Class III antiarrhythmic agents have been considered to lengthen the myocardial effective refractory period (ERP) without any significant effects on the conduction velocity. However, recent investigations have clarified the positive or negative dromotropic effects of these agents. Amiodarone, a representative class III agent, exerts negative dromotropism by suppressing the fast sodium current responsible for conduction in acute administration (class I effects). Chronic amiodarone causes prolongation of ERP (class III effects), which is sometimes associated with negative dromotropism based on the alteration of passive or active membrane properties. Sotalol shows neither significant positive nor negative dromotropism under the normoxic condition, whereas this agent is reported to exert positive dromotropism mediated by the cAMP-dependent facilitation of gap junctional electrical coupling under the hypoxic condition. Some pure class III agents such as nifekalant are suspected to elicit 'apparent' positive dromotropism in the premature impulse propagation. This is explained by the right and upward shift of the strength-interval curve, which theoretically transforms the graded premature response to the all-or-none response. Although the clinical relevancy of these phenomena remains to be investigated, such variable dromotropism of the individual class III agent may contribute to the better understanding and development of antiarrhythmic agents.
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