Oxygen free radical activity during live E. coli septic shock in the dog

Free radicals generated during purine catabolism or by activated granulocytes cause tissue injury by peroxidation of lipid membranes. In a canine model of sepsis initiated by intravenous live Escherichia coli, fluorescent products of lipid peroxidation (FP) were measured in serum. Four groups, of five dogs infused with 10⁹E. coli/kg were analyzed -I: no further treatment; II: prior depletion of granulocytes with a cytotoxic antibody; III: pre-treatment with superoxide dismutase and catalase; and IV: resuscitation after bacterial infusion to maintain cardiac output > 80% of pre-bacteremic levels. In Groups I, II, and III, cardiac output fell to < 50% of baseline within 1 hr and remained there throughout the study. FP in Groups I and II rose to > 200% of baseline (P<.02 and <.03). In Groups III and IV, FP did not rise significantly from baseline. The rise in serum FP and the prevention of this rise by pre-treatment with antioxidants indicate generation of oxygen radicals. Their presence had no effect on hemodynamic parameters. Granulocyte depletion did not alter appearance of FP; however, prevention of low cardiac output blocked FP formation. These data suggest that oxygen free radicals were generated by tissue ischemia, rather than by granulocytes, in this model of septic shock.