Vlaar A P J, Kuipers M T, Hofstra J J, Wolthuis E K, Wieland C W, Roelofs J J T H, Boon L, Schultz M J, Lutter R, Juffermans N P
Department of Intensive Care Medicine, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands.
Crit Care Res Pract. 2012;2012:720950. doi: 10.1155/2012/720950. Epub 2012 Jun 4.
Purpose. Onset of transfusion-related acute lung injury (TRALI) is suggested to be a threshold-event. Data is lacking on the relation between titer of antibodies infused and onset of TRALI. We determined whether onset of TRALI is dependent on the titer of MHC-I antibodies infused in a combined model of ventilator-induced lung injury and antibody-induced TRALl. Methods. BALB/c mice were ventilated for five hours with low (7.5 ml/kg) or high (15 ml/kg) tidal volume. After three hours of MV, TRALI was induced by infusion of 0.5 mg/kg, 2.0 mg/kg or 4.5 mg/kg MHC-I antibodies. Control animals received vehicle. After five hours of MV, animals were sacrificed. Results. MV with high tidal volumes resulted in increased levels of all markers of lung injury compared to animals ventilated with low tidal MV. In ventilator-induced lung injury, infusion of 4.5 mg/kg of antibodies further increased pulmonary wet-to-dry ratio, pulmonary neutrophil influx and pulmonary KC levels, whereas infusion of lower dose of antibodies did not augment lung injury. In contrast, mice ventilated with low tidal volumes did not develop lung injury, irrespective of the dose of antibody used. Conclusions. In the presence of injurious MV, onset of TRALI depends on the titer of antibodies infused.
目的。输血相关急性肺损伤(TRALI)的发病被认为是一个阈值事件。关于输入抗体滴度与TRALI发病之间的关系,目前缺乏相关数据。我们在呼吸机诱导的肺损伤和抗体诱导的TRALI联合模型中,确定TRALI的发病是否取决于输入的MHC-I抗体滴度。方法。将BALB/c小鼠分别以低潮气量(7.5毫升/千克)或高潮气量(15毫升/千克)通气5小时。机械通气3小时后,分别输入0.5毫克/千克、2.0毫克/千克或4.5毫克/千克的MHC-I抗体诱导TRALI。对照动物输入溶剂。机械通气5小时后,处死动物。结果。与低潮气量机械通气的动物相比,高潮气量机械通气导致所有肺损伤标志物水平升高。在呼吸机诱导的肺损伤中,输入4.5毫克/千克抗体进一步增加了肺湿干比、肺中性粒细胞浸润和肺KC水平,而输入较低剂量抗体并未加重肺损伤。相反,无论使用何种剂量的抗体,低潮气量通气的小鼠均未发生肺损伤。结论。在存在损伤性机械通气的情况下,TRALI的发病取决于输入抗体的滴度。