title: How to measure AV nodal refractoriness in the presence of verapamil, amiodarone, digoxin, and diltiazem.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Karl-Franzens-University, Graz, Austria.
authors.forename: G
authors.initials: G
authors.lastname: Stark
authors.forename: K
authors.initials: K
authors.lastname: Kasper
authors.forename: C
authors.initials: C
authors.lastname: Schulze-Bauer
authors.forename: U
authors.initials: U
authors.lastname: Stark
authors.forename: M
authors.initials: M
authors.lastname: Decrinis
authors.forename: H A
authors.initials: HA
authors.lastname: Tritthart
mesh_terms: D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001283:Atrioventricular Node / Q000187:drug effects*; D002304:Cardiac Pacing, Artificial; D004077:Digoxin / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology*; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D005583:Fourier Analysis; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D012815:Signal Processing, Computer-Assisted; D014700:Verapamil / Q000494:pharmacology*
chemical_list: D000889:Anti-Arrhythmia Agents; D004077:Digoxin; D014700:Verapamil; D004110:Diltiazem; D000638:Amiodarone