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BACKGROUND Acute kidney injury (AKI) is a well-known complication after cardiac surgery and cardiopulmonary bypass (CPB). In the present secondary analysis of a blinded randomized controlled trial, we evaluated the effects of a colloid-based versus a conventional crystalloid-based prime on tubular injury and postoperative renal function in patients undergoing cardiac surgery with CPB. METHODS Eighty-four adult patients undergoing cardiac surgery with CPB were randomized to receive either a crystalloid- or colloid- (dextran 40) based CPB priming solution. The crystalloid solution was based on Ringer-Acetate plus mannitol. The tubular injury biomarker, N-acetyl-b-D-glucosaminidase (NAG), serum creatinine and diuresis were measured before, during and after CPB. The incidence of AKI was assessed according to the KDIGO criteria. RESULTS The urinary-NAG/urinary-creatinine ratio rose in both groups during and after CPB, with a more pronounced increase in the crystalloid group (p = .038). One hour after CPB, the urinary-NAG/urinary-creatinine ratio was 88% higher in the crystalloid group (4.7 ± 6.3 vs. 2.5 ± 2.7, p = .045). Patients that received the dextran 40-based priming solution had a significantly lower intraoperative diuresis (p

The optimum priming fluid for the cardiopulmonary bypass (CPB) circuit is still debated. We compared a new hyperoncotic priming solution containing dextran 40, which has an electrolyte composition that mimics extracellular fluid, with a standard crystalloid-based prime.Eighty cardiac surgery patients were included in this double-blind, randomized, single-center study. Patients were randomized to either a dextran-based prime or a crystalloid prime containing Ringer's acetate and mannitol. The primary end point was colloid oncotic pressure in serum during CPB. Secondary end points included fluid balance, bleeding and transfusion requirements, pulmonary function, hemolysis, systemic inflammation, and markers of renal, hepatic, myocardial, and brain injury. Blood samples were collected before, during, and after CPB.Colloid oncotic pressure was higher in the dextran group than in the crystalloid prime group during CPB (18.8 ± 2.9 versus 16.4 ± 2.9 mm Hg; P.001) and 10 minutes after CPB (19.2 ± 2.7 versus 16.8 ± 2.9 mm Hg; P.001). Patients in the dextran group required less intravenous fluid during CPB (1090 ± 499 versus 1437 ± 543 mL; P = .004) and net fluid balance was less positive 12 hours after surgery (1431 ± 741 versus 1901 ± 922 mL; P = .014). Plasma-free hemoglobin was significantly lower in the dextran group 2 hours after CPB (0.18 ± 0.11 versus 0.41 ± 0.33; P = .001). There were no significant differences in bleeding, transfusion requirements, organ function, systemic inflammation, or brain and myocardial injury markers between groups at any time point.Our results suggest that a hyperoncotic dextran-based priming solution preserves intraoperative colloid oncotic pressure compared with crystalloid prime. Larger studies with clinically valid end points are necessary to evaluate hyperoncotic prime solutions further.

Postoperative cognitive dysfunction is common after cardiac surgery. Postoperative measurements of brain injury biomarkers may identify brain damage and predict cognitive dysfunction. We describe the release patterns of five brain injury markers in serum and plasma after uncomplicated cardiac surgery.Sixty-one elective cardiac surgery patients were randomized to undergo surgery with either a dextran-based prime or a crystalloid prime. Blood samples were taken immediately before surgery, and 2 and 24 h after surgery. Concentrations of the brain injury biomarkers S100B, glial fibrillary acidic protein (GFAP), tau, neurofilament light (NfL) and neuron-specific enolase (NSE)) and the blood-brain barrier injury marker β-trace protein were analyzed. Concentrations of brain injury biomarkers were correlated to patients' age, operation time, and degree of hemolysis.No significant difference in brain injury biomarkers was observed between the prime groups. All brain injury biomarkers increased significantly after surgery (tau +456% (25th-75th percentile 327%-702%), NfL +57% (28%-87%), S100B +1145% (783%-2158%), GFAP +17% (-3%-43%), NSE +168% (106%-228%), while β-trace protein was reduced (-11% (-17-3%). Tau, S100B, and NSE peaked at 2h, NfL and GFAP at 24 h. Postoperative concentrations of brain injury markers correlated to age, operation time, and/or hemolysis.Uncomplicated cardiac surgery with cardiopulmonary bypass is associated with an increase in serum/plasma levels of all the studied injury markers, without signs of blood-brain barrier injury. The biomarkers differ markedly in their levels of release and time course. Further investigations are required to study associations between perioperative release of biomarkers, postoperative cognitive function and clinical outcome.

