title: Effects of the I(Kr)-blocking agent dofetilide and of the I(Ks)-blocking agent chromanol 293b on regional disparity of left ventricular repolarization in the intact canine heart.
abstract: Recent in vitro studies have described regional differences of ion current expression and function, possibly accounting for reduced homogeneity of repolarization in the heart. In 11 intact canine hearts regional disparity of repolarization was determined at baseline and after administration of the I(Kr) blocking agent dofetilide (30 microg/kg) and the I(Ks)-blocking agent chromanol 293b (10 mg/kg). Effective refractory periods (ERPs) were determined through up to 10 needle electrodes inserted into basal, midwall and apical regions of the left ventricular wall using the extrastimulus technique (cycle length [CL] 300 and 850 ms). At baseline (CL of 850 ms), ERPs were significantly longer in epicardial muscle layers of the apex compared to the base. In deeper muscle layers regional differences of ERPs were not detectable. Administration of dofetilide increased apico-basal disparity of repolarization, due to a more marked increase of ERPs in the apex than in the base. In contrast, homogeneous ERPs were evident along the apico-basal axis after administration of chromanol 293b. Transmural dispersion of refractoriness could not be observed in any region at baseline, or after drug-administration. In the intact canine heart, apico-basal disparity of repolarization varies between individual muscle layers. Dependent on their current specificity, antiarrhythmic agents may enhance or diminish regional disparity of repolarization.
authors.affiliation: Department of Cardiology, University of Heidelberg, Heidelberg, Germany. alme.bauer@gmx.net
authors.forename: Alexander
authors.initials: A
authors.lastname: Bauer
authors.forename: Ruediger
authors.initials: R
authors.lastname: Becker
authors.forename: Christoph
authors.initials: C
authors.lastname: Karle
authors.forename: Kirsten D
authors.initials: KD
authors.lastname: Schreiner
authors.forename: Julia C
authors.initials: JC
authors.lastname: Senges
authors.forename: Frederik
authors.initials: F
authors.lastname: Voss
authors.forename: Patricia
authors.initials: P
authors.lastname: Kraft
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kuebler
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schoels
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002304:Cardiac Pacing, Artificial; D017115:Catheter Ablation; D002839:Chromans / Q000494:pharmacology*; D004285:Dogs; D004594:Electrophysiology; D006352:Heart Ventricles / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D010496:Pericardium / Q000378:metabolism; D010627:Phenethylamines / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D024661:Potassium Channels, Inwardly Rectifying / Q000037:antagonists & inhibitors*; D013449:Sulfonamides / Q000494:pharmacology*; D016276:Ventricular Function; D016277:Ventricular Function, Left / Q000187:drug effects* / Q000502:physiology
chemical_list: D000889:Anti-Arrhythmia Agents; D002839:Chromans; D010627:Phenethylamines; D026902:Potassium Channel Blockers; D024661:Potassium Channels, Inwardly Rectifying; D013449:Sulfonamides; C103474:6-cyano-4-(N-ethylsulfonyl-N-methylamino)-3-hydroxy-2,2-dimethylchromane; C063533:dofetilide