Abstract
BackgroundPancreatic duct ligation in a minipig model leads to exocrine pancreatic insufficiency (EPI). This allows the study of digestive processes and pancreatic enzyme replacement therapies. However, detailed descriptions of the surgical procedure, perioperative management, a determination of exocrine pancreatic insufficiency are scarce in the literature. Data of the long-term health status of minipigs upon EPI induction are still not available. Therefore, the present study describes in detail an experimental approach to the induction of exocrine pancreatic insufficiency via pancreatic duct ligation in minipigs and the long term follow up of the animal’s health state.Methods14 Goettingen minipigs underwent pancreatic duct ligation via midline laparotomy for the induction of exocrine pancreatic insufficiency. Fecal fat content, fat absorption, chymotrypsin levels, body weight and blood vitamin and glucose levels were determined.ResultsExocrine pancreatic insufficiency was successfully induced in 12 Goettingen minipigs. Two minipigs failed to develop exocrine insufficiency most likely due to undetected accessory pancreatic ducts. All animals tolerated the procedure very well and gained weight within 8 weeks after surgery without requiring pancreatic enzyme replacement therapy. The follow up for approx. 180 weeks showed a stable body weight and health state of the animals with normal blood glucose levels (Table 1). From approx. 130 weeks post pancreatic duct ligation, all animals were supplemented with pancreatic enzymes and vitamins resulting in blood concentrations almost within the reference range.ConclusionsPancreatic duct ligation in minipigs is an excellent method of inducing exocrine pancreatic insufficiency. It is important to identify and ligate accessory pancreatic ducts since persistence of accessory ducts will lead to maintenance of exocrine pancreatic function. The EPI model caused no persistent side effects in the animals and has the potential to be used in long-term EPI studies with up to 100 weeks post-OP without supplementation with enzymes and vitamins.
Highlights
Pancreatic duct ligation in a minipig model leads to exocrine pancreatic insufficiency (EPI)
EPI can be induced by several disorders like cystic fibrosis (CF), acute (AP) or chronic pancreatitis (CP), cancer or diabetes mellitus or as a complication of gastrointestinal surgery [1,2,3]
Animals with an EPI were used for repeated pancreatic enzyme replacement therapy (PERT) studies and the animal health state and dietary and nutrient requirements documented for the following years
Summary
Pancreatic duct ligation in a minipig model leads to exocrine pancreatic insufficiency (EPI). This allows the study of digestive processes and pancreatic enzyme replacement therapies. Exocrine pancreatic insufficiency (EPI) leads to maldigestion of food and malabsorption of nutrients due to an impaired secretion or activity of pancreatic digestive enzymes. Because of the high similarity in digestion compared to humans and the feasibility to ligate the separated pancreatic duct, pigs and especially minipigs are preferred as EPI model to study digestion and absorption of metabolites [7,8,9,10,11,12,13,14,15]. Pancreatic duct ligation without fistulation is sufficient for a streamlined PERT study and allows keeping in groups during non-study periods and comes closer to the 3-R principle
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