Lung development and susceptibility to ventilator-induced lung injury

Lung development and susceptibility to ventilator-induced lung injury
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DOI:
10.1164/rccm.200408-1053oc
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发表时间:
2005-04-01
影响因子:
24.7
通讯作者:
Kavanagh, BP
Kavanagh, BP
中科院分区:
医学1区
文献类型:
--
作者:
Kornecki, A;Tsuchida, S;Kavanagh, BP

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原理:呼吸机诱导的肺损伤主要在成人中进行研究。目的:探讨年龄和肺发育对肺损伤易感性的影响。研究方法:对离体分离的非灌注大鼠肺(婴儿、幼年和成年)进行机械通气,其中V-T基于毫升/千克体重或作为测量的总肺容量(TLC)的百分比。在体内麻醉大鼠(婴儿,成年)机械通气与压力限制V-TS。随机分配至通气策略。测量值:通过压力-容积分析、TLC减少和组织学评估离体损伤,通过肺顺应性、细胞因子产生和湿干重比评估体内损伤。主要结果:离体通气(V-T 30 ml(.)kg(-1))导致成人肺TLC显著降低(36.0 +/-10.1%,p < 0.05),但在婴儿肺中没有。离体通气(V-T 50% TLC)导致成人(27.8 +/- 2.8%)和婴儿(110.6 +/- 7.0%)肺的TLC显著降低,但成人肺中的TLC更显著(p < 0.05);这些变化通过组织学和压力-容积特征证实。在体内高拉伸通气后,成年大鼠而非幼年大鼠发生肺损伤(总肺顺应性、湿/干比、肿瘤坏死因子a)。表面视频显微镜显示更大的异质性肺泡扩张在离体成人与婴儿肺。结论:这些数据提供了离体和体内证据,表明可比的呼吸机设置在成年大鼠肺中比在幼年大鼠肺中的损伤更大,可能反映了内在易感性或充气模式的差异。
Rationale: Ventilator-induced lung injury has been predominantly studied in adults. Objectives: To explore the effects of age and lung development on susceptibility to such injury. Methods: Ex vivo isolated nonperfused rat lungs (infant, juvenile, and adult) were mechanically ventilated where V-T was based on milliliters per kilogram of body weight or as a percentage of the measured total lung capacity (TLC). In vivo anesthetized rats (infant, adult) were mechanically ventilated with pressure-limited V-TS. Allocation to ventilation strategy was randomized. Measurements: Ex vivo injury was assessed by pressure-volume analysis, reduction in TLC, and histology, and in vivo injury by lung compliance, cytokine production, and wet-to dry-weight ratio. Main Results: Ex vivo ventilation (V-T 30 ml (.) kg(-1)) resulted in a significant reduction (36.0 +/- 10.1%, p < 0.05) in TLC in adult but not in infant lungs. Ex vivo ventilation (V-T 50% TLC) resulted in a significant reduction in TLC in both adult (27.8 +/- 2.8%) and infant (110.6 +/- 7.0%) lungs, but more so in the adult lungs (p < 0.05); these changes were paralleled by histology and pressure-volume characteristics. After high stretch in vivo ventilation, adult but not infant rats developed lung injury (total lung compliance, wet/dry ratio, tumor necrosis factor a). Surface video microscopy demonstrated greater heterogeneity of alveolar distension in ex vivo adult versus infant lungs. Conclusion: These data provide ex vivo and in vivo evidence that comparable ventilator settings are significantly more injurious in the adult than infant rat lung, probably reflecting differences in intrinsic susceptibility or inflation pattern.