TY - JOUR
T1 - Pericardial Mitochondrial DNA Levels Are Associated With Atrial Fibrillation After Cardiac Surgery
AU - Manghelli, Joshua L.
AU - Kelly, Meghan O.
AU - Carter, Daniel I.
AU - Gauthier, Jason M.
AU - Scozzi, Davide
AU - Lancaster, Timothy S.
AU - MacGregor, Robert M.
AU - Khiabani, Ali J.
AU - Schuessler, Richard B.
AU - Gelman, Andrew E.
AU - Damiano, Ralph J.
AU - Melby, Spencer J.
N1 - Funding Information:
Ralph J. Damiano receives research funding from Atricure. This work was supported by T32-HL007776 , Barnes Jewish Hospital Foundation , and the Department of Veterans Affairs Grant Merit Review ( I01 CX001526 ).
Publisher Copyright:
© 2021
PY - 2021/5
Y1 - 2021/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85092050846&partnerID=8YFLogxK
U2 - 10.1016/j.athoracsur.2020.07.011
DO - 10.1016/j.athoracsur.2020.07.011
M3 - Article
C2 - 32946846
AN - SCOPUS:85092050846
SN - 0003-4975
VL - 111
SP - 1593
EP - 1600
JO - Annals of Thoracic Surgery
JF - Annals of Thoracic Surgery
IS - 5
ER -