Date of Award


Degree Type


Degree Name

Doctor of Philosophy


The surface activity of Lipid Extract Surfactant (LES), a clinical preparation used for the treatment of Neonatal Respiratory Distress Syndrome, and the effects of addition of surfactant-associated protein A (SP-A) and palmitic acid were assayed in vitro in the presence and absence of challenge by inhibitory agents. Measurements of surface activity were made with the pulsating bubble surfactometer and the captive bubble technique. The addition of SP-A to LES enhances the surface activity of the preparation, especially at low surfactant concentrations. SP-A accelerates the adsorption of surfactant lipids from the aqueous subphase to the air-liquid interface and causes enrichment of the monolayer film in dipalmitoylphosphatidylcholine.;Blood proteins are potent inhibitors of LES. The addition of SP-A completely reverses the inhibition by fibrinogen, albumin and alpha-globulin. As little as 0.5% (w/w of the surfactant lipid concentration) of SP-A causes reversal of inhibition. This effect is absolutely dependent upon the presence of calcium in the assay mixture. The addition of SP-A to another clinical preparation, Survanta, does not result in enhancement of surface activity or reversal of blood protein inhibition.;The addition of palmitic acid to LES enhances the surface activity, and accelerates adsorption. This effect requires relatively high concentrations of palmitic acid ({dollar}\sim{dollar}8% w/w). Addition of palmitic acid causes a partial reversal of inhibition by blood proteins. Lysophosphatidylcholine (lyso-PC) also inhibits LES. This inhibition is reversed by the addition of palmitic acid, but not SP-A.;The presence of small amounts of lyso-PC in preparations of LES sensitizes the surfactant to inhibition by fibrinogen. This effect is observed regardless of whether the lyso-PC is endogenous, exogenous, or endogenously generated in vitro.;The results of these experiments demonstrate the importance of SP-A in the surface activity of surfactant and the interactions of palmitic acid and lyso-PC with LES. The addition of SP-A and/or palmitic acid should be considered for some applications of surfactant replacement therapy.



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