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

Wallace, Megan Jane; Probyn, Megan Elizabeth; Zahra, Valerie; Crossley, Kelly J.; Cole, Timothy J.; Davis, Peter G; Morley, Colin J; Hooper, Stuart B.

doi:10.1186/1465-9921-10-19

Cited by 109 publications

(126 citation statements)

References 51 publications

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“…Previous premature newborn animal studies used to assess lung injury during resuscitation were ventilated with a target VT of more than 15 ml/kg (19,24,31). In clinical practice, resuscitation of manually ventilated premature newborns is often performed by observing chest wall movement without monitoring VT.…”

Section: Discussionmentioning

confidence: 99%

Surfactant Protein-D Inhibits Lung Inflammation Caused by Ventilation in Premature Newborn Lambs

Sato¹,

Whitsett²,

Scheule³

et al. 2010

Am J Respir Crit Care Med

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Rationale: Premature newborns frequently require manual ventilation for resuscitation during which lung injury occurs. Although surfactant protein (SP)-D regulates pulmonary inflammation, SP-D levels are low in the preterm lung. Commercial surfactants for treatment of respiratory distress syndrome do not contain SP-D. Objectives: To determine whether addition of recombinant human SP-D (rhSP-D) to commercial surfactant influences lung inflammation in ventilated premature newborn lambs. Methods: Prematurely delivered lambs (130 d gestation age) were resuscitated with 100% O 2 and peak inspiratory pressure 40 cm H 2 O for 20 minutes and then treated with Survanta or Survanta containing rhSP-D. Ventilation was then changed to regulate tidal volume at 8 to 9 ml/kg. At 5 hours of age lambs were killed for sample collection. Measurements and Main Results: Sequential blood gas and tidal volume were similar in lambs treated with or without rhSP-D, indicating that lung immaturity and ventilatory stress used to support premature lambs were comparable between the two groups. Ventilation caused pulmonary inflammation in lambs treated with surfactant alone. In contrast, surfactant containing rhSP-D decreased neutrophil numbers in bronchoalveolar lavage fluid and decreased neutrophil elastase activity in lung tissue. IL-8 mRNA and IL-8 protein were significantly decreased in the 1rhSP-D group lamb lungs, to 20% of those in controls. The addition of rhSP-D also rendered Survanta more resistant to plasma protein inhibition of surfactant function. Conclusions: Treatment with rhSP-D-containing surfactant inhibited lung inflammation and enhanced the resistance of surfactant to inhibition, supporting its potential usefulness for prevention of lung injury in the preterm newborn.

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Section: Discussionmentioning

confidence: 99%

Surfactant Protein-D Inhibits Lung Inflammation Caused by Ventilation in Premature Newborn Lambs

Sato¹,

Whitsett²,

Scheule³

et al. 2010

Am J Respir Crit Care Med

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“…It is possible the transient rerecruitment to 20 cmH 2 O was not needed. These may have influenced the results as even brief period of injurious ventilation can initiate injury pathways (10,28). Future studies of SEP at birth should explore titrating both optimal and maximum PEEP to the C dyn response.…”

Section: Articlesmentioning

confidence: 99%

“…Lung tissue samples were taken from the right lower lobe and immediately frozen in liquid nitrogen for quantitative real-time PCR analysis of early biomarkers of lung injury; CTGF, CYR61, EGR1, IL-1β, IL-6 and IL-8 mRNA as described previously (28). Quantitative real-time PCR results were analyzed using the 2 −ΔΔCT method (28).…”

