title: Kynurenine metabolism predicts cognitive function in patients following cardiac bypass and thoracic surgery.
abstract: Cardiac surgery involving extra-corporeal circulation can lead to cognitive dysfunction. As such surgery is associated with signs of inflammation and pro-inflammatory mediators activate tryptophan oxidation to neuroactive kynurenines which modulate NMDA receptor function and oxidative stress, we have measured blood concentrations of kynurenines and inflammatory markers in 28 patients undergoing coronary arterial graft surgery and, for comparison, 28 patients undergoing non-bypass thoracic surgery. A battery of cognitive tests was completed before and after the operations. The results show increased levels of tryptophan with decreased levels of kynurenine, anthranilic acid and 3-hydroxyanthranilic acid associated with bypass, and a later increase in kynurenic acid. Levels of neopterin and lipid peroxidation products rose after surgery in non-bypass patients whereas tumour necrosis factor-α and S100B levels increased after bypass. Changes of neopterin levels were greater after non-bypass surgery. Cognitive testing showed that the levels of tryptophan, kynurenine, kynurenic acid and the kynurenine/tryptophan ratio, correlated with aspects of post-surgery cognitive function, and were significant predictors of cognitive performance in tasks sensitive to frontal executive function and memory. Thus, anaesthesia and major surgery are associated with inflammatory changes and alterations in tryptophan oxidative metabolism which predict, and may play a role in, post-surgical cognitive function.
authors.affiliation: Institute of Neuroscience & Psychology, University of Glasgow, Glasgow, UK.
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Forrest
authors.forename: Gillian M
authors.initials: GM
authors.lastname: Mackay
authors.forename: Lynn
authors.initials: L
authors.lastname: Oxford
authors.forename: Keith
authors.initials: K
authors.lastname: Millar
authors.forename: L Gail
authors.initials: LG
authors.lastname: Darlington
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Higgins
authors.forename: Trevor W
authors.initials: TW
authors.lastname: Stone
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003071:Cognition / Q000502:physiology*; D001026:Coronary Artery Bypass / Q000523:psychology*; D004797:Enzyme-Linked Immunosorbent Assay; D005112:Extracorporeal Circulation; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007737:Kynurenine / Q000097:blood*; D015227:Lipid Peroxidation; D008297:Male; D008875:Middle Aged; D019798:Neopterin / Q000097:blood; D009414:Nerve Growth Factors / Q000378:metabolism; D009483:Neuropsychological Tests; D011183:Postoperative Complications / Q000175:diagnosis* / Q000523:psychology*; D011237:Predictive Value of Tests; D011597:Psychomotor Performance / Q000502:physiology; D015203:Reproducibility of Results; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000378:metabolism; D057190:Stroop Test; D019616:Thoracic Surgical Procedures / Q000523:psychology*; D014145:Trail Making Test; D014364:Tryptophan / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014706:Verbal Learning
chemical_list: D015415:Biomarkers; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human; D014409:Tumor Necrosis Factor-alpha; D007737:Kynurenine; D019798:Neopterin; D014364:Tryptophan