Prevention of sepsis-induced gastric lesions in dogs by cimetidine via inhibition of gastric secretion and by prostaglandin via cytoprotection.
The cytoprotective and acid-inhibitory effects of cimetidine and 16,16-dimethyl PGE2 were evaluated in a septic canine erosive gastritis model. In 21 dogs, total gastric fistulas were created, and after a 3-wk recovery period, basal, food-, and pentagastrin-stimulated acid output were measured. Then bacterial peritonitis was created by the intraperitoneal instillation of Pseudomonas, Bacteroides, Streptococcus Fecalis, Klebsiella and canine gallbladder bile. In 5 dogs no drug were given throughout the septic period while in 16 dogs either cimetidine, 6 or 12 mg/kg i.m. every 6 h, or 16,16-dimethyl PGE2, 0.2 or 0.4 microgram/kg i.m. every 6 h, was given 24 h before the induction of peritonitis and continued for 3 days. All 21 dogs had positive blood cultures on the 1st septic day. In the control animals, basal, food-, and pentagastrin-stimulated acid output significantly increased during the first 2 septic days, and gastroscopy demonstrated bleeding acute fundic erosions. Cimetidine decreased basal, food-, and pentagastrin-stimulated acid output in a dose-related manner, and only with the higher dose did it prevent gastric mucosal damage. 16,16-Dimethyl PGE2, 0.4 microgram/kg, significantly decreased acid output and prevented gastric mucosal damage. 16,16-Dimethyl PGE2 0.2 microgram/kg, although having no apparent effect on basal, food-, and pentagastrin-stimulated acid output, prevented the development of acute gastric erosions. Thus, in the canine septic model, acid output significantly increases during sepsis. Cimetidine prevents the development of sepsis-induced gastric erosions by inhibition of acid secretion and 16,16-dimethyl PGE2 by cytoprotection.
D000818:Animals; D001424:Bacterial Infections / Q000150:complications* / Q000503:physiopathology; D002927:Cimetidine / Q000494:pharmacology* / Q000627:therapeutic use; D004285:Dogs; D005744:Gastric Acid / Q000378:metabolism*; D006146:Guanidines / Q000494:pharmacology*; D010538:Peritonitis / Q000150:complications; D011453:Prostaglandins / Q000494:pharmacology* / Q000627:therapeutic use; D013270:Stomach / Q000187:drug effects / Q000473:pathology; D013272:Stomach Diseases / Q000517:prevention & control*
D006146:Guanidines; D011453:Prostaglandins; D002927:Cimetidine