Fluid restriction reduces pulmonary edema in a model of acute lung injury in mechanically ventilated rats

Experimental acute lung injury models are often used to increase our knowledge on the acute respiratory distress syndrome (ARDS), however, existing animal models often do not take into account the impact of specific fluid strategies on the development of lung injury. In contrast, the current literature strongly suggests that fluid management strategies have a significant impact on clinical outcome of patients with ARDS. Thus, it is important to characterize the role of fluid management strategies in experimental models of lung injury. In this study we investigated the effect of two different fluid strategies on commonly used outcome variables in a short-term model of acute lung injury, in relation to age. Infant (2–3 weeks) and adult (3–4 months) Wistar rats received intratracheal instillations of lipopolysaccharide and 24 hours later were mechanically ventilated for 6 hours. During mechanical ventilation, rats from both age groups were randomized to either a standard or conservative intravenous fluid strategy. We found that the hemodynamic response in infant and adult rats was similar in both fluid strategies. Lung wet-to-dry ratios were lower in adult, but not in infant rats receiving the conservative fluid strategy as compared to the standard fluid strategy. There were age-related differences in markers of alveolar capillary barrier disruption and alveolar fluid clearance, yet these were unaffected by fluid strategy. Finally, we found significantly higher IL-1β and TNF-α concentrations in the adult rats treated with the conservative as compared to the standard fluid regimen. In conclusion, the choice of fluid strategy in mechanically ventilated rats with experimental LPS-induced acute lung injury has a significant effect on pulmonary extravascular water, an important and well-recognized lung injury marker, and on the local pro-inflammatory cytokine profiles. We advocate the use of a more uniform, conservative, fluid strategy regimen in experimental models of acute lung injury.

实验性急性肺损伤模型常被用于加深我们对急性呼吸窘迫综合征（Acute Respiratory Distress Syndrome, ARDS）的认知，但现有动物模型往往未纳入考量特异性液体治疗策略对肺损伤发生发展的影响。与之相对，当前大量研究文献明确表明，液体管理策略对ARDS患者的临床结局具有显著影响。因此，阐明液体管理策略在肺损伤实验模型中的作用具有重要意义。
本研究以年龄为关联因素，探究了两种不同液体治疗策略对急性肺损伤短期模型中常用结局指标的影响。本研究选取2~3周龄幼年及3~4月龄成年Wistar大鼠，经气管内滴注脂多糖（lipopolysaccharide, LPS），24小时后对其实施6小时机械通气。
机械通气期间，将两个年龄组的大鼠随机分配至标准静脉液体治疗组或限制性静脉液体治疗组。
研究结果显示，两种液体治疗策略下，幼年与成年大鼠的血流动力学反应均无显著差异。
与标准液体治疗组相比，接受限制性液体治疗的成年大鼠肺湿干比更低，而幼年大鼠则无此差异。
肺泡毛细血管屏障损伤标志物及肺泡液体清除率存在年龄相关差异，但此类差异不受液体治疗策略的影响。
最后，与标准液体治疗方案相比，接受限制性液体治疗的成年大鼠肺组织中白细胞介素-1β（interleukin-1β, IL-1β）和肿瘤坏死因子-α（tumor necrosis factor-α, TNF-α）浓度显著升高。
综上，在脂多糖诱导的实验性急性肺损伤机械通气大鼠中，液体治疗策略的选择对肺血管外水含量（公认的重要肺损伤标志物）及局部促炎细胞因子谱均具有显著影响。本研究建议在急性肺损伤实验模型中采用更为统一的限制性液体治疗方案。