Antiarrhythmic Effects of Chronic Melatonin Treatment Are Not Associated with Its Antioxidative Action in Rat Myocardial Ischemia/Reperfusion Model

Abstract

IntroductionMelatonin was proposed as a potential antiarrhythmic agent, and its antioxidative properties are considered to be the basis for the antiarrhythmic effect. The present study was aimed at the evaluation of association between ventricular tachycardia and/or ventricular fibrillation (VT/VF) incidence, oxidative stress parameters and electrophysiological changes in myocardial ischemia/reperfusion setting.Methods18 rats were treated by melatonin (10 mg/kg/day, orally) for 7 days, while 13 control animals were given placebo. The left anterior descending artery was reversibly ligated for 5 min to induce ischemia and subsequent reperfusion in the anesthetized animals. Unipolar electrograms were recorded from ventricular epicardium with a 64‐lead array connected to a custom‐made high‐resolution (4 kHz) mapping system. Local activation and repolarization times were measured as instants of dV/dt min during QRS complexes and dV/dt max during T waves in unipolar electrograms, respectively. Local repolarization durations and dispersion of repolarization were calculated. After experiments, the hearts were excised, and parameters of the oxidative stress were determined in ventricular myocardium.ResultsVT/VF incidence was less in the animals given melatonin as compared to controls (6/18 vs 9/13, p=0.047, respectively). Superoxide dismutase activity was higher in the melatonin group as compared to the control group (69.6±0.5 vs 60.2±2.0 inhibition rate %, p=0.001, respectively), while total antioxidant capacity, 4‐HNE adduct and total glutathione content did not differ in the studied groups. No parameters of oxidative stress were associated with arrhythmia susceptibility. Among the studied ventricular epicardial electrophysiological parameters, local activation times at the baseline (preischemic) state were both reduced by melatonin treatment (9.39±0.26 vs 10.58±0.33 ms, p=0.012) and associated with VT/VF incidence (B=1.872, 95% CI 1.106–3.169, p=0.020) in logistic regression analysis. No association between parameters of ventricular electrical excitation and oxidative stress were found.ConclusionThough chronic melatonin treatment enhanced enzymatic antioxidant activity, its antiarrhythmic action in ischemia/reperfusion model was associated with its direct effect on ventricular activation pattern.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.