Effect of penehyclidine hydrochloride on TLR4/NF-κB signaling pathway in myocardium of pediatric patients undergoing radical correction of tetralogy of Fallot with cardiopulmonary bypass / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the effect of penehyclidine hydrochloride on Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signaling pathway in the myocardium of pediatric patients undergoing radical correction of tetralogy of Fallot with cardiopulmonary bypass (CPB).Methods One hundred pediatric patients of both sexes,aged 5 months-3 yr,with body mass index of 13.9-16.0 kg/m2,of American Society of Anesthesiologists physical status Ⅱ or Ⅲ (New York Heart Association classification Ⅱ or Ⅲ),with the left ventricular ejection fraction＞50％,scheduled for elective radical correction of tetralogy of Fallot with CPB,were divided into 2 groups (n =50 each) using a random number tablepenehyclidine hydrochloride group (group P) and control group (group C).Penehyclidine hydrochloride was intravenously injected at a dose of O.04 mg/kg immediately after successful internal jugular vein puncture in group P,and the equal volume of normal saline was given instead at the same time in group C.Before anesthesia induction,at 10 min after induction,after re warming to 36 ℃,at 1 h after termination of CPB,at the end of surgery and at 24 h after surgery,venous blood samples were collected to detect the concentrations of tumor necrosis factor-alpha,interleukin-6 (IL-6),IL-8 and cardiac troponin T in plasma (by enzyme-linked immunosorbent assay).Myocardial specimens were obtained from the right auricular appendage after opening of pericardium and at 1 h after aortic unclamping for microscopic examination and for determination of activated NF-κB and TLR4 protein and mRNA expression (by Western blot and real-time polymerase chain reaction,respectively).Results Compared to group C,the concentrations of plasma tumor necrosis factor-alpha,IL-6,IL-8 and cardiac tropnin T were significantly decreased after re-warming to 36 ℃C,at 1 h after termination of CPB,at the end of surgery and at 24 h after surgery,the expression of activated NF-κB and TLR4 protein and mRNA was down-regulated at 1 h after aortic unclamping (P＜0.05),and the pathological changes of myocardium were significantly attenuated in group P.Conclusion The mechanism by which penehyclidine hydrochloride reduces inflammatory responses is related to inhibition of the activation of NF-κB/TLR4 signaling pathway in the myocardium of pediatric patients undergoing radical correction of tetralogy of Fallot with CPB.