A Digestive Cartridge Reduces Parenteral Nutrition Dependence and Increases Bowel Growth in a Piglet Short Bowel Model

Author:

Tsikis Savas T.12,Fligor Scott C.12,Hirsch Thomas I.12,Mitchell Paul D.3,Pan Amy12,Moskowitzova Kamila2,Whitlock Ashlyn E.2,Loring Greta4,First Eric4,Nedder Arthur5,Gura Kathleen M.6,Puder Mark12

Affiliation:

1. Vascular Biology Program, Boston Children’s Hospital, Harvard Medical School, Boston, MA

2. Department of Surgery, Boston Children’s Hospital, Harvard Medical School, Boston, MA

3. Institutional Centers for Clinical and Translational Research, Boston Children’s Hospital, Boston, MA

4. Alcresta Therapeutics, Newton, MA

5. Animal Care Resources Children’s Hospital, Boston Children’s Hospital, Boston, MA

6. Department of Pharmacy and the Division of Gastroenterology and Nutrition, Boston Children’s Hospital, Harvard Medical School, Boston, MA

Abstract

Objective: To determine whether the use of an immobilized lipase cartridge (ILC) to hydrolyze fats in enteral nutrition (EN) reduces parenteral nutrition (PN) dependence in a porcine model of short bowel syndrome with intestinal failure (SBS-IF). Background: SBS-IF occurs after intestinal loss resulting in malabsorption and PN dependence. Limited therapeutic options are available for achieving enteral autonomy. Methods: Eleven Yorkshire piglets underwent 75% jejunoileal resection and were randomized into control (n=6) and treatment (n = 5) groups. PN was initiated postoperatively and reduced as EN advanced if predefined clinical criteria were fulfilled. Animals were studied for 14 days and changes in PN/EN calories were assessed. Intestinal adaptation, absorption, and nutrition were evaluated at the end of the study (day 15). Comparisons between groups were performed using analysis of covariance adjusted for baseline. Results: ILC animals demonstrated a 19% greater reduction in PN calories (P < 0.0001) and higher mean EN advancement (66% vs 47% of total calories, P < 0.0001) during the 14-day experiment. 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 with 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), low-density lipoprotein (P = 0.02), and high-density lipoprotein (P = 0.04). There were no differences in liver enzymes or total bilirubin between the two groups. Conclusions: ILC use in conjunction with enteral feeding reduced PN dependence, improved nutrient absorption, and increased bowel growth in a porcine SBS-IF model. These results support a potential role for the ILC in clinical SBS-IF.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Surgery

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