Pericardial Mitochondrial DNA Levels Are Associated With Atrial Fibrillation After Cardiac Surgery.

Pericardial Mitochondrial DNA Levels Are Associated With Atrial Fibrillation After Cardiac Surgery.
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DOI:
10.1016/j.athoracsur.2020.07.011
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发表时间:
2021-05
期刊:
The Annals of thoracic surgery
影响因子:
--
通讯作者:
Melby SJ
Melby SJ
中科院分区:
其他
文献类型:
--
作者:
Manghelli JL;Kelly MO;Carter DI;Gauthier JM;Scozzi D;Lancaster TS;MacGregor RM;Khiabani AJ;Schuessler RB;Gelman AE;Damiano RJ;Melby SJ

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术后心房颤动(POAF)是心脏手术后最常见的并发症,与发病率和死亡率增加有关。炎症已被认为是POAF的病因之一。线粒体DNA (mtDNA)已被证明可以引发炎症。本研究通过评估心脏手术后心包液(PCF)和血液中的mtDNA、中性粒细胞和细胞因子/趋化因子来分析POAF的炎症机制。术中、术后4小时、12小时、24小时和48小时采集冠状动脉搭桥和/或心脏瓣膜手术患者的血液和PCF。采用Real-Time PCR定量PCF和血液中的mtDNA。采用luminex法检测细胞因子和趋化因子水平。流式细胞术检测PCF中中性粒细胞的浸润和活化情况。来自100名患者的样本可供分析。术后,PCF中mtDNA和多种细胞因子水平高于血液。与未发生POAF的患者相比,发生POAF的患者PCF中mtDNA水平显著升高(p<0.0001, AUC =0.74)。POAF组与非POAF组血mtDNA浓度差异无统计学意义(p=0.897)。随着时间的推移,PCF中性粒细胞浓度从基线的0.8%增加到48小时时的56% (p<0.01)。术后心包间隙有高浓度的炎症介质。PCF中的mtDNA与POAF的发生密切相关。这一发现提供了对可能导致POAF的炎症机制的深入了解,并可能提供新的治疗靶点。
Postoperative atrial fibrillation (POAF) is the most common complication following 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 (PCF) and blood following cardiac surgery. Blood and PCF from patients who underwent coronary bypass and/or heart valve surgery were collected intraoperatively and at 4, 12, 24, and 48 hours postoperatively. Real-Time PCR was used to quantify mtDNA in the PCF and blood. A luminex assay was used to study cytokine and chemokine levels. Flow cytometry was employed to analyze neutrophil infiltration and activation in the PCF. Samples from 100 patients were available for analysis. Postoperatively, mtDNA and multiple cytokine levels were higher in the PCF versus blood. Patients who developed POAF had significantly higher levels of mtDNA in the PCF compared to those who did not (p<0.0001, AUC =0.74). There was no difference in the mtDNA concentration in the blood between the POAF and non-POAF groups (p=0.897). Neutrophil concentration increased in the PCF over time from a baseline of 0.8% to 56% at 48 hours (p<0.01). The pericardial space has a high concentration of inflammatory mediators postoperatively. mtDNA in the PCF 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.
循环线粒体 DAMP 会引起对损伤的炎症反应。
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