远程缺血预处理在冠状动脉旁路手术期间保护心房心肌线粒体功能并影响心肌 microRNA 表达。
Remote ischemic preconditioning preserves mitochondrial function and influences myocardial microRNA expression in atrial myocardium during coronary bypass surgery.
机构信息
From the K.G. Jebsen Center of Exercise in Medicine, Department of Circulation and Medical Imaging, Faculty of Medicine, Norwegian University of Science and technology, Trondheim, Norway (K.H.S., O.R., M.H., U.W., A.W.); and Department of Cardiothoracic Surgery, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway (K.H.S., A.W.).
出版信息
Circ Res. 2014 Feb 28;114(5):851-9. doi: 10.1161/CIRCRESAHA.114.302751. Epub 2013 Dec 26.
RATIONALE
Remote ischemic preconditioning (RIPC) has been suggested to induce cardioprotection during cardiac surgery. Maintaining proper atrial function is imperative in preventing arrhythmia and thrombus formation. Mitochondria have been proposed as key targets in conveying RIPC mechanisms and effects. MicroRNA (miR) is emerging as an important regulator of mitochondrial function, arrhythmia, and protection from ischemia and reperfusion.
OBJECTIVE
This study aimed to evaluate the effect of RIPC on mitochondrial respiration and miR expression in human atrial tissue.
METHODS AND RESULTS
Sixty patients undergoing coronary artery bypass graft surgery were randomized to RIPC (n=30) or control (n=30). RIPC was performed preoperatively by inflating a blood pressure cuff on the upper arm to 200 mm Hg for 3×5 minutes, with 5 minutes reperfusion intervals. Biopsies were obtained from the right atrial appendage before and after aortic cross-clamping. Mitochondrial respiration was measured in situ and miR assessed by commercial miR array and quantitative reverse transcription polymerase chain reaction. Postoperative atrial fibrillation occurrence was monitored by biotelemetry. Maximal mitochondrial respiration was preserved throughout surgery after RIPC but significantly reduced (-28%; P<0.05) after aortic cross-clamping in control. Incidence of postoperative atrial fibrillation was lower after RIPC versus control (14% versus 50%; P<0.01). Myocardial expression of miR-133a and miR-133b increased after aortic cross-clamping in both RIPC and control, whereas miR-1 was upregulated in control only. MiR-338-3p expression was higher in RIPC versus control after aortic cross-clamping.
CONCLUSIONS
RIPC preserves mitochondrial respiration and prevents upregulation of miR-1 in the right atrium during coronary artery bypass graft.
CLINICAL TRIAL REGISTRATION URL
http://www.clinicaltrials.gov. Unique identifier: NCT01308138.
背景
远程缺血预处理（RIPC）已被提出可在心脏手术期间诱导心脏保护。维持适当的心房功能对于预防心律失常和血栓形成至关重要。线粒体被认为是传递 RIPC 机制和效应的关键靶点。microRNA（miR）作为调节线粒体功能、心律失常以及缺血再灌注保护的重要调节因子而崭露头角。
目的
本研究旨在评估 RIPC 对人心房组织中线粒体呼吸和 miR 表达的影响。
方法和结果
60 例行冠状动脉旁路移植术的患者被随机分为 RIPC 组（n=30）或对照组（n=30）。RIPC 在术前通过充气上臂血压袖带至 200mmHg 进行，每次充气 3×5 分钟，每次充气 5 分钟。在主动脉夹闭前后从右心耳获取活检。在位测量线粒体呼吸，通过商业 miR 阵列和定量逆转录聚合酶链反应评估 miR。通过生物遥测监测术后心房颤动的发生。在 RIPC 后，整个手术过程中线粒体呼吸最大程度地保持，但在对照组中主动脉夹闭后明显降低（-28%；P<0.05）。与对照组相比，RIPC 组术后心房颤动的发生率较低（14%对 50%；P<0.01）。在 RIPC 和对照组中，miR-133a 和 miR-133b 的心肌表达在主动脉夹闭后增加，而仅在对照组中 miR-1 上调。与对照组相比，miR-338-3p 在 RIPC 后夹闭主动脉时表达更高。
结论
RIPC 可在冠状动脉旁路移植术期间保护右心房中线粒体呼吸，并防止 miR-1 的上调。
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