A model of hemorrhagic pancreatitis in cats--role of 16,16-dimethyl prostaglandin E2.
Acute edematous pancreatitis was induced in cats by perfusing activated pancreatic enzymes through their pancreatic ducts. The ducts had been made permeable to large molecules by one of two techniques. The cats either received ethanol (2 ml/kg every 8 h) and aspirin (25 mg/kg every 8 h) orally for 48 h or had their pancreatic ducts perfused for 1 h with 7.5 mM glycodeoxycholate. When the same procedure was followed, but using 16,16-dimethyl prostaglandin E2 (dmPGE2) (2 micrograms/kg X h infused intravenously for 1 h before and during ductal perfusion with activated enzymes), hemorrhagic pancreatitis developed instead. To investigate whether an increase in pancreatic blood flow or microvascular permeability (both caused by dmPGE2) was important in this phenomenon, we tested the effects of isoproterenol (which increased blood flow) and histamine (which increased microvascular permeability) in the model. Thus in similar experiments, either isoproterenol (0.3 micrograms/kg . min) or histamine phosphate (2 micrograms/kg . min) was infused instead of dmPGE2. The animals that received histamine also developed hemorrhagic pancreatitis. Those that received isoproterenol did not. These observations suggested that an increase in microvascular permeability in the pancreas converted edematous pancreatitis to hemorrhagic pancreatitis. These findings suggest also that clinical studies using prostaglandins to treat patients with pancreatitis should be approached with caution.
D015064:16,16-Dimethylprostaglandin E2 / Q000633:toxicity*; D000818:Animals; D001241:Aspirin / Q000633:toxicity; D002199:Capillary Permeability / Q000187:drug effects*; D002415:Cats; D000431:Ethanol / Q000633:toxicity; D006002:Glycodeoxycholic Acid / Q000633:toxicity; D006470:Hemorrhage / Q000139:chemically induced / Q000473:pathology; D006632:Histamine / Q000031:analogs & derivatives / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D010179:Pancreas / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D010189:Pancreatic Juice; D010195:Pancreatitis / Q000139:chemically induced* / Q000473:pathology; D011459:Prostaglandins E, Synthetic / Q000633:toxicity*; D012039:Regional Blood Flow / Q000187:drug effects
D011459:Prostaglandins E, Synthetic; D006002:Glycodeoxycholic Acid; D000431:Ethanol; D006632:Histamine; D007545:Isoproterenol; D015064:16,16-Dimethylprostaglandin E2; C027556:histamine phosphate; D001241:Aspirin