RESUMEN
Neonates and young infants exposed to extracorporeal circulation during extracorporeal membrane oxygenation (ECMO) and cardiopulmonary bypass are at risk of developing a systemic inflammatory response syndrome with multi-organ dysfunction. We used a piglet model of ECMO to investigate the hypothesis that epithelial apoptosis is an early event that precedes villous damage during ECMO-related bowel injury. Healthy 3-week-old piglets were subjected to ECMO for up to 8 h. Epithelial apoptosis was measured in histopathological analysis, nuclear imaging, and terminal deoxynucleotidyl transferase dUTP nick end labeling. Plasma intestinal fatty acid-binding protein (I-FABP) levels were measured by enzyme immunoassay. Intestinal mast cells were isolated by fluorescence-assisted cell sorting. Cleaved caspase-8, caspase-9, phospho-p38 MAPK, and fas ligand expression were investigated by immunohistochemistry, western blots, and reverse transcriptase-quantitative PCR. Piglet ECMO was associated with increased gut epithelial apoptosis. Extensive apoptotic changes were noted on villus tips and in scattered crypt cells after 2 h of ECMO. After 8 h, the villi were denuded and apoptotic changes were evident in a majority of crypt cells. Increased circulating I-FABP levels, a marker of gut epithelial injury, showed that epithelial injury occurred during ECMO. We detected increased cleaved caspase-8, but not cleaved caspase-9, in epithelial cells indicating that the extrinsic apoptotic pathway was active. ECMO was associated with increased fas ligand expression in intestinal mast cells, which was induced through activation of the p38 mitogen-activated protein kinase. We conclude that epithelial apoptosis is an early event that initiates gut mucosal injury in a piglet model of ECMO.
Asunto(s)
Apoptosis/fisiología , Oxigenación por Membrana Extracorpórea/efectos adversos , Mucosa Intestinal/lesiones , Mucosa Intestinal/fisiopatología , Animales , Animales Recién Nacidos , Western Blotting , Caspasa 8/metabolismo , Caspasa 9/metabolismo , Núcleo Celular/ultraestructura , Cartilla de ADN/genética , Ensayo de Inmunoadsorción Enzimática , Proteína Ligando Fas/metabolismo , Proteínas de Unión a Ácidos Grasos/sangre , Citometría de Flujo , Inmunohistoquímica , Etiquetado Corte-Fin in Situ , Mucosa Intestinal/citología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Estadísticas no Paramétricas , Porcinos , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
Lower extremity ischemia is an important source of morbidity with femoral venoarterial extracorporeal membrane oxygenation support. We describe our experience with the use of a side-arm graft sewn to the femoral artery that facilitates adequate extracorporeal membrane oxygenation flow while preventing lower extremity ischemia.
Asunto(s)
Oxigenación por Membrana Extracorpórea/efectos adversos , Oxigenación por Membrana Extracorpórea/métodos , Arteria Femoral/cirugía , Isquemia/prevención & control , Pierna/irrigación sanguínea , Adolescente , Adulto , Anastomosis Quirúrgica , Cateterismo , Humanos , Isquemia/etiología , Masculino , Procedimientos Quirúrgicos Vasculares/métodos , Adulto JovenRESUMEN
Extracorporeal membrane oxygenation (ECMO) is universally accepted as a potential lifesaving therapy for neonates suffering severe cardiorespiratory failure, with survival reported as 81% weaning off ECMO and 69% to hospital discharge in this population. Although ECMO may reduce mortality in certain neonatal patients, it is associated with significant complications. Air in the circuit complicates 4.9% of neonatal ECMO runs, and it is crucial that all ECMO caregivers are trained in the prevention of air embolism and possess the knowledge necessary to efficiently identify and remove air from the ECMO circuit to prevent life threatening consequences. We present a fatal case of neonatal systemic air embolism leading to massive entrainment of air into the ECMO venous return cannula of a neonatal patient with acute respiratory distress syndrome following repair of obstructed total anomalous pulmonary venous connection. We describe the pathophysiology and presentation of this rare condition and the importance of early recognition, due to its high mortality rate.
Asunto(s)
Embolia Aérea/etiología , Oxigenación por Membrana Extracorpórea/efectos adversos , Síndrome de Dificultad Respiratoria/terapia , Embolia Aérea/diagnóstico , Resultado Fatal , Femenino , Humanos , Recién NacidoRESUMEN
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.
Asunto(s)
Animales Recién Nacidos , Permeabilidad de la Membrana Celular , Oxigenación por Membrana Extracorpórea/efectos adversos , Mucosa Intestinal/patología , Animales , Bacterias/metabolismo , Niño , Citoesqueleto/metabolismo , Citoesqueleto/ultraestructura , Expresión Génica , Humanos , Recién Nacido , Absorción Intestinal , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiología , Mucosa Intestinal/ultraestructura , Lipopolisacáridos/sangre , Porcinos , Uniones Estrechas/fisiología , Uniones Estrechas/ultraestructuraRESUMEN
Extracorporeal membrane oxygenation (ECMO) is a life-saving support system used in neonates and young children with severe cardiorespiratory failure. Although ECMO has reduced mortality in these critically ill patients, almost all patients treated with ECMO develop a systemic inflammatory response syndrome (SIRS) characterized by a 'cytokine storm', leukocyte activation, and multisystem organ dysfunction. We used a neonatal porcine model of ECMO to investigate whether rising plasma concentrations of inflammatory cytokines during ECMO reflect de novo synthesis of these mediators in inflamed tissues, and therefore, can be used to assess the severity of ECMO-related SIRS. Previously healthy piglets (3-week-old) were subjected to venoarterial ECMO for up to 8 h. SIRS was assessed by histopathological analysis, measurement of neutrophil activation (flow cytometry), plasma cytokine concentrations (enzyme immunoassays), and tissue expression of inflammatory genes (PCR/western blots). Mast cell degranulation was investigated by measurement of plasma tryptase activity. Porcine neonatal ECMO was associated with systemic inflammatory changes similar to those seen in human neonates. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8) concentrations rose rapidly during the first 2 h of ECMO, faster than the tissue expression of these cytokines. ECMO was associated with increased plasma mast cell tryptase activity, indicating that increased plasma concentrations of inflammatory cytokines during ECMO may result from mast cell degranulation and associated release of preformed cytokines stored in mast cells. TNF-alpha and IL-8 concentrations rose faster in plasma than in the peripheral tissues during ECMO, indicating that rising plasma levels of these cytokines immediately after the initiation of ECMO may not reflect increasing tissue synthesis of these cytokines. Mobilization of preformed cellular stores of inflammatory cytokines such as in mucosal mast cells may have an important pathophysiological role in ECMO-related SIRS.