Section: Lung Injury Analysismentioning

confidence: 99%

Effect of sustained inflation vs. stepwise PEEP strategy at birth on gas exchange and lung mechanics in preterm lambs

et al. 2013

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Background: Sustained inflation (SI) at birth facilitates establishment of functional residual capacity (FRC) in the preterm lung, but the ideal lung recruitment strategy is unclear. We have compared the effect of SI and a stepwise positive endexpiratory pressure (PEEP; SEP) strategy in a preterm model. Methods: 127 d gestation lambs received either 20-s SI (n = 9) or 2 cmH 2 O stepwise PEEP increases to 20 cmH 2 O every 10 inflations, and then decreases to 6 cmH 2 O (n = 10). Ventilation continued for 70 min, with surfactant administered at 10 min. Alveolar-arterial oxygen gradient (AaDO 2 ), compliance (C dyn ), end-expiratory thoracic volume (EEV RIP ; respiratory inductive plethysmography), and EEV and C dyn in the gravitydependent and nondependent hemithoraces (electrical impedance tomography) were measured throughout. Early mRNA markers of lung injury were analyzed using quantitative real-time PCR. results: From 15 min of life, AaDO2 was lower in SEP group (P < 0.005; two-way ANOVA). SEP resulted in higher and more homogeneous C dyn (P < 0.0001). Mean (SD) EEV RIP at 5 min was 18 (9) ml/kg and 6 (5) ml/kg following SEP and SI, respectively (P = 0.021; Bonferroni posttest); this difference was due to a greater nondependent hemithorax EEV. There was no difference in markers of lung injury. conclusion: An SEP at birth improved gas exchange, lung mechanics, and EEV, without increasing lung injury, compared to the SI strategy used.

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“…As fluid is cleared from the airways, initial breaths may distend the airway and cause injury (2). Egr-1 protein activated as early as 15 min after ventilation in preterm sheep (38) and has been localized to the cells surrounding the airways when ventilation is initiated in fetal sheep (27). Ureaplasma colonization tends to decrease Egr-1 protein signaling when animals are ventilated, but even small increases in this transcription factor can lead to activation of the inflammatory cascade.…”

Section: Table 2 Markers Of Lung Inflammation and Injurymentioning

confidence: 99%

Ventilation-Mediated Injury After Preterm Delivery of Ureaplasma parvum Colonized Fetal Lambs

et al. 2010

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Ureaplasma species are the microorganisms most frequently isolated from women with preterm birth and are associated with an increased risk of bronchopulmonary dysplasia. Initiation of ventilation with high tidal volumes (V T ) causes lung injury and inflammation. We investigated whether antenatal colonization with Ureaplasma parvum serovar 3 (UP) would alter the inflammatory response to mechanical ventilation of preterm lambs. Merino ewes were given intraamniotic injections of UP at 55-d gestation, and the lambs were surgically delivered at 128 Ϯ 1 d gestation and assigned to three groups: 1) gentle ventilation (GV), 2) high V T ventilation, or 3) unventilated control. Lambs delivered from noncolonized ewes were assigned to parallel groups. GV lambs received surfactant before ventilation with a V T of 7 mL/kg, positive end expiratory pressure (PEEP) 5 cm H 2 O . High V T lambs received no PEEP and escalating V T to 15 mL/kg by 15 min. At 15 min, surfactant was given, V T was reduced to 7 mL/kg, and PEEP was increased to 5 cm H 2 O. Monocytes in bronchoalveolar lavage were increased by UP, but colonization did not affect lung function. High V T ventilation increased Egr-1 signaling, proinflammatory cytokine expression, and injury scores compared with GV. Antenatal colonization with UP did not change lung function or modulate the lung injury and inflammation caused by high V T ventilation. (Pediatr Res 67: 630-635, 2010)

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

Cited by 109 publications

References 51 publications

Surfactant Protein-D Inhibits Lung Inflammation Caused by Ventilation in Premature Newborn Lambs

Surfactant Protein-D Inhibits Lung Inflammation Caused by Ventilation in Premature Newborn Lambs

Effect of sustained inflation vs. stepwise PEEP strategy at birth on gas exchange and lung mechanics in preterm lambs

Ventilation-Mediated Injury After Preterm Delivery of Ureaplasma parvum Colonized Fetal Lambs

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