Cincinnati Children's Hospital Medical Center, Division of Pulmonary Biology, Cincinnati, OH 45236, USA.
Respir Res. 2009 Dec 15;10(1):124. doi: 10.1186/1465-9921-10-124.
Initiation of ventilation using high tidal volumes in preterm lambs causes lung injury and inflammation. Antenatal corticosteroids mature the lungs of preterm infants and postnatal corticosteroids are used to treat bronchopulmonary dysplasia.
To test if antenatal or postnatal corticosteroids would decrease resuscitation induced lung injury.
129 d gestational age lambs (n = 5-8/gp; term = 150 d) were operatively delivered and ventilated after exposure to either 1) no medication, 2) antenatal maternal IM Betamethasone 0.5 mg/kg 24 h prior to delivery, 3) 0.5 mg/kg Dexamethasone IV at delivery or 4) Cortisol 2 mg/kg IV at delivery. Lambs then were ventilated with no PEEP and escalating tidal volumes (VT) to 15 mL/kg for 15 min and then given surfactant. The lambs were ventilated with VT 8 mL/kg and PEEP 5 cmH20 for 2 h 45 min.
High VT ventilation caused a deterioration of lung physiology, lung inflammation and injury. Antenatal betamethasone improved ventilation, decreased inflammatory cytokine mRNA expression and alveolar protein leak, but did not prevent neutrophil influx. Postnatal dexamethasone decreased pro-inflammatory cytokine expression, but had no beneficial effect on ventilation, and postnatal cortisol had no effect. Ventilation increased liver serum amyloid mRNA expression, which was unaffected by corticosteroids.
Antenatal betamethasone decreased lung injury without decreasing lung inflammatory cells or systemic acute phase responses. Postnatal dexamethasone or cortisol, at the doses tested, did not have important effects on lung function or injury, suggesting that corticosteroids given at birth will not decrease resuscitation mediated injury.
在早产儿羊中使用大潮气量启动通气会导致肺损伤和炎症。产前皮质类固醇使早产儿的肺部成熟，而产后皮质类固醇则用于治疗支气管肺发育不良。
测试产前或产后皮质类固醇是否会减少复苏引起的肺损伤。
129 天胎龄的羔羊（n=5-8/组；足月=150 天）在手术分娩后进行通气，然后暴露于以下情况之一：1）不给予药物，2）分娩前 24 小时 IM 倍他米松 0.5 mg/kg，3）分娩时给予 0.5 mg/kg 地塞米松 IV，或 4）分娩时给予 2 mg/kg IV 氢化可的松。然后，羔羊在没有 PEEP 的情况下进行通气，潮气量（VT）逐渐增加至 15 mL/kg，持续 15 分钟，然后给予表面活性剂。羔羊以 8 mL/kg 的 VT 和 5 cmH20 的 PEEP 通气 2 小时 45 分钟。
大潮气量通气导致肺生理功能恶化、肺炎症和损伤。产前倍他米松改善了通气，减少了促炎细胞因子 mRNA 表达和肺泡蛋白渗漏，但不能防止中性粒细胞浸润。产后地塞米松降低了促炎细胞因子的表达，但对通气没有有益作用，产后皮质醇没有作用。通气增加了肝脏血清淀粉样蛋白 mRNA 的表达，皮质类固醇对此没有影响。
产前倍他米松减少了肺损伤，而不减少肺炎症细胞或全身急性期反应。在测试剂量下，产后地塞米松或皮质醇对肺功能或损伤没有重要影响，提示出生时给予皮质类固醇不会减少复苏介导的损伤。
