Increased pulmonary lactate production is correlated with severity of lung injury and outcome in acute respiratory distress syndrome (ARDS) patients. This study was conducted to investigate the relative contributions of inflammation and hypoxia to the lung's metabolic shift to glycolysis in an experimental animal model of ARDS using hyperpolarized (HP) ¹³C MRI. Fifty‐three intubated and mechanically ventilated male rats were imaged using HP ¹³C MRI before, and 1, 2.5 and 4 hours after saline (sham) or hydrochloric acid (HCl; 0.5 ml/kg) instillation in the trachea, followed by protective and nonprotective mechanical ventilation (HCl‐PEEP and HCl‐ZEEP) or the start of moderate or severe hypoxia (Hyp90 and Hyp75 groups). Pulmonary and cardiac HP lactate‐to‐pyruvate ratios were compared among groups for different time points. Postmortem histology and immunofluorescence were used to assess lung injury severity and quantify the expression of innate inflammatory markers and local tissue hypoxia. HP pulmonary lactate‐to‐pyruvate ratio progressively increased in rats with lung injury and moderate hypoxia (HCl‐ZEEP), with no significant change in pulmonary lactate‐to‐pyruvate ratio in noninjured but moderately hypoxic rats (Hyp90). Pulmonary lactate‐to‐pyruvate ratio was elevated in otherwise healthy lung tissue only in severe systemic hypoxia (Hyp75 group). ex vivo histological and immunopathological assessment further confirmed the link between elevated glycolysis and the recruitment into and presence of activated neutrophils in injured lungs. HP lactate‐to‐pyruvate ratio is elevated in injured lungs predominantly as a result of increased glycolysis in activated inflammatory cells, but can also increase due to severe inflammation‐induced hypoxia.

中文翻译：

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肺丙酮酸代谢作为急性呼吸窘迫综合征大鼠模型炎症和损伤的指标。

肺乳酸生成增加与急性呼吸窘迫综合征 (ARDS) 患者的肺损伤严重程度和预后相关。本研究旨在使用超极化 (HP) ¹³ C MRI在 ARDS 实验动物模型中研究炎症和缺氧对肺代谢转变为糖酵解的相对贡献。使用 HP ¹³对 53 只插管和机械通气的雄性大鼠进行成像C MRI 在气管内滴注生理盐水（假手术）或盐酸（HCl；0.5 ml/kg）之前和之后 1、2.5 和 4 小时，然后进行保护性和非保护性机械通气（HCl-PEEP 和 HCl-ZEEP）或开始中度或重度缺氧（Hyp90 和 Hyp75 组）。比较不同时间点的肺和心脏 HP 乳酸与丙酮酸的比率。死后组织学和免疫荧光用于评估肺损伤的严重程度并量化先天炎症标志物和局部组织缺氧的表达。在肺损伤和中度缺氧（HCl-ZEEP）大鼠中，HP 肺乳酸与丙酮酸的比率逐渐增加，未受伤但中度缺氧的大鼠（Hyp90）肺乳酸与丙酮酸的比率没有显着变化。仅在严重全身缺氧（Hyp75 组）中，其他健康肺组织中肺乳酸与丙酮酸的比率升高。离体组织学和免疫病理学评估进一步证实了糖酵解升高与受损肺中活化中性粒细胞的募集和存在之间的联系。HP 乳酸与丙酮酸的比率在受伤的肺中升高，主要是由于激活的炎症细胞中糖酵解增加，但也可能由于严重的炎症引起的缺氧而增加。