Hyaluronan Reduces Surfactant Inhibition and Improves Rat Lung Function after Meconium Injury

Abstract

Hyaluronan (HA), an ionic polymer, is normally present in the alveolar subphase and is known to decrease lung surfactant inactivation caused by serum in vitro. In this study, we examined whether HA can ameliorate the inactivating effects of meconium in vitro and in vivo. Surface activities of various mixtures of Survanta, HA, and meconium were measured using a modified pulsating bubble surfactometer. With meconium, almost all surface activity measures were improved by the addition of HA of several molecular weights at a concentration of 0.25%. Anesthetized, paralyzed rats were maintained on positive-pressure ventilation. After lung injury by instillation of meconium, they were treated with Survanta, Survanta with HA, or control mixtures. Serial measures of blood gases and peak inspiratory pressure were recorded for the duration of the experiment. When the Survanta plus HA group was compared with the Survanta alone group, arterial oxygen tension averaged 117% higher, peak inspiratory pressure was 27% lower at the end of the experiment, and lung compliance also showed significant improvement. These results indicate that HA added to Survanta decreases inactivation caused by meconium in vitro and improves gas exchange and pulmonary mechanics of animals with meconiuminduced acute lung injury. Abbreviations HA, hyaluronan (hyaluronic acid) PEG, polyethylene glycol PIP, peak inspiratory pressure PV, pressure-volume SA, surface area ⌬A 10 , percentage decrease in surface area from the maximum to reach a surface tension of 10 mN/m Hyaluronan (HA) is an ionic polymer of alternating Nacetylglucosamine and glucuronate units. It is one of the glycosaminoglycans that includes chondroitin, keratan, and heparan sulfates. Although HA has a simple chemical structure, it can assume a large number of conformations in aqueous solutions. These conformations allow HA to play many roles in biologic systems, such as being a space filler in the vitreous humor and serving as a viscoelastic substance in joints. In addition, HA interacts with cell surface receptors such as the receptor to HA-mediated motality RHAMM and CD44 (1-3). The biocompatibility of HA has led to many applications, including viscosurgery to allow the creation of space between tissues (4) and lubrication of arthritic joints.The role of HA in a variety of respiratory diseases has also been investigated by several groups. found that HA binds to elastic fibers, preventing elastolysis and limiting airspace enlargement in experimental models of emphysema induced by elastases. Forteza et al. (8) proposed that HA plays a major role in mucosal host defense by stimulating ciliary beating via the RHAMM. Because HA is secreted into the alveolar subphase by type II cells (9,10), it has been suggested that it may interact with lung surfactant (11).Our previous work has shown that adding HA to different lung surfactants improved the surface activity and decreased surfactant inactivation caused by serum (12). In this study, we investigated the effects of using HA Survanta mixtures i...

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

“…(1) suggested the use of low-cost, water-soluble nonionic polymers, such as dextran, PEG, and polyvinylpyrrolidone (PVP), as additives to therapeutic lung surfactants. Both in vitro (1-6) and in vivo (7-9) 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.More recently, Lu et al (10,11) reported the use of an anionic polymer, HA, as a surfactant additive. Both in vitro (10) and in vivo (11) tests showed that the addition of HA at different molecular weights to various therapeutic lung surfactants can effectively reverse serum-and meconium-induced inactivation.…”

“…More recently, Lu et al (10,11) reported the use of an anionic polymer, HA, as a surfactant additive. Both in vitro (10) and in vivo (11) tests showed that the addition of HA at different molecular weights to various therapeutic lung surfactants can effectively reverse serum-and meconium-induced inactivation.…”

“…Both in vitro (10) and in vivo (11) tests showed that the addition of HA at different molecular weights to various therapeutic lung surfactants can effectively reverse serum-and meconium-induced inactivation. These studies, therefore, tentatively proved the feasibility of using an ionic polymer as a lung surfactant additive.…”

Toxic effects of different meconium fractions on lung function: new therapeutic strategies for meconium aspiration syndrome?

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