Ineffective aeration during the first inflations at birth creates regional aeration and ventilation defects, initiating injurious pathways. This study aimed to compare a sustained first inflation at birth or dynamic end-expiratory supported recruitment during tidal inflations against ventilation without intentional recruitment on gas exchange, lung mechanics, spatiotemporal regional aeration and tidal ventilation, and regional lung injury in preterm lambs. Lambs (127 ± 2 d gestation), instrumented at birth, were ventilated for 60 minutes from birth with either lung-protective positive pressure ventilation (control) or as per control after either an initial 30 seconds of 40 cm H2O sustained inflation (SI) or an initial stepwise end-expiratory pressure recruitment maneuver during tidal inflations (duration 180 s; open lung ventilation [OLV]). At study completion, molecular markers of lung injury were analyzed. The initial use of an OLV maneuver, but not SI, at birth resulted in improved lung compliance, oxygenation, end-expiratory lung volume, and reduced ventilatory needs compared with control, persisting throughout the study. These changes were due to more uniform inter- and intrasubject gravity-dependent spatiotemporal patterns of aeration (measured using electrical impedance tomography). Spatial distribution of tidal ventilation was more stable after either recruitment maneuver. All strategies caused regional lung injury patterns that mirrored associated regional volume states. Irrespective of strategy, spatiotemporal volume loss was consistently associated with up-regulation of early growth response-1 expression. Our results show that mechanical and molecular consequences of lung aeration at birth are not simply related to rapidity of fluid clearance; they are also related to spatiotemporal pressure-volume interactions within the lung during inflation and deflation.

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.

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.