2011 Dec 1 - Intestinal Injury and Endotoxemia in Children Undergoing Surgery for Congenital Heart Disease

Nazima Pathan1,3,4, Margarita Burmester4,*, Tanja Adamovic4,*, Maurice Berk2,*, Keng Wooi Ng3, Helen Betts4, Duncan Macrae4, Simon Waddell5, Mark Paul-Clark3, Rosamund Nuamah6, Charles Mein6, Michael Levin1, Giovanni Montana2 and Jane A. Mitchell3. Published ahead of print on August 25, 2011, doi: 10.1164/rccm.201104-0715OC. Am. J. Respir. Crit. Care Med. December 1, 2011 vol. 184 no. 11 1261-1269
Rationale: Children with congenital heart disease are at risk of gut barrier dysfunction and translocation of gut bacterial antigens into the bloodstream. This may contribute to inflammatory activation and organ dysfunction postoperatively.

Objectives: To investigate the role of intestinal injury and endotoxemia in the pathogenesis of organ dysfunction after surgery for congenital heart disease.

Methods: We analyzed blood levels of intestinal fatty acid binding protein and endotoxin (endotoxin activity assay) alongside global transcriptomic profiling and assays of monocyte endotoxin receptor expression in children undergoing surgery for congenital heart disease.

Measurements and Main Results: Levels of intestinal fatty acid binding protein and endotoxin were greater in children with duct-dependent cardiac lesions. Endotoxemia was associated with severity of vital organ dysfunction and intensive care stay. We identified activation of pathogen-sensing, antigen-processing, and immune-suppressing pathways at the genomic level postoperatively and down-regulation of pathogen-sensing receptors on circulating immune cells.

Conclusions: Children undergoing surgery for congenital heart disease are at increased risk of intestinal mucosal injury and endotoxemia. Endotoxin activity correlates with a number of outcome variables in this population, and may be used to guide the use of gut-protective strategies.

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