CONICET | Buscador de Institutos y Recursos Humanos

Reperfusion arrhythmias are currently attributed to ionic imbalance and oxidative stress. Tamoxifen is a potent antioxidant that also modulates some ionic transport systems. In this work we tried to correlate the lectrophysiologic effects of 1, 2 and 5 μM tamoxifen with the incidence and severity of arrhythmias appearing on reperfusion after 10 min of coronary occlusion in isolated hearts from female rat. Tamoxifen prolonged the PR and the QT intervals in all groups. All tamoxifen concentrations inhibited the action potential shortening observed in the control hearts during late ischemia (6 to 10 min), whereas 2 and 5 μM also reduced the resting depolarization. The incidence of sustained Ventricular tachycardia and/or ventricular fibrillation decreased from 10/12 (control group) to 5/10 (1 μM, P=0.1718), 4/12 (2 μM, P=0.0361) and 2/10 (5 μM, P=0.0083). Tamoxifen produced a similar level of increase in the total antioxidant capacity of myocardial samples excised at the end of the experimental protocol. We also explored the possible role of currents activated by cell swelling studying the electrophysiologic effects of a 10 min hypotonic challenge. Similar to its action during ischemia, 5 μM tamoxifen blocked the action potential shortening and the late resting depolarization produced by hypotonicity. Consequently, we conclude that the dose-dependent antiarrhythmic action of this agent is closely related to the modulation of ionic currents activated under stressful situations.