Physical and Biological Activity of Domestic Product of Modified Bovine Lung Surfactant

ABSTRACT

PURPOSE: Neonatal respiratory distress syndrome is caused by the deficiency of lung surfactant in premature babies. For the treatment of RDS at present surfactants such as Surfacten (Tokyo-Tanabe Co., Japan) and Exosurf (Wellcome Co., USA) are used. As awarded the grant from the Ministry of Science and Technology for a model research project of Medium-Technology program, we have modified (supplemented) the bovine lung extracts to get YY-38, for which we have performed physical and biological activities. METHODS: For physical properties, we performed stable microbubble test (SMR) and measured surface tension lowering activity using a pulsating bubble surfactometer. Minimum and maximum surface tensions measured at 1 and 5 minutes gave surface tension-surface area diagrams, from which compressibility at surface tension 10mN/m was also calculated. As to the biological activity, we used premature rabbit fetuses as a model for the study of pressure-lung volume relationship. The lung pathology was examined on the lung tissues subsequently obtained, and aerated area ratios were calculated based on the area measured by an image analyzer. RESULTS: The minimum surface tensions of YY-38 at 1 and 5 minutes for all different concentrations were low at 10mN/m, while the maximum surface tensions ranged from 33.01mN/m to 41.07mN/m. The surface tension-surface area curve showed a definite hysteresis at 1 and 5 minutes for all concentrations, and the surface tension fell below 10mN/m with 20% surface area compression. The compressibilities at surface tension 10mN/m at 5minutes for all concentrations were all below 0.02. In animal experiments, the mean lung volume of premature rabbit fetuses was inflated to 80.9ml/kg at maximum 30cmH2O, while the lung volume was maintained at 38.3mg/kg when the lung was deflated to 5cmH2O. The overall aerated area ratio was 45.4%. CONCLUSIONS: YY-38 formed sufficient amount of stable microbubbles and had a surface tension low enough to maintain alveolar stability and to exhibit a good hysteresis curve. In animal experiments it helped the expansion of premature lungs during inspiratory phase and was effective in the prevention of collapse during expiratory phase.