Brain injury with systemic inflammation in newborns with congenital heart disease undergoing heart surgery

作者：Pironkova Rossitza P; Giamelli Joseph; Seiden Howard; Parnell Vincent A; Gruber Dorota; Sison Cristina P; Kowal Czeslawa; Ojamaa Kaie^*

来源：Experimental and Therapeutic Medicine, 2017, 14(1): 228-238.

DOI：10.3892/etm.2017.4493

• neonates
• phosphorylated neurofilament heavy chain
• neuron specific enolase
• S100B
• cytokines
• cardiopulmonary bypass

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)-1 beta, IL-6, IL-8, IL-10, IL12p70, interferon 7 and tumor necrosis factor (TNF)-alpha. 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 (p=0.442, P<0.05). pNF-H was inversely correlated with arterial PO, prior to surgery (p=-0.493, P=0.01) and directly correlated with arterial pCO(2) post-CPB (p=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-alpha 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 p0,, high pCO(2) 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.

• 出版日期2017-7
• 单位河北医科大学