The poorly understood tolerance towards high tidal volume (V_T) ventilation observed in critically ill children and age-equivalent animal models may be explained by surfactant homeostasis. The aim of our prospective animal study was to test whether high V_T with adequate positive end-expiratory pressure (PEEP) is associated with surfactant de novo synthesis and secretion leading to improved lung function and whether extreme mechanical ventilation affects intracellular lamellar body formation and exocytosis. Fourteen days old rats were allocated to five groups: non-ventilated controls, PEEP 5 cmH₂O with V_T of 8, 16, and 24 mL/kg, respectively, and PEEP 1 cmH₂O with V_T 24 mL/kg. Following 6 hours of ventilation, lung function, surfactant proteins and phospholipids, and lamellar bodies were assessed by forced oscillation technique, quantitative real-time polymerase chain reaction, mass spectrometry, immunohistochemistry, and transmission electron microscopy, respectively. High V_T (24 mL/kg) with PEEP of 5 cmH₂O improved respiratory system mechanics and was not associated with lung injury, elevated surfactant protein expression, or surfactant phospholipid content. Extreme ventilation with V_T 24 mL/kg and PEEP 1 cmH₂O produced a mild inflammatory response and correlated with higher surfactant phospholipid concentrations in bronchoalveolar lavage fluid without affecting lamellar body count and morphology. Elevated phospholipid concentrations in the potentially most injurious strategy (V_T 24 mL/kg, PEEP 1 cmH₂O) need further evaluation and might reflect accumulation of biophysically inactive small aggregates. In conclusion, our data confirm the resilience of infant rats towards high V_T-induced lung injury and challenge the relevance of surfactant synthesis, storage, and secretion as protective factors.

中文翻译：

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高潮气量通气对新生大鼠表面活性剂代谢和肺损伤的影响。

表面活性剂的体内稳态可以解释在危重儿童和与年龄相当的动物模型中对潮气量（V _T）高通气的耐受性知之甚少。我们的前瞻性动物研究的目的是测试具有适当正呼气末正压（PEEP）的高V _T是否与表面活性剂从头合成和分泌相关，从而改善肺功能，以及极端的机械通气是否影响细胞内层状体的形成和胞吐作用。将十四天大的大鼠分为五组：不通风的对照组，PET 5 cmH ₂ O，V _T分别为8、16和24 mL / kg，PEEP 1 cmH ₂ O，V _T24 mL /公斤。通气6小时后，分别通过强迫振荡技术，定量实时聚合酶链反应，质谱，免疫组织化学和透射电镜对肺功能，表面活性剂蛋白和磷脂以及层状体进行了评估。PE值为5 cmH ₂ O的高V _T（24 mL / kg）改善了呼吸系统的力学，并且与肺损伤，表面活性剂蛋白表达升高或表面活性剂磷脂含量无关。V _T 24 mL / kg和PEEP 1 cmH _2的极端通风O产生轻度的炎症反应，并与支气管肺泡灌洗液中较高的表面活性剂磷脂浓度相关，而不会影响层状体数和形态。潜在最有害策略中的磷脂浓度升高（V _T 24 mL / kg，PEEP 1 cmH ₂ O）需要进一步评估，并可能反映出没有生物物理活性的小聚集体。总之，我们的数据证实了幼鼠对高V _T诱导的肺损伤的恢复能力，并挑战了表面活性剂合成，储存和分泌作为保护因子的相关性。