A chronic conscious dog model for direct transhepatic studies in normal and pancreatic islet cell transplanted dogs

A chronic conscious, large mammal model for repeated transhepatic studies over a period of 6-8 weeks has been developed for application to the study of the hepatic effects of pancreatic hormone secretion and glucose metabolism, studies of the hepatic mechanisms associated with high first-pass drug metabolism and food interactions, and studies of insulin balance in dogs that have undergone previous pancreatectomy and islet cell auto-transplantation. The preparation of specialized blood sampling catheters and blood flow probes, surgical preparations, pre- and postoperative care, catheter maintenance, and possible complications are described. Data from an oral glucose meal (OMT) are presented. Frequent blood samples from portal, hepatic and jugular veins, and carotid artery were collected and analyzed for plasma insulin concentrations (IRI) and glucose. IRI fluxes were determined for each time period by interpolation of flux X time curves. Total IRI flux was determined as the sum of the areas under the curves for each sampling period. Hepatic insulin extraction was calculated for each sampling interval. By this method of analysis, it was possible to determine hepatic IRI extraction during non-steady-state conditions. The techniques described in the development of this complex animal model, which allows for repeated transhepatic studies in the same conscious subject, may also have application in other chronic studies involving organs other than the liver.