Vol. 292, Issue 1, 381-386, January 2000

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

Anne M. Gillis, Heather J. Mathison, Elzbieta Kulisz and Wanda M. Lester

The Cardiovascular Research Group, Departments of Medicine and Pathology, The University of Calgary, Calgary, Alberta, Canada

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 and I_Kr blockers cause greater prolongation APD and increased APD dispersion in left ventricular hypertrophy, and this is associated with the development of ventricular fibrillation.