title: Analysis of unipolar electrograms in rabbit heart demonstrated the key role of ventricular apicobasal dispersion in arrhythmogenicity.
abstract: Reduced repolarization reserve and increased transmural dispersion of repolarization (TDR) are known risk factors for Torsade de Pointes development, but less is known about the role of apex-to-base (apicobasal) repolarization in arrhythmogenesis. Three needles were inserted in rabbit left ventricle to record unipolar electrograms from endocardium to epicardium and base to apex. Total repolarization interval (TRI) and peak-to-end repolarization interval (Tp) were assessed after quinidine (n = 6) and D,L-sotalol (n = 6) perfusion in combination with the IKs inhibitor chromanol 293B. About 30 µM D,L-sotalol increased TRI and Tp more at the base (TRI + 40 ± 4 %; Tp +89 ± 11 %) relative to the apex (TRI + 28 ± 3 %, Tp + 30 ± 8 %). Similar results were obtained with quinidine: TRI and Tp increased more at the base compared to the apex. No significant differences were recorded from the endocardium to the epicardium. Our results show that combined IKr + IKs block prolonged TRI and Tp significantly more at the ventricular base than at the apex, in the absence of transmural dispersion of refractoriness. Regional changes in TRI and Tp indicate the contribution of apicobasal dispersion to arrhythmogenicity compared to TDR in a rabbit heart model.
authors.affiliation: Novartis Institutes for Biomedical Research, Novartis Pharma AG, Werk Klybeck, Klybeckstrasse 141, WKL.136.176, 4057, Basel, Switzerland, nico.guerard@gmail.com.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Guérard
authors.forename: Pierre
authors.initials: P
authors.lastname: Jordaan
authors.forename: Bérengère
authors.initials: B
authors.lastname: Dumotier
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D000975:Antioxidants / Q000378:metabolism; D001145:Arrhythmias, Cardiac / Q000209:etiology*; D002839:Chromans / Q000494:pharmacology; D022062:Electrophysiologic Techniques, Cardiac; D004699:Endocardium / Q000503:physiopathology; D010496:Pericardium / Q000503:physiopathology; D011802:Quinidine / Q000494:pharmacology; D011817:Rabbits; D013015:Sotalol / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D016171:Torsades de Pointes / Q000209:etiology
chemical_list: D000889:Anti-Arrhythmia Agents; D000975:Antioxidants; D002839:Chromans; D013449:Sulfonamides; C103474:6-cyano-4-(N-ethylsulfonyl-N-methylamino)-3-hydroxy-2,2-dimethylchromane; D013015:Sotalol; D011802:Quinidine