Long-term total parenteral nutrition and cholecystostomy tube in a rabbit model surgical procedure: management and preliminary results.

ABSTRACT

A rabbit model for long-term total parenteral nutrition (TPN), specially provided with cholecystostomy tube, was designed to investigate further aspects of TPN-associated cholestasis (TPN-AC). Modified surgical procedures concerning vascular access, cholecystostomy tube implantation and authors' original modalities for prolonged infusion management in the rabbit were used. Continuous TPN was performed in 30 young rabbits. Five animals died during the experiment (16.6%) and were excluded from final evaluation. Twenty-five rabbits were successfully maintained on continuous TPN for 28 days without restraint, having a cholecystostomy tube implanted 1 week after initiation of TPN. The collection of blood samples and daily parenteral administration of drugs were simply accomplished via a central venous catheter. At the same time the cholecystostomy tube enabled us to perform daily bile sampling. Saline irrigation of the biliary tree could be carried out in conscious animals maintained on TPN. A 4-week duration of TPN in this rabbit model made it possible for the first time to accomplish serial liver biopsies in order to verify the evolution of histologic changes in TPN-related hepatic dysfunction and possible effects of surgical and medical treatment. A preliminary analysis of operative findings and histology was carried out. An enlarged gallbladder containing hyperviscous bile was found in 80% of the animals 1 week after initiation of TPN. At this time it was possible to observe the first histologic changes consistent with TPN-associated hepatic disease, such as moderate to severe hepatocyte degeneration and portal inflammation. Biliary sludge was seen after 3 weeks of TPN in 70% of the rabbits, as well as a subsequent progression of TPN-associated histologic findings. Portal fibrosis and fatty liver degeneration occurred in 50% of the rabbits and bile duct proliferation in all animals. After 4 weeks of TPN (at autopsy) gallstones were found in 20% of TPN animals, as well as further progression of bile duct proliferation and fibrosis. Our first experiences with this model and preliminary results suggest that this concept offers new possibilities for further elucidation of TPN-associated hepatic dysfunction.