Uni-ventricular palliation vs. bi-ventricular repair: differential inflammatory response.

BACKGROUND: To examine whether uni-ventricular palliation (UVP) and bi-ventricular repair (BVR) result in a different pattern of systemic inflammatory response to pediatric cardiac surgery with extra-corporeal circulation (ECC). METHODS: In 20 children (median age 39.5 months) undergoing either UVP (n = 12) or BVR (n = 8), plasma levels of the inflammatory cytokines TNF-α, IL-6, IL-10, and IL-12 and of procalcitonin (PCT), were measured before, during and after open cardiac surgery up to postoperative day (POD) 10. RESULTS: Epidemiologic, operative- and outcome variables were similar in both groups but post-operative central venous pressure that was higher in UVP. In the whole cohort, the inflammatory response was characterized by an early important, significant and parallel increase of IL-6 and IL-10 that reached their peak values either at the end of ECC (IL-10) or 4 h postoperatively (IL-6), respectively and by a significant and parallel decrease of TNF-α and IL-12 levels after connection to ECC, followed by a bi-phasic significant increase with a first peak 4 h after ECC and a second at POD 10, respectively. Patients after UVP showed a shift of the cytokine balance with lower IL-6- (p = 0.01) after connection to ECC, lower early post-operative TNF-α - (p = 0.02) and IL-12- (p = 0.04) concentrations and lower TNF-α/IL-10-ratio (p = 0.03) as compared with patients with BVR. Levels of PCT were similar in both groups. CONCLUSIONS: UVP is associated with an anti-inflammatory shift of the inflammatory response to cardiac surgery that might be related to the particular hemodynamic situation of patients with UVP.

Myocardial Expression of Estrogen Receptor-mRNA Is Associated With Lower Markers of Post-operative Organ Damage in Young Patients With Congenital Cardiac Defect.

Background: Estrogen receptors (ERs) relate to cardio-protection in adults, but their role in younger patients is not known. We aimed to assess the myocardial expression of ERα- and ERß- mRNA in young patients with congenital cardiac disease and to analyze their putative protective role. Patients and Methods: Twenty children and young adults (seven females and 13 males) with a median age of 13.8 years (interquartile range: 12.3 years) were enrolled in this prospective study. The myocardial expression of ER-mRNA and genes involved in inflammation, growth, and stress response was assessed by real-time PCR and was correlated to post-operative (po) outcome. Results: ER-mRNA was detected in the myocardium of all patients, independently of gender and age. The expression of ER-mRNA correlated with that of mRNA coding for brain natriuretic peptide and for all cytokines tested. A higher ERα-mRNA expression correlated with lower troponin T concentrations at 24 h po (p = 0.032), higher PaO2/FiO2 ratio at 4 h po (p = 0.059), lower fluid retention at 4 h po (p = 0.048), and lower aspartate aminotransferase (AST) levels at 24 h po (p = 0.047). A higher ERß-mRNA expression was also correlated with lower fluid retention at 24 h po (p = 0.048). Patients in whom the levels of ERα- and ERß-mRNA were >P50 had lower troponin T (p = 0.003, respectively) and lower AST concentrations at 24 h po (p = 0.043, respectively) than the others. Conclusions: The expression of ERα- and ERß-mRNA is present in the myocardium of children and young adults with congenital cardiac defect and is associated with lower markers of po organ damage. This suggests that ERs may provide perioperative organ protection in this population.

Right Atrial Myocardial Remodeling in Children With Atrial Septal Defect Involves Inflammation, Growth, Fibrosis, and Apoptosis.

Introduction: Myocardial remodeling due to large atrial septum defect (ASD) is macroscopically characterized by dilation of the right-sided cardiac cavities secondary to volume overload, the cellular mechanisms of which are not yet understood. We postulated that inflammation, fibrosis, and cell death are actors of right atrial remodeling secondary to ASD. Patients and Methods: In 12 children with large ASD (median age: 63 months), expression of genes coding for proteins involved in the response to cell stress and -protection, inflammation, growth and angiogenesis, fibrosis, and apoptosis was assessed by RT-PCR in right atrial myocardial biopsies taken during cardiac surgery. The presence of cytokines in myocardial cells was confirmed by immunohistochemistry and effective apoptosis by TUNEL assay. Results: In all patients investigated, a cellular response to early mechanical stress with the initiation of early protective mechanisms, of inflammation (and its control), -growth, and -angiogenesis, of fibrosis and apoptosis was present. The apoptotic index assessed by TUNEL assay averaged 0.3%. Conclusions: In children with large ASD, macroscopic right atrial remodeling relates to cellular mechanisms involving the expression of numerous genes that either still act to protect cells and tissues but that also harm as they initiate and/or sustain inflammation, fibrosis, and cell death by apoptosis. This may contribute to long term morbidity in patients with ASD.