A rat model to study hypercalcemia-induced acute pancreatitis.
Hypercalcemia causes acute pancreatitis in humans, a phenomenon reproduced experimentally in cats and guinea pigs. Because the rat is the most frequently used animal for the study of experimental pancreatitis, the present studies were performed to evaluate the effects of hypercalcemia in the rat. In in vitro studies, pancreatic lobules were prepared from fasted Wistar rats (200-250 g) and incubated in HEPES bicarbonate-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 medium 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 calcium (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 evaluated in a blinded fashion. Pancreatic lobules showed a higher basal amylase output when incubated in higher calcium medium. The largest, significant 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-fold) between 0.6 and 2.5 mM CaCl2 (p < 0.05). In vivo calcium-treated animals showed accumulation of zymogen granules in the cytoplasm, cytoplasmic vacuolization, focal acinar cell depolarization, acinar necrosis, and edema. Calcium causes amylase release from rat pancreatic lobules in vitro. Higher medium calcium levels both significantly increase amylase release from unstimulated and carbachol stimulated lobules. Twelve-hour in vivo calcium infusion leads to accumulation of zymogen granules in acinar cells and acinar injury.(ABSTRACT TRUNCATED AT 250 WORDS)
Frick
T W
TW
Department of Surgery, Massachusetts General Hospital, Boston 02114.
Wiegand
D
D
Bimmler
D
D
Fernández-del Castillo
C
C
Rattner
D W
DW
Warshaw
A L
AL
D000208:Acute Disease; D000681:Amylases / Q000378:metabolism; D000818:Animals; D002122:Calcium Chloride / Q000633:toxicity; D004195:Disease Models, Animal; D006934:Hypercalcemia / Q000139:chemically induced / Q000150:complications*; D008297:Male; D010179:Pancreas / Q000378:metabolism / Q000648:ultrastructure; D010195:Pancreatitis / Q000209:etiology* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
D000681:Amylases; D002122:Calcium Chloride