Developing a Novel Ambulatory Total Parenteral Nutrition-Dependent Short Bowel Syndrome Animal Model

Abstract

Background: Short Bowel Syndrome (SBS) results from extensive bowel resection. Patients with SBS require Total Parenteral Nutrition (TPN) for survival. Understanding mechanisms contributing to TPN-associated liver injury and gut atrophy are critical in developing SBS therapies. Existing SBS models using tethered animals have significant limitations and are unlike ambulatory human SBS patients. We hypothesized that we could induce SBS in piglets and develop an ambulatory TPN-SBS model. Material and Methods: 18 neonatal pigs received duodenal and jugular catheters. They were fitted with a jacket holding TPN and a miniaturized pump. 6 piglets had 90% small bowel resection and catheter placement (SBS group). Non-SBS piglets were randomized into enteral nutrition (EN) or TPN. Results: Bowel resection was successfully accomplished in SBS animals. Weight gain was similar in all groups. SBS animals had increased serum bilirubin compared to EN. Mean conjugated bilirubin ± SD was 0.045 ± 0.01 for EN, (p=0.03 EN vs TPN and p=0.03 SBS vs EN) and 1.09 ± 1.25 for TPN, (p=0.62 TPN vs SBS). Gut density was reduced in the TPN group compared to EN and SBS groups. Mean gut density ± SD was 0.11 ± 0.04 for TPN (p=0.0004 TPN vs SBS and p=0.00007 TPN vs EN) and not statistically different for EN vs SBS (p=0.32). Conclusion: We created a novel, ambulatory TPN-SBS model using piglets, mimicking longterm TPN delivery in human SBS patients. Our model demonstrated TPN-related conjugated

Impaired Gut–Systemic Signaling Drives Total Parenteral Nutrition-Associated Injury

“…The nutritional constituents are included in Table 1. These formulations, as we have published before, conform to applicable doses in humans [19,20,22]. Table 1.…”

“…In consultation with our university statistician, for our calculations, we used historical data of 5-10-fold changes in serum bilirubin [1,18,30,31], as well as a 2-3 fold reduction in the V/C ratio [1,22,29] with TPN to model the sample size calculation. From our previous work [1,7,8,20,21,32], we predicted that the actual effects across variables would be larger, thus reasonably obtainable with eight animals per group.…”

“…For the EN group, a swine replacement formula was provided enterally, as previously described. For the TPN group, a commercially available parenteral nutrition preparation and lipid was delivered via the jugular catheter, as previously described [1,20,21]. The nutritional constituents are included in Table 1.…”

Beyond lipids: Novel mechanisms for parenteral nutrition–associated liver disease

“…This requires that lipid, carbohydrate, protein, essential vitamins, minerals, and micronutrients are all provided directly into the bloodstream intravenously via an infusion pump, bypassing the alimentary system. 1,2 When a patient receives all nutrients using this process, it is referred to as exclusive PN. A patient might require exclusive PN as a © 2022 American Society for Parenteral and Enteral Nutrition result of intestinal failure, in which there is a lack of functional gut to absorb the nutrients required to support life, or secondary to short-bowel syndrome (SBS) from bowel resection or trauma to the gastrointestinal tract.…”

“…Parenteral nutrition (PN) is a therapy that delivers nutrients intravenously to patients who are unable to meet their nutrition needs via standard enteral feeding routes. This requires that lipid, carbohydrate, protein, essential vitamins, minerals, and micronutrients are all provided directly into the bloodstream intravenously via an infusion pump, bypassing the alimentary system 1,2 . When a patient receives all nutrients using this process, it is referred to as exclusive PN.…”