Experimental Evaluation of Surfactants for Replacement Therapy

Abstract

Since Fujiwara et al. [1] published the first promising results of surfactant replacement in neonatal respiratory distress syndrome (RDS), there has been rapidly growing interest in the potential of this new therapeutic regimen. During the past few years, several surfactant substitutes have been tested in clinical pilot studies and multiple randomized trials have been completed or are in progress [2-13]. In general, the results of these trials indicate efficacy of “natural” surfactant preparations isolated from mammalian lungs [5, 7, 8, 11-13] or human amniotic fluid [6, 10], whereas synthetic surfactant substitutes (devoid of specific surfactant-associated proteins) seem to be less effective [2, 3, 9]. To some extent, this difference could have been anticipated from variations in the physical properties of the surfactant preparations. However, more precise guidelines can be obtained from properly designed animal studies.

The purpose of this article is to review methods currently used for experimental evaluation of new surfactant substitutes. The first section below, summarizing some basic facts on the composition and surface chemistry of pulmonary surfactant, serves as a background to subsequent brief sections on surface balance and pulsating bubble systems for evaluation of the physical properties of surfactant preparations. The major parts of our review deal with techniques for pressure-volume recordings and determination of in vivo lung function following surfactant replacement in animal models of neonatal and adult RDS. Some discrepancies between the in vitro and in vivo properties of surfactant substitutes are discussed in the final section. Our objective is to suggest improved standards for experimental work in this area in order to avoid predictable failures or disappointing results from unwarranted clinical trials. Immunological and toxicological aspects of surfactant replacement therapy are beyond the scope of the present review.