High-frequency oscillatory ventilation: Effects on lung function, mechanics, and airway cytokines in the immature baboon model for neonatal chronic lung disease

B. A. Yoder, T. Siler-Khodr, V. T. Winter, J. J. Coalson

Research output: Contribution to journalArticlepeer-review

140 Scopus citations

Abstract

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-α), IL-1β, 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 (Fl(O2)) 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-α, IL-1β, 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.

Original languageEnglish (US)
Pages (from-to)1867-1876
Number of pages10
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume162
Issue number5
DOIs
StatePublished - 2000

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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