Apolipoprotein E Levels in Pediatric Patients Undergoing Cardiopulmonary Bypass *Mehmet Ag ˆ irbas ¸li, †Jianxun Song, †Fengyang Lei, ‡Shigang Wang, ‡Allen R. Kunselman, ‡Joseph B. Clark, ‡John L. Myers, and ‡Akif Ündar *Department of Cardiology, Marmara University College of Medicine, Istanbul, Turkey; †Department of Microbiology & Immunology, Penn State Milton S. Hershey Medical Center, Penn State Hershey College of Medicine, Penn State Hershey Children’s Hospital; and ‡Penn State Hershey Pediatric Cardiovascular Research Center, Department of Pediatrics, Public Health and Sciences, Surgery and Bioengineering, Penn State Milton S. Hershey Medical Center, Penn State Hershey College of Medicine, Penn State Hershey Children’s Hospital, Hershey, PA, USA Abstract: Apolipoprotein E (apoE) may play a critical role in modulating the response to neurological injury after car- diopulmonary bypass (CPB) in children. Plasma samples were collected from 38 pediatric patients. Half of the patients received nonpulsatile flow and the other half underwent pulsatile flow during CPB. Plasma samples were collected at three time points: at baseline prior to incision (T1), 1 h after CPB (T2), and 24 h after CPB (T3). The study included 38 pediatric patients undergoing heart surgery (mean age 2.5 ± 2.1 years). Baseline apoE levels were low (<30 μg/mL) in 21 patients (55%). ApoE levels were significantly decreased at 1 h after CPB compared with baseline (22 ± 14 vs. 34 ± 18 μg/mL, P = 0.001). At 24 h after CPB, apoE levels were significantly increased compared with baseline (47 ± 25 vs. 34 ± 18 μg/mL, P = 0.002). Pulsatile mode was associated with lower apoE levels at 24 h after CPB compared with nonpulsatile mode (38 ± 14 vs. 57 ± 29 μg/mL, P = 0.018). ApoE levels corre- lated negatively with pump time (r = -0.525, P = 0.021) and cross-clamp time (r = -0.464, P = 0.045) at 24 h following CPB for the nonpulsatile group but not for the pulsatile group. In this cohort of young children with congenital heart disease, baseline apoE levels were low in the majority of patients prior to surgery. ApoE levels decreased further at 1 h after CPB, and then significantly increased by 24 h. The mode of perfusion and the duration of pump time and clamp time influence the apoE levels after CPB. An improved understanding of these mechanisms may trans- late into the development of new techniques to improve the clinical outcomes after pediatric CPB. Key Words: Cardiopulmonary bypass—Apolipoprotein E levels—Pulsatile flow—Nonpulsatile flow—Pediatrics. Cerebral injury is a major cause of morbidity fol- lowing cardiopulmonary bypass (CPB) in children (1). The molecular events underlying brain damage following CPB are complex (2), and the precise inflammatory mechanisms leading to neurological injury following CPB in children remain to be fully elucidated. Monitoring of inflammatory biomarkers may help us to understand the pathophysiology of cerebral damage after CPB in children. We have previously shown that as many as 90 different biomarkers can be serially monitored using only a small sample of plasma during and after pediatric heart surgery (3). Additionally, we have demon- strated that the levels of lipoprotein including apolipoprotein A1, CIII, H, and lipoprotein (a) increase following pediatric CPB (3). Although the synthesis and metabolism of plasma lipoproteins are well characterized, little is known about their role on the central nervous system injury after CPB (4). The clinical significance of the variations in apolipo- protein levels after CPB remains to be demonstrated. Previous studies report that apolipoprotein E (apoE) plays a crucial role in the pathophysiology of neuro- logical injury in several disease states (5,6). ApoE is doi:10.1111/aor.12444 Received August 2014; revised October 2014. Address correspondence and reprint requests to Dr. Akif Ündar, Penn State Hershey College of Medicine, Department of Pediatrics, H085, 500 University Drive, PO Box 850, Hershey, PA 17033-0850, USA. E-mail: aundar@psu.edu Presented in part at the 10th International Conference on Pedi- atric Mechanical Circulatory Support Systems & Pediatric Cardio- pulmonary Perfusion held May 28–31, 2014 in Philadelphia, PA, USA. Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc. Artificial Organs 2015, 39(1):28–33