Increased sensitivity to endotoxemia by tissue necrosis.
In this study the interaction of endotoxemia and ischemic organ injury was investigated in a rat model. Animals received lipopolysaccharide to induce endotoxemia and were simultaneously subjected to renal ischemia. If only renal ischemia was induced, moderate azotemia occurred and all animals survived. Lipopolysaccharide treatment caused neither renal failure nor death. However, rats with both endotoxemia and renal ischemia showed severe azotemia, and 50% of the animals died within 48 hours. The observed mortality rate is unlikely related to renal failure since animals subjected to bilateral nephrectomy did not die within 48 hours after treatment with lipopolysaccharide. To further exclude the role of renal failure in the enhanced effect of endotoxemia, experiments were performed in which ischemic kidneys were excised from littermates and were placed in the abdomens of lipopolysaccharide-treated animals. A similar effect was observed: 50% of the animals died within 48 hours. Azotemia did not occur. Since tumor necrosis factor (TNF) is an important cytokine involved in endotoxemia-induced morbidity and death, we studied the role of TNF in our model. Plasma levels of TNF were increased during endotoxemia. Concomitant renal ischemic injury did not influence the concentration of TNF. When animals were treated with recombinant TNF and were subsequently subjected to renal ischemic injury, again a 50% mortality was observed, a rate similar to that in lipopolysaccharide-treated animals. We conclude that the sensitivity to endotoxemia is enhanced by tissue necrosis and may lead to death in the experimental model used in this study.
Maessen
J G
JG
Department of Surgery, University of Limburg, Maastricht, The Netherlands.
Greve
J W
JW
Buurman
W A
WA
D000818:Animals; D001806:Blood Urea Nitrogen; D004731:Endotoxins / Q000633:toxicity*; D004926:Escherichia coli; D007511:Ischemia / Q000473:pathology*; D007700:Kinetics; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D009336:Necrosis; D009392:Nephrectomy; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D012079:Renal Circulation; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014511:Uremia / Q000139:chemically induced / Q000503:physiopathology*
D004731:Endotoxins; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha