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, amiodaron e, 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 (S-1) (during mea surement of refractoriness at a high pacing rate [cycle length = 180 m s]) might influence the AV-ERP in isolated guinea pig hearts in a Lang endorff preparation. Verapamil (10 nM), amiodarone (10 nM), digoxin (0 .6 nM), and diltiazem (30 nM) caused a comparable prolongation of the AV conduction time (AVCT). All four drugs caused a significant prolong ation of the AV-ERP when evaluated by a standard stimulation protocol with a conditioning train of 10 stimuli (10 S-1) at a pacing cycle len gth of 180 ms followed by the test stimulus (S-2). When the number of stimuli during the conditioning train (S-1) was increased (>10), until the prolongation of AVCT reached steady state, the AV-ERP in the pres ence 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 s ignificantly further. These results indicate that the effect of drugs on AV-ERP should be measured with a modified stimulation protocol, whe reby the number of conditioning stimuli is comparable to the time cons tant characterizing the prolongation of AVCT at fast pacing rates.