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Preventive Antiarrhythmic Properties of Melatonin in Experimental Diabetic Cardiomyopathy in Rats
Alexey O Ovechkin1, Mikhail A Gonotkov1, Alena S Abramochkina1,2
1Department of Cardiac Physiology, Institute of Physiology, Komi Science Center, Ural Branch of Russian Academy of Sciences, Syktyvkar, Komi Republic, Russia.
Abstract:
Diabetes mellitus (DM) promotes cardiac arrhythmias, whereas melatonin confers antiarrhythmic effects. Cellular targets modified by DM and melatonin largely overlap, which warrants testing melatonin as an antiarrhythmic agent in DM. Herein, we evaluated electrophysiological and antiarrhythmic properties of melatonin in the experimental DM model. Experiments were performed in 41 control and 71 diabetic rats. 34 diabetic animals were treated with melatonin (orally, 10 mg/kg daily) for 1 month, and 37 diabetic animals received a placebo. Electrophysiological studies included electrocardiography, in vivo epicardial mapping with induction of ischemia-reperfusion, and patch-clamp studies in ventricular cardiomyocytes. Collagen deposition was assessed in postmortem histological studies. RT-PCR and Western blotting methods were used to estimate Gja1 gene expression and Cx43 protein level, respectively. Melatonin treatment in diabetic animals did not influence the level of glycaemia, but mitigated the progression of myocardial fibrosis. Melatonin treatment prevented the DM-related decrease in conduction velocity, increase in duration and dispersion of repolarization, as well as corresponding changes in their electrocardiographic correlates (QRS, QT, and Tpeak-Tend intervals, respectively). Melatonin also prevented the development of reperfusion ventricular tachycardia/fibrillation. The patch-clamp studies showed that melatonin treatment significantly reduced calcium current, prevented DM-related action potential duration prolongation, but did not modify DM-related increase in sodium current. RT-PCR studies demonstrated that melatonin treatment prevented the DM-related upregulation of Gja1 gene expression and increase in Cx43 level. Melatonin treatment of diabetic rats conferred antiarrhythmic effects associated with electrophysiological changes reflected in ECG parameters, which warrants further testing of melatonin in a clinical context.
Insights
Melatonin treatment in diabetic rats improved cardiac electrical stability and reduced fibrosis. This suggests melatonin may be a potential antiarrhythmic therapy for diabetes-related heart issues.
Area of Science:
- Cardiology
- Endocrinology
- Pharmacology
Background:
- Diabetes mellitus (DM) is linked to cardiac arrhythmias.
- Melatonin exhibits antiarrhythmic properties.
- Overlapping cellular targets suggest potential therapeutic synergy.
Purpose of the Study:
- To investigate melatonin's electrophysiological and antiarrhythmic effects in a rat model of DM.
- To assess melatonin's impact on myocardial fibrosis and electrical parameters.
Main Methods:
- Utilized a rat model of diabetes mellitus.
- Conducted electrocardiography, in vivo epicardial mapping, and patch-clamp studies.
- Assessed myocardial collagen deposition, Gja1 gene expression, and Cx43 protein levels.
Main Results:
- Melatonin mitigated myocardial fibrosis and prevented DM-related electrical abnormalities.
- Treatment normalized conduction velocity, repolarization duration/dispersion, and ECG intervals (QRS, QT, Tpeak-Tend).
- Melatonin prevented reperfusion-induced ventricular arrhythmias and reduced calcium current, without affecting sodium current or Gja1/Cx43 expression.
Conclusions:
- Melatonin demonstrates significant antiarrhythmic effects in diabetic rats.
- These effects are linked to improved electrophysiological parameters and reduced fibrosis.
- Melatonin warrants further clinical investigation as an antiarrhythmic agent for diabetic patients.
