PANCREATIC FLUID HYPERSECRETION IN RATS AFTER ACUTE-PANCREATITIS

Pancreatic exocrine function was examined in rats during the early sta ge of acute pancreatitis induced by four subcutaneous injections of 20 mu g/kg body weight of cerulein at hourly intervals. Basal pancreatic fluid secretion at 6 hr after the first of four cerulein injections w as significantly elevated (27.6 +/- 3.7 vs 17.4 +/- 2.1 mu l/30 min in control, P < 0.01) and further increased with time, reaching the peak level at 24 hr (105.1 +/- 4.6 mu l/30 min). Intravenous infusion of l oxiglumide (50 mg/kg body wt/hr), atropine (100 mu g/kg body wt/hr), o r anti-secretin serum did not modify the fluid hypersecretion observed at 24 hr after induction of acute pancreatitis. Loxiglumide, when giv en 30 min before the first cerulein injection, markedly reduced fluid secretion, but could not inhibit the fluid hypersecretion when applied after the last cerulein injection. Leakage of Evans blue dye into pan creatic juice was slightly but significantly increased in postpancreat itic rats compared with that in the control rats (1.30 +/- 0.17 vs 0.7 5 +/- 0.08 mu g/ml, P < 0.01), whereas that in the pancreas was not di fferent from the control rats. In vivo labeling with 5-bromo-2'-deoxyu ridine showed active proliferation of acinar and ductular cells at 6 h r. In addition, the fluid was rich in chloride (137.1 +/- 2.5 at 24 hr vs 92.4 +/- 3.3 meq/liter in control, P < 0.01) but poor in bicarbona te concentration (39.0 +/- 2.0 at 24 hr vs 46.5 +/- 1.9 mmol/liter in control, P < 0.01), indicating acinar cell secretion. These results in dicate that pancreatic fluid secretion during the early stage of acute pancreatitis induced by supramaximal doses of cerulein was markedly i ncreased not by CCK-, secretin-, or cholinergic-dependent mechanisms b ut probably by acinar cell proliferation.