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

Lee, Chul; Park, Min Soo; Park, Moon Sung; Kim, Jung Nyeon; Lee, Jong Wook; You, Kwang Hyun; Kwag, Won Jae; Park, Kook In; Namgung, Ran; Han, Dong Gwan

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.