EFFECTS OF DELAYED ADMINISTRATION OF OCTREOTIDE IN ACUTE EXPERIMENTALPANCREATITIS

Multiple therapeutic modalities studied for acute pancreatitis often s how a poor correlation between results obtained in experimental studie s and results of clinical trials. One of the main reasons for this dis crepancy is that in most experimental studies the drugs were administe red immediately after induction of pancreatitis, whereas in the clinic al setting there is almost always a delay between the onset of the dis ease and initiation of the treatment. We studied the effects of a dela yed treatment with octreotide, the synthetic analogue of the hormone s omatostatin, on acute experimental pancreatitis in rats. The disease w as induced by intraparenchymal injections of 0.5 ml 5% sodium taurocho late, and octreotide (10 mg/kg/day s.c.) was started either 4 or 12 hr later, Subcutaneous saline injections were used in controls. One-half of the animals of each study group was sacrificed after 36 hr, and th e following parameters were examined: pancreatic weight, plasma pH, se rum calcium and amylase, and histopathological damage. The same parame ters, as well as survival, were assessed after 20 days in the remainin g rats. Neither intrapancreatic saline injections, nor octreotide admi nistration without the induction of pancreatitis, caused any biochemic al or histological alterations. Hypocalcemia and acidosis in pancreati tis-induced rats were improved by octreotide, but, as expected, it had no effect on amylase levels, Octreotide ameliorated pancreatic edema, intestinal dilatation, and the histopathological injury score 36 hr a fter induction of pancreatitis. Mortality was 40% in control animals, and only 20% in rats treated with octreotide. Overall, octreotide had beneficial effects in acute experimental pancreatitis, and was more ef fective when started earlier. These results indicate that octreotide m ay have a role in the management of acute pancreatitis. (C) 1996 Acade mic Press, Inc.