Petersen B, Busch T, Gaertner J, Haitsma J J, Krabbendam S, Ebsen M, Lachmann B, Kaisers U X
Department of Anesthesiology and Intensive Care Medicine, University of Leipzig Medical Faculty, Leipzig, Germany.
Department of Anesthesiology and Intensive Care Medicine, Schoen Clinics, Vogtareuth, Germany.
J Physiol Pharmacol. 2016 Dec;67(6):911-918.
The complement system contributes to ventilator induced lung injury (VILI). We hypothesized that pretreatment with the C1 esterase inhibitor (C1INH) Berinert® constrains complement activation consecutively inducing improvements in arterial oxygenation and histological pulmonary damage. At baseline, male Sprague-Dawley rats underwent mechanical ventilation in a conventional mode (PIP 13 cm HO, PEEP 3 cm HO). In the Control group, the ventilator setting was maintained (Control, n = 15). The other animals randomly received intravenous pretreatment with either 100 units/kg of the C1-INH Berinert® (VILI-C1INH group, n = 15) or 1 ml saline solution (VILI-C group, n = 15). VILI was induced by invasive ventilation (PIP 35 cm HO, PEEP 0 cm HO). After two hours of mechanical ventilation, the complement component C3a remained low in the Control group (258 ± 82 ng/ml) but increased in both VILI groups (VILI-C: 1017 ± 283 ng/ml; VILIC1INH: 817 ± 293 ng/ml; P < 0.05 for both VILI groups versus Control). VILI caused a profound deterioration of arterial oxygen tension (VILI-C: 193 ± 167 mmHg; VILI/C1-INH: 154 ± 115 mmHg), whereas arterial oxygen tension remained unaltered in the Control group (569 ± 26 mmHg; P < 0.05 versus both VILI groups). Histological investigation revealed prominent overdistension and interstitial edema in both VILI groups compared to the Control group. C3a plasma level in the VILI group were inversely correlated with arterial oxygen tension (R = -0.734; P < 0.001). We conclude that in our animal model of VILI the complement system was activated in parallel with the impairment in arterial oxygenation and that pretreatment with 100 units/kg Berinert® did neither prevent systemic complement activation nor lung injury.
补体系统参与呼吸机诱导的肺损伤（VILI）。我们假设用C1酯酶抑制剂（C1INH）百林妥英（Berinert®）进行预处理可抑制补体激活，进而改善动脉氧合及肺部组织学损伤。在基线时，雄性Sprague-Dawley大鼠以常规模式进行机械通气（气道峰压13 cmH₂O，呼气末正压3 cmH₂O）。在对照组中，维持通气设置不变（对照组，n = 15）。其他动物随机接受静脉预处理，分别给予100单位/千克的C1-INH百林妥英（VILI-C1INH组，n = 15）或1毫升生理盐水（VILI-C组，n = 15）。通过有创通气（气道峰压35 cmH₂O，呼气末正压0 cmH₂O）诱导VILI。机械通气两小时后，对照组补体成分C3a水平较低（258±82 ng/ml），但在两个VILI组中均升高（VILI-C组：1017±283 ng/ml；VILI-C1INH组：817±293 ng/ml；两个VILI组与对照组相比，P<0.05）。VILI导致动脉氧分压显著下降（VILI-C组：193±167 mmHg；VILI/C1-INH组：154±115 mmHg），而对照组动脉氧分压保持不变（569±26 mmHg；与两个VILI组相比，P<0.05）。组织学研究显示，与对照组相比，两个VILI组均有明显的过度膨胀和间质水肿。VILI组的C3a血浆水平与动脉氧分压呈负相关（R = -0.734；P<0.001）。我们得出结论，在我们的VILI动物模型中，补体系统与动脉氧合受损同时被激活，且用100单位/千克百林妥英进行预处理既不能预防全身补体激活，也不能预防肺损伤。
