Inactivation of Pulmonary Surfactant Due to Serum-Inhibited Adsorption and Reversal by Hydrophilic Polymers: Experimental

Abstract

The rate of change of surface pressure, pi, in a Langmuir trough following the deposition of surfactant suspensions on subphases containing serum, with or without polymers, is used to model a likely cause of surfactant inactivation in vivo: inhibition of surfactant adsorption due to competitive adsorption of surface active serum proteins. Aqueous suspensions of native porcine surfactant, organic extracts of native surfactant, and the clinical surfactants Curosurf, Infasurf, and Survanta spread on buffered subphases increase the surface pressure, pi, to approximately 40 mN/m within 2 min. The variation with concentration, temperature, and mode of spreading confirmed Brewster angle microscopy observations that subphase to surface adsorption of surfactant is the dominant form of surfactant transport to the interface. However (with the exception of native porcine surfactant), similar rapid increases in pi did not occur when surfactants were applied to subphases containing serum. Components of serum are surface active and adsorb reversibly to the interface increasing pi up to a concentration-dependent saturation value, pi(max). When surfactants were applied to subphases containing serum, the increase in pi was significantly slowed or eliminated. Therefore, serum at the interface presents a barrier to surfactant adsorption. Addition of either hyaluronan (normally found in alveolar fluid) or polyethylene glycol to subphases containing serum reversed inhibition by restoring the rate of surfactant adsorption to that of the clean interface, thereby allowing surfactant to overcome the serum-induced barrier to adsorption.

Chitosan Enhances the In Vitro Surface Activity of Dilute Lung Surfactant Preparations and Resists Albumin-Induced Inactivation

“…This function of chitosan closely resembles the effect of nonionic polymers in improving surface activity of therapeutic lung surfactants by inducing large surfactant aggregates (5,6) and hence leads us to consider its potential use as a lung surfactant additive. In this study, the effects of chitosan on surface activity of a dilute therapeutic lung surfactant, BLES (BLES Biochemicals Inc, London, ON, Canada), and on the resistance to albumin-induced inactivation are investigated using a CSD method (18).…”

“…Both in vitro (1)(2)(3)(4)(5)(6) and in vivo (7)(8)(9) trials have shown that these nonionic polymers can significantly improve the surface activity of different therapeutic lung surfactants and effectively reverse inactivation due to a variety of inhibitory substances.…”

Interaction of metal oxide nanoparticles with lung surfactant protein A

“…pBALF preparation was modified after Taeusch et al [55]. In short, three porcine lungs, derived from a local butcher and removed in toto, were each filled with about 0.6 l of cold (4 °C) purified water and gently massaged for about 5 min.…”

Synthetic Pulmonary Surfactant Preparations: New Developments and Future Trends

“…As a secondary consequence of several types of lung injury, inflammation and disruption of the alveolarcapillary barrier lead to the leakage of serum components into the airspaces, which are responsible for a severe inactivation of the biophysical activities of the surfactant complex [18]. Several trials have addressed the potential treatment of ARDS with exogenous surfactant in animal models and patients, but with limited success [19,20].…”

“…Phospholipids constitute around 80% per mass of surfactant and are the main surface active molecules, able to form interfacial films capable of reducing the surface tension at the alveolar air-liquid interface until values close to 0 mN/m, which are reached at the end of expiration, a strict Another pathology related to pulmonary surfactant dysfunction is ARDS associated with acute lung injury (ALI) [17]. As a secondary consequence of several types of lung injury, inflammation and disruption of the alveolarcapillary barrier lead to the leakage of serum components into the airspaces, which are responsible for a severe inactivation of the biophysical activities of the surfactant complex [18]. Several trials have addressed the potential treatment of ARDS with exogenous surfactant in animal models and patients, but with limited success [19,20].…”