Historical development of the concept of controlling cardiac arrhythmias by lengthening repolarization: particular reference to sotalol.

Although numerous pathophysiologic states, such as hypocalcemia and hypothyroidism, lengthen repolarization and are associated with a reduced incidence of cardiac fibrillation, the concept of the pharmacologic control of rhythm disorders by prolonging the action potential duration is relatively new. There is now a great deal of interest in the relative merits and applicability of delaying conduction or prolonging refractoriness as ways to prevent arrhythmias. Prolonging the action potential duration in cardiac tissues lengthens the refractory period without affecting conduction, prolongs the cycle length of the tachycardia, and prevents it from deteriorating into fibrillation. Lengthening the action potential duration is also associated with a positive inotropic effect demonstrated most readily in isolated cardiac tissues, an important feature in antiarrhythmic agents intended for use in life-threatening tachyarrhythmias in patients with reduced ventricular function. This array of properties was first recognized in the beta blocker sotalol and formed the basis for a discrete class of antiarrhythmic mechanism--the so-called class III electrophysiologic effect. Such a series of actions was also recognized early in the case of amiodarone, which has a much more complex pharmacologic profile. Clinical studies with sotalol and amiodarone have done much to establish the clinical use of prolonging the action potential duration in controlling a broad spectrum of cardiac arrhythmias. Both amiodarone and sotalol prolong the action potential duration and attenuate adrenergic stimulation, but they do so by fundamentally different mechanisms. The electrophysiologic properties of sotalol represent the combined effects of beta blockade and lengthening the action potential duration.(ABSTRACT TRUNCATED AT 250 WORDS)