Positive end-expiratory pressure modulates local and systemic inflammatory responses in a sepsis-induced lung injury model
Positive end-expiratory pressure modulates local and systemic inflammatory responses in a sepsis-induced lung injury model
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DOI：
10.1007/s00134-003-1756-5
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发表时间：
2003-08-01
影响因子：
38.9
通讯作者：
Villar, J
中科院分区：
文献类型：
--
作者：
Herrera, MT;Toledo, C;Villar, J
目的：以往的动物研究表明，某些模式的机械通气（MV）可损伤肺。这些研究中的大多数是使用与呼吸衰竭临床原因不同的模型进行的。我们研究了呼气末正压（PEEP）在临床相关的脓毒症诱导的急性肺损伤动物模型中的作用，该模型采用低潮气量或损伤潮气量通气。研究方法：将脓毒症雄性Sprague-Dawley大鼠麻醉并随机分为自主呼吸组或四种不同的MV策略，在低（6 ml/kg）或高（20 ml/kg）潮气量（V-T）下持续3 h，PEEP为零或PEEP高于压力-容积曲线的拐点。通过盲肠结扎和穿孔诱导脓毒症。分析所有实验组的死亡率、病理学评价、肺组织细胞因子基因表达和血浆细胞因子浓度。结果：在脓毒症存在的情况下，MV方法显著影响肺损伤、细胞因子的合成和释放以及死亡率。在低V-T通气3 h期间，高于拐点的PEEP显著减轻了肺损伤并降低了死亡率（25% vs. 0%），而在高V-T组中增加了肺损伤和死亡率（19% vs. 50%）。PEEP降低低V-T机械通气时肺细胞因子基因表达和血浆浓度。结论：在脓毒症诱导的急性肺损伤动物模型中使用高于拐点的PEEP水平调节与脓毒症相关的肺和全身炎症反应，并降低MV 3小时期间的死亡率。
Objective: Previous animal studies have shown that certain modes of mechanical ventilation (MV) can injure the lungs. Most of those studies were performed with models that differ from clinical causes of respiratory failure. We examined the effects of positive end-expiratory pressure (PEEP) in the setting of a clinically relevant, in vivo animal model of sepsis-induced acute lung injury ventilated with low or injurious tidal volume. Methods: Septic male Sprague-Dawley rats were anesthetized and randomized to spontaneous breathing or four different strategies of MV for 3 h at low (6 ml/kg) or high (20 ml/kg) tidal volume (V-T) with zero PEEP or PEEP above inflection point in the pressure-volume curve. Sepsis was induced by cecal ligation and perforation. Mortality rates, pathological evaluation, lung tissue cytokine gene expression, and plasma cytokine concentrations were analyzed in all experimental groups. Results: Lung damage, cytokine synthesis and release, and mortality rates were significantly affected by the method of MV in the presence of sepsis. PEEP above the inflection point significantly attenuated lung damage and decreased mortality during 3 h of ventilation with low V-T (25% vs. 0%) and increased lung damage and mortality in the high V-T group (19% vs. 50%). PEEP attenuated lung cytokine gene expression and plasma concentrations during mechanical ventilation with low V-T. Conclusions: The use of a PEEP level above the inflection point in a sepsis-induced acute lung injury animal model modulates the pulmonary and systemic inflammatory responses associated with sepsis and decreases mortality during 3 h of MV.