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World J Pediatr Congenit Heart Surg. 2018 Jul;9(4):412-418. doi: 10.1177/2150135118762390.

Ubiquitin C-Terminal Hydrolase 1 and Phosphorylated Axonal Neurofilament Heavy Chain in Infants Undergoing Cardiac Surgery: Preliminary Assessment as Potential Biomarkers of Brain Injury.

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1 Division of Pediatric and Adult Congenital Cardiac Surgery, Department of Cardiothoracic Surgery, New York University School of Medicine, New York, NY, USA.
2 Division of Pediatric Cardiology, Department of Pediatrics, New York University School of Medicine, New York, NY, USA.
3 Department of Neuroscience, University of Florida College of Medicine, Gainesville, FL, USA.
4 EnCor Biotechnology Inc, Gainesville, FL, USA.



There are no reliable markers to assess brain injury in neonates following cardiac surgery. We examine ubiquitin C-terminal hydrolase 1 (UCHL1) and phosphorylated axonal neurofilament heavy chain (pNF-H), neuronal-specific biomarkers released following axonal and cortical injury, in neonates undergoing cardiac surgery involving cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA).


Twenty-six patients younger than three months were prospectively enrolled (CPB only, n = 12 and DHCA, n = 14). Healthy newborns (n = 22) served as the control. Blood samples were collected preoperatively and postoperatively upon intensive care unit admission (hour 0) and subsequently at 12, 24, 36, and 48 hours. Serum was tested for UCHL1 and pNF-H using enzyme-linked immunosorbent assay. Concomitant arterial blood gas, lactate, and cerebral near-infrared spectroscopy (NIRS) monitoring were performed.


Ubiquitin C-terminal hydrolase 1 showed a significant rise at 0 hours in the DHCA group compared to baseline (74.9 ± 13.7 pg/mL vs 33.9 ± 37.3 pg/mL, P < .0001). Levels returned to baseline at 12 hours. There was an early rise in UCHL1 at 0 hours in the CPB group, P = .09. Phosphorylated axonal neurofilament heavy chain was decreased at 0 hours in both the CPB and DHCA groups compared to baseline, P = .06. There was no difference between control and baseline levels of UCHL1 ( P = .9) or pNF-H ( P = .77). Decreased NIRS was observed in the DHCA group at 0 hours (57.3 ± 10.5) versus baseline (64.2 ± 12.3), but not significant ( P = .21). There was no correlation between biomarkers and NIRS at 0 hours.


A rapid rise in UCHL1 levels was observed in the DHCA group, suggesting that it may be a marker for acute brain injury. Follow-up with neurodevelopmental studies is ongoing.


cardiac surgery; cardiopulmonary bypass; congenital heart disease; deep hypothermic circulatory arrest; neuronal injury biomarkers; phosphorylated axonal neurofilament heavy chain; ubiquitin C-terminal hydrolase

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