Mitochondrial Dysfunction as an Arrhythmogenic Substrate
Mitochondrial Dysfunction as an Arrhythmogenic Substrate
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DOI：
10.1016/j.jacc.2013.03.061
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发表时间：
2013-10-15
影响因子：
24
通讯作者：
Neviere, Remi
中科院分区：
文献类型：
--
作者：
Montaigne, David;Marechal, Xavier;Neviere, Remi
目的本研究旨在提供床旁证据心脏线粒体功能障碍和心律失常之间的潜在联系，如在实验室study.Background心房颤动（AF）是心脏手术的常见并发症。术后房颤（POAF）的潜在机制在很大程度上仍不清楚。由于心脏线粒体功能障碍已被报道在临床条件下具有高风险的POAF，我们调查是否存在因果关系POAF发病和术前功能的心脏mitochondrial.Methods术前线粒体呼吸和钙潴留能力，呼吸复合物的活动，心肌氧化应激定量右心房组织从104例连续代谢综合征，结果在这一高危人群中，44%的患者发生POAF。术前线粒体呼吸减少和对钙诱导的线粒体通透性转换孔开放的敏感性增加与POAF显著相关。在POAF患者中，棕榈酰-L-肉碱支持的腺苷二磷酸刺激的线粒体呼吸显著降低，并且在调整年龄、体重指数、心率、β受体阻滞剂使用和他汀类药物后，与AF发作独立相关（每单位的多变量logistic回归系数= -0.314 +/- 0.144; p = 0.028）。基因表达谱分析确定了一个普遍下调的线粒体/氧化磷酸化基因簇在术前心房组织中的患者AF developed.Conclusions我们的前瞻性研究确定了术前线粒体功能障碍的心房心肌和AF发生之间的关联心脏手术后的代谢性疾病患者，线粒体和心律失常患者之间的联系提供了新的见解。(C)2013年美国心脏病学会基金会
Objectives This study sought to provide bedside evidence of the potential link between cardiac mitochondrial dysfunction and arrhythmia as reported in bench studies.Background Atrial fibrillation (AF) is a frequent complication of cardiac surgery. Underlying mechanisms of post-operative atrial fibrillation (POAF) remain largely unknown. Because cardiac mitochondrial dysfunction has been reported in clinical conditions with a high risk of POAF, we investigated whether a causal link exists between POAF onset and pre-operative function of cardiac mitochondria.Methods Pre-operative mitochondrial respiration and calcium retention capacity, respiratory complex activity, and myocardial oxidative stress were quantified in right atrial tissue from 104 consecutive patients with metabolic syndrome, in sinus rhythm, and undergoing coronary artery bypass graft surgery.Results In this high-risk population, POAF occurred in 44% of patients. Decreased pre-operative mitochondrial respiration and increased sensitivity to calcium-induced mitochondrial permeability transition pore opening were significantly associated with POAF. Adenosine diphosphate-stimulated mitochondrial respiration supported by palmitoyl-L-carnitine was significantly lower in POAF patients and remained independently associated with AF onset after adjustment for age, body mass index, heart rate, beta-blocker use, and statin medication (multivariate logistic regression coefficient per unit = -0.314 +/- 0.144; p = 0.028). Gene expression profile analysis identified a general downregulation of the mitochondria/oxidative phosphorylation gene cluster in pre-operative atrial tissue of patients in whom AF developed.Conclusions Our prospective study identifies an association between pre-operative mitochondrial dysfunction of the atrial myocardium and AF occurrence after cardiac surgery in patients with metabolic disease, providing novel insights into the link between mitochondria and arrhythmias in patients. (C) 2013 by the American College of Cardiology Foundation