Injurious ventilatory strategies increase cytokines and c-fos m-RNA expression in an isolated rat lung model
Injurious ventilatory strategies increase cytokines and c-fos m-RNA expression in an isolated rat lung model
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DOI：
10.1172/jci119259
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发表时间：
1997-03-01
影响因子：
15.9
通讯作者：
Slutsky, AS
中科院分区：
文献类型：
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作者：
Tremblay, L;Valenza, F;Slutsky, AS
我们研究了在存在和不存在预先存在的炎症刺激的情况下，通气策略对肺部炎症介质的影响。55只Sprague-Dawley大鼠随机分为静脉生理盐水组和脂多糖组。自主呼吸50分钟后，切除肺，随机给予2小时通气，采用以下四种策略之一：(a)对照(C)，潮气量(V-t) = 7 cc/kg，呼气末正压(PEEP) = 3 cm H2O；(b)体积适中，PEEP （MVHP）高，V-t = 15 cc/kg；PEEP = 10 cm H2O；(c)容积适中，零PEEP (MVZP), V-t = 15 cc/kg, PEEP = 0；或(d)高容积，零PEEP (HVZP), V-t = 40 cc/kg, PEEP = 0。零PEEP通气（MVZP， HVZP）导致肺顺应性显著降低。ELISA法检测肺灌洗液中TNF α、IL-1 β、IL-6、IL-10、MIP-2、IFN γ水平。零PEEP联合大容量通气（HVZP）对细胞因子水平有协同作用（例如，TNF α比对照组增加56倍）。与PEEP相同的末吸气性肺扩张（MVHP）仅导致TNF - α增加3倍，而MVZP则使灌洗TNF - α增加6倍。Northern blot分析显示了相似的模式（C, MVHP < MVZP < HVZP）诱导C -fos mRNA。这些数据支持机械通气可以对肺的炎症/抗炎环境产生重大影响的概念，因此可能在启动或传播局部甚至全身炎症反应中发挥作用。
We examined the effect of ventilation strategy on lung inflammatory mediators in the presence and absence of a preexisting inflammatory stimulus. 55 Sprague-Dawley rats were randomized to either intravenous saline or lipopolysaccharide (LPS). After 50 min of spontaneous respiration, the lungs were excised and randomized to 2 h of ventilation with one of four strategies: (a) control (C), tidal volume (V-t) = 7 cc/kg, positive end expiratory pressure (PEEP) = 3 cm H2O; (b) moderate volume, high PEEP (MVHP), V-t = 15 cc/kg; PEEP = 10 cm H2O; (c) moderate volume, zero PEEP (MVZP), V-t = 15 cc/kg, PEEP = 0; or (d) high volume, zero PEEP (HVZP), V-t = 40 cc/kg, PEEP = 0. Ventilation with zero PEEP (MVZP, HVZP) resulted in significant reductions in lung compliance. Lung lavage levels of TNF alpha, IL-1 beta, IL-6, IL-10, MIP-2, and IFN gamma were measured by ELISA. Zero PEEP in combination with high volume ventilation (HVZP) had a synergistic effect on cytokine levels (e.g., 56-fold increase of TNF alpha versus controls). Identical end inspiratory lung distention with PEEP (MVHP) resulted in only a three-fold increase in TNF alpha, whereas MVZP produced a six-fold increase in lavage TNF alpha. Northern blot analysis revealed a similar pattern (C, MVHP < MVZP < HVZP) for induction of c-fos mRNA. These data support the concept that mechanical ventilation can have a significant influence on the inflammatory/anti-inflammatory milieu of the lung, and thus may play a role in initiating or propagating a local, and possibly systemic inflammatory response.