Department of Cardiac Physiology, Institute of Physiology, Komi Science Center, Ural Branch, Russian Academy of Sciences, Syktyvkar, Russia.
Department of Biomedical Technology, Faculty of Biomedical Engineering, Czech Technical University in Prague, Kladno, Czech Republic.
J Pineal Res. 2022 Aug;73(1):e12798. doi: 10.1111/jpi.12798. Epub 2022 Apr 13.
Melatonin treatment was reported to reduce the risk of cardiac arrhythmias, and crucial for this antiarrhythmic action was the effect of melatonin on activation spread. The aim of the present study was evaluation of the mechanisms of this activation enhancement. Experiments were performed in a total of 123 control and melatonin-treated (10 mg/kg, daily, for 7 days) male Wistar rats. In epicardial mapping studies (64 leads, interlead distance 0.5 mm) in the anesthetized animals, activation times (ATs) were determined in each lead as dV/dt minimum during QRS complex under sinus rhythm. Epicardial pacing was performed to measure conduction velocity (CV) across the mapped area. Average left ventricular ATs were shorter in the treated animals as compared to the controls, whereas the minimal epicardial ATs indicating the duration of activation propagation via the ventricular conduction system did not differ between the groups. CV was higher in the treated groups indicating that melatonin affected conduction via contractile myocardium The area of Cx43-derived fluorescence, as well as the expression of Cx43 protein, was similar in ventricles in the control and melatonin-treated groups. Expression of Gja1 gene transcripts encoding Cx43, was increased in the last group. An uncoupling agent octanol modified myocardial conduction properties (time of activation, action potential upstroke velocity, passive electrotonic phase duration) similarly in both groups. On the other hand, the expression of both Scn5a gene transcripts encoding Nav1.5 proteins, as well as peak density of transmembrane sodium current were increased in the ventricular myocytes from the melatonin-treated animals. Thus, a week-long melatonin treatment caused the increase of conduction velocity via enhancement of sodium channel proteins expression and increase of sodium current in the ventricular myocytes.
褪黑素治疗据报道可降低心律失常的风险，褪黑素对激活传播的影响对这种抗心律失常作用至关重要。本研究的目的是评估这种激活增强的机制。
实验在总共 123 只雄性 Wistar 大鼠（对照组和褪黑素处理组各 61 只）中进行。在麻醉动物的心外膜标测研究（64 个导联，导联间距离 0.5mm）中，在窦性节律下 QRS 复合波中 dV/dt 最小值确定每个导联的激活时间（AT）。进行心外膜起搏以测量标测区域的传导速度（CV）。与对照组相比，处理组的平均左心室 AT 较短，而最小心外膜 AT 不表示通过心室传导系统的激活传播持续时间，两组之间无差异。CV 在处理组中较高，表明褪黑素影响通过收缩心肌的传导。Cx43 衍生荧光的面积以及 Cx43 蛋白的表达在对照组和褪黑素处理组的心室中相似。编码 Cx43 的 Gja1 基因转录本的表达在最后一组中增加。解偶联剂辛醇在两组中均以相似的方式改变心肌传导特性（激活时间、动作电位上升速度、被动电紧张期持续时间）。另一方面，来自褪黑素处理动物的心室心肌细胞中 Nav1.5 蛋白编码的 Scn5a 基因转录本的表达以及跨膜钠电流的峰值密度均增加。因此，一周的褪黑素治疗通过增强钠通道蛋白表达和增加心室肌细胞中的钠电流来增加传导速度。
