Adaptation of pancreas to repeated caerulein-induced pancreatitis in rats

Induction by caerulein of acute pancreatitis with tissue damage and acinar cells loss is followed by recovery. We studied biochemical, histological and functional regeneration of pancreatic tissue after repeated acute pancreatitis. Pancreatitis was evoked in rats by s.c. infusion of caerulein (10 micrograms/kg/h) for 5 h. After infusion, rats were divided into three groups. First group was infused with caerulein one time, in the second group infusion of caerulein was repeated 10 days later. The third groups was infused with caerulein for the 3rd time 10 days after the 2nd infusion. Rats were sacrificed at time sequence of 0, 12, 24, 48, 72 hours and at 5th, and 10th day after last infusion of caerulein. Pancreatic blood flow (PBF) was measured using laser Doppler flowmeter. Plasma and pancreatic amylase, pancreatic weight, RNA and DNA contents, and histological changes were determined. We found that DNA and RNA content, as well, as histological changes in 1st group showed progressive regeneration after 3 days. Regeneration after 1st time caerulein-induced pancreatitis was almost completed within 10 days and amylase content in the tissue and plasma amylase level returned to normal values. Each subsequent infusion of caerulein caused significantly less pronounced destruction of the pancreatic tissue, however, the regeneration occurred progressively later than after the 1st or 2nd infusion. Tissue repair after the 2nd infusion reached peak at 5th day while after 3rd infusion at 10th day. PBF dropped after 1st caerulein induced pancreatitis by about 50% but with repeated caerulein induced pancreatitis lower decreases in PBF were observed and they returned in shorter time back to control value. These results indicate that the pancreas is able to adapt to repeated injury and this is manifested by cumulative decrease of pancreatic damage after each repetition of induction of acute pancreatitis and correlated with the preservation of PBF, however, the pancreatic tissue regeneration is significantly delayed.