An In-Line Digestive Cartridge Reduces Dependence on Parenteral Nutrition and Promotes Intestinal Adaptation in a Porcine Model of Short Bowel Syndrome
Savas T. Tsikis1,2, Scott C. Fligor1,2, Thomas I. Hirsch1,2, Paul D. Mitchell3, Amy Pan1,2, Kamila Moskowitzova2, Ashlyn Whitlock2, Greta Loring4, Eric First4, Arthur P. Nedder5, Kathleen M. Gura6, Mark Puder1,2
1Vascular Biology Program, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; 2Department of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; 3Institutional Centers for Clinical and Translational Research, Boston Children's Hospital, Boston, MA, USA; 4Alcresta Therapeutics, Newton, MA, USA; 5Animal Care Resources Children's Hospital, Boston Children's Hospital, Boston, MA, USA; 6Department of Pharmacy and the Division of Gastroenterology and Nutrition, Boston Children's Hospital, Boston, MA, USA
Background: Short bowel syndrome (SBS) occurs after intestinal loss resulting in malabsorption and parenteral nutrition (PN) dependence. Utilizing a porcine SBS model, we studied an immobilized lipase cartridge (ILC) that hydrolyzes fats in enteral nutrition (EN). The primary aim was to determine whether use of the ILC will reduce PN dependence.
Methods: Eleven male Yorkshire piglets underwent 75% jejunoileal resection and were randomized to control (n=6) and treatment (n=5). PN was initiated postoperatively and reduced as EN advanced. EN advancement occurred if pre-defined clinical criteria were fulfilled. Animals were studied for 14 days and the change in PN/EN calories was assessed. Intestinal adaptation, absorption, and nutrition were evaluated at the end of the study (day 15).
Results: Animals randomized to ILC treatment demonstrated 19% greater reduction in PN calories (P<0.0001) and higher EN advancement (66% vs. 47% of total calories, P<0.0001). Treatment animals had increased intestinal length (19.5% vs. 0.7%, P=0.03) and 1.9-fold higher crypt cell proliferation (P=0.02) compared to controls. By day 15, ILC treatment resulted in higher plasma concentrations of glucagon-like-peptide-2 (P=0.02), eicosapentaenoic acid (P<0.0001), docosahexaenoic acid (P=0.004), Vitamin A (P=0.02), LDL (P=0.02), and HDL (P=0.04).
Conclusion: ILC use in conjunction with enteral feeding reduced PN dependence, improved nutritional markers, and increased bowel adaptation and growth in a porcine SBS model. These results support a potential role for the ILC in clinical SBS.
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