Antiarrhythmic actions of diltiazem during experimental atrioventricular reentrant tachycardias: Importance of use-dependent calcium channel-blocking properties

Abstract

The purpose of this study was to determine if the known frequency-dependent effects of diltiazem on inward calcium current result in selective actions during supraventricular tachycardia. These effects were evaluated by use of an experimental model of orthodromic atrioventricular reentrant tachycardia (AVRT). AVRT was induced in 15 dogs over a wide range of retrograde conduction times before and after two doses of diltiazem. Diltiazem produced a tachycardia-related suppression of atrioventricular nodal conduction resulting in greater efficacy for faster than for slower AVRTs. The degree of slowing for tachycardias that remained inducible after diltiazem administration was greater for AVRTs with a rapid initial rate (dose 1, 29%; dose 2, 40%) than for slower AVRTs (dose 1, 11%, p<0.01; dose 2, 18%, p<0.001). Rate-dependent AVRT slowing occurred because of a time-dependent phase of AH interval prolongation after the onset of tachycardia, which was observed only after diltiazem administration. To further clarify the mechanism of diltiazem's selective actions against faster tachycardias, its effects on the minimum pathway for reentry, or wavelength, were examined in four dogs. The ratio of refractory period to revolution time (RP/RT), an index of wavelength, was measured for each AVRT before and after diltiazem administration. Diltiazem increased the positive slope of the relation between RP/RT and the AVRT rate threefold compared with control (p<0.05). This rate-dependent effect prevented AVRT when RP/RT became greater than unity. In conclusion, rate-dependent atrioventricular node depression by diltiazem results in greater tachycardia slowing and higher rates of termination during atrioventricular reentrant tachycardias with faster initial rates and shorter retrograde conduction intervals.