Extracorporeal Membrane Oxygenation Causes Loss of Intestinal Epithelial Barrier in the Newborn Piglet

Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Pediatric Research (Impact Factor: 2.31). 05/2010; 68(2):128-33. DOI: 10.1203/PDR.0b013e3181e4c9f8
Source: PubMed


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.

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Available from: Yolanda E Hartman, Aug 22, 2014
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    • "Rapid rise of plasma concentrations of inflammatory cytokines during ECMO-related SIRS is due to the release of pre-formed stores in the intestine [19]. Breakdown of mucosal barrier during ECMO increases intestinal permeability and allows translocation of intraluminal bacteria across the mucosa leading to distant organ injury [15]. Strategies to protect gut barrier function and thereby prevent bacterial translocation during ECMO merit comprehensive and further explorations. "
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    ABSTRACT: Backgrounds: Extracorporeal membrane oxygenation (ECMO) has been recommended for treatment of acute, potentially reversible, life-threatening respiratory failure unresponsive to conventional therapy. Intestinal mucosal barrier dysfunction is one of the most critical pathophysiological disorders during ECMO. This study aimed to determine whether combination with CRRT could alleviate damage of intestinal mucosal barrier function during VV ECMO in a porcine model. Twenty-four piglets were randomly divided into control(C), sham(S), ECMO(E) and ECMO + CRRT(EC) group. The animals were treated with ECMO or ECMO + CRRT for 24 hours. After the experiments, piglets were sacrificed. Jejunum, ileum and colon were harvested for morphologic examination of mucosal injury and ultrastructural distortion. Histological scoring was assessed according to Chiu's scoring standard. Blood samples were taken from the animals at -1, 2, 6, 12 and 24 h during experiment. Blood, liver, spleen, kidney and mesenteric lymphnode were collected for bacterial culture. Serum concentrations of diamine oxidase (DAO) and intestinal fatty acid binding protein (I-FABP) were tested as markers to assess intestinal epithelial function and permeability. DAO levels were determined by spectrophotometry and I-FABP levels by enzyme linked immunosorbent assay. Microscopy findings showed that ECMO-induced intestinal microvillus shedding and edema, morphological distortion of tight junction between intestinal mucous epithelium and loose cell-cell junctions were significantly improved with combination of CRRT. No significance was detected on positive rate of serum bacterial culture. The elevated colonies of bacterial culture in liver and mesenteric lymphnode in E group reduced significantly in EC group (p < 0.05). Compared with E group, EC group showed significantly decreased level of serum DAO and I-FABP (p < 0.05). CRRT can alleviate the intestinal mucosal dysfunction and bacterial translocation during VV ECMO, which may extenuate the ECMO-associated SIRS and raise the clinical effect and safety.
    Full-text · Article · Apr 2014 · Journal of Cardiothoracic Surgery
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    • "More recent animal experiments confirmed that after two hours of ECMO treatment, blood and tissues (liver, lung, intestinal and renal) inflammatory cytokines’ (IL-1β, IL-6, IL-8, TNF-a) expression was significantly increased [12]. Another experimental study showed that ECMO treatment can lead to damage of the intestinal mucosal barrier, bacterial translocation, and increased systemic immune inflammatory response [13]. However, it is uncertain whether ECMO treatment can lead to immune inflammatory response as peripheral in cerebral tissues. "
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    ABSTRACT: Extra-Corporeal Membrane Oxygenation (ECMO) therapy is associated with high risk of neurologic injury. But the mechanism of neurologic injury during and/or after ECMO therapy is still unclear. Recent animal experiments confirmed that ECMO treatment increases the immune inflammatory response. The aim of this study is to investigate the effect of VV- ECMO on immune inflammatory response of cerebral tissues and neurological impairment. 18 porcine were randomly divided into control, sham and ECMO group (n = 6/group). ECMO was run 24h in the ECMO group, and serum collected at 0, 2, 6, 12 and 24h during ECMO treatment for the analysis of cytokine(IL-1beta, IL-6, IL-10, TNF-a) and cerebral injury specific biomarker S100B and NSE. After 24h ECMO treatment, all animals were euthanized and cerebral tissues (hypothalamus, hippocampus and cortex) were collected for measure of mRNA and protein levels of cytokine (IL-1beta, IL-6, IL-10, TNF-a). The results during ECMO treatment showed that all the pro-inflammation cytokines were increased significantly after 2h, and anti-inflammation IL-10 showed transient hoist in the first 2h in serum. After 24h ECMO therapy, the mRNA levels of pro-inflammation cytokines and anti-inflammation IL-10 were simultaneously up-regulated in cerebral tissues (hypothalamus, hippocampus and cortex). And protein concentrations also showed different increasing levels in cerebral tissues. However, during the ECMO treatment, S100B and NSE protein in serum did not change significantly. These findings suggest VV-ECMO treatment can not only lead to immune inflammatory response in blood, but can also produce immune and inflammatory response in cerebral tissues. However the extent of immune inflammation was not sufficient to cause significant neurological impairment in this study. But the correlation between cerebral inflammatory response and cerebral impairment need to further explore.
    Full-text · Article · Aug 2013 · Journal of Cardiothoracic Surgery
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    ABSTRACT: Extracorporeal membrane oxygenation (ECMO) is a lifesaving procedure used in neonates, children, and adults with severe, reversible, cardiopulmonary failure. On the basis of single-center studies, the incidence of AKI occurs in 70%-85% of ECMO patients. Those with AKI and those who require renal replacement therapy (RRT) are at high risk for mortality, independent of potentially confounding variables. Fluid overload is common in ECMO patients, and is one of the main indications for RRT. RRT to maintain fluid balance and metabolic control is common in some but not all centers. RRT on ECMO can be performed via an in-line hemofilter or by incorporating a standard continuous renal replacement machine into the ECMO circuit. Both of these methods require specific technical considerations to provide safe and effective RRT. This review summarizes available epidemiologic data and how they apply to our understanding of AKI pathophysiology during ECMO, identifies indications for RRT while on ECMO, reviews technical elements for RRT application in the setting of ECMO, and finally identifies specific research-focused questions that need to be addressed to improve outcomes in this at-risk population.
    Full-text · Article · Apr 2012 · Clinical Journal of the American Society of Nephrology
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