synthase activity. Therefore, inhaled NO may have greater clinical benefit if administered earlier in the natural history of acute lung injury in patients.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据