From Manchester Royal Infirmary EDITORIAL SYNOPSIS In this study of pancreatitis induced by ethionine the outputs of amylase, trypsin, and lipase were diminished simultaneously.The pancreatic enzymes, amylase, trypsinogen, and lipase, are excreted concurrently in healthy man (Lagerlof, 1942;Burton, Evans, Harper, Howat, Oleesky, Scott, and Varley, 1960). In some cases of chronic pancreatitis a loss of activity of one enzyme has been reported while the concentration of the other two has not been affected (Lagerldf, 1939;Diamond and Siegel, 1941). In the present study ethionine was given to produce pancreatitis in rats. Using this model experiments were designed to investigate the pattern of the output of enzymes in the ethionine-poisoned state.
METHODSMale rats only were used, because an excessive fatty degeneration of the liver occurs in female rats in the early stage of ethionine toxicity (Farber, Koch-Weser, and Popper, 1951, Becker;1957).Sixty-one male albino rats ranging in weight from 200 to 300 g. were injected subcutaneously with 4 mg. atropine. Fifteen minutes later light ether anaesthesia was induced, the abdomen opened and anaesthesia continued by the injection of 0-75 ml. of a 5 % urethane solution into the caecum. After tying off the pylorus the main bile duct was occluded by a ligature tied close to the hilum of the liver, and cannulated by a polyethylene catheter (0-98 mm. o.d.) introduced close to the duodenal wall. Samples of pancreatic juice from the numerous pancreatic ducts entering the main bile duct were drained by continuous suction using a negative pressure of I to 2 cm. of water.Exocrine pancreatic secretion was stimulated by secretin and pancreozymin (Boots). For the first 60 minutes 2 units of secretin (Crick, Harper, and Raper, 1949) were infused into the jugular vein every five minutes; for the subsequent 30 minutes 2 units of both secretin and pancreozymin were given every five minutes.Pancreatic juice was fractionated into glass tubes surrounded by ice, the volume measured, and the specimens kept in a deep freeze chamber until amylase activity was Pancreatitis was induced by ethionine. Four animals (group 10) were given ethionine two hours before the test by continuous infusion. Ethionine was also given to other batches of rats intraperitoneally. In the first series (groups 1 to 5) the dose was increased from 0-33 to 1-66 mg./g. of body weight. Each injection contained 0-33 mg./g. body weight and in 24 hours not more than 1-00 mg./g. body weight was given. Pancreatic function was estimated 12 hours after the last injection. The second series was designed to study recovery from ethionine pancreatitis. In groups 3, 6, 7, and 8 the animals were each given the same dose of 1-0 mg./g. body weight of ethionine and pancreatic function was studied at intervals of 24, 48, 72, and 120 hours, after the initial injection of ethionine.In order to investigate the early changes in ethionine pancreatitis, in group 10 033 mg./g. body weight of ethionine was administered intravenously and the test...