Evaluation of factors affecting mortality rate after sepsis in a murine cecal ligation and puncture model.
A murine model was used to test the effects of various therapeutic modalities on the rate of death following intra-abdominal sepsis as produced by cecal ligation and puncture (CLP). There were no deaths among sham-operated control mice after ether anesthesia, whereas CLP produced a mortality rate of 100% by 24 hours. When CLP was followed at 16 hours by excision of the cecum and saline peritoneal lavage (CLPE), the mortality rate was 20% at 24 hours and 60% at 72 hours. The therapeutic modalities consisted of gentamicin (1.5 mg/kg) alone or in combination with methylprednisolone (50 mg/kg) or tuftsin (1 mg/kg) administered before CLP and at 16 and 24 hours after CLP. Separate groups of animals also received only methylprednisolone or tuftsin, a tetrapeptide produced by the spleen. Compared with the mortality rate in the CLPE group, mortality at 24 and 72 hours was decreased for gentamicin alone (0% and 10%, respectively), tuftsin alone (10%, 40%), or the two in combination (0%, 20%). As compared with CLPE, methylprednisolone led to increased mortality rates at 24 and 72 hours (70%, 80%). The data (significant at P less than 0.01, X2 analysis) suggest that gentamicin and tuftsin may improve the rate of early survival after intra-abdominal sepsis in this Model. Steroids do not seem to be beneficial and may, in fact, be harmful.
D000758:Anesthesia / Q000401:mortality; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D001424:Bacterial Infections / Q000188:drug therapy / Q000401:mortality*; D002432:Cecum / Q000601:surgery*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004986:Ether; D005069:Evaluation Studies as Topic; D005260:Female; D008026:Ligation; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D011292:Premedication; D011677:Punctures; D007507:Therapeutic Irrigation; D013997:Time Factors
D000900:Anti-Bacterial Agents; D004986:Ether