Prostaglandins and acute pancreatitis--experimental and clinical studies.
Acute pancreatitis has a mortality of 10-20 per cent, and in cases of acute haemorrhagic pancreatitis this rises to 80-90 per cent. At present there is no reliable treatment for this condition. Based on the hypothesis that the release locally and systemically of the intracellularly activated pancreatic digestive enzymes is due to cell membrane instability, we have studied the cytoprotective (cell membrane stabilizing) role of prostaglandins in this condition. In the first part of this study, an animal model of acute pancreatitis with a mortality of 100 per cent by 14 days has been established by feeding mice a choline-deficient ethionine supplemented diet. Using this model we have demonstrated improved survival (16 out of 50 survived 14 days or longer) by administering prostaglandin E2 subcutaneously (P less than 0 X 02). We have demonstrated that the improved survival is dose-dependent, in the range 2 X 5-5 X 0 mg/kg body weight 8 hourly (P less than 0 X 02) and time-dependent, still being effective if treatment is delayed for 24 h (P less than 0 X 02). Great emphasis has been placed on not commencing treatment until after the induction of acute pancreatitis. In the second part we have used cell membrane marker enzymes to study the cell membrane stabilizing effect of prostaglandin E2 in the human. It has been demonstrated that cell membrane instability occurs. In 12 of 50 episodes treated by prostaglandin E2 infusion, the lysosomal, mitochondrial and cell membranes are stabilized, thus decreasing the release of intracellular enzymes.
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D015232:Dinoprostone; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D010195:Pancreatitis / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality; D011458:Prostaglandins E / Q000008:administration & dosage / Q000627:therapeutic use*; D012306:Risk; D013997:Time Factors
D011458:Prostaglandins E; D015232:Dinoprostone