Prostaglandins are profoundly involved in endotoxaemic
shock. Twenty pigs were given
endotoxin at various doses (0.063-16 microg kg(-1) h(-1)). Three non-endotoxaemic pigs served as controls. Two
eicosanoids were measured in plasma (8-iso-
PGF(2alpha), a
free radical-mediated lipid peroxidation product, and 15-keto-dihydro-
PGF(2alpha) 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(2alpha) and 15-keto-dihydro-PGF(2alpha). An increase in the
endotoxin dose induced significant log-linear responses in
8-iso-PGF(2alpha) and 15-keto-dihydro-PGF(2alpha). Oxidative injury correlated to the
TNF-alpha,
IL-6, reductions in cardiac performance and to
oxygen delivery and utilisation. COX-mediated inflammatory responses correlated to
TNF-alpha,
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.