Equipe d'Accueil 4484, Department of Physiology, Faculty of Medicine Lille, University Lille 2, Lille, France; Service d'Explorations Fonctionnelles CardioVasculaires, University Hospital of Lille, Lille, France.
J Am Coll Cardiol. 2013 Oct 15;62(16):1466-73. doi: 10.1016/j.jacc.2013.03.061. Epub 2013 May 1.
This study sought to provide bedside evidence of the potential link between cardiac mitochondrial dysfunction and arrhythmia as reported in bench studies.
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.
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.
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.
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.
本研究旨在提供心脏线粒体功能障碍与心律失常之间潜在关联的床边证据，该关联在实验室研究中已有报道。
心房颤动（AF）是心脏手术后的常见并发症。术后心房颤动（POAF）的潜在机制仍知之甚少。由于心脏线粒体功能障碍在发生 POAF 风险较高的临床情况下已有报道，因此我们研究了 POAF 发作与术前心脏线粒体功能之间是否存在因果关系。
对 104 例连续患有代谢综合征、窦性节律并接受冠状动脉旁路移植术的患者的右心房组织进行了术前线粒体呼吸和钙保留能力、呼吸复合物活性以及心肌氧化应激的检测。
在该高危人群中，44%的患者发生 POAF。术前线粒体呼吸降低和钙诱导的线粒体通透性转换孔开放敏感性增加与 POAF 显著相关。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使用后，POAF 患者的棕榈酰肉碱刺激的二磷酸腺苷刺激的线粒体呼吸显著降低，并且与 AF 发作独立相关（多元逻辑回归系数单位 = -0.314 ± 0.144；p = 0.028）。基因表达谱分析表明，在发生 AF 的患者的术前心房组织中，线粒体/氧化磷酸化基因簇普遍下调。
我们的前瞻性研究确定了代谢疾病患者心脏手术后术前心房心肌线粒体功能障碍与 AF 发生之间的关联，为患者中线粒体与心律失常之间的联系提供了新的见解。
