The synergistic effects of mechanical ventilation and intrauterine inflammation on cerebral inflammation in preterm fetal sheep.

Background: Intrauterine inflammation and the requirement for mechanical ventilation independently increase the risk of perinatal brain injury and adverse neurodevelopmental outcomes. We aimed to investigate the effects of mechanical ventilation for 24 h, with and without prior exposure to intrauterine inflammation, on markers of brain inflammation and injury in the preterm sheep brain.

Methods: Chronically instrumented fetal sheep at ~115 days of gestation were randomly allocated to receive a single intratracheal dose of 1 mg lipopolysaccharide (LPS) or isovolumetric saline, then further randomly allocated 1 h after to receive mechanical ventilation with room air or no mechanical ventilation (unventilated control + saline [UVC,  = 7]; mechanical ventilation + saline [VENT,  = 8], unventilated control + intratracheal LPS [UVC + LPS,  = 7]; ventilation + intratracheal LPS [VENT + LPS,  = 7]).

Respiratory Support of the Preterm Neonate: Lessons About Ventilation-Induced Brain Injury From Large Animal Models.

Many preterm neonates require mechanical ventilation which increases the risk of cerebral inflammation and white matter injury in the immature brain. In this review, we discuss the links between ventilation and brain injury with a focus on the immediate period after birth, incorporating respiratory support in the delivery room and subsequent mechanical ventilation in the neonatal intensive care unit. This review collates insight from large animal models in which acute injurious ventilation and prolonged periods of ventilation have been used to create clinically relevant brain injury patterns.

Umbilical Cord Blood Cells Do Not Reduce Ventilation-Induced Lung Injury in Preterm Lambs.

Background: Preterm infants often have immature lungs and, consequently, many require respiratory support at birth. However, respiratory support causes lung inflammation and injury, termed ventilation-induced lung injury (VILI). Umbilical cord blood (UCB) contains five cell types that have been shown to reduce inflammation and injury.

Dose-dependent exacerbation of ventilation-induced lung injury by erythropoietin in preterm newborn lambs.

Erythropoietin (EPO) is being trialled in preterm infants to reduce brain injury, but high doses increase lung injury in ventilated preterm lambs. We aimed to determine whether early administration of lower doses of EPO could reduce ventilation-induced lung injury and systemic inflammation in preterm lambs. Ventilation was initiated in anaesthetized preterm lambs [125 ± 1 (SD) days gestation] using an injurious strategy for the first 15 min.

Diffusion tensor imaging detects ventilation-induced brain injury in preterm lambs.

Purpose: Injurious mechanical ventilation causes white matter (WM) injury in preterm infants through inflammatory and haemodynamic pathways. The relative contribution of each of these pathways is not known. We hypothesised that in vivo magnetic resonance imaging (MRI) can detect WM brain injury resulting from mechanical ventilation 24 h after preterm delivery.

Optimizing the Dose of Erythropoietin Required to Prevent Acute Ventilation-Induced Cerebral White Matter Injury in Preterm Lambs.

Erythropoietin (EPO) is being trialed in preterm neonates for neuroprotection. We have recently demonstrated that a single high bolus dose (5,000 IU/kg) of recombinant human EPO amplified preterm lung and brain ventilation-induced injury. We aimed to determine the optimal dose of EPO to reduce ventilation-induced cerebral white matter inflammation and injury in preterm lambs.