Melatonin Prevents 1A Phase Ventricular Fibrillation in Porcine Acute Myocardial Infarction Model

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IntroductionVentricular fibrillation (VF) is a frequent complication of acute myocardial ischemia. Its prevention necessitates development of an antiarrhythmic cardioprotective strategy, and melatonin is considered to be a candidate antiarrhythmic agent. Though mechanisms of its action are largely unclear, generation of reactive oxygen species are thought to be its probable target. The objective of the present study was to find out an electrophysiological parameter subject to modification by melatonin and associated with VF incidence.MethodsAcute ischemia was induced in 25 anesthetized pigs by a 40‐min ligation of the left anterior descending coronary artery. After tightening the ligature, 12 animals were given melatonin (4 mg/kg, i.v.) and 13 placebo (control group). Intramyocardial unipolar electrograms were led from flexible electrodes (a total of 48 leads) positioned across ventricular walls and interventricular septum (IVS). Local activation times (AT, dV/dt min during QRS), end of repolarization times (RT, dV/dt max during T wave) and activation‐repolarization intervals (ARI, difference between RT and AT) were measured. After experiments, the hearts were excised, and parameters of oxidative stress were determined in the ischemic and nonischemic zones of ventricular myocardium.ResultsIn the control group, VFs were typically clustered during occlusion in 1A (1–5 min, 4 episodes) and 1B (17–40 min, 4 episodes) phases. Melatonin prevents development of 1A VFs (0 episodes, p=0.016) but did not modify occurence of 1B VFs (4 episodes). In the base of IVS (border ischemic zone), ATs in the period corresponding to 1A phase arrhythmias were shorter in the melatonin group as compared to the control group (Mean ± SD: 22±11 ms vs 39±18 ms, p=0.026, respectively) and were associated with VF incidence (OR 1.05 95% CI 1.01–1.10, p=0.023), while parameters of ventricular repolarization and oxidative stress did not differ between the treated and untreated animals.In conclusion, melatonin treatment improves conduction in the border ischemic zone and thereby prevents early ischemic VFs independently of oxidative stress development.Support or Funding InformationThe study was supported by Russian Science Foundation (RSF 18‐15‐00309).