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Research Project: Molecular, Cellular, and Regulatory Aspects of Nutrition During Development

Location: Children's Nutrition Research Center

Title: Validating hyperbilirubinemia and gut mucosal atrophy with a novel ultramobile ambulatory total parenteral nutrition piglet model

Author
item Jain, Ajay - St Louis University
item Wen, Joy - St Louis University
item Arora, Sumit - St Louis University
item Blomenkamp, Keith - St Louis University
item Rodrigues, Jonathan - St Louis University
item Blaufuss, Timothy - St Louis University
item Liou, Victor - St Louis University
item Burrin, Douglas - Doug
item Long, John - St Louis University
item Teckman, Jeffrey - St Louis University

Submitted to: Nutrition Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/28/2014
Publication Date: 12/31/2014
Citation: Jain, A.K., Wen, J.X., Arora, S., Blomenkamp, K.S., Rodrigues, J., Blaufuss, T.A., Liou, V., Burrin, D.G., Long, J.P., Teckman, J.H. 2014. Validating hyperbilirubinemia and gut mucosal atrophy with a novel ultramobile ambulatory total parenteral nutrition piglet model. Nutrition Research. 35(2):169-174.

Interpretive Summary: Many premature infants born in the United States rely on intravenous nutrition support by a technique called Total Parenteral Nutrition (TPN). We have previously established that piglets are an excellent animal to model the nutrition effects of TPN. The aim of this study was to establish a more clinically relevant and non-invasive approach of ultramobile ambulatory pumps to deliver the TPN in piglets. Such an approach would also reduce the costs compared to our previously established tethered TPN model system. The results suggest that the ambulatory model is feasible and reproduced the hallmark effects of TPN such as reduced gut growth and mild liver disease seen in previous studies.

Technical Abstract: Total parenteral nutrition (TPN) provides all nutrition intravenously. Although TPN therapy has grown enormously, it causes significant complications, including gut and hepatic dysfunction. Current models use animal tethering which is unlike ambulatory human TPN delivery and is cost prohibitive. We hypothesize that using ultramobile infusion pumps, TPN can be delivered cost-effectively, resulting in classical gut and hepatic injury, and we thus aim to establish a new model system. Neonatal pigs (n = 8) were implanted with jugular vein and duodenal catheters. Animals were fitted in dual-pocket jackets. An ultramobile ambulatory pump was placed in one pocket and connected to the jugular vein or duodenal catheter. Isocaloric TPN or swine formula was placed in the other pocket. Rigorous Wifi-based video and scheduled monitoring was performed. After 14 days, the animals were euthanized. The mean (+/- SD) daily weight gain (in grams) for enteral-fed control (EN) vs TPN animals was 102.4 +/- 10.8 and 91.03 +/- 12.1 respectively (P < .05). Total parenteral nutrition resulted in significant conjugated bilirubin elevation and hepatomegaly. Mean (+/-SD) serum conjugated bilirubin (in micromol/L) was 1.5 +/-0.7 for EN and 6.3 +/- 2.8 for TPN (P < .05). Marked gut atrophy was noted with TPN. The mean (+/-SD) gut weight as a percent of body weight was 4.30 +/- 0.26 for EN and 2.62 +/- 0.48 for TPN (P < .05). Surgical sites healed well. All animals remained completely mobile. We thus established that TPN can be successfully delivered using ultramobile pumps and believe that this remains the first such description of an ambulatory piglet TPN model system. In addition to cholestasis and gut atrophy, classical TPN-induced injury was documented.