Abstract
BACKGROUND On a cellular level, Brugada syndrome has been attributed to a deep phase 1 notch and subsequent shallow and prolonged repolarization in the right ventricular outflow tract (RVOT). A sodium channel mutation that leads to early inactivation of the late sodium current has been identified in some patients. Thus, drugs that inhibit the transient outward current (I(to)) responsible for the phase 1 notch and/or enhance the late sodium current might suppress arrhythmic events in patients with Brugada syndrome. The effects of quinidine gluconate, a potent inhibitor of I(to), on RVOT action potential duration (APD) restitution kinetics in patients with Brugada syndrome were evaluated. METHODS AND RESULTS Programmed ventricular stimulation was performed in 9 Brugada syndrome patients by delivering up to 3 extrastimuli from the right ventricular apex and RVOT. RVOT monophasic action potentials (MAPs) were recorded before and after intravenous administration of quinidine (n=6) or ibutilide (n=3). All patients had inducible ventricular fibrillation (VF) before drug administration. Both quinidine and ibutilide increased steady-state and minimum RVOT MAP duration during programmed stimulation. Quinidine decreased the maximum slope of the RVOT APD restitution curve and VF could not be induced after administration of quinidine in 5 of the 6 patients. CONCLUSIONS Quinidine appears to suppress the induction of VF by increasing RVOT MAP duration and decreasing the maximum slope of the restitution curve.
