Lipid peroxidation induced by an early inflammatory response in endotoxaemia

Background: Endotoxaemic challenge promptly causes lipid peroxidation. Porcine endotoxaemia can be used to replicate severe human septic shock. This model was used to evaluate nonenzymatic [8-Iso-prostaglandin F-2 alpha (8-Iso-PGF(2 alpha))] and enzymatic [15-keto-13,14-dihydro-prostaglandin F-2 alpha (15-K-DH-PGF(2 alpha))] lipid peroxidation, respectively, in relation to survival. The aim of this study was to correlate, if possible, pathophysiologic events during endotoxaemia to the levels of these arachidonic acid metabolites. Methods: Nineteen pigs were anaesthetised, monitored (circulatory and respiratory variables in relation to lipid peroxidation) and given a continuous 6 h E. coli endotoxin (10 mu g.kg(-1).h(-1)) infusion. All animals were mechanically ventilated at constant tidal volumes and the inspired oxygen fraction was kept constant during the experimental period. Results: This endotoxin infusion caused expressed derangements in all pigs and death in 9 of them. The levels of 8-Iso-PGF(2 alpha), indicating oxidative injury, were different in time course, magnitude and fashion between survivors and non-survivors. The levels of 15-K-DH-PGF(2 alpha), indicating inflammatory response, showed a similar pattern. At 1 h the CO2 partial pressure in arterial blood was significantly higher in non-surviving pigs and correlated (r: 0.7; P<0.05) to the levels of 15-K-DH-PGF(2 alpha). Prostaglandin F-2 alpha is mainly metabolised in the lung. The lung weights were significantly (P<0.05) higher in non-surviving than in surviving animals. Both free radical and cyclooxygenase catalysed oxidative modification occurs during endotoxaemia. Conclusion: Increased metabolism and inflammation, as evaluated by 15-K-DH-PGF(2 alpha), in the group of non-survivors may mediate the increase in arterial CO2. Thus, increased lipid peroxidation seems to be associated with endotoxaemic organ dysfunction and increased mortality.