Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, 1090 Vienna, Austria.
Department of Pharmacology and Pharmacotherapy, Semmelweis University, 1089 Budapest, Hungary.
Int J Mol Sci. 2019 Apr 30;20(9):2140. doi: 10.3390/ijms20092140.
We investigated the antiarrhythmic effects of ischemic preconditioning (IPC) and postconditioning (PostC) by intracardiac electrocardiogram (ECG) and measured circulating microRNAs (miRs) that are related to cardiac conduction. Domestic pigs underwent 90-min. percutaneous occlusion of the mid left anterior coronary artery, followed by reperfusion. The animals were divided into three groups: acute myocardial infarction (AMI, = 7), ischemic preconditioning-acute myocardial infarction (IPC-AMI) ( = 9), or AMI-PostC ( = 5). IPC was induced by three 5-min. episodes of repetitive ischemia/reperfusion cycles (rI/R) before AMI. PostC was induced by six 30-s rI/R immediately after induction of reperfusion 90 min after occlusion. Before the angiographic procedure, a NOGA endocardial mapping catheter was placed again the distal anterior ventricular endocardium to record the intracardiac electrogram (R-amplitude, ST-Elevation, ST-area under the curve (AUC), QRS width, and corrected QT time (QTc)) during the entire procedure. An arrhythmia score was calculated. Cardiac MRI was performed after one-month. IPC led to significantly lower ST-elevation, heart rate, and arrhythmia score during ischemia. PostC induced a rapid recovery of R-amplitude, decrease in QTc, and lower arrhythmia score during reperfusion. Slightly higher levels of miR-26 and miR-133 were observed in AMI compared to groups IPC-AMI and AMI-PostC. Significantly lower levels of miR-1, miR-208, and miR-328 were measured in the AMI-PostC group as compared to animals in group AMI and IPC-AMI. The arrhythmia score was not significantly associated with miRNA plasma levels. Cardiac MRI showed significantly smaller infarct size in the IPC-AMI group when compared to the AMI and AMI-PostC groups. Thus, IPC led to better left ventricular ejection fraction at one-month and it exerted antiarrhythmic effects during ischemia, whereas PostC exhibited antiarrhythmic properties after reperfusion, with significant downregulaton of ischemia-related miRNAs.
我们通过心内心电图（ECG）研究了缺血预处理（IPC）和后处理（PostC）的抗心律失常作用，并测量了与心脏传导相关的循环 microRNAs（miRs）。家猪经历了 90 分钟的经皮左前中冠状动脉闭塞，随后再灌注。动物分为三组：急性心肌梗死（AMI，n=7）、缺血预处理-急性心肌梗死（IPC-AMI，n=9）或 AMI-PostC（n=5）。IPC 在 AMI 前通过三个 5 分钟的重复缺血/再灌注循环（rI/R）发作诱导。PostC 在闭塞后 90 分钟再灌注后立即通过六个 30 秒的 rI/R 诱导。在血管造影程序之前，再次将 NOGA 心内膜标测导管放置在心尖前心室的心内膜上，以记录整个程序期间的心内电图（R 波振幅、ST 抬高、ST 曲线下面积（AUC）、QRS 宽度和校正 QT 时间（QTc））。计算心律失常评分。在一个月后进行心脏 MRI。IPC 导致缺血期间 ST 抬高、心率和心律失常评分明显降低。PostC 在再灌注期间迅速恢复 R 波振幅，降低 QTc，并降低心律失常评分。与 IPC-AMI 和 AMI-PostC 组相比，AMI 组观察到 miR-26 和 miR-133 的水平略高。与 AMI 组相比，AMI-PostC 组测量到 miR-1、miR-208 和 miR-328 的水平明显降低。心律失常评分与 miRNA 血浆水平无显著相关性。心脏 MRI 显示 IPC-AMI 组的梗死面积明显小于 AMI 和 AMI-PostC 组。因此，IPC 在一个月时导致左心室射血分数更好，并且在缺血期间发挥抗心律失常作用，而 PostC 在再灌注后表现出抗心律失常特性，与缺血相关的 miRNAs 明显下调。
