Effect of intraperitoneal application of an endotoxin inhibitor on survival time in a laparoscopic model of peritonitis in rats.
Gram-negative sepsis due to fecal peritonitis is a hazardous disease with a high percentage having a lethal course. The inflammatory effects are induced by endotoxin release. We performed this study to evaluate the potential of direct intraperitoneal application of an endotoxin inhibitor in a laparoscopic peritonitis model in rats. The human feces specimen was prepared, and a standard fecal specimen (0.5 ml/kg b.w.) was applied via minilaparotomy. The rats were randomized to two studies. First, rats were randomized to three groups to define the survival time: (1) rats without further manipulation; (2) rats with laparoscopic lavage using NaCl; (3) rats with laparoscopic lavage using endotoxin inhibitor. Second, rats underwent the same procedure used in the first part of the study and an additional group with only NaCl lavage without peritonitis was randomized. To evaluate the immunologic or biochemical effects, animals were killed at a standard time of 20 hours until the postmortem examination was established. Interleukins 6 and 10 (IL-6, IL-10), malondialdehyde, and protein carbonyl group levels in plasma and particularly in peritoneal fluid were assayed. The first part of the experiment showed significantly increased survival after endotoxin inhibitor lavage. In the second part, administration of endotoxin inhibitor intraperitoneally caused a significant reduction of IL-6 in the peritoneal fluid, in contrast to that in the other groups. Laparoscopic application of endotoxin inhibitor intraperitoneally thus produced a beneficial effect on survival and reduction of IL-6 in peritoneal fluid. Hence, it is possible to influence the inflammation cascade by causing intraperitoneal endotoxin inhibition.
Kuhn
Roger
R
Department of Surgery, Otto-von-Guericke University, Leipziger Strasse 44, D-39120, Magdeburg, Germany. Roger.Kuhn@medizin.uni-magdeburg.de
Schubert
Daniel
D
Tautenhahn
Joerg
J
Nestler
Gerd
G
Schulz
Hans-Ulrich
HU
Bartelmann
Maike
M
Lippert
Hans
H
Pross
Matthias
M
D000818:Animals; D001202:Ascitic Fluid / Q000378:metabolism; D004195:Disease Models, Animal; D004731:Endotoxins / Q000037:antagonists & inhibitors*; D005243:Feces; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D010535:Laparoscopy; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009842:Oligopeptides / Q000008:administration & dosage*; D010533:Peritoneal Lavage; D010538:Peritonitis / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D004731:Endotoxins; C505856:H-Lys-Thr-Lys-Cys-Lys-Phe-Leu-Lys-Lys-Cys-OH; D015850:Interleukin-6; D009842:Oligopeptides; D016753:Interleukin-10; D008315:Malondialdehyde