Abstract
BackgroundThe onset of mechanical ventilation is a critical time for the initiation of cerebral white matter (WM) injury in preterm neonates, particularly if they are inadvertently exposed to high tidal volumes (VT) in the delivery room. Protective ventilation strategies at birth reduce ventilation-induced lung and brain inflammation and injury, however its efficacy in a compromised newborn is not known. Chorioamnionitis is a common antecedent of preterm birth, and increases the risk and severity of WM injury. We investigated the effects of high VT ventilation, after chorioamnionitis, on preterm lung and WM inflammation and injury, and whether a protective ventilation strategy could mitigate the response.MethodsPregnant ewes (n = 18) received intra-amniotic lipopolysaccharide (LPS) 2 days before delivery, instrumentation and ventilation at 127±1 days gestation. Lambs were either immediately euthanased and used as unventilated controls (LPSUVC; n = 6), or were ventilated using an injurious high VT strategy (LPSINJ; n = 5) or a protective ventilation strategy (LPSPROT; n = 7) for a total of 90 min. Mean arterial pressure, heart rate and cerebral haemodynamics and oxygenation were measured continuously. Lungs and brains underwent molecular and histological assessment of inflammation and injury.ResultsLPSINJ lambs had poorer oxygenation than LPSPROT lambs. Ventilation requirements and cardiopulmonary and systemic haemodynamics were not different between ventilation strategies. Compared to unventilated lambs, LPSINJ and LPSPROT lambs had increases in pro-inflammatory cytokine expression within the lungs and brain, and increased astrogliosis (p<0.02) and cell death (p<0.05) in the WM, which were equivalent in magnitude between groups.ConclusionsVentilation after acute chorioamnionitis, irrespective of strategy used, increases haemodynamic instability and lung and cerebral inflammation and injury. Mechanical ventilation is a potential contributor to WM injury in infants exposed to chorioamnionitis.
Highlights
Cerebral white matter (WM) injury is common in preterm infants, and can result from a multitude of insults during pregnancy and after birth [1]
The major mechanisms leading to ventilation-induced brain injury include: 1) altered pulmonary blood flow, leading to adverse cardiac output and consequent abnormal changes to cerebral blood flow [2] and 2) the initiation of a profound pulmonary inflammatory response [7,8,9] that initiates a systemic inflammatory cascade [10,11,12] resulting in a localized inflammatory response within the cerebral WM [2,13]
Oxygenation index was higher in LPSINJ lambs compared to LPSPROT lambs at 10 and 15 min (p = 0.09; Fig. 1F) but was not different thereafter
Summary
Cerebral white matter (WM) injury is common in preterm infants, and can result from a multitude of insults during pregnancy and after birth [1]. The major mechanisms leading to ventilation-induced brain injury include: 1) altered pulmonary blood flow, leading to adverse cardiac output and consequent abnormal changes to cerebral blood flow [2] and 2) the initiation of a profound pulmonary inflammatory response [7,8,9] that initiates a systemic inflammatory cascade [10,11,12] resulting in a localized inflammatory response within the cerebral WM [2,13] These mechanisms are consistent with previously identified pathways of brain injury in preterm infants [14]. The onset of mechanical ventilation is a critical time for the initiation of cerebral white matter (WM) injury in preterm neonates, if they are inadvertently exposed to high tidal volumes (VT) in the delivery room. We investigated the effects of high VT ventilation, after chorioamnionitis, on preterm lung and WM inflammation and injury, and whether a protective ventilation strategy could mitigate the response
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