Article ; Online: Lucinactant attenuates pulmonary inflammatory response, preserves lung structure, and improves physiologic outcomes in a preterm lamb model of RDS.
2012 Volume 72, Issue 4, Page(s) 375–383
Abstract: ... may modulate lung inflammatory response to mechanical ventilation in the management of RDS and may confer ... without significant difference between SRT groups. Lucinactant attenuated lung and systemic inflammatory response ... Gas exchange and pulmonary function were assessed serially. Lung inflammation biomarkers and lung histology ...
| Abstract | Background: Acute inflammatory responses to supplemental oxygen and mechanical ventilation have been implicated in the pathophysiological sequelae of respiratory distress syndrome (RDS). Although surfactant replacement therapy (SRT) has contributed to lung stability, the effect on lung inflammation is inconclusive. Lucinactant contains sinapultide (KL4), a novel synthetic peptide that functionally mimics surfactant protein B, a protein with anti-inflammatory properties. We tested the hypothesis that lucinactant may modulate lung inflammatory response to mechanical ventilation in the management of RDS and may confer greater protection than animal-derived surfactants. Methods: Preterm lambs (126.8 ± 0.2 SD d gestation) were randomized to receive lucinactant, poractant alfa, beractant, or no surfactant and studied for 4 h. Gas exchange and pulmonary function were assessed serially. Lung inflammation biomarkers and lung histology were assessed at termination. Results: SRT improved lung compliance relative to no SRT without significant difference between SRT groups. Lucinactant attenuated lung and systemic inflammatory response, supported oxygenation at lower ventilatory requirements, and preserved lung structural integrity to a greater degree than either no SRT or SRT with poractant alfa or beractant. Conclusion: These data suggest that early intervention with lucinactant may more effectively mitigate pulmonary pathophysiological sequelae of RDS than the animal-derived surfactants poractant alfa or beractant. |
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| MeSH term(s) | Animals ; Anti-Inflammatory Agents/pharmacology ; Biological Products/pharmacology ; Biomarkers/metabolism ; Disease Models, Animal ; Drug Combinations ; Fatty Alcohols/pharmacology ; Gestational Age ; Inflammation Mediators/metabolism ; Lung/drug effects ; Lung/immunology ; Lung/pathology ; Lung/physiopathology ; Lung Compliance/drug effects ; Phosphatidylglycerols/pharmacology ; Phospholipids/pharmacology ; Pneumonia/immunology ; Pneumonia/pathology ; Pneumonia/physiopathology ; Pneumonia/prevention & control ; Proteins/pharmacology ; Pulmonary Gas Exchange/drug effects ; Pulmonary Surfactants/pharmacology ; Respiration, Artificial/adverse effects ; Respiratory Distress Syndrome, Newborn/immunology ; Respiratory Distress Syndrome, Newborn/pathology ; Respiratory Distress Syndrome, Newborn/physiopathology ; Respiratory Distress Syndrome, Newborn/therapy ; Sheep ; Time Factors ; Ventilator-Induced Lung Injury/immunology ; Ventilator-Induced Lung Injury/pathology ; Ventilator-Induced Lung Injury/physiopathology | ||||||||||
| Chemical Substances | Anti-Inflammatory Agents ; Biological Products ; Biomarkers ; Drug Combinations ; Fatty Alcohols ; Inflammation Mediators ; Phosphatidylglycerols ; Phospholipids ; Proteins ; Pulmonary Surfactants ; lucinactant ; poractant alfa (KE3U2023NP) ; beractant (S866O45PIG) | ||||||||||
| Language | English | ||||||||||
| Publishing date | 2012-07-20 | ||||||||||
| Publishing country | United States | ||||||||||
| Document type | Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. | ||||||||||
| ZDB-ID | 4411-8 | ||||||||||
| ISSN | 1530-0447 ; 0031-3998 | ||||||||||
| ISSN (online) | 1530-0447 | ||||||||||
| ISSN | 0031-3998 | ||||||||||
| DOI | 10.1038/pr.2012.96 | ||||||||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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