Abstract
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) (p = 0.031). Melatonin prevented AT increase in the IVS base, (p < 0.001) precluding development of early VF (1–5 min, p = 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.
Highlights
In this work in a porcine myocardial infarction model, we aimed to explore the effects of melatonin on the myocardial electrophysiological parameters known to be related to reentrant arrhythmias, heart rate as a surrogate index for autonomic output, and their associations with oxidative stress parameters and VT/Ventricular fibrillation (VF) incidence during ischemia progression
Due to the coronary anatomy and location of occlusion (just distal to the first diagonal branch of the left anterior descending (LAD)coronary artery), the most pronounced effects were observed in the left ventricular (LV) apex, interventricular septum (IVS) apex and IVS middle portion
As the minimal Activation-repolarization intervals (ARIs) duration characteristic of deeply affected ischemic regions decrease during occlusion, and the maximal ARI duration observed in the normal regions was unchanged, dispersion of repolarization (DOR) progressively increased (Figure 2C)
Summary
Ventricular fibrillation (VF) is a frequent life-threatening complication of myocardial ischemia, and search for effective antiarrhythmic agents to be applied in myocardial infarction patients remains an important challenge. Possible proarrhythmic effects of antiarrhythmic drugs continue to be a limitation hampering their use for arrhythmia prevention [1]. A natural pineal secretory product, has been demonstrated to confer versatile beneficial effects including cardioprotection [2]. Melatonin brought about antiarrhythmic effects [3,4,5,6,7,8,9] during ischemia/reperfusion. These properties make melatonin a promising substance for further testing as a potential antiarrhythmic treatment in the setting of myocardial infarction
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