OBJECTIVES Perioperative stroke is a severe complication of cardiac surgery. We assessed the incidence of stroke over time, the association between stroke and mortality and identified preoperative factors independently associated with perioperative stroke, in a large nationwide cardiac surgery population. METHODS All patients who underwent coronary artery bypass grafting in Sweden 2006–2017 were included in a registry-based observational cohort study based on prospectively collected data. Multivariable logistic and Cox regression models were used to assess associations between perioperative stroke and mortality and to identify factors associated with stroke. The median follow-up was 6 years (range 0–12). RESULTS There were 441 perioperative strokes in 36 898 patients. The mean incidence was 1.2% and decreased marginally over time [adjusted odds ratio (OR) 0.97 per year (95% confidence interval 0.94–1.00), P = 0.035]. Stroke patients had a higher overall mortality risk during follow-up [adjusted hazard ratio 2.30 (2.00–2.64), P < 0.001], with the highest risk during the first 30 postoperative days [adjusted hazard ratio (7.29 (5.58–9.54), P < 0.001]. The strongest independent preoperative factors associated with stroke were prior cardiac surgery [adjusted OR 2.89 (1.40–5.96)], critical preoperative condition [adjusted OR 2.55 (1.73–3.76)], previous stroke [adjusted OR 1.77 (1.35–2.33)], preoperative angina requiring intravenous nitrates [adjusted OR 1.67 (1.28–2.17)], peripheral vascular disease [OR 1.63 (1.25–2.13)] and advanced age [OR 1.05 (1.03–1.06) per year]. CONCLUSIONS The incidence of perioperative stroke after coronary artery bypass grafting has remained stable. Patients with perioperative stroke had a markedly higher adjusted risk of death early after surgery. The risk declined over time but remained higher during the entire follow-up period.

AIMS: Excessive bleeding impairs outcome after coronary artery bypass grafting (CABG). Current guidelines recommend withdrawal of clopidogrel and ticagrelor 5 days (120 h) before elective surgery. Shorter discontinuation would reduce the risk of thrombotic events and save hospital resources, but may increase the risk of bleeding. We investigated whether a shorter discontinuation time before surgery increased the incidence of CABG-related major bleeding complications and compared ticagrelor- and clopidogrel-treated patients. METHODS AND RESULTS: All acute coronary syndrome patients in Sweden on dual antiplatelet therapy with aspirin and ticagrelor (n = 1266) or clopidogrel (n = 978) who underwent CABG during 2012-13 were included in a retrospective observational study. The incidence of major bleeding complications according to the Bleeding Academic Research Consortium-CABG definition was 38 and 31%, respectively, when ticagrelor/clopidogrel was discontinued 120 h before surgery [odds ratio (OR) 0.93 (95% confidence interval, CI, 0.53-1.64), P = 0.80]. In contrast, clopidogrel-treated patients had a higher incidence when discontinued 72-120 vs. >120 h before surgery (OR 1.71 (95% CI 1.04-2.79), P = 0.033). The overall incidence of major bleeding complications was lower with ticagrelor [12.9 vs. 17.6%, adjusted OR 0.72 (95% CI 0.56-0.92), P = 0.012]. CONCLUSION: The incidence of CABG-related major bleeding was high when ticagrelor/clopidogrel was discontinued Funding agencies: AstraZeneca; Swedish Heart and Lung Foundation [20120372, 2014021]

Oxidative stress has been implicated in the etiology of neurodegenerative disorders with α-synuclein pathology. Lipid peroxidation products such as 4-oxo-2-nonenal (ONE) and 4-hydroxy-2-nonenal (HNE) can covalently modify and structurally alter proteins. Herein, we have characterized ONE- or HNE-induced α-synuclein oligomers. Our results demonstrate that both oligomers are rich in β-sheet structure and have a molecular weight of about 2000 kDa. Atomic force microscopy analysis revealed that ONE-induced α-synuclein oligomers were relatively amorphous, with a diameter of 40-80 nm and a height of 4-8 nm. In contrast, the HNE-induced α-synuclein oligomers had a protofibril-like morphology with a width of 100-200 nm and a height of 2-4 nm. Furthermore, neither oligomer type polymerized into amyloid-like fibrils despite prolonged incubation. Although more SDS and urea stable, because of a higher degree of cross-linking, ONE-induced α-synuclein oligomers were less compact and more sensitive to proteinase K treatment. Finally, both ONE- and HNE-induced α-synuclein oligomers were cytotoxic when added exogenously to a neuroblastoma cell line, but HNE-induced α-synuclein oligomers were taken up by the cells to a significantly higher degree. Despite nearly identical chemical structures, ONE and HNE induce the formation of off-pathway α-synuclein oligomers with distinct biochemical, morphological, and functional properties.