The major goals of this study proposal are to evaluate: 1) normal motor function and flow dynamics of the biliary-pancreatic duct systems in humans and experimental animals, and 2) abnormalities of sphincter of Oddi(SO) function in humans. For this purpose a large number of investigators have been assembled representing the disciplines of gastroenterology, surgery, bioengineering, radiology and pathology. Recent advances in instrumentation now allow high-fidelity intraluminal manometry of the biliary-pancreatic duct systems in both humans and experimental animals. In humans, manometry of the SO segment can be readily performed during ERCP examination. We have selected the opossum as a major experimental model because: 1) the SO segment in this species is largely extraduodenal, thereby avoiding unwanted """"""""noise"""""""" from duodenal motor activity, and 2) phasic contractile activity in the opossum SO exhibits pressure characteristics similar to those recorded from the SO in man. From experimental data mathematical modelling will be done to accouhnt for flow dynamics within the common bile duct and SO segment. Further, we have developed a chronic surgical preparation in the opossum, featuring bipolar electrodes sutured into the SO, stomach and intestine that for the first time yields long-term recordings of SO motor activity in awake, unmedicated animals. This chronic preparation permits: 1) analysis of the pattern of SO myoelectric activity in the fasting and fed states, 2) correlation of SO activity with intestinal motor activity, and 3) determination of the effects of drugs and hormones on the motor function of the SO as well as on the intestine.
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