Abstract 20360: Triiodothyronine Supplementation and Cytokine Responses During Cardiopulmonary Bypass in Infants and Children
Introduction: The TRiiodothyronine supplementation in Infants and Children undergoing Cardiopulmonary bypass (TRICC) study was a prospective double blind placebo controlled clinical trial in children age < 2 years. The TRICC trial demonstrated that T3 supplementation shortened time to extubation (TTE) and improved cardiac function in children aged < 5 months undergoing cardiopulmonary bypass (CPB) for congenital heart surgery. CPB precipitates a systemic inflammatory response, which can impact clinical recovery from surgery. In some disease states T3 impacts inflammation by genomic mechanisms effecting cytokine release. Therefore, we tested the hypothesis: T3 influence on postoperative clinical outcome may relate to age-dependent response of inflammatory pathways.
Methods: Using multiplex techniques we measured six cytokines (IL-1B, IL-6, IL-8, IL-10, CCL2, and CCL4) in serum at preoperative- time 0, and 6 and 24 hours after bypass in the first 66 patients enrolled in the TRICC cohort: (placebo, n = 30; intravenous T3 treated, n = 36). Using regression and non-parametric analyses, we evaluated relationships between cytokine levels and age, treatment, TTE and inotropic score.
Results: In the placebo group age was inversely related with CCL4 (MIP-1B) at 0 hours (−9.9 pg/mL per month, p < 0.01) and IL-8 at 6 hours (−1.5 pg/mL per month, p = 0.05), and positively related with IL1-B at 24 hours (0.02 pg/mL per month, p = 0.03). In all patients, lower IL-6 and IL-1B levels at 0 hours was associated with a lower TTE (Kruskal-Wallis tests, p = 0.01 and p = 0.02). CCL4 at 0 hours was related to the inotropic score at 24 hours (0.01 pg/mL per unit inotrope score, p = 0.01). Treatment with T3 raised IL-8 levels at 6 hours compared to placebo (58.1 pg/mL vs. 36.0 pg/mL, p = .03) but accelerated the drop in CCL4 at 24 hours from 0 hours (−139.3 pg/mL vs. −41.2 pg/mL, p = .05).
Conclusions: We identified previously unrecognized age-related differences in the preoperative cytokine profile. Furthermore, the profile prior to surgery may predict operative risk indexed by clinical outcome parameters. T3 treatment was related to the cytokine response over 24 hours and may impact the post-operative response of the chemokine CCL4 suggesting a potential mechanism for therapeutic action.
- © 2010 by American Heart Association, Inc.