The Potential Role of Bioactive Plasmalogens in Lung Surfactant

Neonatal respiratory distress syndrome (NRDS) is a type of newborn disorder caused by the deficiency or late appearance of lung surfactant, a mixture of lipids and proteins. Studies have shown that lung surfactant replacement therapy could effectively reduce the morbidity and mortality of NRDS, and the therapeutic effect of animal-derived surfactant preparation, although with its limitations, performs much better than that of protein-free synthetic ones. Plasmalogens are a type of ether phospholipids present in multiple human tissues, including lung and lung surfactant. Plasmalogens are known to promote and stabilize non-lamellar hexagonal phase structure in addition to their significant antioxidant property. Nevertheless, they are nearly ignored and underappreciated in the lung surfactant-related research. This report will focus on plasmalogens, a minor yet potentially vital component of lung surfactant, and also discuss their biophysical properties and functions as anti-oxidation, structural modification, and surface tension reduction at the alveolar surface. At the end, we boldly propose a novel synthetic protein-free lung surfactant preparation with plasmalogen modification as an alternative strategy for surfactant replacement therapy.

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Lung Surfactant in an Era of Replacement Therapy

PEDIATRICS ◽

10.1542/peds.68.6.781 ◽

1981 ◽

Vol 68 (6) ◽

pp. 781-789

Author(s):

Robert H. Notter ◽

Donald L. Shapiro

Keyword(s):

Replacement Therapy ◽

Current Knowledge ◽

Lung Surfactant ◽

Potential Effect ◽

Human Infant ◽

Strong Interactions ◽

Exogenous Surfactant ◽

Surfactant Replacement ◽

Surfactant Replacement Therapy

In this paper current knowledge of the palmonary surfactant system with particular emphasis on aspects that relate to exogenous surfactant replacement therapy for the neonatal respiratory distress syndrome (RDS) is considered. The work provides an overview, but concentrates on several facets of lung surfactant research that help to elucidate and evaluate past and present attempts toward such therapy. Subjects addressed include the functional need for specific lung surfactant components to obtain optimal surface activity and some of the required surface property measurements to characterize such activity. Also discussed is current knowledge of lung surfactant synthesis and secretion and the potential effect of exogenous surfactant on the endogenous pulmonary surfactant sytem. A primary theme throughout is that an analysis of previous clinical trials involving surfactant replacement shows the necessity for strong interactions with related basic science investigations. It is suggested that future human infant surfactant replacement trials proceed deliberately, and include maximal correlations with basic in vitro research on lung surfactant biophysics and biochemistry and with experiments in animal models.

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Natural and artificial lung surfactant replacement therapy in premature lambs

Journal of Applied Physiology ◽

10.1152/jappl.1983.55.3.875 ◽

1983 ◽

Vol 55 (3) ◽

pp. 875-883 ◽

Cited By ~ 56

Author(s):

E. A. Egan ◽

R. H. Notter ◽

M. S. Kwong ◽

D. L. Shapiro

Keyword(s):

Replacement Therapy ◽

Dynamic Compression ◽

Lung Surfactant ◽

Blood Gases ◽

Lung Compliance ◽

Molar Ratio ◽

Exogenous Surfactant ◽

Surfactant Replacement ◽

Surfactant Replacement Therapy

The effect of tracheal instillation of surface-active mixtures in premature lambs was studied as an animal model of exogenous surfactant replacement therapy for the respiratory distress syndrome (RDS). Specific mixtures studied were 7:3 (molar ratio) dipalmitoyl phosphatidylcholine (DPPC):egg phosphatidylglycerol (PG) and extracted mixed lipids (with 1% protein) from cow lung lavage (CLL). Preventilatory tracheal instillation of greater than 15 mg/kg of CLL in 10 ml 0.15 M NaCl to premature lambs gave improved alveolar-arterial O2 gradient and blood gases and increased lung compliance, compared with control lambs over a 15-h period. Lambs receiving 7:3 DPPC:PG dispersions were not improved over controls with regard to pressure-volume characteristics and were worse than controls in arterial oxygenation. In terms of in vitro surface properties, both extracted natural CLL and 7:3 DPPC:egg PG were able to lower aqueous surface tension to 1 dyn/cm under dynamic compression. However, the dynamic respreading of CLL films on successive surface cycles was superior to that of 7:3 DPPC:PG. Moreover, after dispersal in 0.15 M NaCl by vortexing (5 mg/80 ml), CLL adsorbed to surface pressure (tau values of 45 dyn/cm within 10 min. 7:3 DPPC:PG adsorbed to significantly lower tau values after subphase dispersal by a variety of methods.

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Surfactant Replacement Therapy

10.1007/978-3-642-73305-5 ◽

1988 ◽

Cited By ~ 3

Keyword(s):

Replacement Therapy ◽

Surfactant Replacement ◽

Surfactant Replacement Therapy

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Veno-venous ECMO as a platform to evaluate lung lavage and surfactant replacement therapy in an animal model of severe ARDS

Intensive Care Medicine Experimental ◽

10.1186/s40635-020-00352-w ◽

2020 ◽

Vol 8 (1) ◽

Author(s):

Robert Qaqish ◽

Yui Watanabe ◽

Marcos Galasso ◽

Cara Summers ◽

A adil Ali ◽

...

Keyword(s):

Replacement Therapy ◽

Lung Lavage ◽

Post Injury ◽

Surfactant Replacement ◽

Recruitment Maneuvers ◽

Surfactant Replacement Therapy ◽

Dosing Strategies ◽

Yorkshire Pigs ◽

Saline Lavage ◽

Protective Systems

Abstract Background There are limited therapeutic options directed at the underlying pathological processes in acute respiratory distress syndrome (ARDS). Experimental therapeutic strategies have targeted the protective systems that become deranged in ARDS such as surfactant. Although results of surfactant replacement therapy (SRT) in ARDS have been mixed, questions remain incompletely answered regarding timing and dosing strategies of surfactant. Furthermore, there are only few truly clinically relevant ARDS models in the literature. The primary aim of our study was to create a clinically relevant, reproducible model of severe ARDS requiring extracorporeal membrane oxygenation (ECMO). Secondly, we sought to use this model as a platform to evaluate a bronchoscopic intervention that involved saline lavage and SRT. Methods Yorkshire pigs were tracheostomized and cannulated for veno-venous ECMO support, then subsequently given lung injury using gastric juice via bronchoscopy. Animals were randomized post-injury to either receive bronchoscopic saline lavage combined with SRT and recruitment maneuvers (treatment, n = 5) or recruitment maneuvers alone (control, n = 5) during ECMO. Results PaO2/FiO2 after aspiration injury was 62.6 ± 8 mmHg and 60.9 ± 9.6 mmHg in the control and treatment group, respectively (p = 0.95) satisfying criteria for severe ARDS. ECMO reversed the severe hypoxemia. After treatment with saline lavage and SRT during ECMO, lung physiologic and hemodynamic parameters were not significantly different between treatment and controls. Conclusions A clinically relevant severe ARDS pig model requiring ECMO was established. Bronchoscopic saline lavage and SRT during ECMO did not provide a significant physiologic benefit compared to controls.

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