Melatonin reduces ventricular arrhythmias and preserves capillary perfusion during ischemia-reperfusion events in cardiomyopathic hamsters

Earlier studies showed that melatonin has powerful antioxidative effects on ischemia-reperfusion (I/R) injury in healthy hamsters. In the present study, the possible protective effects of melatonin in 10-month-old cardiomyopathic (CM) hamsters were evaluated in a model of I/R in the cheek pouches observed by intravital microscopy. In CM (BIO 14.6) hamsters diameter, red blood cell (RBC) velocity and flow in arterioles as well as lipid peroxide and nitrite/nitrate concentrations in the systemic blood, perfused capillary length, vascular permeability, and leukocyte adhesion were measured after melatonin injection (6 mg/kg intraperitoneally daily for 3 weeks), and after I/R. The influence of melatonin on the incidence of postischemic-reperfusion-induced ventricular tachycardia (VT) and ventricular fibrillation (VF) were also measured. Changes in the arteriolar response to NG-monomethyl-L-arginine (L-NMMA), a nitric oxide inhibitor, norepinephrine (NE), and angiotensin II (ANG II) were studied before and after melatonin injection (10 mg/kg intravenously). In CM hamsters, melatonin restored normal arteriolar responses to L-NMMA, NE, and ANG II. I/R elevated lipid peroxide and nitrate/nitrite levels, and vascular permeability while arteriolar diameter, RBC velocity, flow and capillary perfusion were reduced. These effects were more marked in CM versus healthy hamsters. During I/R melatonin reduced oxidative and nitrosative stress, vasoconstriction, leukocyte adhesion, and vascular permeability and increased capillary perfusion. Melatonin reduced the incidence of VT while VF during reperfusion disappeared totally. In conclusion, melatonin prevents both microvascular injury and ventricular arrhythmias during postischemic reperfusion by modulating the lipid peroxide overproduction and nitrative stress which are involved in the development of cardiomyopathy.