title: Lipid peroxidation induced by an early inflammatory response in endotoxaemia.
abstract: BACKGROUND
  Endotoxaemic challenge promptly causes lipid peroxidation. Porcine endotoxaemia can be used to replicate severe human septic shock. This model was used to evaluate non-enzymatic [8-Iso-prostaglandin F2alpha (8-Iso-PGF2alpha)] and enzymatic [15-keto-13,14-dihydro-prostaglandin F2alpha (15-K-DH-PGF2alpha)] 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 microg x kg(-1) x 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-PGF2alpha, indicating oxidative injury, were different in time course, magnitude and fashion between survivors and non-survivors. The levels of 15-K-DH-PGF2alpha, 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-PGF2alpha. Prostaglandin F2alpha 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.
  
  
  CONCLUSIONS
  Increased metabolism and inflammation, as evaluated by 15-K-DH-PGF2alpha, 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.
authors.affiliation: Department of Geriatrics, Faculty of Medicine, Uppsala University Hospital, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Basu
authors.forename: M
authors.initials: M
authors.lastname: Eriksson
mesh_terms: D000818:Animals; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D019446:Endotoxemia / Q000378:metabolism* / Q000503:physiopathology*; D005260:Female; D007249:Inflammation / Q000378:metabolism; D015227:Lipid Peroxidation; D008297:Male; D011454:Prostaglandins A / Q000378:metabolism; D013552:Swine; D013997:Time Factors
chemical_list: C117466:8-isoprostaglandin A2; D011454:Prostaglandins A; C008228:15-keto-13,14-dihydroprostaglandin F2alpha; D015237:Dinoprost