Effects of delayed administration of octreotide in acute experimental pancreatitis.
Multiple therapeutic modalities studied for acute pancreatitis often show a poor correlation between results obtained in experimental studies and results of clinical trials. One of the main reasons for this discrepancy is that in most experimental studies the drugs were administered immediately after induction of pancreatitis, whereas in the clinical setting there is almost always a delay between the onset of the disease and initiation of the treatment. We studied the effects of a delayed treatment with octreotide, the synthetic analogue of the hormone somatostatin, on acute experimental pancreatitis in rats. The disease was induced by intraparenchymal injections of 0.5 ml 5% sodium taurocholate, 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 the following parameters were examined: pancreatic weight, plasma pH, serum calcium and amylase, and histopathological damage. The same parameters, as well as survival, were assessed after 20 days in the remaining rats. Neither intrapancreatic saline injections, nor octreotide administration without the induction of pancreatitis, caused any biochemical or histological alterations. Hypocalcemia and acidosis in pancreatitis-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 after 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 effective when started earlier. These results indicate that octreotide may have a role in the management of acute pancreatitis.
Kaplan
O
O
Department of Surgery, Tel-Aviv Medical Center, Israel.
Kaplan
D
D
Casif
E
E
Siegal
A
A
Paran
H
H
Graf
E
E
Skornick
Y
Y
D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D002118:Calcium / Q000097:blood; D004195:Disease Models, Animal; D005765:Gastrointestinal Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D006863:Hydrogen-Ion Concentration; D008297:Male; D015282:Octreotide / Q000008:administration & dosage* / Q000627:therapeutic use; D009929:Organ Size; D010179:Pancreas / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013656:Taurocholic Acid; D013997:Time Factors
D005765:Gastrointestinal Agents; D013656:Taurocholic Acid; D000681:Amylases; D015282:Octreotide; D002118:Calcium