ACUTE HYPERCALCEMIA CAUSES ACUTE-PANCREATITIS AND ECTOPIC TRYPSINOGENACTIVATION IN THE RAT

Background & Aims: Clinical and experimental observations have associa ted acute and chronic hypercalcemia with pancreatitis. The aim of this study was to determine whether acute hypercalcemia can induce acute p ancreatitis and, if so, whether the pathogenesis involves premature pr otease activation. Methods: Rats given bolus infusions of CaCl2 (200 m g/kg; n = 76) were compared with saline-treated controls (n = 40). Ser um [Ca2+], serum amylase activity, trypsinogen activation peptide (TAP ) concentration in serum and pancreatic tissue, pancreatic wet/dry wei ght ratio, and histology were assessed for 24 hours. For dose-response analysis, CaCl2 was injected at a dose of 50-200 mg/kg, and the afore mentioned indices were assayed for 1 hour (n = 5 each). Results: There were no significant changes in the controls. Calcium infusion increas ed serum [Ca2+] 3-fold after 5 minutes (P < 0.001). Within 1 hour, ser um amylase (2.5-fold) and tissue TAP (3-fold) levels increased along w ith macroscopic and microscopic edema formation and leukocytic infiltr ation. The extent of the changes at 1 hour correlated with the calcium dose. Amylase and tissue TAP concentrations remained elevated until 2 4 hours when serum TAP concentration had increased (P < 0.001) and foc al acinar necrosis became evident. Conclusions: Acute experimental hyp ercalcemia induces dose-dependent morphological alterations characteri stic of acute pancreatitis, acute hyperamylasemia, and early ectopic t rypsinogen activation. This supports the pathophysiological relevance of excess calcium and offers a possible pathogenetic mechanism for its association with clinical pancreatitis.