HYPERCALCEMIA CAUSES ACUTE-PANCREATITIS BY PANCREATIC SECRETORY BLOCK, INTRACELLULAR ZYMOGEN ACCUMULATION, AND ACINAR CELL INJURY

BACKGROUND: Because hypercalcemia is a known etiologic factor for huma n acute pancreatitis, studies of the pancreatic pathophysiology and pa thomorphology of experimental hypercalcemia have potential clinical si gnificance. MATERIALS AND METHODS: Rats received central venous infusi on of either 0.6 mmol/kg per hour CaCl2 or 0.9% NaCl infusion for 12 h ours, Pancreatic tissue samples were obtained and prepared for electro n microscopy. Tissue homogenates were examined for DNA, lactate dehydr ogenase (LDH), protein, amylase, and calcium contents, Basal or stimul ated (cerulein 0.25 mu L/kg per hour) pancreatic secretions were analy zed for volume, protein, and amylase output, as well as protein compos ition on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SD S-PAGE). RESULTS: The tissue calcium content and the ratio of LDI-I to DNA was unchanged after calcium infusion, but the ratios of total pro tein to DNA and of amylase to DNA were significantly larger. Basal out put of pancreatic juice vola volume, protein, and amylase were signifi cantly lower. SDS-PAGE of pancreatic juice revealed weakening of a 70, 000-d band and appearance of lower molecular weight bands in two sampl es. Ultrastructural examination demonstrated accumulation of zymogen g ranules in the acinar cell, large autophagic vacuoles containing remna nts of condensing vacuoles. CONCLUSIONS: These findings suggest that h ypercalcemia induces pancreatic injury via a secretory block, accumula tion of secretory proteins, and possibly activation of proteases.