Sphincter of Oddi dysfunction produces acute pancreatitis in the possum

Background - Sphincter of Oddi dysfunction has been implicated as a cause of various forms of acute pancreatitis. However, there is no direct evidence to show that sphincter of Oddi dysfunction can cause obstruction of trans-sphincteric flow resulting in acute pancreatitis. Aims - To determine if induced sphincter of Oddi spasm can produce trans-sphincteric obstruction and, in combination with stimulated pancreatic secretion, induce acute pancreatitis. Methods - In anaesthetised possums, the pancreatic duct was ligated and pancreatic exocrine secretion stimulated by cholecystokinin octapeptide/secretin to induce acute pancreatitis. In separate animals, carbachol was applied topically to the sphincter of Oddi to cause transient sphincter obstruction. Sphincter of Oddi motility, trans-sphincteric flow, pancreatic duct pressure, pancreatic exocrine secretion, plasma amylase levels, and pancreatic tissue damage (histology score) were studied and compared with variables in ligation models. Results - Acute pancreatitis developed following stimulation of pancreatic exocrine secretion with peptides after pancreatic duct ligation (p<0.05). Neither pancreatic duct ligation nor stimulation of pancreatic exocrine secretion with cholecystokinin octapepti31yde/secretin alone resulted in acute pancreatitis. Topical carbachol stimulated sphincter of Oddi motility abolished trans-sphincteric flow, and increased pancreatic exocrine secretion (p<0.05) and pancreatic duct pressure to levels comparable with pancreatic duct ligation (p<0.001). Carbachol application (with or without combined peptide stimulation) elevated plasma amylase levels (p<0.01) and produced pancreatic tissue damage (p<0.05). Decompression of pancreatic duct ameliorated these effects (p<0.05). Conclusion - Induced sphincter of Oddi dysfunction when coupled with stimulated pancreatic secretion causes acute pancreatitis. This may be an important pathophysiological mechanism causing various forms of acute pancreatitis.