A RAT MODEL TO STUDY HYPERCALCEMIA-INDUCED ACUTE-PANCREATITIS

Hypercalcemia causes acute pancreatitis in humans, a phenomenon reprod uced experimentally in cats and guinea pigs. Because the rat is the mo st frequently used animal for the study of experimental pancreatitis, the present studies were performed to evaluate the effects of hypercal cemia in the rat. In in vitro studies, pancreatic lobules were prepare d from fasted Wistar rats (200-250 g) and incubated in HEPES bicarbona te-buffered medium (pH 7.4) containing 0, 0.6, 1.2, 2.5, 5, and 10 mM CaCl2 with or without carbachol 10(-6)M. Amylase was measured in the m edium after 30 min to 3 h, and expressed as percent of total amylase. In in vivo studies, fasted male Wistar rats (300-400 g) received calci um (CaCl2; 0.6 mmol/kgh) into the tail vein for 12 h. Control animals received NaCl 0.9% infusion. Histologic slides (H&E-stained) were eval uated in a blinded fashion. Pancreatic lobules showed a higher basal a mylase output when incubated in higher calcium medium. The largest, si gnificant difference (2.6-fold) was between 0.6 and 5 mM medium CaCl2 (p < 0.05). Carbachol-stimulated amylase release was again higher with increasing medium calcium with the most pronounced difference (1.3-fo ld) between 0.6 and 2.5 mM CaCl2 (p < 0.05). In vivo calcium-treated a nimals showed accumulation of zymogen granules in the cytoplasm, cytop lasmic vacuolization, focal acinar cell depolarization, acinar necrosi s, and edema. Calcium causes amylase release from rat pancreatic lobul es in vitro. Higher medium calcium levels both significantly increase amylase release from unstimulated and carbachol stimulated lobules. Tw elve-hour in vivo calcium infusion leads to accumulation of zymogen gr anules in acinar cells and acinar injury. These findings are consisten t with pancreatitis evolving from calcium-induced hypersecretion to a secretion block lesion in the rat.