Histologic and biochemical alterations in experimental acute pancreatitis induced by supramaximal caerulein stimulation.

We studied the histologic and biochemical alterations in experimental acute pancreatitis induced by supramaximal caerulein stimulation in rats. All rats received 4 subcutaneous injections of various doses of caerulein (5-50 micrograms/kg body weight) at hourly intervals over 3 h, and 9 h after the first injection all animals were killed. Subcutaneous injections of 20 micrograms/kg body weight of caerulein induced a significant increase in serum amylase activity and histologic evidence of acute interstitial pancreatitis similar to those observed with the 50 micrograms/kg body weight dosage of caerulein. Therefore, a total of 4 subcutaneous injections of 20 micrograms/kg body weight of caerulein was chosen to study the time-course of structural and biochemical alterations in caerulein-induced acute pancreatitis. Serum amylase activity reached a maximal value of 10-fold increase over the basal values at 6 h, and then decreased gradually to normal values at 18 h after the first injection. Remarkable interstitial edema and cytoplasmic vacuoles in acinar cells were the earliest histologic alterations. Cellular infiltration was prominent at 9-12 h after the first injection. Although these histologic changes almost completely disappeared after 24 h, the reduction in the number of zymogen granules was still detectable by electron microscopic examination even after 7 days. DNA content in the pancreas showed no significant changes following the induction of acute pancreatitis, whereas a moderate to marked reduction in enzyme content persisted after 7 days. Within 14 days after the initiation of the injections, both structural and biochemical changes had completely disappeared.