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Effect of increasing endotoxin doses on oxidative injury and cyclooxygenase-mediated inflammation in the anaesthetised pig
Critical Care volume 12, Article number: P391 (2008)
In this study the effect of the endotoxin dose on production of an F2-isoprostane, 8-iso-PGF2α, a free radical-mediated lipid peroxidation product, and 15-keto-dihydro-PGF2α, a major metabolite of PGF2α and cyclooxygenase (COX)-mediated inflammatory response, was investigated. Oxidative injury and COX-mediated inflammation play a central role in the manifestation of endotoxaemic shock. These eicosanoids are therefore markers of key processes in the pathophysiology of endotoxaemic shock. However, their relationship to the endotoxin dose has not been established.
Twenty pigs were anesthetised and given endotoxin at logarithmically increasing doses (0.063–16 μg/kg/hour). Three nonendotoxaemic pigs served as controls. 8-Iso-PGF2α and 15-keto-dihydro-PGF2α were measured in plasma at baseline and hourly for 6 hours. The dose–response to increasing doses of endotoxin was determined using the two-sided Jonckheere–Terpstra test.
Endotoxin induced the formation of both 8-iso-PGF2α and 15-keto-dihydro-PGF2α. Increases in the endotoxin dose induced significant log-linear responses in 8-iso-PGF2α and 15-keto-dihydro-PGF2α (P < 0.001, P < 0.05, respectively) as depicted in Figure 1.
Our findings indicate that free radical-mediated lipid peroxidation and COX-mediated inflammatory response are dependent on the endotoxin dose in a log-linear fashion in this model.
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Lipcsey, M., Söderberg, E., Basu, B. et al. Effect of increasing endotoxin doses on oxidative injury and cyclooxygenase-mediated inflammation in the anaesthetised pig. Crit Care 12, P391 (2008). https://doi.org/10.1186/cc6612
- Public Health
- Lipid Peroxidation
- Inflammatory Response
- Emergency Medicine