Cardiac Surgery is Associated with Neuronal Damage

Abstract

Background: Post-operative cognitive (POCD) decline is common in cardiac surgery and may be caused by neuronal damage. Plasma concentrations of the neuronal proteins tau and neurofilament light (NFL) are established biomarkers for acute neuronal injury. Our objective was to investigate if cardiac surgery is associated with neuronal injury reflected by changes in these plasma biomarkers. Methods: We performed a single centre case-control study of 25 patients undergoing cardiac surgery and 26 patients undergoing otolaryngeal surgery. The cohorts were sampled at several time-points before, during and after surgery and plasma concentrations of tau, NFL, and betaamyloid (Aβ40 and Aβ42) were measured. Findings: s Tau levels increased greatly by 1700% during cardiac surgery compared to baseline and normalized seven days post-surgery. NFL levels rose sharply seven days post-surgery (1100%). No changes were observed in patients undergoing otolaryngeal surgery. Furthermore, cardiac surgery patients on extracorporeal circulation (on-pump) had higher levels of tau (up to 2200%) and NFL (up to 430%) compared to cardiac surgery patients off-pump. However, the levels of tau and NFL were still significantly elevated in the cardiac surgery patients off-pump compared to the patients undergoing otolaryngeal surgery. Only minor fluctuations were observed for Aβ40 and Aβ42. Interpretation: Cardiac surgery, but not otolaryngeal surgery, is associated with massive release of neuronal-specific proteins indicating neuronal injury, which is aggravated by extracorporeal circulation. Thus, neuronal damage may contribute to the increased frequency of POCD in cardiac surgery. Analyses of NFL and tau may help to improve surgical procedures to minimize neuronal damage and possibly POCD. Funding Statement: This study was funded by grants no. N/ST/ZB/14/001/1128, 143-28594L, 133-28785L, N/ST/ZB/16/001/1128 from Medical University of Bialystok Clinical Hospital, Poland, the Swedish Research Council, Swedish State Support for Clinical Research, Alzheimer’s Association, the Knut and Alice Wallenberg Foundation, the Torsten Soderberg Foundation, the Alzheimer Foundation (Sweden), the European Research Council (grant number 681712), the Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement n° 115372, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies. Declaration of Interests: PL received consultation and/or lecture honoraria from IBL International, Fujirebio Europe, AJ Roboscreen, and Roche. KB has served as a consultant or at advisory boards for Alzheon, BioArctic, Biogen, Eli Lilly, Fujirebio Europe, IBL International, Merck, Novartis, Pfizer and Roche Diagnostics. HZ has served on scientific advisory boards for Eli Lilly, Roche 17 Diagnostics, Wave, Samumed and CogRx, and has received travel support from Teva. None of the other authors declares competing interests. Ethics Approval Statement: The study was approved by the Ethical Committee, Medical University of Bialystok Clinical Hospital, Poland. All patients gave written informed consent.