BIOPHYSICAL AND PHYSIOLOGICAL-PROPERTIES OF A MODIFIED PORCINE SURFACTANT ENRICHED WITH SURFACTANT PROTEIN-A

Surfactant protein A (SP-A), a major protein component of natural pulm onary surfactant, is absent in exogenous surfactants currently used in clinical practice. We investigated the physical and physiological pro perties of one of these modified natural surfactants (Curosurf(R)) aft er enrichment with 5% SIP-A (SP-A-Curosurf), A pulsating bubble system was used for in vitro assessments and ventilated newborn rabbits for evaluation of in vivo effects. In the presence of various potential in hibitors (meconium 5 mg.mL(-1), fibrinogen 5 mg.mL(-1), albumin 25 mg. mL(-1), or whole serum proteins 25 mg.mL(-1)), Curosurf at a concentra tion of 5 mg.mL(-1) was inactivated while SP-A-Curosurf and natural po rcine surfactant at the same concentration had normal maximum and mini mum surface tension, This protective effect of SP-A was calcium depend ent. In immature newborn rabbits, the improvement of lung-thorax compl iance observed after treatment with 100 mg.kg(-1) of SP-A-Curosurf was equivalent to that obtained with 200 mg.kg(-1) of Curosurf, Similarly , in near-term newborn rabbits with respiratory failure induced by ins tillation of fibrinogen via the airways, the increase in compliance af ter administration of 100 mg.kg(-1) of SP-A-Curosurf corresponded to t hat seen after treatment with 200 mg.kg(-1) of Curosurf, whereas Curos urf at a dose of 100 mg.kg(-1) had no substantial effect.Our data thus indicate that surfactant protein A increases the resistance of Curosu rf to inactivation under in vivo conditions.