Jennifer S McLeod1, Joseph T Church2, Prathusha Yerramilli2, Megan A Coughlin2, Elena M Perkins2, Raja Rabah3, Robert H Bartlett2, Alvaro Rojas-Pena2, Joel K Greenson4, Erin E Perrone5, George B Mychaliska5. 1. Extracorporeal Life Support Laboratory, Department of Surgery, Michigan Medicine, Ann Arbor, MI. Electronic address: mcleodj@umich.edu. 2. Extracorporeal Life Support Laboratory, Department of Surgery, Michigan Medicine, Ann Arbor, MI. 3. Department of Pathology, Michigan Medicine, Ann Arbor, MI. 4. Department of Gastrointestinal Pathology, Michigan Medicine, Ann Arbor, MI. 5. Extracorporeal Life Support Laboratory, Department of Surgery, Michigan Medicine, Ann Arbor, MI; Fetal Diagnosis and Treatment Center, C.S. Mott Children's Hospital, Michigan Medicine, Ann Arbor, MI.
Abstract
BACKGROUND: An Artificial Placenta (AP) utilizing extracorporeal life support (ECLS) could revolutionize care of extremely premature newborns, but its effects on gastrointestinal morphology and injury need investigation. METHODS: Lambs (116-121days GA, term=145; n=5) were delivered by C-section, cannulated for ECLS, had total parenteral nutrition (TPN) provided, and were supported for 7days before euthanasia. Early and Late Tissue Controls (ETC, n=5 and LTC, n=5) delivered at 115-121days and 125-131days, respectively, were immediately sacrificed. Standardized jejunal samples were formalin-fixed for histology. Crypt depth (CD), villus height (VH), and VH:CD ratios were measured. Measurements also included enterocyte proliferation (Ki-67), Paneth cell count (Lysozyme), and injury scores (H&E). ANOVA and Chi Square were used with p<0.05 considered significant. RESULTS: CD, VH, and VH:CD were similar between groups (p>0.05). AP demonstrated more enterocyte proliferation (95.7±21.8) than ETC (49.4±23.4; p=0.003) and LTC (66.1+11.8; p=0.04), and more Paneth cells (81.7±17.5) than ETC (41.6±7.0; p=0.0005) and LTC (40.7±8.2, p=0.0004). Presence of epithelial injury and congestion in the bowel of all groups were not statistically different. No villus atrophy or inflammation was present in any group. CONCLUSIONS: This suggests preserved small bowel mucosal architecture, high cellular turnover, and minimal evidence of injury. STUDY TYPE: Research paper/therapeutic potential. LEVEL OF EVIDENCE: N/A.
BACKGROUND: An Artificial Placenta (AP) utilizing extracorporeal life support (ECLS) could revolutionize care of extremely premature newborns, but its effects on gastrointestinal morphology and injury need investigation. METHODS:Lambs (116-121days GA, term=145; n=5) were delivered by C-section, cannulated for ECLS, had total parenteral nutrition (TPN) provided, and were supported for 7days before euthanasia. Early and Late Tissue Controls (ETC, n=5 and LTC, n=5) delivered at 115-121days and 125-131days, respectively, were immediately sacrificed. Standardized jejunal samples were formalin-fixed for histology. Crypt depth (CD), villus height (VH), and VH:CD ratios were measured. Measurements also included enterocyte proliferation (Ki-67), Paneth cell count (Lysozyme), and injury scores (H&E). ANOVA and Chi Square were used with p<0.05 considered significant. RESULTS:CD, VH, and VH:CD were similar between groups (p>0.05). AP demonstrated more enterocyte proliferation (95.7±21.8) than ETC (49.4±23.4; p=0.003) and LTC (66.1+11.8; p=0.04), and more Paneth cells (81.7±17.5) than ETC (41.6±7.0; p=0.0005) and LTC (40.7±8.2, p=0.0004). Presence of epithelial injury and congestion in the bowel of all groups were not statistically different. No villus atrophy or inflammation was present in any group. CONCLUSIONS: This suggests preserved small bowel mucosal architecture, high cellular turnover, and minimal evidence of injury. STUDY TYPE: Research paper/therapeutic potential. LEVEL OF EVIDENCE: N/A.
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