title: Serum UCH-L1 as a Novel Biomarker to Predict Neuronal Apoptosis Following Deep Hypothermic Circulatory Arrest.
abstract: BACKGROUND
  Deep hypothermic circulatory arrest (DHCA) has been used in cardiac surgery involving infant complex congenital heart disease and aortic dissection. DHCA carries a risk of neuronal apoptotic death in brain. Serum ubiquitin C-terminal hydrolase L1 (UCH-L1) level is elevated in a number of neurological diseases involving neuron injury and death. We studied the hypothesis that UCH-L1 may be a potential biomarker for DHCA-induced ischemic neuronal apoptosis.
  
  
  METHODS
  Anesthetized piglets were used to perform cardiopulmonary bypass (CPB). DHCA was induced for 1 hour followed by CPB rewarming. Blood samples were collected and serum UCH-L1 levels were measured. Neuron apoptosis and Bax and Bcl-2 proteins in hippocampus were examined. The relationship between neuron apoptosis and UCH-L1 level was determined by receiver operating characteristics (ROC) curves and correlation analysis.
  
  
  RESULTS
  DHCA resulted in marked neuronal apoptosis, significant increase in Bax:Bcl-2 ratio in hippocampus and UCH-L1 level elevations in serum (all P<0.05). Positive correlation was obtained between serum UCH-L1 level and the severity of neuron apoptosis (r= 0.78, P<0.01). By ROC, the area under the curve were 0.88 (95% CI: 0.74-0.99; P<0.01), 0.81 (95% CI: 0.81-0.96; P<0.05), 0.71 (95% CI: 0.47-0.92; P=0.11) for UCH-L1, Bax/Bcl-2 ratio and Bax, respectively. Using a cut-off point of 0.25, the UCH-L1 predicted neuronal apoptosis with a sensitivity of 85% and specificity of 57%.
  
  
  CONCLUSIONS
  Serum UCH-L1, as an easy and quick measurable biomarker, can predict neural apoptosis induced by DHCA. The elevation in UCH-L1 concentration is consistent with the severity of neural apoptosis following DHCA.
authors.affiliation: 1. Pediatric Heart Center, Beijing Anzhen Hospital, Capital Medical University, Beijing, China 100029.
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Zhang
authors.affiliation: 1. Pediatric Heart Center, Beijing Anzhen Hospital, Capital Medical University, Beijing, China 100029.
authors.forename: Yao-Bin
authors.initials: YB
authors.lastname: Zhu
authors.affiliation: 2. Laboratory of Cardiovascular Phenomics, the Department of Pharmacology, University of Nevada School of Medicine, Reno, Nevada, USA 89557.
authors.forename: Dayue Darrel
authors.initials: DD
authors.lastname: Duan
authors.affiliation: 1. Pediatric Heart Center, Beijing Anzhen Hospital, Capital Medical University, Beijing, China 100029.
authors.forename: Xiang-Ming
authors.initials: XM
authors.lastname: Fan
authors.affiliation: 1. Pediatric Heart Center, Beijing Anzhen Hospital, Capital Medical University, Beijing, China 100029.
authors.forename: Yan
authors.initials: Y
authors.lastname: He
authors.affiliation: 1. Pediatric Heart Center, Beijing Anzhen Hospital, Capital Medical University, Beijing, China 100029.
authors.forename: Jun-Wu
authors.initials: JW
authors.lastname: Su
authors.affiliation: 1. Pediatric Heart Center, Beijing Anzhen Hospital, Capital Medical University, Beijing, China 100029.
authors.forename: Ying-Long
authors.initials: YL
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D002545:Brain Ischemia / Q000097:blood* / Q000209:etiology / Q000503:physiopathology; D006348:Cardiac Surgical Procedures / Q000009:adverse effects; D002315:Cardiopulmonary Bypass / Q000009:adverse effects; D050792:Circulatory Arrest, Deep Hypothermia Induced; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D009474:Neurons / Q000473:pathology; D013552:Swine; D043222:Ubiquitin Thiolesterase / Q000097:blood* / Q000235:genetics
chemical_list: D015415:Biomarkers; D043222:Ubiquitin Thiolesterase
keywords: cardiopulmonary bypass; deep hypothermic circulatory arrest; neuronal apoptosis; ubiquitin C-terminal hydrolase-L1