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Pericardial Mitochondrial DNA Levels Are Associated With Atrial Fibrillation After Cardiac Surgery
Joshua L Manghelli1, Meghan O Kelly1, Daniel I Carter1
1Division of Cardiothoracic Surgery, Barnes-Jewish Hospital, Washington University School of Medicine, St Louis, Missouri.
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.
Insights
Mitochondrial DNA (mtDNA) in pericardial fluid, not blood, is linked to postoperative atrial fibrillation (POAF) after heart surgery. This finding suggests a new inflammatory pathway and potential therapeutic targets for POAF.
Area of Science:
- Cardiovascular Surgery
- Immunology
- Molecular Biology
Background:
- Postoperative atrial fibrillation (POAF) is a common cardiac surgery complication.
- Inflammation is a suspected cause of POAF.
- Mitochondrial DNA (mtDNA) can trigger inflammation.
Purpose of the Study:
- To investigate the role of mtDNA, neutrophils, and cytokines in POAF pathogenesis.
- To analyze inflammatory mechanisms in pericardial fluid and blood post-cardiac surgery.
Main Methods:
- Collected blood and pericardial fluid from 100 cardiac surgery patients.
- Quantified mtDNA using real-time PCR.
- Assessed cytokine/chemokine levels with Luminex assay.
- Analyzed neutrophil infiltration via flow cytometry.
Main Results:
- Postoperatively, mtDNA and cytokines were elevated in pericardial fluid compared to blood.
- Higher pericardial fluid mtDNA levels significantly correlated with POAF development.
- No difference in blood mtDNA levels between POAF and non-POAF groups.
- Neutrophil concentration in pericardial fluid increased significantly over time.
Conclusions:
- The pericardial space accumulates inflammatory mediators post-cardiac surgery.
- Pericardial fluid mtDNA is strongly associated with POAF development.
- This suggests a novel inflammatory mechanism contributing to POAF, offering potential therapeutic targets.
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