title: Extracorporeal membrane oxygenation causes loss of intestinal epithelial barrier in the newborn piglet.
abstract: Extracorporeal membrane oxygenation (ECMO) is an important life-support system used in neonates and young children with intractable cardiorespiratory failure. In this study, we used our porcine neonatal model of venoarterial ECMO to investigate whether ECMO causes gut barrier dysfunction. We subjected 3-wk-old previously healthy piglets to venoarterial ECMO for up to 8 h and evaluated gut mucosal permeability, bacterial translocation, plasma levels of bacterial products, and ultrastructural changes in gut epithelium. We also measured plasma lipopolysaccharide (LPS) levels in a small cohort of human neonates receiving ECMO. In our porcine model, ECMO caused a rapid increase in gut mucosal permeability within the first 2 h of treatment, leading to a 6- to 10-fold rise in circulating bacterial products. These changes in barrier function were associated with cytoskeletal condensation in epithelial cells, which was explained by phosphorylation of a myosin II regulatory light chain. In support of these findings, we also detected elevated plasma LPS levels in human neonates receiving ECMO, indicating a similar loss of gut barrier function in these infants. On the basis of these data, we conclude that ECMO is an independent cause of gut barrier dysfunction and bacterial translocation may be an important contributor to ECMO-related inflammation.
authors.affiliation: Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Ashish R
authors.initials: AR
authors.lastname: Kurundkar
authors.forename: Cheryl R
authors.initials: CR
authors.lastname: Killingsworth
authors.forename: R Britt
authors.initials: RB
authors.lastname: McIlwain
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Timpa
authors.forename: Yolanda E
authors.initials: YE
authors.lastname: Hartman
authors.forename: Dongning
authors.initials: D
authors.lastname: He
authors.forename: Rajendra K
authors.initials: RK
authors.lastname: Karnatak
authors.forename: Mary L
authors.initials: ML
authors.lastname: Neel
authors.forename: John P
authors.initials: JP
authors.lastname: Clancy
authors.forename: G M
authors.initials: GM
authors.lastname: Anantharamaiah
authors.forename: Akhil
authors.initials: A
authors.lastname: Maheshwari
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001419:Bacteria / Q000378:metabolism; D002463:Cell Membrane Permeability; D002648:Child; D003599:Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D015199:Extracorporeal Membrane Oxygenation / Q000009:adverse effects*; D015870:Gene Expression; D006801:Humans; D007231:Infant, Newborn; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism / Q000382:microbiology / Q000473:pathology* / Q000648:ultrastructure; D008070:Lipopolysaccharides / Q000097:blood; D013552:Swine; D019108:Tight Junctions / Q000502:physiology / Q000648:ultrastructure
chemical_list: D008070:Lipopolysaccharides