Our major goals are to evaluate: 1) normal motor function and pressure-flow kinetics of the biliary-pancreatic duct systems in humans and experimental animals, and 2) abnormalities of sphincter of Oddi (SO) and gallbladder 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 modeling will be done to account for pressure-flow dynamics within the common bile duct, SO segment, and gallbladder. Further, we have developed a chronic surgical preparation in the opossum, featuring bipolar electrodes sutured into the SO, stomach and intestine and a gallbladder catheter that the for first time yields long-term recordings of SO motor activity and gallbladder volume in awake, unmedicated animals. This chronic preparation permits: 1) analysis of the pattern of SO myoelectric activity and gallbladder volume in the fasting and fed states, 2) correlation of SO activity and gallbladder volume wit 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. A major goal of our studies is to evaluate potential hormonal and neural physiological mechanisms that may control or regulate SO and gallbladder contractile activity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK030024-07
Application #
3229209
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1982-04-01
Project End
1991-03-31
Budget Start
1988-04-01
Budget End
1989-03-31
Support Year
7
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Medical College of Wisconsin
Department
Type
Schools of Medicine
DUNS #
073134603
City
Milwaukee
State
WI
Country
United States
Zip Code
53226
Hanyu, N; Dodds, W J; Layman, R D et al. (1991) Effect of two new cholecystokinin antagonists on gallbladder emptying in opossums. Am J Physiol 260:G258-64
Ren, J L; Dodds, W J; Martin, C J et al. (1991) Effect of increased intra-abdominal pressure on peristalsis in feline esophagus. Am J Physiol 261:G417-25
Hanyu, N; Dodds, W J; Layman, R D et al. (1990) Mechanism of cholecystokinin-induced contraction of the opossum gallbladder. Gastroenterology 98:1299-306
Hanyu, N; Dodds, W J; Layman, R D et al. (1990) Cholecystokinin-induced contraction of opossum sphincter of Oddi. Mechanism of action. Dig Dis Sci 35:567-76
Dodds, W J (1990) Biliary tract motility and its relationship to clinical disorders. AJR Am J Roentgenol 155:247-58
Helm, J F; Dodds, W J; Christensen, J et al. (1989) Intramural neural control of opossum sphincter of Oddi. Am J Physiol 257:G925-9
Suzuki, T; Dodds, W J; Sarna, S K et al. (1988) Control mechanisms of sphincter of Oddi contraction rate in the opossum. Am J Physiol 255:G619-26
Darweesh, R M; Dodds, W J; Hogan, W J et al. (1988) Roscoe Miller award. Fatty-meal sonography for evaluating patients with suspected partial common duct obstruction. AJR Am J Roentgenol 151:63-8
Darweesh, R M; Dodds, W J; Hogan, W J et al. (1988) Efficacy of quantitative hepatobiliary scintigraphy and fatty-meal sonography for evaluating patients with suspected partial common duct obstruction. Gastroenterology 94:779-86