Model of TPN-associated hepatobiliary dysfunction in the young pig

Abstract

Gallbladder 'sludge' and cholestasis are two common complications associated with total parenteral nutrition (TPN), but the aetiology of each is uncertain. An animal model has been developed in the young pig which demonstrates these two complications. Five female piglets, of Landrace Large White Cross variety weighing 4.5-5.9 kg, received nutritional support for 2 weeks with a continuous infusion of TPN solution at a dose of 150 kcal kg-1 day-1. The solution was 35 per cent dextrose, 5 per cent L-amino acids with conventional electrolyte, mineral and vitamin additives. No lipid was used in the solution. Five weight-matched animals were used as controls. All animals in the TPN group developed 'sludge' in their gallbladders, decreased basal bile flow, decreased bile salt excretion and a diminished response to bile salt stimulated bile flow, as compared with controls. There was no abnormality in routine liver function tests or liver histology. It is concluded that TPN therapy in this animal model is associated with the appearance of gallbladder 'sludge', and cholestasis as demonstrated by direct bile flow studies. It is suggested that this bile flow abnormality is due to a decrease in bile salt dependent and bile salt independent fractions of canalicular bile flow. The model provides the opportunity to investigate TPN related hepatobiliary dysfunction in an animal that has similar liver function to man and comparable nutritional requirements.

Effects of Lipid-Supplemented Total Parenteral Nutrition on Fatty Liver Disease in a Premature Neonatal Piglet Model

“…Animal models allow co- trolled experimental development of TPN. We have shown that piglets can be maintained for up to 7 days on the same TPN regimes used for human neonates, something that cannot be done in the rat [25] . During TPN, the piglets showed typical responses previously reported in human infants.…”

“…Most infants on TPN suffer clinical complications, therefore metabolic requirements are complex and data interpretation is difficult [25] . Animal models allow co- trolled experimental development of TPN.…”

“…The TPN solution was formulated according to the prescription used by the local neonatal care centre (The William Harvey Hospital, Ashford, Kent). As humans and pigs have similar nutritional requirements [27] it is possible to provide adequate nutritional support in the pig using clinical TPN regimes, which is useful in establishing an animal model with clinical relevance [25] .…”

“…When modelling liver function and metabolism in human neonates, the pig has advantages over other animal models, as it has similar hepatic structure, histology and physiology [22][23][24] and unlike the rat, both humans and pigs possess a gall bladder [25] . The piglet is less mature at birth than the human neonate, due to reduced growth rate and maturation during the final stages of development [26] .…”

Influence of Fatty Acid Profile of Total Parenteral Nutrition Emulsions on the Fatty Acid Composition of Different Tissues of Piglets

“…The TPN solution was formulated according to the prescription used by the local neonatal care centre (The William Harvey Hospital, Ashford, Kent). As humans and pigs have similar nutritional requirements [25] it is possible to provide adequate nutritional support in the pig using clinical TPN regimes, which is useful in establishing an animal model with clinical relevance [26].…”