Association Between Antiarrhythmic, Electrophysiological, and Antioxidative Effects of Melatonin in Ischemia/Reperfusion

Abstract

Melatonin is assumed to confer cardioprotective action via antioxidative properties. We evaluated the association between ventricular tachycardia and/or ventricular fibrillation (VT/VF) incidence, oxidative stress, and myocardial electrophysiological parameters in experimental ischemia/reperfusion under melatonin treatment. Melatonin was given to 28 rats (10 mg/kg/day, orally, for 7 days) and 13 animals received placebo. In the anesthetized animals, coronary occlusion was induced for 5 min followed by reperfusion with recording of unipolar electrograms from ventricular epicardium with a 64-lead array. Effects of melatonin on transmembrane potentials were studied in ventricular preparations of 7 rats in normal and “ischemic” conditions. Melatonin treatment was associated with lower VT/VF incidence at reperfusion, shorter baseline activation times (ATs), and activation-repolarization intervals and more complete recovery of repolarization times (RTs) at reperfusion (less baseline-reperfusion difference, ΔRT) (p < 0.05). Superoxide dismutase (SOD) activity was higher in the treated animals and associated with ΔRT (p = 0.001), whereas VT/VF incidence was associated with baseline ATs (p = 0.020). In vitro, melatonin led to a more complete restoration of action potential durations and resting membrane potentials at reoxygenation (p < 0.05). Thus, the antioxidative properties of melatonin were associated with its influence on repolarization duration, whereas the melatonin-related antiarrhythmic effect was associated with its oxidative stress-independent action on ventricular activation.

Reperfusion Arrhythmias Increase after Superior Cervical Ganglionectomy Due to Conduction Disorders and Changes in Repolarization

“…Melatonin receptors are coupled to Kir3.x channels, and melatonin receptor activation shortens the action potential duration [23,47]. However, we recently showed that melatonin-induced changes on myocardial repolarization were associated with melatonin antioxidative properties but not with its antiarrhythmic actions [15,48,49]. Our negative results with nitrotyrosine ( Figure 7) as a marker of nitroxidative stress agree with antioxidant been unrelated to antiarrhythmic effects.…”

Antiarrhythmic Effects of Melatonin and Omega-3 Are Linked with Protection of Myocardial Cx43 Topology and Suppression of Fibrosis in Catecholamine Stressed Normotensive and Hypertensive Rats

“…Recent studies suggest that targeting arrhythmogenic redox imbalance may provide novel therapeutics to treat or prevent life-threatening arrhythmias and SCD [3,16]. In harmony with it, a large body of evidence of experimental studies point out the benefit of pineal hormone melatonin due to its pleiotropic anti-oxidant and anti-inflammatory actions [11,[21][22][23]. Arrhythmias and abnormalities of Cx43 can be prevented predominantly by mitochondria-targeted antioxidants and the property of melatonin is that it can easily penetrate cells and mitochondria, where it can eliminate the excess of free radicals [24].…”

Therapeutic Algorithm for Use of Melatonin in Patients With COVID-19

“…The uncontrolled innate immune response promotes a massive inflammatory reaction and causes irreversible tissue damage and mortality. Melatonin is a potent antioxidant and immune regulator that not only suppresses oxidative stress but also controls the innate immune response and promotes the adaptive immune response (15,16). The pineal gland produces and maintains the concentration of melatonin in the blood.…”

“…The melatonin produced in the mitochondria is not discharged into the circulation, but is used by the cells that produce it (15). If patients do not generate sufficient amounts of melatonin their health status is likely compromised (16).…”