BACKGROUND: Postoperative atrial fibrillation (POAF) is the most common complication after cardiac surgery, and is associated with increased morbidity and mortality. Inflammation has been implicated as an etiology of POAF. Mitochondrial DNA (mtDNA) has been shown to initiate inflammation. This study analyzed inflammatory mechanisms of POAF by evaluating mtDNA, neutrophils, and cytokines/chemokines in the pericardial fluid and blood after cardiac surgery. METHODS: Blood and pericardial fluid from patients who underwent coronary artery bypass or heart valve surgery, or both, were collected intraoperatively and at 4, 12, 24, and 48 hours postoperatively. Real-time polymerase chain reaction was used to quantify mtDNA in the pericardial fluid and blood. A Luminex (Luminex Corp, Austin, TX) assay was used to study cytokine and chemokine levels. Flow cytometry was used to analyze neutrophil infiltration and activation in the pericardial fluid. RESULTS: Samples from 100 patients were available for analysis. Postoperatively, mtDNA and multiple cytokine levels were higher in the pericardial fluid versus blood. Patients who had POAF had significantly higher levels of mtDNA in the pericardial fluid compared with patients who did not (P < .001, area under the curve 0.74). There was no difference in the mtDNA concentration in the blood between the POAF group and non-POAF group (P = .897). Neutrophil concentration increased in the pericardial fluid over time from a baseline of 0.8% to 56% at 48 hours (P < .01). CONCLUSIONS: The pericardial space has a high concentration of inflammatory mediators postoperatively. Mitochondrial DNA in the pericardial fluid was strongly associated with the development of POAF. This finding provides insight into a possible mechanism of inflammation that may contribute to POAF, and may offer novel therapeutic targets.
BACKGROUND: Postoperative atrial fibrillation (POAF) is the most common complication after cardiac surgery, and is associated with increased morbidity and mortality. Inflammation has been implicated as an etiology of POAF. Mitochondrial DNA (mtDNA) has been shown to initiate inflammation. This study analyzed inflammatory mechanisms of POAF by evaluating mtDNA, neutrophils, and cytokines/chemokines in the pericardial fluid and blood after cardiac surgery. METHODS: Blood and pericardial fluid from patients who underwent coronary artery bypass or heart valve surgery, or both, were collected intraoperatively and at 4, 12, 24, and 48 hours postoperatively. Real-time polymerase chain reaction was used to quantify mtDNA in the pericardial fluid and blood. A Luminex (Luminex Corp, Austin, TX) assay was used to study cytokine and chemokine levels. Flow cytometry was used to analyze neutrophil infiltration and activation in the pericardial fluid. RESULTS: Samples from 100 patients were available for analysis. Postoperatively, mtDNA and multiple cytokine levels were higher in the pericardial fluid versus blood. Patients who had POAF had significantly higher levels of mtDNA in the pericardial fluid compared with patients who did not (P < .001, area under the curve 0.74). There was no difference in the mtDNA concentration in the blood between the POAF group and non-POAF group (P = .897). Neutrophil concentration increased in the pericardial fluid over time from a baseline of 0.8% to 56% at 48 hours (P < .01). CONCLUSIONS: The pericardial space has a high concentration of inflammatory mediators postoperatively. Mitochondrial DNA in the pericardial fluid was strongly associated with the development of POAF. This finding provides insight into a possible mechanism of inflammation that may contribute to POAF, and may offer novel therapeutic targets.
Authors: Brittany Butts; Lee A Goeddel; David J George; Chad Steele; James E Davies; Chih-Chang Wei; Jasmina Varagic; James F George; Carlos M Ferrario; Spencer J Melby; Louis J Dell'Italia Journal: Circulation Date: 2017-12-05 Impact factor: 29.690
Authors: Davide Scozzi; Mohsen Ibrahim; Fuyi Liao; Xue Lin; Hsi-Min Hsiao; Ramsey Hachem; Laneshia K Tague; Alberto Ricci; Hrishikesh S Kulkarni; Howard J Huang; Seiichiro Sugimoto; Alexander S Krupnick; Daniel Kreisel; Andrew E Gelman Journal: Am J Transplant Date: 2019-01-25 Impact factor: 8.086
Authors: Nicola Sandler; Elzbieta Kaczmarek; Kiyoshi Itagaki; Yi Zheng; Leo Otterbein; Kamal Khabbaz; David Liu; Venkatachalam Senthilnathan; Russell L Gruen; Carl J Hauser Journal: Heart Lung Circ Date: 2017-03-24 Impact factor: 2.975
Authors: Yosuke Ishii; Richard B Schuessler; Sydney L Gaynor; Kiyomi Yamada; Annabel S Fu; John P Boineau; Ralph J Damiano Journal: Circulation Date: 2005-05-31 Impact factor: 29.690
Authors: Philip A Kramer; Balu K Chacko; Saranya Ravi; Michelle S Johnson; Tanecia Mitchell; Stephen Barnes; Alireza Arabshahi; Louis J Dell'Italia; David J George; Chad Steele; James F George; Victor M Darley-Usmar; Spencer J Melby Journal: Lab Invest Date: 2014-12-01 Impact factor: 5.662
Authors: Thomas Zajonz; Christian Koch; Jan Schwiddessen; Melanie Markmann; Matthias Hecker; Fabian Edinger; Götz Schmidt; Andreas Boening; Michael Sander; Emmanuel Schneck Journal: J Clin Med Date: 2022-05-25 Impact factor: 4.964