Back to Search
Start Over
Early biomarkers and potential mediators of ventilation-induced lung injury in very preterm lambs.
- Source :
-
Respiratory research [Respir Res] 2009 Mar 10; Vol. 10, pp. 19. Date of Electronic Publication: 2009 Mar 10. - Publication Year :
- 2009
-
Abstract
- Background: Bronchopulmonary dysplasia (BPD) is closely associated with ventilator-induced lung injury (VILI) in very preterm infants. The greatest risk of VILI may be in the immediate period after birth, when the lungs are surfactant deficient, still partially filled with liquid and not uniformly aerated. However, there have been very few studies that have examined this immediate post-birth period and identified the initial injury-related pathways that are activated. We aimed to determine if the early response genes; connective tissue growth factor (CTGF), cysteine rich-61 (CYR61) and early growth response 1 (EGR1), were rapidly induced by VILI in preterm lambs and whether ventilation with different tidal volumes caused different inflammatory cytokine and early response gene expression.<br />Methods: To identify early markers of VILI, preterm lambs (132 d gestational age; GA, term approximately 147 d) were resuscitated with an injurious ventilation strategy (V(T) 20 mL/kg for 15 min) then gently ventilated (5 mL/kg) for 15, 30, 60 or 120 min (n = 4 in each). To determine if early response genes and inflammatory cytokines were differentially regulated by different ventilation strategies, separate groups of preterm lambs (125 d GA; n = 5 in each) were ventilated from birth with a V(T) of 5 (VG5) or 10 mL/kg (VG10) for 135 minutes. Lung gene expression levels were compared to levels prior to ventilation in age-matched control fetuses.<br />Results: CTGF, CYR61 and EGR1 lung mRNA levels were increased approximately 25, 50 and 120-fold respectively (p < 0.05), within 30 minutes of injurious ventilation. VG5 and VG10 caused significant increases in CTGF, CYR61, EGR1, IL1- , IL-6 and IL-8 mRNA levels compared to control levels. CTGF, CYR61, IL-6 and IL-8 expression levels were higher in VG10 than VG5 lambs; although only the IL-6 and CYR61 mRNA levels reached significance.<br />Conclusion: CTGF, CYR61 and EGR1 may be novel early markers of lung injury and mechanical ventilation from birth using relatively low tidal volumes may be less injurious than using higher tidal volumes.
- Subjects :
- Animals
Animals, Newborn
Connective Tissue Growth Factor genetics
Cysteine-Rich Protein 61 genetics
Disease Models, Animal
Early Growth Response Protein 1 genetics
Genetic Markers
Gestational Age
Interleukins genetics
Lung physiopathology
RNA, Messenger metabolism
Respiration, Artificial methods
Sheep
Tidal Volume
Time Factors
Up-Regulation
Ventilator-Induced Lung Injury etiology
Ventilator-Induced Lung Injury prevention & control
Lung metabolism
Premature Birth
Respiration, Artificial adverse effects
Ventilator-Induced Lung Injury genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1465-993X
- Volume :
- 10
- Database :
- MEDLINE
- Journal :
- Respiratory research
- Publication Type :
- Academic Journal
- Accession number :
- 19284536
- Full Text :
- https://doi.org/10.1186/1465-9921-10-19