Aerosolized surfactant in lung-lavaged adult rats: factors influencing the therapeutic response

Abstract

Objective: To evaluate the effect of aerosolized modified natural surfactant in adult rats with respiratory failure.

Methods: Lung-lavaged adult rats were treated with aerosolized surfactant, aerosolized saline or a bolus of surfactant. Surfactant was labelled with dimyristoylphosphatidylcholine (DMPC) and human serum albumin was given intravenously for evaluation of lung protein leakage. Blood gases and dynamic compliance were measured intermittently. At the end of ventilation, the lungs were either fixed by vascular perfusion for histological examination or washed for determination of total phospholipids, DMPC and human albumin in the lavage fluid.

Results: Treatment with bolus surfactant led to a quick and sustained restoration of pre-lavage blood gas values in most animals. The response to aerosolized surfactant varied considerably, with an overall moderate improvement of gas exchange. The saline-treated group failed to show any significant recovery of lung function. No histopathological differences were found between any of the groups. On average 0.46% of total administered aerosolized surfactant could be recovered. Vascular-to-alveolar leakage of human albumin averaged 11%, with no significant differences between the groups. Final values for PaO2 were significantly correlated with total phospholipids in the lavage fluid, and inversely related to the vascular-to-alveolar leakage of albumin.

Conclusion: Neither bolus nor aerosolized surfactant influenced lung morphology. Nebulized surfactant improved lung function but the effect was inferior to that obtained with bolus surfactant, and the outcome depended on the balance between the combined pool size of exogenous and endogenous surfactant and the vascular-to-alveolar leakage of serum protein.