We evaluated the effects of abrupt versus gradual PEEP decrease, combined with standard versus high-volume fluid administration, on cardiac function, as well as lung and kidney damage in an established model of mild-moderate acute respiratory distress syndrome (ARDS). Wistar rats received endotoxin intratracheally. After 24 h, they were treated with Ringer’s lactate at standard (10 mL/kg/h) or high (30 mL/kg/h) dose. For 30 min, all animals were mechanically ventilated with tidal volume = 6 mL/kg and PEEP = 9 cmH2O (to keep alveoli open), then randomized to undergo abrupt or gradual (0.2 cmH2O/min for 30 min) PEEP decrease from 9 to 3 cmH2O. Animals were then further ventilated for 10 min at PEEP = 3 cmH2O, euthanized, and their lungs and kidneys removed for molecular biology analysis. At the end of the experiment, left and right ventricular end-diastolic areas were greater in animals treated with high compared to standard fluid administration, regardless of PEEP decrease rate. However, pulmonary arterial pressure, indicated by the pulmonary acceleration time (PAT)/pulmonary ejection time (PET) ratio, was higher in abrupt compared to gradual PEEP decrease, independent of fluid status. Animals treated with high fluids and abrupt PEEP decrease exhibited greater diffuse alveolar damage and higher expression of interleukin-6 (a pro-inflammatory marker) and vascular endothelial growth factor (a marker of endothelial cell damage) compared to the other groups. The combination of standard fluid administration and gradual PEEP decrease increased zonula occludens-1 expression, suggesting epithelial cell preservation. Expression of club cell-16 protein, an alveolar epithelial cell damage marker, was higher in abrupt compared to gradual PEEP decrease groups, regardless of fluid status. Acute kidney injury score and gene expression of kidney injury molecule-1 were higher in the high versus standard fluid administration groups, regardless of PEEP decrease rate. In the ARDS model used herein, decreasing PEEP abruptly increased pulmonary arterial hypertension, independent of fluid status. The combination of abrupt PEEP decrease and high fluid administration led to greater lung and kidney damage. This information adds to the growing body of evidence that supports gradual transitioning of ventilatory patterns and warrants directing additional investigative effort into vascular and deflation issues that impact lung protection.

中文翻译：

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液体状态和递减PEEP策略对轻中度实验性急性呼吸窘迫综合征心功能及肺肾损伤的影响

我们在已建立的轻中度急性呼吸窘迫综合征 (ARDS) 模型中评估了突然与逐渐 PEEP 降低，结合标准与大容量输液对心脏功能以及肺和肾损伤的影响。Wistar 大鼠气管内接受内毒素。24小时后，用标准剂量（10 mL/kg/h）或高剂量（30 mL/kg/h）乳酸林格氏液治疗。30 分钟内，所有动物均采用机械通气，潮气量 = 6 mL/kg，PEEP = 9 cmH2O（以保持肺泡开放），然后随机接受突然或逐渐（0.2 cmH2O/min，持续 30 分钟）PEEP 从 9 降低至3厘米水柱。然后将动物在 PEEP = 3 cmH2O 下进一步通气 10 分钟，实施安乐死，并取出肺和肾进行分子生物学分析。实验结束时，无论 PEEP 下降率如何，与标准输液治疗的动物相比，接受高浓度输液治疗的动物的左心室和右心室舒张末期面积更大。然而，与逐渐下降的 PEEP 相比，由肺加速时间 (PAT)/肺射血时间 (PET) 比值表示的肺动脉压突然升高，且与液体状态无关。与其他组相比，接受高液体和突然降低 PEEP 治疗的动物表现出更大的弥漫性肺泡损伤以及更高的白细胞介素 6（促炎标记物）和血管内皮生长因子（内皮细胞损伤标记物）表达。标准输液和逐渐 PEEP 相结合可增加闭锁小带-1 的表达，表明上皮细胞得以保存。无论液体状态如何，与逐渐减少 PEEP 的组相比，突然减少 PEEP 的组中 Club cell-16 蛋白（一种肺泡上皮细胞损伤标志物）的表达较高。无论 PEEP 降低率如何，高剂量输液组的急性肾损伤评分和肾损伤分子 1 基因表达均高于标准输液组。在本文使用的 ARDS 模型中，降低 PEEP 会突然增加肺动脉高压，与液体状态无关。PEEP 突然降低和大量输液相结合会导致更大的肺和肾损伤。这些信息增加了越来越多的证据，支持通气模式的逐渐转变，并保证对影响肺保护的血管和通气问题进行更多的调查工作。