Controlled reoxygenation attenuates neuroinflammation and cognitive dysfunction after on-pump cardiac surgery in cyanotic congenital heart disease by TLR4/MyD88/NF-κB signaling pathway
Y Jin, T Gao, Y Liu, Q Liu, J Liu, J LiuAbstract
Background
Cyanotic congenital heart disease (CCHD) in children is characterized by chronic hypoxemia resulting from cardiopulmonary vascular malformations and shunting. Cardiopulmonary bypass (CPB) plays an indispensable role in the surgical treatment of these pediatric patients, and hyperoxic CPB is frequently utilized for blood oxygenation in current clinical practice. However, accumulating evidence indicates that hyperoxic CPB can be detrimental, particularly in pediatric patients with CCHD. Chronically adapted to hypoxia and possessing immature neurological systems, these patients are especially vulnerable. Hyperoxic CPB can impair neurodevelopment and cognitive function, ultimately affecting their long-term quality of life. Controlled reoxygenation, which incrementally elevates oxygen levels according to patient demand, aims to prevent secondary reperfusion injury by maintaining an optimal PaO₂ during CPB, thereby avoiding the adverse effects of intraoperative hyperoxia.
Purpose
We aimed to investigate whether controlled reoxygenation exerts a neuroprotective effect during on-pump cardiac surgery in CCHD and to explore the underlying mechanisms.
Methods
A cyanotic Sprague-Dawley (SD) rat model was established by maintaining chronic hypoxia, simulating the preoperative hypoxemic state of infants with CCHD. Subsequently, a CPB model was established in these cyanotic rats, and postoperative neuroinflammation and cognitive function were assessed.
Results
Compared to the hyperoxic group, controlled reoxygenation significantly attenuated postoperative neuroinflammation and improved cognitive function in cyanotic rats undergoing CPB. Mechanistic exploration revealed that controlled reoxygenation reduced activation of the TLR4/MyD88/NF-κB signaling pathway and diminished astrocyte and microglial activation, thereby ameliorating neuroinflammation and cognitive dysfunction. Additionally, controlled reoxygenation decreased plasma levels of inflammatory cytokines compared to the hyperoxic group.
Conclusion
Our findings indicate that controlled reoxygenation plays a pivotal role in regulating TLR4-mediated inflammatory signaling. This study offers a novel therapeutic strategy and empirical evidence for mitigating neuroinflammation and cognitive dysfunction following cardiac surgery with CPB in infants with CCHD.Hyperoxia exacerbated neuroinflammationControlled reoxygenation regulated TLR4 axis