No Inflammatory Response Related to Pulmonary Hemodynamics in Children with Systemic to Pulmonary Shunts Henrik Brun, MD,* Thor Ueland, PhD, †‡ Erik Thaulow, MD, PhD,* Jan K. Damas, MD, PhD, †§ Arne Yndestad, PhD, † Pal Aukrust, MD, PhD, †§ and Henrik Holmstrøm, MD, PhD* *Unit for Pediatric Heart, Lung and Allergic Diseases, † Research Institute of Internal Medicine, ‡ Section of Endocrinology, § Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, Rikshospitalet, Oslo, Norway ABSTRACT Objective. The hypothesis was that the levels of circulating inflammatory mediators are related to the degree of volume and pressure stress on the pulmonary vasculature in children with congenital systemic to pulmonary shunts. Design. Prospective, cross-sectional study. Setting. Tertiary center covering all pediatric heart surgery and interventions in Norway. Patients. Seventy-four children, aged 0–12 years, admitted for surgical or interventional treatment of congenital systemic to pulmonary shunts. Outcome Measures. Plasma levels of eight mediators of vascular inflammation and endothelial activation, sampled from different vascular compartments. Results. Patients with the most pronounced pulmonary flow and pressure stress demonstrated no elevation of inflammatory mediator levels when compared with healthy controls. No pulmonary production or uptake of the measured markers was found. Hemodynamic explanatory factors showed weak correlations to the inflammatory marker levels by univariate analysis. Age was the only factor that significantly explained inflammatory response in the multivariate model. The presence of Down syndrome, irrespective of hemodynamic category, was associated with elevated plasma levels of soluble tumor necrosis factor receptor I, when controlling for age. Conclusions. Inflammatory mediators show no significant relationship to pulmonary hemodynamics in children with systemic to pulmonary shunts. Children with Down syndrome may have an increased inflammatory response. Key Words. Congenital Heart Disease; Inflammation; Heart Septal Defects; Pulmonary Hemodynamics; Pulmo- nary Hypertension Introduction C ongenital systemic to pulmonary shunts are the most frequently occurring congenital heart defects. Related to increased pressure and flow load, the consequent pulmonary vascular wall changes represent one of the major causes of pul- monary arterial hypertension (PAH) in child- hood. 1 Earlier studies indicate that pulmonary vascular pathology is reversible after repair of the heart defect, until approximately 1 year of age, in the case of nonrestrictive, posttricuspid defects, e.g., ventricular septal defect (VSD). 2–4 Without surgical treatment, a substantial proportion of these patients would develop irreversible pulmo- nary vascular disease and Eisenmenger physiology. With pretricuspid shunts, e.g., secundum atrial septal defect (ASD), vascular wall pathology is more variably occurring and may take decades to develop into clinical disease. 5 Pulmonary vascular stress from systemic to pul- monary shunts has been suggested to start the development of arteriolar pathology by leak of serum factors into the vascular wall. Protease cas- cades triggering inflammatory responses could be involved. 6 Levy et al. reported that in congenital heart disease, irreversible PAH was strongly asso- ciated with impaired endothelial cell apoptosis, 338 © 2011 Copyright the Authors Congenital Heart Disease © 2011 Wiley Periodicals, Inc. Congenit Heart Dis. 2011;6:338–346