Abstract

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-PGF 2 α , a free radical-mediated lipid peroxidation product, and 15-keto-dihydro-PGF 2 α 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-PGF 2 α and 15-keto-dihydro-PGF 2 α . An increase in the endotoxin dose induced significant log-linear responses in 8-iso-PGF 2 α and 15-keto-dihydro-PGF 2 α . 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.

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