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Early biomarkers and potential mediators of ventilation-induced lung injury in very preterm lambs.

Wallace MJ, Probyn ME, Zahra VA, Crossley K, Cole TJ, Davis PG, Morley CJ, Hooper SB - Respir. Res. (2009)

Bottom Line: Bronchopulmonary dysplasia (BPD) is closely associated with ventilator-induced lung injury (VILI) in very preterm infants.VG5 and VG10 caused significant increases in CTGF, CYR61, EGR1, IL1- , IL-6 and IL-8 mRNA levels compared to control levels.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Physiology, Monash University, Victoria, Australia. megan.wallace@med.monash.edu.au

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.

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.

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.

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.

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Related in: MedlinePlus

IL-1β, -6 and -8 mRNA levels following injurious ventilation. IL-1β, IL-6 and IL-8 mRNA levels (mean ± SEM) in preterm lamb lungs at 132 days of gestation resuscitated at birth using an injurious ventilation (IV) strategy for 15 minutes, then ventilated gently for 15–120 minutes. Values are expressed as a fold change relative to values in unventilated age-matched control fetuses (T = 0 values). IL-6 and IL-8 mRNA levels were significantly higher than the levels in unventilated control fetuses (p < 0.05) at all timepoints after the IV period. IL-1β mRNA levels were significantly higher than the levels in unventilated control fetuses at 15, 30 and 60 minutes after the IV period.
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Figure 2: IL-1β, -6 and -8 mRNA levels following injurious ventilation. IL-1β, IL-6 and IL-8 mRNA levels (mean ± SEM) in preterm lamb lungs at 132 days of gestation resuscitated at birth using an injurious ventilation (IV) strategy for 15 minutes, then ventilated gently for 15–120 minutes. Values are expressed as a fold change relative to values in unventilated age-matched control fetuses (T = 0 values). IL-6 and IL-8 mRNA levels were significantly higher than the levels in unventilated control fetuses (p < 0.05) at all timepoints after the IV period. IL-1β mRNA levels were significantly higher than the levels in unventilated control fetuses at 15, 30 and 60 minutes after the IV period.

Mentions: IV induced a large and sustained increase in IL-1β, IL-6 and IL-8 mRNA levels; 28.3 ± 16.6, 25.6 ± 13.9 and 74.1 ± 20.4 fold increase respectively (p < 0.05), compared with pre-ventilation control values, within 15 mins of completing IV (Fig 2). Although IL-1β mRNA levels had returned to control levels at 120 mins after completion of the IV period, IL-6 and IL-8 mRNA levels remained significantly elevated (p < 0.05) at 11.0 ± 3.2 and 42.8 ± 11.3 fold, respectively, above pre-ventilation control values at this time (Fig 2).


Early biomarkers and potential mediators of ventilation-induced lung injury in very preterm lambs.

Wallace MJ, Probyn ME, Zahra VA, Crossley K, Cole TJ, Davis PG, Morley CJ, Hooper SB - Respir. Res. (2009)

IL-1β, -6 and -8 mRNA levels following injurious ventilation. IL-1β, IL-6 and IL-8 mRNA levels (mean ± SEM) in preterm lamb lungs at 132 days of gestation resuscitated at birth using an injurious ventilation (IV) strategy for 15 minutes, then ventilated gently for 15–120 minutes. Values are expressed as a fold change relative to values in unventilated age-matched control fetuses (T = 0 values). IL-6 and IL-8 mRNA levels were significantly higher than the levels in unventilated control fetuses (p < 0.05) at all timepoints after the IV period. IL-1β mRNA levels were significantly higher than the levels in unventilated control fetuses at 15, 30 and 60 minutes after the IV period.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2662809&req=5

Figure 2: IL-1β, -6 and -8 mRNA levels following injurious ventilation. IL-1β, IL-6 and IL-8 mRNA levels (mean ± SEM) in preterm lamb lungs at 132 days of gestation resuscitated at birth using an injurious ventilation (IV) strategy for 15 minutes, then ventilated gently for 15–120 minutes. Values are expressed as a fold change relative to values in unventilated age-matched control fetuses (T = 0 values). IL-6 and IL-8 mRNA levels were significantly higher than the levels in unventilated control fetuses (p < 0.05) at all timepoints after the IV period. IL-1β mRNA levels were significantly higher than the levels in unventilated control fetuses at 15, 30 and 60 minutes after the IV period.
Mentions: IV induced a large and sustained increase in IL-1β, IL-6 and IL-8 mRNA levels; 28.3 ± 16.6, 25.6 ± 13.9 and 74.1 ± 20.4 fold increase respectively (p < 0.05), compared with pre-ventilation control values, within 15 mins of completing IV (Fig 2). Although IL-1β mRNA levels had returned to control levels at 120 mins after completion of the IV period, IL-6 and IL-8 mRNA levels remained significantly elevated (p < 0.05) at 11.0 ± 3.2 and 42.8 ± 11.3 fold, respectively, above pre-ventilation control values at this time (Fig 2).

Bottom Line: Bronchopulmonary dysplasia (BPD) is closely associated with ventilator-induced lung injury (VILI) in very preterm infants.VG5 and VG10 caused significant increases in CTGF, CYR61, EGR1, IL1- , IL-6 and IL-8 mRNA levels compared to control levels.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Physiology, Monash University, Victoria, Australia. megan.wallace@med.monash.edu.au

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.

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.

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.

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.

Show MeSH
Related in: MedlinePlus