High-frequency oscillatory ventilation (HFOV) permits adequate gas exchange but avoids the large phasic pressure-volume excursions of conventional mechanical ventilation (CMV); such avoidance may reduce the lung injury associated with hyaline membrane disease (HMD). We hypothesized that premature monkeys ventilated from birth with HFOV would have reduced lung injury compared to those assigned to CMV. Macaca nemestrina were delivered at 134 days (80% of term gestation) and ventilated from the first breath with either HFOV (n = 10) or CMV (n = 10). The mean airway pressure (Paw) was kept at 15 cm H2O pressure in HFOV animals; in CMV animals Paw was increased from 8 cm H2O at 2 h to 13 cm H2O at 6 h to prevent hypoxemia. At the conclusion of the 6-h experiment the HFOV animals had better oxygenation (p less than 0.05) and less evidence of HMD by chest radiograph (p less than 0.05). At 6 h of age a piece of the right middle lung lobe was removed, divided, and placed in fixatives for light and transmission electron microscopy. The lungs were subsequently inflated to 30 cm H2O pressure, and the right lower lobe was rapidly frozen in situ for morphometric studies. The proportion of peripheral lung tissue occupied by clear alveoli was greater in HFOV animals (66.3 +/- 14.8%) than in those assigned to CMV (44.2 +/- 16.9%, p less than 0.01); less alveolar debris and fluid was present in the HFOV animals (12.7 +/- 9.9%) compared with CMV animals (27.1 +/- 12.5%, p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

To determine whether the cause of reduced total lung capacity (TLC) in hyaline membrane disease (HMD) is due to alveolar collapse, alveolar edema, or both, TLC was measured by N2-washout in premature Macaca nemestrina monkeys during the first 3 h of life. The TLC of animals with HMD was only one-third that of healthy premature monkeys over the first 3 h of life (p less than 0.01). At 3.5 h, lung tissue was rapidly frozen in situ during lung inflation to TLC. Samples of frozen lung tissue were freeze dried, embedded, sectioned, and examined by point counting. Animals with HMD had alveolar saccules filled with the residue of proteinaceous fluid, but little alveolar collapse was noted. The proportion of points falling on empty alveolar spaces was 74% in the healthy animals but only 18% in animals with HMD (p less than 0.01); there was a 70-fold increase in the residue present in alveoli of animals with HMD (p less than 0.05). In a separate experiment, rapid serial measurements of TLC by N2-washout showed that healthy premature monkeys, but not those with HMD, have a steady increase in TLC during the first few minutes of life, presumably due to clearance of lung liquid. Although the initial cause of reduced TLC in HMD appears to be inadequate clearance of fetal lung liquid, by 3 h of age proteinaceous alveolar edema is primarily responsible.