REGRESSION OF LEFT-VENTRICULAR HYPERTROPHY WITH CAPTOPRIL RESTORES NORMAL VENTRICULAR ACTION-POTENTIAL DURATION, DISPERSION OF REFRACTORINESS, AND VULNERABILITY TO INDUCIBLE VENTRICULAR-FIBRILLATION

Background Left ventricular hypertrophy (LVH) is associated with multi ple cellular electrophysiological abnormalities, susceptibility to ven tricular arrhythmias, and an increased risk of sudden death. Several p harmacological therapies have been shows to produce regression of hype rtrophy, but the value of regression is unclear. The present study exa mines whether pharmacological regression of LVH has effects on the sus ceptibility to ventricular arrhythmia or the cellular electrophysiolog ical abnormalities of LVH. Methods and Results Rabbits underwent unila teral renal artery banding and contralateral nephrectomy to induce LVH or were placed in the control group. Both groups were studied 3 month s later by in vivo and in vitro electrophysiological techniques. Bande d rabbits had increased mean arterial pressure, increased left ventric ular weight and wall thickness, increased dispersion of refractoriness , and lower ventricular fibrillation thresholds than control rabbits. Action potential duration and cell capacitance were also greater in th e banded group. Additional rabbits were treated beginning 3 months aft er banding with either captopril (5 mg.kg(-1).d(-1)) or vehicle added to their diet for an additional 3 months. These rabbits and age-matche d controls were then studied by in vivo and in vitro electrophysiologi cal techniques. In banded rabbits that received vehicle and were: stud ied 6 months after banding, increased dispersion of refractoriness, a lower ventricular fibrillation threshold, and action potential prolong ation persisted and were unchanged from animals studied 3 months after banding. Captopril, started 3 months after banding, caused regression of hypertrophy and normalization of the in vivo and in vitro electrop hysiological abnormalities. Addition of captopril to the tissue bath d uring in vitro electrophysiological study showed no effect on cells fr om control or banded rabbits. Conclusions Pharmacological regression o f LVH with captopril normalizes the in vivo and in vitro electrophysio logical abnormalities of ventricular hypertrophy and reduces the vulne rability to ventricular fibrillation in a renovascular model of LVH.