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 electrophysiologic 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 rats. 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 increase of the total antioxidant capacity of myocardial samples. We also explored the possible role of currents activated by cell swelling studying the electrophysiologic effects of a 10 min hypotonic challenge. Tamoxifen (5 µM) blocked the action potential shortening and the late resting depolarization produced by hypotonicity, mimicking its action in late ischemia. Consequently, we conclude that the dose-dependent antiarrhythmic action of this agent is related to the modulation of ionic currents activated by cell swelling.