Melatonin, given at the time of reperfusion, prevents ventricular arrhythmias in isolated hearts from fructose‐fed rats and spontaneously hypertensive rats

Abstract

Melatonin reduces reperfusion arrhythmias when administered before coronary occlusion, but in the clinical context of acute coronary syndromes, most of the therapies are administered at the time of reperfusion. Patients frequently have physiological modifications that can reduce the response to therapeutic interventions. This work determined whether acute melatonin administration starting at the moment of reperfusion protects against ventricular arrhythmias in Langendorff-perfused hearts isolated from fructose-fed rats (FFR), a dietary model of metabolic syndrome, and from spontaneous hypertensive rats (SHR). In both experimental models, we confirmed metabolic alterations, a reduction in myocardial total antioxidant capacity and an increase in arterial pressure and NADPH oxidase activity, and in FFR, we also found a decrease in eNOS activity. Melatonin (50 μm) initiated at reperfusion after 15-min regional ischemia reduced the incidence of ventricular fibrillation from 83% to 33% for the WKY strain, from 92% to 25% in FFR, and from 100% to 33% in SHR (P = 0.0361, P = 0.0028, P = 0.0013, respectively, by Fisher's exact test, n = 12 each). Although, ventricular tachycardia incidence was high at the beginning of reperfusion, the severity of the arrhythmias progressively declined in melatonin-treated hearts. Melatonin induced a shortening of the action potential duration at the beginning of reperfusion and in the SHR group also a faster recovery of action potential amplitude. We conclude that melatonin protects against ventricular fibrillation when administered at reperfusion, and these effects are maintained in hearts from rats exposed to major cardiovascular risk factors. These results further support the ongoing translation to clinical trials of this agent.

Inflammaging, Metabolic Syndrome and Melatonin: A Call for Treatment Studies

“…In rats fed from weaning with a high-fat diet melatonin decreased body weight gain, feed efficiency and plasma glucose, leptin and triglyceride levels [44] In middle-aged rats receiving a high caloric liquid diet, melatonin reduced weight gain and plasma insulin and leptin levels [45] In high-fat diet-fed mice, melatonin improved insulin sensitivity and glucose tolerance [46] In ovariectomized rats, melatonin was effective to reduce obesity [47][48][49] In olanzapine-treated rats, melatonin was effective to reduce obesity [50] In gold fish body weight gain and specific growth rate were reduced by melatonin treatment [51] Melatonin and its analog piromelatonin inhibited weight gain and improves insulin sensitivity in high-fat fed rats [52] In high-fat fed rats, melatonin attenuated body weight increase, the increase in plasma glucose, insulin, adiponectin, leptin, triglycerides and cholesterol levels, and counteracted disrupted 24 h patterns [53] Melatonin reduced body weight gain, visceral adiposity, blood triglyceride and insulin levels and TBARS under a high calorie diet in rats. [54] In young male Zucker diabetic fatty rats melatonin treatment reduced mean weight gain without affecting food intake, decreased in a non-significant way blood pressure, and improved dyslipidemia [55] Melatonin improves MS induced by high fructose intake in rats without affecting food intake [56][57][58][59] Melatonin and its analog piromelatonin reduced blood pressure in spontaneously hypertensive rats [60] Melatonin prevents the development of the MS in male rats exposed to different light/dark regimens [61] Melatonin attenuates high fat diet-induced fatty liver disease in rats [62] Melatonin, given at the time of reperfusion, prevents ventricular arrhythmias in isolated hearts from fructose-fed rats and spontaneously hypertensive rats [63] Melatonin ameliorates low-grade inflammation and oxidative stress in young Zucker diabetic fatty rats [64] Protective effects of melatonin against metabolic and reproductive disturbances in polycystic ovary syndrome in rats [65] Melatonin normalizes clinical and biochemical parameters of mild inflammation in diet-induced MS syndrome in rats [66] Melatonin counteracts changes in hypothalamic gene expression of signals regulating feeding behavior in high-fat fed rats…”

A review of melatonin as a suitable antioxidant against myocardial ischemia–reperfusion injury and clinical heart diseases

“…A large amount of data published by a variety of investigations has demonstrated that melatonin can effectively reduce myocardial IR injury (Table 1). In a study using a working heart model, Dobsak et al [31] document that the treatment with melatonin caused a significant improvement of hemodynamic parameters and a reduction of postischemic arrhythmias during reperfusion; the ability of melatonin to correct cardiac arrhythmias was also noted by Diez et al [32]. A review by Dominguez-Rodriguez et al [33] suggests that melatonin plays a key role in coronary heart disease; this is consistent with observations that melatonin reduces infarct size after experimental heart attack [34].…”

Antiarrhythmic mechanisms of Malbec wine and resveratrol in isolated rat heart

“…These concentrations are impossible to be achieved by Malbec or any red wine consumption alone [12,33]. Catechin, melatonin, and quercetin are also wine components, but the effective concentrations are at least two orders of magnitude below the active electrophysiological levels [7,12,36,[57][58][59].…”

“…All samples were homogenized keeping the temperature low by immersion of the tubes in ice during the process. The total antioxidant capacity was determined as previously described [36,37]. In brief, the radical ABTS•+, monocation of 2,29-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) is generated by ABTS oxidation with potassium persulfate and read at 600 nm with a UV-visible Spectrometer (Helios Gama, Helios Delta, Unicam instruments, UK), In the presence of hydrogen-donating antioxidants the cation is reduced and the color inhibited.…”