Tsvetkova Alena S, Bernikova Olesya G, Mikhaleva Natalya J, Khramova Darya S, Ovechkin Alexey O, Demidova Marina M, Platonov Pyotr G, Azarov Jan E
Department of Cardiac Physiology, Institute of Physiology, Komi Science Center, Ural Branch, Russian Academy of Sciences, 167000 Syktyvkar, Russia.
Department of Molecular Immunology and Biotechnology, Institute of Physiology, Komi Science Center, Ural Branch, Russian Academy of Sciences, 167000 Syktyvkar, Russia.
Int J Mol Sci. 2020 Dec 30;22(1):328. doi: 10.3390/ijms22010328.
Antiarrhythmic effects of melatonin have been demonstrated ex vivo and in rodent models, but its action in a clinically relevant large mammalian model remains largely unknown. Objectives of the present study were to evaluate electrophysiological and antiarrhythmic effects of melatonin in a porcine model of acute myocardial infarction. Myocardial ischemia was induced by 40-min coronary occlusion in 25 anesthetized pigs. After ischemia onset, 12 animals received melatonin (4 mg/kg). 48 intramyocardial electrograms were recorded from left ventricular wall and interventricular septum (IVS). In each lead, activation time (AT) and repolarization time (RT) were determined. During ischemia, ATs and dispersion of repolarization (DOR = RTmax - RTmin) increased reaching maximal values by 3-5 and 20-25 min, respectively. Ventricular fibrillation (VF) incidence demonstrated no relations to redox state markers and was associated with increased DOR and delayed ATs (specifically, in an IVS base, an area adjacent to the ischemic zone) ( = 0.031). Melatonin prevented AT increase in the IVS base, ( < 0.001) precluding development of early VF (1-5 min, = 0.016). VF occurrence in the delayed phase (17-40 min) where DOR was maximal was not modified by melatonin. Thus, melatonin-related enhancement of activation prevented development of early VF in the myocardial infarction model.
褪黑素的抗心律失常作用已在体外和啮齿动物模型中得到证实，但其在临床相关的大型哺乳动物模型中的作用仍 largely 未知。本研究的目的是评估褪黑素在猪急性心肌梗死模型中的电生理和抗心律失常作用。在 25 只麻醉猪中通过 40 分钟的冠状动脉闭塞诱导心肌缺血。缺血发作后，12 只动物接受褪黑素（4mg/kg）。从左心室壁和室间隔（IVS）记录 48 个心内膜电图。在每个导联中，确定激活时间（AT）和复极时间（RT）。在缺血期间，AT 和复极离散度（DOR = RTmax - RTmin）增加，分别在 3 - 5 分钟和 20 - 25 分钟达到最大值。室颤（VF）发生率与氧化还原状态标志物无关，并且与 DOR 增加和 AT 延迟有关（特别是在 IVS 基部，即与缺血区相邻的区域）（P = 0.031）。褪黑素可防止 IVS 基部的 AT 增加（P < 0.001），从而预防早期室颤的发生（1 - 5 分钟，P = 0.016）。在 DOR 最大的延迟期（17 - 40 分钟）发生的室颤未被褪黑素改变。因此，褪黑素相关的激活增强可预防心肌梗死模型中早期室颤的发生。
