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Background: Left ventricular hypertrophy (LVH) is associated with multiple cellular electrophysiological abnormalities, susceptibility to ventricular arrhythmias, and an increased risk of sudden death. Several pharmacological therapies have been shown to produce regression of hypertrophy, but the value of regression is unclear. The present study examines whether pharmacological regression of LVH has effects on the susceptibility to ventricular arrhythmia or the cellular electrophysiological abnormalities of LVH., Methods and Results: Rabbits underwent unilateral renal artery banding and contralateral nephrectomy to induce LVH or were placed in the control group. Both groups were studied 3 months later by in vivo and in vitro electrophysiological techniques. Banded rabbits had increased mean arterial pressure, increased left ventricular 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 the banded group. Additional rabbits were treated beginning 3 months after banding with either captopril (5 mg x kg(-1) x d(-1)) or vehicle added to their diet for an additional 3 months. These rabbits and age-matched controls were then studied by in vivo and in vitro electrophysiological techniques. In banded rabbits that received vehicle and were studied 6 months after banding, increased dispersion of refractoriness, a lower ventricular fibrillation threshold, and action potential prolongation 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 electrophysiological abnormalities. Addition of captopril to the tissue bath during in vitro electrophysiological study showed no effect on cells from control or banded rabbits., Conclusions: Pharmacological regression of LVH with captopril normalizes the in vivo and in vitro electrophysiological abnormalities of ventricular hypertrophy and reduces the vulnerability to ventricular fibrillation in a renovascular model of LVH.

Intravenous amiodarone was approved in 1995 for the treatment of malignant and resistant ventricular arrhythmia. Although it is an "old drug," much has been learned recently about this complex drug and its application in a variety of cardiac arrhythmias. The objectives of this review were to summarize what is known about intravenous amiodarone, including its pharmacologic and electrophysiologic effects, to review its efficacy for the treatment of patients with highly malignant ventricular arrhythmia and to provide specific information about its clinical use for this and other indications. The studies that were reviewed were selected on the basis of time published (from 1983 to 1995) and the completeness of information provided regarding patient clinical characteristics, drug dosing and methods of evaluation, efficacy analyses, long-term follow-up and complications. The full data from the three controlled trials that formed the basis of the drug's approval are contained in published reports that were also extensively reviewed. Intravenous amiodarone has demonstrable efficacy for the treatment of frequently recurrent destabilizing ventricular tachycardia and ventricular fibrillation, with suppression rates of 63% to 91% in uncontrolled trials. The three pivotal trials confirmed these findings and demonstrated a dose-response relation, with at least comparable efficacy to bretylium, a drug with a similar indication. The safety profile has also been well described; cardiovascular adverse effects are the most frequent, especially hypotension. Intravenous amiodarone is a useful addition to the drugs available for the treatment of patients with very severe ventricular arrhythmia. Its use in patients with other rhythm disorders appears promising, but final recommendations must await development of definitive data from ongoing clinical trials.

The acute management of life-threatening ventricular tachyarrhythmias often includes the use of parenteral antiarrhythmics. There are a number of agents currently available for this purpose. They are used to suppress inducible monomorphic ventricular tachycardia during programmed electrical stimulation, they terminate spontaneous sustained ventricular tachycardia, and prevent ventricular fibrillation in the setting of an acute myocardial infarction. Serious adverse reactions include proarrhythmia, hypotension, severe bradyarrhythmias, and precipitation of congestive heart failure. A comparative evaluation of intravenous antiarrhythmics is difficult due to inherent differences in the choice of agents for study, protocol design, patient population, defined endpoint, and serum drug levels. Likewise, the reported adverse reaction rates vary from 0.4% to 75%. To understand the difficulties in clinical decision-making in this problem area, particularly drug selection, we present here a review of pertinent clinical trials evaluating parenteral drug efficacy and adverse effects.