Mohr M, Höpken U, Oppermann M, Mathes C, Goldmann K, Siever S, Götze O, Burchardi H
Department of Anaesthesiology, Critical Care and Emergency Medicine, University of Goettingen, Germany.
Eur J Clin Invest. 1998 Mar;28(3):227-34. doi: 10.1046/j.1365-2362.1998.00260.x.
We analysed the effects of complement depletion and of C5a inhibition on haemodynamic parameters, oxygen delivery (DO2), oxygen consumption (VO2), oxygen extraction ratio (OER) and blood lactate levels after live bacteria infusion in pigs.
In the first series of experiments, animals were decomplemented by cobra venom factor (CVF, 125 micrograms kg-1) and challenged with 1.3 x 10(9) Escherichia coli kg-1. In a second series, animals were treated with neutralizing anti-C5a monoclonal antibodies (mAb) T13/9 before infusion of an increased E. coli dosage (1 x 10(10) E. coli kg-1). Administration of Gram-negative bacteria resulted in hypotension, tachycardia, pulmonary hypertension and decreased cardiac output typical for severe sepsis. These alterations were more pronounced in animals challenged with a higher bacteria concentration (1 x 10(10) E. coli kg-1, n = 5) than with a lower dosage (1.3 x 10(9) E. coli kg-1, n = 4). Complement depletion by CVF injection 24 h before E. coli infusion (n = 4), or anti-C5a mAb T13/9 administration (n = 4) had no effect on the changes in haemodynamic parameters and in DO2 associated with E. coli challenge. Application of either 1.3 x 10(9) or 1 x 10(10) E. coli kg-1 resulted in a marked decrease in VO2 and an increase in blood lactate levels, whereas the OER did not change throughout the experiment. In contrast, pretreatment with CVF 24 h before low-dose E. coli (1.3 x 10(9) kg-1) administration resulted in a significant increase in VO2 (P < 0.05) and in OER (P < 0.05) compared with untreated septic animals (n = 4). No hyperlactaemia occurred in complement-depleted septic animals compared with complement-sufficient animals (P < 0.05). Animals challenged with a high E. coli dose (1 x 10(1) kg-1) and treated with anti-C5a mAbs showed a pronounced increase in VO2 and OER (P < 0.05) accompanied by an attenuated increase in lactate levels (P < 0.05) compared with untreated septic animals.
The results demonstrate an improved oxygen use after complement depletion in this model of severe Gram-negative sepsis. Furthermore, a similar effect was seen after specifically neutralizing C5a by mAbs, indicating a role of C5a in the underlying mechanism.
我们分析了补体耗竭和C5a抑制对猪输注活细菌后血流动力学参数、氧输送（DO2）、氧消耗（VO2）、氧摄取率（OER）及血乳酸水平的影响。
在第一组实验中，用眼镜蛇毒因子（CVF，125微克/千克）使动物补体耗竭，然后用1.3×10⁹大肠杆菌/千克进行攻击。在第二组实验中，在输注增加剂量的大肠杆菌（1×10¹⁰大肠杆菌/千克）前，用中和性抗C5a单克隆抗体（mAb）T13/9对动物进行治疗。给予革兰氏阴性菌导致典型的严重脓毒症的低血压、心动过速、肺动脉高压及心输出量降低。这些改变在接受较高细菌浓度（1×10¹⁰大肠杆菌/千克，n = 5）攻击的动物中比接受较低剂量（1.3×10⁹大肠杆菌/千克，n = 4）的动物更明显。在大肠杆菌输注前24小时注射CVF使补体耗竭（n = 4）或给予抗C5a mAb T13/9（n = 4）对与大肠杆菌攻击相关的血流动力学参数和DO2的变化没有影响。给予1.3×10⁹或1×10¹⁰大肠杆菌/千克均导致VO2显著降低及血乳酸水平升高，而在整个实验过程中OER没有变化。相反，在低剂量大肠杆菌（1.3×10⁹/千克）给药前24小时用CVF预处理导致与未治疗的脓毒症动物（n = 4）相比VO2（P < 0.05）和OER（P < 0.05）显著增加。与补体充足的动物相比，补体耗竭的脓毒症动物未出现高乳酸血症（P < 0.05）。与未治疗的脓毒症动物相比，接受高剂量大肠杆菌（1×10¹⁰/千克）攻击并用抗C5a mAb治疗的动物VO2和OER显著增加（P < 0.05），同时乳酸水平升高减弱（P < 0.05）。
结果表明在这个严重革兰氏阴性脓毒症模型中补体耗竭后氧利用得到改善。此外，用mAb特异性中和C5a后也观察到类似效果，表明C5a在潜在机制中起作用。
