1. New Biomarkers in an Acute Model of Live Escherichia coli-induced Sepsis in Pigs.
- Author
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Castellheim, A., Thorgersen, E. B., Hellerud, B. C., Pharo, A., Johansen, H. T., Brosstad, F., Gaustad, P., Brun, H., Fosse, E., Tønnessen, T. I., Nielsen, E. W., and Mollnes, T. E.
- Subjects
BIOMARKERS ,BIOINDICATORS ,BIOCHEMISTRY ,SEPSIS ,BLOOD diseases ,COMMUNICABLE diseases - Abstract
We developed a live Escherichia coli model of acute sepsis in pigs with emphasize on biomarkers reflecting the early inflammatory response of sepsis. Healthy pigs, 25–35 kg, were challenged intravenously (IV) ( n = 12) or intrapulmonary ( n = 6) with live E. coli and observed for 3 and 5 h respectively. Control pigs received culture medium ( n = 6 + 3). Haemodynamic parameters and a broad panel of inflammatory mediators were measured. The dose of bacteria was carefully titrated to obtain a condition resembling the early phase of human septic shock. The IV group displayed a pro-inflammatory response [significant increase in tumour necrosis factor-α, interleukin (IL)-6 and IL-8] and an early anti-inflammatory response (significant increase in IL-10). For the first time, we demonstrate a significant increase in IL-12 and matrix metalloproteinase-9 (MMP) early in pig sepsis. Coagulation was activated (significant increase in thrombin–antithrombin complexes) and there was a significant decrease in the serum proteins suggesting capillary leakage. Haemodynamic parameters reflected a septic condition with significant decrease in systemic blood pressure, increases in heart rate, pulmonary artery pressure and base deficit. None of these changes was observed in the control group. Interleukin-1β and vascular endothelial growth factor increased in both groups. Nitric oxide measurements suggested an initial pulmonary vascular endothelial inflammatory response. The intrapulmonary group, which did not resemble septic condition, showed a substantial increase in MMP-9. In this porcine model of sepsis, IL-12 and MMP-9 were detected for the first time. These biomarkers may have an impact in the understanding and future treatment of sepsis. [ABSTRACT FROM AUTHOR]
- Published
- 2008
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