N[lc]a(+) channel blockade causes a prolongation of electrical diastole during spiral-type reentry in the ventricle

Abstract

Spiral-type reentry is crucial for genesis and maintenance of the life-threatening ventricular tachyarrhythmia, but little information is available for its pharmacological control. Examined were the effects of pilsicainide (Pil), an antiarrhythmic drug having a specific Na(+) channel blocking action, on the spiral dynamics during ventricular tachycardia (VT). Optical action potential signals were recorded with the aid of a voltage-sensitive dye from the epicardial ventricular surface of rabbit heart perfused in-vitro. The endocardial side of the left ventricule was cryoablated to prepare 2-D subepicardial ventricular muscle layers. A high-resolution video-imaging system combined with fiber optic probes was employed for signal recordings. Pil (3 micro-M) caused a significant reduction of conduction velocity under basal stimulation (S1, 2.5 Hz) without affecting action potential duration. Ventricular tachycardia (VT) induced by cross-field stimulation (S2, 20 V) in the presence of Pil were characterized by slower cycle length (by 22.7 percent) and longer electrical diastole (by 107.2 percent) compared with controls. Pil also caused an enlargement of core area in stational spiral-type excitation. Possible mechanisms involved in the modulation of spiral-type reentry in the ventricle are discussed.