Ritchie Centre, Monash Institute of Medical Research, Monash University, Clayton, Victoria, Australia.
J Appl Physiol (1985). 2012 Feb;112(3):481-9. doi: 10.1152/japplphysiol.00995.2011. Epub 2011 Nov 3.
Cerebral blood flow disturbance is a major contributor to brain injury in the preterm infant. The initiation of ventilation may be a critical time for cerebral hemodynamic disturbance leading to brain injury in preterm infants, particularly if they are exposed to inflammation in utero. We aimed to determine whether exposure to inflammation in utero alters cardiopulmonary hemodynamics, resulting in cerebral hemodynamic disturbance and related brain injury during the initiation of ventilation. Furthermore, we aimed to determine whether inflammation in utero alters the cerebral hemodynamic response to challenge induced by high mean airway pressures. Pregnant ewes received intra-amniotic lipopolysaccharide (LPS) or saline either 2 or 4-days before preterm delivery (at 128 ± 1 days of gestation). Lambs were surgically instrumented for assessment of pulmonary and cerebral hemodynamics before delivery and positive pressure ventilation. After 30 min, lambs were challenged hemodynamically by incrementing and decrementing positive end-expiratory pressure. Blood gases, arterial pressures, and blood flows were recorded. The brain was collected for biochemical and histological assessment of inflammation, brain damage, vascular extravasation, hemorrhage, and oxidative injury. Carotid arterial pressure was higher and carotid blood flow was more variable in 2-day LPS lambs than in controls during the initial 15 min of ventilation. All lambs responded similarly to the hemodynamic challenge. Both 2- and 4-day LPS lambs had increased brain interleukin (IL)-1β, IL-6, and IL-8 mRNA expression; increased number of inflammatory cells in the white matter; increased incidence and severity of brain damage; and vascular extravasation relative to controls. Microvascular hemorrhage was increased in 2-day LPS lambs compared with controls. Cerebral oxidative injury was not different between groups. Antenatal inflammation causes adverse cerebral hemodynamics and increases the incidence and severity of brain injury in ventilated preterm lambs.
脑血流紊乱是早产儿脑损伤的主要原因。通气的开始可能是导致早产儿脑血流紊乱和相关脑损伤的关键时期，特别是如果他们在子宫内暴露于炎症的情况下。我们旨在确定宫内炎症是否会改变心肺血液动力学，导致通气开始时的脑血流紊乱和相关脑损伤。此外，我们旨在确定宫内炎症是否会改变大脑对高平均气道压力引起的挑战的血液动力学反应。在早产（妊娠 128±1 天）前 2 或 4 天，给怀孕的母羊注射羊膜内脂多糖（LPS）或盐水。在分娩前和正压通气时，对羔羊进行肺部和脑部血液动力学评估。30 分钟后，通过增加和减少呼气末正压来对羔羊进行血液动力学挑战。记录血气、动脉压和血流。收集大脑用于炎症、脑损伤、血管外渗、出血和氧化损伤的生化和组织学评估。与对照组相比，在通气的最初 15 分钟内，2 天 LPS 组的颈动脉压更高，颈动脉血流更不稳定。所有羔羊对血液动力学挑战的反应相似。与对照组相比，2 天和 4 天 LPS 组的脑白细胞介素（IL）-1β、IL-6 和 IL-8mRNA 表达增加；白质中炎性细胞数量增加；脑损伤的发生率和严重程度增加；血管外渗增加。与对照组相比，2 天 LPS 组的微血管出血增加。脑氧化损伤在各组之间没有差异。产前炎症导致早产儿通气时出现不良的脑血流动力学，并增加脑损伤的发生率和严重程度。
