We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Inhibitors of inflammation and endogenous surfactant pool size as modulators of lung injury with initiation of ventilation in preterm sheep.
- Authors
Hillman, Noah H.; Kallapur, Suhas G.; Pillow, J. Jane; Nitsos, Ilias; Polglase, Graeme R.; Ikegami, Machiko; Jobe, Alan H.
- Abstract
<bold>Background: </bold>Increased pro-inflammatory cytokines in tracheal aspirates correlate with the development of BPD in preterm infants. Ventilation of preterm lambs increases pro-inflammatory cytokines and causes lung inflammation.<bold>Objective: </bold>We tested the hypothesis that selective inhibitors of pro-inflammatory signaling would decrease lung inflammation induced by ventilation in preterm newborn lambs. We also examined if the variability in injury response was explained by variations in the endogenous surfactant pool size.<bold>Methods: </bold>Date-mated preterm lambs (n = 28) were operatively delivered and mechanically ventilated to cause lung injury (tidal volume escalation to 15 mL/kg by 15 min at age). The lambs then were ventilated with 8 mL/kg tidal volume for 1 h 45 min. Groups of animals randomly received specific inhibitors for IL-8, IL-1, or NF-κB. Unventilated lambs (n = 7) were the controls. Bronchoalveolar lavage fluid (BALF) and lung samples were used to quantify inflammation. Saturated phosphatidylcholine (Sat PC) was measured in BALF fluid and the data were stratified based on a level of 5 μmol/kg (~8 mg/kg surfactant).<bold>Results: </bold>The inhibitors did not decrease the cytokine levels or inflammatory response. The inflammation increased as Sat PC pool size in BALF decreased. Ventilated lambs with a Sat PC level > 5 μmol/kg had significantly decreased markers of injury and lung inflammation compared with those lambs with < 5 μmol/kg.<bold>Conclusion: </bold>Lung injury caused by high tidal volumes at birth were decreased when endogenous surfactant pool sizes were larger. Attempts to decrease inflammation by blocking IL-8, IL-1 or NF-κB were unsuccessful.
- Subjects
INFLAMMATION; CYTOKINES; PNEUMONIA; PREMATURE infants; LECITHIN; LUNG injury prevention; AGE distribution; ANIMAL experimentation; ANIMAL populations; ARTIFICIAL respiration; COMPARATIVE studies; INFLAMMATORY mediators; LUNG injuries; RESEARCH methodology; MEDICAL cooperation; NONSTEROIDAL anti-inflammatory agents; PULMONARY surfactant; PYRIDINE; RESEARCH; STATISTICAL sampling; SHEEP; EVALUATION research; PHARMACODYNAMICS
- Publication
Respiratory Research, 2010, Vol 11, p151
- ISSN
1465-9921
- Publication type
journal article
- DOI
10.1186/1465-9921-11-151