Pironkova Rossitza P, Giamelli Joseph, Seiden Howard, Parnell Vincent A, Gruber Dorota, Sison Cristina P, Kowal Czeslawa, Ojamaa Kaie
Division of Pediatric Cardiology, Department of Pediatrics, Cohen Children's Medical Center of New York at Northwell Health, New Hyde Park, NY 11040, USA.
Division of Pediatric Cardiothoracic Surgery, Department of Pediatrics, Cohen Children's Medical Center of New York at Northwell Health, New Hyde Park, NY 11040, USA.
Exp Ther Med. 2017 Jul;14(1):228-238. doi: 10.3892/etm.2017.4493. Epub 2017 May 22.
The potential role of systemic inflammation on brain injury in newborns with congenital heart disease (CHD) was assessed by measuring levels of central nervous system (CNS)-derived proteins in serum prior to and following cardiac surgery. A total of 23 newborns (gestational age, 39±1 weeks) with a diagnosis of CHD that required cardiac surgery with cardiopulmonary bypass (CPB) were enrolled in the current study. Serum samples were collected immediately prior to surgery and 2, 24 and 48 h following CPB, and serum levels of phosphorylated neurofilament-heavy subunit (pNF-H), neuron-specific enolase (NSE) and S100B were analyzed. Systemic inflammation was assessed by measuring serum concentrations of complement C5a and complement sC5b9, and the following cytokines: Interleukin (IL)-1β, IL-6, IL-8, IL-10, IL12p70, interferon γ and tumor necrosis factor (TNF)-α. Analysis of cord blood from normal term deliveries (n=26) provided surrogate normative values for newborns. pNF-H and S100B were 2.4- to 2.8-fold higher (P<0.0001) in patient sera than in cord blood prior to surgery and remained elevated following CPB. Pre-surgical serum pNF-H and S100B levels directly correlated with interleukin (IL)-12p70 (ρ=0.442, P<0.05). pNF-H was inversely correlated with arterial pO prior to surgery (ρ=-0.493, P=0.01) and directly correlated with arterial pCO post-CPB (ρ=0.426, P<0.05), suggesting that tissue hypoxia and inflammation contribute to blood brain barrier (BBB) dysfunction and neuronal injury. Serum IL12p70, IL-6, IL-8, IL-10 and TNF-α levels were significantly higher in patients than in normal cord blood and levels of these cytokines increased following CPB (P<0.001). Activation of complement was observed in all patients prior to surgery, and serum C5a and sC5b9 remained elevated up to 48 h post-surgery. Furthermore, they were correlated (P<0.05) with low arterial pO, high pCO and elevated arterial pressure in the postoperative period. Length of mechanical ventilation was associated directly with post-surgery serum IL-12p70 and IL-8 concentrations (P<0.05). Elevated serum concentrations of pNF-H and S100B in neonates with CHD suggest BBB dysfunction and CNS injury, with concurrent hypoxemia and an activated inflammatory response potentiating this effect.
通过测量心脏手术前后血清中中枢神经系统（CNS）衍生蛋白的水平，评估全身炎症在先天性心脏病（CHD）新生儿脑损伤中的潜在作用。本研究共纳入23例诊断为CHD且需要进行体外循环（CPB）心脏手术的新生儿（胎龄39±1周）。在手术前以及CPB后2、24和48小时立即采集血清样本，并分析血清中磷酸化神经丝重链亚基（pNF-H）、神经元特异性烯醇化酶（NSE）和S100B的水平。通过测量血清补体C5a和补体sC5b9以及以下细胞因子的浓度来评估全身炎症：白细胞介素（IL）-1β、IL-6、IL-8、IL-10、IL12p70、干扰素γ和肿瘤坏死因子（TNF）-α。对正常足月分娩的脐带血（n = 26）进行分析，为新生儿提供替代的正常参考值。手术前患者血清中的pNF-H和S100B比脐带血高2.4至2.8倍（P<0.0001），并且在CPB后仍保持升高。手术前血清pNF-H和S100B水平与白细胞介素（IL）-12p70直接相关（ρ = 0.442，P<0.05）。手术前pNF-H与动脉血氧分压呈负相关（ρ = -0.493，P = 0.01），与CPB后动脉血二氧化碳分压呈正相关（ρ = 0.426 , P<0.05），这表明组织缺氧和炎症导致血脑屏障（BBB）功能障碍和神经元损伤。患者血清中IL12p70、IL-6、IL-8、IL-10和TNF-α水平显著高于正常脐带血，并且这些细胞因子的水平在CPB后升高（P<0.001）。所有患者在手术前均观察到补体激活，并且血清C5a和sC5b9在术后48小时内一直保持升高。此外，它们与术后低动脉血氧分压、高二氧化碳分压和动脉压升高相关（P<0.05）。机械通气时间与术后血清IL-12p70和IL-8浓度直接相关（P<0.05）。CHD新生儿血清中pNF-H和S100B浓度升高表明BBB功能障碍和CNS损伤，同时低氧血症和激活的炎症反应会增强这种作用。
