Neutrophil extracellular traps formation is associated with postoperative complications in congenital cardiac surgery

Backgrounds: Pediatric patients with congenital heart disease (CHD) often require surgical repair using cardiopulmonary bypass. Despite advancements, mortality and complication rates remain significant. Methods & Results: We prospectively examined 101 patients undergoing congenital cardiac surgery, identifying a mortality rate of 4.0% and a complication rate of 31.6%. Neonates and infants exhibited multiple complications more frequently. Prolonged bypass time was significantly associated with complications, with each additional 30 min increasing the odds by 1.46 times (95% CI 1.01–2.10, p = 0.042). We further investigated the involvement of damage-associated molecular pattern (DAMP) molecules by proteomics and ELISA. Plasma levels of DAMPs, including histones and high mobility group box 1 (HMGB1), were significantly elevated in the complication group. As these molecules target Toll-like receptor (TLR)2 and TLR4, mRNA expression of TLR2 and TLR4 in neutrophils was upregulated in the complication group. In vitro and in vivo analyses demonstrated that histones and HMGB1 induced the formation of neutrophil extracellular traps (NETs). This finding aligned with greater NETs formation observed at the end of CPB and during the postoperative period in neonates and infants who developed postoperative complications. Conclusion: Targeting NETs and associated DAMPs may provide a novel therapeutic approach to mitigate complications in this patient population.