The artificially ventilated preterm rabbit neonate as experimental model of hyaline membrane disease

Bronchiolar epithelial lesions, similar to those in human hyaline membrane disease (HMD), can be induced by artificial ventilation of newborn rabbits, delivered on day 27 of gestation. As verified by electron microscopy, these epithelial lesions develop within only 1-5 min of artificial ventilation. Tracheal instillation of natural surfactant at birth improves lung-thorax compliance in these animals, enhances the aeration of the alveolar compartment, and prevents the development of bronchiolar epithelial lesions. This prophylactic effect is obtained even when the compliant lungs of the surfactant-treated animals are greatly overventilated, i.e. when the ventilator is set at standardized high insufflation pressure. The application of a low positive end-expiratory pressure (5 cmH2O) also results in increased lung-thorax compliance, and reduces the extent of bronchiolar epithelial lesions. These findings suggest that the epithelial lesions are secondary to an abnormal expansion pattern. In a premature neonate with surfactant deficiency, overdistension of airways and irregular aeration of the alveolar compartment might produce shear stress in the airway mucosa leading to disruption of the epithelium and formation of hyaline membranes. The same mechanism is probably also involved in the pathogenesis of the epithelial lesions in human neonatal HMD.