Developments in the technique of sphincter of Oddi manometry and investigation of sphincter of Oddi dysfunction

MDThe hazardous technique of endoscopic manometry precludes the investigation of "normal volunteers" required to advance our knowledge of the physiology and pathophysiology of the sphincter of Oddi, a suitable animal model is required. Large and small animal models have been proposed, as yet no one model has been accepted as being representative of the human sphincter of Oddi. Furthermore no animal model of sphincter of Oddi dysfunction has been developed. In this thesis a porcine animal model of sphincter of Oddi function has been developed. The importance of selecting the appropriate anaesthetic agent, enflurane, has been proven. The effect of cholecystectomy on the porcine sphincter of Oddi is shown to have no overall significant effect on sphincter motility when compared to a sham laparotomy group. However, two of the seven pigs after cholecystectomy showed a paradoxical rise in sphincter basal pressure after cholecystokinin infusion, these animal may represent porcine sphincter of Oddi dysfunction. Although substance P is found throughout the intestinal tract including the sphincter of Oddi of man and pig its action was hitherto unknown. In this thesis exogenous substance P was shown to stimulate the sphincter of Oddi in vivo. In this thesis the first development in sphincter of Oddi manometry catheter design in nearly twenty years is presented. A superior nine lumen catheter has been evaluated in porcine model and subsequently used to assess sphincter of Oddi asymmetry in man. Two retrospective studies are reported in this thesis; an audit of the largest U. K. series, and a study assessing the relationship of sphincter of Oddi motility and duodenal activity. Tachyoddia dissociated from the duodenal migrating motor complex was associated with a raised sphincter of Oddi basal pressure and may be a part of sphincter of Oddi dysfunction