TY - JOUR
T1 - Brain injury with systemic inflammation in newborns with congenital heart disease undergoing heart surgery
AU - Pironkova, Rossitza P.
AU - Giamelli, Joseph
AU - Seiden, Howard
AU - Parnell, Vincent A.
AU - Gruber, Dorota
AU - Sison, Cristina P.
AU - Kowal, Czeslawa
AU - Ojamaa, Kaie
N1 - Publisher Copyright:
© 2017, Spandidos Publications. All rights reserved.
PY - 2017/7
Y1 - 2017/7
N2 - 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 pO2 prior to surgery (ρ=-0.493, P=0.01) and directly correlated with arterial pCO2 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 pO2, high pCO2 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.
AB - 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 pO2 prior to surgery (ρ=-0.493, P=0.01) and directly correlated with arterial pCO2 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 pO2, high pCO2 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.
KW - Cardiopulmonary bypass
KW - Cytokines
KW - Neonates
KW - Neuron specific enolase
KW - Phosphorylated neurofilament heavy chain
KW - S100B
UR - http://www.scopus.com/inward/record.url?scp=85020525053&partnerID=8YFLogxK
U2 - 10.3892/etm.2017.4493
DO - 10.3892/etm.2017.4493
M3 - Article
AN - SCOPUS:85020525053
SN - 1792-0981
VL - 14
SP - 228
EP - 238
JO - Experimental and Therapeutic Medicine
JF - Experimental and Therapeutic Medicine
IS - 1
ER -