Dispersion of Ventricular Repolarization and Ventricular Fibrillation in Left Ventricular Hypertrophy: Influence of Selective Potassium Channel Blockers1

Abstract

This study tested the hypothesis that combination ion channel blockers of the transient outward current (I_to) and the rapid component of the delayed rectifying current (I_Kr) would produce greater prolongation of the ventricular action potential duration (APD) and increased dispersion of the APD in hypertrophied hearts compared with control hearts. Isolated rabbit hearts were studied 48 ± 5 days postabdominal aortic banding. Left ventricular endocardial and epicardial APDs were significantly greater at baseline in the hypertrophied group than in controls (P < .05). The magnitude of APD prolongation induced by the I_to blocker 4-aminopyridine (4-AP) and combination 4-AP and the I_Kr blocker dofetilide was greater in the hypertrophied hearts than in the normal hearts (P < .01). Mean APD dispersion was significantly greater in the hypertrophied group than in the control hearts at baseline (P < .05). 4-AP increased APD dispersion by a similar magnitude in the hypertrophied hearts (10 ± 10 ms) and the control hearts (8 ± 8 ms, P= NS), whereas the combination 4-AP and dofetilide increased APD dispersion by a greater magnitude in the hypertrophied hearts (41 ± 28 ms) than the control hearts (21 ± 11 ms,P < .05). Ventricular fibrillation occurred spontaneously in four hypertrophied hearts (40%) during combination drug perfusion and in none of the control hearts (P< .05). Thus, combination I_to andI_Kr blockers cause greater prolongation APD and increased APD dispersion in left ventricular hypertrophy, and this is associated with the development of ventricular fibrillation.