CONICET | Buscador de Institutos y Recursos Humanos

Melatonin reduces reperfusion arrhythmias when administered before coronary occlusion but in the clinical context of acute coronary syndromes most of the therapies can be administered at the time of reperfusion. Patients frequently have physiological modifications that can reduce the response to therapeutic interventions. The aim of this work was to determine 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, 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 exact test, n=12 each). Although, ventricular tachycardia incidence persisted high at the beginning of reperfusion, the severity of the arrhythmias progressively declined in 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.