16-16-dimethylprostaglandin-e and Peritonitis

Administration of a long-acting prostaglandin E, 16,16-dimethyl-PGE (dPGE), to rats improves their survival of bacterial peritonitis. We examined the mechanism of this protective effect with reference to its interaction with the release of cachectin (TNF). Sixty rats received saline, 20 micrograms/kg dPGE, or 80 micrograms/kg dPGE 12 hr prior to endotoxin and continuing for 48 hr. Survival rates for the saline, 20 micrograms/kg dPGE, and 80 micrograms/kg dPGE groups were 0, 40, and 85%, respectively. Forty rats received saline or 80 micrograms/kg dPGE, with the initial dose being 3 hr following endotoxin challenge and continuing for 48 hr. Survival rates for both groups were 0%. Sixty rats received saline or 80 micrograms/kg dPGE at 12 and 1 hr prior to endotoxin. Two hours after challenge, they were sacrificed and plasma TNF levels were assayed. The plasma TNF level in saline-treated rats was 22.72 +/- 0.83 ng/ml and in the dPGE-treated group, 16.03 +/- 1.13 ng/ml (P less than 0.001).

Topics: Animals; Escherichia coli Infections; Male; Peritonitis; Prostaglandins E, Synthetic; Rats; Rats, Inbred Lew; Shock, Septic; Tumor Necrosis Factor-alpha

Prostaglandin cytoprotection may be related to lysosomal stability. In six mongrel dogs, bacterial peritonitis was created by the intraperitoneal instillation of Bacteroides fragilis, Pseudomonas aeruginosa, Streptococcus faecalis and Klebsiella pneumoniae in addition to canine gallbladder bile. In three dogs, gallbladder bile alone was instilled. Three of the six dogs with bacterial peritonitis also received 16,16-dimethyl prostaglandin E2 (PGE2) (0.2 micrograms/kg intramuscularly q6h) 24 hours before and for 3 days after the induction of peritonitis. In the dogs with bacterial peritonitis not receiving PGE2, gastroscopic examination demonstrated acute fundic erosions. None of the other dogs developed acute gastric erosions. In the dogs with bacterial peritonitis not receiving PGE2, fundic mucosal biopsy specimens demonstrated decreased lysosomal stability. In the dogs receiving PGE2, lysosomal stability was similar to that in the animals with bile peritonitis. These experiments demonstrate that PGE2 prevents the development of acute gastric erosions by stabilizing lysosomal membranes.

Topics: Animals; Dogs; Gastric Mucosa; Lysosomes; Male; Peritonitis; Prostaglandins E, Synthetic; Stomach Diseases