Rate-dependent effect of verapamil on atrial refractoriness.

Objectives: The purpose of this study was to determine whether verapamil has rate-dependent effects on the atrial effective refractory period (AERP).
Background: Block of calcium current (I(Ca)) and rapid component of the delayed rectifier potassium current (I(Kr)) by verapamil is frequency-dependent. This may result in variable effects of verapamil on the AERP, depending on the rate.
Methods: The subjects of this study were 30 adults with a mean age of 45 +/- 13 years who did not have structural heart disease. In 20 subjects, the AERP was measured at basic drive cycle lengths (BDCLs) of 650 to 250 ms, in 50 ms decrements, before and after infusion of 0.1 mg/kg verapamil. The effective refractory periods (ERPs) were measured in the setting of autonomic blockade in 10 subjects and without autonomic blockade in 10 subjects. Ten subjects served as a control group and received a saline infusion instead of verapamil.
Results: Verapamil significantly prolonged the AERP at BDCLs of 650 to 500 ms (p < 0.01 or p < 0.05) and significantly shortened the ERP at BDCLs of 300 and 250 ms (p < 0.01). In the control group, there were no significant differences between the baseline and post-saline measurements of ERP.
Conclusions: Verapamil prolongs AERP at slow rates and shortens AERP at rapid rates. These findings are consistent with a predominant effect on I(Ca) at rapid rates and a predominant effect on I(Kr) at slow rates.