Abstract 2353: Angiopoietin Expression in Children Following Cardiopulmonary Bypass

Abstract

Introduction: Capillary leak syndrome (CLS) is a serious, potentially life-threatening problem in children with congenital heart disease (CHD) that is partly related to the host inflammatory response following cardiopulmonary bypass (CPB). The angiopoietins are a family of vascular growth factors that are necessary for angiogenesis. Two members of the angiopoietin family are well characterized in humans - angiopoietin-1 (angpt-1) and angpt-2 - both of which appear to act on the Tie2 receptor, found primarily on vascular endothelial cells. Angpt-1 protects against capillary leak, while angpt-2 promotes increased vascular permeability and potentiates inflammation. Hypothesis: We hypothesized that plasma angpt-2 levels increase following CPB and correlate with indices of systemic inflammation and capillary leak. Methods: Plasma samples were obtained at baseline and at 0, 4, and 24 h after CPB in 49 children (median age 5 mo) with CHD. Troponin-I, angpt-1, angpt-2, VEGF, and soluble Tie2 (sTie2) were measured via a commercially available ELISA. Cytokines were measured using a multiplex cytokine assay. Results: CPB (mean CPB 119 min, cross-clamp, 71 mins) increased troponin-I, IL-6, IL-8, and IL-10 expression. Plasma angpt-2 levels increased by 6 h (952 pg/mL vs 462 pg/mL, p<0.05) and remained significantly elevated at 24 h after CPB (1850 pg/mL, p<0.05). Plasma angpt-1 levels remained unchanged immediately after CPB, but were significantly decreased at 24 h after CPB (635 pg/mL vs 991 pg/mL, p<0.05). Similarly, plasma sTie2 levels increased after CPB (6.4 ng/mL vs 2.86 ng/mL, p<0.05) before returning to baseline by 6 h after CPB. Plasma VEGF levels were not different at any timepoint. Plasma angpt-2 levels after CPB signficantly correlated with troponin-I, IL-6, IL-8, and IL-10 levels. There was a significant correlation between plasma angpt-2 levels and CPB time. Finally, higher plasma angpt-2 levels at 6 h correlated significantly with increased length of stay in the CICU (r=0.86; p<0.0001). Conclusions: Angpt-2 appears to be an important biomarker of vascular endothelial injury and capillary leak following CPB in children with CHD. Further studies on the role of angpt-2 in the pathophysiology of CLS following CPB are warranted.