How to Measure AV Nodal Refractoriness in the Presence of Verapamil, Amiodarone, Digoxin, and Diltiazem

On the AV node the negative dromotropic action of verapamil, amiodarone, digoxin, and diltiazem is known to be rate dependent. The effective refractory period of the AV node (AV-ERP) at a short cycle length is related to the AV conduction at that cycle length. We investigated how the number of stimuli during the conditioning train (S1) (during measurement of refractoriness at a high pacing rate [cycle length = 180 ms]) might influence the AV-ERP in isolated guinea pig hearts in a Langendorff preparation. Verapamil (10 nM), amiodarone (10 microM), digoxin (0.6 nM), and diltiazem (30 nM) caused a comparable prolongation of the AV conduction time (AVCT). All four drugs caused a significant prolongation of the AV-ERP when evaluated by a standard stimulation protocol with a conditioning train of 10 stimuli (10 S1) at a pacing cycle length of 180 ms followed by the test stimulus (S2). When the number of stimuli during the conditioning train (S1) was increased (> 10), until the prolongation of AVCT reached steady state, the AV-ERP in the presence of verapamil (132 +/- 4 vs 141 +/- 3 ms; P < 0.05, mean +/- S.E.M.) and diltiazem (143 +/- 3 vs 151 +/- 3 ms; P < 0.05) was prolonged significantly further. These results indicate that the effect of drugs on AV-ERP should be measured with a modified stimulation protocol, whereby the number of conditioning stimuli is comparable to the time constant characterizing the prolongation of AVCT at fast pacing rates.