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首页> 外文期刊>BMC Anesthesiology >TIP peptide inhalation in experimental acute lung injury: effect of repetitive dosage and different synthetic variants
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TIP peptide inhalation in experimental acute lung injury: effect of repetitive dosage and different synthetic variants

机译：吸入TIP肽在实验性急性肺损伤中的作用：重复剂量和不同合成变异体的作用

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Background Inhalation of TIP peptides that mimic the lectin-like domain of TNF-α is a novel approach to attenuate pulmonary oedema on the threshold to clinical application. A placebo-controlled porcine model of acute respiratory distress syndrome (ARDS) demonstrated a reduced thermodilution-derived extravascular lung water index (EVLWI) and improved gas exchange through TIP peptide inhalation within three hours. Based on these findings, the present study compares a single versus a repetitive inhalation of a TIP peptide (TIP-A) and two alternate peptide versions (TIP-A, TIP-B). Methods Following animal care committee approval ARDS was induced by bronchoalveolar lavage followed by injurious ventilation in 21 anaesthetized pigs. A randomised-blinded three-group setting compared the single-dosed peptide variants TIP-A and TIP-B as well as single versus repetitive inhalation of TIP-A (n?=?7 per group). Over two three-hour intervals parameters of gas exchange, transpulmonary thermodilution, calculated alveolar fluid clearance, and ventilation/perfusion-distribution were assessed. Post-mortem measurements included pulmonary wet/dry ratio and haemorrhage/congestion scoring. Results The repetitive TIP-A inhalation led to a significantly lower wet/dry ratio than a single dose and a small but significantly lower EVLWI. However, EVLWI changes over time and the derived alveolar fluid clearance did not differ significantly. The comparison of TIP-A and B showed no relevant differences. Gas exchange and ventilation/perfusion-distribution significantly improved in all groups without intergroup differences. No differences were found in haemorrhage/congestion scoring. Conclusions In comparison to a single application the repetitive inhalation of a TIP peptide in three-hour intervals may lead to a small additional reduction the lung water content. Two alternate TIP peptide versions showed interchangeable characteristics.
机译：背景技术吸入模仿TNF-α凝集素样结构域的TIP肽是一种在临床应用阈值上减轻肺水肿的新方法。安慰剂对照的急性呼吸窘迫综合征（ARDS）猪模型显示，热稀释引起的血管外肺水指数（EVLWI）降低，并且通过吸入TIP肽在3小时内改善了气体交换。基于这些发现，本研究比较了一次吸入和重复吸入的TIP肽（TIP-A）和两个替代肽版本（TIP-A，TIP-B）。方法经动物保护委员会批准，对21头麻醉猪进行支气管肺泡灌洗，然后进行有害通气，诱发ARDS。一个随机盲的三组实验比较了单剂量肽变体TIP-A和TIP-B以及TIP-A的单次吸入与重复吸入（每组n == 7）。在两个三个小时的间隔内，评估了气体交换，经肺热稀释，计算出的肺泡液清除率和通气/灌注分布的参数。死后测量包括肺干/湿比和出血/充血评分。结果重复吸入TIP-A导致湿/干比明显低于单剂量，并且EVLWI较小但明显较低。但是，EVLWI随时间变化，并且得出的肺泡液清除率没有显着差异。 TIP-A和B的比较没有相关差异。所有组的气体交换和通气/灌注分布均得到显着改善，而组间没有差异。出血/充血评分无差异。结论与单一应用相比，每隔3小时重复吸入TIP肽可能会导致肺水含量的少量额外降低。两个替代的TIP肽版本显示出可互换的特征。

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