16-16-dimethylprostaglandin-e2 and Biliary-Tract-Diseases

Perfusion of the main pancreatic duct in cats with a dilute solution of bile salts increases ductal permeability. Subsequent perfusion of a permeable duct with activated pancreatic enzymes results in acute edematous pancreatitis. Simultaneous infusion of 16-16 dimethyl-PgE2 converts edematous pancreatitis to acute hemorrhagic pancreatitis (AHP). AHP may be associated with a reduction in pancreatic blood flow; it is certainly associated with increases in microvascular permeability. Low dose dopamine is a splanchnic vasodilator and may also reduce pancreatic microvascular permeability through beta agonist effects. In these studies, we investigated the effect of dopamine in an established feline model of biliary AHP. We also studied its effect on blood flow in both normal pancreas and after induction of AHP. We found that dopamine significantly reduced the degree of pancreatic inflammation, even when administered up to 12 h after onset of biliary AHP. However, the drug had no significant effect on blood flow either in normal pancreas or in the gland affected by hemorrhagic pancreatitis. We concluded that the effect of dopamine was most likely due to its ability to reduce pancreatic microvascular permeability.

Topics: 16,16-Dimethylprostaglandin E2; Acute Disease; Animals; Biliary Tract Diseases; Capillary Permeability; Cats; Disease Models, Animal; Dopamine; Infusions, Intravenous; Pancreas; Pancreatitis; Regional Blood Flow

Pharmacological attempts to alter the course of experimental pancreatitis in the opossum were made using synthetic 16, 16-dimethyl prostaglandin E2 (16, 16-dm PGE2). Anatomically, the opossum has an elongated ampulla resulting in a supraduodenal pancreatic duct-common bile duct junction allowing for bile reflux pancreatitis to be produced by ligating the distal common bile duct. Preliminary evaluation demonstrated that at 72 hours common bile duct ligation distal to the pancreatic duct orifice produced pancreatitis comparable in severity to that produced by a Pfeffer loop. When the oppossum distal common bile duct was ligated, serum amylase concentrations progressively increased from control values of 182 +/- 43 to 742 +/- 62 Somogyi units/dl at 5 hours. Administration of 0.2 microgram-kg-1-min-1 16, 16-dm PGE2 significantly decreased the hyperamylasemia associated with bile reflux pancreatitis and, in addition, decreased the pancreatic gland weights when compared to control values. Subsequent evaluation of the administration of 75 micrograms-kg-1 16, 16-dm PGE2 every 12 hours for 72 hours to opossums with distal common bile duct ligation demonstrated no significant differences in serum amylase concentrations when compared to control values. Histologic evaluation of the pancreas glands at 72 hours demonstrated increased glandular integrity when the pancreas glands from the opossums receiving 16,16-dm PGE2 were compared to the glands subjected to distal common bile duct ligation alone. This report identifies several favorable characteristics in the course of experimental pancreatitis associated with the administration of a synthesis PGE analog at the onset of the inflammatory process.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 16,16-Dimethylprostaglandin E2; Amylases; Animals; Bile Reflux; Biliary Tract Diseases; Disease Models, Animal; Female; Male; Opossums; Pancreatitis; Prostaglandins E, Synthetic