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)

SummaryDelivery of M. nemestrina at 80% of normal gestation provides a population of neonates at high risk for hyaline membrane disease (HMD). The diagnosis of HMD was made by the presence of reticulogranular densities and air bronchograms on chest radiographs. Patchy atelectasis was seen in the lungs of animals assigned by clinical and radiographic criteria to the HMD group and not in the normal lungs of animals matched for gestational and postnatal age. Total phospholipid and phosphatidylcholine in whole lung, airway lavage fluid, and surface-active materials were lower in animals with HMD. Amniotic fluid L/S ratios were lower in the group that developed HMD. Pressure-volume measurements indicated decreased distensibility and unstable terminal air spaces in the HMD group. Alveolar-arterial oxygen pressure differences were greater in animals with HMD. There were no differences between HMD and normal groups in body weight, lung weight, percent dry lung weight, gestational age, and postnatal age at death. This primate species, subjected to premature delivery, is a suitable animal model of HMD in human neonates. Speculation An animal model of hyaline membrane disease (HMD) in a primate species is of interest to investigators of developmentally related pulmonary disorders. More complete knowledge of abnormalities in pulmonary function in HMD will contribute to development of both preventive and therapeutic measures and affords the opportunity to determine risks and benefits of such treatments to the fetus and newborn.

To assess maturational changes in collagen synthesis, lung tissue was obtained from healthy Macaca nemestrina monkeys at different ages, ranging from 68% of term gestation to adulthood. We hypothesized that infants delivered prematurely have a greater rate of collagen synthesis than do older animals because of their greater rate of lung growth during gestation. Secondly, we hypothesized that lung repair in infants with hyaline membrane disease (HMD) is associated with an additional increase in lung collagen synthesis rate. Therefore, lung tissue was obtained during the first week of life from monkeys delivered at 82% of term gestation, a stage at which half of them developed HMD. The rate of total protein synthesis in lung samples was determined by measuring the incorporation of [3H]proline; the rate of collagen synthesis was determined by measuring the conversion of proline into hydroxyproline. Premature monkeys had a higher rate of collagen synthesis (9.9 +/- 2.7 nmol/mg DNA/h) than did term infants (5.3 +/- 1.1) or older animals (2.1 +/- 0.4, p less than 0.05). There was no additional increase in rate of collagen synthesis in animals with HMD from 3 h (14.3 +/- 6.9) to 7 days of age (15.1 +/- 6.1); control premature animals also had no significant change during the first week of life (10.9 +/- 3.0 at 3 h; 11.6 +/- 4.6 at 7 days). The early stage of recovery from HMD in premature monkeys does not appear to be associated with an increase in collagen production beyond the already increased synthesis rate associated with lung growth.