F2-isoprostane, inflammation, cardiac function and oxygenation in the endotoxaemic pig

Prostaglandins are profoundly involved in endotoxaemic shock. Twenty pigs were given endotoxin at various doses (0.063–16 μg kg−1 h−1). Three non-endotoxaemic pigs served as controls. Two eicosanoids were measured in plasma (8-iso-PGF2α, a free radical-mediated lipid peroxidation product, and 15-keto-dihydro-PGF2α a major metabolite of COX activity) and evaluated against the pathophysiological responses that occur during endotoxaemic shock.Endotoxin mediates an increase in both 8-iso-PGF2α and 15-keto-dihydro-PGF2α. An increase in the endotoxin dose induced significant log-linear responses in 8-iso-PGF2α and 15-keto-dihydro-PGF2α. Oxidative injury correlated to the TNF-α, IL-6, reductions in cardiac performance and to oxygen delivery and utilisation. COX-mediated inflammatory responses correlated to TNF-α, IL-6 and to reductions in arterial oxygen tension.Thus, oxidative injury and COX-mediated inflammation play a central role in the manifestation of endotoxaemic shock. Furthermore, formation of these eicosanoids on endotoxin-mediated alterations in pulmonary hypertension, oxygen delivery and oxygen utilisation seems to be independent of the administered endotoxin dose.