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Effects of anti-C5a monoclonal antibodies on oxygen use in a porcine model of severe sepsis

Item Type:Article
Title:Effects of anti-C5a monoclonal antibodies on oxygen use in a porcine model of severe sepsis
Creators Name:Mohr, M. and Hoepken, U. and Oppermann, M. and Mathes, C. and Goldmann, K. and Siever, S. and Goetze, O. and Burchardi, H.
Abstract:Methods: 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. Results: In the first series of experiments, animals were decomplemented by cobra venom factor (CVF, 125 μg kg−1) and challenged with 1.3 × 109Escherichia 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 × 1010 E. coli kg−1). Administration of Gram-negative bacteria resulted in hypotension, tachycardia, pulmonary hypertension and decreased cardiac output typical for severe sgifis. These alterations were more pronounced in animals challenged with a higher bacteria concentration (1 × 1010 E. coli kg−1, n = 5) than with a lower dosage (1.3 × 109E. 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 × 109 or 1 × 1010 E. coli kg−1resulted 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 × 109 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 × 101 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. Conclusion: The results demonstrate an improved oxygen use after complement depletion in this model of severe Gram-negative sgifis. Furthermore, a similar effect was seen after specifically neutralizing C5a by mAbs, indicating a role of C5a in the underlying mechanism.
Keywords:Complement, C5a, Cobra Venom Factor, Lactate, Oxygen Consumption, Oxygen Use, Sgifis, Septic Shock, Animals, Swine
Source:European Journal of Clinical Investigation
ISSN:0014-2972
Volume:28
Number:3
Page Range:227-234
Date:March 1998
Official Publication:https://doi.org/10.1046/j.1365-2362.1998.00260.x
PubMed:View item in PubMed

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