title: Propofol (Diprivan-EDTA) counteracts oxidative injury and deterioration of the arterial oxygen tension during experimental septic shock.
abstract: OBJECTIVE
  Human septic shock can be replicated in the endotoxaemic pig. Endotoxaemia causes a multitude of events, including reduced PaO(2) and increased lipid peroxidation. This study was designed to evaluate the possible effects of a commonly used anaesthetic drug with known antioxidant properties (propofol) during porcine endotoxaemia.
  
  
  METHODS
  Ten pigs were anaesthetised and given a 6 h E. coli endotoxin infusion. The animals received, randomly, a supplementary continuous infusion of propofol emulsion (containing 0.005% EDTA) or the corresponding volume of vehicle (controls). Pathophysiologic responses were determined. Non-enzymatic (by measuring plasma 8-iso-PGF(2 alpha) and enzymatic (by measuring plasma 15-keto-dihydro-PGF(2 alpha)) lipid peroxidations were evaluated. Plasma levels of the endogenous antioxidants alpha- and gamma-tocopherols, were also analysed.
  
  
  RESULTS
  Endotoxaemia increased plasma levels of 8-iso-PGF(2 alpha) (1st-4th h) and 15-keto-dihydro-PGF(2 alpha) (1st-4th h) significantly more in controls than in the propofol+endotoxin group. PaO(2) was significantly less affected by endotoxin in the propofol treated animals (2nd-4th h). Mean arterial pressure (4th-6th h) and systemic vascular resistance (6th h) were reduced significantly more by endotoxin among the propofol-treated animals. Vitamin E (alpha-tocopherol) increased in all animals, significantly more in the propofol+endotoxin group (1/2-6th h) than in the control group.
  
  
  CONCLUSIONS
  Propofol reduced endotoxin-induced free radical mediated and cyclooxygenase catalysed lipid peroxidation significantly. The implication is that propofol counteracts endotoxin-induced deterioration of PaO(2).
authors.affiliation: Department of Geriatrics and Clinical Nutrition Research, Uppsala University Hospital, S-751 85 Uppsala, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Basu
authors.forename: D K
authors.initials: DK
authors.lastname: Mutschler
authors.forename: A O
authors.initials: AO
authors.lastname: Larsson
authors.forename: R
authors.initials: R
authors.lastname: Kiiski
authors.forename: A
authors.initials: A
authors.lastname: Nordgren
authors.forename: M B
authors.initials: MB
authors.lastname: Eriksson
mesh_terms: D018686:Anesthetics, Intravenous / Q000627:therapeutic use*; D000818:Animals; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000097:blood; D019446:Endotoxemia / Q000503:physiopathology*; D004927:Escherichia coli Infections / Q000503:physiopathology*; D028441:F2-Isoprostanes / Q000097:blood; D007249:Inflammation / Q000628:therapy; D015227:Lipid Peroxidation / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects*; D015742:Propofol / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D011863:Radioimmunoassay; D012772:Shock, Septic / Q000097:blood* / Q000188:drug therapy*; D013552:Swine; D014810:Vitamin E / Q000097:blood / Q000502:physiology*
chemical_list: D018686:Anesthetics, Intravenous; D028441:F2-Isoprostanes; D014810:Vitamin E; C075750:8-epi-prostaglandin F2alpha; C026528:15-ketoprostaglandin F2alpha; D015237:Dinoprost; D015742:Propofol