Preventive Melatonin Administration Decreased Dispersion of Repolarization and Myocardium Susceptibility to Ventricular Tachyarrhythmias in a Model of Acute Coronary Occlusion in Rabbits

Abstract

IntroductionMelatonin is known to have a spectrum of antioxidative and cardioprotective properties, which may be beneficial in ischemia/reperfusion conditions, but a mechanism of its antiarrhythmic effects remains to be established. This study aimed to assess effects of preventive melatonin treatment on spatiotemporal ventricular electrophysiological parameters and susceptibility of myocardium to ventricular tachycardia and/or ventricular fibrillation (VT/VF) in an experimental model of acute ischemia/reperfusion in rabbits.MethodsExperiments were performed in 28 anesthetized open‐chest rabbits. Melatonin (10 mg/kg, i.v.) was administrated to the animals (n = 5) one hour before coronary occlusion, whereas the control rabbits (n = 23) received placebo. Unipolar electrograms were recorded with 64‐electrodes epicardial sock connected to a custom‐designed high resolution system (4 kHz) in a baseline state, at 15 min of the left circumflex coronary artery occlusion and after subsequent 15‐min reperfusion. Activation times and repolarization times (RTs) were measured in each lead as dV/dt minimum during QRS complex and dV/dt maximum during T wave, respectively. A border dispersion of repolarization (DOR) was measured as a difference between the minimal and maximal RTs of ischemic and border zone. The VT/VF susceptibility was tested by high frequency stimulation.ResultsMelatonin administration did not change baseline spatiotemporal activation and repolarization parameters. Median RTs were shortened in the ischemic zone at 15 min of coronary occlusion as compared to baseline (control: 90 [IQR 77–109] vs 148 [IQR 112–174] ms, p<0.05; melatonin: 111 [IQR 108–117] vs 158 [IQR 155–160] ms, p<0.05, respectively], with the “ischemic” RTs being significantly longer in the melatonin group (p = 0.038). At 15 min of reperfusion, the melatonin group demonstrated partial restoration of RTs (132 [IQR 123–140] ms), which was not observed in the control group (102 [IQR 95–126] ms, p = 0.044 vs melatonin group). Thus, the border DOR was greater in the control group as compared to the melatonin group at 15 min of ischemia (42 [IQR 21–47] ms vs 21 [IQR 16–21] ms, p = 0.043, respectively) and at 15 min of reperfusion (19 [IQR 8–33] ms vs 7 [IQR 1–8] ms, p = 0.038, respectively). In ischemia the melatonin‐treated animals demonstrated a lower arrhythmia susceptibility (0 vs 13 VT/VF episodes, p = 0.022, respectively).ConclusionIn the rabbit model of acute coronary occlusion/reperfusion, the melatonin‐related mitigation of VT/VF susceptibility was associated with the limitation of repolarization shortening in ischemic zone and decrease of DOR.Support or Funding InformationThe study was supported by Russian Science Foundation (RSF 18‐15‐00309).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.