Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093-0412, USA.
Departments of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Biomed Pharmacother. 2022 Apr;148:112705. doi: 10.1016/j.biopha.2022.112705. Epub 2022 Feb 12.
Acute respiratory distress syndrome (ARDS) is a condition hallmarked by high permeability pulmonary edema and hypoxemic respiratory failure and is associated with high mortality. Current treatment protocols rely on improving O delivery, decreasing O consumption, and treating the underlying cause of the initial insult. In this study, we used a small rodent model of ARDS, where we induced lung injury with inhalation of lipopolysaccharide (LPS). We investigated three different treatments, namely inhaled NO at 70 ppm, inhaled NO at 140 ppm, and NO-np (10 mg/mL), compared with untreated rodents 72 h after initial insult. Concurrent with treatment, the fraction of inspired O was increased after 30 min from 21% to 40% and finally to 60%. At an FiO of 60% and 72 h post induction of ARDS, NO-np treated mice had an arterial PO (PaO) of 142 ± 9 mmHg, higher than mice treated with inhaled NO at 70 ppm (87 ± 5 mmHg, p = 8.4 × 10) and inhaled NO at 140 ppm (107 ± 6 mmHg, p = 6.1 × 10). Neutrophils in both the periphery (1.6 × 10 ± 0.4 × 10 cells) and bronchoalveolar lavage fluid (BALF; 2.7 × 10 ± 0.8 × 10 cells) were reduced in NO-np treated mice compared to mice treated with inhaled NO at 70 ppm (p = 0.0097, 2.4 × 10 ± 0.5 × 10 cells for periphery, p = 0.0075, 3.8 × 10 ± 0.8 × 10 cells for BALF). In summary, we found that treatment with NO-np improved arterial PO at a high FiO compared to inhaled NO alone and NO-np reduced both circulating and pulmonary interstitial neutrophil count, while inhaled NO did not. Future studies should aim to elucidate the precise mechanisms behind how NO-np mediate neutrophilic inflammation in ARDS.
急性呼吸窘迫综合征（ARDS）是一种以高通透性肺水肿和低氧性呼吸衰竭为特征的疾病，死亡率高。目前的治疗方案依赖于改善 O 输送、降低 O 消耗以及治疗初始损伤的根本原因。在这项研究中，我们使用了一种小型啮齿动物 ARDS 模型，通过吸入脂多糖（LPS）诱导肺损伤。我们研究了三种不同的治疗方法，即吸入 70ppm 的 NO、吸入 140ppm 的 NO 和 NO-np（10mg/mL），与初始损伤后 72 小时未接受治疗的啮齿动物进行比较。在治疗的同时，在 30 分钟内将吸入 O 的分数从 21%增加到 40%，最后增加到 60%。在 FiO 为 60%和 ARDS 诱导后 72 小时，NO-np 治疗的小鼠的动脉 PO（PaO）为 142±9mmHg，高于吸入 70ppm 的 NO 治疗的小鼠（87±5mmHg，p=8.4×10）和吸入 140ppm 的 NO 治疗的小鼠（107±6mmHg，p=6.1×10）。与吸入 70ppm 的 NO 治疗的小鼠相比，NO-np 治疗的小鼠外周血（1.6×10±0.4×10 个细胞）和支气管肺泡灌洗液（BALF；2.7×10±0.8×10 个细胞）中的中性粒细胞减少（p=0.0097，2.4×10±0.5×10 个细胞用于外周血，p=0.0075，3.8×10±0.8×10 个细胞用于 BALF）。总之，我们发现与单独吸入 NO 相比，NO-np 治疗可在高 FiO 下改善动脉 PO，并减少循环和肺间质中性粒细胞计数，而吸入 NO 则没有。未来的研究应旨在阐明 NO-np 介导 ARDS 中性粒细胞炎症的确切机制。
