Yoder B A, Siler-Khodr T, Winter V T, Coalson J J
Southwest Foundation for Biomedical Research, San Antonio, Texas, USA.
Am J Respir Crit Care Med. 2000 Nov;162(5):1867-76. doi: 10.1164/ajrccm.162.5.9912145.
Acute lung injury models demonstrate that high-frequency oscillatory ventilation (HFOV) improves lung function, mechanics, and histopathology with reduced inflammatory mediators. Neither human HFOV trials nor premature animal studies have adequately evaluated these factors during prolonged HFOV. The objective of this study was to compare the effect of prolonged HFOV with low tidal volume (VT) positive pressure ventilation (LV-PPV) in an immature baboon model for neonatal chronic lung disease (CLD). After administration of prenatal steroids, 18 baboons were delivered by cesarean section at 125 d (term = 185 d), treated with exogenous surfactant, then randomized to either HFOV or LV-PPV by 5 min age. Animals were maintained on oxygen on an "as needed" basis and on nutritional support for 1 to 2 mo. Serial pulmonary function testing (PFT) was performed. Tracheal aspirates were analyzed for interleukin-6 (IL-6), IL-8, tumor necrosis factor-alpha (TNF-alpha), IL-1beta, and IL-10. Lungs were inflation fixed for morphometric analyses. From 12 h through 10 d age, HFOV animals had consistently lower fraction of inspired oxygen (FI(O(2))) and higher a/ A ratio. Pulmonary mechanics were significantly improved in HFOV animals at nearly every time point analyzed from 12 h to 28 d. There were no consistent differences in tracheal IL-6, TNF-alpha, IL-1beta, or IL-10 after 24 h age. Higher tracheal IL-8 values and macrophage/monocyte numbers were found in LV-PPV animals after 1 wk and 3 to 4 wk ventilation. Both groups exhibited pulmonary pathologic lesions found in extremely immature humans, including alveolar hypoplasia, variable saccular wall fibrosis, and minimal airway disease. HFOV animals had significantly better lung inflation patterns by panel of standards analysis. Early, prolonged HFOV significantly improved early lung function with sustained improvement in pulmonary mechanics out to 28 d. Immature baboons managed with HFOV had less pulmonary inflammation in the hyaline membrane disease (HMD) recovery phase. Though enhanced alveolization was not observed, HFOV for 1 to 2 mo resulted in consistently more uniform lung inflation than LV-PPV.
急性肺损伤模型表明，高频振荡通气（HFOV）可改善肺功能、力学特性和组织病理学，同时减少炎症介质。无论是人体HFOV试验还是早产动物研究，均未对长时间HFOV期间的这些因素进行充分评估。本研究的目的是在未成熟狒狒模型中比较长时间HFOV与低潮气量（VT）正压通气（LV-PPV）对新生儿慢性肺病（CLD）的影响。给予产前类固醇后，18只狒狒在125天（足月为185天）时剖宫产分娩，接受外源性表面活性剂治疗，然后在出生5分钟时随机分为HFOV组或LV-PPV组。动物根据“按需”原则给予氧气，并给予营养支持1至2个月。进行系列肺功能测试（PFT）。分析气管吸出物中的白细胞介素-6（IL-6）、IL-8、肿瘤坏死因子-α（TNF-α）、IL-1β和IL-10。肺膨胀固定后进行形态计量分析。从出生12小时至10天，HFOV组动物的吸入氧分数（FI(O₂)）持续较低，而a/A比值较高。从出生12小时至28天的几乎每个分析时间点，HFOV组动物的肺力学均显著改善。出生24小时后，气管IL-6、TNF-α、IL-1β或IL-10没有一致的差异。通气1周和3至4周后，LV-PPV组动物的气管IL-8值和巨噬细胞/单核细胞数量较高。两组均表现出在极不成熟人类中发现的肺部病理病变，包括肺泡发育不全、不同程度的囊壁纤维化和轻微的气道疾病。通过标准分析，HFOV组动物的肺膨胀模式明显更好。早期、长时间的HFOV显著改善早期肺功能，并使肺力学持续改善至28天。采用HFOV治疗的未成熟狒狒在透明膜病（HMD）恢复期的肺部炎症较轻。虽然未观察到肺泡化增强，但1至2个月的HFOV导致肺膨胀比LV-PPV始终更均匀。
