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SP-B and SP-C Containing New Synthetic Surfactant for Treatment of Extremely Immature Lamb Lung

Although superiority of synthetic surfactant over animal-driven surfactant has been known, there is no synthetic surfactant commercially available at present. Many trials have been made to develop synthetic surfactant comparable in function to animal-driven surfactant. The efficacy of treatment with...

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Autores principales: Sato, Atsuyasu, Ikegami, Machiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3396642/
https://www.ncbi.nlm.nih.gov/pubmed/22808033
http://dx.doi.org/10.1371/journal.pone.0039392
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author Sato, Atsuyasu
Ikegami, Machiko
author_facet Sato, Atsuyasu
Ikegami, Machiko
author_sort Sato, Atsuyasu
collection PubMed
description Although superiority of synthetic surfactant over animal-driven surfactant has been known, there is no synthetic surfactant commercially available at present. Many trials have been made to develop synthetic surfactant comparable in function to animal-driven surfactant. The efficacy of treatment with a new synthetic surfactant (CHF5633) containing dipalmitoylphosphatidylcholine, phosphatidylglycerol, SP-B analog, and SP-C analog was evaluated using immature newborn lamb model and compared with animal lung tissue-based surfactant Survanta. Lambs were treated with a clinical dose of 200 mg/kg CHF5633, 100 mg/kg Survanta, or air after 15 min initial ventilation. All the lambs treated with air died of respiratory distress within 90 min of age. During a 5 h study period, Pco(2) was maintained at 55 mmHg with 24 cmH(2)O peak inspiratory pressure for both groups. The preterm newborn lamb lung functions were dramatically improved by CHF5633 treatment. Slight, but significant superiority of CHF5633 over Survanta was demonstrated in tidal volume at 20 min and dynamic lung compliance at 20 and 300 min. The ultrastructure of CHF5633 was large with uniquely aggregated lipid particles. Increased uptake of CHF5633 by alveolar monocytes for catabolism was demonstrated by microphotograph, which might be associated with the higher treatment dose of CHF5633. The higher catabolism of CHF5633 was also suggested by the similar amount of surfactant lipid in bronchoalveolar lavage fluid (BALF) between CHF5633 and Survanta groups, despite the 2-fold higher treatment dose of CHF5633. Under the present ventilation protocol, lung inflammation was minimal for both groups, evaluated by inflammatory cell numbers in BALF and expression of IL-1β, IL-6, IL-8, and TNFα mRNA in the lung tissue. In conclusion, the new synthetic surfactant CHF5633 was effective in treating extremely immature newborn lambs with surfactant deficiency during the 5 h study period.
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spelling pubmed-33966422012-07-17 SP-B and SP-C Containing New Synthetic Surfactant for Treatment of Extremely Immature Lamb Lung Sato, Atsuyasu Ikegami, Machiko PLoS One Research Article Although superiority of synthetic surfactant over animal-driven surfactant has been known, there is no synthetic surfactant commercially available at present. Many trials have been made to develop synthetic surfactant comparable in function to animal-driven surfactant. The efficacy of treatment with a new synthetic surfactant (CHF5633) containing dipalmitoylphosphatidylcholine, phosphatidylglycerol, SP-B analog, and SP-C analog was evaluated using immature newborn lamb model and compared with animal lung tissue-based surfactant Survanta. Lambs were treated with a clinical dose of 200 mg/kg CHF5633, 100 mg/kg Survanta, or air after 15 min initial ventilation. All the lambs treated with air died of respiratory distress within 90 min of age. During a 5 h study period, Pco(2) was maintained at 55 mmHg with 24 cmH(2)O peak inspiratory pressure for both groups. The preterm newborn lamb lung functions were dramatically improved by CHF5633 treatment. Slight, but significant superiority of CHF5633 over Survanta was demonstrated in tidal volume at 20 min and dynamic lung compliance at 20 and 300 min. The ultrastructure of CHF5633 was large with uniquely aggregated lipid particles. Increased uptake of CHF5633 by alveolar monocytes for catabolism was demonstrated by microphotograph, which might be associated with the higher treatment dose of CHF5633. The higher catabolism of CHF5633 was also suggested by the similar amount of surfactant lipid in bronchoalveolar lavage fluid (BALF) between CHF5633 and Survanta groups, despite the 2-fold higher treatment dose of CHF5633. Under the present ventilation protocol, lung inflammation was minimal for both groups, evaluated by inflammatory cell numbers in BALF and expression of IL-1β, IL-6, IL-8, and TNFα mRNA in the lung tissue. In conclusion, the new synthetic surfactant CHF5633 was effective in treating extremely immature newborn lambs with surfactant deficiency during the 5 h study period. Public Library of Science 2012-07-13 /pmc/articles/PMC3396642/ /pubmed/22808033 http://dx.doi.org/10.1371/journal.pone.0039392 Text en Sato, Ikegami. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Sato, Atsuyasu
Ikegami, Machiko
SP-B and SP-C Containing New Synthetic Surfactant for Treatment of Extremely Immature Lamb Lung
title SP-B and SP-C Containing New Synthetic Surfactant for Treatment of Extremely Immature Lamb Lung
title_full SP-B and SP-C Containing New Synthetic Surfactant for Treatment of Extremely Immature Lamb Lung
title_fullStr SP-B and SP-C Containing New Synthetic Surfactant for Treatment of Extremely Immature Lamb Lung
title_full_unstemmed SP-B and SP-C Containing New Synthetic Surfactant for Treatment of Extremely Immature Lamb Lung
title_short SP-B and SP-C Containing New Synthetic Surfactant for Treatment of Extremely Immature Lamb Lung
title_sort sp-b and sp-c containing new synthetic surfactant for treatment of extremely immature lamb lung
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3396642/
https://www.ncbi.nlm.nih.gov/pubmed/22808033
http://dx.doi.org/10.1371/journal.pone.0039392
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