Karzai Waheedullah, Cui Xizhong, Heinicke Norbert, Niemann Christian, Gerstenberger Eric P, Correa Rosaly, Banks Steven, Mehlhorn Bjoern, Bloos Frank, Reinhart Konrad, Eichacker Peter Q
Department of Anesthesiology and Critical Care Medicine, Friedrich-Schiller-University Hospital, Jena, Germany.
Anesthesiology. 2005 Nov;103(5):996-1005. doi: 10.1097/00000542-200511000-00014.
Based on the association between the neutrophil and ventilator-induced lung injury, the authors hypothesized that neutrophil inhibition with fucoidin would be beneficial and stimulation with granulocyte colony-stimulating factor (G-CSF) would be harmful in a rat model of lethal ventilator-induced lung injury.
Animals (n = 111) were randomly assigned to be pretreated with fucoidin, G-CSF, or placebo (control) before 4 h of low-tidal-volume (10 ml/kg) or high-tidal-volume (40 ml/kg) mechanical ventilation.
All low-volume animals survived. With high volumes, compared with controls, fucoidin did not improve survival (3 of 20 control animals and 5 of 20 fucoidin animals died; P = 0.51) but G-CSF significantly worsened it (18 of 22 animals died; P < 0.001). Circulating neutrophils were increased early with G-CSF and late with fucoidin with low and high tidal volumes (P < 0.05 for each treatment and tidal volume). Fucoidin decreased lung neutrophils, but these were only significant with high tidal volumes, whereas G-CSF increased lung neutrophils but only significantly with low tidal volumes (P < or = 0.01 for each). Fucoidin did not alter any cardiopulmonary measure significantly. Compared with control, G-CSF increased airway pressures with high tidal volumes and worsened lung edema and arterial oxygen with both tidal volumes (P < 0.05 for each).
In this model, neutrophil stimulation by G-CSF increased lung dysfunction and with high tidal volumes worsened survival rates. Extrapolated clinically, neutrophil stimulation either by agents such as G-CSF or conditions such as sepsis may aggravate ventilator-induced lung injury.
基于中性粒细胞与呼吸机诱导的肺损伤之间的关联，作者推测在致死性呼吸机诱导的肺损伤大鼠模型中，岩藻依聚糖抑制中性粒细胞将有益，而粒细胞集落刺激因子（G-CSF）刺激中性粒细胞将有害。
将111只动物随机分为三组，在低潮气量（10 ml/kg）或高潮气量（40 ml/kg）机械通气4小时前，分别用岩藻依聚糖、G-CSF或安慰剂（对照）进行预处理。
所有低潮气量动物均存活。在高潮气量组中，与对照组相比，岩藻依聚糖未改善生存率（20只对照动物中有3只死亡，20只岩藻依聚糖处理动物中有5只死亡；P = 0.51），但G-CSF显著降低了生存率（22只动物中有18只死亡；P < 0.001）。无论是低潮气量还是高潮气量，G-CSF早期使循环中性粒细胞增加，岩藻依聚糖晚期使循环中性粒细胞增加（每种处理和潮气量下P < 0.05）。岩藻依聚糖减少了肺内中性粒细胞，但仅在高潮气量时显著，而G-CSF增加了肺内中性粒细胞，但仅在低潮气量时显著（每种情况下P≤0.01）。岩藻依聚糖未显著改变任何心肺指标。与对照组相比，G-CSF在高潮气量时增加气道压力，在两种潮气量时均加重肺水肿和动脉血氧不足（每种情况P < 0.05）。
在该模型中，G-CSF刺激中性粒细胞增加了肺功能障碍，在高潮气量时降低了生存率。从临床推断，G-CSF等药物或脓毒症等情况刺激中性粒细胞可能会加重呼吸机诱导的肺损伤。
