Serum levels of neuron-specific ubiquitin carboxyl-terminal esterase-L1 predict brain injury in a canine model of hypothermic circulatory arrest George.

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Serum levels of neuron-specific ubiquitin carboxyl-terminal esterase-L1 predict brain injury in a canine model of hypothermic circulatory arrest George J. Arnaoutakis, MD, Timothy J. George, MD, Kevin K. Wang, PhD, Mary Ann Wilson, PhD, Jeremiah G. Allen, MD, Chase W. Robinson, MHS, Kara A. Haggerty, BS, Eric S. Weiss, MD, MPH, Mary E. Blue, PhD, Charles C. Talbot, BA, Juan C. Troncoso, MD, Michael V. Johnston, MD, William A. Baumgartner, MD The Journal of Thoracic and Cardiovascular Surgery Volume 142, Issue 4, Pages 902-910.e1 (October 2011) DOI: 10.1016/j.jtcvs.2011.06.027 Copyright © 2011 The American Association for Thoracic Surgery Terms and Conditions

Figure 1 Average neurologic scores (based on 2 independent observers) for animals 24 hours after 2h-HCA, 1h-HCA, or CPB, using the University of Pittsburgh Canine Neurological Score (0-480, with higher scores corresponding with greater functional neurologic impairment). ∗Indicates P < .05 by Tukey-Kramer method post hoc pairwise comparisons. ANOVA, Analysis of variance; HCA, hypothermic circulatory arrest; CPB, cardiopulmonary bypass; h, hours. The Journal of Thoracic and Cardiovascular Surgery 2011 142, 902-910.e1DOI: (10.1016/j.jtcvs.2011.06.027) Copyright © 2011 The American Association for Thoracic Surgery Terms and Conditions

Figure 2 Linear regression analysis depicting correlation between histopathology scores and University of Pittsburgh Functional Assessment Scores. Strength of correlation was determined using linear regression analysis with the Pearson coefficient and R2 value. HCA, Hypothermic circulatory arrest; CPB, cardiopulmonary bypass. The Journal of Thoracic and Cardiovascular Surgery 2011 142, 902-910.e1DOI: (10.1016/j.jtcvs.2011.06.027) Copyright © 2011 The American Association for Thoracic Surgery Terms and Conditions

Figure 3 UCHL1 immunoreactivity (left panel) and corresponding Nissl-stained sections (right panel) in CA3 region of hippocampus for CPB (A, B), 1h-HCA (C, D), and 2h-HCA (E, F). UCHL1, Ubiquitin carboxyl-terminal esterase-L1; HCA, hypothermic circulatory arrest; CPB, cardiopulmonary bypass; SO, stratum oriens; P, pyramidal neurons; MF, mossy fiber layer; SR, stratum radiatum. The Journal of Thoracic and Cardiovascular Surgery 2011 142, 902-910.e1DOI: (10.1016/j.jtcvs.2011.06.027) Copyright © 2011 The American Association for Thoracic Surgery Terms and Conditions

Figure 4 Line graph (A) showing serum levels of UCHL1 by treatment groups across 3 time points. Scatter plots (B) for serum UCHL1 levels correlated with functional assessment score. Break point denoted by dashed line indicates highest sensitivity for predicting outcome of interest (Neuro Score >100) by univariate logistic regression analysis. ANOVA, Analysis of variance; HCA, hypothermic circulatory arrest; CPB, cardiopulmonary bypass; UCHL1, ubiquitin carboxyl-terminal esterase-L1. The Journal of Thoracic and Cardiovascular Surgery 2011 142, 902-910.e1DOI: (10.1016/j.jtcvs.2011.06.027) Copyright © 2011 The American Association for Thoracic Surgery Terms and Conditions

Figure E1 Line graph (A) depicting CSF levels of UCHL1 by treatment groups across 3 time points. Scatter plots (B) for CSF UCHL1 concentration correlated with functional assessment score. Break point denoted by dashed line indicates highest sensitivity for predicting outcome of interest (Neuro score > 100) by univariate logistic regression analysis. ANOVA, Analysis of variance; HCA, hypothermic circulatory arrest; CPB, cardiopulmonary bypass; UCHL1, ubiquitin carboxyl-terminal esterase-L1; CSF, cerebrospinal fluid. The Journal of Thoracic and Cardiovascular Surgery 2011 142, 902-910.e1DOI: (10.1016/j.jtcvs.2011.06.027) Copyright © 2011 The American Association for Thoracic Surgery Terms and Conditions