Gastrointestinal mucosal development and injury in premature lambs supported by the artificial placenta

J Pediatr Surg. 2018 Jun;53(6):1240-1245. doi: 10.1016/j.jpedsurg.2018.02.092. Epub 2018 Mar 8.

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.

Keywords: Artificial placenta; Extracorporeal membrane oxygenation; Gastrointestinal development; Gastrointestinal injury; Premature gastrointestinal tract; Premature lambs.

MeSH terms

  • Animals
  • Artificial Organs*
  • Cell Count
  • Cell Proliferation
  • Enterocytes / cytology
  • Extracorporeal Membrane Oxygenation / methods*
  • Female
  • Gastric Mucosa / growth & development*
  • Gastric Mucosa / pathology
  • Humans
  • Intestinal Mucosa / growth & development*
  • Intestinal Mucosa / pathology
  • Jejunum / growth & development
  • Jejunum / pathology
  • Paneth Cells / cytology
  • Parenteral Nutrition, Total
  • Placenta*
  • Pregnancy
  • Premature Birth
  • Sheep